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/index.php/Zimelidine

# Zimelidine Zimelidine (Normud®, Zelmid®) was the first marketed selective serotonin reuptake inhibitor (SSRI) antidepressant. It is a pyridylallylamine, structurally different from other antidepressants. The substance was developed in the early 1980s by the Swedish company Astra AB following a search for drugs with structures similar to chlorpheniramine (it is a derivative of Chlorphenamine), an antihistamine with antidepressant activity. It was then licensed to other drug producers. Zimelidine has been banned worldwide due to serious, sometimes fatal, cases of central and/or peripheral neuropathy known as Guillain-Barré syndrome and due to a peculiar hypersensitivity reaction involving many organs including skin exanthema, flu-like symptoms, arthralgias, and sometimes eosinophilia. Additionally, zimelidine was charged to cause an increase in suicidal ideation and/or attempts among depressive patients. After its ban, it was succeeded by fluvoxamine and fluoxetine (derived from the antihistamine diphenhydramine) in that order, and the other SSRIs. Zimelidine was reported by Montplaisir and Godbout to be very effective for cataplexy in 1986, back when this was usually controlled by tricyclic antidepressants, which often had anticholinergic effects. Zimelidine was able to improve cataplexy without causing daytime sleepiness.

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/index.php/Zinc

# Zinc Zinc (Template:PronEng) is a metallic chemical element with the symbol Zn and atomic number 30. In some historical and sculptural contexts, it is (or was) known as spelter. Zinc is a moderately reactive, blue gray metal that tarnishes in moist air and burns in air with a bright bluish-green flame, giving off plumes of zinc oxide. It reacts with acids, alkalis and other non-metals. If not completely pure, zinc reacts with dilute acids to release hydrogen. The one common oxidation state of zinc is +2. From 100 °C to 210 °C (212 °F to 410 °F) zinc metal is malleable and can easily be beaten into various shapes. Above 210 °C (410 °F), the metal becomes brittle and will be pulverized by beating. Zinc is nonmagnetic. Zinc is an essential element, necessary for sustaining all life. It is estimated that 3,000 of the hundreds of thousands of proteins in the human body contain zinc prosthetic groups, one type of which is the so-called zinc finger. In addition, there are over a dozen types of cells in the human body that secrete zinc ions, and the roles of these secreted zinc signals in medicine and health are now being actively studied. Zinc ions are now considered neurotransmitters. Cells in the salivary gland, prostate, immune system and intestine are other types that secrete zinc. Zinc is an activator of certain enzymes, such as carbonic anhydrase. Carbonic anhydrase is important in the transport of carbon dioxide in vertebrate blood. It is also required in plants for leaf formation, the synthesis of indole acetic acid (auxin) and anaerobic respiration (alcoholic fermentation). Zinc is found in oysters, and to a far lesser degree in most animal proteins, beans, nuts, almonds, whole grains, pumpkin seeds and sunflower seeds. A turkey's neck and beef's chuck or shank also contain good amounts of zinc. Phytates, which are found in whole grain breads, cereals, legumes and other products, have been known to decrease zinc absorption. Clinical studies have found that zinc, combined with antioxidants, may delay progression of age-related macular degeneration. Significant dietary intake of zinc has also recently been shown to impede the onset of flu. Soil conservation analyzes the vegetative uptake of naturally occurring zinc in many soil types. The (US) recommended dietary allowance of zinc from puberty on is 11mg for males and 8mg for females, with higher amounts recommended during pregnancy and lactation. Zinc deficiency results from inadequate intake of zinc, or inadequate absorption of zinc into the body. Signs of zinc deficiency include hair loss, skin lesions, diarrhea, and wasting of body tissues. Eyesight, taste, smell and memory are also connected with zinc. A deficiency in zinc can cause malfunctions of these organs and functions. Congenital abnormalities causing zinc deficiency may lead to a disease called Acrodermatitis enteropathica. Obtaining a sufficient zinc intake during pregnancy and in young children is a very real problem, especially among those who cannot afford a good and varied diet. Brain development is stunted by zinc insufficiency in utero and in youth. It is rarely recognised that lack of zinc can contribute to acne. Leukonychia, purple spots on the fingernails, are often seen as an indication of zinc deficiency. Zinc deficiency causes a decrease in appetite -- which could degenerate in anorexia nervosa (AN). Appetite disorders, in turn, cause malnutrition and, notably, inadequate zinc intake. The use of zinc in the treatment of anorexia nervosa has been advocated since 1979 by Bakan. At least 15 trials showed that zinc improved weight gain in anorexia. A 1994 randomized, double-blind, placebo-controlled trial showed that zinc (14 mg per day) doubled the rate of body mass increase in the treatment of anorexia nervosa (AN). Deficiency of other nutrients such as tyrosine and tryptophan (precursors of the monoamine neurotransmitters norepinephrine and serotonin, respectively), as well as vitamin B1 (thiamine) could contribute to this phenomenon of malnutrition-induced malnutrition. Even though zinc is an essential requirement for a healthy body, too much zinc can be harmful. Excessive absorption of zinc can also suppress copper and iron absorption. The free zinc ion in solution is highly toxic to plants, invertebrates, and even vertebrate fish. The Free Ion Activity Model (FIAM) is well-established in the literature, and shows that just micromolar amounts of the free ion kills some organisms. A recent example showed 6 micromolar killing 93% of all daphnia in water. Swallowing a post 1982 American one cent piece (97.5% zinc) can also cause damage to the stomach lining due to the high solubility of the zinc ion in the acidic stomach. Zinc toxicity, mostly in the form of the ingestion of US pennies minted after 1982, is commonly fatal in dogs where it causes a severe hemolytic anemia. In pet parrots zinc is highly toxic and poisoning can often be fatal . There is evidence of induced copper deficiency at low intakes of 100–300 mg Zn/d. The USDA RDA is 15 mg Zn/d. Even lower levels, closer to the RDA, may interfere with the utilization of copper and iron or to adversely affect cholesterol. . Zinc salts are effective against pathogens in direct application. Gastroenteritis is strongly attenuated by ingestion of zinc, and this effect could be due to direct antimicrobial action of the zinc ions in the GI tract, or to absorption of the zinc and re-release from immune cells (all granulocytes secrete zinc), or both. In clinical trials, both zinc gluconate and zinc gluconate glycine (the formulation used in lozenges) have been shown to shorten the duration of symptoms of the common cold. The amount of glycine can vary from two to twenty moles per mole of zinc gluconate. Zinc oxide is perhaps the best known and most widely used zinc compound, as it makes a good base for white pigments in paint. It also finds industrial use in the rubber industry, and is sold as opaque sunscreen. A variety of other zinc compounds find use industrially, such as zinc chloride (in deodorants), zinc pyrithione (anti-dandruff shampoos), zinc sulfide (in luminescent paints), and zinc methyl or zinc diethyl in the organic laboratory. Roughly one quarter of all zinc output is consumed in the form of zinc compounds. Metallic zinc is not considered to be toxic, but free zinc ions in solution (like copper or iron ions) are highly toxic. There is also a condition called zinc shakes or zinc chills (see metal fume fever) that can be induced by the inhalation of freshly formed zinc oxide formed during the welding of galvanized materials. Excessive intake of zinc can promote deficiency in other dietary minerals.

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/index.php/Zinc-activated_ion_channel

# Zinc-activated ion channel Zinc-activated ion channel (ZAC), is a human protein encoded by the ZACN gene. ZAC forms a cation-permeable ligand-gated ion channel of the "Cys-loop" superfamily. The ZAC gene is present in humans and dogs, but no ortholog is thought to exist in the rat or mouse genomes. ZAC mRNA is expressed in prostate, thyroid, trachea, lung, brain (adult and fetal), spinal cord, skeletal muscle, heart, placenta, pancreas, liver, kidney and stomach. The endogenous ligand for ZAC is thought to be Zn2+, although ZAC has also been found to activate spontaneously. The function of spontaneous ZAC activation is unknown.

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/index.php/Zinc_deficiency

# Zinc deficiency Zinc deficiency is a condition where insufficient Zinc is available for metabolic needs. Its etiology is usually nutritional, but can also be associated with malabsorption, or can be congenital (acrodermatitis enteropathica).

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/index.php/Zinc_dependent_phospholipase_C

# Zinc dependent phospholipase C Bacillus cereus contains a monomeric phospholipase C EC 3.1.4.3 (PLC) of 245 amino-acid residues. Although PLC prefers to acton phosphatidylcholine, it also shows weak catalytic activity with sphingomyelin and phosphatidylinositol . Sequence studies have shown the protein to be similar both to alpha toxin fromClostridium perfringens and Clostridium bifermentans, a phospholipase C involved in haemolysis and cell rupture , and to lecithinase from Listeria monocytogenes, which aids cell-to-cell spread by breaking down the 2-membrane vacuoles that surround the bacterium during transfer . Each of these proteins is a zinc-dependent enzyme, binding 3 zinc ions per molecule . The enzymes catalyse the conversion of phosphatidylcholine and water to 1,2-diacylglycerol and choline phosphate . In Bacillus cereus, there are nine residues known to be involved in binding the zinc ions: 5 His, 2 Asp, 1 Glu and 1 Trp. These residues are all conserved in the Clostridium alpha-toxin.

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/index.php/Zinc_finger_protein_180

# Zinc finger protein 180 Zinc finger proteins have been shown to interact with nucleic acids and to have diverse functions. The zinc finger domain is a conserved amino acid sequence motif containing two specifically positioned cysteines and two histidines that are involved in coordinating zinc. Kruppel-related proteins form one family of zinc finger proteins. See MIM 604749 for additional information on zinc finger proteins.

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/index.php/Zinc_finger_protein_208

# Zinc finger protein 208 Zinc finger proteins (ZNFs), such as ZNF208, bind DNA and, through this binding, regulate gene transcription. Most ZNFs contain conserved C2H2 motifs and are classified as Kruppel-type zinc fingers. A conserved protein motif, termed the Kruppel-associated box (KRAB) domain, mediates protein-protein interactions (Eichler et al., 1998 [PubMed 9724325]). See ZNF91 (MIM 603971) for further information on ZNFs.

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/index.php/Zinc_finger_protein_280b

# Zinc finger protein 280b The protein encoded by this gene is a transcription factor that upregulates expression of MDM2, which negatively regulates p53 expression. This gene is highly expressed in prostate cancer cells, which leads to a reduction in p53 levels and an increase in growth of the cancer cells. Several transcript variants have been found for this gene, but only one of them is protein-coding.

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/index.php/Zinc_finger_protein_426

# Zinc finger protein 426 Kaposi's sarcoma-associated herpesvirus (KSHV) can be reactivated from latency by the viral protein RTA. The protein encoded by this gene is a zinc finger transcriptional repressor that interacts with RTA to modulate RTA-mediated reactivation of KSHV. While the encoded protein can repress KSHV reactivation, RTA can induce degradation of this protein through the ubiquitin-proteasome pathway to overcome the repression. Several transcript variants encoding different isoforms have been found for this gene.

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/index.php/Zinc_finger_protein_516

# Zinc finger protein 516 Zinc-finger proteins bind nucleic acids and play important roles in various cellular functions, including cell proliferation, differentiation, and apoptosis. This gene encodes a zinc-finger protein, and belongs to the Krüppel C2H2-type zinc-finger protein family. It may be involved in transcriptional regulation.

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/index.php/Zinc_gluconate

# Zinc gluconate Zinc gluconate is a lozenge that is FDA approved for the treatment of common cold. It reduces the severity of cold symptoms. Common adverse reactions include stomach upset.

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/index.php/Zinc_iodide

# Zinc iodide Zinc iodide is composed of Zinc and Iodine. It is an inorganic compound with a molecular weight of 319.22. It is a white, granular, odorless solid that absorbs water from the atmosphere and then dissolves into a solution. At 1150°C, zinc iodide vapor dissociates into zinc and iodine. United States Patent 4109065 describes a rechargeable aqueous zinc-halogen cell which includes an aqueous electrolytic solution containing a zinc salt selected from the class consisting of zinc bromide, zinc iodide, and mixtures thereof, in both positive and negative electrode compartments.

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/index.php/Zinc_oxide

# Zinc oxide Zinc oxide is a chemical compound with the formula ZnO. It is nearly insoluble in water but soluble in acids and alkalis. It occurs as white hexagonal crystals or a white powder commonly known as zinc white. It remains white when exposed to hydrogen sulfide or ultraviolet light. Crystalline zinc oxide exhibits the piezoelectric effect and is thermochromic (it will change colour from white to yellow when heated, and back again when cooled down). Zinc oxide decomposes into zinc vapor and oxygen at around 1975 °C. High-quality single-crystalline ZnO is almost transparent. Zinc oxide occurs in nature as the mineral zincite. Zinc oxide lozenges are a popular over-the-counter cold remedy, but numerous studies have failed to demonstrate any significant effect. Zinc oxide in a mixture with about 0.5% iron(III) oxide (Fe2O3) is called calamine and is used in calamine lotion. There are also two minerals, zincite and hemimorphite, which have been called calamine historically (see: calamine (mineral)). When mixed with eugenol, zinc oxide eugenol forms which has restorative and prosthodontic applications in dentistry. Zinc white is used as a pigment in paints and is more opaque than lithopone, but less opaque than titanium dioxide. It is also used in coatings for paper. Chinese white is a special grade of zinc white used in artists' pigments. Because it absorbs both UVA and UVB rays of ultraviolet light, zinc oxide can be used in ointments, creams, and lotions to protect against sunburn and other damage to the skin caused by ultraviolet light (see sunscreen). It is the broadest spectrum UVA and UVB absorber that is approved for use as a sunscreen by FDA, and is completely photostable. Additionally, since zinc oxide has antimicrobial and antifungal activities, it is the number one active ingredient recommended by pediatricians for the treatment of diaper rash. Zinc oxide and stearic acid are ingredients in the commercial manufacture of rubber goods. A mixture of these two compounds allows a quicker and more controllable rubber cure. Zinc oxide can also be used as a filler in some rubber mixtures. ZnO is a semiconductor with a direct bandgap energy of 3.37 eV at room temperature. The most common applications are in laser diodes and light emitting diodes since it has a exciton and biexciton energies of 60 meV and 15 meV, respectively. It is expected that this exciton properties of ZnO will be improved further by epitaxy. n-type doped films are often used in thin film technology, where zinc oxide serves as a TCO (transparent conducting oxide). n-type doping is possible by introduction of aluminum, indium, or excess zinc . Oxygen vacancies generate states in the band gap and hence also cause an increase in conductivity. p-type doping is difficult and is currently an active area of research, with arsenic as the leading candidate dopant . Thin-film solar cells, LCD and flat panel displays are typical applications of this material. Appropriately doped Zinc oxide may be transparent and conductive, and can therefore be used as a transparent electrode. Indium tin oxide (ITO) is another transparent conducting oxide often used in microelectronics. ZnO has also been considered for spintronics applications because of theoretical predictions of room temperature ferromagnetism. Unsubstantiated reports of ferromagnetism have been made, but presence of dilute magnetic semiconductors remains a large unanswered question in physics. ZnO layers are mainly deposited by sputter deposition and chemical vapor deposition (CVD). The latter method allows the growth of a rough layer, which can diffuse the incoming light by scattering, increasing the efficiency of solar cells. Metallic zinc is melted in a graphite crucible and vaporized above 907 °C. Zinc vapor instantaneously reacts with the oxygen in the air to give ZnO, accompanied by a drop in its temperature and bright luminescence. Zinc oxide particles are transported into a cooling duct and collected in a bag house. This indirect method is commonly known as the French process (FP) which was popularised by LeClaire (France) in 1844. A typical FP, zinc oxide normally consists of agglomerated zinc oxide particles with an average size of 0.1 micrometres to a few micrometres. By weight, most of the world's zinc oxide is manufactured via French process and major applications involve industries related to rubber, varistors, suncreens, paints, healthcare, and poultry nutrients. Recent developments involve acicular nanostructures (rods, wires, tripods, tetrapods, plates) synthesized using a modified French process known as catalyst-free combust-oxidized mesh (CFCOM) process. Acicular nanostructures usually have micrometre-length nanorods with nanometric diameters (below 100 nm). The so-called direct method is related to the FP. In this process, zinc ores or roasted sulfide concentrates are mixed with coal. In a reduction furnace, ore is reduced to metallic zinc and the vaporized zinc is allowed to react with oxygen to form zinc oxide. In this process ore of zinc (zinc ash) is dissolved (as ZnCl2) and precipitated with alkali. Zinc oxide made from this process is known as "Active Zinc Oxide" Fumes of zinc oxide are generated when melting brass, because the melting point of brass is close to the boiling point of zinc. Exposure to zinc oxide in the air (also while welding) can result in a nervous malady called metal fume fever.

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/index.php/Zinc_protoporphyrin

# Zinc protoporphyrin Zinc protoporphyrin is a compound found in red blood cells when heme production is inhibited by lead. It has been used as a test for lead poisoning.

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/index.php/Zinc_pyrithione

# Zinc pyrithione Zinc pyrithione is an shampoo that is FDA approved for the prophylaxis of flaking and itching recurrence associated with dandruff. Common adverse reactions include irritation of mucous membranes. Pregnancy Category (FDA): There is no FDA guidance on usage of Zinc pyrithione in women who are pregnant. Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Zinc pyrithione in women who are pregnant. There is limited information regarding Zinc pyrithione overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

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/index.php/Zipeprol

# Zipeprol Zipeprol is a centrally acting cough suppressant developed in France in the 1970s. It is not an morphinan derivative (in contrast to codeine and dextromethorphan). Zipeprol acts as a local anaesthetic and has mucolytic, antihistamine and anticholinergic properties. It is sold with several brand names such as Zinolta and Respilene. It is not available in the United States or Canada and has been discontinued in Europe. It is still available in some countries in Asia and South America. Zipeprol has been misused in Korea, mainly for the hallucinations it produces. Such use has become an issue due to the seizures and various neurological side effects it causes at high dosages.

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/index.php/Ziprasidone_(injection)

# Ziprasidone (injection) Ziprasidone (injection) is an atypical antipsychotic that is FDA approved for the treatment of schizophrenia. There is a Black Box Warning for this drug as shown here. Common adverse reactions include Somnolence, extrapyramidal symptoms, dizziness, akathisia, abnormal vision, asthenia, and vomiting. Drug-drug interactions can be pharmacodynamic (combined pharmacologic effects) or pharmacokinetic (alteration of plasma levels). The risks of using ziprasidone in combination with other drugs have been evaluated as described below. All interactions studies have been conducted with oral ziprasidone. Based upon the pharmacodynamic and pharmacokinetic profile of ziprasidone, possible interactions could be anticipated: Please refer to the patient package insert. To assure safe and effective use of GEODON, the information and instructions provided in the patient information should be discussed with patients.

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/index.php/Zirconium

# Zirconium Template:Elementbox header Template:Elementbox series Template:Elementbox groupperiodblock Template:Elementbox appearance img Template:Elementbox atomicmass gpm Template:Elementbox econfig Template:Elementbox epershell Template:Elementbox section physicalprop Template:Elementbox phase Template:Elementbox density gpcm3nrt Template:Elementbox densityliq gpcm3mp Template:Elementbox meltingpoint Template:Elementbox boilingpoint Template:Elementbox heatfusion kjpmol Template:Elementbox heatvaporiz kjpmol Template:Elementbox heatcapacity jpmolkat25 Template:Elementbox vaporpressure katpa Template:Elementbox section atomicprop Template:Elementbox crystalstruct Template:Elementbox oxistates Template:Elementbox electroneg pauling Template:Elementbox ionizationenergies4 Template:Elementbox atomicradius pm Template:Elementbox atomicradiuscalc pm Template:Elementbox covalentradius pm Template:Elementbox section miscellaneous Template:Elementbox magnetic Template:Elementbox eresist ohmmat20 Template:Elementbox thermalcond wpmkat300k Template:Elementbox thermalexpansion umpmkat25 Template:Elementbox speedofsound rodmpsat20 Template:Elementbox youngsmodulus gpa Template:Elementbox shearmodulus gpa Template:Elementbox poissonratio Template:Elementbox mohshardness Template:Elementbox vickershardness mpa Template:Elementbox brinellhardness mpa Template:Elementbox cas number |- ! colspan="2" style="background:#ffc0c0; color:black" | Selected isotopes |- | colspan="2" |

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/index.php/Zirconium(IV)_iodide

# Zirconium(IV) iodide This orange-coloured species is volatile, subliming as intact tetrahedral ZrI4 molecules. It is prepared by the direct reaction of powdered zirconium metal and iodine.

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/index.php/Zolazepam

# Zolazepam Zolazepam (Flupyrazapon) is a pyrazolodiazepinone derivative structurally related to the benzodiazepine drugs, which is used as an anaesthetic for a wide range of animals in veterinary medicine. Zolazepam is usually administered in combination with other drugs such as the NMDA antagonist Tiletamine or the alpha-2 adrenergic receptor agonist Xylazine, depending on what purpose it is being used for.

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/index.php/Zoledronic_acid

# Zoledronic acid Zoledronic acid is a bisphosphonate that is FDA approved for the treatment of hypercalcemia of malignancy, multiple myeloma, bone metastases of solid tumors, osteoporosis,paget's disease, postmenopausal osteoporosis. Common adverse reactions include nausea, fatigue, anemia, bone pain, constipation, fever, vomiting, dyspnea. Zoledronic acid Injection is indicated for the treatment of hypercalcemia of malignancy defined as an albumin-corrected calcium (cCa) of greater than or equal to 12 mg/dL [3.0 mmol/L] using the formula: cCa in mg/dL =Ca in mg/dL + 0.8 ( 4.0 g/dL – patient albumin [g/dL]). Zoledronic acid Injection is indicated for the treatment of patients with multiple myeloma and patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy. Prostate cancer should have progressed after treatment with at least one hormonal therapy. The safety and efficacy of Zoledronic acid Injection in the treatment of hypercalcemia associated with hyperparathyroidism or with other nontumor-related conditions have not been established. The maximum recommended dose of Zoledronic acid Injection in hypercalcemia of malignancy (albumin-corrected serum calcium greater than or equal to 12 mg/dL [3.0 mmol/L]) is 4 mg. The 4-mg dose must be given as a single-dose intravenous infusion over no less than 15 minutes. Patients who receive Zoledronic acid Injection should have serum creatinine assessed prior to each treatment. Dose adjustments of Zoledronic acid Injection are not necessary in treating patients for hypercalcemia of malignancy presenting with mild-to-moderate renal impairment prior to initiation of therapy (serum creatinine less than 400 mcmol/L or less than 4.5 mg/dL). Consideration should be given to the severity of, as well as the symptoms of, tumor-induced hypercalcemia when considering use of Zoledronic acid Injection. Vigorous saline hydration, an integral part of hypercalcemia therapy, should be initiated promptly and an attempt should be made to restore the urine output to about 2 L/day throughout treatment. Mild or asymptomatic hypercalcemia may be treated with conservative measures (i.e., saline hydration, with or without loop diuretics). Patients should be hydrated adequately throughout the treatment, but overhydration, especially in those patients who have cardiac failure, must be avoided. Diuretic therapy should not be employed prior to correction of hypovolemia. Retreatment with Zoledronic acid Injection 4 mg may be considered if serum calcium does not return to normal or remain normal after initial treatment. It is recommended that a minimum of 7 days elapse before retreatment, to allow for full response to the initial dose. Renal function must be carefully monitored in all patients receiving Zoledronic acid Injection and serum creatinine must be assessed prior to retreatment with Zoledronic acid Injection. The recommended dose of Zoledronic acid Injection in patients with multiple myeloma and metastatic bone lesions from solid tumors for patients with creatinine clearance (CrCl) greater than 60 mL/min is 4 mg infused over no less than 15 minutes every 3 to 4 weeks. The optimal duration of therapy is not known. Upon treatment initiation, the recommended Zoledronic acid Injection doses for patients with reduced renal function (mild and moderate renal impairment) are listed in Table 1. These doses are calculated to achieve the same area under the curve (AUC) as that achieved in patients with creatinine clearance of 75 mL/min. CrCl is calculated using the Cockcroft-Gault formula . During treatment, serum creatinine should be measured before each Zoledronic acid Injection dose and treatment should be withheld for renal deterioration. In the clinical studies, renal deterioration was defined as follows: In the clinical studies, Zoledronic acid Injection treatment was resumed only when the creatinine returned to within 10% of the baseline value. Zoledronic acid Injection should be reinitiated at the same dose as that prior to treatment interruption. Zoledronic acid Injection must not be mixed with calcium or other divalent cation-containing infusion solutions, such as Lactated Ringer's solution, and should be administered as a single intravenous solution in a line separate from all other drugs. Vials of Zoledronic acid Injection concentrate for infusion contain overfill allowing for the withdrawal of 5 mL of concentrate (equivalent to 4 mg zoledronic acid). This concentrate should immediately be diluted in 100 mL of sterile 0.9% Sodium Chloride, USP, or 5% Dextrose Injection, USP, following proper aseptic technique, and administered to the patient by infusion. Do not store undiluted concentrate in a syringe, to avoid inadvertent injection. To prepare reduced doses for patients with baseline CrCl less than or equal to 60 mL/min, withdraw the specified volume of the Zoledronic acid Injection concentrate from the vial for the dose required (see Table 2) If not used immediately after dilution with infusion media, for microbiological integrity, the solution should be refrigerated at 2°C-8°C (36°F-46°F). The refrigerated solution should then be equilibrated to room temperature prior to administration. The total time between dilution, storage in the refrigerator, and end of administration must not exceed 24 hours. The safety of Zoledronic acid Injection was studied in 185 patients with hypercalcemia of malignancy (HCM) who received either Zoledronic acid Injection 4 mg given as a 5-minute intravenous infusion (n=86) or pamidronate 90 mg given as a 2-hour intravenous infusion (n=103). The population was aged 33-84 years, 60% male and 81% Caucasian, with breast, lung, head and neck, and renal cancer as the most common forms of malignancy. NOTE: pamidronate 90 mg was given as a 2-hour intravenous infusion. The relative safety of pamidronate 90 mg given as a 2-hour intravenous infusion compared to the same dose given as a 24-hour intravenous infusion has not been adequately studied in controlled clinical trials. Administration of Zoledronic acid Injection 4 mg given as a 5-minute intravenous infusion has been shown to result in an increased risk of renal toxicity, as measured by increases in serum creatinine, which can progress to renal failure. The incidence of renal toxicity and renal failure has been shown to be reduced when Zoledronic acid Injection 4 mg is given as a 15-minute intravenous infusion. Zoledronic acid Injection should be administered by intravenous infusion over no less than 15 minutes. Table 3 provides adverse events that were reported by 10% or more of the 189 patients treated with Zoledronic acid Injection 4 mg or Pamidronate 90 mg from the two HCM trials. Adverse events are listed regardless of presumed causality to study drug. In vitro studiesindicate that the plasma protein binding of zoledronic acid is low, with the unbound fraction ranging from 60% to77%. In vitrostudies also indicate that zoledronic acid does not inhibit microsomal CYP450 enzymes. In vivo studies showed that zoledronic acid is not metabolized, and is excreted into the urine as the intact drug. Caution is advised when bisphosphonates are administered with aminoglycosides, since these agents may have an additive effect to lower serum calcium level for prolonged periods. This effect has not been reported in Zoledronic acid Injection clinical trials. No dose adjustment for Zoledronic acid Injection 4 mg is needed when co-administered with thalidomide. In a pharmacokinetic study of 24 patients with multiple myeloma, Zoledronic acid Injection 4 mg given as a 15 minute infusion was administered either alone or with thalidomide (100 mg once daily on days 1-14 and 200 mg once daily on days 15-28). Co-administration of thalidomide with Zoledronic acid Injection did not significantly change the pharmacokinetics of Zoledronic acid or creatinine clearance. It is not known whether Zoledronic acid is excreted in human milk and because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from Zoledronic acid Injection, a decision should be made to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Zoledronic acid binds to bone long term and may be released over weeks to years. Clinical studies of Zoledronic acid Injection in hypercalcemia of malignancy included 34 patients who were 65 years of age or older. No significant differences in response rate or adverse reactions were seen in geriatric patients receiving Zoledronic acid Injection as compared to younger patients. Because decreased renal function occurs more commonly in the elderly, special care should be taken to monitor renal function. Due to the risk of clinically significant deterioration in renal function, which may progress to renal failure, single doses of Zoledronic acid Injection should not exceed 4 mg and the duration of infusion should be no less than 15 minutes. In the trials and in postmarketing experience, renal deterioration, progression to renal failure and dialysis, have occurred in patients, including those treated with the approved dose of 4 mg infused over 15 minutes. There have been instances of this occurring after the initial Zoledronic acid Injection dose. The principal pharmacologic action of zoledronic acid is inhibition of bone resorption. Although the antiresorptive mechanism is not completely understood, several factors are thought to contribute to this action. In vitro, zoledronic acid inhibits osteoclastic activity and induces osteoclast apoptosis. Zoledronic acid also blocks the osteoclastic resorption of mineralized bone and cartilage through its binding to bone. Zoledronic acid inhibits the increased osteoclastic activity and skeletal calcium release induced by various stimulatory factors released by tumors. Secondary efficacy variables from the pooled HCM studies included the proportion of patients who had normalization of corrected serum calcium (CSC) by Day 4; the proportion of patients who had normalization of CSC by Day 7; time to relapse of HCM; and duration of complete response. Time to relapse of HCM was defined as the duration (in days) of normalization of serum calcium from study drug infusion until the last CSC value less than 11.6 mg/dL (less than 2.90 mmol/L). Patients who did not have a complete response were assigned a time to relapse of 0 days. Duration of complete response was defined as the duration (in days) from the occurrence of a complete response until the last CSC ≤10.8 mg/dL (2.70 mmol/L). The results of these secondary analyses for Zoledronic acid Injection 4 mg and pamidronate 90 mg are shown in Table 10. Table 11 describes an overview of the efficacy population in three randomized Zoledronic acid Injection trials in patients with multiple myeloma and bone metastases of solid tumors. These trials included a pamidronate-controlled study in breast cancer and multiple myeloma, a placebo-controlled study in prostate cancer, and a placebo-controlled study in other solid tumors. The prostate cancer study required documentation of previous bone metastases and 3 consecutive rising PSAs while on hormonal therapy. The other placebo-controlled solid tumor study included patients with bone metastases from malignancies other than breast cancer and prostate cancer, including NSCLC, renal cell cancer, small cell lung cancer, colorectal cancer, bladder cancer, GI/genitourinary cancer, head and neck cancer, and others. These trials were comprised of a core phase and an extension phase. In the solid tumor, breast cancer and multiple myeloma trials, only the core phase was evaluated for efficacy as a high percentage of patients did not choose to participate in the extension phase. In the prostate cancer trials, both the core and extension phases were evaluated for efficacy showing the Zoledronic acid Injection effect during the first 15 months was maintained without decrement or improvement for another 9 months. The design of these clinical trials does not permit assessment of whether more than one-year administration of Zoledronic acid Injection is beneficial. The optimal duration of Zoledronic acid Injection administration is not known. The studies were amended twice because of renal toxicity. The Zoledronic acid Injection infusion duration was increased from 5 minutes to 15 minutes. After all patients had been accrued, but while dosing and follow-up continued, patients in the 8 mg Zoledronic acid Injection treatment arm were switched to 4 mg due to toxicity. Patients who were randomized to the Zoledronic acid Injection 8 mg group are not included in these analyses. Each study evaluated skeletal-related events (SREs), defined as any of the following: pathologic fracture, radiation therapy to bone, surgery to bone, or spinal cord compression. Change in antineoplastic therapy due to increased pain was a SRE in the prostate cancer study only. Planned analyses included the proportion of patients with a SRE during the study and time to the first SRE. Results for the two Zoledronic acid Injection placebo-controlled studies are given in Table 12. In the breast cancer and myeloma trial, efficacy was determined by a noninferiority analysis comparing Zoledronic acid Injection to pamidronate 90 mg for the proportion of patients with a SRE. This analysis required an estimation of pamidronate efficacy. Historical data from 1,128 patients in three pamidronate placebo-controlled trials demonstrated that pamidronate decreased the proportion of patients with a SRE by 13.1% (95% CI = 7.3%, 18.9%). Results of the comparison of treatment with Zoledronic acid Injection compared to pamidronate are given in Table 13.

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# Zollinger-Ellison syndrome CT ## Abdominal CT Abdominal CT scan may be helpful in the diagnosis of Zollinger-Ellison syndrome caused by gastrinoma. Gastrinomas are frequently multiple and often extrapancreatic (90% located in the gastrinoma triangle). Thus, they can be difficult to locate. For this reason, multiphase contrast enhanced thin slice cross-sectional imaging is ideal. Findings on Abdominal CT scan suggestive of gastrinoma include clearly defined, well-enhanced mass.

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# Zollinger-Ellison syndrome CT scan ## CT scan CT scan can aide in making the diagnosis of Zollinger-Ellison syndrome. On CT scan, gastric rugal folds can appear thickened and multiple gastric masses or nodules can also be seen.

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# Zollinger-Ellison syndrome MRI ## MRI Abdominal MRI may be helpful in the diagnosis of Zollinger-Ellison syndrome caused by gastrinoma. Findings on abdominal MRI suggestive of Zollinger-Ellison syndrome include solitary lesion or multiple lesions.

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# Zollinger-Ellison syndrome causes ## Causes The cause of Zollinger-Ellison syndrome has not been identified. However, 25 to 30 percent of gastrinomas, which can cause Zollinger-Ellison syndrome, are caused by multiple endocrine neoplasia type 1 (MEN1).

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# Zollinger-Ellison syndrome diagnostic study of choice Laboratory testing is the diagnostic study of choice for Zollinger-Ellison syndrome. Serum gastrin measurements with calcium and especially with secretin challenge is the most important method of diagnosis.

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# Zollinger-Ellison syndrome differential diagnosis Zollinger-Ellison syndrome must be differentiated from diseases that cause abdominal pain and chronic diarrhea. The table below summarizes the findings that differentiate watery causes of chronic diarrhea:

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# Zollinger-Ellison syndrome echocardiography and ultrasound ## Echocardiography/Ultrasound Abdominal ultrasound may be helpful in the diagnosis of Zollinger-Ellison syndrome caused by gastrinoma. . Ultrasonography can detect gastrinomas in 30%. Endoscopic ultrasonography (EUS) is a highly sensitive and specific procedure for the localization of pancreatic endocrine tumors and duodenal as well as pancreatic gastrinomas.

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# Zollinger-Ellison syndrome epidemiology and demographics ## Epidemiology and Demographics The incidence of gastrinoma, which can cause Zollinger-Ellison syndrome, is approximately 0.05 - 0.2 per 100,000 individuals worldwide. About 25 to 30 percent of gastrinomas are caused by multiple endocrine neoplasia type 1 (MEN1).

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# Zollinger-Ellison syndrome natural history, complications and prognosis In mild cases if left untreated, patients with Zollinger-Ellison syndrome may further develop abdominal pain, diarrhea, heartburn. Common complications of Zollinger-Ellison syndrome include upper gastrointestinal bleeding, anemia, and duodenal ulcer perforation. Prognosis is generally good when treated and the 5 and 10-year survival rate of patients with Zollinger-Ellison syndrome is around 94% and 75%, respectively. In severe cases if left untreated, ZES results in refractory peptic ulcer disease, severe gastroesophageal reflux disease, diarrhea, weight loss, anemia and finally death, mainly due to the complications of the refractory peptic ulcer disease.

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# Zollinger-Ellison syndrome overview Patients with Zollinger-Ellison syndrome may experience abdominal pain and diarrhea. The diagnosis is also suspected in patients without symptoms who have severe ulceration of the stomach and small bowel, especially if they fail to respond to treatment. Gastrinomas may occur as single tumors or as multiple, small tumors. About one-half to two-thirds of single gastrinomas are malignant tumors that most commonly spread to the liver and lymph nodes near the pancreas and small bowel. Nearly 25 percent of patients with gastrinomas have multiple tumors as part of a condition called multiple endocrine neoplasia type I (MEN I). MEN I patients have tumors in their pituitary gland and parathyroid glands in addition to tumors of the pancreas. Development of Zollinger-Ellison syndrome is the result of increased levels of gastrin due to an existing gastrinoma in the duodenum or pancreas. Zollinger-Ellison syndrome must be differentiated from gastric antrum syndrome, antral G-cell hyperplasia, peptic ulcer, gastroesophageal reflux disease (GERD), and hypergastrinemia. The incidence of gastrinoma, which can cause Zollinger-Ellison syndrome, is approximately 0.5-2 persons per 100,000 individuals worldwide. Pharmacologic medical therapies for Zollinger-Ellison syndrome include proton pump inhibitors, H2-receptor antagonists, chemotherapy, and hormonal therapy. Effective measures for the primary prevention of Zollinger-Ellison syndrome include genetic testing, if family history presents. The incidence of gastrinoma, which can cause Zollinger-Ellison syndrome, is approximately 0.05-0.2 per 100,000 individuals worldwide. About 25 to 30 percent of gastrinomas are caused by multiple endocrine neoplasia type 1 (MEN1). Zollinger-Ellison syndrome is a disease that tends to affect the middle-aged adult population. Males are more commonly affected with Zollinger-Ellison syndrome than females. If left untreated, patients with Zollinger-Ellison syndrome may progress to develop abdominal pain, diarrhea, and heartburn. Common complications of Zollinger-Ellison syndrome include upper gastrointestinal bleeding, anemia, and duodenal ulcer perforation. Prognosis is generally good, and the 5 and 10-year survival rate of patients with Zollinger-Ellison syndrome is approximately 94% and 75%, respectively. The feasibility of surgery depends on the stage of gastrinoma causing Zollinger-Ellison syndrome at the time of diagnosis. However, all patients diagnosed with Zollinger-Ellison syndrome with no metastasis should be offered surgical exploration and resection.

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# Zollinger-Ellison syndrome screening ## Screening Measurement of fasting serum gastrin levels is the single best screening test for Zollinger-Ellison syndrome (ZES). Other tests such as provocative tests include, the secretin stimulation test, calcium stimulation test, secretin-plus-calcium stimulation tests, bombesin test, and protein meal test.

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# Zolmitriptan (nasal spray) Zolmitriptan (nasal spray) is a serotonin (5‑HT) 1B/1D receptor agonist that is FDA approved for the treatment of migraine with or without aura in adults. Common adverse reactions include unusual taste, paresthesia, dizziness, and hyperesthesia.

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# Zolmitriptan adverse reactions Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. In a long-term, open-label study where patients were allowed to treat multiple migraine attacks for up to 1 year, 8% (167 out of 2,058) withdrew from the trial because of adverse reaction. The most common adverse reactions (≥ 5% and > placebo) in these trials were neck/throat/jaw pain, dizziness, paresthesia, asthenia, somnolence, warm/cold sensation, nausea, heaviness sensation, and dry mouth. Table 1 lists the adverse reactions that occurred in ≥2% of the 2,074 patients in any one of the zolmitriptan tablets 1 mg, 2.5 mg, or 5 mg dose groups in the controlled clinical trials of zolmitriptan tablets in patients with migraines (Studies 1, 2, 3, 4, and 5) [see Clinical Studies (14)]. Only adverse reactions that were at least 2% more frequent in a zolmitriptan tablets group compared to the placebo group are included. Several of the adverse reactions appear dose related, notably paresthesia, sensation of heaviness or tightness in chest, neck, jaw, and throat, dizziness, somnolence and possibly asthenia and nausea. There were no differences in the incidence of adverse reactions in controlled clinical trials in the following subgroups: gender, weight, age, use of prophylactic medications, or presence of aura. There were insufficient data to assess the impact of race on the incidence of adverse reactions. In the paragraphs that follow, the frequencies of less commonly reported adverse clinical reactions are presented. Because the reports include reactions observed in open and uncontrolled studies, the role of zolmitriptan in their causation cannot be reliably determined. Furthermore, variability associated with adverse reaction reporting, the terminology used to describe adverse reactions, etc., limit the value of the quantitative frequency estimates provided. Adverse reaction frequencies were calculated as the number of patients who used zolmitriptan tablets and reported a reaction divided by the total number of patients exposed to zolmitriptan tablets (n=4,027). Reactions were further classified within body system categories and enumerated in order of decreasing frequency using the following definitions: infrequent adverse reactions (those occurring in 1/100 to 1/1,000 patients) and rare adverse reactions (those occurring in less than 1/1,000 patients). The following adverse reactions were identified during post approval use of zolmitriptan. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The reactions enumerated include all except those already listed in the Clinical Trials Experience section above or the Warnings and Precautions section. As with other 5-HT1B/1D agonists, there have been reports of anaphylaxis, anaphylactoid, and hypersensitivity reactions including angioedema in patients receiving zolmitriptan. Zolmitriptan is contraindicated in patients with a history of hypersensitivity reaction to zolmitriptan.

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# Zolmitriptan clinical pharmacology Zolmitriptan binds with high affinity to human recombinant 5-HT1D and 5-HT1B receptors, and moderate affinity for 5-HT1A receptors. The N-desmethyl metabolite also has high affinity for 5-HT1B/1D and moderate affinity for 5-HT1A receptors. Migraines are likely due to local cranial vasodilatation and/or to the release of sensory neuropeptides (vasoactive intestinal peptide, substance P and calcitonin gene-related peptide) through nerve endings in the trigeminal system. The therapeutic activity of zolmitriptan for the treatment of migraine headache is thought to be due to the agonist effects at the 5-HT1B/1D receptors on intracranial blood vessels (including the arteriovenous anastomoses) and sensory nerves of the trigeminal system which result in cranial vessel constriction and inhibition of pro-inflammatory neuropeptide release. Zolmitriptan is well absorbed after oral administration for both zolmitriptan tablets and zolmitriptan orally disintegrating tablets. Zolmitriptan displays linear kinetics over the dose range of 2.5 to 50 mg. The AUC and Cmax of zolmitriptan are similar following administration of zolmitriptan tablets and zolmitriptan orally disintegrating tablets, but the Tmax is somewhat later with zolmitriptan orally disintegrating tablets, with a median Tmax of 3 hours for zolmitriptan orally disintegrating tablet compared with 1.5 hours for the zolmitriptan tablet. The AUC, Cmax, and Tmax for the active N-desmethyl metabolite are similar for the two formulations. During a moderate to severe migraine attack, mean AUC0-4 and Cmax for zolmitriptan, dosed as a zolmitriptan tablet, were decreased by 40% and 25%, respectively, and mean Tmax was delayed by one-half hour compared to the same patients during a migraine free period. Mean absolute bioavailability is approximately 40%. The mean apparent volume of distribution is 7 L/kg. Plasma protein binding of zolmitriptan is 25% over the concentration range of 10 to 1000 ng/mL. Zolmitriptan is converted to an active N-desmethyl metabolite; the metabolite concentrations are about two-thirds that of zolmitriptan. Because the 5HT1B/1D potency of the metabolite is 2 to 6 times that of the parent compound, the metabolite may contribute a substantial portion of the overall effect after zolmitriptan administration. Total radioactivity recovered in urine and feces was 65% and 30% of the administered dose, respectively. About 8% of the dose was recovered in the urine as unchanged zolmitriptan. Indole acetic acid metabolite accounted for 31% of the dose, followed by N-oxide (7%) and N-desmethyl (4%) metabolites. The indole acetic acid and N-oxide metabolites are inactive. Mean total plasma clearance is 31.5 mL/min/kg, of which one-sixth is renal clearance. The renal clearance is greater than the glomerular filtration rate suggesting renal tubular secretion. In patients with severe hepatic impairment, the mean Cmax, Tmax, and AUC0-∞ of zolmitriptan were increased 1.5-fold, 2-fold (2 vs. 4 hours), and 3-fold, respectively, compared to subjects with normal hepatic function. Seven out of 27 patients experienced 20 to 80 mm Hg elevations in systolic and/or diastolic blood pressure after a 10 mg zolmitriptan dose. Adjust the zolmitriptan dose in patients with moderate or severe hepatic impairment [see Dosage and Administration (2.3) and Use in Specific Populations (8.6)]. Clearance of zolmitriptan was reduced by 25% in patients with severe renal impairment (Clcr ≥ 5 ≤ 25 mL/min) compared to subjects with normal renal function (Clcr ≥ 70 mL/min); no significant change in clearance was observed in patients with moderate renal impairment (Clcr≥ 26 ≤ 50 mL/min). Zolmitriptan pharmacokinetics in healthy elderly non-migraineur volunteers (age 65 to 76 years) was similar to those in younger non-migraineur volunteers (age 18 to 39 years). No differences in the pharmacokinetics of zolmitriptan or its effects on blood pressure were seen in mild to moderate hypertensive volunteers compared with normotensive controls. All drug interaction studies were performed in healthy volunteers using a single 10 mg dose of zolmitriptan and a single dose of the other drug except where otherwise noted. Following one week of administration of moclobemide (150 mg twice daily), a specific MAO-A inhibitor, there was an increase of about 25% in both Cmax and AUC for zolmitriptan and a 3-fold increase in the Cmax and AUC of the active N-desmethyl metabolite of zolmitriptan. MAO inhibitors are contraindicated in zolmitriptan-treated patients [see Contraindications (4), Warnings and Precautions (5.7), and Drug Interactions (7.2, 7.4)]. Selegiline, a selective MAO-B inhibitor, at a dose of 10 mg/day for 1 week, had no effect on the pharmacokinetics of zolmitriptan and its metabolite. Following the administration of cimetidine, the half-life and AUC of zolmitriptan (5 mg dose), and its active metabolite, were approximately doubled [see Dosage and Administration (2.4), Drug Interactions (7.5)]. Cmax and AUC of zolmitriptan were increased 1.5-fold after one week of dosing with propranolol (160 mg/day). Cmax and AUC of the N-desmethyl metabolite were reduced by 30% and 15%, respectively. There were no changes in blood pressure or pulse rate following administration of propranolol with zolmitriptan. A single 1 gram dose of acetaminophen did not alter the pharmacokinetics of zolmitriptan and its N-desmethyl metabolite. However, zolmitriptan administration delayed the Tmax of acetaminophen by one hour. Retrospective analysis of pharmacokinetic data across studies indicated that mean Cmax and AUC of zolmitriptan were increased by 30% and 50%, respectively, and Tmax was delayed by one-half hour in women taking oral contraceptives. The effect of zolmitriptan on the pharmacokinetics of oral contraceptives has not been studied.

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# Zolmitriptan clinical studies The efficacy of zolmitriptan tablets in the acute treatment of migraine headaches was demonstrated in five randomized, double-blind, placebo-controlled studies (Studies 1, 2, 3, 4, and 5), of which two utilized the 1 mg dose, two utilized the 2.5 mg dose and four utilized the 5 mg dose. In Study 1, patients treated their headaches in a clinic setting. In the other studies, patients treated their headaches as outpatients. In Study 4, patients who had previously used sumatriptan were excluded, whereas in the other studies no such exclusion was applied. Patients enrolled in these 5 studies were predominantly female (82%) and Caucasian (97%) with a mean age of 40 years (range 12 to 65). Patients were instructed to treat a moderate to severe headache. Headache response, defined as a reduction in headache severity from moderate or severe pain to mild or no pain, was assessed at 1, 2, and, in most studies, 4 hours after dosing. Associated symptoms such as nausea, photophobia, and phonophobia were also assessed. Maintenance of response was assessed for up to 24 hours post-dose. A second dose of zolmitriptan tablets or other medication was allowed 2 to 24 hours after the initial treatment for persistent and recurrent headache. The frequency and time to use of these additional treatments were also recorded. In all studies, the effect of zolmitriptan was compared to placebo in the treatment of a single migraine attack. In all five studies, the percentage of patients achieving headache response 2 hours after treatment was significantly greater among patients who received zolmitriptan tablets at all doses (except for the 1 mg dose in the smallest study) compared to those who received placebo. In Studies 1 and 3, there was a statistically significant greater percentage of patients with headache response at 2 hours in the higher dose groups (2.5 and/or 5 mg) compared to the 1 mg dose group. There were no statistically significant differences between the 2.5 and 5 mg dose groups (or of doses up to 20 mg) for the primary end point of headache response at 2 hours in any study. The results of these controlled clinical studies are summarized in Table 2. The estimated probability of achieving an initial headache response by 4 hours following treatment in pooled Studies 2, 3, and 5 is depicted in Figure 1. For patients with migraine associated photophobia, phonophobia, and nausea at baseline, there was a decreased incidence of these symptoms following administration of zolmitriptan tablets as compared with placebo. Two to 24 hours following the initial dose of study treatment, patients were allowed to use additional treatment for pain relief in the form of a second dose of study treatment or other medication. The estimated probability of patients taking a second dose or other medication for migraine over the 24 hours following the initial dose of study treatment is summarized in Figure 2. The efficacy of zolmitriptan was unaffected by presence of aura; duration of headache prior to treatment; relationship to menses; gender, age, or weight of the patient; pre-treatment nausea or concomitant use of common migraine prophylactic drugs. The efficacy of zolmitriptan 2.5 mg orally disintegrating tablets was demonstrated in a randomized, placebo-controlled trial (Study 6) that was similar in design to the trials of zolmitriptan tablets. Patients were instructed to treat a moderate to severe headache. Of the 471 patients treated in Study 6, 87% were female and 97% were Caucasian, with a mean age of 41 years (range 18 to 62). At 2 hours post-dosing, there was a statistically significant greater percentage of patients treated with zolmitriptan orally disintegrating tablets 2.5 mg with a headache response (reduction in headache severity from moderate or severe pain to mild or no headache) compared to patients treated with placebo (63% vs. 22%). The estimated probability of achieving an initial headache response by 2 hours following treatment with zolmitriptan orally disintegrating tablets is depicted in Figure 3. For patients with migraine-associated photophobia, phonophobia and nausea at baseline, there was a decreased incidence of these symptoms following administration of zolmitriptan orally disintegrating tablets as compared to placebo. Two to 24 hours following the initial dose of study treatment, patients were allowed to use additional treatment in the form of a second dose of study treatment or other medication. The estimated probability of patients taking a second dose or other medication for migraine over the 24 hours following the initial dose of study treatment in Study 6 is summarized in Figure 4.

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# Zolmitriptan description Zolmitriptan orally disintegrating tablets contain zolmitriptan, which is a selective 5-hydroxytryptamine1B/1D (5-HT1B/1D) receptor agonist. Zolmitriptan is chemically designated as (S)-4-[[3-[2-(dimethylamino)ethyl]-1H-indol-5-yl]methyl]-2-oxazolidinone and has the following chemical structure: The molecular formula is C16H21N3O2, representing a molecular weight of 287.36. Zolmitriptan is a white to off-white powder that is soluble in methanol and acetone, insoluble in water. Zolmitriptan orally disintegrating tablets are available as 2.5 mg and 5 mg white uncoated tablets for oral administration. The orally disintegrating tablets contain mannitol, microcrystalline cellulose, crospovidone, aspartame [see Warnings and Precautions (5.9)], colloidal silicon dioxide, talc, magnesium stearate and peppermint flavor. The peppermint flavor contains corn starch.

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# Zolmitriptan dosage and administration The recommended starting dose of zolmitriptan is 1.25 mg or 2.5 mg. The 1.25 mg dose can be achieved by manually breaking the functionally-scored 2.5 mg zolmitriptan tablet in half. The maximum recommended single dose of zolmitriptan is 5 mg. In controlled clinical trials, a greater proportion of patients had headache response following a 2.5 mg or 5 mg dose than following a 1 mg dose. There was little added benefit from the 5 mg dose compared to the 2.5 mg dose, but adverse reactions were more frequent with the 5 mg dose. If the migraine has not resolved by 2 hours after taking zolmitriptan, or returns after a transient improvement, a second dose may be administered at least 2 hours after the first dose. The maximum daily dose is 10 mg in any 24-hour period. Instruct patients not to break zolmitriptan orally disintegrating tablets because they are not functionally-scored. Administration with liquid is not necessary. Orally disintegrating tablets are packaged in a blister pack. Instruct patients not to remove the tablet from the blister until just prior to dosing. Subsequently, instruct patients to peel the blister pack open, and to place the orally disintegrating tablet on the tongue, where it will dissolve and it will be swallowed with the saliva. The recommended dose of zolmitriptan in patients with moderate to severe hepatic impairment is 1.25 mg (one-half of one 2.5 mg zolmitriptan tablet) because of increased zolmitriptan blood levels in these patients and elevation of blood pressure in some of these patients. Limit the total daily dose in patients with severe hepatic impairment to no more than 5 mg per day. The use of zolmitriptan orally disintegrating tablets is not recommended in patients with moderate or severe hepatic impairment because these orally disintegrating tablets should not be broken in half [see Use in Specific Populations (8.6), and Clinical Pharmacology (12.3)]. If zolmitriptan is co-administered with cimetidine, limit the maximum single dose of zolmitriptan to 2.5 mg, not to exceed 5 mg in any 24-hour period [see Drug Interactions (7.5), Clinical Pharmacology (12.3)].

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# Zolmitriptan drug interactions Ergot-containing drugs have been reported to cause prolonged vasospastic reactions. Because these effects may be additive, use of ergotamine-containing or ergot-type medications (like dihydroergotamine or methysergide) and zolmitriptan within 24 hours of each other is contraindicated [see Contraindications (4)]. MAO-A inhibitors increase the systemic exposure of zolmitriptan and its active N-desmethyl metabolite. Therefore, the use of zolmitriptan in patients receiving MAO-A inhibitors is contraindicated [see Contraindications (4) and Clinical Pharmacology (12.3)]. Concomitant use of other 5-HT1B/1D agonists (including triptans) within 24 hours of zolmitriptan treatment is contraindicated because the risk of vasospastic reactions may be additive [see Contraindications (4)]. Cases of life-threatening serotonin syndrome have been reported during co-administration of triptans and selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) [see Warnings and Precautions (5.7)]. Following administration of cimetidine, the half-life and blood levels of zolmitriptan and its active N-desmethyl metabolite were approximately doubled [see Clinical Pharmacology (12.3)]. If cimetidine and zolmitriptan are used concomitantly, limit the maximum single dose of zolmitriptan to 2.5 mg, not to exceed 5 mg in any 24-hour period [see Dosage and Administration, (2.4) and Clinical Pharmacology (12.3)].

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# Zolmitriptan how supplied storage and handling 2.5 mg Orally Disintegrating Tablets - White to off white, round tablets debossed 'F7' on one side and plain on the other side are supplied in cartons containing a blister pack of 6 unit-dose tablets (NDC 68462-499-76) 5 mg Orally Disintegrating Tablets - White to off-white, round tablets debossed 'F11'on one side and plain on the other side are supplied in cartons containing a blister pack of 3 unit-dose tablets (NDC 68462-500-33)

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# Zolmitriptan nonclinical toxicology Zolmitriptan was administered to mice and rats at doses up to 400 mg/kg/day. Mice were dosed for 85 weeks (males) and 92 weeks (females); rats were dosed for 101 weeks (males) and 86 weeks (females). There was no evidence of drug-induced tumors in mice at plasma exposures (AUC) up to approximately 700 times that in humans at the maximum recommended human dose (MRHD) of 10 mg/day. In rats, there was an increase in the incidence of thyroid follicular cell hyperplasia and thyroid follicular cell adenomas in male rats receiving 400 mg/kg/day. No increase in tumors was observed in rats at 100 mg/kg/day, a dose associated with a plasma AUC approximately 700 times that in humans at the MRHD. Zolmitriptan was positive in an in vitro bacterial reverse mutation (Ames) assay and in an in vitro chromosomal aberration assay in human lymphocytes. Zolmitriptan was negative in an in vitro mammalian gene cell mutation (CHO/HGPRT) assay and in oral in vivo mouse micronucleus assays in mouse and rat. Studies of male and female rats administered zolmitriptan prior to and during mating and up to implantation showed no impairment of fertility at oral doses up to 400 mg/kg/day. The plasma exposure (AUC) at this dose was approximately 3000 times that in humans at the MRHD.

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# Zolmitriptan overdosage There is no specific antidote to zolmitriptan. In cases of severe intoxication, intensive care procedures are recommended, including establishing and maintaining a patent airway, ensuring adequate oxygenation and ventilation, and monitoring and support of the cardiovascular system. The elimination half-life of zolmitriptan is 3 hours [see Clinical Pharmacology (12.1)]; therefore, monitor patients after overdose with zolmitriptan for at least 15 hours or until symptoms or signs resolve. It is unknown what effect hemodialysis or peritoneal dialysis has on the plasma concentrations of zolmitriptan.

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# Zolmitriptan patient counseling information Inform patients that zolmitriptan may cause serious cardiovascular adverse reactions such as myocardial infarction or stroke, which may result in hospitalization and even death. Although serious cardiovascular reactions can occur without warning symptoms, instruct patients to be alert for the signs and symptoms of chest pain, shortness of breath, weakness, slurring of speech, and instruct them to ask for medical advice when observing any indicative sign or symptoms. Instruct patients to seek medical advice if they have symptoms of other vasospastic reactions [see Warnings and Precautions (5.1, 5.2, 5.4, 5.5)]. Inform patients about the risk of serotonin syndrome with the use of zolmitriptan or other triptans, particularly during combined use with selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) [see Warnings and Precautions (5.7)]. Inform patients that zolmitriptan should not be used during pregnancy unless the potential benefit justifies the potential risk to the fetus [see Use in Specific Populations (8.1)]. Inform patients not to break zolmitriptan orally disintegrating tablets. Inform patients that the orally disintegrating tablet is packaged in a blister. Instruct patients not to remove the orally disintegrating tablet from the blister until just prior to dosing. Instruct patients that prior to dosing, peel open the blister pack and place the orally disintegrating tablet on the tongue, where it will dissolve and be swallowed with the saliva [see Dosage and Administration (2.2)].

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/index.php/Zolmitriptan_use_in_specific_populations

# Zolmitriptan use in specific populations Pregnancy Category C: There are no adequate and well-controlled studies in pregnant women; therefore, zolmitriptan should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. In reproductive toxicity studies in rats and rabbits, oral administration of zolmitriptan to pregnant animals resulted in embryolethality and fetal abnormalities (malformations and variations) at clinically relevant exposures. When zolmitriptan was administered to pregnant rats during the period of organogenesis at oral doses of 100, 400, and 1200 mg/kg/day (plasma exposures (AUCs) ≈280, 1100, and 5000 times the human AUC at the maximum recommended human dose (MRHD) of 10 mg/day), there was a dose-related increase in embryolethality. A no-effect dose for embryolethality was not established. When zolmitriptan was administered to pregnant rabbits during the period of organogenesis at oral doses of 3, 10, and 30 mg/kg/day (plasma AUCs ≈1, 11, and 42 times the human AUC at the MRHD), there were increases in embryolethality and in fetal malformations and variations. The no-effect dose for adverse effects on embryo-fetal development was associated with a plasma AUC similar to that in humans at the MRHD. When female rats were given zolmitriptan during gestation, parturition, and lactation at oral doses of 25, 100, and 400 mg/kg/day (plasma AUCs ≈70, 280, and 1100 times that in human at the MRHD), an increased incidence of hydronephrosis was found in the offspring. The no-effect dose was associated with a plasma AUC ≈280 times that in humans at the MRHD. It is not known whether zolmitriptan is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from zolmitriptan, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. In rats, oral dosing with zolmitriptan resulted in levels in milk up to 4 times higher than in plasma. The safety and effectiveness in pediatric patients have not been established. Therefore, zolmitriptan orally disintegrating tablets are not recommended for use in patients under 18 years of age. One randomized, placebo-controlled clinical trial of zolmitriptan tablets (2.5, 5 and 10 mg) evaluated 696 pediatric patients (aged 12 to 17 years) with migraines. This study did not demonstrate the efficacy of zolmitriptan compared to placebo in the treatment of migraine in adolescents. Adverse reactions in the adolescent patients treated with zolmitriptan were similar in nature and frequency to those reported in clinical trials in adults treated with zolmitriptan. Zolmitriptan has not been studied in pediatric patients less than 12 years old. Clinical studies of zolmitriptan did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. A cardiovascular evaluation is recommended for geriatric patients who have other cardiovascular risk factors (e.g., diabetes, hypertension, smoking, obesity, strong family history of coronary artery disease) prior to receiving zolmitriptan [see Warnings and Precautions (5.1)]. After oral zolmitriptan administration, zolmitriptan blood levels were increased in patients with moderate to severe hepatic impairment, and significant elevation in blood pressure was observed in some of these patients [see Warnings and Precautions (5.8)]. Therefore, adjust the zolmitriptan dose and administer with caution in patients with moderate or severe hepatic impairment [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3)].

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/index.php/Zolmitriptan_warnings_and_precautions

# Zolmitriptan warnings and precautions Zolmitriptan is contraindicated in patients with ischemic or vasospastic coronary artery disease (CAD). There have been rare reports of serious cardiac adverse reactions, including acute myocardial infarction, occurring within a few hours following administration of zolmitriptan. Some of these reactions occurred in patients without known CAD. 5-HT1agonists including zolmitriptan may cause coronary artery vasospasm (Prinzmetal Angina), even in patients without a history of CAD. Perform a cardiovascular evaluation in triptan-naïve patients who have multiple cardiovascular risk factors (e.g., increased age, diabetes, hypertension, smoking, obesity, strong family history of CAD) prior to receiving zolmitriptan. Do not administer zolmitriptan if there is evidence of CAD or coronary artery vasospasm [see Contraindications (4)]. For patients with multiple cardiovascular risk factors who have a negative cardiovascular evaluation, consider administering the first zolmitriptan dose in a medically-supervised setting and performing an electrocardiogram (ECG) immediately following zolmitriptan administration. For such patients, consider periodic cardiovascular evaluation in intermittent long-term users of zolmitriptan. Life-threatening disturbances of cardiac rhythm including ventricular tachycardia and ventricular fibrillation leading to death have been reported within a few hours following the administration of 5-HT1 agonists. Discontinue zolmitriptan if these disturbances occur. Zolmitriptan is contraindicated in patients with Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders [see Contraindications (4)]. As with other 5-HT1 agonists, sensations of tightness, pain, and pressure in the chest, throat, neck, and jaw commonly occur after treatment with zolmitriptan and is usually non-cardiac in origin. However, perform a cardiac evaluation if these patients are at high cardiac risk. 5-HT1 agonists including zolmitriptan are contraindicated in patients with CAD or Prinzmetal's variant angina [see Contraindications (4)]. As with other acute migraine therapies, before treating headaches in patients not previously diagnosed as migraineurs, and in migraineurs who present with symptoms atypical for migraine, exclude other potentially serious neurological conditions. Zolmitriptan is contraindicated in patients with a history of stroke or transient ischemic attack [see Contraindications (4)]. 5-HT1 agonists, including zolmitriptan, may cause non-coronary vasospastic reactions, such as peripheral vascular ischemia, gastrointestinal vascular ischemia and infarction (presenting with abdominal pain and bloody diarrhea), splenic infarction, and Raynaud's syndrome. In patients who experience symptoms or signs suggestive of a vasospastic reaction following the use of any 5-HT1 agonist, rule out a vasospastic reaction before receiving additional zolmitriptan doses [see Contraindications (4)]. Reports of transient and permanent blindness and significant partial vision loss have been reported with the use of 5-HT1 agonists. Since visual disorders may be part of a migraine attack, a causal relationship between these events and the use of 5-HT1 agonists have not been clearly established. Overuse of acute migraine drugs (e.g. ergotamine, triptans, opioids, or a combination of drugs for 10 or more days per month) may lead to exacerbation of headache (medication overuse headache). Medication overuse headache may present as migraine-like daily headaches or as a marked increase in frequency of migraine attacks. Detoxification of patients, including withdrawal of the overused drugs, and treatment of withdrawal symptoms (which often includes a transient worsening of headache) may be necessary. Serotonin syndrome may occur with triptans, including zolmitriptan, particularly during co-administration with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and MAO inhibitors [see Drug Interactions (7.5)]. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The onset of symptoms usually rapidly occurs within minutes to hours of receiving a new or a greater dose of a serotonergic medication. Discontinue zolmitriptan if serotonin syndrome is suspected [see Drug Interactions (7.4)]. Significant elevations in systemic blood pressure have been reported in patients treated with 5-HT1 agonists including patients without a history of hypertension; very rarely, these increases in blood pressure have been associated with serious adverse reactions. In healthy subjects treated with 5 mg of zolmitriptan, an increase of 1 and 5 mm Hg in the systolic and diastolic blood pressure, respectively, was seen. In a study of patients with moderate to severe liver impairment, 7 of 27 patients experienced 20 to 80 mm Hg elevations in systolic and/or diastolic blood pressure after a dose of 10 mg of zolmitriptan. As with all triptans, blood pressure should be monitored in zolmitriptan-treated patients. Zolmitriptan is contraindicated in patients with uncontrolled hypertension [see Contraindications (4)]. Phenylalanine can be harmful to patients with phenylketonuria (PKU). Zolmitriptan orally disintegrating tablets contain phenylalanine (a component of aspartame). Each 2.5 mg and 5 mg orally disintegrating tablet contains 1.12 and 2.24 mg of phenylalanine, respectively.

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/index.php/Zolpidem_(mucous_membrane_spray)

# Zolpidem (mucous membrane spray) Zolpidem (mucous membrane spray) is a gamma-aminobutyric acid (GABA) A agonist that is FDA approved for the treatment of insomnia characterized by difficulties with sleep initiation. Common adverse reactions include drowsiness, dizziness, diarrhea, and drugged feelings.

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/index.php/Zolpidem_detailed_information

# Zolpidem detailed information Zolpidem is a prescription short-acting nonbenzodiazepine hypnotic that potentiates gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, by binding to benzodiazepine receptors which are located on the gamma-aminobutyric acid receptors. Zolpidem is used for the short-term treatment of insomnia. It works quickly (usually within 15 minutes) and has a short half-life (2-3 hours). Some trade names of zolpidem are Ambien, Stilnox, Stilnoct, Hypnogen, Zolt, Zolfresh, Nimadorm, Sanval, and Myslee. Its hypnotic effects are similar to those of the benzodiazepine class of drugs, but it is molecularly distinct from the classical benzodiazepine molecule and is actually classified as an imidazopyridine. Flumazenil, a benzodiazepine receptor antagonist, which is used for benzodiazepine overdose, can also reverse zolpidem's sedative/hypnotic effects. As an anticonvulsant and muscle relaxant, the beneficial effects start to emerge at 10 and 20 times the dose required for sedation, respectively. For that reason, it has never been approved for either muscle relaxation or seizure prevention. Such drastically increased doses are more inclined to induce one or more negative side effects, including hallucinations and/or amnesia. (See below.) The patent 4382938 in the United States on zolpidem was held by the French pharmaceutical corporation Sanofi-Aventis. On April 23, 2007 the US FDA approved 13 generic versions of zolpidem tartrate. Zolpidem is available from several generic manufacturers in the UK, as generic from Sandoz in South Africa, as well as from other manufacturers such as ratiopharm. Recently, zolpidem has been cited in various medical reports mainly in the United Kingdom as waking persistent vegetative state (PVS) patients, and dramatically improving the conditions of people with brain injuries. Zolpidem is approved for the short-term (usually two to six weeks) treatment of insomnia, and it has been studied for nightly use up to six months in a single-blind trial published in 1991, an open-label study lasting 180 days published in 1992 (with continued efficacy in patients who had kept taking it as of 180 days after the end of the trial), and in an open-label trial lasting 179 days published in 1993. The United States Air Force uses zolpidem, under trade name Ambien, as "no-go pills" to help pilots sleep after a mission; another drug used for the same purpose is temazepam (Restoril). (Cf. the "go-pills" amphetamine, served under the name Dexedrine, or its recent modafinil (Provigil) replacement, act as a stimulant for the same pilots, the effects of which are reversed by the aforementioned "no-go pills") Zolpidem is also used off-label to treat restless leg syndrome and, as is the case with many prescription sedative/hypnotic drugs, it is sometimes used by stimulant users to "come down" after the use of stimulants such as methamphetamine, cocaine, MDMA (ecstasy), or amphetamine. Recently, the drug has been reported anecdotally to have positive effects for patients in persistent vegetative state. Results from phase IIa trials are expected in June 2007. The trials are being conducted by Regen Therapeutics of the UK, who have a patent pending on this new use for Zolpidem. A clinical trial on a single patient performed at the Toulouse University Hospital using PET shows that zolpidem repeatably improves brain function and mobility of a patient immobilized by akinetic mutism caused by hypoxia. Zolpidem binds with high affinity to the α1 containing GABAA receptors, about 10-fold lower affinity for those containing the α2, α3-GABAA receptor subunits, and with no appreciable affinity for α5 subunit containing receptors. Like the vast majority of benzodiazepine like molecules, zolpidem has no affinity for α4 and α6 subunit containing receptors. Zolpidem positively modulates GABAA receptors, probably by increasing the GABAa receptor complexes apparent affinity for GABA, without effect desensitization, or peak current. Zolpidem increases slow wave sleep and caused no effect on stage 2 sleep in laboratory tests. A meta-analysis of the randomised controlled clinical trials which compared benzodiazepines against Z drugs has shown that there are few consistent differences between zolpidem and benzodiazepines in terms of sleep onset latency, total sleep duration, number of awakenings, quality of sleep, adverse events, tolerance, rebound insomnia and daytime alertness. Zolpidem recreational users may take the drug orally, crush and snort it, or cook it for an intravenous injection. Intravenous use is especially hazardous as doses as low as 5mg can produce complete unconsciousness within seconds. The transition from medicinal use to recreational use of Zolpidem can occur when used longer than recommended (no longer than a few weeks), at high doses (more than the usual 10mg), and in people who have been dependent on other drugs or alcohol in the past. Zolpidem effects can increase and intensify if mixed with other substances like alcohol. Recreational use of this drug (specifically the Ambien brand) is becoming more common in young people. Recreational users claim that "fighting" the effects of the drug by forcing themselves to stay awake will sometimes cause vivid visuals and a body high (see side-effects below). However, in some people who are already in an anxious state, or suffer from neurosis it is not hard, if a struggle at all, to fight the main effect of sedation, experiencing the side-effect of euphoria more than the sedation itself. Thus some users report decreased anxiety, and even mild euphoria, as well as perceptual changes, visual distortions, and light-based hallucinations. Auditory distortions have been reported in some users. Odd behavior, confusion, and loss of balance have been reported among the various effects of the drug. To counteract recreational use of zolpidem in the United States, Sanofi-Aventis coats their pills with a flexible plastic-like coating, which sticks to unpulverized "bumps" or "chunks" and can be difficult to remove, thus hindering the process of insufflation; although this is a relatively minor obstacle to an experienced recreational drug user. With high dose regular use or abuse of zolpidem there can be a risk of a severe physical dependence on zolpidem with cases being reported in the medical literature of epileptic seizures forming part of the withdrawal syndrome. One case involved a woman detoxing off a high dose of zolpidem experiencing a generalised seizure. The clinical withdrawal and dependence effects were reported to be similar to those of benzodiazepines in this case report. Zolpidem and other sedative hypnotic drugs are detected frequently in cases of people suspected of driving under the influence of drugs. Other drugs including the benzodiazepines and zopiclone are also found in high numbers of suspected drugged drivers. Many drivers have blood levels far exceeding the therapeutic dose range suggesting a high degree of excessive-use potential for benzodiazepines, zolpidem and zopiclone. As Ambien's patent expired April 21, 2007, new generic versions were approved, which do not have the "protective cover" present on the Sanofi name-brand Ambien. Alcohol has cross tolerance with GABAa receptor positive modulators such as the benzodiazepines and the nonbenzodiazepine drugs. For this reason alcoholics or recovering alcoholics may be at increased risk of physical dependency on zolpidem. Also, alcoholics and drug abusers may be at increased risk of abusing and or becoming psychologically dependent on zolpidem. Zolpidem should be avoided in those with a history of Alcoholism, drug misuse (illicit or prescription misuse), or in those with history of physical dependency or psychological dependency on sedative-hypnotic drugs. Overdose of zolpidem may present with excessive sedation, pin-point pupils, depressed respiratory function, which may progress to coma and possibly death. Zolpidem combined with alcohol, opiates or other CNS depressants may be even more likely to lead to fatal overdoses. Zolpidem overdosage can be treated with the benzodiazepine receptor antagonist flumazenil which displaces zolpidem from its binding site the benzodiazepine receptor and therefore rapidly reverses the effects of zolpidem. Some users take zolpidem recreationally for these side effects. However, it may be less common than benzodiazepine abuse. In the United States, recreational use may be less common than in countries where the drug is available as a less expensive generic (or in countries, such as the UK, where prescriptions are free or heavily subsidised). It is not yet known whether there is a link between the cost and availability of zolpidem and the level at which it is abused. Zolpidem can become addictive if taken for extended periods of time, due to dependence on its ability to put one to sleep or to the euphoria it can sometimes produce. Like most addictive drugs, a tolerance in the zolpidem user develops and increases all the more quickly the longer the user has been regularly taking it. Under the influence of the drug it is common to take more zolpidem than is necessary due to either forgetting that one has already taken a pill (elderly users are particularly at risk here), or knowingly taking more than the prescribed dosage. Users with a predilection for abuse are advised to keep additional zolpidem in a safe place that is unlikely to be remembered or accessed while intoxicated to avoid this risk. A trustworthy friend or relative is the best defense if such people are available; otherwise, a box or cupboard locked with a combination padlock is a good defense against this tendency, as the above-mentioned side-effects can easily prevent a user from operating such a lock while under the drug's influence. The recent release of Ambien CR® (zolpidem tartrate extended release) in the United States renewed interest in the drug among recreational drug users. Before a user becomes fully acclimated to these effects (or if the user does not become acclimated), these symptoms can be severe enough to be deemed as drug-induced psychosis. Incidentally, antipsychotics like ziprasidone (Geodon®) or quetiapine (Seroquel®) may be prescribed alongside zolpidem to both combat these side effects and to aid in sleep-induction, as both of them contain mild hypnotic properties. However, because some antidepressants are known for being mildly sedating (i.e., paroxetine), it may be inadvisable to use zolpidem and an antidepressant simultaneously. Some zolpidem users (especially those suffering from chronic insomnia), however, commonly use these drug combination due to the relative ease with which the user gains no benefit from one or the others of these drugs, while both together can assist sufferers of insomnia in getting to sleep. Some users have reported unexplained sleepwalking while using Ambien, and a few have reported driving, binge eating, sleep talking, and performing other daily tasks while sleeping. The sleepwalker can sometimes perform these tasks as normally as they might if they were awake. They can sometimes carry on complex conversations and respond appropriately to questions or statements so much so that the observer may believe the sleepwalker to be awake. This is similar to, but unlike typical sleep talking, which can usually be identified easily and is characterised by incoherent speech that often has no relevance to the situation or that is so disorganised as to be completely unintelligible. These statements bear a strong resemblance to that of schizophasia, one of many symptoms commonly seen in individuals suffering from schizophrenia. A person under the influence of this medication may seem fully aware of their environment even though they are still asleep. This can bring about concerns for the safety of the sleepwalker and others. Driving while under the drug's influence is generally considered several orders of magnitude more dangerous than the average drunk driver, due to the diminished motor controls and delusions that may affect the user. It is unclear if the drug is responsible for the behavior, but a class-action lawsuit was filed against Sanofi-Aventis in March 2006 on behalf of those who reported symptoms. Residual 'hangover' effects such as sleepiness, impaired psychomotor and cognitive after nighttime administration may persist into the next day which may impair the ability of users to drive safely, increase risks of falls and hip fractures. More recently, the Sydney Morning Herald in Australia reported on 4 March 2007 that a man who fell 30 metres to his death from a high-rise unit balcony may have been sleepwalking under the influence of Stilnox. The coverage prompted over 40 readers to contact the newspaper with their own accounts of Stilnox related automatism and the drug is now under review by the Adverse Drug Reactions Advisory Committee. On March 14, 2007, the US Food and Drug Administration ordered stronger warnings on 13 prescription sleep-hypnotic drugs including zolpidem and eszopiclone. The dangers of allergic reactions and driving while intoxicated, while serious, are not thought to be sufficient to withdraw the drugs from the market. The media reports of side effects of Zolpidem have caused them to become referred to in popular culture. In the Simpsons episode Crook and Ladder, Homer Simpson becomes addicted to an insomnia pill known as Nappien and starts experiencing strange side effects. To this, Lisa Simpsons says "I've read that people do strange things in their sleep when they've taken Ambien... I mean Nappien."

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/index.php/Zomepirac

# Zomepirac Zomepirac is an orally effective NSAID that has antipyretic actions. It was developed by McNeil Pharmaceutical and approved by the FDA in 1980 and sold as the sodium salt, zomepirac sodium, under the brand name Zomax. Due to its clinical effectiveness, it was preferred by doctors in many situations and obtained a large share of the analgesics market; however, it was subsequently withdrawn in March 1983 due to its tendency to cause serious anaphylaxis in an unpredictable subset of the patient population. Zomepirac was indicated for the management of mild to severe pain. Multiple clinical trials demonstrated zomepirac to be more effective than aspirin or codeine alone and to be as effective as analgesic combinations containing codeine or other opioids. Zomepirac provided analgesia comparable with usual intramuscular doses of morphine in postoperative pain and that with long-term use, neither tolerance to its analgesic effect nor psychological or physical dependence had been demonstrated.

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/index.php/Zona_fasciculata

# Zona fasciculata Cells of the zona fasciculata, the middle zone of the adrenal cortex, sits directly beneath the zona glomerulosa and are organized in bundles (or fascicles).

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/index.php/Zona_glomerulosa

# Zona glomerulosa The zona glomerulosa of the adrenal gland is the most superficial layer of the adrenal cortex, lying directly beneath the adrenal gland's capsule. Its cells are ovoid in shape and are arranged in clusters or arches (glomus is Latin for "ball"). In response to increased potassium levels or decreased blood flow to the kidneys, cells of the zona glomerulosa secrete the mineralocorticoid aldosterone into the blood as part of the renin-angiotensin system. Aldosterone regulates the body's concentration of electrolytes, primarily sodium and potassium, by acting on the distal convoluted tubule of kidney nephrons to:

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/index.php/Zona_limitans_intrathalamica

# Zona limitans intrathalamica Template:Cleanup The zona limitans intrathalamica (ZLI) is a transverse boundary located between the prethalamus (previously also known as ventral thalamus) and the functional distinct thalamus (dorsal thalamus. Besides its morphological characteristics, it bears the hallmarks of a signalling centre. Fate mapping experiments in chick have shown that the ZLI is cell lineage restricted at its boundaries and therefore can be termed a true developmental compartment in the forebrain. Besides morphological characteristics, the ZLI is the only structure in the alar plate of the neural tube that expresses the signalling molecule Sonic hedgehog; Shh. In mouse, the function of Hh signalling at the ZLI has not been addressed directly due to a complete absence of the diencephalon in Shh mutants. Studies in chick have shown that Shh is necessary and sufficient for both prethalamic expression of Dlx2 and thalamic expression of Gbx2 and Sox14. In zebrafish, the structure corresponding to the Shh expression has been termed as mid-diencephalic boundary (MDB) but subsequently referred to as ZLI, in keeping with pre-existing terminology for other vertebrates. In zebrafish, it was shown that the expression of two shh genes, shh-a and shh-b (formerly described as twhh) mark the ZLI territory, and that ZLI development is accompanied by expression of pro-neural genes: anteriorly of dlx2a, a marker of the prethalamus, and posteriorly of dbx1a, a marker of the thalamus. Shh signalling is sufficient for the molecular differentiation of both the prethalamus and the thalamus but is not required for their maintenance and Shh signalling from the ZLI in the alar plate is sufficient for the maturation of prethalamic and thalamic territory while ventral Shh signals are dispensable. The Zona limitans intrathalamica (ZLI) expresses the Sonic-hedgehog (Shh) gene. The picture show a lateral view of the brain of a zebrafish embryo at 42 post fertilisation after double in situ hybridization with a probe against shh-a and dlx2a. The ZLI (red) marks the V-shaped boundary between the two Prethalami (PT; blue) and Thalamus (Th; yellow) in a pseudo-frontal view. by Steffen Scholpp

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/index.php/Zona_reticularis

# Zona reticularis The Zona reticularis is the innermost layer of the adrenal cortex, which is the outer portion of the adrenal gland, a gland found above the kidneys (which is why it is also known as the suprarenal gland). The adrenal gland produces norepinephrine and epineprhine (known as adrenaline in British nomenclature, hence the gland's name) in the adrenal medulla. Within the cortex, the gland produces mineralocorticoids such as aldosterone in the outermost zona glomerulosa (regulating salt balance), glucocorticoids such as cortisol in the middle zona fasciculata (regulating carbohydrate, protein and lipid metabolism), and androgens such as dehydroepiandrosterone (DHEA), which is an important sex hormone in females. The zona reticularis lies beneath the zona fasciculata and above the adrenal medulla, and its cells are arranged in a network of cords (a reticulum).

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/index.php/Zone_diet

# Zone diet The Zone diet is a diet popularized in books by Barry Sears. It advocates balancing protein and carbohydrate in 3:4 ratios. It is not primarily a weight-loss "diet", though it can be used quite successfully for that purpose . The diet centers on a "40:30:30" ratio of calories obtained daily from carbohydrates, proteins, and fats, respectively. The exact formula is always under debate, but studies over the past several years (including a non-scientific study by the PBS documentary show Scientific American Frontiers) have shown that it can produce weight loss at reasonable rates. The Scientific American Frontiers study compared the effectiveness of several popular 'diet' regimes including the Zone; somewhat to the surprise of the show's staff, the participants on the Zone experienced the greatest fat loss while simultaneously gaining muscle mass. Participants also reported the Zone as the easiest regime to adjust to, i.e. having the fewest adverse affects such as fatigue or hunger. "The Zone" is Sears' term for proper hormone balance. When insulin levels are neither too high nor too low, and glucagon levels are not too high, then specific anti-inflammatory chemicals (types of eicosanoids) are released, which have similar effects to aspirin, but without downsides such as gastric bleeding. Sears claims that a 30:40 ratio of protein to carbohydrates triggers this effect, and this is called 'The Zone.' Sears claims that these natural anti-inflammatories are heart and health friendly. Additionally, the human body in caloric balance is more efficient and does not have to store excess calories as fat. The human body cannot store fat and burn fat at the same time, and Sears believes it takes time (significant time if insulin levels were high because of unbalanced eating) to switch from the former to the latter. Using stored fat for energy causes weight loss. Another key feature of the Zone diet, introduced in his later books, is an intake of the proper ratio of Omega-3 to Omega-6 fatty acids. Dr. Sears is believed to have popularized the taking of pharmaceutical grade Omega 3 fish oils. Sears emphasizes a hormonal paradox of which "low-fat" advocates were unaware, namely that low-fat diets increase the production of the hormone insulin, causing the body to store more fat. He points to the cattle ranching practice of fattening livestock efficiently by feeding them lots of low-fat grain. He and others have noted the irony that human diets in the West for the last twenty years have been full of low-fat carbohydrates, yet people are more obese. Additionally, Sears describes fat consumption as essential for "burning" fat. Monounsaturated fats in a meal contribute to a feeling of fullness and decreases the rate at which carbohydrates are absorbed into the bloodstream. Slower carbohydrate absorption means lower insulin levels which means less stored fat and a faster transition to fat burning. If the body needs energy and can't burn fat because of high insulin levels, a person feels tired as their brain starves and metabolism slows to compensate. This occurs because the brain runs on glucose and high insulin levels deplete blood glucose levels. Such condition, rebound hypoglycemia causes sweet cravings (which just starts the high-insulin cycle all over again). Sears describes a Zone meal as follows: Eat as much protein as the palm of your hand, as much nonstarchy raw vegetables as you can stand for the vitamins, enough carbohydrates to maintain mental clarity because the brain runs on glucose, and enough monounsaturated oils to keep feelings of hunger away. Low-carbohydrate diets like the Atkins diet became extremely popular throughout the United States in 2003 and 2004, but Sears claims that they miss the point. According to him, they ignore the importance of hormonal balance, as well as the influence of dietary balance on digestion and hormone production. The introduction of the Zone in Italy began in 1997 by a physician, Aronne Romano M.D. who applied this nutritional style to patients and athletes. Since the 2nd edition of the book "Come Raggiungere la Zona" (The Zone), in 1999, the Chef Memo Romano and his brother Aronne modified the original recipes and menu to suit the local food and habits. The diffusion of the Zone continues with the efforts of many people including Paolo Perucci, Gigliola Braga, Simone Masci and Daniela Morandi. Possibly the most famous case of someone using the diet effectively has been Mexican Manuel Uribe. After weighing in at around 560 kg (1234 lbs or over 88 stone) but within a year had lost about 180 kg. . The American Heart Association does not recommend the Zone Diet due to high-protein, lack of essential nutrients and little information on long-term effects. It should be noted that AMA's characterization of the Zone diet as 'high-protein' is false, or at least a serious exaggeration, given that 70% of the calories in the Zone diet come from non-protein sources(i.e. carbohydrates, 40%, and fats 30%). The Zone does not emphasize an increase of protein intake in the standard American diet, but rather, a reduction in the intake of unhealthy carbohydrates (i.e. refined breads, starches, sugars, etc.) and an increase in healthy carbohydrates from high-fiber vegetables and fruits and healthy monounsaturated fats. A vegetarian diet, according to Sears, is as far as you can get from The Zone. Individuals who promote a vegetarian diet are critical of Zone and similar diets.

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/index.php/Zones_of_the_lung

# Zones of the lung The zones of the lung proposed by West in 1964, divide the lung into three vertical regions, based upon the relationship between the pressure in the alveoli (PA), in the arteries (Pa), and the veins (Pv): The ventilation/perfusion ratio is higher in zone #1 (the apex of lung when a person is standing) than it is in zone #3 (the base of lung.)

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/index.php/Zonular_cataract_and_nystagmus

# Zonular cataract and nystagmus Zonular cataract and nystagmus, also referred as Nystagmus with congenital zonular cataract is a rare congenital disease associated with Nystagmus and zonular cataract of the eye. It has been suggested that the disease follows a x-linked pattern of inheritance though studies done on this particular disease are few.

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/index.php/Zonulin

# Zonulin Zonulin is a protein that participates in tight junctions between cells of the wall of the digestive tract. Initially discovered in 2000 as the target of zonula occludens toxin, secreted by cholera pathogen Vibrio cholerae, it has been implicated in the pathogenesis of coeliac disease and diabetes mellitus type 1. It is being studied as a target for vaccine adjuvants. ALBA Therapeutics is developing a zonulin receptor agonist, AT-1001, that is currently in phase 2 clinical trials.

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/index.php/Zoonosis

# Zoonosis A zoonosis (pronounced Template:IPA) is any infectious disease that is able to be transmitted (vectored) from other animals, both wild and domestic, to humans or from humans to animals (the latter is sometimes called reverse zoonosis).Many serious diseases fall under this category. The word is derived from the Greek words zoon (animal) (IPA: zo'on) and nosos (disease). The plural of zoonosis is zoonoses, from which an alternative singular zoonose'. The simplest definition of a zoonosis is a disease that can be transmitted from other animals to humans. A slightly more technical definition is a disease that normally exists in other animals, but also infects humans. A partial list of agents that can carry infectious organisms that may be zoonotic includes: bats, birds, cats, cattle, chimpanzees, dogs, fish, fleas, geese, goats, horses, humans, monkeys, mosquitos, opposums, pigs, rabbits, raccoons, rats, rodents, snails, sloths, sheep This list is by no means complete. The influenza virus is an interesting example: it continually recombines genes between strains found in humans, swine and avians, producing new strains with changed characteristics, and occasionally, as in 1918, killing millions worldwide. Most of human prehistory was spent as small bands of hunter-gatherers; these bands were rarely larger than 150 individuals, and were not in contact with other bands very often. Because of this, epidemic or pandemic diseases, which depend on a constant influx of humans who have not developed an immune response, tended to burn out after their first run through a population. To survive, a biological pathogen had to be a chronic infection, stay alive in the host for long periods of time, or have a non-human reservoir in which to live while waiting for new hosts to pass by. In fact, for many 'human' diseases, the human is actually an accidental victim and a dead-end host. (This is the case with rabies, anthrax, tularemia, West Nile virus, and many others). Thus much of human development has been in relation to zoonotic, not epidemic, diseases. Many modern diseases, even epidemic diseases, started out as zoonotic diseases. It is hard to be certain which diseases jumped from other animals to humans, but there is good evidence that measles, smallpox, influenza, and diphtheria came to us this way. HIV, the common cold, and tuberculosis may also have started in other species. In modern days, zoonoses are of practical interest because they are often previously unrecognized diseases or have increased virulence in populations lacking immunity. The West Nile virus appeared in the United States in 1999 in the New York City area, and moved through the country in the summer of 2002, causing much distress. Bubonic plague is a zoonotic disease, as are salmonella, Rocky Mountain spotted fever, and Lyme disease. The major factor contributing to the appearance of new zoonotic pathogens in human populations is increased contact between humans and wildlife (Daszak et al., 2001). This can be caused either by encroachment of human activity into wilderness areas or by movement of wild animals into areas of human activity due to anthropological or environmental disturbances. An example of this is the outbreak of Nipah virus in peninsular Malaysia in 1999, when intensive pig farming intruded into the natural habitat of fruit bats carrying the virus. Unidentified spillover events caused infection of the pig population which acted as an amplifier host, eventually transmitting the virus to farmers and resulting in 105 human deaths (Field et al., 2001). Similarly, in recent times avian influenza and West Nile virus have spilled over into human populations probably due to interactions between the carrier host and domestic animals. Highly mobile animals such as bats and birds may present a greater risk of zoonotic transmission than other animals due to the ease with which they can move into areas of human habitation. Diseases like malaria, schistosomiasis, river blindness, and elephantiasis are not zoonotic, even though they may be transmitted by insects or use intermediate hosts vectors, because they depend on the human host for part of their life-cycle. Outbreaks of zoonosis have been traced to human interaction with and exposure to animals at fairs, petting zoos, and in other settings. In 2005, the Centers for Disease Control and Prevention (CDC) issued an updated list of recommendations for preventing zoonosis transmission in public settings. The CDC recommendations, which were developed in conjunction with the National Association of State Public Health Veterinarians, include sections on the educational responsibilities of venue operators, managing public and animal contact, and animal care and management. In 1988, a person became ill with Swine Influenza Virus (Swine Flu) and died after visiting the display area of the pig barn at a Wisconsin county fair. Three healthcare personnel treating the case patient also developed flu-like illness with laboratory evidence of Swine Influenza Virus infection. Investigators from the CDC indicated in their final report that the Swine Flu had been transmitted directly from pig to human host. In 1994, seven cases of ''E. coli'' O157:H7 infection were traced to a farm in Leicestershire, United Kingdom. An epidemiological investigation into the outbreak revealed that the strain of ''E. coli'' O157:H7 isolated from nine animals on the farm was indistinguishable from the strain isolated from human samples. Investigators concluded that the most likely cause of this outbreak was direct human contact with animals. In 1995, 43 children who had visited a rural farm in Wales became ill with Cryptosporidiosis. ''Cryptosporidium'' was isolated from seven of the ill children. An epidemiological investigation indicated that the source of the children's illness was contact with calves at the farm. Also in 1995, at least thirteen children became ill with ''Cryptosporidiosis'' after visiting a farm in Dublin, Ireland. In a case-control study, researchers compared the activities of the thirteen ill children, or cases, to the activities of 52 out of 55 people who had visited the farm – the controls. The study revealed that illness was significantly associated with playing in the sand in a picnic area beside a stream where animals had access. In 1997, an ''E. coli'' O157:H7 outbreak was identified among one child who lived on an open farm and two children who visited the farm during school parties. Two of the three children developed hemolytic uremic syndrome (HUS). Isolates collected from the three children and from samples taken at the farm were indistinguishable, demonstrating evidence of the link between the farm and the children's illness. In 1999, what is believed to be the largest outbreak of waterborne ''E. coli'' O157:H7 illness in United States history occurred at the Washington County, New York, fair. The New York State Department of Health identified 781 individuals who were suspected of being infected with either ''E. coli'' O157:H7 or ''Campylobacter jejuni''. An investigation into the outbreak revealed that consumption of beverages purchased from vendors supplied with water drawn from an unchlorinated fairgrounds well was associated with illness. In all, 127 outbreak victims were confirmed ill with ''E. coli'' O157:H7 infections; 71 were hospitalized, 14 developed HUS, and two died. In 2000, 51 people became ill with confirmed or suspected ''E. coli'' O157:H7 infections after visiting a dairy farm in Pennsylvania. Eight children developed HUS. A case-control study among visitors to the dairy was conducted jointly by the CDC, Pennsylvania Department of Health, and the Montgomery County Health Department. The study's authors concluded that ''E. coli'' was transmitted to visitors as a result of contamination on animal hides and in the environment. Also in 2000, 43 visitors to the Medina County fair in Ohio were confirmed ill with ''E. coli'' O157:H7 infections. An investigation into the outbreak suggested that the water system from which food vendors were supplied was the source of the ''E. coli'' outbreak. Several months later, five children became ill with ''E. coli'' infections after attending a "Carnival of Horrors" event held at the Medina County fairgrounds. PFGE analysis of the strains of ''E. coli'' isolated from members of both outbreaks revealed an indistinguishable pattern, and investigators from the Medina County Health Department and the CDC determined that the Medina County Fairgrounds water distribution system was the source of both ''E. coli'' outbreaks. In 2001, an ''E. coli'' O157:H7 outbreak was traced to exposure in the Cow Palace at the Lorain County Fair in Ohio. CDC investigators identified 23 cases of ''E. coli'' infection associated with attendance at the Lorain County Fair, with additional secondary cases likely. Two people developed HUS. An environmental and site investigation revealed ''E. coli'' contamination on doorways, rails, bleachers, and sawdust. Investigators concluded that the Lorain County Fair was the source of the outbreak. Wyandot County, Ohio, also reported an ''E. coli'' O157:H7 outbreak in 2001. Ninety-two ''E. coli'' infections were reported to the Wyandot County Health Department and the CDC, with 27 cases confirmed using laboratory analysis. Two cases developed HUS. Contact with infected cattle was believed to be the source of the outbreak; however, a specific cause was never identified. In 2002, seven people became ill with ''E. coli'' O157:H7 infections after visiting a large agricultural fair in Ontario, Canada. Outbreak investigators conducted a case-control study, which indicated that goats and sheep from a petting zoo were the source of the ''E. coli'' among fair visitors. Other indications were that the fencing and environment surrounding the petting zoo could have been a source of transmission. What is believed to be the largest ''E. coli'' O157:H7 outbreak in Oregon State history occurred among attendees at the Lane County Fair in 2002. An Oregon Department of Human Services – Health Services investigation led to the belief that the ''E. coli'' outbreak originated from exposure in the sheep and goat barn. In all, 79 people were confirmed ill with ''E. coli'' infections as part of the outbreak; 22 were hospitalized, and 12 suffered HUS. In 200, fair visitors and animal exhibitors at the Fort Bend County Fair in Texas became ill with ''E. coli'' O157:H7 infections. An outbreak investigation led to the determination that 25 people had become ill with ''E. coli'' infections after attending the Fort Bend County Fair; seven people were laboratory-confirmed with ''E. coli'', and 5 developed HUS or TTP (Thrombotic Thrombocytopenic Purpura). Investigators isolated a strain of ''E. coli'' indistinguishable from the outbreak strain from four animal husbandry sites, and found high levels of ''E. coli'' contamination in both rodeo and animal exhibit areas. In 2004, a large ''E. coli'' O157:H7 outbreak occurred among visitors at the 2004 North Carolina State Fair. During its investigation into the outbreak, the North Carolina Department of Health and Human Services (NCDHHS) received over 180 reports of illness, and documented 33 culture-confirmed cases of ''E. coli'' O157:H7 associated with attendance at the fair, with 15 children developing HUS. In its final investigation report, NCDHHS concluded that the North Carolina State Fair ''E. coli'' outbreak had originated at a petting zoo exhibit. The conclusion was supported by a case-control study, environmental sampling, and laboratory analysis of samples collected from the fair and members of the outbreak. In 2005, a petting zoo that exhibited at two Florida fairs and a festival was traced as the source of an ''E. coli'' O157:H7 outbreak. Sixty-three people who had visited either the Florida State Fair, the Central Florida Fair, or the Florida Strawberry Festival reported illness to investigators for the Florida Department of Health, including 20 who were culture-confirmed and 7 with HUS. A case-control study revealed that illness was associated with exposure to a petting zoo exhibit present at all three events.

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/index.php/Zoonotic

# Zoonotic A zoonosis (pronounced Template:IPA) is any infectious disease that is able to be transmitted (vectored) from other animals, both wild and domestic, to humans or from humans to animals (the latter is sometimes called reverse zoonosis). This list is by no means complete. The influenza virus is an interesting example: It continually recombines genes between strains found in humans, swine and avians, producing new strains with changed characteristics, and occasionally, as in 1918, killing millions worldwide. In 1997, an ''E. coli'' O157:H7 outbreak was identified among one child who lived on an open farm and two children who visited the farm during school parties. Two of the three children developed hemolytic uremic syndrome (HUS). Isolates collected from the three children and from samples taken at the farm were indistinguishable, demonstrating evidence of the link between the farm and the children's illness. In 1999, what is believed to be the largest outbreak of waterborne ''E. coli'' O157:H7 illness in United States history occurred at the Washington County, New York fair. The New York State Department of Health identified 781 individuals who were suspected of being infected with either ''E. coli'' O157:H7 or ''Campylobacter jejuni''. An investigation into the outbreak revealed that consumption of beverages purchased from vendors supplied with water drawn from an unchlorinated fairgrounds well was associated with illness. In all, 127 outbreak victims were confirmed ill with ''E. coli'' O157:H7 infections; 71 were hospitalized, 14 developed HUS, and two died. In 2000, 51 people became ill with confirmed or suspected ''E. coli'' O157:H7 infections after visiting a dairy farm in Pennsylvania. Eight children developed HUS. A case-control study among visitors to the dairy was conducted jointly by the CDC, Pennsylvania Department of Health, and the Montgomery County Health Department. The study's authors concluded that ''E. coli'' was transmitted to visitors as a result of contamination on animal hides and in the environment. Also in 2000, 43 visitors to the Medina County fair in Ohio were confirmed ill with ''E. coli'' O157:H7 infections. An investigation into the outbreak suggested that the water system from which food vendors were supplied was the source of the ''E. coli'' outbreak. Several months later, five children became ill with ''E. coli'' infections after attending a "Carnival of Horrors" event held at the Medina County fairgrounds. PFGE analysis of the strains of ''E. coli'' isolated from members of both outbreaks revealed an indistinguishable pattern, and investigators from the Medina County Health Department and the CDC determined that the Medina County Fairgrounds water distribution system was the source of both ''E. coli'' outbreaks. In 2001, an ''E. coli'' O157:H7 outbreak was traced to exposure in the Cow Palace at the Lorain County Fair in Ohio. CDC investigators identified 23 cases of ''E. coli'' infection associated with attendance at the Lorain County Fair, with additional secondary cases likely. Two people developed HUS. An environmental and site investigation revealed ''E. coli'' contamination on doorways, rails, bleachers, and sawdust. Investigators concluded that the Lorain County Fair was the source of the outbreak. Wyandot County, Ohio, also reported an ''E. coli'' O157:H7 outbreak in 2001. Ninety-two ''E. coli'' infections were reported to the Wyandot County Health Department and the CDC, with 27 cases confirmed using laboratory analysis. Two cases developed HUS. Contact with infected cattle was believed to be the source of the outbreak; however, a specific cause was never identified. In 2002, seven people became ill with ''E. coli'' O157:H7 infections after visiting a large agricultural fair in Ontario, Canada. Outbreak investigators conducted a case-control study, which indicated that goats and sheep from a petting zoo were the source of the ''E. coli'' among fair visitors. Other indications were that the fencing and environment surrounding the petting zoo could have been a source of transmission. What is believed to be the largest ''E. coli'' O157:H7 outbreak in Oregon State history occurred among attendees at the Lane County Fair in 2002. An Oregon Department of Human Services – Health Services investigation led to the belief that the ''E. coli'' outbreak originated from exposure in the sheep and goat barn. In all, 79 people were confirmed ill with ''E. coli'' infections as part of the outbreak; 22 were hospitalized, and 12 suffered HUS. In 2003, fair visitors and animal exhibitors at the Fort Bend County Fair in Texas became ill with ''E. coli'' O157:H7 infections. An outbreak investigation led to the determination that 25 people had become ill with ''E. coli'' infections after attending the Fort Bend County Fair; seven people were laboratory-confirmed with ''E. coli'', and 5 developed HUS or TTP (Thrombotic Thrombocytopenic Purpura). Investigators isolated a strain of ''E. coli'' indistinguishable from the outbreak strain from four animal husbandry sites, and found high levels of ''E. coli'' contamination in both rodeo and animal exhibit areas. In 2004, a large ''E. coli'' O157:H7 outbreak occurred among visitors at the 2004 North Carolina State Fair. During its investigation into the outbreak, the North Carolina Department of Health and Human Services (NCDHHS) received over 180 reports of illness, and documented 33 culture-confirmed cases of ''E. coli'' O157:H7 associated with attendance at the fair, with 15 children developing HUS. In its final investigation report, NCDHHS concluded that the North Carolina State Fair ''E. coli'' outbreak had originated at a petting zoo exhibit. The conclusion was supported by a case-control study, environmental sampling, and laboratory analysis of samples collected from the fair and members of the outbreak. In 2005, a petting zoo that exhibited at two Florida fairs and a festival was traced as the source of an ''E. coli'' O157:H7 outbreak. Sixty-three people who had visited either the Florida State Fair, the Central Florida Fair, or the Florida Strawberry Festival reported illness to investigators for the Florida Department of Health, including 20 who were culture-confirmed and 7 with HUS. A case-control study revealed that illness was associated with exposure to a petting zoo exhibit present at all three events.

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/index.php/Zoophilia_and_health

# Zoophilia and health Infections that are transmitted from animals to humans are called zoonoses. A few of zoonoses may be transferred through casual contact, but others are much more readily transferred by activities that expose humans to the semen, vaginal fluids, urine, saliva, feces and blood of animals. This means that sexual activity with animals is sometimes a high risk activity. It is advisable for practitioners of bestiality to assess their relative risk, since risk varies for each species involved, for each disease mentioned below (and others not mentioned), and for each region in the world. Some of the more common zoonoses are listed at the National Agricultural Safety Database (NASD) and the Centers for Disease Control (CDC). Brucellosis in humans is a potentially life-threatening multisystem disease that can be extremely difficult to treat. There are several varieties of Brucellosis, all caused by bacteria of the genus Brucella, the most notable being B. abortus and B. melitensis which affect larger species of domestic animals, and B. canis which infects dogs and other canids. All are widely spread around the world. The most severe infections are thought to be associated with B. melitensis which primarily infects goats, sheep, and camels in the Mediterranean, Asia, Latin America, parts of Africa and some southern European countries. Humans can catch B. canis through contact with the body fluids of infected dogs, especially semen. urine and vaginal fluids. Dogs can be infected with Brucellosis without showing any signs or symptoms, and infection can only be diagnosed with specific blood tests. The typical symptoms of the type of brucellosis contracted from dogs are: fever that comes and goes, loss of appetite, fatigue, weakness, malaise, sore joints, low back pain, spine pain, headache, depression, abdominal pain, constipation, diarrhoea, vomiting, weakness, dizziness, unsteadiness of gait, and urinary retention. Heart and lung complications can occur. Infected people exhibit only some of these symptoms. Other forms of brucellosis can be more severe. With approximately 500,000 zoonotic infections a year worldwide (source:CDC), brucellosis places a large burden on humanity. Brucellosis has been reduced to rare disease status in North America (excluding Mexico) and northern Europe through vaccination and eradication programs, but it remains rife throughout the rest of the world. In most countries up to 10% of dogs carry this bacterium, and even up to 42.7% in some provinces of China, representing a major threat to the health of veterinarians and people who handle the blood or semen of infected animals. In the USA, there are only about 100 cases of human brucellosis diagnosed per year, although some sources consider it underdiagnosed and underreported. Most other countries have much higher rates, with high risk areas including the Mediterranean Basin (Portugal, Spain, Southern France, Italy, Greece, Turkey, North Africa), South and Central America (including Mexico), Eastern Europe, Asia, Africa, the Caribbean, and the Middle East. New diseases that can jump from animals to humans are called emerging zoonoses. The emerging zoonosis situation changes constantly, in an upward trend. An example from the equine species is the rare Hendra virus, originally passed from flying foxes to horses. The implications for zoophilic sexual contact of each emerging disease should be carefully assessed by practitioners. HIV (the "AIDS" virus) was originally a zoonosis acquired from primates (notably monkeys) in Africa, probably via hunting and eating but possibly via animal bite. It only lives in primates (humans, apes and monkeys) and is not believed to survive long in other species or away from the human body and fluids. The myth that sex with an animal can cure AIDS is false. However, many human pathogens can survive in animal fluids for a limited time, and therefore STDs may theoretically be transmitted by an animal that has multiple consecutive human sexual partners in a short enough time frame to allow pathogen survival. Humans may be at substantial physical risk and seriously harmed by sexual activity with animals. Larger animals may have the strength and defensive attributes (e.g. teeth, hooves, horns, claws) to injure a human, either in rejecting physical or sexual contact, or during sexual arousal. Many animals bite as part of sexual excitement and foreplay. Animals carry numerous bacteria in their mouths capable of causing disease after a bite. The most common risk after an animal bite is simple infection (infection risk approximately 15-20% in the USA, may be higher elsewhere), and for dogs and other large animals injury from the force of the bite. Bacterial bite infections are usually fully curable, although dog bites may cause Pasteurella and Capnocytophaga canimorsus infections, which may have severe consequences. The sexual organs of other species may not safely conform to the human anatomy. For example, the penis of a sexually aroused dog has a broad bulb at the base which can cause injury if forcibly pulled from a body orifice, and equines can thrust suddenly and "flare". In 2005, Kenneth Pinyan, a resident of WA state died from internal injury after being anally penetrated by a stallion. In 2002, a 62-year-old farmer in Bulgaria was treated for a torn rectum after sex with a boar (male pig). In 1976, a 46-year-old French farmer underwent surgery for peritonitis after sex with a boar. Sensitization and allergic reactions to animal saliva and semen may occur, ranging from mild irritation to anaphylaxis. Although dried skin flakes, known as dander, are the most commonly cited allergen, dog saliva is a more potent allergen than dander. An estimated 10% of people are allergic to animals in general, rising to 20-30% amongst asthma sufferers; the percentage of people allergic to animal secretions in particular is currently unknown. Repeated exposure to secretions after sensitization has already occurred may subsequently provoke an anaphylactic reaction, which can be life-threatening, and should be avoided.

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/index.php/Zooxanthella

# Zooxanthella Zooxanthellae (Template:IPAEng) are golden-brown intracellular endosymbionts of various marine animals and protozoa, especially anthozoans. They are members of the phylum Dinoflagellata and are typically dinoflagellate algae, although algae such as diatoms can also be zooxanthellae. They may be acquired by direct ingestion, and subsequently reproduce by splitting apart; a process known as budding. In other cases, zooxanthellae may be transmitted by the coral eggs and planulae. Most are autotrophs and provide the host with energy in the form of translocated reduced carbon compounds derived from photosynthesis. Zooxanthellae can provide up to 90% of a coral's energy requirements. In return, the coral provides the zooxanthellae with protection, shelter, and a constant supply of the carbon dioxide required for photosynthesis. Their population in the host tissue is limited by available nutrients and incident light, and by expulsion of excess cells. However, zooxanthellae do not appear to be digested by their hosts. Hermatypic (reef-building) corals have zooxanthellae and are largely dependent on them, limiting their growth to the photic zone. The symbiotic relationship is probably responsible for the phenomenal success of corals as reef-building organisms in tropical waters. However, when corals are subjected to high environmental stress, they can lose their zooxanthellae by either expulsion or digestion and die. The process known as coral bleaching occurs when the zooxanthellae densities within the coral tissue become low or the concentration of photosynthetic pigments within each zooxanthella decline. Color loss is also attributed to the loss or lowering of concentrations of Green Fluorescent Proteins (GFP) from the cellular pigments of the cnidarian itself. The result is a ghostly white calcareous skeleton, absent of zooxanthellae, with the inevitable death of the coral unless conditions improve, allowing for the zooxanthellae to return. Coral are under constant disturbance, which is ultimately felt by the zooxanthellae living within their tissues. Exposure to air during extremely low tides or damage from intensifying solar radiation in shallow water environments are some of the ecological stressors zooxanthellae face. Temperature changes have provided the most stress to the zooxanthellae-coral relationship. A rise in temperature of 1-2 degrees Celsius for 5-10 weeks or a decline in temperature of 3-5 degrees Celsius for 5-10 days has resulted in a coral bleaching event. Strong temperature changes shock the zooxanthellae and cause them to suffer cell adhesion dysfunction which sees the detachment of the cnidarian endodermal cells from the zooxanthellae. Other organisms which may have zooxanthellae include jellyfish, clams, sea slugs, and radiolaria. There are several different species of zooxanthellae, typically grouped together as the genus Symbiodinium, which appears to be monophyletic. The genus, Symbiodinium, was created by Hugo Freudenthal in 1959, after his identification of the life cycle of zooxanthella from Cassiopea. At that time he proved that they had a motile stage which resembled a "gymnodinioid" dinoflagellate. Being both symbiotic and a dinoflagellate, he named the Genus Symbiodinium, and the species "microadriaticium," after its resemblance to a similar free-living species. There is considerable disagreement as to whether there are a single or many species of Symbiodinium. DNA testing shows differences between the symbionts from different corals, but the issue is whether or not these are significant enough to represent different species. Dr. Freudenthal demonstrated that the zooxanthellae go through a vegetative stage, a cyst stage, and a motile stage as part of their life cycle.

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/index.php/Zopiclone

# Zopiclone Zopiclone is a central nervous system agent , nonbarbiturate hypnotic that is FDA approved for the treatment of insomnia. Common adverse reactions include unpleasant taste, headache, somnolence, respiratory infection, dizziness, dry mouth, rash, anxiety, hallucinations, and viral infections..

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/index.php/Zostavax

# Zostavax Zostavax is a live vaccine developed by Merck & Co. which has been shown to reduce the incidence of herpes zoster (known as Shingles) by 51.3% in a pivotal phase III study of 38,000 adults aged 60 and older who received the vaccine. The vaccine also reduced by 66.5% the number of cases of postherpetic neuralgia and reduced the severity and duration of pain and discomfort associated with shingles, by 61.1%. On October 25th, 2006, the CDC's Advisory Committee on Immunization Practices (ACIP) voted to recommend that Zostavax be given to all adults age 60 and over, including those who have had a previous episode of shingles .

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/index.php/Zosuquidar

# Zosuquidar Zosuquidar is a compound of antineoplastic drug candidates currently under development. It is now in "Phase 3" of clinical tests in the United States. Its action mechanism consists of the inhibition of P-glycoproteins; other drugs with this mechanism include tariquidar and laniquidar. P-glycoproteins are proteins which convert the energy derived from the hydrolysis of ATP to structural changes in protein molecules, in order to perform coupling, thus discharging medicine from cells. If P-glycoprotein coded with the MDR1 gene manifests itself in cancer cells, it discharges much of the antineoplastic drugs from the cells, making cancer cells medicine tolerant, and rendering antineoplastic drugs ineffective. This protein also manifests itself in normal organs not affected by the cancer (such as the liver, small intestine, and skin cells in blood vessels of the brain), and participates in the transportation of medicine. The compound Zosuquidar inhibits this P-glycoprotein, causing the cancer cells to lose their medicine tolerance, and making antineoplastic drugs effective.

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/index.php/Zotepine

# Zotepine Zotepine (brand names: Losizopilon (JP), Lodopin (ID, JP), Setous (JP), Zoleptil (CZ, PT, TR, UK†); where † indicates a formulation that has been discontinued) is an atypical antipsychotic drug indicated for acute and chronic schizophrenia. It has been used in Germany since 1990 (although it has been discontinued in Germany) and Japan since 1982. Zotepine's primary use is as a treatment for schizophrenia although clinical trials have been conducted (with positive results) into its efficacy as an antimanic agent in patients with acute bipolar mania. The antipsychotic effect of zotepine is thought to be mediated through antagonist activity at dopamine and serotonin receptors. Zotepine has a high affinity for the D1 and D2 receptors. It also affects the 5-HT2A, 5-HT2C, 5-HT6, and 5-HT7 receptors. In addition, its active metabolite, norzotepine, serves as a potent norepinephrine reuptake inhibitor. The most common dosage used is 150 mg daily. It is suggested that zotepine therapy starts at 75 mg to 150 mg divided into three daily doses. Some people may need to have their dosage increased to 300 mg.

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/index.php/Zucapsaicin

# Zucapsaicin Zucapsaicin (Civanex) is a medication used to treat osteoarthritis of the knee and other neuropathic pain. It is applied three times daily for a maximum of three months. It reduces pain, and improves articular functions. It is the cis-isomer of capsaicin. Civamide, manufactured by Winston Pharmaceuticals, is produced in formulations for oral, nasal, and topical use (patch and cream). Zucapsaicin has been tested for treatment of a variety of conditions associated with ongoing nerve pain. This includes herpes simplex infections; cluster headaches and migraine; and knee osteoarthritis.

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/index.php/Zuclopenthixol

# Zuclopenthixol Zuclopenthixol (marketed as Cisordinol, Clopixol or Acuphase) is a typical antipsychotic neuroleptic drug of the thioxanthene group. It mainly acts by antagonism of D1 and D2 dopamine receptors, though it also has some antihistamine activity. It is produced and marketed by Lundbeck pharmaceutical company. The side effects are similar to many other typical antipsychotics, namely extrapyramidal symptoms as a result of dopamine blockade in subcortical areas of the brain. This may result in symptoms similar to those seen in Parkinsons Disease and include a restlessness and inability to sit still known as akathisia, a slow tremor and stiffness of the limbs. Zuclopenthixol is thought to be more sedating than the related flupentixol, though possibly less likely to induce extrapyramidal syproms than other typical depots. As with other dopamine antagonists, zuclopenthixol may sometimes elevate prolactin levels; this may occasionally result in amenorrhoea or galactorrhoea in severe cases. Neuroleptic malignant syndrome is a rare but potentially fatal side effect. Any unexpected deterioration in mental state with confusion and muscle stiffness should be seen by a physician. As a long acting injection, zuclopenthixol decanoate comes in a 200 mg ampoule. Doses can vary from 50 mg 3 weekly to (rarely) 400 mg 2 weekly. In general, the lowest effective dose to prevent relapse is preferred. The interval may be shorter as a patient starts on the medication before extending to 3 weekly intervals subsequently. The dose should be reviewed and reduced in side effects occur, though in the short term an anticholinergic medication benztropine may be helpful for tremor and stiffness, while diazepam may be helpful for akathisia. 100 mg of zuclopenthixol decanoate is roughly equivalent to 20 mg of flupentixol decanoate or 12.5 mg of fluphenazine decanoate. In acutely psychotic and agitated inpatients, 50 - 200 mg of zuclopenthixol acetate may be given for a calming effect over the subsequent three days, with a maximum dose of 400 mg in total to be given. As it is a long-acting medication, care must be taken not to give an excessive dose.

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/index.php/Zwitterion

# Zwitterion A zwitterion (from German "Zwitter" — "hybrid," "hermaphrodite") is a chemical compound that is electrically neutral but carries formal positive and negative charges on different atoms. Zwitterions are polar and usually have a high solubility in water and a poor solubility in most organic solvents. Ampholytes are molecules that contain both acidic and basic groups (and are therefore amphoteric) and will exist as zwitterions at a certain pH. This pH is known as the molecule's isoelectric point. Ampholytic molecules make good buffer solutions — they resist change to the pH of a solution by selective ionization. In the presence of acids, they will accept the hydrogen ions, removing them from the solution. In the presence of bases, they will donate hydrogen ions to the solution, again balancing the pH.

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/index.php/Zygomatic_bone

# Zygomatic bone The zygomatic bone (malar bone) is a paired bone of the human skull. It articulates with the maxilla, the temporal bone, the sphenoid bone and the frontal bone. It forms part of the orbit and is commonly referred to as the cheekbone. It is situated at the upper and lateral part of the face: it forms the prominence of the cheek, part of the lateral wall and floor of the orbit, and parts of the temporal and infratemporal fossae [Fig. 1]. It presents a malar and a temporal surface; four processes, the frontosphenoidal, orbital, maxillary, and temporal; and four borders. The malar surface is convex and perforated near its center by a small aperture, the zygomaticofacial foramen, for the passage of the zygomaticofacial nerve and vessels; below this foramen is a slight elevation, which gives origin to the Zygomaticus. The temporal surface, directed backward and medialward, is concave, presenting medially a rough, triangular area, for articulation with the maxilla, and laterally a smooth, concave surface, the upper part of which forms the anterior boundary of the temporal fossa, the lower a part of the infratemporal fossa. Near the center of this surface is the zygomaticotemporal foramen for the transmission of the zygomaticotemporal nerve. The zygomatic process is a protrusion from the rest of the skull, like the bumper of a car. Most of it belongs to the zygomatic bone, but there are other bones contributing to it too, namely the frontal bone, maxilla and temporal bone. The antero-inferior or maxillary border is rough, and bevelled at the expense of its inner table, to articulate with the maxilla; near the orbital margin it gives origin to the Quadratus labii superioris. The postero-superior or temporal border, curved like an italic letter f, is continuous above with the commencement of the temporal line, and below with the upper border of the zygomatic arch; the temporal fascia is attached to it. The zygomatic bone is generally described as ossifying from three centers - one for the malar and two for the orbital portion; these appear about the eighth week and fuse about the fifth month of fetal life.

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/index.php/Zygomycosis_(patient_information)

# Zygomycosis (patient information) Zygomycosis is caused by common fungi frequently found in the soil and in decaying vegetation. Most individuals are exposed to these fungi on a daily basis, but people with weakened immune systems are more susceptible to infection. Conditions most commonly associated with zygomycosis include diabetes (usually poorly controlled diabetes), chronic steroid use, metabolic acidosis, organ transplantation, leukemia, lymphoma, treatment with deferoxamine, and AIDS. Zygomycosis should be suspected if symptoms appear in individuals with weakened immune systems, such as organ transplant recipients. Symptoms of rhinocerebral zygomycosis are most likely to occur among immunosuppressed people. Depending on where the symptoms are, CT scans or MRIs may be done. Evaluation by an ear-nose-throat specialist is recommended if sinus involvement is suspected. People with weakened immune systems and immune disorders (including diabetes) should seek medical attention if they develop fever, headache, sinus pain, eye swelling, or any of the other symptoms listed above. Surgery should be done immediately to remove all dead and infected tissue. Surgery can lead to disfiguration because it may involve removal of the palate, parts of the nose, or parts of the eye. Without such aggressive surgery, however, chances of survival are greatly decreased. Zygomycosis has an extremely high death rate even when aggressive surgery is done. Death rates range from 25 - 85% depending on the body area involved and your overall health.

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/index.php/Zygomycosis_case_study_one

# Zygomycosis case study one A 63-year-old white male was in his usual state of good health until eight weeks before his death when he developed sudden onset of shortness of breath. A thoracotomy was performed for plication of ruptured emphysematous blebs. Following improvement and discharge from the hospital he developed weakness, lethargy, and a left lower lobe lung infiltrate. The patient's condition soon deteriorated further, with almost every organ system having failed. The patient developed DIC and peripheral embolic phenomena, including gangrene of his extremities and face. Autopsy revealed severe emphysema, severe widespread abscessiform and necrotizing pneumonia, and bacterial endocarditis (Staphylococcus aureus) of the pulmonic valve. The right internal carotid artery was occluded by a thrombus and there were areas of necrosis (due to CVAs) in the brain. This is an even higher-power photomicrograph of the wall of the carotid artery (1) and the thrombus (2). Within the wall of the artery and in the thrombus there are multiple variably shaped clear areas (3). At this magnification and with this stain, it is impossible to determine what these clear spaces represent. This is a higher-power photomicrograph of just the wall of the carotid artery. Note the ribbon-like clear structure with roughly parallel walls (non-septate hyphae) and right-angle branching (arrow). This is the Mucor organism. This is another high-power photomicrograph of the wall of the artery and the thrombus. Within the thrombus there are multiple variably-shaped clear areas that represent longitudinal sections and cross sections of the Mucor organisms (arrows).

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/index.php/Zygomycosis_causes

# Zygomycosis causes Zygomycosis usually is a disease of the skin, but can also occur in the sinuses or gastrointestinal tract. Zygomycosis caused by Mucorales causes a rapidly progressing disease of sudden onset in sick or immunocompromised animals. Entomophthorales cause chronic, local infections in otherwise healthy animals. The important species that cause entomophthoromycosis are Conidiobolus coronatus, C. incongruous, and Basidiobolus ranarum. Conidiobolus infections of the upper respiratory system have been reported in humans, sheep, horses, and dogs, and Basidiobolus has been reported less commonly in humans and dogs. Horses are one of the most common domestic animals to be affected by entomophthoromycosis. C. coronatus causes lesions in the nasal and oral mucosa of horses that may cause nasal discharge or difficulty breathing. B. ranarum causes large circular nodules on the upper body and neck of horses. Entomophthorales is found in soil and decaying plant matter, and specifically Basidiobolus can be contracted from insects and the feces of reptiles or amphibians. Zygomycosis of the sinuses can extend from the sinuses into the orbit and the cranial vault, leading to rhinocerebral mucormycosis.

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/index.php/Zygomycosis_epidemiology_and_demographics

# Zygomycosis epidemiology and demographics Zygomycosis is a very rare infection, and as such it is hard to note histories of patients and incidence of the infection. However, one American oncology center revealed that zygomycosis was found in 0.7% of autopsies and roughly 20 patients per every 100,000 admissions to that center. In the United States, zygomycosis was most commonly found in the form of Rhinocerebral disease. In most cases the patient is immunocompromised, although rare cases have occurred in which the subject was not immunocompromised, most often due to a traumatic inoculation of fungal spores. Internationally, zygomycosis was found in 1% of patients with acute leukemia in an Italian review. Outbreaks and clusters of mucormycosis are rare but when they do occur they are often serious. In hospitals, mucormycosis outbreaks of skin and soft tissue infection have been linked to contact with contaminated objects, such as tongue depressors. Additionally, clusters of mucormycosis have occurred in association with organ transplantation. The most recent investigation was in response to an outbreak of mucormycosis among victims of the Joplin, Missouri tornado in May 2011. CDC is assisting the Missouri Department of Health and Senior Services (MDHSS) with an investigation into a number of reports of fungal skin infection in people who were injured by the tornado that struck Joplin in May 2011. People who had trauma that resulted in an open wound that is not healing or are experiencing continued symptoms, such as worsening redness, tenderness, pain, heat in the area of the wound, or fever, should see a health care provider for evaluation.

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/index.php/Zygomycosis_history_and_symptoms

# Zygomycosis history and symptoms Zygomycosis frequently involves the sinuses, brain, or lungs as the sites of infection. Whilst orbitorhinocerebral Zygomycosis is the most common type of the disease, this infection can also manifest in the gastrointestinal tract, skin, and in other organ systems. Rarely, maxilla may be affected by Zygomycosis. The lack of case reports regarding maxillofacial Zygomycosis lies in the rich vascularity of the maxillofacial areas preventing fungal infections, although this can be overcome by more prevalent fungi, bacteria or viruses such as those responsible for Zygomycosis. Basidiobolomycosis is usually a superficial infection of skin, but may very rarely cause lesions of the bowel or liver, mimicking bowel cancer, or Crohn's disease.

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/index.php/Zygomycosis_laboratory_findings

# Zygomycosis laboratory findings Diagnosis for phycomycosis is through a biopsy or culture, although an ELISA test has been developed for Pythium insidiosum in animals. As swabs of tissue or discharge are generally unreliable, the diagnosis of zygomycosis tends to be established by a biopsy specimen of the involved tissue. Diagnosis for basidiobolomycosis is by laboratory culture of the organism, usually from pieces of tissue taken from the patient. It grows easily on most media, but risks being discarded as irrelevant or being reported as a contaminant because laboratory staff are unfamiliar with it. Diagnosis is often difficult because basidiobolomycosis is a rare disease and therefore often not recognized. The lesions often look like tumors rather than infection, so often no sample is sent for microbiology, however, the histopathology is characteristic: the Splendore-Hoeppli phenomenon describes the presence of fungal hyphae (which may exist only as ghosts on the slide) surrounded by eosinophilic material.

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/index.php/Zygomycosis_medical_therapy

# Zygomycosis medical therapy If mucormycosis is suspected, prompt amphotericin B therapy should be administered due to the rapid spread and mortality rate of the disease. Amphotericin B (which works by damaging the cell walls of the fungi) is usually administered for a further 4-6 weeks after initial therapy begins to ensure eradication of the infection. Posaconazole has been shown to be effective against mucormycosis, perhaps more so than amphotericin B, but has not yet replaced it as the standard of care. After administration the patient must then be admitted to surgery for removal of the "fungus ball". The disease must be monitored carefully for any signs of reemergence. Treatment for skin lesions is traditionally with potassium iodide, but itraconazole has also been used successfully. Treatment include surgical debridement of involved tissues, antifungal therapy, use of growth factors to accelerate recovery from neutropenia, provision of granulocyte transfusions with sustained circulating neutrophils until the patient recovers from neutropenia, and discontinuation or reduction in the dose of glucocorticoids, correction of metabolic acidosis and hyperglycemia.

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/index.php/Zygomycosis_natural_history,_complications_and_prognosis

# Zygomycosis natural history, complications and prognosis In most cases, the prognosis of zygomycosis is poor and has varied mortality rates depending on its form and severity. In the Rhinocerebral form, the mortality rate is between 30% and 70%, whereas disseminated mucormycosis presents with the highest mortality rate in an otherwise healthy patient with a mortality rate of up to 100%. Patients with AIDS have a mortality rate of almost 100%. Possible complications of mucormycosis include the partial loss of neurological function, blindness and clotting of brain or lung vessels. If left untreated, mucormycosis can be fatal. The survival rate of immunosuppressed patients with rhino sinusal mucormycosis without cerebral involvement is between 50-80% and only 10% if the infection spreads into the brain. In uncontrolled diabetes mellitus patients with ketoacidosis that are diagnosed with rhino-orbital mucormycosis we should suspect a cerebral spread of the fungi if after 24 hours since the beginning of treatment. In 70% of cases mucormycosis occurs in diabetics, and the percentage increases if there is concomitant immunosupression and comorbities.

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/index.php/Zygomycosis_overview

# Zygomycosis overview Zygomycosis is a rare yet life threatening and serious infection of fungi, usually affecting the face or oropharyngeal cavity. Occasionally, when caused by Pythium or other similar fungi, the condition may affect the gastrointestinal tract or the skin. It usually begins in the nose and paranasal sinuses and is one of the most rapidly spreading fungal infections in humans. The most common fungi responsible for mucormycosis in humans are Mucor and Rhizopus. Other fungi include Apophysomyces, Absidia, Mortierella, Cunninghamella, Saksenaea, Syncephalastrum and Cokeromyces, although the spectrum is far wider and can also contain Entomophthorales or Mucorales. It usually affects patients who are immunocompromised. Zygomycosis caused by Mucorales causes a rapidly progressing disease of sudden onset in sick or immunocompromised animals. Entomophthorales cause chronic, local infections in otherwise healthy animals. The important species that cause entomophthoromycosis are Conidiobolus coronatus, C. incongruous, and Basidiobolus ranarum. Conidiobolus infections of the upper respiratory system have been reported in humans, sheep, horses, and dogs, and Basidiobolus has been reported less commonly in humans and dogs. Horses are one of the most common domestic animals to be affected by entomophthoromycosis. C. coronatus causes lesions in the nasal and oral mucosa of horses that may cause nasal discharge or difficulty breathing. B. ranarum causes large circular nodules on the upper body and neck of horses. Entomophthorales is found in soil and decaying plant matter, and specifically Basidiobolus can be contracted from insects and the feces of reptiles or amphibians. Zygomycosis of the sinuses can extend from the sinuses into the orbit and the cranial vault, leading to rhinocerebral mucormycosis. While most individuals are exposed to the fungi on a regular basis those with immune disorders are more prone to an infection. In humans zygomycosis is most prevalent in immunocompromised patients (HIV/AIDS, the elderly, SCID, etc) and patients in acidosis (diabetes, burns), particularly after barrier injury to the skin or mucus membranes, malignancies such as lymphomas and leukemias, renal failure, organ transplant, long term corticosteroid and immunosuppressive therapy, cirrhosis, burns and energy malnutrition. Some 50-75% of patients diagnosed with zygomycosis are estimated to have underlying poorly controlled diabetes mellitus and ketoacidosis. In most cases, the prognosis of zygomycosis is poor and has varied mortality rates depending on its form and severity. In the Rhinocerebral form, the mortality rate is between 30% and 70%, whereas disseminated zygomycosis presents with the highest mortality rate in an otherwise healthy patient with a mortality rate of up to 90%. Patients with AIDS have a mortality rate of almost 100%. Possible complications of Zygomycosis include the partial loss of neurological function, blindness and clotting of brain or lung vessels. Diagnosis for phycomycosis is through a biopsy or culture, although an ELISA test has been developed for Pythium insidiosum in animals. As swabs of tissue or discharge are generally unreliable, the diagnosis of zygomycosis tends to be established by a biopsy specimen of the involved tissue. Diagnosis for basidiobolomycosis is by laboratory culture of the organism, usually from pieces of tissue taken from the patient. It grows easily on most media, but risks being discarded as irrelevant or being reported as a contaminant because laboratory staff are unfamiliar with it. Diagnosis is often difficult because basidiobolomycosis is a rare disease and therefore often not recognized. The lesions often look like tumors rather than infection, so often no sample is sent for microbiology, however, the histopathology is characteristic: the Splendore-Hoeppli phenomenon describes the presence of fungal hyphae (which may exist only as ghosts on the slide) surrounded by eosinophilic material. If zygomycosis is suspected, prompt amphotericin B therapy should be administered due to the rapid spread and mortality rate of the disease. Amphotericin B (which works by damaging the cell walls of the fungi) is usually administered for a further 4-6 weeks after initial therapy begins to ensure eradication of the infection. Posaconazole has been shown to be effective against zygomycosis, perhaps more so than amphotericin B, but has not yet replaced it as the standard of care. After administration the patient must then be admitted to surgery for removal of the "fungus ball". The disease must be monitored carefully for any signs of reemergence. Treatment for skin lesions is traditionally with potassium iodide, but itraconazole has also been used successfully. Antifungal drugs show only limited effect on treatment of phycomycosis, but itraconazole and terbinafine hydrochloride are often used for two to three months following surgery. Humans with Basidiobolus infections have been treated with amphotericin B and potassium iodide. Immunotherapy has been used successfully in humans and horses with pythiosis. Surgical therapy can be very drastic for zygomycosis, and in some cases of Rhinocerebral disease removal of infected brain tissue may be required. In some cases surgery may be disfiguring because it may involve removal of the palate, nasal cavity, or eye structures. Surgery may be extended to more than one operation. It has been hypothesised that hyperbaric oxygen may be beneficial as an adjunctive therapy because higher oxygen pressure increases the ability of neutrophils to kill the organism. Treatment for Phycomycosis is very difficult and includes surgery when possible. Postoperative recurrence is common. For pythiosis and lagenidiosis, a new drug targeting water moulds called caspofungin is available, but it is very expensive. For pythiosis and lagenidiosis, a new drug targeting water moulds called caspofungin is available, but it is very expensive.

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/index.php/Zygomycosis_primary_prevention

# Zygomycosis primary prevention Because these fungi are common in the environment, such as soil and decaying wood, preventing exposure is difficult. There is no vaccine available to prevent an infection with mucormycosis. To help reduce the risk for disease:

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/index.php/Zygomycosis_risk_factors

# Zygomycosis risk factors While most individuals are exposed to the fungi on a regular basis those with immune disorders are more prone to an infection. In humans zygomycosis is most prevalent in immunocompromised patients (HIV/AIDS, the elderly, SCID, etc) and patients in acidosis (diabetes, burns), particularly after barrier injury to the skin or mucus membranes, malignancies such as lymphomas and leukemias, renal failure, organ transplant, long term corticosteroid and immunosuppressive therapy, cirrhosis, burns and energy malnutrition. Some 50-75% of patients diagnosed with zygomycosis are estimated to have underlying poorly controlled diabetes mellitus and ketoacidosis. Mucormycosis is a rare infection caused by fungi typically found in the soil and in decaying organic matter, including leaves and rotten wood. The infection is more common among people with weakened immune systems, but it can occur (rarely) in people who are otherwise healthy. Risk factors for developing mucormycosis include:

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/index.php/Zygomycosis_surgery

# Zygomycosis surgery Treatment for Phycomycosis is very difficult and includes surgery when possible. Postoperative recurrence is common. For pythiosis and lagenidiosis, a new drug targeting water moulds called caspofungin is available, but it is very expensive.

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/index.php/Zygomycota

# Zygomycota ## Contents Zygomycota, or zygote fungi, are a phylum of fungi. The name of the phylum comes from zygosporangia, resistant spherical spores formed during sexual reproduction. Approximately 600 species of zygomycetes are known. They are mostly terrestrial in habitat, living in soil or on decaying plant or animal material. Zygomycete hyphae may be coenocytic, forming septa only where gametes are formed or to wall off dead hyphae. ## Reproduction A common example of a zygomycete is [{black bread mold]] (Rhizopus stolonifer), a member of the Mucorales. It spreads over the surface of bread and other food sources, sending hyphae inward to absorb nutrients. In its asexual phase it develops bulbous black sporangia at the tips of upright hyphae, each containing hundreds of haploid spores. If the mycelia of complementary mating types are present, the fungus reproduces sexually and produces zygosporangia. Zygosporangia are typically thick-walled, highly resilient to environmental hardships, and are metabolically inert. When conditions improve, however, they germinate to produce a sporangium or vegetative hyphae. ## Phylogeny Some zygomycetes disperse their spores in a more precise manner than simply allowing them to drift aimlessly on air currents. Pilobolus, a fungus which grows on animal dung, bends its sporangiophores towards light with the help of a light sensitive pigment and then "fires" them with an explosive squirt of high-pressure cytoplasm. Sporangia can be launched as far as 2m, placing them far away from the dung and hopefully on vegetation which will be eaten by an herbivore, eventually to be deposited with dung elsewhere. Different mechanisms for forcible spore discharge have evolved among members of the zygomycete order Entomophthorales. ## Notes The Zygomycota are generally placed near the base of the fungal phylogenetic tree, having diverged from other fungi after chytrids. Molecular phylogenetics reveal that they form a polyphyletic group and could see a split into several new phyla. The order Glomales was removed in 2001 and elevated to Division Glomeromycota due their lack of zygospore formation, their mycorrhizal habit, and lack of DNA sequence homology.

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/index.php/Zygosity

# Zygosity Zygosity refers to the genetic condition of a zygote. In genetics, zygosity describes the similarity or dissimilarity of DNA between homologous chromosomes at a specific allelic position or gene. Every gene in a diploid organism has two alleles at the gene's locus. These alleles are defined as dominant or recessive, depending on the phenotype resulting from the two alleles. If a gene's two alleles are both dominant or both recessive, that specific gene is homozygous. If one allele is dominant and the other is recessive, the gene is heterozygous. The terms homozygous, heterozygous and hemizygous are used to simplify the description of the genotype of a diploid organism at a single genetic locus. At a given gene or position along a chromosome (a locus), the DNA sequence can vary among individuals in the population. The variable DNA segments are referred to as alleles, and diploid organisms generally have two alleles at each locus, one allele for each of the two homologous chromosomes. Simply stated, homozygous describes two identical alleles or DNA sequences at one locus, heterozygous describes two different alleles at one locus, and hemizygous describes the presence of only a single copy of the gene in an otherwise diploid organism. Zygosity is also used to describe the genetic condition of the zygote(s) from which twins emerge, where it refers to the similarity or dissimilarity of the twins' DNA. Identical twins are monozygotic - they develop from one zygote (one fertilized egg that develops into two embryos). Fraternal twins are dizygotic - they developed separately from two zygotes (two fertilized eggs). For a description of these terms, see twins. An organism is referred to as being homozygous (Basically meaning of the same alleles) at a specific locus when it carries two identical copies of the gene affecting a given trait on the two corresponding homologous chromosomes (e.g., the genotype is PP or pp when P and p refer to different possible alleles of the same gene). Such a cell or such an organism is called a homozygote. A homozygous dominant genotype occurs when a particular locus has two copies of the dominant allele (e.g. PP). A homozygous recessive genotype occurs when a particular locus has two copies of the recessive allele (e.g. pp). Pure-bred or true breeding organisms are homozygous. For example a homozygous individual could have the allele combinations PP or pp. All homozygous alleles are either allozygous or autozygous. An organism is a heterozygote or is heterozygous at a locus or gene when it has different alleles occupying the gene's position in each of the homologous chromosomes. In other words, it describes an individual that has 2 different alleles for a trait. In diploid organisms, the two different alleles were inherited from the organism's two parents. For example a heterozygous individual would have the allele combination Pp. Hemizygous describes a diploid individual who has only one allele of a gene or chromosome segment rather than the usual two. A hemizygote refers to a cell or organism whose genome includes only one allele at a given locus. For organisms where the male is heterogametic, such as humans, it refers in particular to X-linked genes, since males normally possess only one X-chromosome. They are hemizygous for (nearly) all genes that are located on the X-chromosome. The relationship between different alleles and the phenotypes that they affect is described in Dominance relationship. Some alleles are neither dominant nor recessive to another allele. In such cases, both alleles affect the phenotype of the heterozygote. Sometimes the result is an intermediate phenotype, such as when a snapdragon plant producing red flowers is crossed to one producing white flowers: the result is a heterozygous plant producing pink flowers. This is called incomplete dominance. To symbolize how a gene is inherited, the dominant allele is indicated with an upper case character and the recessive with a lower case character. The colour of flowers in Mendel's inheritance experiments are often indicated as PP for the dominant homozygote, which produces a red flower, and pp for the recessive homozygote, which produces a white flower. When these two are crossed, the F1 or first filial generation receives one chromosome with the P allele from the red-flowered parent and a corresponding chromosome with the p allele from the white-flowered parent. All of the F1 generation are heterozygous, and this genotype is indicated with Pp. All of the F1 plants produce red flowers, as this is the dominant allele. Heterozygosity refers to the state of being a heterozygote. Heterozygosity can also refer to the fraction of loci within an individual that are heterozygous. In population genetics, it is commonly extended to refer to the population as a whole, i.e. the fraction of individuals in a population that are heterozygous for a particular locus. H_e = 1 - \sum_{i=1}^{m}{(f_i)^2} </math> where <math>m</math> is the number of alleles at the target locus, and <math>f_i</math> is the frequency of the <math>i^{th}</math> allele at the target locus.

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/index.php/Zymurgy

# Zymurgy ## Contents Zymurgy or zymology is the study of fermentation. The word was originally used to describe the science involved in these processes but it has since become more broadly used to describe the brewing of alcoholic beverages. A zymurgist (or zymologist) is one who studies zymurgy. ## Trivia Louis Pasteur is considered to have been the first zymologist when, in 1857, he connected yeast to fermentation. Pasteur originally defined fermentation as "respiration without air". The German Eduard Buchner, winner of the 1907 Nobel Prize in chemistry, later determined that fermentation was actually caused by the yeast's secretion of an enzyme that he called zymase.

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/index.php/Zyxin

# Zyxin ## Function Focal adhesions are actin-rich structures that enable cells to adhere to the extracellular matrix and at which protein complexes involved in signal transduction assemble. Zyxin is a zinc-binding phosphoprotein that concentrates at focal adhesions and along the actin cytoskeleton. Zyxin has an N-terminal proline-rich domain and three LIM domains in its C-terminal half. The proline-rich domain may interact with SH3 domains of proteins involved in signal transduction pathways while the LIM domains are likely involved in protein-protein binding. Zyxin may function as a messenger in the signal transduction pathway that mediates adhesion-stimulated changes in gene expression and may modulate the cytoskeletal organization of actin bundles. Alternative splicing results in multiple transcript variants that encode the same isoform.

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