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The Orbiting Carbon Observatory-3 (OCO-3) is a NASA-JPL instrument designed to measure carbon dioxide in Earths atmosphere. The instrument is mounted on the Japanese Experiment Module-Exposed Facility on board the International Space Station (ISS). OCO-3 was scheduled to be transported to space by a SpaceX Dragon from a Falcon 9 rocket on 30 April 2019, but the launch was delayed to 3 May, due to problems with the space stations electrical power system. This launch was further delayed to 4 May due to electrical issues aboard Of Course I Still Love You (OCISLY), the barge used to recover the Falcon 9’s first stage. OCO-3 was launched as part of CRS-17 on 4 May 2019 at 06:48 UTC. The nominal mission lifetime is ten years. OCO-3 was assembled using spare materials from the Orbiting Carbon Observatory-2 satellite. Because the OCO-3 instrument is similar to the OCO-2 instrument, it is expected to have similar performance with its measurements used to quantify to 1 ppm precision or better at 3 Hz.
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Greenhouse Gases
Escitalopram increases intrasynaptic levels of the neurotransmitter serotonin by blocking the reuptake of the neurotransmitter into the presynaptic neuron. Over time, this leads to a downregulation of pre-synaptic 5-HT receptors, which is associated with an improvement in passive stress tolerance, and delayed downstream increase in expression of brain-derived neurotrophic factor, which may contribute to a reduction in negative affective biases. Of the SSRIs currently available, escitalopram has the highest selectivity for the serotonin transporter (SERT) compared to the norepinephrine transporter (NET), making the side-effect profile relatively mild in comparison to less-selective SSRIs. Escitalopram is a substrate of P-glycoprotein and hence P-glycoprotein inhibitors such as verapamil and quinidine may improve its blood brain barrier penetrability. In a preclinical study in rats combining escitalopram with a P-glycoprotein inhibitor, its antidepressant-like effects were enhanced.
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Enantiopure drugs
In 2004, separate civil suits alleging illegal marketing of citalopram and escitalopram for use by children and teenagers by Forest were initiated by two whistleblowers: a physician named Joseph Piacentile and a Forest salesman named Christopher Gobble. In February 2009, the suits were joined. Eleven states and the District of Columbia filed notices of intent to intervene as plaintiffs in the action. The suits alleged that Forest illegally engaged in off-label promotion of Lexapro for use in children; hid the results of a study showing lack of effectiveness in children; paid kickbacks to physicians to induce them to prescribe Lexapro to children; and conducted so-called "seeding studies" that were, in reality, marketing efforts to promote the drug's use by doctors. Forest denied the allegations but ultimately agreed to settle with the plaintiffs for over $313 million.
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Enantiopure drugs
UNEP banned the use of Halon gases in the Montreal Protocol treaty in 1987 due to ozone depletion and the ozone-depleting effect of Halon gases. Developing countries were granted an extension to still use Halon until 2010. After 2010 UNEP recommended that those countries replace Halon with ozone friendly alternatives.
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After an intake of 1.5 mg levonorgestrel in clinical trials, very common side effects (reported by 10% or more) included: hives, dizziness, hair loss, headache, nausea, abdominal pain, uterine pain, delayed menstruation, heavy menstruation, uterine bleeding, and fatigue; common side effects (reported by 1% to 10%) included diarrhea, vomiting, and painful menstruation; these side effects usually disappeared within 48 hours. However, the long term side effects common with oral contraceptives such as arterial disease are lower with levonorgestrel than in combination pills. Levonorgestrel as a contraceptive intrauterine device is associated with a higher risk of breast cancer than with non-use.
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Enantiopure drugs
With a relatively low global warming potential (GWP) index of 124 and favorable thermophysical properties, 1,1-difluoroethane has been proposed as an environmentally friendly alternative to R134a. Despite its flammability, R152a also presents operating pressures and volumetric cooling capacity (VCC) similar to R134a so it can be used in large chillers or in more particular applications like heat pipe finned heat exchangers. Furthermore, 1,1-difluoroethane is also commonly used in gas dusters and numerous other retail aerosol products, particularly those subject to stringent volatile organic compound (VOC) requirements. The molecular weight of difluoroethane is 66, making it a useful and convenient tool for detecting vacuum leaks in Gas chromatography–mass spectrometry (GC-MS) systems. The cheap and freely available gas has a molecular weight and fragmentation pattern (base peak 51 m/z in typical EI-MS, major peak at 65 m/z) distinct from anything in air. If mass peaks corresponding to 1,1-difluoroethane are observed immediately after spraying a suspect leak point, leaks may be identified.
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NASA Launch Services Program (LSP) investigators have determined the technical root cause for the Taurus XL launch failures of NASAs Orbiting Carbon Observatory (OCO) and Glory missions in 2009 and 2011, respectively: faulty materials provided by aluminium manufacturer, Sapa Profiles, Inc. (SPI). LSPs technical investigation led to the involvement of NASA's Office of the Inspector General and the U.S. Department of Justice (DOJ). The efforts of the DOJ, recently made public, resulted in the resolution of criminal charges and alleged civil claims against SPI, and its agreement to pay $46 million to the U.S. government and other commercial customers. This relates to a 19-year scheme that included falsifying thousands of certifications for aluminium extrusions to hundreds of customers. On 24 February 2009, a Taurus XL rocket (Taurus T8) carrying NASAs Orbiting Carbon Observatory (OCO) satellite failed to reach orbit. The Taurus T8 mission failed because the payload fairing did not separate during ascent, causing the rocket to not shed weight. As a result of the extra weight, the Taurus rocket failed to reach orbital velocity, resulting in a total loss of the mission. On 4 March 2011, another Taurus rocket (Taurus T9) carrying NASAs Glory scientific satellite failed to reach orbit. The Taurus T9 mission also concluded in a failure of the payload fairing to separate. The Taurus T8 and T9 missions both reentered earths atmosphere resulting in break-up and/or burnup of the rocket and satellite, and any surviving pieces would have been dispersed in the Pacific Ocean near Antarctica. The combined cost of both mission failures was in excess of $700 million. This documents purpose is to provide a top-level outline of NASA's updated findings pertaining to the cause of both mishaps. The Taurus T8 and T9 rockets both used 63-inch diameter payload fairings to cover and protect the spacecraft during ground operations and launch. The payload fairing halves are structurally joined and attached to the rocket using frangible joints. A frangible joint is a structural separation system that is initiated using ordnance. Initiation of the ordnance causes the ligament of the frangible joint extrusion to fracture, allowing the two payload fairing halves to be separated and subsequently jettisoned from the Taurus rocket. The frangible joints for T8 and T9 were made and assembled together, at the same time. The T8 and T9 frangible joint extrusions were manufactured by Sapa Profiles, Inc. (SPI) in its Technical Dynamics Aluminum (TDA) plant, in Portland, Oregon.
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Clean agent FS 49 C2 is an environmentally engineered, human safe, fast acting Clean Agent fire extinguishing gas for gaseous fire suppression installed in a suited fire suppression system. The gas consists of tetrafluoroethane, pentafluoroethane and carbon dioxide. FS 49 C2 maintains breathable concentrations of oxygen in the air. It can extinguish a fire with less danger to people in the room at extinguishing concentrations in contrast to pure carbon dioxide based fire suppression system that is deadly to humans when released in extinguishing amounts. The gas was initially called Halotron II B/FS49C2.
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Greenhouse Gases
Esketamine is approved under the brand name Spravato in the form of a nasal spray added to a conventional antidepressant as a therapy for treatment-resistant depression (TRD) as well as major depressive disorder (MDD) associated with suicidal ideation or behavior in adults in the United States. In the clinical trials that led to approval of esketamine, TRD was defined as MDD with inadequate response to at least two different conventional antidepressants. The nasal spray formulation of esketamine used for depression delivers two sprays containing a total of 28 mg esketamine and doses of 56 mg (2 devices) to 84 mg (3 devices) are used. The recommended dosage of Spravato is 56 mg on day 1, 56 or 84 mg twice per week during weeks 1 to 4, 56 or 84 mg once per week during weeks 5 to 8, and 56 or 84 mg every 2 weeks or once weekly during week 9 and thereafter. Dosing is individualized to the least frequent dosing necessary to maintain response or remission. Spravato is administered under the supervision of a healthcare provider and patients are monitored for at least 2 hours during each treatment session. Due to concerns about sedation, dissociation, and misuse, esketamine is available for treatment of depression only from certified providers through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called Spravato REMS. Five clinical studies of esketamine for TRD (TRANSFORM-1, -2, and -3, and SUSTAIN-1 and -2) were submitted to and evaluated by the FDA when approval of esketamine for treatment of TRD was sought by Janssen Pharmaceuticals. Of these five studies, three were short-term (4-week) efficacy studies (the TRANSFORM studies). Two of these three studies (TRANSFORM-1 and -3) did not find a statistically significant antidepressant effect of esketamine relative to placebo. In the one positive short-term efficacy study (TRANSFORM-2), there was a 4.0-point difference between esketamine and placebo on the Montgomery–Åsberg Depression Rating Scale (MADRS) after 4 weeks of treatment (P = 0.020). This scale ranges from 0 to 60 and the average score of the participants at the start of the study was about 37.0 in both the esketamine and placebo groups. The total change in score after 4 weeks was –19.8 points in the esketamine group and –15.8 points in the placebo group. This corresponded to a percentage change in MADRS score from baseline of –53.5% with esketamine and –42.4% with placebo (a difference and reduction of depression score of –11.1% potentially attributable to the pharmacological action of esketamine) in these patient samples. Placebo showed 80.0% of the antidepressant effect of esketamine for TRD in this study and hence approximately 20.0% of the antidepressant response was attributable to esketamine. In the two negative short-term efficacy trials that did not reach statistical significance (TRANSFORM-1 and -3), the differences in MADRS reductions between esketamine and placebo were –3.2 (P = 0.088) and –3.6 (P = 0.059) after 4 weeks of treatment. The 4.0-point additional reduction in MADRS score with esketamine over placebo in the single positive efficacy trial corresponds to less than "minimal improvement" and has been criticized as being below the threshold for clinically meaningful change. A difference of at least 6.5 points was originally suggested by the trial investigators to be a reasonable threshold for clinical significance. In other literature, MADRS reductions have been interpreted as "very much improved" corresponding to 27–28 points, "much improved" to 16–17 points, and "minimally improved" to 7–9 points. It has additionally been argued that the small advantage in scores with esketamine may have been related to an enhanced placebo response in the esketamine group due to functional unblinding caused by the psychoactive effects of esketamine. In other words, it is argued that the study was not truly a double-blind controlled trial. Dissociation was experienced as a side effect by a majority of participants who received esketamine (61–75% with esketamine and 5–12% with placebo; ~7-fold difference) and "severe" dissociation was experienced by 25%. Deblinding and expectancy confounds are problems with studies of hallucinogens for psychiatric indications in general. The FDA normally requires at least two positive short-term efficacy studies for approval of antidepressants, but this requirement was loosened for esketamine and a relapse-prevention trial was allowed to fill the place of the second efficacy trial instead. This is the first time that the FDA is known to have made such an exception and the decision has been criticized as lowering regulatory standards. In the relapse-prevention trial (SUSTAIN-2), the rate of depression relapse was significantly lower with esketamine continued than with it discontinued and replaced with placebo in esketamine-treated stable responders and remitters (51% rate reduction in remitters and 70% reduction in responders). Esketamine was approved for the treatment of MDD with co-occurring suicidal ideation or behavior on the basis of two short-term (4-week) phase 3 trials (ASPIRE-1 and -2) of esketamine nasal spray added to a conventional antidepressant. The primary efficacy measure was reduction in MADRS total score after 24 hours following the first dose of esketamine. In both trials, MADRS scores were significantly reduced with esketamine relative to placebo at 24 hours. The mean MADRS scores at baseline were 39.4 to 41.3 in all groups and the MADRS reductions at 24 hours were –15.9 and –16.0 with esketamine and –12.0 and –12.2 with placebo, resulting in mean differences between esketamine and placebo of –3.8 and –3.9. The secondary efficacy measure in the trials was change in Clinical Global Impression of Suicidal Severity - Revised (CGI-SS-r) 24 hours after the first dose of esketamine. The CGI-SS-r is a single-item scale with scores ranging from 0 to 6. Esketamine was not significantly effective in reducing suicidality relative to placebo on this measure either at 24 hours or after 25 days. At 24 hours, CGI-SS-r scores were changed by –1.5 with esketamine and –1.3 with placebo, giving a non-significant mean difference between esketamine and placebo of –0.20. Hence, while efficacious in reducing depressive symptoms in people with depression and suicidality, antisuicidal effects of esketamine in such individuals have not been demonstrated. Expectations were initially very high for ketamine and esketamine for treatment of depression based on early small-scale clinical studies, with discovery of the rapid and ostensibly robust antidepressant effects of ketamine described by some authors as "the most important advance in the field of psychiatry in the past half century". According to a 2018 review, ketamine showed more than double the antidepressant effect size over placebo of conventional antidepressants in the treatment of depression based on the preliminary evidence available at the time (Cohens d = 1.3–1.7 for ketamine, Cohens d = 0.8 for midazolam (active placebo), and Cohens d = 0.53–0.81 for conventional antidepressants). However, the efficacy of ketamine/esketamine for depression declined dramatically as studies became larger and more methodologically rigorous. The effectiveness of esketamine for the indication of TRD is described as "modest" and is similar in magnitude to that of other antidepressants for treatment of MDD. The comparative effectiveness of ketamine and esketamine in the treatment of depression has not been adequately characterized. A January 2021 meta-analysis reported that ketamine was similarly effective to esketamine in terms of antidepressant effect size ( for depression score of –1.1 vs. –1.2) but more effective than esketamine in terms of response and remission rates ( = 3.01 vs. RR = 1.38 for response and RR = 3.70 vs. RR = 1.47 for remission). A September 2021 Cochrane review found that ketamine had an effect size (SMD) for depression at 24hours of –0.87, with very low certainty, and that esketamine had an effect size (SMD) at 24hours of –0.31, based on moderate-certainty evidence. However, these meta-analyses have involved largely non-directly comparative studies with dissimilar research designs and patient populations. Only a single clinical trial has directly compared ketamine and esketamine for depression as of May 2021. This study reported similar antidepressant efficacy as well as tolerability and psychotomimetic effects between the two agents. However, the study was small and underpowered, and more research is still needed to better-characterize the comparative antidepressant effects of ketamine and esketamine. Preliminary research suggests that arketamine, the R'(−) enantiomer of ketamine, may also have its own independent antidepressant effects and may contribute to the antidepressant efficacy of racemic ketamine, but more research likewise is needed to evaluate this possibility. In February 2019, an outside panel of experts recommended in a 14–2 vote that the FDA approve the nasal spray version of esketamine for TRD, provided that it be given in a clinical setting, with people remaining on site for at least two hours after. The reasoning for this requirement is that trial participants temporarily experienced sedation, visual disturbances, trouble speaking, confusion, numbness, and feelings of dizziness during immediately after. The approval of esketamine for TRD by the FDA was controversial due to limited and mixed evidence of efficacy and safety. In January 2020, esketamine was rejected by the National Health Service (NHS) of Great Britain. The NHS questioned the benefits of the medication for depression and claimed that it was too expensive. People who have been already using esketamine were allowed to complete treatment if their doctors considered this necessary. Spravato debuted to a cost of treatment of per year when it launched in the United States in March 2019. The Institute for Clinical and Economic Review (ICER), which evaluates cost effectiveness of drugs analogously to the National Institute for Health and Care Excellence (NICE) in the United Kingdom, declined to recommend esketamine for depression due to its steep cost and modest efficacy, deeming it not sufficiently cost-effective. Esketamine is the second drug to be approved for TRD by the FDA, following olanzapine/fluoxetine (Symbyax) in 2009. Other agents, like the atypical antipsychotics aripiprazole (Abilify) and quetiapine (Seroquel), have been approved for use in the adjunctive therapy of MDD in people with a partial response to treatment. In a meta-analysis conducted internally by the FDA during its evaluation of esketamine for TRD, the FDA reported a standardized mean difference (SMD) of esketamine for TRD of 0.28 using the three phase 3 short-term efficacy trials conducted by Janssen. This was similar to an SMD of 0.26 for olanzapine/fluoxetine for TRD and lower than SMDs of 0.35 for aripiprazole and 0.40 for quetiapine as adjuncts for MDD. These drugs are less expensive than esketamine and may serve as more affordable alternatives to it for depression with similar effectiveness.
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Enantiopure drugs
Hydrofluorocarbons are included in the Kyoto Protocol and are regulated under the Kigali Amendment to the Montreal Protocol due to their very high Global Warming Potential and the recognition of halocarbon contributions to climate change. On September 21, 2007, approximately 200 countries agreed to accelerate the elimination of hydrochlorofluorocarbons entirely by 2020 in a United Nations-sponsored Montreal summit. Developing nations were given until 2030. Many nations, such as the United States and China, who had previously resisted such efforts, agreed with the accelerated phase out schedule. India successfully phased out HCFCs by 2020.
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Greenhouse Gases
Carbon tetrachloride was originally synthesized in 1820 by Michael Faraday, who named it "protochloride of carbon", by decomposition of hexachloroethane ("perchloride of carbon") which he synthesized by chlorination of ethylene. The protochloride of carbon has been previously misidentified as tetrachloroethylene because it was made with the same reaction of hexachloroethane. Later in the 19th century, the name protochloride of carbon was used for tetrachloroethylene, and carbon tetrachloride was called "bichloride of carbon" or "perchloride of carbon". Henri Victor Regnault developed another method to synthesise carbon tetrachloride from chloroform, chloroethane or methanol with excess chlorine in 1839. Kolbe made carbon tetrachloride in 1845 by passing chlorine over carbon disulfide through a porcelain tube. Prior to the 1950s, carbon tetrachloride was manufactured by the chlorination of carbon disulfide at 105 to 130 °C: :CS + 3 Cl → CCl + SCl But now it is mainly produced from methane: :CH + 4 Cl → CCl + 4 HCl The production often utilizes by-products of other chlorination reactions, such as from the syntheses of dichloromethane and chloroform. Higher chlorocarbons are also subjected to this process named "chlorinolysis": :CCl + Cl → 2 CCl The production of carbon tetrachloride has steeply declined since the 1980s because of environmental concerns and the decreased demand for CFCs, which were derived from carbon tetrachloride. In 1992, production in the U.S./Europe/Japan was estimated at 720,000 tonnes.
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Greenhouse Gases
In January 2017, the US Food and Drug Administration approved an over-the-counter preparation. Levocetirizine had previously received authorization by the FDA as a prescription drug in 2007, having already been brought to market throughout much of Europe. In India, a prescription-only drug containing levocetirizine hydrochloride and montelukast is sold as Crohist MK.
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Enantiopure drugs
Schotten–Baumann reaction between 4-nitro-3-(trifluoromethyl)aniline [393-11-3] (1) with isobutanoyl chloride [79-30-1] (2) in the presence of triethylamine.
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Enantiopure drugs
Water molecules stay close to each other (cohesion), due to the collective action of hydrogen bonds between water molecules. These hydrogen bonds are constantly breaking, with new bonds being formed with different water molecules; but at any given time in a sample of liquid water, a large portion of the molecules are held together by such bonds. Water also has high adhesion properties because of its polar nature. On clean, smooth glass the water may form a thin film because the molecular forces between glass and water molecules (adhesive forces) are stronger than the cohesive forces. In biological cells and organelles, water is in contact with membrane and protein surfaces that are hydrophilic; that is, surfaces that have a strong attraction to water. Irving Langmuir observed a strong repulsive force between hydrophilic surfaces. To dehydrate hydrophilic surfaces—to remove the strongly held layers of water of hydration—requires doing substantial work against these forces, called hydration forces. These forces are very large but decrease rapidly over a nanometer or less. They are important in biology, particularly when cells are dehydrated by exposure to dry atmospheres or to extracellular freezing.
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Greenhouse Gases
It is prepared by electrofluorination of tributylamine using hydrogen fluoride as solvent and source of fluorine:
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Greenhouse Gases
Side effects include amenorrhea, gynecomastia, galactorrhea, changes in libido, and neuroleptic malignant syndrome. In the U.S., as of 2013 only one case of adverse reaction to levosulpiride had been recorded on the FDA Adverse Event Reporting System Database. A case of rapid onset resistant dystonia caused by low dose levosulpiride was reported in India.
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Enantiopure drugs
Inhalation of chloromethane gas produces central nervous system effects similar to alcohol intoxication. The TLV is 50 ppm and the MAC is the same. Prolonged exposure may have mutagenic effects.
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Greenhouse Gases
The North Australian Pastoral Company (NAPCO) is a large, privately owned, Australian cattle company which operates 13 cattle stations (as well as the Wainui farm and feedlot) covering over 60,000 km, managing about 200,000 cattle, in Queensland and the Northern Territory. It produces beef cattle which are grass fed and grain finished before sale to Australian meat processors who onsell beef to domestic and international customers.
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Greenhouse Gases
Cloxacillin was discovered and developed by Beecham (now GlaxoSmithKline). It is sold under a number of trade names, including Cloxapen, Cloxacap, Tegopen and Orbenin.
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Enantiopure drugs
Chiral drugs with stereo-labile configuration are likely to undergo interconversion of the enantiomers that may be enzymatic (biological) or non-enzymatic. Enzyme-mediated conversion is the process of chiral inversion that happens in a living organism. Non-enzymatic inversion of drugs is important and relevant in the pharmaceutical manufacturing process. This may have impact on the shelf-life of a drug and the economic feasibility of the resolution. Inversion can also happen without enzymes when precolumn derivatization is used in enantioselective chromatographic separation techniques. Racemization can also happen in the acidic environment of the stomach and other bodily fluids.
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Enantiopure drugs
Levoamphetamine{{#tag:ref|Synonyms and alternate spellings include: (IUPAC name), levamfetamine (International Nonproprietary Name [INN]), , , , and is a central nervous system (CNS) stimulant known to increase wakefulness and concentration in association with decreased appetite and fatigue. Pharmaceuticals that contain levoamphetamine are currently indicated and prescribed for the treatment of attention deficit hyperactivity disorder (ADHD), obesity, and narcolepsy in some countries. Levoamphetamine is the levorotatory stereoisomer of the amphetamine molecule. While pharmaceutical formulations containing enantiopure levoamphetamine are no longer manufactured, levomethamphetamine (levmetamfetamine) is still marketed and sold over-the-counter as a nasal decongestant.
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Enantiopure drugs
Escitalopram is sold under many brand names worldwide such as Cipralex, Lexapro, Lexam, Mozarin, Aciprex, Depralin, Ecytara, Elicea, Gatosil, Nexpram, Nexito, Nescital, Szetalo, Stalopam, Pramatis, Betesda, Scippa and Rexipra.
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Enantiopure drugs
Drospirenone is a progestin and antiandrogen medication which is used in birth control pills to prevent pregnancy and in menopausal hormone therapy, among other uses. It is available both alone under the brand name Slynd and in combination with an estrogen under the brand name Yasmin among others. The medication is an analog of the drug spironolactone. Drospirenone is taken by mouth. Common side effects include acne, headache, breast tenderness, weight increase, and menstrual changes. Rare side effects may include high potassium levels and blood clots (when taken as a combined oestrogen-progestogen pill), among others. Drospirenone is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone. It has additional antimineralocorticoid and antiandrogenic activity and no other important hormonal activity. Because of its antimineralocorticoid activity and lack of undesirable off-target activity, drospirenone is said to more closely resemble bioidentical progesterone than other progestins. Drospirenone was patented in 1976 and introduced for medical use in 2000. It is available widely throughout the world. The medication is sometimes referred to as a "fourth-generation" progestin. It is available as a generic medication. In 2020, a formulation of drospirenone with ethinylestradiol was the 145th most commonly prescribed medication in the United States, with more than 4million prescriptions.
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Enantiopure drugs
The absorption of levetiracetam tablets and oral solution is rapid and essentially complete. The bioavailability of levetiracetam is close to 100 percent, and the effect of food on absorption is minor.
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Enantiopure drugs
* The burning of long-buried fossil fuels releases containing carbon of different isotopic ratios to those of living plants, enabling distinction between natural and human-caused contributions to concentration. * There are higher atmospheric concentrations in the Northern Hemisphere, where most of the world's population lives (and emissions originate from), compared to the southern hemisphere. This difference has increased as anthropogenic emissions have increased. * Atmospheric O levels are decreasing in Earth's atmosphere as it reacts with the carbon in fossil fuels to form .
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Greenhouse Gases
The dextrorotary (+)- or d- enantiomer is (1S,2S)-pseudoephedrine, whereas the levorotating (−)- or l- form is (1R,2R)-pseudoephedrine. In the outdated system (+)-pseudoephedrine is also referred to as pseudoephedrine and (−)-pseudoephedrine as pseudoephedrine (in the Fisher projection then the phenyl ring is drawn at bottom). Often the system (with small caps) and the d/l system (with lower-case) are confused. The result is that the dextrorotary d-pseudoephedrine is wrongly named pseudoephedrine and the levorotary l-ephedrine (the diastereomer) wrongly ephedrine. The IUPAC names of the two enantiomers are (1S,2S)- respectively (1R,2R)-2-methylamino-1-phenylpropan-1-ol. Synonyms for both are psi-ephedrine and threo-ephedrine. Pseudoephedrine is the International Nonproprietary Name of the (+)-form, when used as pharmaceutical substance.
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Enantiopure drugs
CFC-113 was one of the most heavily produced CFCs. In 1989, an estimated 250,000 tons were produced. It has been used as a cleaning agent for electrical and electronic components. CFC-113’s low flammability and low toxicity made it ideal for use as a cleaner for delicate electrical equipment, fabrics, and metals. It would not harm the product it was cleaning, ignite with a spark or react with other chemicals. It was used as a dry-cleaning solvent, introduced by Du Pont in March 1961 as "Valclene" and was also marketed as the "solvent of the future" by Imperial Chemical Industries in the 1970s under the tradename Arklone. Others from this series were Perklone (Tetrachloroethylene), Triklone (Trichloroethylene), Methoklone (Dichloromethane) and Genklene (1,1,1-Trichloroethane). CFC-113 is one of the three most popular CFCs, along with CFC-11 and CFC-12. CFC-113 in laboratory analytics has been replaced by other solvents. Reduction of CFC-113 with zinc gives chlorotrifluoroethylene:
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Greenhouse Gases
During the early Eocene, the continental configuration was such that the Arctic sea was almost entirely cut off from the wider oceans. This meant that mixing — provided today by deep water currents such as the Gulf Stream — did not occur, leading to a stratified water column resembling today's Black Sea. High temperatures and winds led to high evaporation, increasing the density of the ocean, and — through an increase in rainfall — high discharge from rivers which fed the basin. This low-density freshwater formed a nepheloid layer, floating on the surface of the dense sea. Even a few centimetres of fresh water would be enough to allow colonization by Azolla; further, this river water would be rich in minerals such as phosphorus, which it would accumulate from mud and rocks it interacted with as it crossed the continents. To further aid the growth of the plant, concentrations of carbon (in the form of carbon dioxide) in the atmosphere are known to have been high at this time. Blooms alone are not enough to have any geological impact; to permanently draw down CO and cause climate change, the carbon must be sequestered by the plants being buried and the remains rendered inaccessible to decomposing organisms. The anoxic bottom of the Arctic basin, a result of the stratified water column, permitted just this; the anoxic environment inhibits the activity of decomposing organisms and allows the plants to sit unrotted until they are buried by sediment.
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Greenhouse Gases
Carbon tetrachloride was widely used as a fumigant to kill insect pests in stored grain. It was employed in a mixture known as 80/20, that was 80% carbon tetrachloride and 20% carbon disulfide. The United States Environmental Protection Agency banned its use in 1985. Another carbon tetrachloride fumigant preparation mixture contained acrylonitrile. Carbon tetrachloride reduced the flammability of the mixture. Most common trade names for the preparation were Acritet, Carbacryl and Acrylofume. The most common preparation, Acritet, was prepared with 34 percent acrylonitrile and 66 percent carbon tetrachloride.
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Greenhouse Gases
OCO-3 is constructed from spare equipment from the OCO-2 mission. Thus its physical characteristics are similar, but with some adaptations. A 2-axis pointing mirror was added, which will allow targeting of cities and other areas on order of for area mapping (also called "snapshot mode"). A resolution context camera was also added. An onboard cryocooler will maintain detector temperatures of around . Entrance optics were modified to maintain a similar ground footprint to OCO-2. Similar to OCO and OCO-2, the main measurement will be of reflected near-IR sunlight. Grating spectrometers separate incoming light energy into different components of the electromagnetic spectrum (or wavelengths or "colors"). Because and molecular oxygen absorb light at specific wavelengths, the signal or absorption levels at different wavelengths provide information on the amount of gases. Three bands are used called Weak (around 1.6 μm), Strong (around 2.0 μm), and Oxygen-A (around 0.76 μm). There are 1,016 spectral elements per band, and measurements are made simultaneously at 8 side-by-side locations or "footprints" each about or smaller, 3 times per second.
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Greenhouse Gases
Animal and human data have revealed evidence of harm to the embryo and teratogenicity associated with ACE inhibitors.
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Enantiopure drugs
The age of a water parcel can be estimated by the CFC partial pressure (pCFC) age or SF partial pressure (pSF) age. The pCFC age of a water sample is defined as: where [CFC] is the measured CFC concentration (pmol kg) and F is the solubility of CFC gas in seawater as a function of temperature and salinity. The CFC partial pressure is expressed in units of 10–12 atmospheres or parts-per-trillion (ppt). The solubility measurements of CFC-11 and CFC-12 have been previously measured by Warner and Weiss Additionally, the solubility measurement of CFC-113 was measured by Bu and Warner and SF by Wanninkhof et al. and Bullister et al. Theses authors mentioned above have expressed the solubility (F) at a total pressure of 1 atm as: where F = solubility expressed in either mol l or mol kg atm, T = absolute temperature, S = salinity in parts per thousand (ppt), a, a, a, b, b, and b are constants to be determined from the least squares fit to the solubility measurements. This equation is derived from the integrated Van 't Hoff equation and the logarithmic Setchenow salinity dependence. It can be noted that the solubility of CFCs increase with decreasing temperature at approximately 1% per degree Celsius. Once the partial pressure of the CFC (or SF) is derived, it is then compared to the atmospheric time histories for CFC-11, CFC-12, or SF in which the pCFC directly corresponds to the year with the same. The difference between the corresponding date and the collection date of the seawater sample is the average age for the water parcel. The age of a parcel of water can also be calculated using the ratio of two CFC partial pressures or the ratio of the SF partial pressure to a CFC partial pressure.
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Greenhouse Gases
Drospirenone is an antagonist of the AR, the biological target of androgens like testosterone and dihydrotestosterone (DHT). It has about 1 to 65% of the affinity of the synthetic anabolic steroid metribolone for the AR. The medication is more potent as an antiandrogen than spironolactone, but is less potent than cyproterone acetate, with about 30% of its antiandrogenic activity in animals. Progesterone displays antiandrogenic activity in some assays similarly to drospirenone, although this issue is controversial and many researchers regard progesterone as having no significant antiandrogenic activity. Drospirenone shows antiandrogenic effects on the serum lipid profile, including higher HDL cholesterol and triglyceride levels and lower LDL cholesterol levels, at a dose of 3 mg/day in women. The medication does not inhibit the effects of ethinylestradiol on sex hormone-binding globulin (SHBG) and serum lipids, in contrast to androgenic progestins like levonorgestrel but similarly to other antiandrogenic progestins like cyproterone acetate. SHBG levels are significantly higher with ethinylestradiol and cyproterone acetate than with ethinylestradiol and drospirenone, owing to the more potent antiandrogenic activity of cyproterone acetate relative to drospirenone. Androgenic progestins like levonorgestrel have been found to inhibit the procoagulatory effects of estrogens like ethinylestradiol on hepatic synthesis of coagulation factors, whereas this may occur less or not at all with weakly androgenic progestins like desogestrel and antiandrogenic progestins like drospirenone.
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Enantiopure drugs
The density of water is about : this relationship was originally used to define the gram. The density varies with temperature, but not linearly: as the temperature increases, the density rises to a peak at and then decreases; the initial increase is unusual because most liquids undergo thermal expansion so that the density only decreases as a function of temperature. The increase observed for water from to and for a few other liquids is described as negative thermal expansion. Regular, hexagonal ice is also less dense than liquid water—upon freezing, the density of water decreases by about 9%. These peculiar effects are due to the highly directional bonding of water molecules via the hydrogen bonds: ice and liquid water at low temperature have comparatively low-density, low-energy open lattice structures. The breaking of hydrogen bonds on melting with increasing temperature in the range 0–4 °C allows for a denser molecular packing in which some of the lattice cavities are filled by water molecules. Above 4 °C, however, thermal expansion becomes the dominant effect, and water near the boiling point (100 °C) is about 4% less dense than water at . Under increasing pressure, ice undergoes a number of transitions to other polymorphs with higher density than liquid water, such as ice II, ice III, high-density amorphous ice (HDA), and very-high-density amorphous ice (VHDA). The unusual density curve and lower density of ice than of water is essential for much of the life on earth—if water were most dense at the freezing point, then in winter the cooling at the surface would lead to convective mixing. Once 0 °C are reached, the water body would freeze from the bottom up, and all life in it would be killed. Furthermore, given that water is a good thermal insulator (due to its heat capacity), some frozen lakes might not completely thaw in summer. As it is, the inversion of the density curve leads to a stable layering for surface temperatures below 4 °C, and with the layer of ice that floats on top insulating the water below, even e.g., Lake Baikal in central Siberia freezes only to about 1 m thickness in winter. In general, for deep enough lakes, the temperature at the bottom stays constant at about 4 °C (39 °F) throughout the year (see diagram).
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Greenhouse Gases
Pseudoephedrine is contraindicated in patients with diabetes mellitus, cardiovascular disease, severe or uncontrolled hypertension, severe coronary artery disease, prostatic hypertrophy, hyperthyroidism, closed angle glaucoma, or by pregnant women. The safety and effectiveness of nasal decongestant use in children is unclear.
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Enantiopure drugs
An important feature of water is its polar nature. The structure has a bent molecular geometry for the two hydrogens from the oxygen vertex. The oxygen atom also has two lone pairs of electrons. One effect usually ascribed to the lone pairs is that the H–O–H gas-phase bend angle is 104.48°, which is smaller than the typical tetrahedral angle of 109.47°. The lone pairs are closer to the oxygen atom than the electrons sigma bonded to the hydrogens, so they require more space. The increased repulsion of the lone pairs forces the O–H bonds closer to each other. Another consequence of its structure is that water is a polar molecule. Due to the difference in electronegativity, a bond dipole moment points from each H to the O, making the oxygen partially negative and each hydrogen partially positive. A large molecular dipole, points from a region between the two hydrogen atoms to the oxygen atom. The charge differences cause water molecules to aggregate (the relatively positive areas being attracted to the relatively negative areas). This attraction, hydrogen bonding, explains many of the properties of water, such as its solvent properties. Although hydrogen bonding is a relatively weak attraction compared to the covalent bonds within the water molecule itself, it is responsible for several of the waters physical properties. These properties include its relatively high melting and boiling point temperatures: more energy is required to break the hydrogen bonds between water molecules. In contrast, hydrogen sulfide (), has much weaker hydrogen bonding due to sulfurs lower electronegativity. is a gas at room temperature, despite hydrogen sulfide having nearly twice the molar mass of water. The extra bonding between water molecules also gives liquid water a large specific heat capacity. This high heat capacity makes water a good heat storage medium (coolant) and heat shield.
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Greenhouse Gases
The most common adverse effects of levetiracetam treatment include CNS effects such as somnolence, decreased energy, headache, dizziness, mood swings and coordination difficulties. These adverse effects are most pronounced in the first month of therapy. About 4% of patients dropped out of pre-approval clinical trials due to these side effects. About 13% of people taking levetiracetam experience adverse neuropsychiatric symptoms, which are usually mild. These include agitation, hostility, apathy, anxiety, emotional lability, and depression. Serious psychiatric adverse side effects that are reversed by drug discontinuation occur in about 1%. These include hallucinations, suicidal thoughts, or psychosis. These occurred mostly within the first month of therapy, but they could develop at any time during treatment. Although rare, Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which appears as a painful spreading rash with redness and blistering and/or peeling skin, have been reported in patients treated with levetiracetam. The incidence of SJS following exposure to anti-epileptics such as levetiracetam is about 1 in 3,000. Levetiracetam should not be used in people who have previously shown hypersensitivity to levetiracetam or any of the inactive ingredients in the tablet or oral solution. Such hypersensitivity reactions include, but are not limited to, unexplained rash with redness or blistered skin, difficulty breathing, and tightness in the chest or airways. In a study, the incidence of decreased bone mineral density of patients on levetiracetam was significantly higher than those for other epileptic medications.
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Enantiopure drugs
Fine particles dispersed in the atmosphere can serve as cloud condensation nuclei and thereby cause marine cloud brightening Eventually all FeCl particles are washed out of the air and fall on land or water, where they dissolve into iron compounds and salt. Iron salt aerosols may also therefore contribute to iron fertilization.
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Greenhouse Gases
Levomilnacipran (brand name Fetzima) is an antidepressant which was approved in the United States in 2013 for the treatment of major depressive disorder (MDD) in adults. It is the levorotatory enantiomer of milnacipran, and has similar effects and pharmacology, acting as a serotonin–norepinephrine reuptake inhibitor (SNRI).
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Enantiopure drugs
R-454B is not the only blend of R-32 and R-1234yf to be proposed as a refrigerant. Other blends include R-454A (35 percent R-32, 65 percent R-1234yf) and R-454C (21.5 percent R-32, 78.5 percent R1234yf). There are also several blends that include a third component.
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Greenhouse Gases
NAPCO was the first company which was able to progress to registration of final 14001 certification. This was primarily due to the increased costs of surveillance audits and an absence of market incentives to promote this certificate as the gold standard within the Australian beef industry. A ‘cluster approach’ was utilised by the company when working towards certification; this meant that the entire company qualified for certification, rather than each individual worker. The effect of the ‘cluster approach’ was to reduce the substantive cost involved in certification and the subsequent surveillance audits that would have to be implemented; this meant that cost was able to be reduced by approximately 50%. This approach also provided a means by which workload and ideas between producers could be collectively distributed.
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Greenhouse Gases
Many marine organisms biosynthesize halomethanes, especially bromine-containing compounds. Small amounts of chloromethanes arise from the interaction of chlorine sources with various carbon compounds. The biosyntheses of these halomethanes are catalyzed by the chloroperoxidase and bromoperoxidase enzymes, respectively. An idealized equation is:
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Greenhouse Gases
Dexmedetomidine is a highly selective α-adrenergic agonist. It possesses an α:α selectivity ratio of 1620:1, making it eight times more selective for the α-receptor than clonidine. Unlike opioids and other sedatives such as propofol, dexmedetomidine is able to achieve its effects without causing respiratory depression. Dexmedetomidine induces sedation by decreasing activity of noradrenergic neurons in the locus ceruleus in the brain stem, thereby increasing the downstream activity of inhibitory gamma-aminobutyric acid (GABA) neurons in the ventrolateral preoptic nucleus. In contrast, other sedatives like propofol and benzodiazepines directly increase activity of gamma-aminobutyric acid neurons. Through action on this endogenous sleep-promoting pathway the sedation produced by dexmedetomidine more closely mirrors natural sleep (specifically stage 2 non-rapid eye movement sleep), as demonstrated by EEG studies. As such, dexmedetomidine provides less amnesia than benzodiazepines. Dexmedetomidine also has analgesic effects at the spinal cord level and other supraspinal sites.
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Enantiopure drugs
Benzylpenicillin, also known as penicillin G (PenG) or BENPEN, is an antibiotic used to treat a number of bacterial infections. This includes pneumonia, strep throat, syphilis, necrotizing enterocolitis, diphtheria, gas gangrene, leptospirosis, cellulitis, and tetanus. It is not a first-line agent for pneumococcal meningitis. Due to benzylpenicillin's limited bioavailability for oral medications, it is generally taken as an injection in the form of a sodium, potassium, benzathine, or procaine salt. Benzylpenicillin is given by injection into a vein or muscle. Two long-acting forms benzathine benzylpenicillin and procaine benzylpenicillin are available for use by injection into a muscle only. Side effects include diarrhea, seizures, and allergic reactions including anaphylaxis. When used to treat syphilis or Lyme disease a reaction known as Jarisch–Herxheimer may occur. It is not recommended in those with a history of penicillin allergy. Use during pregnancy is generally safe in the penicillin and β-lactam class of medications. Benzylpenicillin is on the World Health Organization's List of Essential Medicines.
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Enantiopure drugs
Most of the methyl chloride present in the environment ends up being released to the atmosphere. After being released into the air, the atmospheric lifetime of this substance is about 10 months with multiple natural sinks, such as ocean, transport to the stratosphere, soil, etc. On the other hand, when the methyl chloride emitted is released to water, it will be rapidly lost by volatilization. The half-life of this substance in terms of volatilization in the river, lagoon and lake is 2.1 h, 25 h and 18 days, respectively. The amount of methyl chloride in the stratosphere is estimated to be 2 x 10 tonnes per year, representing 20-25% of the total amount of chlorine that is emitted to the stratosphere annually.
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Greenhouse Gases
Bromochlorodifluoromethane (BCF), also referred to by the code numbers Halon 1211 and Freon 12B1, is a haloalkane with the chemical formula CFClBr. It is used for fire suppression, especially for expensive equipment or items that could be damaged by the residue from other types of extinguishers. It is stored as a liquid under pressure and vaporizes when discharged to suppress fires. The use of halons, including Halon 1211, has decreased over time due to their adverse impact on the ozone layer. Alternatives have been developed to mitigate environmental concerns while still providing effective fire suppression capabilities.
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Greenhouse Gases
The Montreal Protocol targeted 1,1,1-trichloroethane as one of those compounds responsible for ozone depletion and banned its use beginning in 1996. Since then, its manufacture and use have been phased out throughout most of the world. Its atmospheric presence has declined rapidly due to its relatively short atmospheric lifetime of about 5 years.
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Greenhouse Gases
Both the oral and intravenous preparations of flucloxacillin are inexpensive and are available as the sodium salt flucloxacillin sodium, in capsules (250 or 500 mg), oral suspensions (125 mg/5 ml or 250 mg/5 ml), and injections (powder for reconstitution, 250, 500, 1000 and 2000 mg per vial). Flucloxacillin is not commonly used in the United States or Canada as of 2011. In several other countries however, it is supplied under a variety of trade names including Floxapen, Flopen, Flubex, Flupen, Phylopen, and Staphylex.
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Enantiopure drugs
Exemestane is indicated for the adjuvant treatment of postmenopausal women with estrogen-receptor positive early breast cancer who have received two to three years of tamoxifen and are switched to it for completion of a total of five consecutive years of adjuvant hormonal therapy. US FDA approval was in October 1999. Exemestane is also indicated for the treatment of advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy. For premenopausal women with hormone-receptor–positive breast cancer, adjuvant treatment with ovarian suppression plus the aromatase inhibitor exemestane, as compared with ovarian suppression plus tamoxifen, provides a new treatment option that reduces the risk of recurrence. The TEXT and SOFT trials demonstrated improved disease free survival in patients treated with exemestane and ovarian suppression compared to the tamoxifen and ovarian suppression group. Premenopausal women who receive ovarian suppression may now benefit from an aromatase inhibitor, a class of drugs that until now has been recommended only for postmenopausal women.
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Enantiopure drugs
A 2006 meta analysis concluded that compared to other proton pump inhibitors, esomeprazole confers a modest overall benefit in esophageal healing and symptom relief. When broken down by disease severity, the benefit of esomeprazole relative to other proton pump inhibitors was negligible in people with mild disease (number needed to treat 50), but appeared more in those with severe disease (number needed to treat 8). A second meta analysis also found increases in erosive esophageal healing (>95% healing rate) when compared to standardized doses in broadly selected patient populations. A 2017 study found esomeprazole to be among a number of effective PPIs.
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Enantiopure drugs
The Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BLA) was a 2005 landmark trial that compared the effects of the established therapy of the combination of atenolol and bendroflumethiazide to the new drug combination of amlodipine and perindopril (trade names Viacoram, AceryCal etc.). The study of more than 19 000 patients world-wide was terminated earlier than anticipated because it clearly demonstrated a statistically significant improvement in mortality and cardiovascular outcomes with the newer treatment. The combination of amlodipine and perindopril remains in the current treatment guidelines for hypertension and the outcomes of the ASCOT-BLA trial paved the way for further research into combination therapy and newer agents.
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Enantiopure drugs
<section begin=Chembox /> <section end=Chembox /> Water () is a polar inorganic compound that is at room temperature a tasteless and odorless liquid, which is nearly colorless apart from an inherent hint of blue. It is by far the most studied chemical compound and is described as the "universal solvent" and the "solvent of life". It is the most abundant substance on the surface of Earth and the only common substance to exist as a solid, liquid, and gas on Earth's surface. It is also the third most abundant molecule in the universe (behind molecular hydrogen and carbon monoxide). Water molecules form hydrogen bonds with each other and are strongly polar. This polarity allows it to dissociate ions in salts and bond to other polar substances such as alcohols and acids, thus dissolving them. Its hydrogen bonding causes its many unique properties, such as having a solid form less dense than its liquid form, a relatively high boiling point of 100 °C for its molar mass, and a high heat capacity. Water is amphoteric, meaning that it can exhibit properties of an acid or a base, depending on the pH of the solution that it is in; it readily produces both hydron (chemistry)| and hydroxide| ions. Related to its amphoteric character, it undergoes self-ionization. The product of the activities, or approximately, the concentrations of and is a constant, so their respective concentrations are inversely proportional to each other.
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Greenhouse Gases
Levomethorphan (LVM) (INN, BAN) is an opioid analgesic of the morphinan family that has never been marketed. It is the -stereoisomer of racemethorphan (methorphan). The effects of the two isomers of racemethorphan are quite different, with dextromethorphan (DXM) being an antitussive at low doses and a dissociative hallucinogen at much higher doses. Levomethorphan is about five times stronger than morphine. Levomethorphan is a prodrug to levorphanol, analogously to DXM acting as a prodrug to dextrorphan or codeine behaving as a prodrug to morphine. As such, levomethorphan has similar effects to levorphanol but is less potent as it must be demethylated to the active form by liver enzymes before being able to produce its effects. As a prodrug of levorphanol, levomethorphan functions as a potent agonist of all three of the opioid receptors, μ, κ (κ and κ but notably not κ), and δ, as an NMDA receptor antagonist, and as a serotonin-norepinephrine reuptake inhibitor. Via activation of the κ-opioid receptor, levomethorphan can produce dysphoria and psychotomimetic effects such as dissociation and hallucinations. Levomethorphan is listed under the Single Convention on Narcotic Drugs 1961 and is regulated like morphine in most countries. In the United States it is a Schedule II Narcotic controlled substance with a DEA ACSCN of 9210 and a 2014 annual aggregate manufacturing quota of 195 grams, up from 6 grams the year before. The salts in use are the tartrate (free base conversion ratio 0.644) and hydrobromide (0.958). At the current time, no levomethorphan pharmaceuticals are marketed in the United States.
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Enantiopure drugs
In the late 19th century, scientists experimentally discovered that and do not absorb infrared radiation (called, at that time, "dark radiation"), while water (both as true vapor and condensed in the form of microscopic droplets suspended in clouds) and and other poly-atomic gaseous molecules do absorb infrared radiation. In the early 20th century, researchers realized that greenhouse gases in the atmosphere made Earths overall temperature higher than it would be without them. The term greenhouse' was first applied to this phenomenon by Nils Gustaf Ekholm in 1901. During the late 20th century, a scientific consensus evolved that increasing concentrations of greenhouse gases in the atmosphere cause a substantial rise in global temperatures and changes to other parts of the climate system, with consequences for the environment and for human health.
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Greenhouse Gases
Dexketoprofen is a nonsteroidal anti-inflammatory drug (NSAID). It is manufactured by Menarini, under the tradename Keral. It is available in the UK, as dexketoprofen trometamol, as a prescription-only drug and in Latin America as Enantyum, produced by Menarini. Also, in Italy and Spain it is available as an over-the-counter drug (OTC) under the trade name Enandol or Enantyum. In Hungary it is available from a pharmacy as "Ketodex". In Turkey, it is an over the counter medicine under the name "Arveles". In Latvia, Lithuania and Estonia it is available as an OTC under the tradename Dolmen In Mexico it is available in tablet form as "Stadium" made by Menarini. It is the dextrorotatory stereoisomer of ketoprofen.
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Enantiopure drugs
As an antibiotic, benzylpenicillin is noted to possess effectiveness mainly against gram-positive organisms. Some gram-negative organisms such as Neisseria gonorrhoeae and Leptospira weilii are also reported to be susceptible to benzylpenicillin.
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Enantiopure drugs
Dextroamphetamine is used to treat attention deficit hyperactivity disorder (ADHD) and narcolepsy (a sleep disorder), and is sometimes prescribed for depression and obesity.
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Enantiopure drugs
Flutamide has been found to be effective in the treatment of hirsutism (excessive body/facial hair growth) in numerous studies. It possesses moderate effectiveness for this indication, and the overall quality of the evidence is considered to be moderate. The medication shows equivalent or superior effectiveness to other antiandrogens including spironolactone, cyproterone acetate, and finasteride in the treatment of hirsutism, although its relatively high risk of hepatotoxicity makes it unfavorable compared to these other options. It has been used to treat hirsutism at dosages ranging from 62.5 mg/day to 750 mg/day. A study found that multiple dosages of flutamide significantly reduced hirsutism in women with polycystic ovary syndrome and that there were no significant differences in the effectiveness for dosages of 125 mg/day, 250 mg/day, and 375 mg/day. In addition, a study found that combination of 125 mg/day flutamide with finasteride was no more effective than 125 mg/day flutamide alone in the treatment of hirsutism. These findings support the use of flutamide at lower doses for hirsutism without loss of effectiveness, which may help to lower the risk of hepatotoxicity. However, the risk has been found to remain even at very low doses.
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Enantiopure drugs
Drospirenone binds with high affinity to the progesterone receptor (PR) and mineralocorticoid receptor (MR), with lower affinity to the androgen receptor (AR), and with very low affinity to the glucocorticoid receptor (GR). It is an agonist of the PR and an antagonist of the MR and AR, and hence is a progestogen, antimineralocorticoid, and antiandrogen. Drospirenone has no estrogenic activity and no appreciable glucocorticoid or antiglucocorticoid activity.
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Enantiopure drugs
Meropenem is administered intravenously as an aqueous solution. Meropenem is stored in vials as white crystalline powder (containing meropenem as the trihydrate blended with anhydrous sodium carbonate). For intravenous administration, the powder is dissolved in 5% monobasic potassium phosphate solution, since meropenem is soluble in 5% monobasic potassium phosphate solution and only sparingly soluble in water (). For intravenous bolus administration, injection vials are reconstituted with sterile water for injection. Reconstituted (dissolved) meropenem degrades over time. The degradation may be associated with color change of the solution, typical for a hydrolysis of the amide bond of the β-lactam ring as seen with most β-lactam antibiotics, while particularly for merapenem the color is changing from colorless or pale yellow to vivid yellowish. Upon reconstitution, the merapenem infusion solution, prepared with 0.9% sodium chloride, exhibits both chemical and physical stability for a duration of 3 hours at a temperature up to °C. If refrigerated (°C), the stability extends to 24 hours. However, when the product is reconstituted in a 5% dextrose solution, it is used immediately to ensure its efficacy. The degradation of meropenem in a water-based solution is affected by factors such as pH, temperature, initial concentration, and the specific type of infusion solution used. Meropenem solutions should not be frozen. Meropenem is administered every 8 hours. Dosing must be adjusted for altered kidney function and for haemofiltration. Studies recomment application of meropenem therapeutic drug monitoring for optimal application. As with other β-lactams antibiotics, the effectiveness of treatment depends on the amount of time during the dosing interval that the meropenem concentration is above the minimum inhibitory concentration for the bacteria causing the infection. For β-lactams, including meropenem, prolonged intravenous administration is associated with lower mortality than bolus intravenous infusion in persons with whose infections are severe, or caused by bacteria that are less sensitive to meropenem, such as Pseudomonas aeruginosa. Meropenem exhibit poor permeability across the gut and low oral bioavailability because of its hydrophilic properties, which inhibit its passive diffusion across the intestinal epithelium. The challenges related to research of oral delivery of meropenem are related to high susceptibility of meropenem to degradation through hydrolysis of the amide bond in the β-lactam ring, even at relatively low temperatures and humidity. This instability can result in the loss of meropenems antibacterial activity. Besides that, neropenem is unstable in the acidic environment of the stomach, leading to extensive degradation and loss of the drug after oral administration. In addition, intestinal efflux (secretory) transport can pump the drug back into the gut: efflux transporters, particularly P-glycoprotein (P-gp), present in the gastrointestinal tract can actively pump meropenem back into the gut lumen, limiting its absorption and reducing oral bioavailability; in the attempts of oral administration bacteria can develop resistance to meropenem by enhancing the active efflux of the antibiotic through efflux transporters, such as the MexAB-OprM tripartite efflux system in Pseudomonas aeruginosa. Thats why meropenem is administered intravenously. There is insufficient data regarding the administration of meropenem during breastfeeding. However, it has been observed that, in general, the concentration of this beta-lactam antibiotic in breast milk is relatively low, therefore, beta-lactam antibiotics are not anticipated to induce detrimental effects in infants who are breastfed. Nonetheless, there have been sporadic reports of disturbances in the gastrointestinal flora of the infant, manifesting as diarrhea or oral candidiasis (thrush), associated with the use of beta-lactam antibiotics, however, these potential side effects have not been thoroughly investigated specifically in the context of meropenem use, therefore, the safety profile of meropenem in breastfeeding mothers and their infants is unknown.
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Enantiopure drugs
Eszopiclone acts on benzodiazepine binding site situated on GABA neurons as a positive allosteric modulator. Eszopiclone is rapidly absorbed after oral administration, with serum levels peaking between .45 and 1.3 hours. The elimination half-life of eszopiclone is approximately 6 hours and it is extensively metabolized by oxidation and demethylation. Approximately 52% to 59% of a dose is weakly bound to plasma protein. Cytochrome P450 (CYP) isozymes CYP3A4 and CYP2E1 are involved in the biotransformation of eszopiclone; thus, drugs that induce or inhibit these CYP isozymes may affect the metabolism of eszopiclone. Less than 10% of the orally administered dose is excreted in the urine as racemic zopiclone. In terms of benzodiazepine receptor binding and relevant potency, 3 mg of eszopiclone is equivalent to 10 mg of diazepam.
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Enantiopure drugs
Cilazapril is an angiotensin-converting enzyme inhibitor (ACE inhibitor) used for the treatment of hypertension and congestive heart failure. It was patented in 1982 and approved for medical use in 1990.
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Enantiopure drugs
Piperacillin irreversibly binds to the enzyme penicillin-binding proteins, inhibiting the biosynthesis of bacterial cell walls.
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Enantiopure drugs
People who are taking meperidine, tramadol, methadone, propoxyphene, dextromethorphan, St. John’s wort, cyclobenzaprine, or another MAO inhibitor should not take rasagiline. The FDA drug label carries a warning of the risk of serotonin syndrome when rasagiline is used with antidepressants or with meperidine. However the risk appears to be low, based on a multicenter retrospective study in 1504 people, which looked for serotonin syndrome in people with PD who were treated with rasagiline plus antidepressants, rasagiline without antidepressants, or antidepressants plus Parkinson's drugs other than either rasagiline or selegiline; no cases were identified. There is a risk of psychosis or bizarre behavior if rasagiline is used with dextromethorphan and there is a risk of non-selective MAO inhibition and hypertensive crisis if rasagiline is used with other MAO inhibitors.
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Enantiopure drugs
Dextroamphetamine is the active metabolite of the prodrug lisdexamfetamine (L-lysine-dextroamphetamine), available by the brand name Vyvanse (Elvanse in the European market) (Venvanse in the Brazil market) (lisdexamfetamine dimesylate). Dextroamphetamine is liberated from lisdexamfetamine enzymatically following contact with red blood cells. The conversion is rate-limited by the enzyme, which prevents high blood concentrations of dextroamphetamine and reduces lisdexamfetamine's drug liking and abuse potential at clinical doses. Vyvanse is marketed as once-a-day dosing as it provides a slow release of dextroamphetamine into the body. Vyvanse is available as capsules, and chewable tablets, and in seven strengths; 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, and 70 mg. The conversion rate between lisdexamfetamine dimesylate (Vyvanse) to dextroamphetamine base is 29.5%.
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Enantiopure drugs
In veterinary medicine, ampicillin is used in cats, dogs, and farm animals to treat: * Anal gland infections * Cutaneous infections, such as abscesses, cellulitis, and pustular dermatitis * E. coli and Salmonella infections in cattle, sheep, and goats (oral form). Ampicillin use for this purpose had declined as bacterial resistance has increased. * Mastitis in sows * Mixed aerobic–anaerobic infections, such as from cat bites * Multidrug-resistant Enterococcus faecalis and E. faecium * Prophylactic use in poultry against Salmonella and sepsis from E. coli or Staphylococcus aureus * Respiratory tract infections, including tonsilitis, bovine respiratory disease, shipping fever, bronchopneumonia, and calf and bovine pneumonia * Urinary tract infections in dogs Horses are generally not treated with oral ampicillin, as they have low bioavailability of beta-lactams. The half-life in animals is around that same of that in humans (just over an hour). Oral absorption is less than 50% in cats and dogs, and less than 4% in horses.
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Enantiopure drugs
In E for Ecstasy (a book examining the uses of the street drug ecstasy in the UK) the writer, activist and ecstasy advocate Nicholas Saunders highlighted test results showing that certain consignments of the drug also contained selegiline. Consignments of ecstasy known as "Strawberry" contained what Saunders described as a "potentially dangerous combination of ketamine, ephedrine and selegiline," as did a consignment of "Sitting Duck" Ecstasy tablets. David Pearce wrote The Hedonistic Imperative six weeks after starting taking selegiline. In Gregg Hurwitzs novel Out of the Dark, selegiline (Emsam') and tyramine-containing food were used to assassinate the president of the United States.
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Enantiopure drugs
In 2005, Myriad Genetics reported the results of its Phase II clinical trial of Flurizan; it was the largest ever Alzheimers drug treatment trial using R-flurbiprofen. Patients were split into three treatment groups, receiving placebo, 400 or 800 mg R-flurbiprofen twice daily for a year. Result from this trial showed that the drug was well tolerated, and positive trends were observed with the 800 mg twice-daily dose in patients with mild Alzheimers disease. A subgroup of patients that were diagnosed with mild disease, and had high plasma drug levels had significantly less decline in two primary behavioral outcomes (Activities of Daily Living scale (ADCS-ADL) and Global Function (CDR-SB)). Approximately 80 patients enrolled in the optional follow-on study showed continuing benefits with R-flurbiprofen, with increasing positive trends over this period for all primary outcomes after 24 months. On March 5, 2007 Myriad reported final results of the two-year trial, showing that 42% of those 80 patients showed improvement or no decline in one or more of the three primary endpoints of cognition, global function and activities of daily living, compared to a typical 10% of patients on placebo. A Phase III clinical study evaluated 800 mg R-flurbiprofen twice-daily versus placebo for 18 months exclusively in 1800 patients with mild Alzheimers disease. This second trial concluded in February 2008 with results reported in the summer. After Phase III testing, which included nearly 1,700 patients with mild Alzheimers disease treated for 18 months with either Flurizan or placebo, Myrial Genetics concluded that the drug did not improve thinking ability or the ability of patients to carry out daily activities significantly more than those patients with placebo. Peter Meldrum, the chief executive of Myriad, announced on June 30, 2008, that the company will no longer be developing Flurizan. Prior to this termination, Myriad had sold distribution rights in the European Union to Lundbeck for an initial payment of $100 million, which Lundbeck has indicated it will now take as a write-down.
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Enantiopure drugs
OCOs measurements are designed to be accurate enough to show for the first time the geographic distribution of carbon dioxide sources and sinks on a regional scale. The data is planned to improve the understanding of the global carbon cycle, the natural processes and human activities that influence the abundance and distribution of the greenhouse gas. This improved understanding is expected to enable more reliable forecasts of future changes in the abundance and distribution of carbon dioxide in the atmosphere and the effect that these changes may have on Earths climate. The OCO spacecraft was provided by Orbital Sciences Corporation. During its two-year mission, OCO will fly in a near polar orbit which enables the instrument to observe most of Earths surface at least once every sixteen days. It is intended to fly in loose formation with a series of other Earth-orbiting satellites known as the Earth Observing System Afternoon Constellation, or the A-train. This coordinated flight formation was intended to enable researchers to correlate OCO data with data acquired by other instruments on other spacecraft. In particular, Earth scientists would like to compare OCO data with nearly simultaneous measurements acquired by the Atmospheric Infrared Sounder (AIRS) instrument aboard NASAs Aqua satellite and ground-based data from the Total Carbon Column Observing Network (TCCON). Alignment with the A-train demands a particularly short launch window of 30 seconds. The original cost of the mission was . It was sponsored by NASAs Earth System Science Pathfinder Program. NASAs Jet Propulsion Laboratory in Pasadena, California, manages OCO for NASA's Science Mission Directorate.
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Greenhouse Gases
Perfluorohexane (), or tetradecafluorohexane, is a fluorocarbon. It is a derivative of hexane in which all the hydrogen atoms are replaced by fluorine atoms. It is used in one formulation of the electronic cooling liquid/insulator Fluorinert for low-temperature applications due to its low boiling point of 56 °C and freezing point of −90 °C. It is odorless and colorless. Unlike typical hydrocarbons, the structure features a helical carbon backbone.
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Greenhouse Gases
A single water molecule can participate in a maximum of four hydrogen bonds because it can accept two bonds using the lone pairs on oxygen and donate two hydrogen atoms. Other molecules like hydrogen fluoride, ammonia, and methanol can also form hydrogen bonds. However, they do not show anomalous thermodynamic, kinetic, or structural properties like those observed in water because none of them can form four hydrogen bonds: either they cannot donate or accept hydrogen atoms, or there are steric effects in bulky residues. In water, intermolecular tetrahedral structures form due to the four hydrogen bonds, thereby forming an open structure and a three-dimensional bonding network, resulting in the anomalous decrease in density when cooled below 4 °C. This repeated, constantly reorganizing unit defines a three-dimensional network extending throughout the liquid. This view is based upon neutron scattering studies and computer simulations, and it makes sense in the light of the unambiguously tetrahedral arrangement of water molecules in ice structures. However, there is an alternative theory for the structure of water. In 2004, a controversial paper from Stockholm University suggested that water molecules in the liquid state typically bind not to four but only two others; thus forming chains and rings. The term "string theory of water" (which is not to be confused with the string theory of physics) was coined. These observations were based upon X-ray absorption spectroscopy that probed the local environment of individual oxygen atoms.
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Greenhouse Gases
In liquid water there is some self-ionization giving hydronium ions and hydroxide ions. The equilibrium constant for this reaction, known as the ionic product of water, , has a value of about at 25 °C. At neutral pH, the concentration of the hydroxide ion () equals that of the (solvated) hydrogen ion (), with a value close to 10 mol L at 25 °C. See data page for values at other temperatures. The thermodynamic equilibrium constant is a quotient of thermodynamic activities of all products and reactants including water: However, for dilute solutions, the activity of a solute such as HO or OH is approximated by its concentration, and the activity of the solvent HO is approximated by 1, so that we obtain the simple ionic product
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Greenhouse Gases
Oxacillin, through its β-lactam ring, covalently binds to penicillin-binding proteins, which are enzymes involved in the synthesis of the bacterial cell wall. This binding interaction interferes with the transpeptidation reaction and inhibits the synthesis of peptidoglycan, a prominent component of the cell wall. By decreasing the integrity of the bacterial cell wall, it is thought that oxacillin and other penicillins kill actively growing bacteria through cell autolysis.
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Enantiopure drugs
The concentration of HCFC-141b in the atmosphere grew to near 25 parts per trillion by year 2016. It has an ozone depletion potential (ODP) of 0.12. This is low compared to the ODP=1 of trichlorofluoromethane (CFC-11, R-11), which also grew about ten times more abundant in the atmosphere prior to introduction of HFC-141b and subsequent adoption of the Montreal Protocol. HFC-141b is also a minor but potent greenhouse gas. It has an estimated lifetime of about 10 years and a 100-year global warming potential ranging 725 to 2500. This compares to the GWP=1 of carbon dioxide, which had a much greater atmospheric concentration near 400 parts per million in year 2020.
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Greenhouse Gases
Products using amphetamine base are now marketed. Dyanavel XR, a liquid suspension form became available in 2015, and contains about 24% levoamphetamine. Adzenys XR, an orally dissolving tablet came to market in 2016 and contains 25% levoamphetamine.
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Enantiopure drugs
It is well documented that (R)-enantiomers of profens in the presence of coenzyme A (CoA), adenosine triphosphate (ATP) and Mg are converted to active (S)-forms. The pathways of chiral inversion is illustrated taking ibuprofen as the prototype, in the scheme below. The pathway consists mainly of three steps: # Stereoselective activation: Stereoselective activation of (R)-profen by the formation of the thioester, in the presence of CoA, ATP and Mg. (S)-profen does not form the thioester. # Epimerization (Racemization): The enzyme epimerase 2-arylpropionic-CoA changes the (R)-thioester to the (S)-thioester. This process is called "racemization" or "epimerization." # Hydrolysis: With the help of hydrolase/thioesterase, thioesters are broken down into their (R)- and (S)-forms Because the acyl-CoA thioester (profenyl-CoA) changes the structure of triglycerides and phospholipids, metabolic chiral inversion may cause toxic effects.
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Enantiopure drugs
Eslicarbazepine acetate is absorbed to at least 90% from the gut, independently of food intake. It is quickly metabolised to eslicarbazepine, so that the original substance cannot be detected in the bloodstream. Peak plasma levels of eslicarbazepine are reached after 2–3 (1–4) hours, and plasma protein binding is somewhat less than 40%. Biological half-life is 10 to 20 hours, and steady-state concentrations are reached after four to five days after start of the treatment. Oxcarbazepine, for comparison, is also nearly completely absorbed from the gut, and peak plasma concentrations of licarbazepine are reached after 4.5 hours on average after oxcarbazepine intake. Plasma protein binding and half-life are of course the same. Other metabolites of ESL are the less active (R)-(−)-licarbazepine (5%; the stereoisomer of eslicarbazepine), the pharmacologically active oxcarbazepine (1%), and inactive glucuronides of all of these substances. The drug is excreted mainly via the urine, of which two thirds are in the form of eslicarbazepine and one third in the form of eslicarbazepine glucuronide. The other metabolites only account for a few percent of the excreted drug.
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Enantiopure drugs
The repulsive effects of the two lone pairs on the oxygen atom cause water to have a bent, not linear, molecular structure, allowing it to be polar. The hydrogen–oxygen–hydrogen angle is 104.45°, which is less than the 109.47° for ideal sp hybridization. The valence bond theory explanation is that the oxygen atoms lone pairs are physically larger and therefore take up more space than the oxygen atoms bonds to the hydrogen atoms. The molecular orbital theory explanation (Bents rule) is that lowering the energy of the oxygen atoms nonbonding hybrid orbitals (by assigning them more s character and less p character) and correspondingly raising the energy of the oxygen atoms hybrid orbitals bonded to the hydrogen atoms (by assigning them more p character and less s character) has the net effect of lowering the energy of the occupied molecular orbitals because the energy of the oxygen atoms nonbonding hybrid orbitals contributes completely to the energy of the oxygen atoms lone pairs while the energy of the oxygen atoms other two hybrid orbitals contributes only partially to the energy of the bonding orbitals (the remainder of the contribution coming from the hydrogen atoms' 1s orbitals).
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Greenhouse Gases
The production of BCF and similar chlorofluorocarbons has been banned in most countries since January 1, 1994 as part of the Montreal Protocol on ozone depleting substances. Halon 1211 is also a potent greenhouse gas with a 100-year global warming potential 2,070 times that of carbon dioxide and an atmospheric lifetime of 16.0 years. Recycling of Halon 1211 allows it to remain in use, although parts availability is limited to a few manufacturers and can be an issue. Halon 1211 is still widely used in the United States, despite its high cost, with the US military being the biggest user. Europe and Australia have banned its use for all but "critical applications" such as aviation, military, and police use. The manufacture of UL Listed halon 1211 extinguishers was supposed to cease on October, 2009. The future listing is still in discussion. Halotron I, the replacement extinguishing agent, requires a larger volume to get the same ratings as 1211.
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Greenhouse Gases
Drospirenone has been found to stimulate the proliferation and migration of breast cancer cells in preclinical research, similarly to certain other progestins. However, some evidence suggests that drospirenone may do this more weakly than certain other progestins, like medroxyprogesterone acetate. The combination of estradiol and drospirenone has been found to increase breast density, an established risk factor for breast cancer, in postmenopausal women. Data on risk of breast cancer in women with newer progestins like drospirenone are lacking at present. Progestogen-only birth control is not generally associated with a higher risk of breast cancer. Conversely, combined birth control and menopausal hormone therapy with an estrogen and a progestogen are associated with higher risks of breast cancer.
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Enantiopure drugs
The roles of regulatory agencies also continue to evolve with respect to the development of chiral switches. An interesting concept brought up in the FDA policy is that of "bridging studies". When a sponsor/innovator seeks to develop a single enantiomer from a racemic drug, the regulatory agencies demand them to conduct bridging studies. Bridging studies are tests (pharmacological and toxicological evaluations) to connect what is known about the already approved racemate and what is unknown about the single enantiomer under study, without going back to square one as for a completely new chemical entity. The intent of the bridging studies is to make sure that the companies are not scarifying some protective effect conferred by the other" isomer when they develop a chiral drug as single enantiomer rather than a racemate. "Bridging" procedure will help to reduce the number of studies required on the "new" enantiopure drug.
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Enantiopure drugs
emissions have also led to the stratosphere contracting by 400 meters since 1980, which could affect satellite operations, GPS systems and radio communications.
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Greenhouse Gases
Ketamine is a widely used anaesthetic agent. It is a chiral molecule that is administered as a racemate. Studies show that (S)-(+)-ketamine is the active anaesthetic and the undesired side-effects (hallucination and agitation) reside in the distomer, (R)-(-)-ketamine.
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Enantiopure drugs
The natural flows of carbon between the atmosphere, ocean, terrestrial ecosystems, and sediments are fairly balanced; so carbon levels would be roughly stable without human influence. Carbon dioxide is removed from the atmosphere primarily through photosynthesis and enters the terrestrial and oceanic biospheres. Carbon dioxide also dissolves directly from the atmosphere into bodies of water (ocean, lakes, etc.), as well as dissolving in precipitation as raindrops fall through the atmosphere. When dissolved in water, carbon dioxide reacts with water molecules and forms carbonic acid, which contributes to ocean acidity. It can then be absorbed by rocks through weathering. It also can acidify other surfaces it touches or be washed into the ocean.
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Greenhouse Gases
Magma contains dissolved volatile components, as described above. The solubilities of the different volatile constituents are dependent on pressure, temperature and the composition of the magma. As magma ascends towards the surface, the ambient pressure decreases, which decreases the solubility of the dissolved volatiles. Once the solubility decreases below the volatile concentration, the volatiles will tend to come out of solution within the magma (exsolve) and form a separate gas phase (the magma is super-saturated in volatiles). The gas will initially be distributed throughout the magma as small bubbles, that cannot rise quickly through the magma. As the magma ascends the bubbles grow through a combination of expansion through decompression and growth as the solubility of volatiles in the magma decreases further causing more gas to exsolve. Depending on the viscosity of the magma, the bubbles may start to rise through the magma and coalesce, or they remain relatively fixed in place until they begin to connect and form a continuously connected network. In the former case, the bubbles may rise through the magma and accumulate at a vertical surface, e.g. the roof of a magma chamber. In volcanoes with an open path to the surface, e.g. Stromboli in Italy, the bubbles may reach the surface and as they pop small explosions occur. In the latter case, the gas can flow rapidly through the continuous permeable network towards the surface. This mechanism has been used to explain activity at Santiaguito, Santa Maria volcano, Guatemala and Soufrière Hills Volcano, Montserrat. If the gas cannot escape fast enough from the magma, it will fragment the magma into small particles of ash. The fluidised ash has a much lower resistance to motion than the viscous magma, so accelerates, causing further expansion of the gases and acceleration of the mixture. This sequence of events drives explosive volcanism. Whether gas can escape gently (passive eruptions) or not (explosive eruptions) is determined by the total volatile contents of the initial magma and the viscosity of the magma, which is controlled by its composition. The term closed system degassing refers to the case where gas and its parent magma ascend together and in equilibrium with each other. The composition of the emitted gas is in equilibrium with the composition of the magma at the pressure, temperature where the gas leaves the system. In open system degassing, the gas leaves its parent magma and rises up through the overlying magma without remaining in equilibrium with that magma. The gas released at the surface has a composition that is a mass-flow average of the magma exsolved at various depths and is not representative of the magma conditions at any one depth. Molten rock (either magma or lava) near the atmosphere releases high-temperature volcanic gas (>400 °C). In explosive volcanic eruptions, the sudden release of gases from magma may cause rapid movements of the molten rock. When the magma encounters water, seawater, lake water or groundwater, it can be rapidly fragmented. The rapid expansion of gases is the driving mechanism of most explosive volcanic eruptions. However, a significant portion of volcanic gas release occurs during quasi-continuous quiescent phases of active volcanism.
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Greenhouse Gases
The bioavailability of levonorgestrel is approximately 95% (range 85 to 100%). The plasma protein binding of levonorgestrel is about 98%. It is bound 50% to albumin and 48% to SHBG. Levonorgestrel is metabolized in the liver, via reduction, hydroxylation, and conjugation (specifically glucuronidation and sulfation). Oxidation occurs primarily at the C2α and C16β positions, while reduction occurs in the A ring. 5α-Dihydrolevonorgestrel is produced as an active metabolite of levonorgestrel by 5α-reductase. The elimination half-life of levonorgestrel is 24 to 32 hours, although values as short as 8 hours and as great as 45 hours have been reported. About 20 to 67% of a single oral dose of levonorgestrel is eliminated in urine and 21 to 34% in feces.
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Enantiopure drugs
Derived from “the addition of a hydrophilic heterocyclic group to the α-amino group of ampicillin”, the structure consists of a thiazolidine ring conjoined to a β-lactam ring contained within several ring compounds. The addition of this substituent increases the compounds affinity to penicillin-binding protein PBP-3, improving activity against Gram-negative bacteria, and thus broadening its spectrum of activity. Susceptible β-lactamase producing bacteria such as Staphylococcus spp. or Haemophilus influenzae', the combination of tazobactam (which shares a similar structure to sulbactam, another β-lactamase inhibitor), and piperacillin significantly improves the stability of the drug against β-lactamases.
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Enantiopure drugs
Estimates in 2023 found that the current carbon dioxide concentration in the atmosphere may be the highest it has been in the last 14 million years. However the IPCC Sixth Assessment Report estimated similar levels 3 to 3.3 million years ago in the mid-Pliocene warm period. This period can be a proxy for likely climate outcomes with current levels of . Carbon dioxide is believed to have played an important effect in regulating Earths temperature throughout its 4.54 billion year history. Early in the Earths life, scientists have found evidence of liquid water indicating a warm world even though the Suns output is believed to have only been 70% of what it is today. Higher carbon dioxide concentrations in the early Earths atmosphere might help explain this faint young sun paradox. When Earth first formed, Earth's atmosphere may have contained more greenhouse gases and concentrations may have been higher, with estimated partial pressure as large as , because there was no bacterial photosynthesis to reduce the gas to carbon compounds and oxygen. Methane, a very active greenhouse gas, may have been more prevalent as well. Carbon dioxide concentrations have shown several cycles of variation from about 180 parts per million during the deep glaciations of the Holocene and Pleistocene to 280 parts per million during the interglacial periods. Carbon dioxide concentrations have varied widely over the Earths history. It is believed to have been present in Earths first atmosphere, shortly after Earth's formation. The second atmosphere, consisting largely of nitrogen and was produced by outgassing from volcanism, supplemented by gases produced during the late heavy bombardment of Earth by huge asteroids. A major part of carbon dioxide emissions were soon dissolved in water and incorporated in carbonate sediments. The production of free oxygen by cyanobacterial photosynthesis eventually led to the oxygen catastrophe that ended Earths second atmosphere and brought about the Earths third atmosphere (the modern atmosphere) 2.4 billion years ago. Carbon dioxide concentrations dropped from 4,000 parts per million during the Cambrian period about 500 million years ago to as low as 180 parts per million 20,000 years ago .
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Greenhouse Gases
5α-Dihydrolevonorgestrel (5α-DHLNG) is an active metabolite of the progestin levonorgestrel which is formed by 5α-reductase. It has about one-third of the affinity of levonorgestrel for the progesterone receptor. In contrast to levonorgestrel, the compound has both progestogenic and antiprogestogenic activity, and hence has a selective progesterone receptor modulator-like profile of activity. This is analogous to the case of norethisterone and 5α-dihydronorethisterone. In addition to the progesterone receptor, 5α-DHLNG interacts with the androgen receptor. It has similar affinity for the androgen receptor relative to levonorgestrel (34.3% of that of metribolone for levonorgestrel and 38.0% of that of metribolone for 5α-DHLNG), and has androgenic effects similarly to levonorgestrel and testosterone. 5α-DHLNG is further transformed into 3α,5α- and 3β,5α-, which bind weakly to the estrogen receptor (0.4 to 2.4% of the of ) and have weak estrogenic activity. These metabolites are considered to be responsible for the weak estrogenic activity of high doses of levonorgestrel.
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Enantiopure drugs
Selegiline belongs to the phenethylamine and amphetamine chemical families. It is also known as -deprenyl, as well as (R)-(–)-N,α-dimethyl-N-(2-propynyl)phenethylamine or (R)-(–)-N-methyl-N-2-propynylamphetamine. The compound is a derivative of levomethamphetamine (-methamphetamine) with a propargyl group attached to the nitrogen atom. This detail is borrowed from pargyline, an older MAO-B inhibitor of the phenylalkylamine group. Selegiline is the levorotatory enantiomer of the racemic mixture deprenyl. Selegiline is synthesized by the alkylation of (–)-methamphetamine using propargyl bromide. Another clinically used MAOI of the amphetamine class is tranylcypromine.
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Enantiopure drugs
There were four named penicillins at the time penicillin V was discovered (penicillins I, II, III, IV), however, Penicillin V was named "V" for Vertraulich (German for confidential); it was not named for the Roman numeral "5". Penicillin VK is the potassium salt of penicillin V (K is the chemical symbol for potassium).
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Enantiopure drugs
Formylation of octabase prior to cyclization avoids ether cleavage as a side reaction and yields higher than without N-substitution or N-methylation. In this example, the purification was done by formation of a brucine salt. This process has also been patented by Roche.
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Enantiopure drugs
Enalapril, sold under the brand name Vasotec among others, is an ACE inhibitor medication used to treat high blood pressure, diabetic kidney disease, and heart failure. For heart failure, it is generally used with a diuretic, such as furosemide. It is given by mouth or by injection into a vein. Onset of effects are typically within an hour when taken by mouth and last for up to a day. Common side effects include headache, tiredness, feeling lightheaded with standing, and cough. Serious side effects include angioedema and low blood pressure. Use during pregnancy is believed to result in harm to the baby. It is in the angiotensin-converting-enzyme (ACE) inhibitor family of medications. Enalapril was patented in 1978, and came into medical use in 1984. It is on the World Health Organization's List of Essential Medicines. In 2021, it was the 278th most commonly prescribed medication in the United States, with more than 800,000 prescriptions. It is available as a generic medicine.
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Enantiopure drugs
Overdose of levonorgestrel as an emergency contraceptive has not been described. Nausea and vomiting might be expected.
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Enantiopure drugs
Sublimation is the process by which water molecules directly leave the surface of ice without first becoming liquid water. Sublimation accounts for the slow mid-winter disappearance of ice and snow at temperatures too low to cause melting. Antarctica shows this effect to a unique degree because it is by far the continent with the lowest rate of precipitation on Earth. As a result, there are large areas where millennial layers of snow have sublimed, leaving behind whatever non-volatile materials they had contained. This is extremely valuable to certain scientific disciplines, a dramatic example being the collection of meteorites that are left exposed in unparalleled numbers and excellent states of preservation. Sublimation is important in the preparation of certain classes of biological specimens for scanning electron microscopy. Typically the specimens are prepared by cryofixation and freeze-fracture, after which the broken surface is freeze-etched, being eroded by exposure to vacuum until it shows the required level of detail. This technique can display protein molecules, organelle structures and lipid bilayers with very low degrees of distortion.
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Greenhouse Gases
There are no known contraindication to the use of dexmedetomidine. It has a biphasic effect on blood pressure with lower readings at lower drug concentrations and higher readings at higher concentrations. Common side effects include: hypotension, hypertension, with slight decreases in heart rate, arrhythmias, and hypoxia. Toxic doses may cause first-degree or second-degree atrioventricular block. These adverse events usually occur briefly after administering a loading dose of the drug. Thus, adverse effects may be reduced by omitting a loading dose.
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Enantiopure drugs
The Advisory Group on Greenhouse Gases, created in 1986, was an advisory body for the review of studies into the greenhouse effect. The group was created by the International Council of Scientific Unions, the United Nations Environment Programme, and the World Meteorological Organization to follow up on the recommendations of the International conference of the Assessment of the role of carbon dioxide and of other greenhouse gases in climate variations and associated impacts, held at Villach, Austria, in October 1985. The seven-member panel included Swedish meteorologist Bert Bolin and Canadian climatologist Kenneth Hare. The group held its last meeting in 1990. It was gradually replaced by the Intergovernmental Panel on Climate Change.
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Greenhouse Gases
Cefuroxime is active against many bacteria including susceptible strains of Staphylococci and Streptococci, as well as a range of gram negative organisms. As with the other cephalosporins, it is susceptible to beta-lactamase, although as a second-generation variety, it is less so. Hence, it may have greater activity against Haemophilus influenzae, Neisseria gonorrhoeae, and Lyme disease. Unlike other second-generation cephalosporins, cefuroxime can cross the blood–brain barrier. A systematic review found high quality evidence that injecting the eye with cefuroxime after cataract surgery will lower the chance of developing endophthalmitis after surgery.
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Enantiopure drugs
Dexlansoprazole was approved by the U.S. Food and Drug Administration (FDA) in 2009, and was approved in Canada in 2010 and in Mexico in 2011. Since Kapidex was approved in 2009, there have been reports of dispensing errors because of confusion with the drugs Casodex (bicalutamide) and Kadian (morphine), which have very different uses from Kapidex and from each other. In 2010, the FDA approved a name change for Kapidex to avoid confusion with the two other medications and Takeda began marketing it under the new name Dexilant. It is also available in Bangladesh for the first time as Dexlan by IBN SINA Pharmaceuticals Ltd. in April 2014 and after them DEXILEND by Ziska Pharmaceuticals Ltd., Desopra by Alco Pharma, Delanix by Incepta Pharmaceuticals, Dexogut by Popular Pharmaceuticals Ltd. also introduced it in BD market. In 2020 many other Pharmaceuticals have launched Dexlansoprazole.
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Enantiopure drugs
In 1987, an elderly couple was exposed to sulfuryl fluoride in their house already cleared for reentry. While the fumigation company opened windows and doors, and aerated the house with fans, sulfuryl fluoride level was not measured. It was not detected when the air was sampled 12 days after aeration. The couple experienced weakness, nausea and shortness of breath that evening. The man suffered a seizure and died the following day. His wife's condition got worse with pulmonary edema, and she died after a cardiovascular arrest 6 days later. In 2015, a 10-year-old boy suffered severe brain damage and lost function of his left arm and leg after his home was treated with sulfuryl fluoride and insufficiently aerated, prompting a criminal investigation by the Department of Justice and the Florida Department of Agricultural and Consumer Services. Two pest control workers later pled guilty to charges of misuse of the pesticide resulting in the boy's poisoning, and were each sentenced to one year in prison. In 2016, a 24-year-old man who allegedly entered an apartment that was being fumigated in Fremont, California to commit a burglary was exposed to sulfuryl fluoride and chloropicrin and died shortly thereafter. According to a police officer, he experienced labored breathing and was sweating before he collapsed just a few steps from the first floor window of the apartment he allegedly burglarized.
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Greenhouse Gases