bluuebunny/crossref_metadata_2025 huggingface dataset:
BETA ADRENERGIC RECEPTOR FUNCTION IN DEPRESSION AND THE EFFECT OF ANTIDEPRESSANT DRUGS
Authors: Pandey Ghanshyam N. , Sudershan Puppala , Davis John M.
Published: July 2010

Abstract:It has been suggested that alterations of monoamine receptor sensitivity in the central nervous system may be associated with some forms of affective illness. It has been observed by several investigators that chronic treatment with antidepressant drugs causes down regulation of NE receptor coupled adenylate cyclase and beta adrenergic receptor binding in rat brain. This observation has led to the suggestion that the therapeutic effects of antidepressant drugs may be related to the changes in the responsivity of beta adrenergic receptors. In order to examine if depressive illness may be associated with altered beta adrenergic function, we studied adenylate cyclase and its responsiveness to norepinephrine and isoproterenol in the leukocytes obtained from patients with psychiatric illness and normal controls as an index of beta adrenergic receptor function. We also studied the effects of antidepressant drugs, in vitro, on isoproterenol sensitive leukocyte adenylate cyclase. We observed that norepinephrine and isoproterenol sensitive leukocyte adenylate cyclase in depressed patients are significantly decreased as compared to normal controls. Our results appear to have been replicated by another group of investigators. We also observed that certain antidepressnt drugs potentiate isoproterenol stimulated accumulation of cyclic AMP in human leukocytes. This potentiation was most pronounced in the case of iprindole. These results thus indicated a decreased beta adrenergic receptor function in patients with depressive illness. Whether or not such decreased receptor function is associated with depressive illness or is a manifestation of some other changes unrelated to the illness is not clear. Our results also indicate that some antidepressant drugs may enhance adrenergic transmission by potentiating the effects of neurotransmitters on beta adrenergic receptors.
OPIOID PEPTIDES AND RECEPTORS IN RELATION TO AFFECTIVE ILLNESS. EFFECTS OF DESIPRAMINE AND LITHIUM ON OPIOID RECEPTORS IN RAT BRAIN.
Authors: Stengaard‐Pedersen K. , Schou M.
Published: July 2010

Abstract: A brief review is given of clinical and experimental evidence supporting the notion that opioid peptides and opioid receptors play a role for the regulation of mood and activity, and that they could be involved in the pathophysiology of affective illness and the action of antimanic and antidepressant treatment modalities.
PRESYNAPTIC AND TRANSYNAPTIC MECHANISMS INVOLVED IN THE SUBSENSITIVITY OF RAT CORTICAL NORADRENERGIC SYSTEM AFTER LONG‐TERM ANTIDEPRESSANT TREATMENT.
Authors: Racagni G. , Brunello N. , Mocchetti I. , Cagiano R. , Cuomo V.
Published: July 2010

Abstract:Chronic treatment with antidepressants has been shown to produce a subsensitivity of noradrenergic neurons, both at presynaptic and postsynaptic sites. Important mechanisms, whereby the activity of noradrenergic neurons is regulated, could be the sensitivity of presynaptic alpha2‐adrenoceptors and the participation of transynaptic mechanisms involving other neurons. In this report we demonstrate that transynaptic factors involving the serotonergic system may be relevant to the regulation of the function of alpha2‐receptors in antidepressant chronically treated animals. In fact, we provide evidence of a markedly deminished responsiveness of noradrenergic neurons to an alpha2‐agonist (clonidine) or antagonist (mianserin) in biochemical and behavioral studies following serotonergic denervation with 5,7‐dihydroxytryptamine. These results indicate that a functional interrelationship between serotonergic and noradrenergic systems might play an important role in the adaptive changes which bring the noradrenergic neurons to a lower level of activity after chronic antidepressant administration.
Some Extracardiac Effects of Diltiazem and Other Calcium Entry Blockers
Authors: Andersson Karl‐Erik
Published: July 2010

Abstract:Calcium entry blockers have a well documented relaxing effect of smooth muscle, vascular as well as non‐vascular. Mainly as a consequence of this action, the drugs have been used for treatment of several non‐cardiac disorders where hyperactivity of smooth muscle is considered to have an important role in the pathogenesis. In this short review some of these extracardiac effects of calcium entry blockers are discussed and also their clinical application.
Metabolism of some Drugs by Intestinal Lactobacilli and their Toxicological Considerations
Authors: Pradhan A. , Majumdar M. K.
Published: July 2010

Abstract:The bacterial metabolism of three drugs (sulphasalazine, phthalylsulphathiazole and chloramphenicol palmitate) and two dyes (tartrazine and methyl red) has been studied using a resting culture technique. The strains used were isolated intestinal lactobacilli,E. coliand mixed cultures of faeces of mice. As high as 94.3% degradation of sulphasalazine was found with a strain ofLactobacillus acidophilus.The highest degradation of phthalylsulphathiazole and chloramphenicol palmitate was found to be 17.6% and 8%, respectively. A kinetic study was conducted on the rate of degradation of sulphasalazine, phthalylsulphathiazole and methyl red. The toxicological aspects of degradation products in relation to the use of lactobacilli as dietary supplement or therapeutic aid are discussed.
Cortical β‐ and α2‐ Adrenoceptor Binding, Hypothalamic Noradrenaline and Pineal Melatonin Concentrations Measured at Different Times of the Day after Repeated Treatment of Rats with Imipramine, Zimeldine, Alaproclate and Amiflamine
Authors: Ask Anna‐Lena , Fowler Christopher J. , Hall Håkan , Kelder Diana , Ross Svante B. , Sääf Jan
Published: July 2010

Abstract:The effect of repeated treatment of rats for 21 days with the monoamine reuptake inhibitors imipramine, zimeldine, alaproclate (in each case 10 μmol/kg b.i.d.) and the reversible monoamine oxidase‐A inhibitor amiflamine (3 μmol/kg b.i.d.) on brain noradrenergic mechanisms measured at different times of the day and night was investigated. Imipramine treatment produced a down‐regulation of the Bmaxfor3H‐dihydroalprenolol binding to cortical β‐adrenoceptors that was not dependent upon the time of day the animals were killed. Zimeldine, on the other hand, reduced both Bmax, and Kdof binding for day‐time, but not night‐time samples. Alaproclate and amiflamine were without effect on the binding. Twenty‐four hour mean values for 1 nM3H‐p‐aminoclonidine binding to α2‐adrenoceptors were lower for the zimeldine‐treated rats than for the saline‐treated rats. Pineal melatonin concentrations, which are regulated by β‐adrenoceptors, showed a pronounced diurnal rhythm, with the highest concentrations being found at 02:00. At this time point, a lower pineal melatonin content was found after amiflamine treatment, whereas imipramine, zimeldine and alaproclate were without significant effect. The importance of the use of more than one time point and the use of more than one biochemical test for the determination of the effects of repeated antidepressant treatment on central noradrenergic systems measuredex vivois discussed.
The Effect of Vitamin E and Selenium on Doxorubicin (Adriamycin®) Induced Delayed Toxicity in Mice
Authors: Hermansen K. , Wassermann K.
Published: July 2010

Abstract:The antagonistic action of repeated administration of vitamin E and selenium on the lethality caused by a single intraperitoneal injection of doxorubicin 15 to 20 mg/kg has been investigated in mice. Mice were treated with vitamin E, 20 to 4100 mg/kg intraperitoneally/intramuscularly daily or once a week and/or selenium 27 μg/kg orally daily for 6 to 7 weeks, i.e. one or two weeks before and five weeks after doxorubicin administration. 30 mg/kg of doxorubicin intraperitoneally caused 100% lethality within 4 days, whereas 15 mg/kg caused no deaths within a week, but resulted in a delayed toxicity with a cumulative lethality of 80% at the end of the observation period of 6 months. Vitamin E protected the mice from the lethal effect of doxorubicin, 15 mg/kg during the administration, but the mice began to die when the vitamin E administration was discontinued. Selenium only protected the mice for two weeks in spite of the continuous administration of selenium. The combined administration of vitamin E and selenium had no protective effect on the lethality caused by doxorubicin, 20 mg/kg. The pathogenesis of the delayed lethality of a single doxorubicin administration in mice is discussed. It is concluded that vitamin E and/or selenium have no significant protective action against doxorubicin induced delayed lethality in mice.
Effects of Remoxipride and some Related New Substituted Salicylamides on Rat Brain Receptors
Authors: Hall* Håkan , Sällemark Maria , Jerning Eva
Published: July 2010

Abstract:A number of potential neuroleptic drugs of the substituted benzamide type have been compared with some reference neuroleptic drugs regarding their affinities for rat brain receptors usingin vitroreceptor binding techniques. The effects on dopamine‐stimulated adenylate cyclase were also investigated. All 6‐methoxysalicylamides were very potent inhibitors of the dopamine‐D2receptor and possessed much less affinity for other receptors as well as for the dopamine‐stimulated adenylate cyclase. In contrast, the classical neuroleptic drugs were not selective dopamine‐D2receptor blockers. Several of these neuroleptics were thus potent inhibitors of α1‐receptors, 5‐HT2receptors, muscarinic receptors and histamine‐H1receptors. Sulpiride was the most selective dopamine‐D2receptor blocker of the reference compounds with a selectivity ratio of 65. The 6‐methoxysalicylamides had selectivity ratios ranging from 18 to 167.
Fluorocarbons and Cardiac Arrhythmia: Does Difluorodichloromethane (FC 12) Inhibit Cardiac Metabolism?
Authors: Lessard Yvon , Begue Jean‐Marc , Paulet Georges
Published: July 2010

Abstract:Certain fluorocarbons, such as difluorodichloromethane (FC 12), depress the cardiovascular system by diminution of all the transmembrane ionic conductances in cardiac tissues. Does FC 12 also inhibit active transport and thus enzymatic activity and cellular energy? We measured phosphocreatine (PC), adenosine triphosphate (ATP) and cyclic adenosine monophosphate (AMPc) in rat hearts. Rats were randomly divided into 4 groups; 2 control groups: one breathing a mixture of oxygen (21%) and nitrogen (79%) (group C) and the other breathing the same mixture but simultaneously perfused with 1 μg/kg/min. epinephrine (groupe E‐C); 2 trial groups T and E‐T where nitrogen was replaced by FC 12. The maximal FC 12 concentration of 720 μg/ml in arterial blood produced no significant difference in the concentrations of these three metabolites compared with controls.
Further Studies on the Cardiomegaly Induced by β‐Adrenoceptor Agonists
Authors: Jeppsson A.‐B. , Waldeck B. , Widmark E.
Published: July 2010

Abstract:Rats received continuous infusions of β‐adrenoceptor agonists by means of Alzet osmotic mini‐pumps implanted subcutaneously. After 7 days of isoprenaline infusion (2 mg/kg per day) the heart/body weight ratio increased about 40 per cent compared with placebo treatment. The difference persisted after freeze‐drying indicating a true hypertrophy and not merely an oedema. When terbutaline (20 mg/kg per day) was substituted for isoprenaline, the increase in wet weight ratio reached only about 5 per cent. Procaterol (2 mg/kg per day) and pirbuterol (20 mg/kg per day) had no effect on the heart weight. It is concluded that in doses expected to cause comparable stimulation of β2‐adrenoceptors the unselective agonist isoprenaline is able, more than the β2‐selective agonists terbutaline, procaterol and pirbuterol to cause cardiac hypertrophy thus indicating the involvement of β1‐adrenoceptors.
The Relaxant Effect of Glyceryltrinitrate on Isolated Human Peripheral Vein and its Relation to Cyclic GMP Metabolism
Authors: Ahlner Johan , Andersson Rolf G. G. , Axelsson Krister L. , Bergdahl Björn , Dahlström Ulf , Rydell Ewa L.
Published: July 2010

Abstract:The relaxant effect of glyceryltrinitrate (GTN) on human vena saphena magna was studiedin vitro.Vessels contracted by serotonin (0.25 μM) and phenylephrine (0.1 mM) were relaxed to the same extent (EC50 = 10 μM) by GTN, whereas in 100 mM K+‐depolarized vessels the relaxation was significantly lower. The relaxant effect produced by GTN was preceeded by an elevation of cyclic guanosine‐3′,5′‐monophosphate (cGMP). For 0.1 mM GTN there was a 3‐fold increase in cGMP after 3 min. A correlation between relaxation and increase in cGMP was established. When GTN was combined with dipyridamole (5 μM) the relaxant effect of GTN was significantly greater (EC50 = 0.1 μM). Phosphodiesterase inhibition, as a possible mechanism behind the observed better relaxation for the combination (GTN + dipyridamole), is briefly discussed. In conclusion, the relaxant effect of GTN on isolated human vena saphena magna seems to be i) dependent on the contractile stimuli used, ii) increased by the addition of DIP and iii) to be mediated via cGMP.
Cadmium Toxicity in Kidney Cells. Resistance induced by Short Term Pretreatment in Vitro and in Vivo
Authors: Jin Taiyi , Nordberg Gunnar F.
Published: July 2010

Abstract: Epithelial cells from the kidney were freshly isolated from rats pretreated by daily subcutaneous doses of CdCl2 in vivo (0.5–2 mg Cd/kg × 5). Such cells were incubated in vitro in media with different concentrations of cadmium chloride (0–200 μg Cd/ml). There was no inhibition of cell growth in such cells. However, in cells isolated from non‐treated rats, in vitro exposure to the same concentrations of CdCl2 caused a dose dependent decrease in viability. When cells, isolated from non‐treated rats were pretreated in vitro with CdCl2 (10 μg/ml) and subsequently exposed to cadmium chloride (0–200 μg/ml), a protective effect was observed, which was similar to the one observed in cells isolated from animals pretreated with CdCl2. The concentration of metallothionein in the cells treated with cadmium was increased. A lower uptake of cadmium chloride, in vitro has been observed in kidney cells pretreated in vivo or in vitro compared to non‐pretreated cells. Subcellular distribution studies indicate that Cd‐distribution was similar in pretreated and non‐pretreated cells, but concentrations were generally lower in the pretreated cells. The decreased uptake of Cd by pretreated kidney cells is a sign of. Cd‐interference with cellular function. These changes are suggested as a contributing mechanism to the prevention of acute toxic effects of cadmium on the kidney.
Effects of Di‐(2‐ethylhexyl) Phthalate and Five of its Metabolites on Rat Testisin Vivoand inin Vitro
Authors: Sjöberg P. , Bondesson U. , Gray T. J. B. , Plöen L.
Published: July 2010

Abstract:In an attempt to establish which compound or compounds are responsible for the testicular damage observed after administration of di‐(2‐ethylhexyl) phthalate (DEHP) in rats, the effects of the parent compound and five of its major metabolites (mono‐(2‐ethylhexyl) phthalate (MEHP), 2‐ethylhexanol (2‐EH), mono‐(5‐carboxy‐2‐ethylpentyl) phthalate, mono‐(2‐ethyl‐5‐oxohexyl) phthalate and mono‐(2‐ethyl‐5‐hydroxyhexyl) phthalate) were investigatedin vivoandin vitro.The concentrations of MEHP and the three MEHP‐derived metabolites in plasma were determined after single and multiple oral doses of DEHP. The plasma concentrations and areas under the plasma concentration‐time curves (AUC's) of each of the MEHP‐derived metabolites were considerably lower than those of MEHP both after single and after repeated administration of 2.7 mmol of DEHP/kg body weight. The mean elimination half‐life of MEHP was significantly shorter in animals given repetitive doses than in those given a single dose, but there was no statistically significant difference between the mean AUC values. No testicular damage was observed in young rats given oral doses of 2.7 mmol of DEHP or 2‐EH/kg body weight daily for five days. In animals which received corresponding doses of MEHP the number of degenerated spermatocytes and spermatids was increased, whereas no such effects were found in animals given the MEHP‐derived metabolites. MEHP was also the only compound that enhanced germ cell detachment from mixed primary cultures of Sertoli and germ cells.
Vagally Mediated Stimulation of Gastric Acid Secretion by Intravenously Administered Adenosine Derivatives in Anaesthetized Rats
Authors: Puurunen Juhani , Aittakumpu Raija , Tanskanen Tiina
Published: July 2010

Abstract:The effects of adenosine and some of its analogues on gastric acid secretion were investigated in rats. These compounds increased gastric acid secretion in anaesthetized rats after intravenous injection, the order of potency being 5′‐N‐ethylcarboxamidoadenosine (NECA) > (—)N6‐phenylisopropyladenosine (L‐PIA), N6‐cyclohexyladenosine (CHA) > (+)N6‐phenylisopropyladenosine (D‐PIA) > 2‐chloroadenosine (2‐CADO) > adenosine (ADO). The stimulation of acid secretion by L‐PIA in anaesthetized rats was antagonized by theophylline and 8‐phenyltheophylline and totally prevented by vagotomy and atropine. Intracerebroventricular administration of L‐PIA had no effect on gastric acid secretion in anaesthetized rats, whereas in conscious rats it inhibited the output of acid, pepsin and fluid. These results indicate that adenosine derivatives stimulate gastric acid secretion in anaesthetized rats by activating the vagus nerve via adenosine receptors in afferent pathways.
Lipid Peroxidationin VivoMonitored as Ethane Exhalation and Malondialdehyde Excretion in Urine after Oral Administration of Chloroform
Authors: Ekström Tomas , Ståhl Annika , Sigvardsson Karl , Högberg Johan
Published: July 2010

Abstract:In vivolipid peroxidation was studied in phenobarbital pretreated rats exposed for chloroform. Lipid peroxidation was monitored as ethane exhalation or malondialdehyde (MDA) excretion in urine. A single oral dose of chloroform (0.7 ml/kg b. wt.) showed a marked increase in ethane exhalation in animals starved for 48 hours prior to chloroform treatment. This increase became evident after a lag‐period of about 100 min. Pretreatment with diethylmaleate (1 ml/kg b. wt.) 1 hour prior to chloroform treatment gave a similar result. MDA excretion in urine from non‐starved animals, exposed to chloroform, markedly increased after 4 hours and after 24 hours 115 nmol/kg had been excreted. In animals starved for 48 hours prior to chloroform treatment about 270 nmol/kg excreted within 24 hours. Small molecular weight thiols were measured in liver, kidneys and lungs. Chloroform decreased the thiol content of the liver by 43.2% within 100 min. while the concentration in the kidneys and the lungs were less affected. It is suggested that chloroform may act as a potent inducer of lipid peroxidationin vivo.The synergistic effects of the pretreatments and the lag phase indicate that glutathione depletion in the liver was an essential factor in this response.
Medroxyprogesterone Acetate Pharmacokinetics Following Oral High‐Dose Administration in Humans: A Bioavailability Evaluation of a New MPA Tablet Formulation
Authors: Johansson E. D. B. , Johansen P. B. , Rasmussen S. N.
Published: July 2010

Abstract: The pharmacokinetics of medroxyprogesterone acetate (MPA) in healthy female volunteers have been investigated following oral administration of single doses of six different high‐dose MPA tablet formulations. Blood samples were obtained over 96 hrs following administration. The plasma was separated and analyzed in duplicate for MPA by radioimmunoassay (RIA) after extraction with petroleum ether. A two compartment open model with first order absorption was computer‐fitted to the plasma concentration of MPA. Following oral administration MPA is rapidly transferred from the gastrointestinal tract to the blood circulation with a half‐life of the absorption process of 15–30 min. The peak plasma concentration is reached 1–3 hrs after administration, and the biological half‐life of MPA is 40–60 hrs. Following administration of 1000 mg MPA the areas under the plasma concentration‐time curves (AUC∞0) were calculated to (mean and S.E.): 3357 (438) nmol/l and 2403 (245) nmol/l for Leo formulation A and Farlutal®, respectively (P < 0.02). Following administration of 500 mg the areas were: 2325 (389) nmol/l, 1793 (312) nmol/l, 1778 (239) nmol/l, 1178 (209) nmol/l, and 556 (89) nmol/l for Gestapuran®, Leo formulation A (P = n.s.), Leo formulation B (P = n.s.), Provera® (P < 0.001), and Lutopolar® (P < 0.001), respectively. The in vitro dissolution rates of MPA from the tablet formulations were determined and compared with the results of the bioavailability studies, indicating that a rapid dissolution rate as well as the particle size of MPA are two important factors to ensure optimal absorption of MPA from the gastrointestinal tract.
Affinity of Various Compounds for Benzodiazepine Binding Sites in Rat Brain, Heart and Kidneysin Vitro
Authors: Saano V.
Published: July 2010

Abstract:Binding of several psychoactive, antiinflammatory, antihypertensive, and antiarrhythmic drugs to central and peripheral benzodiazepine (BZ) binding sites was studied in the brain, heart and kidneys of rats. Diazepam exhibited the highest affinity for all binding sites (Kivalues at 0.01 μM level); another 1,4‐BZ, oxazepam, had markedly lower affinity for peripheral binding sites (Ki21–37 μM). Non‐BZ compounds had low affinity for central BZ receptors; proquazone was the most potent (Ki9.5 μM). The affinities of non‐BZ compounds were higher for peripheral BZ binding sites. The Kivalue for proquazone was approximately 0.1 μM; and many other antiinflammatory agents, and the vasodilators cyclandelate and nifedipine, produced Kivalues in the micromolar level. β‐Blocking drugs, and several other antihypertensive and antiarrhythmic agents lacked affinity for both central and peripheral BZ binding sites. According to the results, the affinity for peripheral binding sites is independent of an affinity for central BZ receptors. Non‐BZ compounds that bound to brain BZ receptors bound with equal affinity to both BZ1 and BZ2 subgroups of receptors. The compounds with affinity for peripheral BZ binding sites did not select between heart and kidneys, which suggests that these organs have similar binding sites. The role of the peripheral BZ binding sites has not yet been established. The findings of this study allow the selection of a more varied group of ligands to be used when investigating the physiological significance of these binding sites.
Pharmacokinetics of14C‐Fenflumizole after Intravenous Administration to Man
Authors: Vinge Ellen , Midskov Carsten , Arnold Elisabeth
Published: July 2010

Abstract:The disposition of14C‐labelled fenflumizole was studied in five healthy subjects who received 0.1 mg/kg of fenflumizole as single intravenous doses. Radioactivity was measured in whole blood, plasma, urine and faeces from prior to until 168 hours after dose administration. Chemical determinations of fenflumizole and its two demethylated derivatives in plasma were made by HPLC followed by fluorescence detection. Concentrations of fenflumizole calculated from radioactivity in plasma were consistently higher than from chemical determinations, suggesting the presence of metabolites. Radioactivity in blood cells decreased more slowly than in plasma. Plasma concentrations versus time could be described by a four‐compartment model, with a terminal half‐life of 119 hours (median). About 50% of the dose was excreted with the faeces, and about 4% was recovered in the urine. Unchanged fenflumizole in the urine accounted for 0.0001% of the total dose. Renal clearance of radioactive material decreased at low concentrations of radioactive compound in plasma, which may indicate changes in unbound fraction of drug and metabolites, or a saturable tubular reabsorption process. The slow elimination of fenflumizole is consistent with slow release from tissues and/or enterohepatic recycling.
Comparisons between thein VitroBinding of Two Substituted Benzamides and Two Butyrophenones to Dopamine‐D2Receptors in the Rat Striatum
Authors: Hall Håkan , Wedel Ilse
Published: July 2010

Abstract:Thein vitrodopamine‐D2receptor binding profiles of two substituted benzamides (3H‐sulpiride and3H‐raclopride) and two butyrophenones (3H‐spiperone and3H‐domperidone) were compared.3H‐Raclopride,3H‐domperidone and3H‐sulpiride labelled approximately the same number of binding sites in the rat striatum, while3H‐spiperone labelled a higher number of binding sites. This latter finding was suggested to be due to the labelling of 5‐HT2receptors in addition to the dopamine‐D2binding sites since the labelling of these 5‐HT2 receptors with3H‐spiperone could be avoided by the addition of the 5‐HT2receptor antagonist ketanserin. The inhibition constants (Ki) of the unlabelled compounds were similar to the Kd values obtained in the saturation analyses with3H‐raclopride,3H‐domperidone and3H‐sulpiride but were significantly higher when3H‐spiperone was used as radioligand. Addition of ketanserin to3H‐spiperone made the Ki values more similar to those obtained with the other radioligands. The implications of these findings in testing antidopaminergic activity is discussed.
The in Vitro Permeability of Human Skin to Benzene, Ethylene Glycol, Formaldehyde, and n‐Hexane
Authors: Lodén Marie
Published: July 2010

Abstract: The permeability of human skin to benzene, ethylene glycol, formaldehyde, and n‐hexane was studied using excised skin in a flow‐through diffusion cell. The rate of resorption was determined by measuring the amount of substance found in the receptor fluid beneath the skin at steady‐state. The rates of resorption (μg · cm−2 · hr−1) were: benzene 99, ethylene glycol 118, formaldehyde from a concentrated solution of formalin 319, formaldehyde from a solution of 10% formalin in phosphate buffer 16.7, and n‐hexane 0.83. The amount of substance in the skin at steady‐state and after 0.5 hr of exposure was also determined. For all substances, the sum of the amount in the receptor medium and in the skin at steady‐state, were larger than the amount obtained by multiplying the resorption rate by the time of exposure. For benzene, ethylene glycol and n‐hexane the amount absorbed during the first half‐hour of exposure was considerable larger than the amount resorbed during a same unit of time at steady‐state. These data call attention to the fact that the absorption rate is higher before steady state is attained.
Inhibitory Effects of Nitrendipine on Myometrial and Vascular Smooth Muscle in Human Pregnant Uterus and Placenta
Authors: Maigaard Svend , Forman Axel , Brogaard‐Hansen Karl P. , Andersson Karl‐Erik
Published: July 2010

Abstract:Human myometrial visceral and vascular preparations and placental chorionic and stem villous vessels were dissected from myometrial and placental specimens obtained at term Caesarean section and after vaginal delivery. Vascular ring preparations and myometrial strips were mounted in organ bath and isometric tension recorded. Only myometrial preparations developed spontaneous contractile activity, which was effectively blocked by the calcium channel blocker nitrendipine (NTD) 10−7M. Pretreatment with calcium‐depleted medium for 30 min. almost abolished myometrial responses to high K+(124 mmol), oxytocin (OX) and prostaglandin F2a(PGF2a). Vascular responses to high K+(124 mmol) were also nearly abolished by such treatment. However, noradrenaline (NA), vasopressin (VP) and PGF2ain myometrial arteries and PGF2ain chorionic vessels and stem villous arteries induced significant, but reduced contractions after calcium depletion. In all vascular preparations, exposed to calcium‐depleted medium, NTD (10−8M) almost abolished contractions induced by calcium (0.1–4.0 mM) in the presence of K+(124 mmol) and depressed responses to calcium in the presence of the other agonists tested. NTD (10−10–10−7M) depressed myometrial contractions induced by K+, OX and PGF2amore effective than vascular responses to K+, NA, VP and PGF2ain the myometrial arteries and K+and PGF2ain the placental arteries. It is concluded that activation of contraction in vessels from the human utero‐placental unit implies multiple cellular sources of calcium, while in myometrial smooth muscle, influx of superficially bound calcium may be an important initial step in contractile activation. Treatment with calcium channel blockers during late human pregnancy might involve relaxation of the myometrium together with vasodilatation of the myometrial and foetal placental vascular beds.
Orphenadrine Citrate Increases and Prolongs the Antinociceptive Effects of Paracetamol in Mice
Authors: Hunskaar Steinar , Berge Odd‐Geir , Hole Kjell
Published: July 2010

Abstract:Orphenadrine, a muscle relaxant with antinociceptive effects, was shown to increase and prolong the antinociceptive effects of paracetamol in mice. Both in the increasing temperature hot plate test and in the formalin test, a combination of the two drugs showed a significantly improved effect compared to either of the drugs alone. The time course of the effects was tested in the increasing temperature hot plate test. The group treated with the drug combination showed a prolonged effect compared to both single drug treated groups, the effect lasting longer than 120 min. for the combination and about 80 min. for the single drugs. Orphenadrine and paracetamol increased antinociception even when orphenadrine was injected 90 min. after paracetamol, which by that time did not exert antinociceptive effects by itself. Thus the combination of orphenadrine and paracetamol enhances the antinociceptive effect of either drug in mice.
Development of Tolerance to Glyceryl Trinitrate in an Isolated Human Peripheral Vein and Its Relation to Cyclic GMP Metabolism
Authors: Ahlner Johan , Andersson Rolf G. G. , Axelsson Krister L. , Dahlström U. , Rydell Ewa L.
Published: July 2010

Abstract:Human peripheral vein (v. saphena magna) was exposedin vitroto glyceryl trinitrate (GTN) 0.1 mM for 1 h. The subsequent relaxant effect of GTN (10nM–0.1 mM) on vessels contracted by serotonin (0.25 μM) was significantly reduced on vessels preexposed to GTN as compared to control vessels, indicating a development of partial tolerance as far as the vascular smooth muscle relaxant effect is concerned. The impaired relaxant effect was paralelled by a reduced increment of intracellular cyclic GMP. This is, in turn, probably a consequence of both a diminished guanylate cyclase activity and an elevated phosphodiesterase activity in the GTN‐tolerant vessels. The relaxant activity as well as the level of intracellular cyclic GMP were restored in GTN‐tolerant vessels by dipyridamole (5 μM), an agent with phosphodiesterase inhibiting properties.
Venous Blood Levels of Inhaled Trichloroethylene in Female Rats and Changes Induced by Interacting Agents
Authors: Jakobson Inga , Holmberg Bo , Ekner Aina
Published: July 2010

Abstract:The concentration from inhalation of trichloroethylene (TCE) in venous blood from female rats was studied. Exposure consisted of 200, 400 and 500 ppm for 6 hrs, or 50 and 100 ppm for 2 hrs. In each experiment, I rat was exposed at a constant concentration of TCE. Blood samples were obtained from an indwelling jugular cannula throughout the experiment. Combination effects with chloral hydrate (0.2 g/kg), ethanol (0.8 ml/kg), isopropanol (0.8 ml/kg), pyrazole (0.2 g/kg), tetraethylthiuram disulfide (TETD; 0.2 g/kg) or tetrachloroethylene (TTCE; 1 g/kg) given orally were observed. The experimental data on the uptake of TCE in blood were fitted, by use of nonlinear regression analysis, to a simple toxicokinetic model. TETD caused the greatest increase in the steady state concentration of TCE (3.7 x), compared to TCE alone at 200 ppm. Isopropanol, pyrazole and TTCE also produced pronounced effects, but chloral hydrate treatment resulted in no significant change. At 50 and 100 ppm TCE exposure for 2 hrs, a significant increase (almost 3 x) in the steady state concentration of TCE from both ethanol and isopropanol was observed.
Embryotoxic and Teratogenic Effects of Interaction of Cadmium and Lindane in Rats
Authors: Saxena D. K. , Murthy R. C. , Chandra S. V.
Published: July 2010

Abstract:Embryotoxic and teratogenic effects of cadmium and lindane were studied in rats. Cadmium or lindane alone did not produce any significant malformations in the 20 day old foetuses whereas their combination caused significant reduction in the body weight of dams and pups and increased total embryonic deaths. Skeletal deformities like wavy ribs, reduced skull ossification and reduced caudal vertebrae were potentiated in coexposure group. The study indicated that the simultaneous exposure to cadmium and lindane may have more deleterious effects on the developing foetus compared to either alone.
Bone Changes in Rats with Adjuvant Arthritis: Treatment with 1α‐Hydroxycholecalciferol
Authors: Binderup Lise
Published: July 2010

Abstract: Adjuvant arthritis was induced in female Lewis rats by the injection of Mycobacterium butyricum in mineral oil in a hindpaw. Bone changes due to polyarthritis were evaluated in the tibia metaphyseal region of the noninjected hind leg. A decrease in bone mass and mineral content was observed in the affected bone, accompanied by a marked increase in bone resorption. Non‐arthritic and arthritic rats were treated with the synthetic vitamin D analogue, 1α‐hydroxycholecalciferol (0.01 to 1.0 μg/kg/day orally) for 28 days. Treatment resulted in a small increase in bone weight and mineral content in the non‐arthritic rats. Arthritic rats exhibited a larger increase in bone weight, hydroxyproline and calcium content. These beneficial effects were correlated with the ability of 1α‐hydroxycholecalciferol to increase extracellular calcium and phosphorus levels, as measured by the increased urinary excretion of calcium and inorganic phosphate and by the increase in serum calcium. Bone resorption and new bone formation were not affected by the treatment.
Effects of Captopril on the Urinary Excretion of Prostanoids and Kallikrein in Spontaneously Hypertensive Rats
Authors: Säynäväulammi Pekka
Published: July 2010

Abstract:The possible roles of vasodilatory prostanoids and the kallikrein‐kinin system in the antihyperten‐sive action of the angiotensin‐converting enzyme (kininase II) inhibitor captopril were examined in spontaneously hypertensive rats. Captopril (20, 50 or 100 mg/kg daily orally) reduced blood pressure markedly and dose‐dependently. It also increased water consumption and urine excretion, measured on the 5th day of treatment. The 24‐hr urinary excretion of PGE2was not changed, whereas that of PGF2αand TxB2tended to be enhanced. A clear increase, significant with all doses of captopril, occurred in the urinary excretion of 6‐keto‐PGF1α. Kallikrein excretion in urine was suppressed by the two larger doses of captopril. The markedly augmented urinary excretion of 6‐keto‐PGF1α, the stable metabolite of vasodilatory prostacyclin (PGI2), suggests that increased prostacyclin production may participate in the antihypertensive mechanism of captopril. Vasodilatory kinins can also contribute, since the captopril‐induced decrease in kallikrein may reflect accumulation of kinins due to their reduced metabolism.
Effects of Manganese Chloride on the Rat Developing Nervous System
Authors: Kristensson K. , Eriksson H. , Lundh B. , Plantin L.‐O. , Wachtmeister L. , el Azazi M. , Morath C. , Heilbronn E.
Published: July 2010

Abstract: Sprague‐Dawley rats were exposed to sublethal doses of manganese chloride during their postnatal development period up to 44 days of age. They showed transient clinical signs of disease and a decreased homovanillic acid (HVA) content in the striatum and hypothalamus between 15 and 22 days of age. The manganese content in the brain was increased 20–40 times during this period as determined with neutron activation analyses. In spite of this no structural damage or signs of maturation disturbances in the nervous system were found. Interruption of manganese exposure reversed the changes in HVA content.
Uptake, Distribution and Elimination of3H‐Gentamicin in Different Organs of the Rat as Determined by Scintillation Counting
Authors: Nässberger Lennart , DePierre Joseph W.
Published: July 2010

Abstract:Radioactivity attained in different tissues at different times after a single intraperitoneal injection of3H‐gentamicin into male rats was determined using scintillation counting. After about 30 min. kidney cortex demonstrated 3‐ to several hundred‐fold greater radioactivity than other tissues. Gentamicin was released from kidney medulla and the urinary bladder relatively rapidly, whereas the radioactivity in kidney cortex and thoracal cartilage was maintained for at least 6 hrs.
3H‐Adrenaline Release from Rabbit Isolated Aorta by Electrical‐Field Stimulation
Authors: Abrahamsen Jan , Nedergaard Ove A.
Published: July 2010

Abstract:The aim of the present work was to study the release of3H‐adrenaline (3H‐A) from rabbit isolated aorta. This release was compared with that of3H‐noradrenaline (3H‐NA). The stimulation‐evoked3H‐overflow from aorta preloaded with3H‐A decreased with repeated stimulation (S1‐S3). In contrast, prestimulation enhanced subsequent stimulation‐evoked3H‐overflows. For both3H‐amines, the3H‐overflow increased concomitantly to the same degree with the number of pulses (30–1000) at 3 Hz. The time course of3H‐overflows with either3H‐A or3H‐NA was compared. In the case of3H‐A, the3H‐overflow increased with time, while for3H‐NA the3H‐overflow remained unchanged both at 3 and 10 Hz. The stimulation‐evoked3H‐overflow from rings preloaded with either3H‐amine was the same at frequencies from 1 to 10 Hz, whereas at 30 Hz the3H‐overflow derived from3H‐A was higher than that using3H‐NA. An analysis of the quantitative aspects of individual stimulation‐evoked3H‐overflows showed that the fractional profile did not differ using either amine. In both cases, at least 96% of the3H‐overflow evoked by stimulation at 3 or 10 Hz was contained in the initial four 2‐min. fractions. The ratio between stimulation‐evoked3H‐overflow and spontaneous3H‐outflow was the same for both amines at 3 Hz, while the ratio was higher for3H‐NA at 10 Hz. Rauwolscine (10−6M) enhanced the3H‐overflow 6‐fold, while (—)‐propranolol (10−7M) had no effect at 3 Hz. It is concluded that3H‐A is released by electrical‐field stimulation in much the same manner as3H‐NA. Furthermore, rabbit isolated aorta is a useful preparation for the study of the release of transmitters as well as the modulation of the release mediated via presynaptic adrenoceptors.
Calcium, Calcium Channel Blockade and Airways Function
Authors: Löfdahl Claes‐Göran , Barnes Peter J.
Published: July 2010

Abstract:This review will highlight recent advances in understanding the physiological role of calcium and effects of calcium channel blockers on pathogenetic factors in asthma, including airway smooth muscle contraction, mast cell degranulation and mucus secretion. A review of clinical studies with calcium channel blockers in asthma will also be presented.
Calcium Channel Blockers and Pulmonary Hypertension
Authors: Andersson Karl‐Erik
Published: July 2010

Abstract:In vascular smooth muscle from the pulmonary circulation, potassium evoked contractions are abolished in calcium‐free medium and by calcium channel blockers (CCB). Noradrenaline, histamine, and serotonin induced contractions are partly resistant. Pulmonary arterial hypertension may occur both as a primary disorder and secondary to cardiac and pulmonary diseases; in both types there may be a component of pulmonary arterial vasoconstriction. In animal models, hypoxic pulmonary hypertension is counteracted by CCBs, nifedipine being particular effective. In patients with this disorder, CCBs also seem able to lower pulmonary arterial pressure and vascular resistance, but no controlled trials documenting their clinical efficacy have been performed. This is valid also for primary pulmonary hypertension, where some of the CCBs may have clinical value.
Effects of Calcium Channel Blockers on Urinary Tract Smooth Muscle
Authors: Andersson Karl‐Erik , Forman Axel
Published: July 2010

Abstract:Influx of calcium from the extracellular medium seems to be important for spontaneous as well as agonist‐induced contractile activity in urinary tract smooth muscle. To a various extent this calcium influx occurs through pathways which can be blocked by calcium channel blockers. These drugs effectively suppress spontaneous ureteral activity in vitro. Whether they affect ureteral motility in vivo or whether they can counteract ureteral spasm associated with ureteral stones have not been established. Calcium channel blockers partially block electrically as well as agonist‐induced detrusor contractions. Some of these drugs abolish even atropine‐resistant contractile responses induced by electrical stimulation in detrusor muscle. Drugs with combined antimuscarinic and calcium channel blocking effect therefore have an attractive effect profile. Experiences with calcium channel blockers in the treatment of patients with ‘unstable bladder’ are limited, but results obtained with terodiline seem promising. Even if calcium channel blockers reduce agonist‐induced contraction in isolated urethral muscle, their clinical effect on urethral function seems to be small. The effects of calcium blockers on urinary tract smooth muscle may be clinically useful and deserve further study.
Nitrate therapy today
Authors: Johansson Bengt W
Published: July 2010

Abstract: A review of nitrate therapy including a short summary of their physiological effects is presented. Both cardiac and non‐cardiac indications are reviewed including esophageal spasm, spasm of bile ducts and urinary tract, Raynaud's disease, pulmonary hypertensive disorders, portal hypertension, bronchial asthma, and effect on arrhythmias.
Digital pulse plethysmography (DPG) in studies of the hemodynamic response to nitrates — A survey of recording methods and principles of analysis
Authors: Lund Fredrik
Published: July 2010

Abstract:Digital pulse plethysmography (DPG) has proved a technically simple, noninvasive, sensitive and informative technique for studying the effects of nitroglycerin and other nitrates on peripheral arteries. The importance of performing nitrate evaluation by DPG mainly in elderly subjects is emphasized. On the basis of observations with DPG some indirect conclusions on the effect of nitrates on the coronary arteries are justified. — A review, with recommendations based on own experience, is given of various recording techniques and principles of evaluating quantitatively the digital volume pulse contour, with special reference to the influence of nitrates on the position and appearance of dicrotism. DPG seems to be a convenient, noninvasive and helpful procedure in studies on the development of nitrate tolerance.
VANADIUM IN DEPRESSIVE STATES
Authors: SIMONOFF M. , CONRI C. , SIMONOFF G.
Published: July 2010

Abstract Serum vanadium levels have been measured by neutron activation analysis. They are higher (3.10 ± 1.38 ng/mL) in patients suffering depressive illness than in normal subjects (0.67 ± 0.32 ng/mL).
POTENTIAL USE OF TETRATHIOMOLYBDATE IN COPPER STORAGE DISEASES
Authors: Gooneratne S.R.
Published: July 2010

Abstract Tetrathiomolybdate (TTM) is an effective decoppering agent. The mechanism of liver copper (Cu) removal by TTM was evaluated, using radiolabelled 67Cu, and 99Mo labelled TTM, with special reference to the relative contribution by the different excretory pathways in liver Cu removal. TTM increased the excretion of Cu via bile, urine and faeces. The increased biliary Cu excretion is relevant, as most of the important Cu storage diseases in man and animals are the result of the inability of the hepatocytes to excrete excess Cu into bile.
Effect of N‐acetylcysteine on markers of skeletal muscle injury after fatiguing contractile activity
Authors: Pinheiro C. H. J. , Vitzel K. F. , Curi R.
Published: July 2010

The effects of N‐Acetylcysteine (NAC), an unspecific antioxidant, on fatiguing contractile activity‐induced injury were investigated. Twenty‐four male Wistar rats were randomly assigned to two groups. The placebo group (N=12) received one injection of phosphate buffer (PBS) 1 h prior to contractile activity induced by electrical stimulation. The NAC group (NAC; N=12) received electrical stimulation for the same time period and NAC (500 mg/kg, i.p.) dissolved in PBS 1 h prior to electrical stimulation. The contralateral hindlimb was used as a control, except in the analysis of plasma enzyme activities, when a control group (rats placebo group not electrically stimulated and not treated) was included. The following parameters were measured: tetanic force, muscle fatigue, plasma activities of creatine kinase (CK) and lactate dehydrogenase (LDH), changes in muscle vascular permeability using Evans blue dye (EBD), muscle content of reactive oxygen species (ROS) and thiobarbituric acid‐reactive substances (TBARS) and myeloperoxidase (MPO) activity. Muscle fatigue was delayed and tetanic force was preserved in NAC‐treated rats. NAC treatment decreased plasma CK and LDH activities. The content of muscle‐derived ROS, TBARS, EBD and MPO activity in both gastrocnemius and soleus muscles were also decreased by NAC pre‐treatment. Thus, NAC has a protective effect against injury induced by fatiguing contractile activity in skeletal muscle.
Clinical evaluation of three toothbrush models tested by schoolchildren
Authors: Stroski ML , de Souza Dal Maso AM , Wambier LM , Chibinski ACR , Pochapski MT , Santos FA , Wambier DS
Published: July 2010

To cite this article:
 
Int J Dent Hygiene
9, 2011; 149–154 DOI: 10.1111/j.1601‐5037.2010.00476.x. Stroski ML, de Souza Dal Maso AM, Wambier LM, Chibinski ACR, Pochapski MT, Santos FA, Wambier DS. Clinical evaluation of three toothbrush models tested by schoolchildren.

Abstract:  Aim:  The aim of this single‐blind cross‐over study was to compare the performance of three different toothbrush models in the control of dental biofilm and maintaining a healthy gingival condition.

Methods:  Twenty‐seven schoolchildren (aged 9–10 years) participated in the study. Three toothbrushes with different bristle arrangements were used: T1 – bristles on the same plane, straight arrangement; T2 – bristles on different planes, straight arrangement; T3 – bristles on different planes, straight and circular arrangement. The participants were then randomly divided into three groups for brushing with one of the three toothbrushes. Each experimental period lasted 15 days each, with three daily brushings and a 7‐day washout interval was used between periods. The oral hygiene and gingival bleeding indices were recorded by a single, calibrated examiner blind to the brush used. Bristle wear was measured with a digital calliper at the end of each period. The data were analysed using parametric (anova and Student’s t‐test) and non‐parametric (Cochran’s Q and McNemar) tests.

Results:  The toothbrushes achieved similar results (P > 0.05) for the clinical parameters investigated. The three models exhibited a similar degree of bristle wear (P > 0.05).

Conclusion:  The arrangement of the bristles had little influence over the removal of biofilm and gingival conditions. Thus, there is no clinical justification for replacing conventional toothbrushes with more expensive models.