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Single Daily Dose (single + daily_dose)
Selected AbstractsEndogenous antioxidant defence system in rat liver following mercury chloride oral intoxicationJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 3 2005Inmaculada Bando Abstract Mercury is a highly toxic metal which induces oxidative stress. Superoxide dismutases, catalase, and glutathion peroxidase are proteins involved in the endogenous antioxidant defence system. In the present study rats were administered orally, by gavage, a single daily dose of HgCl2 for three consecutive days. In order to find a relation between the proteins involved in the antioxidant defence and mercury intoxication, parameters of liver injury, redox state of the cells, as well as intracellular protein levels and enzyme activities of Mn-dependent superoxide dismutase (MnSOD), Cu-Zn-dependent superoxide dismutase (CuZnSOD), catalase, and glutathione peroxidase (GPx) were assayed both in blood and in liver homogenates. HgCl2 at the doses of 0.1 mg/kg produced liver damage which that was detected by a slight increase in serum alanine aminotransferase and gamma glutamyl transferase. Hepatic GSH/GSSG ratio was assayed as a parameter of oxidative stress and a significant decrease was detected, as well as significant increases in enzyme activities and protein levels of hepatic antioxidant defence systems. Changes in both MnSOD and CuZnSOD were parallel to those of liver injury and oxidative stress, while the changes detected in catalase and GPx activities were progressively increased along with the mercury intoxication. Other enzyme activities related to the glutathione redox cycle, such as glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PDH), also increased progressively. We conclude that against low doses of mercury that produce a slight oxidative stress and liver injury, the response of the liver was to induce the synthesis and activity of the enzymes involved in the endogenous antioxidant system. The activities of all the enzymes assayed showed a rapidly induced coordinated response. © 2005 Wiley Periodicals, Inc. J Biochem Mol Toxicol 19:154,161, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20067 [source] Ethanol Feeding Impairs Insulin-Stimulated Glucose Uptake in Isolated Rat Skeletal Muscle: Role of Gs , and cAMPALCOHOLISM, Issue 8 2005Qiang Wan Background: The mechanism by which chronic alcohol consumption impairs insulin sensitivity is unclear. We investigated the role of the Gs ,,mediated pathway in decreasing insulin sensitivity in skeletal muscle after ethanol consumption. Methods: Sixty male Wistar rats, divided into four groups, received either distilled water (controls; group I) or ethanol, which was administered by a gastric tube as a single daily dose of 5 g/kg (group II), 2.5 g/kg (group III), or 0.5 g/kg (group IV). After 20 weeks, fasting plasma glucose and serum insulin levels were measured. The hyperinsulinemic-euglycemic clamp study was performed under anesthesia to estimate whole-body insulin sensitivity. Insulin-stimulated glucose uptake was measured in vitro in dissected gastrocnemius muscle. Expression of glut4, Gs ,, and Gi , was quantified using real-time PCR analysis and western blotting. cAMP levels were measured by ELISA. Results: Compared with controls, the following observations were made: (1) the hyperinsulinemic-euglycemic clamp study revealed impaired insulin action at the whole-body level after ethanol treatment; (2) chronic ethanol feeding at 5 g/kg and 2.5 g/kg significantly decreased both basal and insulin-stimulated glucose uptakes in isolated skeletal muscle (p < 0.05), which was accompanied by decreased expression of glut4 (p < 0.05); (3) Gs , (mRNA and protein) expression in skeletal muscle was significantly increased in all three ethanol groups (p < 0.05), and cAMP levels were also increased by ethanol treatment (p < 0.05); and (4) there was no significant change in Gi , expression in all three ethanol groups. Conclusions: Chronic ethanol exposure decreased insulin-induced glucose uptake in rat skeletal muscle, which was associated with increased expression of Gs ,. Because Gs , is a negative regulator of insulin sensitivity, the alteration in Gs , expression may contribute to the ethanol-induced impairment of insulin signal transduction. [source] An Open Pilot Study Assessing the Benefits of Quetiapine for the Prevention of Migraine Refractory to the Combination of Atenolol, Nortriptyline, and FlunarizinePAIN MEDICINE, Issue 1 2010Abouch V. Krymchantowski MD, FAHS ABSTRACT Background., Migraine is a prevalent neurological disorder. Although prevention is the core of treatment for most, some patients are refractory to standard therapies. Accordingly, the aim of this study was to evaluate the use of Quetiapine (QTP) in the preventive treatment of refractory migraine, defined as previous unresponsiveness to the combination of atenolol, nortriptyline, and flunarizine. Methods., Thirty-four consecutive patients (30 women and 4 men) with migraine (ICHD-II), fewer than 15 days of headache per month, and not overusing symptomatic medications were studied. All participants had failed to the combination of atenolol (60 mg/day), nortriptyline (25 mg/day), and flunarizine (3 mg/day). Failure was defined as <50% reduction in attack frequency after 10 weeks of treatment. After other medications were discontinued, QTP was initiated at a single daily dose of 25 mg, and then titrated to 75 mg. After 10 weeks, headache frequency, consumption of rescue medications, and adverse events were analyzed. Results., Twenty-nine patients completed the study. Three patients withdrew and two were lost to follow-up. Among those who completed, 22 (75.9%; 64.7% of the intention-to-treat population) had greater than 50% headache reduction. The mean frequency of migraine days decreased from 10.2 to 6.2 per month. Use of rescue medications decreased from 2.3 to 1.2 days/week. Adverse events were reported by nine (31%) patients. Conclusions., Although limited by the open design, this study provides pilot data to support the use of QTP in the preventive treatment of refractory migraine. Controlled studies are necessary to confirm these observations. [source] Tropisetron: Optimal dosage for children in prevention of chemotherapy-induced vomitingPEDIATRIC BLOOD & CANCER, Issue 1 2005Carlo Cappelli MD Abstract The antiemetic efficacy and tolerability of Tropisetron (Navoban®, Novartis Pharma Switzerland AG, Bern), a selective 5-hydroxytriptamine receptor antagonist, has been assessed in the prevention of acute vomiting in children receiving chemotherapy for solid tumors. Tropisetron iv was given 30 min before administration of chemotherapy at a dose of 5 mg in children <20 kg body weight and at a dose of 10 mg in those >20 kg. A total of 50 children were studied in 189 courses of chemotherapy. Control of emesis was defined as total in absence of acute vomiting, as major if 1 or 2 events of acute vomiting occurred, and as not controlled if >2 events of acute vomiting occurred. Response was studied, taking into account Tropisetron dosage, degree of emetogenicity of the chemotherapeutic agents in pretreated and non-pretreated patients, and according to age groups. Tropisetron, administered in a single daily dose of 8,12 mg/m2, was found to be very effective in completely controlling acute emesis in 92% of the courses of moderately and highly emetogenic chemotherapy administered to pediatric patients with solid tumors. Moreover, Tropisetron, at this dosage, did not lead to any adverse effects. Pediatr Blood Cancer 2005; 45:48,53. © 2005 Wiley-Liss, Inc. [source] Variability in the pharmacokinetics of intravenous busulphan given as a single daily dose to paediatric blood or marrow transplant recipientsBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 1 2008Christa E. Nath WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , The pharmacokinetics of oral busulphan given four times daily has been extensively studied. , Large inter- and intravariability in oral busulphan exposure has led to attempts at pharmacokinetic monitoring. , However, there have been limitations in the pharmacokinetic analysis due to inadequate characterization of the elimination phase in a 6-h dosing interval, due to late absorption in some patients. , Intravenous (i.v.) busulphan is a relatively new administration method and there have been relatively few studies on the pharmacokinetics of i.v. busulphan, especially when given as a single daily dose. WHAT THIS STUDY ADDS , Inter- and intrapatient variability in i.v. busulphan pharmacokinetics is comparable to that previously observed with oral busulphan, suggesting that pharmacokinetic monitoring is advisable. , Children with immune deficiencies, in particular, have widely variable exposure. AIM To examine inter- and intrapatient variability in the pharmacokinetics of intravenous (i.v.) busulphan given as a single daily dose to children with malignant (n = 19) and nonmalignant (n = 21) disease. METHODS Busulphan (120 mg m,2, 130 mg m,2 or 3.2 mg kg,1) was administered over median 2.1 h. Blood samples (4,10) were collected after the first dose, busulphan concentrations were measured and pharmacokinetic parameters, including clearance (CL) and area under the concentration,time curve (AUC), were determined using the Kinetica software (Innaphase). Interpatient variability was assessed as percent coefficient of variation (% CV). Intrapatient variability was assessed by calculating percent differences between observed full dose AUC and AUC predicted from an initial 65 mg m,2 dose in 13 children who had busulphan pharmacokinetic monitoring. RESULTS Clearance of i.v. busulphan in 40 children was 4.78 ± 2.93 l h,1 (% CV 61%), 0.23 ± 0.08 l h,1 kg,1 (% CV 35%) and 5.79 ± 1.59 l h,1 m,2 (% CV 27%). Age correlated significantly (p < 0.001) with CL (l h,1) and CL (l h,1 kg,1), but not with CL (l h,1 m,2). AUC normalized to the 130 mg m,2 dose ranged from 14.1 to 56.3 mg l,1.h (% CV 37%) and also did not correlate with age. Interpatient variability in CL (l h,1 m,2) was highest in six children with immune deficiencies (60%) and lowest in seven children with solid tumours (14%). Intrapatient variability was <13% for nine (of 13) children, but between 20 and 44% for four children. CONCLUSIONS There is considerable inter- and intrapatient variability in i.v. busulphan CL (l h,1 m,2) and exposure that is unrelated to age, especially in children with immune deficiencies. These results suggest that monitoring of i.v. busulphan pharmacokinetics is required. [source] Mirtazapine and paroxetine: a drug-drug interaction study in healthy subjectsHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 6 2001F. J. L. Ruwe Abstract Paroxetine inhibits cytochrome P450 2D6, which is involved in the metabolism of mirtazapine. The possible drug-drug interaction between two pharmacologically distinct antidepressants, mirtazapine and paroxetine, has been investigated in a randomized, three-way crossover study in 24 healthy male and female subjects. After a titration phase of 3 days, each subject received single daily doses of 30,mg mirtazapine, 40,mg paroxetine or the combination for 6 days. Assessments included serial blood sampling for pharmacokinetics at steady state, cognitive testing using the test battery of CDR Ltd, a visual analogue mood rating scale (Bond and Lader) and the Leeds Sleep Evaluation Questionnaire. Paroxetine inhibits the metabolism of mirtazapine, as shown by increases of approximately 17% and 25% of the 24,h AUC's of mirtazapine and its demethyl metabolite, respectively. Mirtazapine did not alter the pharmacokinetics of paroxetine. The combined administration of mirtazapine and paroxetine probably does not alter cognitive functioning or result in major changes on the visual analogue mood rating scale and Sleep Evaluation Questionnaire, compared with the administration of either drug alone. The incidence of adverse events was lower during combined administration of mirtazapine and paroxetine than during administration of either drug alone. Fatigue, dizziness, headache, nausea, anxiety and somnolence were the most common adverse events during combined administration. These data suggest that the combination of mirtazapine and paroxetine is unlikely to lead to clinically relevant drug-drug interactions and can be used without dose adjustment of either drug. The combination may even be better tolerated than either drug alone. Copyright © 2001 John Wiley & Sons, Ltd. [source] | ||||||||||