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Lower Dosage (lower + dosage)
Selected AbstractsPerinatal exposure to bisphenol-A changes N -methyl- D -aspartate receptor expression in the hippocampus of male rat offspringENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 1 2010Xiao-Hong Xu Abstract Bisphenol-A (BPA) is one of the most common environmental endocrine disrupters with mixed estrogen agonist/antagonist properties. The toxicity of BPA has been extensively evaluated in a variety of tests in rodents, including developmental and reproductive toxicity, and carcinogenicity. The objective of the present study is to evaluate whether or not perinatal maternal exposure to BPA at 0.05, 0.5, 5, 50, and 200 mg/kg/d affects N -methyl- D -aspartate (NMDA) receptor (NMDAR) subunits NR1, NR2A, 2B, estrogen receptor beta (ER,), and aromatase cytochrome P450 (P450arom) protein expressions of hippocampus in male rat offspring during postnatal development. Western-blotting analyses showed that perinatal exposure to BPA significantly affected the expression of NMDAR subunits. At the lower doses of 0.05 to 50 mg/kg/d, BPA concentration dependently inhibited the expression of NMDAR subunits. However, at the higher dose (200 mg/kg/d), the effects of BPA on these subunits were different, with a stronger inhibition of NR1 expression and a slighter inhibition of NR2A, 2B expression when compared with those at the lower dosage of BPA. In addition, perinatal exposure to BPA inhibited the expression of ER, protein, but increased P450arom protein expression in a concentration-dependent manner, especially during the early postnatal period (the first 1,3 postnatal weeks). No significant influence of BPA on P450arom was observed at postnatal week 8. These data suggest that environmental BPA exposure may affect the development of the brain, enhancing the local biosynthesis of estrogen in the brain, inhibiting ER, and NMDAR expressions. Environ. Toxicol. Chem. 2010;29:176,181. © 2009 SETAC [source] The model of fungal population dynamics affected by nystatinINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 1 2010Sergei I. Voychuk Abstract Fungal diseases are acute problems of the up-to-day medicine. Significant increase of resistance of microorganisms to the medically used antibiotics and a lack of new effective drugs follows in a growth of dosage of existing chemicals to solve the problem. Quite often such approach results in side effects on humans. Detailed study of fungi-antibiotic dynamics can identify new mechanisms and bring new ideas to overcome the microbial resistance with a lower dosage of antibiotics. In this study, the dynamics of the microbial population under antibiotic treatment was investigated. The effects of nystatin on the population of Saccharomyces cerevisiae yeasts were used as a model system. Nystatin effects were investigated both in liquid and solid media by viability tests. Dependence of nystatin action on osmotic gradient was evaluated in NaCl solutions. Influences of glucose and yeast extract were additionally analyzed. A "stepwise" pattern of the cell death caused by nystatin was the most intriguing. This pattern manifested in periodical changes of the stages of cell death against stages of resistance to the antibiotic. The mathematical model was proposed to describe cell-antibiotic interactions and nystatin viability effects in the liquid medium. The model implies that antibiotic ability to cause a cells death is significantly affected by the intracellular compounds, which came out of cells after their osmotic barriers were damaged © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010 [source] Effects of sub-antimicrobial dose doxycycline therapy on crevicular fluid MMP-8, and gingival tissue MMP-9, TIMP-1 and IL-6 levels in chronic periodontitisJOURNAL OF PERIODONTAL RESEARCH, Issue 1 2004Dong-Hoon Choi Objective:, To investigate whether sub-antimicrobial dose doxycycline (SDD) therapy for 120 d in chronic adult periodontitis patients had significant effects on gingival crevicular fluid (GCF) matrix metalloproteinase-8 (MMP-8) levels, and on gingival tissue MMP-9, tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) and interleukin-6 (IL-6) levels. Background:, Tetracycline can significantly inhibit MMP activity in GCF and in gingival tissue, even in much lower dosage then a traditional antimicrobial dosage used in conventional therapy. Sub-antimicrobial dose doxycycline (SDD) therapy has been shown to reduce periodontal disease activity to control MMP and pro-inflammatory cytokines. Methods:, A total of 32 patients with incipient to moderate (probing pocket depth ,,4,7 mm) chronic adult periodontitis were included in the study. Subjects were randomly assigned to two groups. After scaling and root planning (SRP), the SRP + SDD group received SDD, 20 mg bid, whereas the SRP + placebo group received placebo, 20 mg bid. In the follow-up, efficacy measures included the change in probing pocket depth (PD), clinical attachment level (CAL), bleeding on probing (BOP) and gingival crevicular fluid MMP-8 levels, gingival tissue MMP-9, TIMP-1 and IL-6 levels from baseline to 120 d. Results:, After 120 d, PD and CAL improved significantly in the SRP + SDD group. Initial MMP-8 levels for the SRP + SDD group and the SRP + placebo group were 407.13 ± 114.45 ng/ml and 378.71 ± 189.39 ng/ml, respectively, with no statistical difference between the two groups. MMP-8 levels for the SRP + SDD group and the SRP + placebo group were: 235.35 ± 134.58 ng/ml and 364.04 ± 219.27 ng/ml at 30 d; 157.50 ± 95.95 ng/ml and 236.60 ± 186.16 ng/ml at 60 d; 102.70 ± 67.64 ng/ml and 208.56 ± 124.54 ng/ml at 90 d; and 63.77 ± 53.33 ng/ml and 229.13 ± 168.09 ng/ml at 120 d, respectively. The amount of decrease in MMP-8 levels for the SRP + SDD group was statistically significant compared to that for the SRP + placebo group, especially apparent at 120 d (p < 0.05). TIMP-1 levels in both groups increased from the baseline to 120 d with statistical significance (p -value < 0.05), but there was no significant difference between the two groups. Changes in MMP-9 and IL-6 levels were not statistically significant. Conclusion:, Adjunctive SDD therapy can improve the clinical parameters and this clinical improvement is reflected by controlled level of MMP-8 in chronic adult periodontitis after the therapy. [source] Prescribing antipsychotic drugs for inpatients with schizophrenia in Asia: Comparison of REAP-2001 and REAP-2004 studiesASIA-PACIFIC PSYCHIATRY, Issue 2 2010Mian-Yoon Chong MD PhD FRCPsych Abstract Introduction: This international collaborative study aimed to investigate the trend and change in prescription patterns of antipsychotic drugs for inpatient schizophrenia in Asia by comparing two surveys in 2001 and 2004. Methods: Prescription patterns of inpatient schizophrenia in China, Hong Kong, Japan, Korea, Singapore and Taiwan were surveyed in July of 2001 and 2004 using a standardized protocol. Patients' social and clinical characteristics, psychiatric symptoms, course of illness and adverse effects of medications were systematically assessed and recorded. Prescription patterns of antipsychotic drugs were compared and analyzed. Results: Altogether, 4535 patients were surveyed. There were no significant differences in their demographic characteristics between 2001 and 2004. Compared with 2001, a significant increase in the use of second-generation antipsychotics (SGA) (from 45.5% to 64.7%) with reciprocal decreasing use of first-generation antipsychotics was found in 2004. The trend was unanimously seen across these Asian countries and among those prescribed with monotherapy or polypharmacy. The proportion using monotherapy significantly increased, from 52.7% in 2001 to 61.1% in 2004. There was a tendency of using a lower dosage of antipsychotic medications and a less concomitant use of anti-Parkinson drugs. Discussion: The present study showed a trend of increasing use of SGA among Asian countries. Except for Japan and Singapore, a relatively low use of antipsychotic polypharmacy was generally found. The increasing use of SGA and policy changes reduced the mean duration of admission days. With increasing awareness of consumers and continuing education for psychiatrists, the trend is expected to continue. [source] Safety and efficacy of oral entecavir given for 28 days in patients with chronic hepatitis B virus infectionHEPATOLOGY, Issue 3 2001Ph.D., Robert A. de Man M.D. Entecavir is an oral antiviral drug with selective activity against hepatitis B virus (HBV). We conducted a randomized, placebo-controlled, dose-escalating study in patients with chronic hepatitis B infection in which we evaluated the efficacy and safety of entecavir given for 28 days. Follow-up was 24 weeks. All doses of entecavir (0.05 mg, 0.1 mg, 0.5 mg, and 1.0 mg) showed a pronounced suppression of replication of the HBV with a 2.21, 2.29, 2.81, and 2.55 mean log10 reduction of viral load, respectively. Approximately 25% of patients on entecavir showed a decline of HBV DNA below the limit of detection of the Chiron HBV-DNA assay (<0.7 MEq/mL). In the postdosing follow-up period patients who were treated with 0.5 and 1.0 mg of entecavir showed a considerably slower return in their HBV DNA levels to baseline compared with those patients treated with lower dosages (P < .05). All doses of entecavir were well tolerated with no significant difference between treated patients and those receiving placebo. No significant changes in alanine transaminase (ALT) levels within the dose groups and the placebo group between baseline and the end of treatment were observed. Three patients (9%) (1 each in the 0.05-, 0.1-, and 0.5-mg groups) experienced asymptomatic hepatitis flares 16 weeks (2 patients) and 24 weeks (1 patient) after withdrawal of entecavir. In conclusion, in this 28-day study of entecavir a pronounced decrease of HBV DNA was observed and there were no significant side effects in entecavir patients in comparison with placebo-treated patients. (HEPATOLOGY 2001;34:578-582.) [source] Antiviral activity of low-dose alovudine in antiretroviral-experienced patients: results from a 4-week randomized, double-blind, placebo-controlled dose-ranging trial,HIV MEDICINE, Issue 3 2007J Ghosn Background Alovudine inhibits replication of highly nucleoside reverse transcriptase inhibitor (NRTI)-resistant HIV strains in vitro. However, dose-dependent safety concerns resulted in its initial development being halted. Recently, a 4-week course of alovudine 7.5 mg/day added to a stavudine-free failing regimen yielded a significant decrease in viral load by ,1.88 log10 HIV-1 RNA copies/mL. The magnitude of the reduction in viral load suggested that lower doses might still be effective while offering adequate safety during long-term use. Objective To determine whether lower dosages of alovudine still provide significant antiviral activity in patients with broad NRTI resistance. Methods A randomized, double-blind, placebo-controlled trial investigating three doses of alovudine (0.5, 1 and 2 mg) or placebo added for 4 weeks to a failing regimen in patients with evidence of NRTI-resistant HIV strains [,2 thymidine-associated mutations (TAMs)]. The primary endpoint was the mean viral load reduction between baseline and week 4. Results Seventy-two patients were enrolled in the study: 21, 13, 18 and 20 in the placebo and 0.5, 1 and 2 mg arms, respectively. Baseline median CD4 count and viral load were 298 cells/,L (range 44,692 cells/,L) and 3.9 log10 copies/mL (range 2.5,5.2 log10 copies/mL), respectively. Baseline viral isolates harboured a median of four TAMs. Alovudine was added to a median four-drug failing regimen. At week 4, compared with placebo, mean viral load changes were ,0.42 log10 [95% confidence interval (CI) ,0.67 to ,0.18] and ,0.30 log10 (,0.55 to ,0.06) in the 2 and 1 mg arms, respectively. There was no significant change in CD4 cell count. Alovudine was well tolerated. Conclusion: A 4-week course of alovudine 2 mg/day provided a modest but significant viral load reduction in patients harbouring viruses with a median of four TAMs. [source] Influence of rabeprazole and lansoprazole on the pharmacokinetics of tacrolimus in relation to CYP2C19, CYP3A5 and MDR1 polymorphisms in renal transplant recipientsBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 4 2007Masatomo Miura Abstract The objective of this study was to evaluate whether genetic polymorphisms of CYP2C19, CYP3A5 and MDR1 significantly impact the interaction between tacrolimus and rabeprazole or lansoprazole. Seventy-three recipients were randomly assigned after renal transplantation to receive repeated doses of tacrolimus for 28 days with a regimen of either 20 mg of rabeprazole or 30 mg of lansoprazole. Blood concentrations of tacrolimus were measured by microparticle enzyme immunoassay. The mean daily dose and the dose-adjusted area under the plasma concentration-time curves from 0 to 12 h (AUC0,12) of tacrolimus coadministered with rabeprazole or lansoprazole were the lowest and highest, respectively, in CYP2C19 poor metabolizers (PMs) having the CYP3A5*3/*3 genotype (0.084 and 0.112 mg/kg/day and 1.269 and 1.033 ng·h/ml/mg/kg, respectively). On the other hand, the mean dose-adjusted AUC0,12 of tacrolimus coadministered with rabeprazole or lansoprazole were the highest in CYP2C19 PMs having the MDR13435CC+CT genotype, but not significantly. The present study indicates that there are significant interactions between tacrolimus and rabeprazole or lansoprazole in CYP2C19 PM renal transplant recipients bearing the CYP3A5*3/*3 genotypes. For recipients having these genetic polymorphisms, lower dosages of tacrolimus are required to achieve the target therapeutic index. Copyright © 2007 John Wiley & Sons, Ltd. [source] | ||||||||||