ABSTRACT
The androgen dehydroepiandrosterone (DHEA) has been reported to protect neuronal cells against dysfunction and apoptosis. Several signaling pathways involved in these effects have been described but little is known about the intracellular trafficking of DHEA. We describe design, synthesis and characterization of DHEA-Bodipy, a novel fluorescent DHEA analog. DHEA-Bodipy proved to be a functional DHEA derivative: DHEA-Bodipy (i) induced estrogen receptor alpha-mediated gene activation, (ii) protected PC12 rat pheochromocytoma cells against serum-deprivation-induced apoptosis, and (iii) induced stress fibers and focal adhesion contacts in SH-SY5Y human neuroblastoma cells. DHEA-Bodipy bound rapidly and specifically to plasma membranes of living PC12 cells. We analyzed metabolism and trafficking of DHEA-Bodipy in human neuroblastoma cells. DHEA-Bodipy is the first functional fluorescent DHEA derivative suitable for live cell imaging of intracellular DHEA transport and localization.
Subject(s)
Boron Compounds/chemistry , Dehydroepiandrosterone/analogs & derivatives , Fluorescent Dyes/chemistry , Microscopy, Fluorescence/methods , Animals , Apoptosis/physiology , Biological Transport , Boron Compounds/metabolism , Cell Membrane/metabolism , Dehydroepiandrosterone/metabolism , Estrogen Receptor alpha/metabolism , Fluorescent Dyes/metabolism , Genes, Reporter , Humans , Molecular Structure , Neuroblastoma , PC12 Cells , RatsABSTRACT
OBJECTIVES: An increased risk of drug-related liver injury has been repeatedly reported in individuals infected with hepatitis C virus (HCV) receiving the antiretroviral drug nevirapine. This study was undertaken to assess the differences in the pharmacokinetics of nevirapine between patients with HIV/HCV coinfection and HIV infection that could explain higher rates of hepatotoxicity. METHODS: A 12 h pharmacokinetic analysis was performed in 18 patients: 7 HIV/HCV-coinfected and 11 HIV-monoinfected. Advanced liver disease was an exclusion criterion in order to assess the impact of chronic HCV infection alone. RESULTS: Comparing the two groups, no difference was observed between minimum and maximum drug levels or total drug exposure in terms of area under the curve. CONCLUSIONS: Hepatitis C coinfection does not alter the pharmacokinetics of nevirapine in patients with preserved liver function.
Subject(s)
Antiviral Agents/pharmacokinetics , Antiviral Agents/therapeutic use , HIV Infections/complications , Hepatitis C, Chronic/complications , Nevirapine/pharmacokinetics , Nevirapine/therapeutic use , Adult , Female , HIV Infections/drug therapy , Hepatitis C, Chronic/drug therapy , Humans , Male , Middle Aged , Serum/chemistryABSTRACT
In the present study 24 hospitalized patients requiring empirical antibiotic treatment were randomly assigned to receive the beta-lactam antibiotic/beta-lactamase inhibitor combination piperacillin-tazobactam either as an intermittent or as a continuous infusion. According to pharmacokinetic modelling, the daily dose was reduced by 33% in patients receiving continuous infusion compared with intermittent infusion. Dose reduction because of impaired renal function was required in the intermittent dosing group for 5 of 12 patients compared with 1 of 12 patients in the continuous infusion group. However, the mean daily dose in the continuous group was 15% less than the intermittent infusion group. Mean serum concentrations of piperacillin were to 39.0 microg/ml after the end of bolus distribution, exceeding by far the minimal inhibitory concentration of the most clinically relevant pathogens. The corresponding mean value for tazobactam was 6.3 microg/ml. Pharmacokinetic/pharmacodynamic modelling suggests that both treatment schemes should produce virtually identical anti-infective responses to sensitive, intermediate and resistant strains. In the present study the continuous infusion of piperacillin/tazobactam provided adequate antibacterial activity over the 24-h dosing period and offers the potential for a substantial reduction in the total daily dose.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacokinetics , Infections/drug therapy , Penicillanic Acid/administration & dosage , Penicillanic Acid/pharmacokinetics , Piperacillin/administration & dosage , Piperacillin/pharmacokinetics , Adult , Aged , Anti-Bacterial Agents/therapeutic use , Cholangitis/drug therapy , Community-Acquired Infections/drug therapy , Cross Infection/drug therapy , Drug Administration Schedule , Female , Fever of Unknown Origin/drug therapy , Hospitalization , Humans , Infections/etiology , Infusions, Intravenous , Male , Middle Aged , Penicillanic Acid/analogs & derivatives , Penicillanic Acid/therapeutic use , Piperacillin/therapeutic use , Piperacillin, Tazobactam Drug Combination , Pneumonia/drug therapy , Prospective Studies , Treatment Outcome , Urinary Tract Infections/drug therapyABSTRACT
This study describes a method for off-line coupling of thin-layer chromatography (TLC) with electron impact ionization (El)-mass spectrometry for routine determination of pesticides in toxicology and forensic medicine. Six TLC solvent systems are described for 151 different pesticides, and 8-peak mass-spectra generated from full El mass spectra are listed.
