RESUMEN
BACKGROUND: GSK1265744 is an HIV integrase strand transfer inhibitor selected for clinical development. OBJECTIVE: This first-time-in-human and phase IIa investigation assessed GSK1265744 antiviral activity, pharmacokinetics, safety, and tolerability in healthy and HIV-1-infected subjects. METHODS: This double-blind, placebo-controlled study consisted of a dose escalation of single (part A) and multiple (part B) oral doses in 48 healthy subjects and an oral dose (part C) in 11 HIV-1-infected subjects. In part A, 2 cohorts of 9 subjects received either 5 and 25 mg or 10 and 50 mg. In part B, 3 cohorts of 10 subjects received 5, 10, or 25 mg once daily for 14 days. In part C and the phase IIa study, subjects received 5 or 30 mg once daily for 10 days. RESULTS: Dose-proportional increases in drug exposure were observed in healthy and HIV-1-infected subjects. In healthy subjects, pharmacokinetic variability was low following single or repeat dosing (coefficient of variation, 13%-34% and 15%-23%, respectively). Mean plasma half-life was 31.5 hours. GSK1265744 monotherapy significantly reduced plasma HIV-1 RNA from baseline to day 11 in HIV-1-infected subjects receiving 5 or 30 mg versus placebo (P < .001); mean decrease was 2.2 to 2.3 log10 copies/mL, respectively. Study drug was generally well tolerated with no clinically relevant trends in laboratory values, vital signs, or electrocardiograms. CONCLUSIONS: GSK1265744 was well tolerated in healthy and HIV-1-infected subjects. Results demonstrate once-daily doses of 5 or 30 mg exceeded minimum target therapeutic concentrations and produced a significant reduction in plasma HIV-1 RNA viral load.
Asunto(s)
Fármacos Anti-VIH/farmacocinética , Infecciones por VIH/tratamiento farmacológico , Piridonas/farmacocinética , Adulto , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Relación Dosis-Respuesta a Droga , Genotipo , VIH-1/genética , VIH-1/metabolismo , Humanos , Masculino , Piridonas/efectos adversos , Piridonas/uso terapéutico , ARN Viral , Carga Viral , Adulto JovenRESUMEN
Clostridium magnum, originally described as a non-autotrophic homoacetogenic bacterium, was found to be able to grow with H2/CO2, formate, or methanol with stoichiometric acetate formation, provided that the growth medium contained at least 0.025% (w/v) yeast extract. Hydrogen was also formed as a byproduct of glucose fermentation, and was consumed again after glucose consumption. Hydrogen formation from glucose was independent of growth conditions and reached similar maximal concentrations in mineral media with or without ammonia added as well as in non-growing cultures or in the presence of carbon monoxide.
Asunto(s)
Clostridium/crecimiento & desarrollo , Hidrógeno/metabolismo , Dióxido de Carbono/metabolismo , Clostridium/metabolismo , CinéticaRESUMEN
In sterilized spinach which was inoculated with bacteria, a reduction of NO3- to NO2-, due to their metabolic activity, was detectable, depending on the holding conditions. The reaction rate was highest in the presence of thermophilic bacteria. A lower reaction rate was altogether found with mesophilic bacteria which, depending on counts and holding time, may temporarily cause high nitrite contents. The reaction rate was lowest with cold-tolerant bacteria.
Asunto(s)
Microbiología de Alimentos , Nitratos/metabolismo , Nitritos/metabolismo , Plantas Comestibles/metabolismo , Plantas Comestibles/microbiología , TemperaturaRESUMEN
The biological activity of the antifungal agents pentachlorophenol (as sodium pentachlorophenolate) and formaldehyde was evaluated by changes in the development of fungal structures following a placement of test strips inoculated with Aspergillus niger conidia on a nutrient agar with the toxicant. The method allows a quantitative assessment of biological activity measured as the development of vegetative structures (growth of the mycelium) by metric, and the development of reproductive structures (conidia) of A. niger by densitometric methods. The use of test strips with dry conidiospores and the evaluation of the results in physical units represent a simple, rapid, exact and inexpensive test of fungitoxic agents.
Asunto(s)
Aspergillus niger/efectos de los fármacos , Desinfectantes/farmacología , Formaldehído/farmacología , Pentaclorofenol/farmacología , Aspergillus niger/crecimiento & desarrollo , Medios de Cultivo , Pruebas de Sensibilidad Microbiana/métodosRESUMEN
Hard-bioled eggs in the shell were without any pretreatment stored in air at 20 degrees C and 4 degrees C. Furthermore the keeping quality of varnish-coated eggs stored in air at 20 degrees C and of untreated eggs stored in 100% carbon dioxide at the same temperature was studied. Hard-boiled eggs stored at 4 degrees C and varnish-coated eggs stored at 20 degrees C were of excellent bacteriological quality up to 5 weeks. Untreated eggs stored in air at 20 degrees C showed high microbiological contamination (more than 10(6)/g) already after one week. The CO2 storage atmosphere inhibited the growth of microorganisms during the first week of storage, but in the days to follow counts increased to more than 10(6)/g as well.
Asunto(s)
Huevos , Microbiología de Alimentos , Conservación de Alimentos/métodos , Aeromonas/aislamiento & purificación , Animales , Bacillus cereus/aislamiento & purificación , Dióxido de Carbono , Pollos , Frío , Contaminación de Alimentos , Pseudomonas/aislamiento & purificación , Factores de TiempoRESUMEN
Bacteria have been found to grow differently at contact sites to both organic and anorganic solids as on pure agar media. Of 16 ad hoc selected bacterial strains, the following species (arranged in decreasing order) responded with stronger colony formation: Bacillus subtilis, B. cereus, Streptococcus sanguis, S. saprophyticus, S. faecalis, Escherichia coli, Micrococcus flavus, Actinomyces viscosus, Veillonella sp., Enterobacter liquefaciens, Yersinia enterocolitica. Lactobacillus casei behaved neutral. Proteus vulgaris, Y. enterocolitica and Chromobacterium violaceum grow on certain media only in the presence of solid particles. The yeasts Endomyces lactis, Saccharomyces cerevisiae, Rhodotorula mucilaginosa and Cryptococcus nigricans did not respond to solid particles during colony formation. The kind of protein-animal (meat) or vegetable (soy beans)-did not influence the behaviour of the microorganisms in these experiments.
Asunto(s)
Bacterias/crecimiento & desarrollo , Medios de Cultivo , Hongos/crecimiento & desarrollo , Agar , Celulosa , Fibras de la Dieta , Vidrio , Gossypium , Especificidad de la Especie , MaderaRESUMEN
The presence of cellulose particles, so in-vitro studies have shown, influences the growth rate and metabolic activity of the bacteria Escherichia coli, Bifidobacterium adolescentis and Chromobacterium violaceum. After the homogenization in Waring Blendor, the growth rate has been found to be highest in a medium containing 10% cellulose particles and to show a decreasing tendency in media containing 5%, 1% and 0% cellulose. The biochemical intensity, judged by glucose consumption and intensity of nitrate reduction, showed an inverse tendency. It seems necessary to add also the factor "biochemical activity" of the microorganisms to the effect of dietary fibres in the intestinal tract.
Asunto(s)
Bifidobacterium/crecimiento & desarrollo , Celulosa , Chromobacterium/crecimiento & desarrollo , Fibras de la Dieta , Escherichia coli/crecimiento & desarrollo , Bifidobacterium/metabolismo , Chromobacterium/metabolismo , Medios de Cultivo , Escherichia coli/metabolismo , Glucosa/metabolismo , Nitratos/metabolismo , Oxidación-Reducción , Especificidad de la EspecieRESUMEN
In experiments on the influence of microscopic capillaries on the growth of Escherichia coli, Brevibacterium linens, Micrococcus flavus and Bacillus cereus, a distinct delay in growth was observed. The difference in counts was greatest after 8 h. Later a slight equilibration of counts was noted. With B. cereus, only slight or no spore formation was observed under microcapillary conditions.
Asunto(s)
Bacillus cereus/crecimiento & desarrollo , Brevibacterium/crecimiento & desarrollo , Escherichia coli/crecimiento & desarrollo , Micrococcus/crecimiento & desarrollo , Bacillus cereus/fisiología , Técnicas Bacteriológicas , Acción Capilar , Vidrio , Cinética , Esporas BacterianasRESUMEN
The adsorption of Escherichia coli as influenced by the surface chemistry of different absorbents was studied with microbeads of (1) polystyrene, hydroxymethylated, chloromethylated and aminomethylated polystyrene, (2) cation and anion exchange resins, (3) glass and siliconized glass using a shake test. The adsorption kinetics can be described by a first order rate law for all materials. The specific surface free energy is not even a rough correlation parameter for the adsorption effect. Polar groups with the exception of those with a negative charge (cation exchange resin) favour adsorption of Escherichia coli, but the type of the polar surface group plays a dominating role. Adsorption was maximum with protonated aminomethylated polystyrene which is attributed to the interaction of the positive charge with the negatively charged bacterial surface.