Rapid, simple and sensitive high-performance liquid chromatographic method for detection and determination of acyclovir in human plasma and its use in bioavailability studies

A rapid, simple and sensitive reversed-phase high-performance liquid chromatographic (HPLC) method has been developed for the measurement of acyclovir concentrations in human plasma and its use in bioavailability studies is evaluated. Unchanged acyclovir has been quantified without the introduction of an internal standard using the present method. Human plasma proteins were selectively precipitated by the addition of 7% perchloric acid to spiked plasma samples or to the plasma samples obtained after acyclovir administration to human volunteers and the mixture was spun at 1000 g for 10 min. The supernatant was directly injected into a Novaflex C₁₈ column and detected at 254 nm. The mobile phase consisted of octane sulfonic acid buffer (pH 2.5) and methanol (92:08). The limit of quantitation for acyclovir in plasma was 20 ng/ml, which enabled the determination of the area under the curve (AUC) more precisely, that is, it is much closer to its extrapolated value. The present method has been successfully applied to samples from bioavailability studies.     

Effect of carbon tetrachloride on gonadal physiology in male rats.

Carbon tetrachloride was administered to male albino rats for varied intervals. It was found to have no significant adverse effect on spermatogenesis after 10 and 15 days of treatment. Severe damage to the spermatogenic cycle was observed after 20 days of treatment, leading to exfoliation of the germinal epithelium, depletion of germ cells, and shrinkage of the tubules.     

Computer analysis of regulatory signals in complete bacterial genomes. Translation initiation of ribosomal protein operons]

Signals of translation initiation of operons of Haemophilus influenzae ribosomal proteins were predicted. This process is regulated by the formation of secondary RNA structures to which one of the proteins encoded in a particular operon binds. In some cases, these structures imitate the region of protein binding to rRNA. Predictions are made by comparing with homologous operons of Escherichia coli and analogous regions of rRNA and by estimating the energy of secondary structure formation. It is shown that this regulatory mechanism occurs: in operons L11, S10, S15, spc, and alpha of H.influenzae and, probably, in operon S15 of Helicobacter pylori, Bacillus subtilis, and Mycoplasma genitalium.     

The Ca2+ channel β2 subunit is selectively targeted to the axon terminals of supraoptic neurons

The assembly of high voltage-activated Ca²⁺ channels with different β subunits influences channel properties and possibly subcellular targeting. We studied β subunit expression in the somata and axon terminals of the magnocellular neurosecretory cells, which are located in the supraoptic nucleus (SON) and neurohypophysis, respectively. Antibodies directed against the 4 Ca_Vβ subunits (Ca_Vβ₁-Ca_Vβ₄) were used for immunoblots and for immunostaining of slices of these two tissues. We found that all 4 β subunits are expressed in both locations, but that Ca_Vβ₂ had the highest relative expression in the neurohypophysis. These data suggest that the Ca_Vβ₂ subunit is selectively targeted to axon terminals and may play a role in targeting and/or regulating the properties of Ca²⁺ channels.     

An Efficiently Cleaved HIV-1 Clade C Env Selectively Binds to Neutralizing Antibodies

An ideal HIV-1 Env immunogen is expected to mimic the native trimeric conformation for inducing broadly neutralizing antibody responses. The native conformation is dependent on efficient cleavage of HIV-1 Env. The clade B isolate, JRFL Env is efficiently cleaved when expressed on the cell surface. Here, for the first time, we report the identification of a native clade C Env, 4-2.J41 that is naturally and efficiently cleaved on the cell surface as confirmed by its biochemical and antigenic characteristics. In addition to binding to several conformation-dependent neutralizing antibodies, 4-2.J41 Env binds efficiently to the cleavage-dependent antibody PGT151; thus validating its native cleaved conformation. In contrast, 4-2.J41 Env occludes non-neutralizing epitopes. The cytoplasmic-tail of 4-2.J41 Env plays an important role in maintaining its conformation. Furthermore, codon optimization of 4-2.J41 Env sequence significantly increases its expression while retaining its native conformation. Since clade C of HIV-1 is the prevalent subtype, identification and characterization of this efficiently cleaved Env would provide a platform for rational immunogen design.     

Climate‐related genetic variation in drought‐resistance of Douglas‐fir (Pseudotsuga menziesii)

There is a general assumption that intraspecific populations originating from relatively arid climates will be better adapted to cope with the expected increase in drought from climate change. For ecologically and economically important species, more comprehensive, genecological studies that utilize large distributions of populations and direct measures of traits associated with drought‐resistance are needed to empirically support this assumption because of the implications for the natural or assisted regeneration of species. We conducted a space‐for‐time substitution, common garden experiment with 35 populations of coast Douglas‐fir (Pseudotsuga menziesii var. menziesii) growing at three test sites with distinct summer temperature and precipitation (referred to as ‘cool/moist’, ‘moderate’, or ‘warm/dry’) to test the hypotheses that (i) there is large genetic variation among populations and regions in traits associated with drought‐resistance, (ii) the patterns of genetic variation are related to the native source‐climate of each population, in particular with summer temperature and precipitation, (iii) the differences among populations and relationships with climate are stronger at the warm/dry test site owing to greater expression of drought‐resistance traits (i.e., a genotype × environment interaction). During midsummer 2012, we measured the rate of water loss after stomatal closure (transpiration_min), water deficit (% below turgid saturation), and specific leaf area (SLA, cm² g^?1) on new growth of sapling branches. There was significant genetic variation in all plant traits, with populations originating from warmer and drier climates having greater drought‐resistance (i.e., lower transpiration_min, water deficit and SLA), but these trends were most clearly expressed only at the warm/dry test site. Contrary to expectations, populations from cooler climates also had greater drought‐resistance across all test sites. Multiple regression analysis indicated that Douglas‐fir populations from regions with relatively cool winters and arid summers may be most adapted to cope with drought conditions that are expected in the future.