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.     

Asymmetric synthesis of (S)-ethyl-4-chloro-3-hydroxybutanoate using Candida parapsilosis ATCC 7330

Asymmetric reduction of ethyl-4-chloro-3-oxobutanoate to (S)-ethyl-4-chloro-3-hydroxybutanoate in aqueous medium by resting cells of Candida parapsilosis ATCC 7330 was optimized. The influence of culture parameters (inoculum size, inoculum age and biocatalyst harvest time) and reaction parameters (co-substrate, resting cell, pH and substrate concentrations) on the asymmetric reduction were studied. It was found that these parameters significantly influenced the rate of the asymmetric reduction. Under the optimum conditions, the final concentration of (S)-ethyl-4-chloro-3-hydroxybutanoate, enantiomeric excess and the isolated yield of (S)-ethyl-4-chloro-3-hydroxybutanoate were 1.38 M (230 g/l), >99 and 95%, respectively. The space time yield was 115 mmol/lh, which is significantly higher than other whole cell biocatalysts reported so far.     

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.     

Mapping Interactions between Myosin Relay and Converter Domains That Power Muscle Function

Intramolecular communication within myosin is essential for its function as motor, but the specific amino acid residue interactions required are unexplored within muscle cells. Using Drosophila melanogaster skeletal muscle myosin, we performed a novel in vivo molecular suppression analysis to define the importance of three relay loop amino acid residues (Ile⁵⁰⁸, Asn⁵⁰⁹, and Asp⁵¹¹) in communicating with converter domain residue Arg⁷⁵⁹. We found that the N509K relay mutation suppressed defects in myosin ATPase, in vitro motility, myofibril stability, and muscle function associated with the R759E converter mutation. Through molecular modeling, we define a mechanism for this interaction and suggest why the I508K and D511K relay mutations fail to suppress R759E. Interestingly, I508K disabled motor function and myofibril assembly, suggesting that productive relay-converter interaction is essential for both processes. We conclude that the putative relay-converter interaction mediated by myosin residues 509 and 759 is critical for the biochemical and biophysical function of skeletal muscle myosin and the normal ultrastructural and mechanical properties of muscle.     

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.     

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.     

大熊猫初生胎儿及幼仔组织器官的病理学研究

To elucidate the cause of prenatal and early postnatal death in giant panda, pathological studies have been carried out on paraffin-fixed tissue sections from two fetuses and four cubs. The fetuses appeared to have classical atrophic changes in lung and hemorrhage in multiple organs, whereas the cubs showed purulent inflmnmation in various organs, most profound in lung and umbilicus. Localized infusion of bacteria and neutrophils were identified in the focus. Acute enteritis and hepatitis were also observed, as well as purulent encephalitis in one case. Variable degrees of congestion, hemorrhage, denaturalization and putrescence were evident in heart, liver, spleen, kidney, intestines, and lymph nodes. The results indicated that the fetuses died from suffocation whereas the cubs died from infection.