The effect of E. coli endotoxin on the developing rat liver. II. Immunohistochemical localization of alpha-fetoprotein in rat liver multinucleated giant cells

Immunoperoxidase histochemical staining techniques have been used previously to localize alpha-fetoprotein (AFP) in hepatocytes from rat and human liver tissues. In this study, we extended these observations by examining liver tissues from rat fetuses exposed to E. coli endotoxin in order to document the presence of AFP in hepatic multinucleated giant cells. Liver sections were examined under light microscopy after incubation with purified antibody-peroxidase conjugates and histochemical stains. These sections showed a positive reaction for AFP in giant cells and hepatocytes that appeared as granular, brown intracytoplasmic deposits in cells throughout the hepatic lobule. Furthermore, a direct correlation was found between the number of positively stained giant cells and the serum concentration of AFP. The findings demonstrated that AFP distribution in endotoxin-induced liver injury is confined to isolated hepatocytes and multinucleated giant cells. This observation provides evidence that the origin of the giant cell in toxin-exposed fetal rat liver may be the hepatocyte.     

Quantifying fear potentiated startle using absolute versus proportional increase scoring methods: implications for the neurocircuitry of fear and anxiety

Abstract Rationale. The fear-potentiated startle paradigm [increased startle in the presence of a conditioned fear stimulus (CS)] has become increasingly popular as a tool for evaluating the potential efficacy of putative anxiolytic compounds. However, when the tested compounds also influence baseline startle, it is unclear how comparisons with control groups can best be made. Objective. To evaluate the validity of absolute difference (startle amplitude on CS minus non-CS test trials) vs. proportional increase (the absolute difference score divided by startle amplitude on non-CS test trials) scoring methods. Methods. The effect on proportional increase and absolute difference scores of baseline shifts that occur with or without concomitant increases in fear was evaluated in rats. A reliable measure should yield similar scores across shifting baselines, provided that fear levels remain constant. Results. Preexisting baseline differences, and those brought about by different startle-eliciting noise burst intensities, by strychnine injections, or by CRH infusions, each increased absolute difference scores without markedly influencing proportional change scores. These baseline differences were not associated with different fear levels. Increases in baseline startle brought about by unsignaled footshocks or by a second CS – increases which are associated with increased fear – partially occluded additional CS-induced increases using either measure. Conclusions. Across different baselines, CS-elicited fear is most accurately reflected in proportional change scores. Under certain conditions saturation effects may interfere with an accurate assessment using either measure. However, these same saturation effects may provide opportunities to explore the neural circuitry of fear and anxiety in novel ways. Electronic Publication     

Biologically active steroidal glycosides from Tribulus terrestris

The steroidal saponin constituents obtained from Tribulus terrestris were tested for their antimicrobial and cytotoxic effects. The spirostanol-based steroidal saponins 1-3 exhibited remarkable activity against fungal organisms (Candida albicans and Cryptococcus neoformans) and cancer cell lines [human malignant melanoma (SK-MEL), human oral epidermoid carcinoma (KB), human breast ductal carcinoma (BT-549), and human ovary carcinoma (SK-OV-3)], while none of the compounds possessing the furostanol framework 4-7 showed activity. The most active spirostanol glycoside, compound 3 exhibited a broad range of anticancer activity against cell lines, SK-MEL, KB, BT-549 and SK-OV-3 at IC50s of 6.0, 7.0, 6.0 and 8.2 micrograms/ml, respectively, while compounds 1 and 2 showed selective cytotoxicity against SK-MEL at 6.7 and 9.1 micrograms/ml, respectively. The minimum inhibitory concentrations (MIC) in antifungal bioassay for compounds 1-3 varied from 1.5 to 6.2 micrograms/ml, which prompted to conclude certain structural features are required for these bioactivities.     

Fundamental and accessory systems in herpesviruses

Evolutionary studies have a large theoretical component and will not directly provide therapies for herpesvirus infections. However, they do provide a conceptual framework within which we can evaluate the origins of the various systems that contribute to viral lifestyle. An evolutionary context allows ancient systems that are fundamental to the replication of all herpesviruses to be distinguished from those that have developed relatively recently in order to tailor viruses to particular biological niches. Both categories are in principle accessible to intervention, either to prevent basic replicative capabilities or to reduce the advantages that the virus has in its interactions with the host. Phylogenetic data provide estimates of evolutionary rate for herpesviruses that are only between one and two orders of magnitude greater than those of their hosts. However, it is becoming apparent that certain genes have evolved much faster under selection pressures and by mechanisms that are not well understood. Nonetheless, the mutation rates of even the most highly conserved genes are sufficient to permit herpesviruses to escape from antiviral therapy. Greater understanding of the origins and functions of herpesvirus genes may lead to new insights into the determinants of pathogenesis and hence to new diagnostic and therapeutic targets.