Evaluation of the hepatotoxicological effects of a drug in an in vivo/in vitro model

Both in vivo and in vitro models have certain disadvantages for the study of the chronic hepatotoxicity of drugs. The aim of this work was to evaluate a new approach based on an in vivo/in vitro model. After chronic in vivo treatment of rats with Vincamine and Vindeburnol (an eburnamenine derivative which exhibits hepatotoxic properties in man) liver cells were isolated, and functional and metabolic disorders (metabolic utilization of fructose and protein biosynthesis) were studied to determine injury. The results showed no modification of blood parameters, but a direct relationship between the dose of Vindeburnol administered in vivo and the metabolic disorders observed in vitro, evidencing the high sensitivity and reliability of this model.     

Flow-induced release of adenosine 5′-triphosphate from endothelial cells of the rat mesenteric arterial bed

Adenosine 5-triphosphate (ATP) was released into the perfusate of rat isolated mesenteric arterial beds during each of two consecutive increases in flow. There was no significant difference between the amounts of ATP released on each occasion. Substance P was also released into the perfusate by increased flow, although its release was more variable. Removal of the endothelium of the mesenteric vessels with sodium deoxycholate led to a significant reduction (74%) in the amount of ATP released compared with the release before the endothelium had been removed. This suggests that the ATP released into the mesenteric arterial perfusate during increased flow arises from endothelial cells.     

In vitro protein synthesis and α amylase activity in F cells from hepatopancreas ofPalaemon serratus (Crustacea; Decapoda)

In crustaceans, all the steps in the assimilation of food take place in the hepatopancreas. To facilitate the study of this organ, a method for the dissociation of cell types was developed. The hepatopancreas of the prawnPalaemon serratus was mechanically dissociated and the cells separated by Percoll density-gradient centrifugation. The E and R cells had similar densities of around 1.05 g/ml. The F cells were separated into two distinct fractions with densities of 1.075 and 1.082 g/ml. The B cells sedimented at a density of 1.12 g/ml. The ratio between the two populations of F cells was found to vary during the intermolt cycle while B cells disappeared after the molt. When the density gradient fractions were incubated with³H-leucine, incorporation was highest in the F cell fractions. Measurements of -amylase activity, indicated that the two populations of F cells may be derived from the same cell type.     

Autophagy and other vacuolar protein degradation mechanisms

Autophagic degradation of cytoplasm (including protein, RNA etc.) is a non-selective bulk process, as indicated by ultrastructural evidence and by the similarity in autophagic sequestration rates of various cytosolic enzymes with different half-lives. The initial autophagic sequestration step, performed by a poorly-characterized organelle called a phagophore, is subject tofeedback inhibition by purines and amino acids, the effect of the latter being potentiated by insulin and antagonized by glucagon. Epinephrine and other adrenergic agonists inhibit autophagic sequestration through a prazosin-sensitive ₁-adrenergic mechanism. The sequestration is also inhibited by cAMP and by protein phosphorylation as indicated by the effects of cyclic nucleotide analogues, phosphodiesterase inhibitors and okadaic acid.Asparagine specifically inhibits autophagic-lysosomal fusion without having any significant effects on autophagic sequestration, on intralysosomal degradation or on the endocytic pathway. Autophaged material that accumulates in prelysosomal vacuoles in the presence of asparagine is accessible to endocytosed enzymes, revealing the existence of an amphifunctional organelle, the amphisome. Evidence from several cell types suggests that endocytosis may be coupled to autophagy to a variable extent, and that the amphisome may play a central role as a collecting station for material destined for lysosomal degradation.Protein degradation can also take place in a salvage compartment closely associated with the endoplasmic reticulum (ER). In this compartment unassembled protein chains are degraded by uncharacterized proteinases, while resident proteins roturn to the ER and assembled secretory and membrane proteins proceed through the Golgi apparatus. In thetrans-Golgi network some proteins are proteolytically processed by Ca²⁺-dependent proteinases; furthermore, this compartment sorts proteins to lysosomes, various membrane domains, endosomes or secretory vesicles/granules. Processing of both endogenous and exogenous proteins can occurr in endosomes, which may play a particularly important role in antigen processing and presentation. Proteins in endosomes or secretory compartments can either be exocytosed, or channeled to lysosomes for degradation. The switch mechanisms which decide between these options are subject to bioregulation by external agents (hormones and growth factors), and may play an important role in the control of protein uptake and secretion.     

Identification of a new predaceous stink bug pheromone and its attractiveness to the eastern yellowjacket

Summary Males ofPodisus fretus (Hemiptera: Pentatomidae) release a long-range attractant pheromone containing linalool (49.0%), (E)-2-hexenal (34.5%), benzyl alcohol (12.0%), nerolidol (2.0%),-terpineol (1.1%), and traces of several other compounds. The eastern yellowjacket,Vespula maculifrons (Hymenoptera: Vespidae), is attracted to artificial pheromones forP. fretus and for the sympatric species,Podisus maculiventris.The authors thank Mr T.J. Henry of the USDA Systematic Entomology Laboratory and Dr J.E. McPherson, Southern Illinois University, for examining the pentatomid species and Dr A.S. Menke, USDA-SEL, for determining the yellowjacket species. We also thank S. Wilzer for technical assistance. Mention of a company name does not imply endorsement by the US Department of Agriculture.     

Immunogenetics

Summary The 1985 Catalog of Mapped Genes (Human Gene Mapping 8; 33) has been used to pick out the known, immunologically important genes; these are then discussed in the following order: 1. genes controlling organs, tissues and cells of the immune apparatus, 2. genes determining self structures, 3. genes determining the structures of immunological specificity, 4. genes determining substances with immunoregulatory and effector properties. The symbols for the genes and the biological functions of their products are explained. The genetics of the ABO blood groups, of the HLA-system and of antibody formation are given in rather more detail.     

Determination of erythrocyte pyrimidine 5′-nucleotidase activity by31P nuclear magnetic resonance: Comparison of normal controls and multiple sclerosis patients

Summary A technique to assay erythrocyte pyrimidine 5-nucleotidase activity in situ using³¹P nuclear magnetic resonance spectroscopy is presented. The assay is chemically specific, simple and applicable to untreated lysates. A comparison of enzyme levels in normal controls and in multiple sclerosis patients employing the assay yielded no significant differences between both groups. Difficulties encountered in the quantitative analysis of the assay using¹H-NMR spectroscopy are briefly discussed.     

Molt-induced muscle atrophy decreases the zinc content of the pectoralis of the Giant Canada Goose (Branta canadensis maxima)

Summary During molt-induced atrophy of the pectoralis muscle of the Giant Canada Goose (Branta canadensis maxima), the zinc content of the muscle was significantly reduced (p0.0139), though the concentration of zinc per unit weight of muscle appeared higher (p0.0232). Zinc lost from the muscle during molt could be utilized for growth of the new flight feathers.Acknowledgments. Funds for this study were obtained from an operating grant awarded to J. C. G. by the Natural Sciences and Engineering Research Council of Canada.