Action of prostanoids on the emetic reflex of Suncus murinus (the house musk shrew)

Several prostanoids were investigated for a potential to induce emesis in Suncus murinus. The TP receptor agonist 11alpha,9alpha-epoxymethano-15S-hydroxyprosta-5Z,13E-dienoic acid (U46619) induced emesis at doses as low as 3 microg/kg, i.p. but the DP receptor agonist 5-(6-Carboxyhexyl)-1-(3-cyclohexyl-3-hydroxypropyl) hydantoin (BW245C) was approximately 1000 times less potent. The emetic action of U46619 (300 microg/kg, i.p.) was antagonized significantly by the TP receptor antagonist, vapiprost (P<0.05). EP (prostaglandin E(2), 17-phenyl-omega-trinor prostaglandin E(2), misoprostol and sulprostone), FP (prostaglandin F(2alpha) and fluprostenol) and IP (iloprost and cicaprost) receptor agonists failed to induce consistent emesis at doses up to 300-1000 microg/kg, i.p. Fluprostenol reduced nicotine (5 mg/kg, s.c.)-but not copper sulphate (120 mg/kg, intragastric)-induced emesis; the other inconsistently emetic prostanoids were inactive to modify drug-induced emesis. The results indicate an involvement of TP and possibly DP and FP receptors in the emetic reflex of S. murinus.     

Analysis of amyloid deposition in a transgenic mouse model of homozygous familial amyloidotic polyneuropathy

Amyloid fibrils derived from the Japanese, Portuguese, and Swedish types of familial amyloidotic polyneuropathy all consist of a variant transthyretin (TTR) with a substitution of methionine for valine at position 30 (TTR Met 30). In an attempt to establish an animal model of TTR Met-30-associated homozygous familial amyloidotic polyneuropathy and to study the structural and functional properties of human TTR Met 30, we generated a mouse line carrying a null mutation at the endogenous ttr locus (ttr-/-) and the human mutant ttr gene (6.0-hMet 30) as a transgene. In these mice, human TTR Met-30-derived amyloid deposits were first observed in the esophagus and stomach when the mice were 11 months of age. With advancing age, amyloid deposits extended to various other tissues. Because no significant difference was detected in the onset, progression, and tissue distribution of amyloid deposition between the ttr-/- and ttr+/+ transgenic mice expressing 6.0-hMet 30, endogenous normal mouse TTR probably does not affect the deposition of human TTR Met-30-derived amyloid in mice. TTR is a tetramer composed of four identical subunits that binds thyroxine (T4) and plasma retinol-binding protein. The introduction of 6.0-hMet 30 into the ttr-/- mice significantly increased their depressed serum levels of T4 and retinol-binding protein, suggesting that human TTR Met 30 binds T4 and retinol-binding protein in vivo. The T4-binding ability of human TTR Met 30 was confirmed by the analysis of T4-binding proteins in the sera of ttr-/- transgenic mice expressing 6.0-hMet 30. The T4-binding studies also demonstrated the presence of hybrid tetramers between mouse and human TTR subunits in the ttr+/+ transgenic mice expressing 6.0-hMet 30.     

Instrumentation and techniques in equine fracture fixation

In recent years fracture fixation in the horse has changed significantly. New devices, mainly adapted from the human field, have been successfully introduced into large animal surgery. Examples of such implants include the DCS/DHS implant system, the self-tapping screw, the cannulated screw, and the pinless external fixator. However, new devices have also been developed exclusively for equine fracture management, including the interlocking intramedullary nail and the external skeletal fixation device. With these devices the surgeon has more options for repairing fractures in horses. Nevertheless, many problems are still unsolved. Indications exist that during the next few years new, exciting fracture fixation systems will be developed, providing further advancements in the quest for the ideal implant for horses. However, the development stages of these devices are such that mentioning the possibilities here is premature.     

Importance of the Arg-Gly-Asp triplet in human thrombin for maintenance of structure and function

Site-directed mutagenesis was employed to assess the importance of the Arg-Gly-Asp triplet that comprises residues 197 to 199 in the B-chain of thrombin. Properties of the R197E and the D199E variants were compared with those of zeta-thrombin and the inactive S205A variant wherein the active site Ser is replaced by Ala. Relative to zeta-thrombin, the R197E thrombin variant under the assay conditions used exhibits 26% activity toward a small chromogenic substrate, 13% activity in the activation of protein C in the presence of thrombomodulin, < 3% activity in processing fibrinogen, and 1% activity in inducing platelet activation. Thus, the substrate specificity of thrombin was altered by the R197-->E replacement. The D199E variant was essentially inactive. It exhibited only 0.02% of the activity of thrombin toward the chromogenic substrate and its reactivity toward the active site-directed alkylating agent D-Phe-Pro-Arg-CH2Cl was 10,000-fold lower than that of thrombin. Like the inactive S205A thrombin variant, the D199E variant antagonized the interactions of thrombin with hirudin and thrombomodulin, but was a less effective antagonist. The dependence of the antagonism of the thrombin-thrombomodulin interaction on the concentration of D199E thrombin variant provided evidence suggesting the presence of two or more domains in thrombin that independently interact with their counterparts in thrombomodulin. Although the S205A thrombin variant antagonized the action of thrombin on platelets no such activity could be demonstrated for the D199E variant in the concentration range studied (< 800 nm). Comparison of the circular dichroism spectra of zeta-thrombin, the D199E, R197E, and S205A variants indicated that subtle differences in conformation exist between the D199E variant and the other thrombins. These differences in conformation might well account for the altered behavior of the D199E variant with respect to its interactions toward thrombomodulin, hirudin, and platelets.     

The interaction of dexamethasone with ondansetron on drug-induced emesis in the ferret

The characteristics of the five Korean isolates of Japanese encephalitis (JE) virus were compared with those of the already reported JE virus strains from Japan and China using the hemagglutination test and polymerase chain reaction direct sequencing of the JE virus genomes (capsid/premembrane, envelope region). The hemagglutination patterns of all the isolates were distinctly different from the Nakayama-NIH strain. The optimal pH of hemagglutination of all the Korean isolates was 6.6-7.0 and the reaction range was broader than that of the Nakayama-NIH strain. The 198 nucleotide sequences in the capsid/premembrane gene region of the five Korean strains indicated that they were classified into the third genotype group, the JE strains from the countries in the temperate zone including the Nakayama-NIH, JaOArS982, and Beijing-1 strains. Four of the five Korean isolates formed a unique phylogenetic tree within the third genotype group, although the last one was genetically highly related to the Nakayama-NIH strain. The 251 nucleotide sequences in the envelope region of the five isolates were more divergent than the capsid/premembrane region. Four of the five isolates showed a large nucleotide divergency as compared with the JaOArS982 strain (< or = 12.4%), but the last one was similar to the JaOArS982 strain (98% of nucleotide homology). These results suggest the evolutionary divergence of the JE viruses isolated in Korea from the Japanese and Chinese strains and that there may exist at least two antigenically different JE virus strains in Korea.     

Peritraumatic dissociation and posttraumatic stress in male Vietnam theater veterans

OBJECTIVE: The aim of this study was to determine the reliability and validity of a proposed measure of peritraumatic dissociation and, as part of that effort, to determine the relationship between dissociative experiences during disturbing combat trauma and the subsequent development of posttraumatic stress disorder (PTSD). METHOD: A total of 251 male Vietnam theater veterans from the Clinical Examination Component of the National Vietnam Veterans Readjustment Study were examined to determine the relationship of war zone stress exposure, retrospective reports of dissociation during the most disturbing combat trauma events, and general dissociative tendencies with PTSD case determination. RESULTS: The total score on the Peritraumatic Dissociation Experiences Questionnaire--Rater Version was strongly associated with level of posttraumatic stress symptoms, level of stress exposure, and general dissociative tendencies and weakly associated with general psychopathology scales from the MMPI-2. Logistic regression analyses supported the incremental value of dissociation during trauma, over and above the contributions of level of war zone stress exposure and general dissociative tendencies, in accounting for PTSD case determination. CONCLUSIONS: These results provide support for the reliability and validity of the Peritraumatic Dissociation Experiences Questionnaire--Rater Version and for a trauma-dissociation linkage hypothesis: the greater the dissociation during traumatic stress exposure, the greater the likelihood of meeting criteria for current PTSD.     

Neurotoxicity following the ingestion of a Chinese medicinal plant, Alocasia macrorrhiza

1. A case of poisoning due to the raw root tuber of a Chinese medicinal plant, Alocasia macrorrhiza is presented. 2. The patient developed neurological (severe pain and numbness in the perioral area and throat) and gastrointestinal (nausea, vomiting, abdominal pain) symptoms immediately after eating the root tuber. 3. A macrorrhiza has properties and morphology very similar to another medical plant. A. odora. The root tuber of the latter is known to contain a neurotoxin sapotoxin.