Further studies on the biochemistry of the toxins from the sea wasp Chironex fleckeri

Extracts from the tentacles of Chironex fleckeri (Cnidaria) were resolved into two lethal fractions by chromatography on CM-Sephadex C-50. These were apparently identical to the two fractions previously resolved on Sephadex G-200. The hemolysin in the extracts was also examined by thin-layer chromatography on Sephadex G-200 and by various electrophoretic techniques. It was shown that the hemolysin associated markedly with the various support media, which made electrophoresis of little use. The tentacle extracts and a toxin obtained by a milking technique were compared by chromatography and shown to be very similar if not identical in their biological activities. Some data on the stability of the hemolysin was also obtained.     

The effect of immunoglobulin M-enriched intravenous immunoglobulins against bacterial infections and on the neutralization of bacterial toxins

Studies on the Efficacy of Immunoglobulin M Enriched Intravenous Immunoglobulins against Bacterial Infections and in Neutralization of Bacterial Toxins. An essential component of the new i.v. immunoglobulin product Pentaglobin is immunoglobulin M (IgM), which is concentrated in this preparation. The efficacy of this IgM containing preparation in comparison to conventional i.v. immunoglobulins was demonstrated in mouse protection tests and by in vitro neutralization of bacterial toxins. The IgM containing immunoglobulin preparation has significantly higher protection rates against gram-positive and gram-negative bacteria in mouse protection tests compared to immunoglobulin G (IgG) preparations. Bacterial toxins of Pseudomonas aeruginosa and Staphylococcus aureus are likewise more effectively neutralized by the IgM containing immunoglobulin preparation.     

Interrelationships between toxins: studies on the cross-reactivity between bacterial or animal toxins and monoclonal antibodies to two jellyfish venoms

Affinity chromatography on columns of immobilized anti-Chrysaora and anti-Physalia monoclonal antibodies can be an effective purification tool for animal and bacterial toxins. Furthermore, the fact that specific fractions of a given species obtained from immunochromatography columns prepared with either monoclonal antibody possessed identical protein bands, were quantitatively similar in in vitro cardiotoxicity and bound like amounts of antibody, as indicated by the enzyme-linked immunosorbent assay, suggested that antigenic targets of the two monoclonal antibodies are cross-reactive and/or are located on the same molecule. Additional enzyme-linked immunosorbent assays were conducted using non-coelenterate toxins. The significant binding of brown recluse spider venom and purified cholera toxin to both our monoclonal antibodies indicated that these toxic substances shared a common or cross-reacting antigenic site(s) with some coelenterate venoms.     

Further studies on the anti-nociceptive effect of vasopressin.

The possible interactions of pathways which mediate anti-nociception when stimulated by alpha 2-adrenoceptor agonists and arginine vasopressin (AVP) were investigated. Yohimbine, an alpha 2-antagonist, failed to modify the anti-nociceptive response of AVP. However, clonidine pretreatment, in sub-effective and effective doses, potentiated the anti-nociceptive response of a sub-effective dose of AVP. This potentiation was attenuated by yohimbine and completely antagonized by naloxone. These studies suggest that pathways related to the opioidergic system and those stimulated by alpha 2-agonists may be utilized by AVP in eliciting the anti-nociceptive response.     

Preliminary studies on the effect of rebamipide against the trypsin and egg-albumin induced experimental model of asthma

The present investigation was carried out to study the effect of rebamipide in experimentally induced bronchial asthma in mice. Trypsin and egg-albumin induced chronic model of asthma was used and various parameters were measured on the 35th day. The asthmatic control group showed lower level of haemoglobin saturation with oxygen, tidal volume, airflow rate and higher respiratory rate, serum bicarbonate level, eosinophil count in bronchoalveolar lavage fluid and histamine level compared to the normal control group. Dexamethasone and rebamipide treated groups showed the return of all the above parameters towards normal values. Histopathological examination of lungs showed more prominent alveolar and muscular layer destruction in the asthmatic control group than in dexamethasone and rebamipide treated groups. Rebamipide showed a beneficial effect and might be used for the treatment of bronchial asthma.     

A highly sensitive bacterial assay for toxins based on swarming inhibition, and comparison with the cup plate assay based on growth inhibition

The motility inhibition of the swarming bacteria Proteus mirabilis and Azospirillum brasilense was found to be an appropriate parameter to indicate toxic effects caused by some mycotoxins, lactones and anhydrides of dicarboxylic acids. If these substances are in contact with the motile bacteria the following phenomena can be observed: at a certain toxin concentration the swarming of the bacteria is inhibited. If the concentration is increased the swarming ceases, and at still higher concentrations the bacteria are inactivated. In some instances swarming is stimulated at very low toxin doses. The sensitivity of this assay is comparable to the cup plate assay based on growth inhibition with Bacillus thuringiensis [Lenz, P. et al., Toxicology, 40 (1986) 199, Boutibonnes et al., Pharmacology, 11 (1983) 430] and in some cases it is even higher.     

水母毒素研究与转化医学

水母蜇伤是最常见的海洋生物伤,其发生率随着近年来环境变化引起的水母爆发性增长在不断上升。水母毒素对心血管、血液、神经、肌肉等具有多种生物毒性,其作用机制不明确,水母蜇伤防治也以对症处理为主。注重水母蜇伤临床症状、救治措施与水母毒素纯化鉴定、作用机制之间的相互联系,将加速水母毒素研究的整体推进。     

悦安欣注射液细菌内毒素检查

目的　试用鲎试剂检查悦安欣注射液中的细菌内毒素。方法　用悦安欣注射液 1∶ 5稀释液进行干扰试验。结果　悦安欣注射液 1∶ 5稀释液不干扰细菌内毒素试验。结论　用细菌内毒素检查法可取代热原检查法控制悦安欣注射液质量。     

Further studies on the xylazine-yohimbine interaction

A study of the Yohimbine-blocking action upon Xylazine-ability to inhibit the abdominal contortions elicited by an intraperitoneal injection of Acetic Acid (60 mg/kg) was carried out. Xylazine (0.75 mg/kg - subcutaneously) inhibited 44% of the abdominal contortions. Such an inhibition activity was reduced to a 19% level after a previous Yohimbine treatment (1 mg/kg - intramuscularly - 30 min before). The results suggested there is a 2.9 times reduction of Xylazine affinity for CNS alpha 2 receptors, and that the antagonism between the two drugs is of a competitive nature.     

Prospects on behavioral studies of marine and freshwater toxins

While there is a long-standing tradition of using behavioral methods to study the effects of manufactured drugs and environmental chemicals, comparatively little attention has focused until recently on the behavioral effects of marine or freshwater toxins. A vast array of microorganisms, found in a variety of waters, are known to occasionally "bloom" and produce toxins that can cause either blatant toxicity (i.e., lethality) or damage to a number of organ systems. The nervous system is a known target for many of the toxins. Considerable research has in the past been carried out to determine toxin effects on the survivability of laboratory rodents (typically mice) following acute exposures. Newer research has shown, however, prominent toxin-induced alterations in motor, sensory, autonomic and cognitive functions at sublethal exposure concentrations. Future toxin research can capitalize upon a wealth of behavioral paradigms already available in toxicology, pharmacology and neuroscience.     

Further studies on the in vivo effect of cephaloridine on the stability of rat kidney lysosomes

The stabilizing effect of cephaloridine, an antibiotic, on rat kidney lysosomal membranes was tested by a single subcutaneous injection. The release of two lyososomal enzymes, acid phosphatase and muramidase, was used as an index of lysosome membrane integrity. The levels of these enzymes in the kidney extracts as well as in the isolated kidney lysosome fractions were found to be raised considerably, compared to the controls. In rats treated with cephaloridine, the supernatant fraction obtained from the kidney homogenates, after centrifugation at 15,000 g_av, contained lower enzyme activities than were found in the control animals. It is suggested that cephaloridine may inhibit the release of acid phosphatase and muramidase from rat kidney lysosomes and, therefore, may exert a stabilizing effect on the lysosomal membrane system. The possible mechanism of interaction of this antibiotic with rat kidney lysosomal membranes is proposed.