In vivo effects of Escherichia coli endotoxin on sulfobromophthalein clearance in the guinea-pig.

In vivo studies indicated that the primary effects of E. coli endotoxin on hepatic clearance of sulfobromophthalein were at the excretory level. Newborns were more sensitive to the LPS than older animals.     

Snake venom action: Are enzymes involved in it?

Summary Enzymes were the first clearly recognized components of snake venoms. When several more were discovered, attempts were made to correlate venom action with enzymic functions. The last few years have seen most successful efforts in the identification, isolation and structural elucidation of highly toxic polypeptides present in snake venoms, in particular of neurotoxins and membrane-active toxins. Following this development the polypeptides were called the true toxic components and the enzymes lost their previous central position in venom pharmacology. The time, therefore, has come to re-evaluate the role of enzymes in the complex interaction between snake and prey. While highly active polypeptides indeed dominate the action of hydrophiid venoms, they appear to play a lesser role in crotalid venom action as compared with enzyme components. Enzymes are involved in many levels of venom action, e. g. by serving as spreading factors, of by producing very active agents, such as bradykinin and lysolecithins in tissues of preys or predators. Some toxins, e. g. the membrane-active polypeptides appear to participate in the interaction between membrane phospholipids and venom phospholipases. The classical neurotoxin, -bungarotoxin, has been recognized as a powerful phospholipase. Several instances are known which indicate that some enzymes potentiate the toxic action of others; the analysis of a single enzyme may, therefore, not fully reveal its biofunction. For 3 enzymes, ophidianl-amino acid oxidase, ATPpyrophosphatase, and acetylcholinesterase, some of the problems pertaining to venom toxicity are discussed.     

Effect of aldosterone and methylprednisolone on cardiac NaK-ATPase

Summary Aldosterone (15 g BID) and methylprednisolone (8 mg QD) administration to female guinea-pigs augmented both the total and the specific activity of NaK-ATPase but not the activity of adenylate cyclase in the cardiac sarcolemma. The rise in NaK-ATPase was due to increase in the number of enzyme molecules; catalytic activity and ouabain-sensitivity of individual molecules did not change.Acknowledgments. This work was supported by grant 1 R01 HL16611 from the National Heart and Lung Institute of the National Institutes of Health, United States Public Health Service. I thank Mr Kooil Kang for his excellent technical assistance.     

Irreversible shock in rats after injection of microspheres into the renal artery

Summary After injection of microspheres into both renal arteries of rats, an irreversible shock syndrome develops, resulting in death within 4–12 h. Ligation of both renal pedicles after injection of microspheres prevents the shock. It is presumed that kininogenases released from the kidneys participate in the pathogenesis of the shock syndrome.These studies were supported in part by the Deutsche Forschungsgemeinschaft within the SFB 90, Cardiovasculäres System.     

Early foetal thrombosis induced by Thalidomide in mouse: Possible explanation for teratogenicity

Summary Mouse foetuses were treated by Thalidomide on days 11–12 in order to verify whether the drug would induce blood abnormalities leading to circulatory troubles. About 18% of the treated foetuses showed both severe limb haemorrhages on day 14, and obvious alterations of the nucleated red blood cells of vitelline origin. These blood abnormalities, occurring suddenly during the well-known critical stage of foetal development, could be responsible for circulatory blocks leading to necrosis.     

Changes in ecdysone levels in the spiderPisaura mirabilis nymphs (Araneae,Pisauridae)

Summary RIA of ecdysones are made on nymphal extracts ofPisaura mirabilis during the intermoulting cycle. The hormone level is low during exuviation and the greatest part of the intermoulting period but increases notably before and after ecdysis. The main hormonal peak or pre-ecdysial peak is due to -ecdysone, characterized by combined TLC/RIA.Acknowledgment. We wish to thank Dr M. Hirn for his help during the manipulations and J. Britton who has translated the text into English.     

A tissue-selective prostaglandin E2 analog with potent antifertility effects

Summary N-methanesulfonyl 16-phenoxy--tetranor PGE₂ is a prostaglandin analog which is markedly more tissue selective than PGE₂. This compound is 10–30 times more potent than PGE₂ in animal models which are considered relevant to antifertility effects in humans. In pharmacological tests which are believed to be predictive for side effects in humans, the compound has potency either equal to or less than that of PGE₂.     

Influence of PGA1 on cartilage growth

Summary Using the Fell technique of organ culture of cartilage in a chemically defined medium, it has been shown that prostaglandin A₁ at a concentration of 25 g/ml caused chondrocyte death in chick embryonic limb rudiments. An equimolar concentration of PGE₂ was not toxic to the cells.Acknowledgments. We are grateful for the support of C. J. K. by the Medical Research Council and of D. L. G. by the Arthritis and Rheumatism Council for Research. Our thanks are due to Dame Honor Fell, F. R. S. for invaluable advice and guidance, to Dr J. Pike (Upjohn Co.) for supplies of prostaglandin A₁, and to Dr Sylvia Fitton-Jackson for the gift of culture medium.