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.     

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.     

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.     

Captopril (SQ 14,225): In vitro and in vivo influence on the proliferative response of rat lymphocytes

Summary Captopril in vitro (50–500 g/ml) increased³H-TdR incorporation in unstimulated and mitogen-stimulated cultures of rat lymphocytes. Unseparated spleen and lymph node cells of rats orally treated with captopril (50 mg/kg/day×4) showed decreased basal and mitogen stimulated³H-TdR incorporation. The removal of macrophages abrogated this inhibitory effect. Leucine aminopeptidase activity of macrophages was reduced — in vivo and in vitro — by captopril.Acknowledgments. The authors thank the Squibb Institute for Medical Research for the gift of Captopril. The excellent technical assistance of Ms B. Hasselriis, Ms B. Rumler and Ms E. Greve Petersen is gratefully acknowledged.     

Identification of an acyclic diterpene alcohol in the defense secretion of soldiers ofReticulitermes lucifugus

Summary The defense secretion of soldiers ofReticulitermes lucifugus has been shown to contain, predominantly, (R)-(–)-(E,E)-geranyllinalool together with germacrene A and -farnesene.This report covers part of a collaborative study with J.-L. Clément, Lab. d'Evolution, Université P. et M. Curie, Paris, to whom we are grateful for supplies of material and discussions. We also thank Dr O.T. Jones for collections ofReticulitermes lucifugus.     

Genetic polymorphisms and intrauterine development. Evidence of decreased heterozygosity in light-for-dates human newborn babies

Summary In 2 independent samples of low-birth-weight infants the proportion of females and homozygotes for a series of polymorphic systems was higher in light-for-dates than in preterm babies. The observation seems to give support to the hypothesis that homozygosity for normal polymorphisms may decrease in general intrauterine growth rate. Since it is known that survival rate is strongly related to birth weight, a correlation between growth retardation and homozygosity may have a major role in the maintenance of such polimorphisms.We thank Prof. L. Ginzburg for helpful comments.     

Production and detection of antibody against estradiol receptor in the calf uterus. Interaction with the estrogen receptor from the hen oviduct]

The antibodies against estrogen receptor were obtained after injecting Rabbits with a cytoplasmic receptor fraction isolated from Calf uterus. The estrogen receptor was partially proteolysed by the action of trypsin and subsequently purified by affinity chromatography (purification 4,000 to 10,000 fold, to a purity of 5-20%). The affinity of the antibody for the proteolysed receptor is KD approximately 1 nM and serum titres have reached values of approximately 50 nM. The values remained constant after the third injection. Preliminary results indicate that the antibody has approximately the same affinity for "native" cytoplasmic estrogen receptor from Calf uterus, as well as for the "trypsinized" forms of estrogen receptor isolated from Calf uterine cytosol and Hen oviduct nuclei.     

Comparative study, in the Allium test, of the cytotoxicity of tubulosine and of 6 synthetized pseudo-tubulosines]

Comparing cytotoxicity of tubulosine and of six newly synthesized pseudo-tubulosines in the Allium test, we have characterized all the current features of protein inhibition. Nevertheless cytotoxicity of the six pseudotubulosines is much weaker. Furthermore, "floating poles anaphasis", a disturbance characteristic of the action of tubulosine, has been found with a lesser intensity with the other compounds.     

The detection of superoxide anion from the reaction of oxyhemoglobin and phenylhydrazine using EPR spectroscopy

Summary The low temperature EPR spectrum of a quickly reacted mixture of oxyhemoglobin and phenylhydrazine was studied. With the use of a computer, the spectral contribution of methemoglobin in the region of g=2 was subtracted. The remaining spectrum was that of an axial free radical (g=2.00, g=2.06) having the magnetic parameters of superoxide anion. In the presence of superoxide dismutase, this axial radical was not seen, confirming that superoxide anion is indeed generated by the reaction.The portion of this investigation carried out at the Albert Einstein College of Medicine was supported in part by US Public Health Service Research Grant HL-93399 from the Heart and Lung Institute and by National Institute Contract Nol-CP-55606 to J.P. This is communication No. 378 from the Joan and Lester Avnet Institute of Molecular Biology.Predoctoral fellow in the Medical Scientist Training Program (United States Public Health Service Grant 5-TO-5-GM 01669-12) at the New York University School of Medicine.Recipient of a grant-in-aid from the New York Heart Association.     

Light transmission. I. An acoustic method able to monitor transmitted light

Summary A method able to monitor transmitted light acoustically is described. It makes use of an amplifier of light variations, provided with a photocell and a sound device, a photometer, an optic probe and a special support.Acknowledgments. The author would like to thank Dr Leonard Salzarulo, chairman of the Physics Department of the New Jersey Institute of Technology, for the critical reading of the paper. The author acknowledges the invaluable assistance of Prof. Araldo Ramundo of the Centro Regionale Professionale in Cosenza, Italy, for designing and assembling the electronic amplifier. Appreciation is also extended to Prof. Giuseppe Battendieri of the Liceo Scientifico Enrico Fermi in Cosenza, Italy, for the schematic reproduction of the apparatus.