Prostaglandin analogue protects pancreatic B-cells against cyclosporin A toxicity

Summary Cyclosporin A toxicity on pancreatic B-cells and its prevention by rioprostil, a prostaglandin E₁ analogue, were studied in the model of the isolated perfused pancreas of rats treated with both compounds for 8 days. At toxic doses of cyclosporin (10 and 20 mg/kg b.wt), the B-cells showed severe hydropic degeneration of the endoplasmatic reticulum and slight degranulation of the B-cells. Accordingly, the insulin secretion was markedly impaired. Administration of rioprostil ameliorated the insulin secretion significantly, but not the ultrastructural changes. At therapeutic levels of cyclosporin (5 mg/kg b.wt), the hydropic degeneration and the drop in insulin secretion were completely prevented by rioprostil. This observation might have therapeutic implications in the treatment of patients, in particular those undergoing pancreatic transplantation.     

Erthrocytes within pancreatic B-cells of corticosteroid-treated mice

Summary An ultrastructural study of the endocrine pancreas of female ICR mice that received 21 daily injections of the synthetic glucocorticoid, Triamcinolone diacetate (8 mg/kg b. wt) revealed some examples of microhaemorrhage within islets of Langerhans, extravasation of erythrocytes, and the presence of erythrocytes within B-cells, where they undergo degradation to form myelin-like configurations.     

Erythrocytes within pancreatic B-cells of corticosteroid-treated mice.

An ultrastructural study of the endocrine pancreas of female ICR mice that received 21 daily injections of the synthetic glucocorticoid, Triamcinolone diacetate (8 mg/kg b.wt) revealed some examples of microhaemorrhage within islets of Langerhans, extravasation of erythrocytes, and the presence of erythrocytes within B-cells, where they undergo degradation to form myelin-like configurations.     

Significance of ionic fluxes and changes in membrane potential for stimulus-secretion coupling in pancreatic B-cells

Conclusions This brief review has tried to shed some light on the mechanisms and significance of the changes in membrane potential and in ionic fluxes occurring in B-cells upon glucose stimulation. There is now strong evidence that, under physiological conditions at least, these electrical events-and the underlying modifications of ionic permeabilities and fluxes — play a causal role in the stimulation of insulin release. It also seems clear that certain accompanying ionic fluxes have no direct stimulatory role, but may be important in maintaining cellular homeostasis. Recent experimental evidence has also shown that the electrical activity in B-cells is not an all-or-none stereotypic response. Not only can its intensity be adjusted to the magnitude of the stimulus, but its characteristics can also be modulated by potentiators Our knowledge of the stimulus-secretion coupling has markedly progressed over the past few years, but elucidation of several important steps remains a challenging goal. There is no doubt that parallel measurements of insulin release, of ionic fluxes and of membrane potential in B-cells will still contribute to that understanding.     

Vasotocin protects rats against convulsions induced by pentylenetetrazol

Summary The AVP analog, vasotocin, administered s. c. effectively antagonized pentylenetetrazol-induced convulsions, supporting the contention that AVP may be a mediator in convulsive disorders.This work was supported by the Medical Research Council of Canada.     

The ether lipid precursor hexadecylglycerol protects against Shiga toxins

Shiga toxin-producing Escherichia coli bacteria cause hemorrhagic colitis and hemolytic uremic syndrome in humans. Currently, only supportive treatment is available for diagnosed patients. We show here that 24-h pretreatment with an ether lipid precursor, the alkylglycerol sn-1-O-hexadecylglycerol (HG), protects HEp-2 cells against Shiga toxin and Shiga toxin 2. Also the endothelial cell lines HMEC-1 and HBMEC are protected against Shiga toxins after HG pretreatment. In contrast, the corresponding acylglycerol, dl-α-palmitin, has no effect on Shiga toxicity. Although HG treatment provides a strong protection (~30 times higher IC₅₀) against Shiga toxin, only a moderate reduction in toxin binding was observed, suggesting that retrograde transport of the toxin from the plasma membrane to the cytosol is perturbed. Furthermore, endocytosis of Shiga toxin and retrograde sorting from endosomes to the Golgi apparatus remain intact, but transport from the Golgi to the endoplasmic reticulum is inhibited by HG treatment. As previously described, HG reduces the total level of all quantified glycosphingolipids to 50–70 % of control, including the Shiga toxin receptor globotriaosylceramide (Gb3), in HEp-2 cells. In accordance with this, we find that interfering with Gb3 biosynthesis by siRNA-mediated knockdown of Gb3 synthase for 24 h causes a similar cytotoxic protection and only a moderate reduction in toxin binding (to 70 % of control cells). Alkylglycerols, including HG, have been administered to humans for investigation of therapeutic roles in disorders where ether lipid biosynthesis is deficient, as well as in cancer therapy. Further studies may reveal if HG can also have a therapeutic potential in Shiga toxin-producing E. coli infections.     

Role of the pituitary in cyproheptadine-induced pancreatic beta-cell toxicity

Summary Hypophysectomized rats given cyproheptadine (40 mg/kg) for 10 days exhibited a loss of pancreatic immunoreactive insulin and ultrastructural changes in the cytoplasm of beta-cells. Sham-operated animals given cyproheptadine showed identical changes in pancreatic beta-cells except that cytoplasmic involvement progressed to the formation of large vacuoles. The pituitary is not directly involved with the cyproheptadine-induced depletion of pancreatic insulin but plays a role in the formation of large cytoplasmic vacuoles.Acknowledgments. This work was supported by U. S. Public Health Service, grant GM 12675.     

Human specific immunoglobulin protects against infection with commonStaphylococcus in mice

Summary Mice infected with non-capsulatedStaphylococcus aureus strains highly resistant to methicillin survived after the administration of specific immunoglobulin extracted from pooled human sera by using homologous capsular type strains, but no protective effect was shown with a conventional immunoglobulin preparation and methicillin, even with high doses.     

Protection by antioxidants against ozone toxicity in mice

Zusammenfassung 16 Antioxidantien wurden auf ihre Schutzwirkung gegen Ozontoxizität in Mäusen geprüft. AHQ, Primaquin und EMQ waren hochwirksam, BHA, NDGA und Ascarbinsäure mässig wirksam, und die übrigen zeigten keinen nennenswerten Effekt.

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We thank Dr. D.Coffin for his advice and for the gift of the exposure chambers. This work was supported by N.I.H. Grants No. C-6516 and No. FR-05526 (to the Children's Cancer Research Foundation, Inc.) and has been submitted in partial fulfillment of requirements for an MS thesis at the North Eastern University, Boston, Massachusetts (by L.Pagnotto).     

Human specific immunoglobulin protects against infection with common Staphylococcus in mice

Mice infected with non-capsulated Staphylococcus aureus strains highly resistant to methicillin survived after the administration of specific immunoglobulin extracted from pooled human sera by using homologous capsular type strains, but no protective effect was shown with a conventional immunoglobulin preparation and methicillin, even with high doses.     

Protective effect of vitamins against trichothecene toxicity towardsSaccharomyces cerevisiae

Summary Several trichothecene mycotoxins were shown to inhibit the growth ofSaccharomyces cerevisiae. This effect was most pronounced with the macrocyclic trichothecenes, especially verrucarin A. Much less growth inhibition was observed with T-2 toxin. Verrucarol, diacetoxyscirpenol, acetyl T-2 toxin, HT-2 toxin, T-2 tetraol and neosolaniol were inactive at a concentration of 75 g of toxin per disc. Incubation ofS. cerevisiae with verrucarin A together with vitamins resulted in a decrease in toxicity. Pyridoxine-HCl, Ca-pantothenate, thiamine-HCl and -tocopheryl acetate were amongst the most potent of the vitamins tested which reversed growth inhibition, overcoming the inhibitory potential of the toxins.9 December 1986The authors thank Dr J. Behrend, Makor Company, Israel, for a generous gift of verrucarin A and roridin A.     

A spindle analogue inSaccharomyces cerevisiae hansen

Zusammenfassung Es gelang der photographische Nachweis einer spindelapparatähnlichen Struktur inSaccharomyces cerevisiae Hansen. Die regelmässige Chromosomenverteilung zwischen Mutterzelle und Knospe wird durch diese Struktur zusammen mit Zentrosomen ermöglicht.     

Contribution to knowledge of the biosynthesis of cyclosporin A

3H- and 13C-NMR spectroscopic investigations on the structure of labeled cyclosporin A were performed after feeding of appropriate precursors. The 6 N-methyl groups and the methyl group in position 4 of the epsilon, zeta-unsaturated amino acid No. 1 (Mebmt) are introduced as intact CH3-units from methionine. Four head-to-tail acetate units are involved in the biosynthesis of the 8-carbon chain of the olefinic amino acid.     

Protection against hyperbaric oxygen toxicity after feedingN,N-diphenyl-p-phenylene diamine

Résumé Des souris adultes traités au préalable par duN,N-diphenyl-p-phénylène diamine sont protégés contre la toxicité du oxygène hyperbarié. La protection est dépendente du dosage. Le méchanisme est inconnu.

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Supported by a grant from the U.S. Rubber Company.     

Protective effect of vitamins against trichothecene toxicity towards Saccharomyces cerevisiae

Several trichothecene mycotoxins were shown to inhibit the growth of Saccharomyces cerevisiae. This effect was most pronounced with the macrocyclic trichothecenes, especially verrucarin A. Much less growth inhibition was observed with T-2 toxin. Verrucarol, diacetoxyscirpenol, acetyl T-2 toxin, HT-2 toxin, T-2 tetraol and neosolaniol were inactive at a concentration of 75 micrograms of toxin per disc. Incubation of S. cerevisiae with verrucarin A together with vitamins resulted in a decrease in toxicity. Pyridoxine-HCl, Ca-pantothenate, thiamine-HCl and alpha-tocopheryl acetate were amongst the most potent of the vitamins tested which reversed growth inhibition, overcoming the inhibitory potential of the toxins.