Prostaglandin-like substances inPropionibacterium acnes. V. Activity profiles using cascade superfusion bioassay and platelet aggregation

Summary The activity spectrum of prostaglandin-like substances (PLS) fromP. acnes was investigated with cascade superfusion technique and by platelet aggregation assay. The biological activity of PLS resembles that of PGI₂: both relax bovine coronary artery, rabbit mesentric and coeliac arteries; both contract the rat stomach strip as well as both typically inhibit spontaneous movements of isolated guinea pig ileum. Also, similarly to PGI₂, PLS inhibits platelet aggregation regardless the inducer used. However, PLS possesses a specific antiaggregatory pattern on platelet, which indicates that these compounds are not indentical with primary prostaglandins or PGI₂.     

The influence of prostacyclin (PGI2) on contractile properties of isolated right ventricle of rat heart

The mechanism of the positive inotropic effect of prostacyclin (PGI₂) (2.6×10^?6 mol/l) on the isolated right ventricle of rat heart was studied. Our results show that the positive inotropic effect of prostacyclin is produced indirectly through beta adrenoceptors and slow Ca²⁺ channels, because blockade of slow Ca²⁺ channels with verapamil (10^?6 mol/l) and beta adrenoceptors with propranolol (10^?6 mol/l) abolishes this effect. Alpha adrenoceptors do not mediate the action of PGI₂.     

An adrenergic participation subserving a positive inotropism and chronotropism of prostacyclin on isolated rat atria

Summary The effects of prostacyclin (PGI₂) on the contractile frequency and on the isometric developed tension of spontaneously beating or paced isolated rat atria were explored. PGI₂ enhanced frequency and contractile tension, both effects being blocked by the presence of propranolol, or following a pretreatment with 6-OHDopamine.This work has been supported by Grant 6638 from the Consejo Nacional de Investigaciones Científicas y Técnicas de la República Argentina.     

Interaction between aldosterone and renomedullary prostaglandins. Competitive action between aspirin and spironolactone

Summary Aldosterone injected i.m. decreased the release of renomedullary PGEs and the index (urinary Na/K ratio) in conscious normotensive intact and adrenalectomized rats. Coadministration of spironolactone increased the release of PGEs as well as the index (urinary Na/K ratio). The effect of spironolactone was partly inhibited by aspirin injected in a ratio 51 (aspirin: spironolactone), an effect which could be reversed by the infusion of a synthetic prostaglandin (PGA₂) in a subhypotensive dose.Acknowledgements. The authors gratefully acknowledge Dr J. Pike, Upjohn Company, Kalamazoo, Michigan, USA, who kindly provided prostaglandins used for this study. This work was supported by a grant from INSERM (ATP 32 76 64) to Dr N. Papanicolaou.     

Is the variation in the susceptibility of various species to atherosclerosis due to inborn differences in prostacyclin (PGI2) formation?

Summary Species exhibiting a higher susceptibility to the development of atherosclerosis have a reduced prostacyclin (PGI₂)-generation in the arterial wall, which differs in various parts of the vascular system. As the difference in PGI₂-formation in various diseases is a generalized vascular effect, the changes can be detected in all vessels. This is a very important point for diagnostic purposes in humans.This study was supported by a grant of the «Fonds 600 Jahre Wiener Universität der Kammer der gewerblichen Wirtschaft für Wien».     

Mechanisms of coronary vasoconstriction induced by Na arachidonate in experimentally diabetic dogs

Summary Na arachidonate (NaA) enhanced the resting basal tone of isolated coronary arteries from diabetic dogs and depressed it in coronary arteries from normal controls. Inhibitors of thromboxane A₂ biosynthesis and of lipoxygenases abolished the vasoconstrictor effect of NaA on diabetic arteries, whereas inhibitors of cyclooxygenase activity and PGI₂ biosynthesis blocked the vasodilating action of NaA on normal arteries.This work has been supported by grant 6638 from CONICET (Argentina).     

Fehlermöglichkeiten bei der Bestimmung von Metabolitgehalten in Hefezellen

Summary The exact assay of metabolites like NAD, ATP and other glycolytic substances in intact yeast cells greatly depends on the method of cell extraction. Reproducible and high levels can be obtained after prolonged incubation at high temperatures or by freezing and thawing of the denatureted cellular material in perchloric acid, thus eliminating possible errors due to different recoveries in the cell-free extracts.     

Pharmakologische Charakteriserung von synthetischem Hypertensin

Summary Synthetic hypertensin, RH II, a Val₅octapeptide shows the same pattern of activity as natural hypertensin (angiotonin). In the normal rat, and in the rat pretreated with ganglionic blocking substances, the hypertensive activity corresponds to that of nor-adrenaline while it is enhanced in the nephrectomised animal. In the intact animal, hydralazine diminishes the hypertensive effect, while Regitin, Chlorpromazine and Reserpine are without effect. On the perfused vessels of the rabbit's hind limb, RH II produces a vasoconstriction which is diminished by Chlorpromazine and hydralazine, but not by Regitin. RH II is not destroyed by heating, but by freshly prepared kidney extract.     

Cationic and secretory effects of BPDZ 44 and diazoxide in rat pancreatic islets

The present study aimed at comparing the effects of low concentrations of BPDZ 44, a new pyridothiadiazine derivative, and diazoxide on⁸⁶Rb outflow,⁴⁵Ca outflow,⁴⁵Ca uptake and insulin release from rat pancreatic islets. Both drugs caused similar modifications, but the effects of BPDZ 44 on the cationic and secretory events were much more marked than those of diazoxide. It is suggested that BPDZ 44 could be valuable tool for further studies of the K_ATP channels.     

Increase in the total reducing substances in the hemolymph of the freshwater crab,Barytelphusa guerini,produced by a pesticide (DDT) and an indolealkylamine (serotonin)

Summary DDT and serotonin produced significant increases in the total reducing substances in the hemolymph of intact crabs,Barytelphusa guerini, apparently by triggering release of the hyperglycemic hormone.     

Evidence for suppression of Na-dependent Ca2+ efflux from rat brain synaptosomes by ovarian steroids in vivo

Summary The possibility that intracellular Ca²⁺, which mediates neurotransmitter release, regulation of membrane permeability, microtubule polymerization and axonal transport, is influenced by gonadal steroids via a Na–Ca exchange mechanism was examined. The resting Ca²⁺ uptake into synaptosomes was measured using crude synaptosomal pellets (P₂ fraction), isolated from the brain stem, mesencephalic reticular formation (MRF), nucleus caudatus (NC) and the hippocampus of intact, long-term ovariectomized (OVX) and OVX plus progesterone (P) or estradiol-17 benzoate (EB) treated adult female rats. Irrespective of the brain structure investigated, the uptake was 1) markedly increased in synaptosomes from OVX animals in comparison to intact controls, and 2) reduced to near control values in synaptosomes from OVX rats treated s.c. with a single dose of 2 mg P or 5 g EB. Since Ca²⁺ influx into synaptosomes was shown earlier to depend on external sodium concentration, which was the same in all experiments described in this work, the results obtained indicate that ovarian steroids modulate basal synaptic activity in the rat brain by suppressing Na-dependent Ca²⁺ efflux from the nerve cell.     

Biochemical and environmental perspectives on nitrogen metabolism in fishes

Catabolism of nitrogen-containing substances makes a major contribution to the oxidative metabolism in teleostean fishes. In this review, we focus on aspects of the formation, transport, detoxification and excretion of the two most important nitrogenous products of fishes: ammonia (NH₃ plus NH ₄ ⁺ ) and urea. While NH ₄ ⁺ makes up the bulk of nitrogenous waste, it is in equilibrium with the highly toxic NH₃. Ammonia is generated in the liver and excreted through branchial, surface and renal routes. Innocuous urea is derived through hepatic uricolysis or argininolysis and voided through kidney, gill, skin or faeces. Under conditions hampering the release of ammonia, such as exposure to exogenous ammonia, water limitation, or alkaline conditions, some teleosts detoxify ammonia through synthesis of urea by the ornithine-urea cycle in liver. Ammonia and possibly alanine are the prevalent vehicles of internal nitrogen transport. Glutamine is immaterial to interorgan nitrogen transport in fishes, but plays a transient role in the detoxification of ammonia by brain glutamine synthetase.     

Peroxovanadate inhibits Ca2+ release from mitochondria

Mitochondria contain a specific Ca²⁺ release pathway which operates when oxidized mitochondrial pyridine nucleotides are hydrolyzed. NAD⁺ hydrolysis and therefore Ca²⁺ release is possible when some vicinal thiols are cross-linked. Here we report that the thiol oxidant peroxovanadate inhibits the specific Ca²⁺ release pathway. In mitochondria, peroxovanadate causes a complete loss of reduced glutathione, which is not accompanied by formation of glutathione disulfide, and a partial loss of protein thiols. In model reactions, peroxovanadate oxidizes reduced glutathione predominantly to the sulfonate derivative, but does not react with glutathione disulfide. When the vicinal thiols relevant for Ca²⁺ release are cross-linked, Ca²⁺ release is no longer inhibited by peroxovanadate. Conversely, pretreatment of mitochondria with peroxovanadate makes them insensitive to compounds promoting the disulfide state. These results suggest that peroxovanadate inhibits the prooxidant-induced Ca²⁺ release from mitochondria by (i) depleting mitochondria of reduced glutathione and (ii) oxidizing the vicinal thiols relevant for Ca²⁺ release to a state higher than disulfide, presumably the sulfonate state. The findings provide further insight into the regulation of Ca²⁺ release from intact mitochondria, and may be relevant for a better understanding of the action of peroxovanadate in cells, where the compound can be insulin mimetic. Received 28 March 2002; received after revision 8 May 2002; accepted 15 May 2002     

Chronic hydrogen peroxide intake and peroxide metabolizing enzyme activities in some tissues of mice and rats

Summary Chronic daily intake of 0.5% H₂O₂ in drinking water decreased Se-dependent glutathione peroxidase (Se-GSHPx) activity in rat skeletal muscle, kidney and liver. Non-Se GSHPx activity decreased in kidney. Deprivation of drinking water decreased Se-GSHPx activity in kidney and non-Se GSHPx activity in kidney and liver. H₂O₂ intake decreased activity of catalase in rat skeletal muscle. H₂O₂ intake or water deprivation caused no changes in these enzyme activities in mice.     

Influence of dopamine infusion on plasma prolactin released by kidney capsule transplanted anterior pituitaries

Summary The infusion of dopamine into the renal artery resulted in decreased prolactin release from 3 anterior pituitary glands transplanted under the kidney capsule. Prolactin levels continually decreased over a 5 min period after DA infusion was terminated and thereafter approached preinfusion levels by the end of 10 min.Supported by NSF Research, grant No. 74-17332.The authors wish to express their appreciation to Mrs Cynthia Van De Walle for her outstanding technical assistance in the performance of the prolactin RIA and the statistical analyses. We also appreciate receiving as a gift from the National Institute for Arthritis, Metabolism and Digestive Diseases the rat prolactin used for iodination (RP-I₂) and standards (RP-1).     

Technik der Kanülierung des Confluens sinuum beim Kaninchen für Versuche mit partiellem extrakorporellem Kreislauf

Summary Since an adequate venous blood outflow from the internal jugular vein is not available in the rabbit, a method for venous blood outflow from the Confluens sinuum was developed. It appeared to be useful in experiments with partial extracorporal circulation and for partial oxygenation of the blood circulation during haemodialysis.     

Contrôle direct,continu, simultané et in situ du taux d'oxyhémoglobine en milieux artériel et veineux profonds chez le Mammifère

Summary An original instrument, the probe-photometer, permits us to evaluate instantaneously, continuously, in situ and simultaneously into arterial and venous vessels the relative amount of Hb-Hb O₂. The CO₂ reflex described previously can also be fully recorded in terms of hemoglobin.     

Untersuchungen an Ionenaustauschmodellen zum Verständnis der Physiologie biogener Amine. Austauschversuche an einem schwefelsäuregruppentragenden Harz zum Verständnis von sogenannten Histaminliberationsvorgängen

Summary Mixtures of histamine and other basic substances as hydrochlorides were added in equivalent amounts to an acid ion exchange system containing SO₄-groups in the H⁺-form (Dowex 50 W × 2). After completion of the equilibrium, the amounts of both the free histamine and the competing substance were determined by potentiometric titration.Values are presented for the relative amounts of each substance which are retained by the resin.The results obtained show that histamine and a given competing substance are selectively distributed on the resin. The method may be useful as a test for the possible histamine-liberating capacity of biologically important substances.     

Zinc ions block the intracellular calcium release induced by caffeine in guinea-pig taenia caeci

Zn²⁺ in low concentrations (0.005–0.1 mM) inhibited the transient contractions in response to caffeine (25 mM) in a dose-dependent manner in smooth muscle of intact guinea-pig taenia caeci. At Zn²⁺ concentrations higher than 0.1 mM, caffeine did not elicit any response. After saponin-treatment of the fibres, which leaves the Ca²⁺ storage sites intact, caffeine contraction was completely inhibited by Zn²⁺ at a relatively low concentration (0.03 mM). However, in Triton-X-100-treated fibres, in which the Ca²⁺ release sites are destroyed, the contraction could be induced in the presence of Zn²⁺ by an increase in Ca²⁺. In conclusion, Zn²⁺ can block the intracellular Ca²⁺ release from caffeine-sensitive release sites in taenia caeci.     

Induction of neovascularization in vivo by glycerol

Glycerol, injected into a site between the femoral vessels of the rat, induced neovascularization, both from the preexisting microcirculation and from the side of the femoral vein facing the artery-vein interstitium where the glycerol was administered. The use of glycerol together with a known angiogenic substance (PGE₂) did not modify the neocapillary density (NCD) obtained with glycerol alone. In contrast, the lower level of NCD achieved with an acylglycerol (triacetylglycerol) was increased when the latter was associated with PGE₂. Values reached were similar to, but never higher than, those for glycerol alone, or combined with PGE₂. The results suggest that glycerol and some substances containing glycerol, amongst which 1-butyrylglycerol has been previously considered¹, may stimulate angiogenesis by a direct or indirect mechanism of action.