Renal action of cholera toxin: I. Effects on urinary excretion of electrolytes and cyclic AMP.

The infusion of cholera toxin (CT), 4 mug/min, into one renal artery of normal and thyroparathyroidectomized (T-PTX) dogs produced ipsilateral increments in the excretion of Na, K, Ca, Mg and Cl. Phosphate excretion increased from both kidneys, but more from the infused kidney in intact dogs. Unilateral phosphaturia occurred in T-PTX dogs studied five or more days after T-PTX. The changes in electrolyte excretion appeared 40 to 80 min after initiation of CT infusion and the maximal effects were noted after 100 to 140 min. The effects of CT on electrolyte excretion could not be accounted for by changes in glomerular filtration rate or renal plasma flow. Urinary cyclic adenosine monophosphate (AMP) increased from both kidneys but slightly more from the infused kidney. Adenylate cyclase activity of cortex and outer medulla of the infused kidney was 109 to 142% higher than that of the control kidney. The results indicate that CT decreases the net transport of various electrolytes by the renal tubule. This effect is probably mediated by the activation of renal adenylate cyclase(s) sensitive to the enterotoxin.     

The effects of gamma-glutamylcysteine ethyl ester, a prodrug of glutathione, on ischemia-reperfusion-induced liver injury in rats.

This study was designed to clarify the effects of changes in liver tissue glutathione (GSH) concentration on postischemic liver injury together with the effects of gamma-glutamylcysteine ethyl ester (GCE), a prodrug of GSH, and GSH. Rats were pretreated with GSH (50 mg/kg, i.v.), or GCE (50 mg/kg, i.v.), or untreated. In each rat, liver was isolated, and liver mitochondria were prepared after 2 h of ischemia or 1 h of reperfusion following 2 h of ischemia. Mitochondrial function was measured polarographically. Liver adenine nucleotide concentrations were also determined using high-performance liquid chromatography. Liver tissue GSH, an oxidized form of glutathione (GSSG) concentrations, and activities of GSH peroxidase and GSSG reductase were determined enzymatically. Liver hypoxanthine and xanthine concentrations were determined by HPLC. Liver tissue concentration of lipid peroxide was measured. Leakages of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and adenine nucleotides into the hepatic vein after reperfusion were also measured. Administration of GCE improved the recovery of mitochondrial function and maintained tissue GSH concentration concomitantly. Increases in liver lipid peroxide concentration after reperfusion, and leakage of liver cell enzymes and adenine nucleotides were mitigated by administration of GCE. Administration of GSH itself failed to maintain tissue GSH concentration and had no protective effects. From these results, it is concluded that in the postischemic process, free radical formation might be enhanced, and the radical scavenging system deteriorated. To enhance the radical scavenging system is a possible maneuver to prevent radical-related cell damage associated with reperfusion, because pharmacological reduction of breakdown of ATP to hypoxanthine and xanthine seems to be difficult. GCE maintained liver GSH concentrations and mitigated postischemic liver injury, concomitantly. Clinical use of GCE might be recommended.     

Involvement of endogenous epinephrine in histamine-induced hyperinsulinemia and hypoglycemia in rats treated with islet-activating protein

Islet-activating protein (IAP), purified from the culture medium of Bordetella pertussis, was injected i.v. into rats at a dose of 5 μg/kg. While the injection of histamine caused hyperglycemia in normal rats, it caused marked hypoglycemia associated with hyperinsulinemia in IAP-treated rats. No hypoglycemia developed after histamine if the IAP-treated rats had been adrenodemedullated or injected with a β-adrenergic antagonist or with anti-insulin serum. Histamine-induced hyperinsulinemia in IAP-treated rats was also abolished by adrenodemedullation or a β-adrenergic antagonist. Ether anesthesia, which provokes the release of epinephrine from the adrenal medullae, mimicked the action of histamine in both normal and IAP-treated rats. Histamine did not influence insulin secretion when it was added directly to the incubation medium islets isolated from IAP-treated rats. It is concluded that epinephrine released from the adrenal medullae in response to histamine challenge enhances insulin secretion via the β-adrebergic receptors, thereby causing severe hypoglycemia in IAP-treated rats.     

Experimental study on the effect of slowly progressive chronic compression on the spinal cord

Summary Experimentally produced rapid and slowly progressive compression of the cervical spinal cord in cats demonstrated two very different patterns of damage, with disturbance of nerve cells and microvasculature.The spinal cord suffered less damage even from more severe pressure if this was applied slowly.The histological and microangiographic results provide confirmation of phenomena observed clinically.

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Résumé La réalisation expérimentale, chez le chat, de compression rapide ou lentement progressive de la moelle cervicale met en évidence deux types très différents de lésions, avec altération des cellules nerveuses et de la microvascularisation.La moelle est moins lésée, même si la compression est plus importante, lorsque celle-ci est appliquée progressivement.Les constatations histologiques et microangiographiques apportent la confirmation des phénomènes observés en clinique.