Effects of chronic glucagon excess on hepatic metabolism.
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Biomedical subjects
Publications and source records attributed to R M Wilson.
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The effect of exogenously administered somatostatin (SRIF) on meal-stimulated secretions of the exocrine pancreas was studied in dogs with chronic pancreatic fistulas. Dogs were fed 600 gm. of raw meat, and pacreatic output of water, bicarbonate, and protein was measured. Bicarbonate and protein secretions rose markedly postfeeding in all control animals. Four hundred micrograms or 100 mug. of SRIF infused for one hour together with a meal completely prevented the postfeeding rise in pancreatic secretions. SRIF (100 mug./hr.) infused one hour after a meal suppressed pancreatic secretions to basal levels within 30 minutes. Pancreatic secretions rose promptly after discontinuation of SRIF in all dogs. These data indicate (1) SRIF completely prevents pancreatic bicarbonate and enzyme responses when given together with a meal; (2) it completely suppresses already initiated pancreatic responses when given one hour after a meal; (3) 100 mug. of SRIF is as effective as 400 mug. in suppressing the postprandial rise in pancreatic secretions. We conclude that SRIF severely interferes with pancreatic secretions during normal alimentation and that this observation should be considered if SRIF is to be used as a therapeutic agent.
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Six anxious schizophrenic patients who were maintained with phenothiazines participated in a double-blind intensive design study of chlordiazepoxide and placebo for 12 weeks or longer. There were substantial differences between patients in their responses to chlordiazepoxide: two patients experienced significant and conspicuous relief of distress and reduction of typical schizophrenic symptoms. In another patient the differences, although statistically significant, were clinically less striking. In the three remaining patients no differences were observed between responses to the two treatments except that one patient was more depressed with chlordiazepoxide than with placebo. The findings suggest that there are at least two kinds of anxiety in schizophrenia. A few anxious schizophrenic patients apparently benefit more from a combination of a phenothiazine with chlordiazepoxide than from a phenothiazine alone.
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We introduce a new member of a family of photochemically active oligonucleotide conjugates. A Phenanthrodihydrodioxin (PDHD)-based agent was synthesized and covalently linked to a 5'-end of the 9-mer oligonucleotide via a hexamethylene linker. The conjugate hybridized to a complementary 30-nucleotide-long target and efficiently cleaved it in a sequence specific manner. Up to 67% of target was specifically damaged (51% cross-links and 16% direct cleavage). While the photosensitizer alone nonspecifically damaged only Gs in a single-stranded target, its conjugate cross-linked to and damaged also A, T, and C sites in a target in agreement with duplex and triplex formation.
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The mechanism whereby hyperglycaemia inhibits neutrophil function is unclear. We have examined neutrophil killing of Candida albicans in the presence of increased concentrations of glucose and galactose. Killing was abolished in 50 mmol/l glucose and 10 and 50 mmol/l galactose. The oxidative phase of killing was examined using lucigenin-enhanced chemiluminescence. An increase in glucose concentration from 5 to 50 mmol/l produced a fall in chemiluminescence output from 128.5 +/- 16.8 (mean +/- SE) to 82.2 +/- 9.8 mV min (a reduction of 36%). These data suggest the existence of aldose reductase activity in neutrophils and using gas chromatography we have demonstrated the presence of sorbitol in extracts of diabetic neutrophils. As oxidative killing and sorbitol production are both NADPH-dependent the inhibition of killing is likely to be due to competition for this electron donor. This abnormality of neutrophil function may aggravate various infections in the patient with diabetes.