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The effects of acetaldehyde (ACA) were examined in isolated electrically driven papillary muscle preparations from normal and streptozotocin-treated diabetic rats. Muscles from diabetic rats developed greater tension than those from normal rats. In muscles from both groups, ACA caused concentration-dependent negative inotropic effects that were independent of cholinergic or purinergic mechanisms and were not attributable to nitric oxide (NO) release. ACA was three to five times more potent with regard to its negative inotropic effect in diabetic than in normal rat muscles. A propranolol-sensitive, sympathetically mediated positive inotropic effect occurred at certain concentrations. Decreasing [Ca2+]o from 2.7 to 0.5 mM reduced basal developed force to a significantly greater extent in muscles from normal rats than in those from diabetic rats. In low [Ca2+]o, concentration-response curves to CaCl2 in diabetic muscles were displaced to the left of that in normal muscles, suggesting that diabetic muscles are more sensitive to the positive inotropic effect of added CaCl2 at low [Ca2+]o, whereas at higher [Ca2+]o (1 mM), normal muscles developed more force in response to added CaCl2. ACA 10 and 30 mM more readily inhibited CaCl2-induced positive inotropic effect in normal than in diabetic muscles. Force-frequency curves, (negative staircase response) were recorded in both normal and diabetic muscles. In diabetic muscles, the curve exhibited a positive component at the lowest frequencies applied and was displaced to the right of that in normal muscle. ACA concentration-dependently inhibited force development, and diabetic muscles were more susceptible to the negative inotropic effect of ACA, when the stimulation frequency was increased.(ABSTRACT TRUNCATED AT 250 WORDS)

The autoregulation of insulin secretion was studied using perifused and incubated pancreatic islets of normal (obOb) mice and of their obese-hyperglycemic (obob) littermates. Islets secreted more insulin when they were perifused than when they were incubated and insulin was allowed to accumulate in the medium. When rat insulin was added to the incubation medium in the concentration of 250 μU/ml, the secretory activity of the normal islets was suppressed almost completely. The concentration of exogenous insulin required to inhibit the islets of obese mice was higher and increased with the age of the animals, until it reached a value that was 20 to 30 times greater than that found in the circulating blood. Similar concentrations may well exist in the extracellular fluid of the pancreatic islets. It is possible that while insulin resistance of the peripheral tissues may be responsible for the hyperglycemia of the obob mice, the progressive loss of insulin sensitivity of their pancreatic islets and, consequently, of the normal autoregulation of insulin secretion, may play a role in the progressive hyperinsulinism and, hence, of the obesity characteristic of these animals.

A. Seaweed.—By means of a three-compartment cell with ceramic diaphragms, suspensions of dried ground Laminaria cloustoni stipe were electrodialysed to remove inorganic material. The total-ash content of the seaweed was reduced from 33.4 to 7.4% in 30 minutes, representing a removal of 78% of the ash. Tests were also made on dried, ground frond, and a much smaller removal was effected. The total-ash content was reduced from 28 to 22.8% in 30 minutes, representing a removal of about 18% of the ash. Duplicate tests were made to determine the amount of alkali and chlorine recovered and the energy required. The following figures were obtained (per Ib. of dry seaweed): alkali recovered, 0.053 Ib.; chlorine recovered (estimated), 0.056 Ib.; energy required, 3.03 kw. B. Fish albumen.—A three-compartment cell, with diaphragms of cellulosic material, was used for tests to reduce the ash content of fish albumen. It was found possible to reduce the ash content from 7.7 to 4.0% in 90 minutes, representing a removal of 52.3% of the inorganic material. The fact that not all the inorganic material is removed in either A or B is tentatively attributed to the presence of a certain proportion of it in an insoluble form such as calcium alginate in seaweed and calcium citrate in fish albumen. Electrodialysis of calcium alginate and calcium citrate gave results which supported this view.

Variables affecting the electrodeposition of basic magnesium carbonate and calcium carbonate from suspension in organic liquids have been investigated. Temperature has little effect. Deposition increases linearly, in most cases, with voltage, time, concentration and electrode surface. An unusual effect has been noted with high concentrations of materials containing a hydroxyl group, the amount of deposit increasing very rapidly with increasing concentration. With different organic liquids as suspending media, the amount of deposit increases with increasing dielectric constant in the series ethyl acetate, n-amyl alcohol, n-butyl alcohol, n-propyl alcohol, ethanol and methanol. With acetone and nitrobenzene little or no deposition is obtained, whereas cyclohexanone gives a result in agreement with the first series where magnesium carbonate is deposited, but gives no appreciable deposit with calcium carbonate. In certain cases a break occurs in the relationships when the deposit is heavy, possibly because the weight of the deposit causes a partial breaking-off. The mechanical strength of the deposit appears to depend upon the conditions of deposition. It has also been shown that the presence of small amounts of water or of acid has no apparent effect, but larger amounts cause, in the first case, an increasingly wet deposit and in the second, complete inhibition. The purity of the suspending medium can affect the action greatly. Heavy currents obtained during tests on calcium carbonate suspended in methanol are thought to be due to a reaction between these substances.

Tolbutamide and glibenclamide (glyburide) were administered to normal hamsters, mice or rats in daily doses proportional to their body weight and equivalent to those used in human therapy. The animals were sacrificed after 6 to 8 weeks of treatment. Pieces of pancreas or isolated pancreatic islets were incubated or perifused in a medium containing glucose or tolbutamide, with or without Ieucine-114C or glucose-U-14C. The results indicate that the B cells of sulfonylurea treated animals synthesized and released less insulin and oxidized less glucose than those of insulin or saline treated controls. Accordingly, at least in the glibenclamide treated animals, the tolerance for glucose and the insulinogenic response to a glucose load in vivo were suppressed. Although insular function tended to return, to normal after treatment was discontinued, the results reported in this paper do not support the generally accepted view that the lasting therapeutic effectiveness of the sulfonylureas is due to a beta-cytotrophic action.