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T S Kern

Publications and source records attributed to T S Kern.

62 records · Page 4Linked to original sources
PubMed1984

Experimental galactosemia produces diabetic-like retinopathy.

Six normal dogs were made galactosemic by feeding a 30% D-galactose diet, and were followed up to 5 yr. For comparison, 10 normal dogs and 10 alloxan-diabetic dogs were concurrently fed the diet less the galactose supplement. Retinopathy occurred in each of four dogs glactosemic 3 or more yr, and was absent at lesser durations of galactosemia, and from normal dogs not given the galactose supplement. The retinopathy was marked by saccular capillary aneurysms, hemorrhages, nonperfused or acellular vessels, tortuous hypertrophic capillaries, loss of capillary pericytes, and other lesions typical of diabetic patients and alloxan-diabetic dogs. In galactose-fed dogs, blood galactose varied between 0 (fasted) and 250 mg/dl (postprandial), and glycosylated hemoglobin levels became supranormal. In contrast to diabetic dogs, blood levels of glucose, free fatty acids, and branched-chain amino acids were not elevated in the galactosemic dogs, and their serum insulin seemed normal. The results suggest that the level of blood hexose is itself an important determinant of retinopathy.

Amino Acids, Branched-Chain↗
PubMed1984

Platelet aggregation in experimental diabetes and experimental galactosemia.

Platelet aggregation and related plasma factors have been studied in experimentally diabetic dogs, experimentally galactosemic dogs, and in normal dogs. Platelet aggregation, when induced in vitro by ADP (up to 22 microM) or collagen (up to 4 micrograms/ml), was not significantly different from normal in the diabetic or galactosemic dogs. Plasma (platelet-deficient) from the diabetic or galactosemic dogs did not enhance ADP-induced aggregation of normal canine platelets. Fibrinogen concentration in blood tended to be elevated in hyperglycemic diabetic dogs, and was significantly correlated with the levels of HbA1 and blood glucose, whereas galactosemic animals had normal fibrinogen concentrations. The quantity of 6-keto prostaglandin F1 alpha released from aortas of diabetic dogs was less than that released from aortas of normal dogs. Since alloxan-diabetic dogs and galactosemic dogs develop microaneurysms, occluded capillaries, and other retinal lesions characteristic of diabetic retinopathy in human patients, these studies suggest that retinopathy can develop in the absence of extraordinary in vitro platelet aggregation.

Adenosine Diphosphate↗
PubMed1983

Abnormal amino acid concentrations in plasma and urine of experimentally diabetic dogs.

Free amino acid concentrations have been determined in plasma and urine of nonketotic, severely diabetic dogs and age-matched normal controls. Plasma from fasted (as well as fed) diabetics contained supranormal concentrations of several amino acids, including the branched-chain amino acids. In contrast to other species, however, the concentration of only one plasma amino acid (tryptophan) was subnormal in fasted diabetic dogs. Urine collected at the same time showed that the excretion of most amino acids was not abnormal in diabetes. Urinary concentrations of some amino acids were not abnormal despite supranormal levels in plasma. Nevertheless, eight of the 21 amino acids studied reached concentrations significantly greater than normal in the urine of diabetic dogs. Six of the eight amino acids (arginine, histidine, phenylalanine, tyrosine, tryptophan, glutamic acid) showed elevated concentrations in urine even though their plasma concentrations were not elevated. The observed disturbance in the urine/plasma ratio of certain amino acids suggests a possible defect in the renal handling of amino acids in diabetes.

Amino Acids↗
PubMed1982

Immunohistochemical distribution of aldose reductase.

Aldose reductase (AR) has been purified from canine kidneys, and a monospecific antibody against the enzyme prepared. These antibodies were used in an immunohistochemical test to detect tissue sites of aldose reductase in the dog, a species known to develop diabetic lesions morphologically identical to those seen in diabetic patients. Using this method, the enzyme has been demonstrated in numerous cell types, including lens epithelium, aortic endothelium and smooth muscle, Schwann cells of peripheral nerves, and, in the kidney, interstitial cells and cells of Henle's loop and the collecting tubules. Many other cells and tissues, including capillaries throughout the body, lack immunoreactive aldose reductase. The distribution of the immunoreactive enzyme is compatible with a potential role of the enzyme in the aetiology of some complications of diabetes, namely cataract, neuropathy, macroangiopathy and renal papillary necrosis, but not the microvascular complications.

Aldehyde Reductase↗
PubMedDate not supplied

Elevated blood viscosity in alloxan diabetic dogs and experimentally galactosemic dogs.

Blood viscosity was investigated in alloxan-diabetic dogs and in dogs made experimentally hyperglycemic by a galactose-rich diet. The diabetics were prospectively assigned to levels of glycemic control ranging from poor to good. After up to 5 years of study, the blood viscosity of hyperglycemic diabetic animals was significantly greater than normal at both high (100 sec-1) and low (0.1 sec-1) shear rates. Blood viscosity at the low shear rate correlated closely with fibrinogen concentration, (r = 0.75; p less than 0.02) but not with HbA1 concentration (r = 0.14) in the diabetics. Galactosemic animals likewise had elevated blood viscosity at the low shear rate, but the correlation of viscosity with fibrinogen concentration in those animals was not statistically significant (r = 0.42). Plasma viscosity tended to be elevated in both diabetes and galactosemia, but not to a statistically significant degree.

Animals↗
PubMedDate not supplied

Aldose reductase and the development of renal disease in diabetic dogs.

Effects of 5 years administration of an aldose reductase inhibitor (Sorbinil) on renal structure and albumin excretion were evaluated in diabetic dogs. Glycemia, estimated by frequent measurements of HbA1, glycated plasma proteins and glucosuria, was kept comparable between the placebo- and Sorbinil-treated diabetic groups. Kidney structure was evaluated using morphometric techniques by light and electron microscopy, and excretion of immunoreactive albumin was measured yearly. Placebo-treated diabetic dogs developed nephromegaly, glomerular enlargement, increased mesangial volume, and basement membrane thickening during the 5 years of study, and by the fifth year, excreted greater than normal quantities of albumin. Sorbinil treatment prevented sorbitol accumulation in erythrocytes and tended to have a similar effect in renal cortex, but had no beneficial effect on renal structure or albuminuria. Experimental galactosemia, another model of polyol over-production, failed to produce nephromegaly, glomerular enlargement, or mesangial expansion in dogs even after 5 years of galactose-feeding. The results suggest that polyol over-production and/or accumulation per se are not sufficient to account for the nephromegaly, glomerular enlargement, or increased mesangial volume observed in diabetic dogs.

Albuminuria↗
PubMedDate not supplied

Capillary basement membrane in retina, kidney, and muscle of diabetic dogs and galactosemic dogs and its response to 5 years aldose reductase inhibition.

Capillary basement membrane thickening has been compared in retina, renal glomerulus, and leg muscle of dogs alloxan-diabetic 5 years and dogs experimentally galactosemic 5 years, and the effects of inhibition of aldose reductase have been examined. Basement membrane in each site became thickened as a result of either galactosemia or diabetes, but showed appreciable variation among the sites. The thickening of basement membrane in retina and muscle of galactosemic animals was similar in quantity and appearance to that seen in the diabetics, notwithstanding large differences between the two animal models with respect to tissue polyol concentrations and nonenzymatic glycation of hemoglobin and plasma protein. Aldose reductase inhibition was without influence on capillary basement membrane thickening in each tissue from dogs diabetic or galactosemic 5 years, despite substantial polyol path inhibition.

Aldehyde Reductase↗