Biomedical subjects
Publications and source records attributed to J Skrha.
A case of a patient with organic hyperinsulinism complicated by the development of hyperosmolar state is described. The hyperosmolar state was induced by vomiting and dehydration during an acute urinary tract infection. Impairment of glucose metabolism was confirmed by the finding of reduced tissue sensitivity to insulin during a euglycaemic clamp.
The therapeutic effect of long-term enalapril administration was studied in 20 patients with severe essential hypertension (EH), resistant to intensive therapy with a combination of 3 or 4 antihypertensive drugs. Addition of enalapril (Renitec MSD from 5 to 40 mg/day) to the previous therapy allowed to maintain blood pressure within limits not exceeding 150/95 mmHg during a 12-month study in more than 80% of previously resistant patients. Left ventricular hypertrophy regressed in all patients and dilatation of the left ventricle seen in 4 patients disappeared during enalapril treatment. Serum sodium creatinine did not change significantly. Serum potassium increased slightly but remained within the normal range. Proteinuria had a tendency to diminish and N-acetyl-beta-D-glucosaminidase activity in the urine dropped within normal limits. Based on their results, the authors conclude that enalapril is suitable for the long-term treatment of patients with severe EH, resistant to intensive antihypertensive therapy, with minimal side effects, good tolerance and a tendency for amelioration of cardiac and renal function.
UNLABELLED: The authors devised a computer model of albumin glycosylation based on irreversible glycosylation reaction of first-order kinetics. The dynamism of glycosylated albumin changes in relation to glycaemic profiles was compared with an earlier model of haemoglobin glycosylation. A non-linear regression analysis was employed to calculate the parameters of the model in three groups of patients. CONCLUSIONS: 1. Erythrocyte pool stratification accounts for the smaller clinical difference between glycosylated protein and haemoglobin than would correspond to their respective half-life values. 2. Glycosylated proteins are probably eliminated more rapidly than non-glycosylated proteins. 3. Higher levels of glycosylated proteins are occasionally at variance with model calculations, a fact which is probably due to other factors.
In 12 patients with the diagnosis of organic hyperinsulinism the authors examined the carbohydrate metabolism on a Biostator, using the method of stabilized glycaemia. They found a highly significantly reduced tissue sensitivity to insulin at the same time a reduced metabolic insulin turnover as compared with healthy subjects (p less than 0.001). Simultaneously they examined the acute action of diazoxide (Proglicem) treatment to which the patients responded in two ways. In one group a decline of the insulin level occurred and the tissue sensitivity to insulin rose, while patients in the second group responded by a rise of serum insulin but there was no response in the insulin sensitivity. In this second group diazoxide treatment obviously does not eliminate hypoglycaemic attacks. Examination on the Biostator thus makes it possible to decide whether conservative treatment is indicated in organic hyperinsulinism.
Fourteen diabetic women without signs of nephropathy were examined during pregnancy. Serum fructosamine concentration indicating short-term metabolic control of diabetes was normalized at the beginning of the second trimester and was within the normal limits till the delivery. A gradual increase of N-acetyl-beta-glucosaminidase activity in serum and urine has been found during pregnancy in diabetic and healthy women. No significant differences of N-acetyl-beta-glucosaminidase activities were observed between the above groups. A successive increase of albuminuria during pregnancy was present in diabetic and healthy women with about 10-times higher values at delivery. A significant positive correlation was observed between albuminuria and urinary NAG activity in both groups of pregnant women (r = 0.77). We did not find any deterioration in N-acetyl-beta-glucosaminidase activities and albuminuria in seven diabetic women one year after delivery.
The use of diazoxide in patients with insulinoma has been evaluated using the euglycaemic clamp technique. There was significantly reduced mean tissue sensitivity to insulin, expressed as the ratio of glucose disposal rate to serum insulin concentration (M/I), in untreated patients compared to the control group. The metabolic clearance rate of insulin (MCRI) was reduced in the patients before treatment in comparison with the controls. The administration of diazoxide (Proglicem1) for three days (3 mg.kg-1 per day) caused a fall in serum insulin concentrations, together with an increase in the metabolic clearance rate of insulin and increased tissue sensitivity to insulin.
Three laboratory indicators of impaired renal function (microalbuminuria (MA), N-acetyl-beta-glucosaminidase (NAG), beta-2-microglobulinaemia (beta-2-M)) were studied in sixty diabetics of type 1. 10 times higher MA levels were found in a subgroup of diabetics with identifiable diabetic retinopathy (DR). In a subgroup of diabetics with normal values of excreted albumin the mean MA value was significantly higher than in those who had already contracted DR. Pathological levels of NAG and beta-2-M were mostly seen in those patients who also had pathological MA results. In only four cases were increased NAG or beta-2-M values as the first and only pathological parameter indicative of possible renal involvement due to diabetic nephropathy.
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The free N-terminal 30-kDa domain of the fibronectin subunit chains had previously been shown to mediate binding of soluble fibrin to phagocytic cells. In order to demonstrate whether the fragment is available in plasma in a suitable concentration, an indirect immunoassay procedure for its quantitative evaluation was developed. The free form of the 30-kDa domain was separated from fibronectin and the bulk of the plasma proteins by two-step affinity chromatography on gelatin- and heparin-Sepharose. In the eluate of the heparin-Sepharose the 30-kDa fragment was determined by its capacity to inhibit the immune reaction between a specific antiserum and the 30-kDa fragment immobilized on microtiter wells. The procedure offered reproductibility comparable with other immunoassays (coefficient of variation 4.0 to 8.0%); the lowest amount of detectable 30-kDa fragment was 0.1 microgram/ml. In human plasma this method detected for the first time ca. 5 micrograms/ml 30-kDa fragment. This concentration is in the range required for binding of fibrin to cells.
The effect of acetyl-salicylic acid administration on insulin receptors on the erythrocytes and the changes of glucose homeostasis examined by hyperglycaemic clamps were evaluated in 8 Type 2 diabetics. Significantly increased number of insulin receptors and decreased insulin affinity constants were found in diabetics after the acetyl-salicylic acid treatment (p less than 0.02). Significantly decreased tissue sensitivity to insulin and metabolic clearance rate of insulin (p less than 0.02) were observed in Type 2 diabetics after the acetyl-salicylic acid treatment. We conclude that acetyl-salicylic acid may impair glucose homeostasis due to interference with insulin action in peripheral tissues.
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N-acetyl-beta-Glucosaminidase activity in serum and urine and microalbuminuria were measured in 70 type-I diabetics and compared with glycated serum protein as well as with the finding of diabetic retinopathy. A significantly increased N-acetyl-beta-glucosaminidase activity in serum correlated positively with glycated protein but not with the development of retinopathy. Urinary N-acetyl-beta-glucosaminidase activity and albuminuria were significantly increased in diabetics with (p less than 0.001) or without (p less than 0.01) retinopathy as compared to healthy controls. A significant positive correlation was observed between urinary N-acetyl-beta-glucosaminidase activity and albuminuria (r = 0.73, p less than 0.01) as well as between blood pressure and albuminuria (r = 0.51, p less than 0.05).