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H C Seftel

Publications and source records attributed to H C Seftel.

172 records · Page 10Linked to original sources
PubMedDate not supplied

The effect of alrestatin on alanine-stimulated release of insulin and glucagon in man.

Alrestatin, an aldose reductase inhibitor, was administered orally to 10 normal men. Its effect on basal plasma glucose, insulin and glucagon levels and on the response of glucose, insulin and glucagon to an oral alanine load was assessed and compared to that of a placebo. There was a significant suppression of both the mean basal insulin level and the mean insulin response to alanine in the group pretreated with alrestatin as compared to the placebo group (p less than 0.05 at 0 and 60 min). Glucagon levels rose slightly in both groups but tended to be lower in the alrestatin-treated subjects, and blood sugar levels fell slightly. There was a significant inverse correlation between the mean insulin and glucose levels in individual subjects. The possible significance and mechanisms of insulin suppression are discussed.

Adult↗
PubMedDate not supplied

Calcium antagonists (nifedipine and nimodipine) and pituitary responses to thyrotropin releasing hormone stimulation.

To assess the possible effect of the calcium antagonists nifedipine and nimodipine on the anterior pituitary responses to thyrotropin releasing hormone (TRH), seven normal males were studied in a double-blind placebo-controlled trial. The rise from basal levels of thyroid stimulating hormone (TSH) and prolactin was similar following the administration of a single therapeutic dose of either of these agents as compared to placebo. Nifedipine and nimodipine do not affect the anterior pituitary release of TSH and prolactin in response to TRH.

Adult↗
PubMedDate not supplied

Changes in glucose disposal and cellular insulin binding in obese black Southern African patients with type 2 diabetes mellitus before and after sulphonylurea therapy.

Peripheral insulin action and cellular insulin binding were studied in 10 newly detected, obese, black, Southern African women with Type 2 diabetes mellitus before and after mid-term oral sulphonylurea therapy and in five obese, non-diabetic controls. Glucose disposal (assessed by the euglycaemic insulin clamp technique) was significantly reduced in diabetic patients compared to control subjects (4.4 +/- 0.5 vs 6.4 +/- 0.5 mg kg-1 min-1, p < 0.05), and increased after 1 and 3 months of sulphonylurea therapy to 6.8 +/- 0.6 mg kg-1 min-1 (p = 0.01) and 6.3 +/- 0.7 mg kg-1 min-1 (p = 0.04), respectively. The major change in the binding kinetics of insulin to peripheral monocytes was an increase in the mean receptor concentration in the diabetic patients which was significant after 3 months of therapy (0.2 +/- 0.08 to 0.6 +/- 0.01 nM, p = 0.05). The basal plasma C-peptide concentration was significantly lower in the diabetic patients than in the controls and remained so following sulphonylurea therapy, despite significant reductions in fasting glucose and HbA1 concentrations. We conclude that newly diagnosed, obese, black Southern Africans with Type 2 diabetes showed diminished peripheral glucose disposal which increased following sulphonylurea therapy. This was accompanied by an increase in insulin receptor concentration but not with changes in basal insulin secretion.

Adult↗
PubMedDate not supplied

Low density lipoprotein receptor mutations in South African homozygous familial hypercholesterolemic patients.

The binding and catabolism of low density lipoprotein (LDL) were studied in cultured skin fibroblasts and/or Epstein-Barr virus-transformed lymphoblastoid cells from 20 familial hypercholesterolemic (FH) homozygotes of 14 Afrikaner kindreds. Cells from available heterozygotes were also analyzed. Good resolution between the normal, heterozygote, and homozygote groups was obtained on the basis of these assays using either cell type. Results obtained with fibroblasts allowed the classification of 13 of these kindreds as being typically receptor-defective, and one kindred with two homozygotes as being receptor-negative. Fibroblasts from homozygotes of the receptor-defective class expressed LDL receptor activities which varied between 3% and 25% of normal. Where two homozygotes from the same family were available for assays (six families), both yielded similar activities. In contrast to fibroblasts, all the lymphoblastoid cells derived from FH homozygotes yielded LDL receptor activities equal to or less than 10% of normal; in a number of cases no significant 125I-LDL binding was detectable. The use of lymphoblastoid cells provides a convenient means for screening for FH at the cellular level. Our results indicate a predominance of a receptor-defective type of abnormality, which is consistent with a founder gene effect in the Afrikaner population.

Adolescent↗
PubMedDate not supplied

Abnormalities of high density lipoproteins in homozygous familial hypercholesterolemia.

The possibility that low high density lipoprotein (HDL) levels may add to the risk of occlusive atherosclerosis in familial hypercholesterolemia (FH) is supported by the frequency and severity of this finding in these patients, particularly homozygotes. To investigate this abnormality in greater detail, we measured HDL lipid and apoprotein values in nine homozygotes with FH. Compared to their unaffected relatives, they had markedly reduced HDL cholesterol and apo A-I and A-II levels. The values found in heterozygote relatives were between those of homozygotes and those of controls. Density gradient ultracentrifugation of serum or isolated HDL from homozygotes demonstrated little or no HDL2; there was also a shift of homozygotes' HDL to an above normal peak density (d = 1.15 g/ml). Heterozygotes had milder abnormalities. The reduced HDL in FH seems to be related to elevated low density lipoprotein levels although the pathophysiology is unknown. These findings add weight to the concept that HDL abnormalities contribute to the relentless course of atherosclerosis in familial hypercholesterolemia.

Adolescent↗
PubMedDate not supplied

Plasma lipoprotein distribution of apolipoprotein E in familial hypercholesterolemia.

Although familial hypercholesterolemia (FH) has been well characterized in terms of the etiology of the major lipoprotein abnormality, that of low density lipoproteins (LDL), less information is available on changes in other lipoproteins which could influence the atherogenic process in this disorder. The present study has focused on such potential abnormalities by studying in detail the lipoprotein association of apolipoprotein E (apo E) in a large group of subjects homozygous for FH. Total plasma apo E levels in homozygous subjects were significantly elevated (p less than 0.001) relative to heterozygous subjects which were, in turn, significantly greater (p less than 0.001) than controls (137.6 micrograms/ml, 69.4 micrograms/ml, 46.5 micrograms/ml respectively). After separation of plasma lipoproteins by 4% agarose chromatography, an increased mass of apo E in lipoproteins of intermediate size was present; this may reflect the absence of LDL receptors that normally mediate their clearance. Homozygous FH subjects also demonstrated an increased mass of apo E-enriched high density lipoproteins (HDL) of large size, but a reduction in HDL cholesterol and apo A-I. The increase in the potentially atherogenic remnant lipoproteins and the decrease in HDL are associated with an increased risk for atherosclerosis, even in the absence of the LDL elevation, which is characteristic of FH. The increase in apo E-enriched HDL could reflect a compensatory mechanism that permits reverse cholesterol transport in the absence of LDL receptors.

Apolipoprotein C-III↗