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

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↗

PubMedDate not supplied

Suppression of circulating interleukin-6 concentrations is associated with decreased endothelial activation in rheumatoid arthritis.

BACKGROUND: Circulating interleukin (IL)-6 concentrations are associated with endothelial activation in rheumatoid arthritis (RA). OBJECTIVE: To assess endothelial activation before and after suppression of cytokine production in RA. METHODS: Twenty-one patients (mean (SD) age 59 (9) years; disease duration 6 (4) years) were treated with intraarticular methylprednisolone acetate (417 (152) mg) together with disease modifying agent (DMARD) initiation (n = 10) or intensification (n = 11) employing methotrexate (n = 11), leflunomide (n = 8), minocyclin (n = 6) and sulphasalazine (n = 1). Disease activity, circulating cytokines (IL-1, tumor necrosis factor alpha (TNF-alpha) and IL-6) and biomarkers of endothelial activation (circulating vascular adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and endothelial leukocyte adhesion molecule-1 (ELAM-1)) were evaluated before and 2 weeks after treatment. RESULTS: The intervention resulted in reductions in 8 disease activity markers (p < or = 0.002). Serum IL-6 concentrations decreased from 17 (2.9) to 4.9 (4.6) pg/ml (p = 0.0008). Serum IL-1 and TNF-alpha levels did not change (p > or = 0.4). Serum VCAM-1 concentrations decreased from 912 (402) to 752 (252) (p = 0.003), ICAM-1 from 398 (205) to 323 (179) (p = 0.04) and ELAM-1 from 68 (28) to 53 (25) (p = 0.02) pg/ml, respectively. Baseline rheumatoid factor titers were associated with reductions in VCAM-1 (r(s) = 0.481, p = 0.03). In multivariable regression models, decreases in circulating interleukin-6 concentrations were associated with reductions in VCAM-1 (p < 0.0001), ICAM-1 (p = 0.005) and ELAM-1 (p = 0.02) independent of changes in disease activity, weight and blood pressure. CONCLUSION: Our results suggest that suppression of circulating IL-6 concentrations attenuates atherogenesis in active RA.

Antirheumatic Agents↗

PubMedDate not supplied

Lack of hormonal effects of a single dose of nifedipine in healthy young men.

Explore the source record for details and available documents.

Adrenocorticotropic Hormone↗