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Biomedical subjects

A Melander

Publications and source records attributed to A Melander.

At least 181 records · Page 10Linked to original sources
PubMed1980

Comparative single-dose kinetics and effects of four sulfonylureas in healthy volunteers.

The single-dose kinetics and effects of tolbutamide (500 mg), chlorpropamide (250 mg), glibenclamide (5 mg) and glipizide (5 mg) were compared in 7 healthy male volunteers by measurements of serum concentrations of the drugs and of plasma insulin and blood glucose. The drugs were administered both on an empty stomach and together with a standardized breakfast. The concentrations of tolbutamide and chlorpropamide were measured by gas chromatography, those of glipizide with high-pressure liquid chromatography, those of glibenclamide and insulin by radioimmunoassay and those of glucose by the hexokinase method. Glipizide and glibenclamide were more potent inducers of insulin release and blood glucose reduction than tolbutamide and chlorpropamide. As the concentrations of the former two drugs were in the range of nmol/l and those of the latter two in the mumol/l range, the findings support the notion that the intrinsic activity of the two second-generation sulfonylureas is at least 1 000 times greater than that of the two first-generation drugs. Glipizide seemed to be a more potent and more rapid insulin releaser than glibenclamide, but this may be secondary to biopharmaceutic differences between the two preparations. The bioavailability of glipizide was apparently greater than that of glibenclamide. Both glibenclamide (t 1/2 = 1.8 h) and glipizide (t 1/2 = 4.3 h) showed much shorter elimination half-lives than tolbutamide (7 h) and chlorpropamide (34 h). It seems probable, however, that these half-lives are not fully informative as to the duration of action of the drugs.

Adult↗
PubMed1980

Comparison of energy and nutrient intakes in women with high and low blood pressure levels.

The present study found no link between the intake of energy and various nutrients, on the one hand, and high or low blood pressure (BP) in women, on the other. Sixty women not on treatment for hypertension were selected from a defined population and examined, applying the duplicate portion technique, with respect to the relationships between BP and the intake of energy and nutrients. They were selected from above the 95th percentile for BP (group A) and from below the 30th (group B). The two groups were age-matched. The food sampling comprised six days, divided into three periods of two consecutive days within a period of four weeks. Twenty-four hour urine specimens were collected in each period and on two other occasions. The mean values for intake of energy, fat, protein, carbohydrates, minerals and electrolytes did not differ between the two groups despite the large differences in BP and obesity. The mean values for urinary excretion of minerals, electrolytes and nitrogen (calculated as crude protein) did not differ between groups. The present findings for the effect of salt on BP do not justify restriction of the salt intake as a means for decreasing BP in the population.

Adult↗
PubMed1980

Effects of antithyroid drugs on lymphocyte function in vitro.

The in vitro influence of 6-propylthiouracil (PTU) and methimazole (MMi) on mitogenic activation of human peripheral blood lymphocytes was studied in order to assess whether antithyroid drugs may have an immunomodulatory capacity. Lymphocytes were cultured for 72 h in the presence of phytohaemagglutinin (PHA; 1.25 microgram/ml), concanavalin A (Con A; 5.0 microgram/ml), or pokeweed mitogen (PWM; 2.5 microgram/ml). Antithyroid drugs were added to yield final concentrations of 1-1000 mu mol/liter. High pressure liquid chromatographic analyses verified that the expected drug concentrations in the incubation media were reached and maintained throughout the incubation period. The degree of lymphocyte activation was assessed by measurements of the cellular uptake of [3H]thymidine added after 48 h. PTU (at 1000 mu mol/liter) slightly suppressed PHA- and Con A-induced activation of lymphocytes but enhanced (at 5-500 mu mol/liter) PWM-induced activation. MMI (500-1000 mu mol/liter) enhanced not only PWM-induced activation but (at 1000 mu mol/liter) also enhanced PHA- and Con A-induced activation. Thus, PTU and MMI might interfere with mitogenic activation of lymphocytes. However, the effects were mainly recorded at drug concentrations exceeding those found in blood samples of patients treated with conventional doses.

Concanavalin A↗
PubMed1980

Presence and influence of cholinergic nerves in the human thyroid.

There is evidence that the sympathetic nervous system exerts a control on human thyroid function via an adrenergic innervation of follicle cells. The present study demonstrates that cholinergic nerve fibers also reach follicle cells in the normal human thyroid. In addition, cholinergic agents were found to enhance cGMP accumulation in human thyroid tissue. This effect was blocked by atropine, a muscarinic receptor antagonist, but not by d-tubocurarine, a nicotinic receptor antagonist. These results provide morphological and biochemical arguments supporting a role of the parasympathetic nervous system in the regulation of thyroid function in man.

Acetylcholine↗
PubMed1980

Ten-year follow-up of subjects with impaired glucose tolerance: prevention of diabetes by tolbutamide and diet regulation.

In a diabetes detection survey carried out between 1962 and 1965, 2477 (1.1%) of 228,883 subjects had Clinistix-positive glucosuria after a carbohydrate-rich luncheon meal. Of these 2477, 578 displayed impaired tolerance to oral glucose without having manifest diabetes. From this group, 267 men were divided into five groups and subjected to the following treatments and controls: (a) diet regulation and 0.5 g tolbutamide t.i.d. (N = 49), annual oral glucose tolerance test (OGTT); (b) diet regulation and one placebo tablet t.i.d. (N = 48), annual OGTT; (c) diet regulation only (N = 50), annual OGTT; (d) no treatment (N = 61), annual OGTT; and (e) no treatment, OGTT at follow-up (N = 59 at follow-up). In addition, a control group was included comprised of men with normal OGTT (N = 52). At follow-up, 29% of those without diet regulation and medication (group e: N = 59) had developed diabetes. Of those on diet regulation, but without active medication (group b plus group c, N = 98), 13% had diabetes. No individual maintaining tolbutamide and diet regulation (N = 23) had progressed to diabetes. In this group, 80% of those later examined (N = 11) had serum tolbutamide concentrations in the therapeutic range. No individual with initially normal OGTT developed diabetes or impaired OGTT. The findings suggest that normal oral glucose tolerance signifies little risk of progress to impaired glucose tolerance and manifest diabetes, whereas impaired glucose tolerance is associated with a high risk of progression to diabetes. In addition, it seems possible that treatment with diet regulation, in combination with tolbutamide, may prevent or postpone progression from impaired glucose tolerance to manifest diabetes.

Diabetes Mellitus↗
PubMed1980

Kinetics-effect relations of glipizide and other sulfonylureas.

The kinetics-effect relations of glipizide (Gz), glibenclamide (Gb), tolbutamide (Tb) and chlorpropamide (Cp) were studied in diabetics and healthy volunteers, by gas chromatographic (Tb, Cp), high-pressure liquid chromatographic (Gz), radioimmunologic (Gb, insulin) and enzymatic (glucose) analyses. For each of the four drugs, the steady state concentrations showed very large between-patient variations, not attributable to dosage or weight differences but to individual differences in drug kinetics and to insufficient compliance. Single-dose comparisons in healthy volunteers showed that Gz and Gb are much more potent than Tb and Cp, and suggested that Gz is the most rapid-acting one. Food did not affect the bioavailability of any of the four drugs, but delayed Gz absorption. Both Gz and Gb yielded better blood glucose reductions when given 30 minutes before, than together with, meals. Each drug could evoke glucose reduction without enhancing peripheral insulin levels; this probably reflects extrapancreatic sulfonylurea effects. In conclusion, it appears that a) the dosage of each sulfonylurea must be individualized, b) Gz and Gb are much more potent than Tb and Cp, c) Gz has the most favourable therapeutic profile as it seems to be the most rapid- and short-acting of the four sulfonylureas. d) Gz and Gb should be given before rather than together with, meals, in order to obtain optimal effects.

Blood Glucose↗
PubMed1980

Kinetic interaction of glipizide and indoprofen in healthy volunteers.

There is accumulating evidence that salicylate and glipizide may exert a clinically relevant interaction. Therefore, it was of interest to examine the possible interactions of glipizide and antirheumatics of non-salicylate character, e.g., phenyl propionic acid derivatives. The present report deals with the possible interaction between glipizide and indoprofen, a novel and potent antirheumatic agent. The subjects studied were 6 healthy volunteers, who took indoprofen 200 mg t.i.d. for 7 days and a single 5 mg dose of glipizide before and during indoprofen medication. Series of blood samples were obtained for measurements of indoprofen, glipizide, and glucose concentrations in blood. In addition, urine concentrations of indoprofen were determined. The concentrations of glipizide and indoprofen were measured by high-pressure liquid chromatography, and that of glucose ezymatically. The results indicate that chronic indoprofen administration may reduce glipizide concentrations in plasma, but this reduction need not lead to a major influence on the blood glucose response to glipizide.

Adult↗
PubMed1979

Influence of food on the absorption of phenytoin in man.

The influence of food intake on the absorption of phenytoin was examined in eight healthy volunteers, by study of single-dose kinetics following ingestion of phenytoin 300 mg either with a standardized breakfast or on an empty stomach. Blood samples were collected at regular intervals from 0 to 48 h, and serum concentrations of unmetabolized phenytoin were determined by gas chromatography. Serum concentrations of the major metabolite of phenytoin, 4-hydroxyphenytoin, were measured by mass fragmentography. Concurrent intake of food and phenytoin appeared to accelerate absorption of the drug from the formulation used, and the peak concentrations were significantly higher (mean increase 40%) in the postprandial than in the preprandial state. As reflected by the AUC (area under the curve), the amount of drug absorbed was increased during postprandial conditions, although the difference only reached borderline significance. It is suggested that phenytoin should always be taken in a defined relation to meals.

Adult↗
PubMed1979

Food-induced reduction in bioavailability of atenolol.

The influence of food intake on the bioavailability of the beta-adrenoceptor blocker atenolol was assessed by measurement of its single-dose kinetics in ten healthy volunteers, who took 100 mg both in the fasting state and together with a standardized breakfast. Food intake significantly shortened the time to reach peak concentration (2.7 h vs 1.5 h), but caused a significant reduction in AUC values, the mean decrease being 20%. The elimination half-life was unaffected. Atenolol, which is relatively hydrophilic, is incompletely absorbed in the fasting state, and escapes first-pass metabolism. The present findings indicate that food intake causes further impairment of its absorption, even though the absorption rate may initially be enhanced. This contrasts with previous observations on the more lipophilic beta-adrenoceptor blockers propranolol and metoprolol.

Adult↗
PubMed1979

In vivo absorption of phenytoin from rat small intestine and its inhibition by phlorizin.

In vivo absorption of phenytoin from the small intestine was studied by an in vivo closed segment technique. Phenytoin in concentrations of 1000, 2000, and 4000 mumol/l was administered in dissolved form. Polythylene glycol 4000 was used as a non-absorbable marker. The concentrations of phenytoin in the intestinal lumen, in the mucosa, and in cardiac blood were measured both by spectrophotometry and by gas chromatography. Phenytoin was absorbed very rapidly, and the proportion absorbed increased with increasing dose. Thus, during the first 10 min. about 85 per cent of the largest dose but only 25 per cent of the smallest dose had been absorbed. The phenytoin concentration in mucosa and serum increased in an analogous way; maximum values were observed within the first ten minutes. The concentrations in mucosa and serum were dose dependent during the first ten minutes. 0.01 mmol/l and 1 mmol/l phlorizin significantly reduced the transfer of phenytoin (4000 and 2000 mumol/l) from the gut lumen to the mucosa. No inhibition was observed when the initial phenytoin dose was 1000 mumol/l. The results suggest that an active transport mechanism, sensitive to phlorizin, is involved in the intestinal absorption of phenytoin in the rat.

Animals↗
PubMed1979

Presence and influence of cholinergic nerves in the mouse thyroid.

The presence and influence of cholinergic nerves in the mouse thyroid was studied by histochemistry and measurements of changes in blood radioiodine (BRI) levels. Numerous nerve fibers displaying specific acetyl choline esterase activity were found, not only as a dense network around vessesl but also as single fibers running around and between thyroid follicles. In stress-adapted normal mice, injection of carbamyl choline (CCh) reduced the BRI levels. In mice whose TSH secretion was suppressed by L-T4, neither CCh nor atropine had any measurable influence on the BRI levels when given alone. However, CCh pretreatment reduced and atropine pretreatment enhanced the TSH-induced BRI increase in such animals. It is concluded that the murine thyroid contains numerous cholinergic nerves that may influence not only thyroid blood flow but also thyroid hormone secretion directly. This direct influence appears to be an inhibitory one, mediated via muscarinic receptors in the follicle cells.

Animals↗
PubMed1979

Thyroid and adrenomedullary reactions during sleep deprivation.

The possible influence of a 48 h period of sleep deprivation on the serum concentrations of total and unbound 3,5,3',5'-thyroxine (T4) and 3,5,3'-triiodothyronine (T3), and of total 3,3',5'-triiodothyronine (reverse T3, rT3) was studied in 12 young male volunteers. In addition, plasma concentrations of TSH and the urinary excretion of noradrenaline and adrenaline were examined. Both total S-T4, S-T3 and S-rT3, and unbound S-T4 and S-T3 (unbound rT3 was not calculated) were significantly enhanced following sleep deprivation. P-TSH showed a numerical but statistically not significant increase, while the catecholamines remained unaltered. The results suggest that sleep deprivation provokes enhanced secretion of thyroid hormone(s), supposedly via increased secretion of TSH.

Adrenal Medulla↗
PubMed1979

Active and inactive thyroid hormone levels in elective and acute surgery.

The changes in the plasma or serum concentration of thyrotrophin (TSH), thyroxine (T4), 3,5,3'-triiodothyronine (T3), 3,3',5-triiodothyronine (reverse T3, rT3) and cortisol were examined in patients undergoing elective cholecystectomy (n = 10) or acute laparotomy due to peritonitis (n = 11). TSH and T4 showed no essential changes in either group. T3 was reduced already during initiation of anaesthesia and continued to fall during and after surgery in both groups. In the peritonitis group, T3 was reduced already before medical intervention. rT3 displayed changes opposite to those of T3. An increase in cortisol peceded the changes in T3 and rT3 in both groups. T3 and rT3 returned towards normal levels when the patients recovered and resumed oral nutrition. It seems likely that both elective and acute uncomplicated surgery is accompanied by a transient reduction in the extrathyroidal production of the most active hormone, T3, and by a reciprocal increase in the levels of the virtually inactive rT3. The underlying mechanism behind this metabolic adaptation is unclear but may be related to adrenocortical activation and/or to changes in the mode of nutrition.

Aged↗
PubMed1978

Enhancement of dicoumarol bioavailability by concomitant food intake.

The influence of food intake on the bioavailability of dicoumarol from a non-micronized formulation was examined in ten healthy volunteers, by examination of its single-dose kinetics after ingestion of dicoumarol 250 mg with a standardized breakfast and on an empty stomach. Blood samples were collected at regular intervals from 0 to 72 h, and the serum concentration of unmetabolized dicoumarol was determinded by spectrophotometry. Postprandial AUC (area under the curve) values were significantly (p less than 0.01) greater than the preprandial figures, the mean increase being 85 per cent. The results suggest that dicoumarol should always be taken with food.

Adult↗
PubMed1978

Transplacental passage of atenolol in man.

Maternal and umbilical serum concentrations of atenolol, a hydrophilic, cardioselective beta-adrenoceptor antagonist, were studied at delivery in seven cases of pregnancy hypertension. The drug had been administered to each patient for at least one week. Atenolol was detected in both maternal and umbilical serum in six cases, showing that there is transplacental passage of the drug. In the seventh case, who had stopped taking atenolol more than one day before delivery, neither maternal nor umbilical serum contained a measurable quantity of the drug. Atenolol concentration varied 3- to 6-fold between individuals, but there was no systematic difference between maternal and umbilical levels. It seems reasonable to assume that during steady state conditions the blood level of atenolol in mother and fetus is approximately equal, and that fetal accumulation of the drug does not occur.

Adult↗