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Biomedical subjects

B Schellenberg

Publications and source records attributed to B Schellenberg.

At least 19 recordsLinked to original sources
PubMed2001

L-ascorbic acid potentiates endothelial nitric oxide synthesis via a chemical stabilization of tetrahydrobiopterin.

Ascorbic acid has been shown to stimulate endothelial nitric oxide (NO) synthesis in a time- and concentration-dependent fashion without affecting NO synthase (NOS) expression or l-arginine uptake. The present study investigates if the underlying mechanism is related to the NOS cofactor tetrahydrobiopterin. Pretreatment of human umbilical vein endothelial cells with ascorbate (1 microm to 1 mm, 24 h) led to an up to 3-fold increase of intracellular tetrahydrobiopterin levels that was concentration-dependent and saturable at 100 microm. Accordingly, the effect of ascorbic acid on Ca(2+)-dependent formation of citrulline (co-product of NO) and cGMP (product of the NO-activated soluble guanylate cyclase) was abolished when intracellular tetrahydrobiopterin levels were increased by coincubation of endothelial cells with sepiapterin (0.001-100 microm, 24 h). In contrast, ascorbic acid did not modify the pterin affinity of endothelial NOS, which was measured in assays with purified tetrahydrobiopterin-free enzyme. The ascorbate-induced increase of endothelial tetrahydrobiopterin was not due to an enhanced synthesis of the compound. Neither the mRNA expression of the rate-limiting enzyme in tetrahydrobiopterin biosynthesis, GTP cyclohydrolase I, nor the activities of either GTP cyclohydrolase I or 6-pyruvoyl-tetrahydropterin synthase, the second enzyme in the de novo synthesis pathway, were altered by ascorbate. Our data demonstrate that ascorbic acid leads to a chemical stabilization of tetrahydrobiopterin. This was evident as an increase in the half-life of tetrahydrobiopterin in aqueous solution. Furthermore, the increase of tetrahydrobiopterin levels in intact endothelial cells coincubated with cytokines and ascorbate was associated with a decrease of more oxidized biopterin derivatives (7,8-dihydrobiopterin and biopterin) in cells and cell supernatants. The present study suggests that saturated ascorbic acid levels in endothelial cells are necessary to protect tetrahydrobiopterin from oxidation and to provide optimal conditions for cellular NO synthesis.

Ascorbic Acid↗
PubMed1988

Effect of long-term treatment with antiepileptic drugs on the vitamin status.

The status of vitamins A, B1, B2, B6, B12, C, D, and E as well as that of beta-carotene, biotin, and folate in the blood of over 500 epileptics was compared with that of a normal population. Male and female epileptics showed a poorer supply of vitamins B2, biotin, folate, and 25-hydroxycholecalciferol; the males, of only vitamin B6, B12, and E, and the women, of only vitamin A. Concentrations of beta-carotene and vitamin E in female epileptics were higher. The evaluation of relations between vitamin concentrations and mean daily dose, total dose of anticonvulsants, and duration of therapy suggested a possible influence of anticonvulsant medication on vitamins B1, B2, B6, C, D, E, beta-carotene, biotin, and folate. Concentrations of B vitamins as well as of folate were distinctly lower in patients under monotherapy with enzyme-inducing drugs than in those under valproate sodium. There was no relationship between bone mineral content and 25-hydroxycholecalciferol levels and between the neurographic parameters and the neurotropic vitamins of the B group, which also had no influence on concentration performance. Patients with poorer results in tests of the function of the central and the peripheral nervous system displayed a tendency towards lower vitamin-C levels. There were indications of potential links between immunological status and vitamin B6 and biotin. Males and females with a poorer supply of vitamin C, as well as males with lower riboflavin levels, showed a tendency towards macrocytic anaemia. Cerebellar disturbances were associated with lower concentrations of folate, of vitamin C or D, and possibly of biotin. The incidence of gingival hyperplasia could be linked to riboflavin, to biotin, and possibly also to vitamin C, D, or folate status.

Adult↗
PubMed1987

Antiepileptic drugs reduce serum uric acid.

Uric acid examination in 554 epileptic out-patients under long-term anticonvulsant medication revealed significantly lower serum concentrations compared to a group of normal controls. In patients taking enzyme-inducing drugs, uric acid levels were found to be lower than in those under valproate sodium. In addition, uric acid concentrations showed a negative correlation with duration of therapy in epileptic males. At this time, we can only speculate on the mechanism involved in the reduction of uric acid by enzyme-inducing anticonvulsants as well as on the possible implication of this finding in the treatment of hyperuricemia.

Adult↗
PubMed1984

Decreased plasma phosphate under hormonal contraceptives.

Plasma phosphate (Pi) and several indices of Ca-Pi metabolism were measured in 129 randomly selected healthy female individuals of the general population, of whom 59 were on hormonal contraceptives and 70 were not. Fasting plasma Pi was significant (p less than 0.01) lower in those taking hormonal contraceptives (0.96 +/- 0.17 mmol/l) than in those not taking them (1.06 +/- 0.16). Those on hormonal contraceptives had identical age, body weight and UVcr. Systolic and diastolic blood pressure was higher in those on hormonal contraceptives, and there was an inverse relationship between blood pressure and plasma Pi. Between those on hormonal contraceptives and those not on them, no significant difference of urinary cAMP (non-hormone 4.69 +/- 1.48 nmol/l GF; hormone 4.43 +/- 1.18) or iPTH could be shown. The present study documents that hormonal contraceptives with estrogen (less than or equal to microgram/dl) decrease plasma Pi and urinary Ca in premenopausal nonosteoporotic women.

Adult↗
PubMed1982

Effects of estrogens and progestogens on lipid metabolism.

Because the incidence of venous thromboembolism, coronary heart disease, and stroke is increased in users of oral contraceptives (OCs), the possible causal metabolic side effects of OCs have been widely investigated. In this article we present epidemiologic data associated with OC use. Total plasma triglycerides and cholesterol levels were elevated in OC users while high-density lipoprotein cholesterol levels were lowered. Another section discusses some hormone-dependent physiologic and pathophysiologic aspects of lipid metabolism. Finally, we report on the isolated influence of estrogens and progestogens and their interrelation, including some recent findings about the effects of different progestogens on lipoproteins.

Adolescent↗
PubMed1982

"Low dose" colestipol in children, adolescents and young adults with familial hypercholesterolemia.

The effect of colestipol on plasma lipids and lipoproteins was studied in children, adolescents and young adults with familial hypercholesterolemia. O.125 g or 0.25 g/kg body weight were given in randomized sequence for period of 4 weeks. Total cholesterol was lowered by 13 and 18% with the smaller and larger dose , respectively, and LDL cholesterol lowered by 15% with the smaller and 12% with the larger dose. HDL cholesterol rose by 18 an 32%. LDL composition before and during the study was abnormal due to a markedly reduced triglyceride content. "Low-dose" colestipol is less effective lowering total plasma and LDL cholesterol than conventional doses but may, due to very few side effects, by advantageously used in cases of familial hypercholesterolemia when plasma cholesterol levels after dietary management are only 15-20% above normal.

Adolescent↗
PubMed1982

Vitamin status in patients on chronic anticonvulsant therapy.

Vitamin levels in blood were estimated in 146 epileptics, aged 20-40 years. Compared to healthy subjects, no higher risk rates of a vitamin deficiency were found in epileptics for vitamins B1, B12, A, C, E and beta-carotene. alpha EGR was elevated only in epileptic females, alpha EGOT in epileptic males, indicating a higher risk of a vitamin B2 and B6 deficiency in these groups. Markedly reduced levels of folate, 25-hydroxy-cholecalciferol, and biotin were found in the epileptics; folate and biotin levels showed a significant negative correlation with the total amount and the average daily dose of anticonvulsants administered.

Adult↗
PubMed1981

Diet and high density lipoproteins.

The acute and subacute effects of different diets on serum high density lipoprotein (HDL) cholesterol concentration and/or HDL composition are described. In obese normolipemic, hypercholesterolemic (type II) and hypertriglyceridemic (type IV) patients, low HDL cholesterol values remained low during total starvation for 2 weeks. Prudent diets in patients with type II and IV hyperlipoproteinemia had no significant effects on HDL cholesterol within 3 weeks, whereas in normal individuals, a high carbohydrate diet given for 10 days caused significant decreases in HDL cholesterol with concomitant increases in HDL triglycerides as compared to a high-fat diet. The HDL triglyceride fatty acid composition changed in healthy volunteers during the day, depending on the type of ingested fat. The data demonstrate the possibility of acute manipulations of HDL in normal patients and the difficulties of normalizing low HDL cholesterol levels in patients by dietary means. Additional information on the function of HDL is desirable before the therapeutic manipulation of HDL cholesterol or other constituents of HDL can be evaluated regarding their effectiveness in the prevention of ischemic vascular disease.

Adult↗
PubMed1981

Biliary cholesterol saturation and weight reduction--effects of fasting and low calorie diet.

The effects of fasting or a 600-cal diet on biliary lipid composition were studied in 20 persons with overweight. With complete fasting for 20 days and a mean weight loss of 650 g/day, biliary cholesterol fell significantly from 10.1 to 6.9 mol% and the 'lithogenic index' from 1.0 to 0.7. Following fasting, the index, in 10 of the 11 patients, was in the normal range below 1.0. With a 600-cal diet, in agreement with findings by other authors, there was no significant change of individual bile lipids or of the lithogenic index. While it has been shown that lithogenicity increases up to 16 h of fasting, it obviously significantly decreases with continued fasting. Fasting, therefore, in addition to manipulation of dietary cholesterol and, possibly, fiber consumption, appears to be an effective method for rapid lowering of biliary cholesterol saturation.

Adult↗
PubMed1980

Urinary sodium excretion in renal stone formers. An epidemiological study.

In the present investigation 238 randomly selected male individuals of the general population (age 19--41 years) and 42 age-matched male patients with recurrent renal stone formation (calcium oxalate and/or calcium phosphate) were studied under outpatient conditions without dietary restrictions. Urinary Na excretion was 207 +/- 82 mmol/24 h (range 55--570) in controls and 208 +/- 100 (range 76--575) in recurrent renal stone formers. Both in controls (r = 0.36; p less than 0.01) and in stone formers (r = 0.4; p less than 0.01) a significant correlation was observed between urinary excretion of sodium and calcium. Urinary sodium excretion was unrelated to systolic or diastolic blood pressure in normotensive or hypertensive individuals. This finding indicates that factors other than sodium are involved in the maintenance of hypertension. Urinary sodium, presumably an index of intake of nutrients, was significantly correlated to several coronary risk factors, e.g. fasting glucose, cholesterol and overweight. There existed a significant inverse relationship between fasting plasma phosphate and urinary sodium, but not between fasting plasma phosphate and serum iPTH or urinary cAMP. This finding points to some function of sodium excretion as one determinant of plasma phosphate.

Adult↗