Biomedical subjects
H Toplak
Publications and source records attributed to H Toplak.
Effects of low-dose L-arginine on insulin-mediated vasodilatation and insulin sensitivity.
The present study was carried out to evaluate the effect of a low-dose intravenous supplementation of L-arginine on insulin-mediated vasodilatation and insulin sensitivity. The study was performed in healthy subjects (n = 7) and patients with obesity (n = 9) and non-insulin-dependent diabetes mellitus (NIDDM) (n = 9). Insulin-mediated vasodilatation was measured by venous occlusion plethysmography during the insulin suppression test, evaluating insulin sensitivity. Experiments were performed twice in each subject in the presence or absence of a concomitant infusion of L-arginine (0.52 mg kg-1 min-1). L-Arginine restored the imparied insulin-mediated vasodilatation observed in obesity (22.4 +/- 4.1%, P < 0.01 vs. without L-arginine) and NIDDM (20.3 +/- 3.2%, P < 0.01 vs. without L-arginine). In healthy subjects, no effect on insulin mediated-vasodilatation was observed (24.8 +/- 3.1% vs. 21.4 +/- 3.1%). Insulin sensitivity was improved significantly (P < 0.001) in all three groups by infusion of L-arginine. No effect of L-arginine was observed on insulin, insulin-like growth factor I (IGF-I), free fatty acids (FFAs) or C-peptide levels during the insulin suppression test. Our data indicate that defective insulin-mediated vasodilatation in obesity and NIDDM can be normalized by intravenous L-arginine. Furthermore, L-arginine improves insulin sensitivity in obese patients and NIDDM patients as well as in healthy subjects, indicating a possible mechanism that is different from the restoration of insulin-mediated vasodilatation.
[Effect of chromium yeast and chromium picolinate on body composition of obese, non-diabetic patients during and after a formula diet].
The objective of this study was to assess the effects of chromium yeast and chromium picolinate on lean body mass during and after weight reduction with a very-low-calorie diet. 36 obese (BMI 33.7 +/- 5.4 kg/m2), non-diabetic patients aged 45 +/- 6 years undergoing a 8-week very-low-calorie diet followed by a 18-week maintenance period. During the whole 26 week treatment period subjects received either placebo or chromium yeast (200 micrograms/d) or chromium-picolinate (200 micrograms/d) in a double-blind manner. Body weight was measured as BMI and body composition after calculation from skinfold thickness. As a result all three groups showed comparable weight loss after 8 and 26 weeks. Lean body mass was reduced in all groups after 8 weeks. However, after 26 weeks chromium picolinate supplemented subjects showed increased lean body mass (p < 0.029) whereas the other treatment groups still had reduced lean body mass. Chromium picolinate, but not chromium yeast, is able to increase lean body mass in obese patients in the maintenance period after a very-low-calorie diet without counteracting the weight loss achieved.
Increased prevalence of IgA-Chlamydia antibodies in NIDDM patients.
Chlamydia trachomatis oculogenital infection is a common disease in western societies. Despite the fact that diabetes is accompanied by increased risk for infections, no data on chlamydial infections in the non-insulin-dependent diabetic (NIDDM) patient exist. In our study Chlamydia antibodies were determined using an immunoperoxidase reaction in NIDDM patients (n = 79) and in a local nondiabetic control population (n = 125) which was randomly invited to a medical control visit without any preselection criteria. In total, 46% of diabetics and 55% of controls were IgG-Chlamydia antibody positive (ns). Using IgA-Chlamydia antibodies to define 'seroactive' chlamydial infection, 22% of NIDDM patients and 14% of controls were positive. Thus seroactive chlamydial infection of all patients with proven contact to Chlamydia (IgG-Chlamydia antibody positive) was 47% in diabetics versus 25% in controls, respectively (P < 0.05). Forming subgroups, significance was reached in females (52% vs. 32%, P < 0.05) only, but a similar trend was observed in males (36% vs. 21%, ns). Seroactivity was neither correlated with HbA1c nor with nephelometrically determined total serum immunoglobulins (IgG, IgA). Additionally we observed significantly elevated total IgM and IgA-levels in NIDDM patients whereas IgG-levels were comparable in both groups. In conclusion, seroactive chlamydial infections in subjects with proven contact to Chlamydia are more frequent in NIDDM patients than in nondiabetic controls. Additionally, higher IgM and IgA serum levels might indicate a higher susceptibility to active surface infections in NIDDM.
Involvement of the L-arginine-nitric oxide pathway in hyperglycaemia-induced coronary artery dysfunction of isolated guinea pig hearts.
The effects of hyperglycaemia and L-arginine on flow-induced reduction of coronary artery resistance were investigated in isolated guinea pig hearts. In the presence of indomethacin, hyperglycaemia caused an increase in flow-induced vasodilatation (P < 0.05). Hyperosmotic controls failed to mimic this effect. Addition of L-arginine strongly enhanced this effect. Addition of D-arginine failed to mimic the effects of L-arginine. The effect of L-arginine was abolished by co-administration of NG-nitro-L-arginine. In the absence of indomethacin and L-arginine, the effect of hyperglycaemia was blunted, suggesting the formation of vasoconstrictive prostanoids. Addition of L-arginine again resulted in a significant increase in flow-induced vasodilatation. In conclusion our results suggest that increased flow-induced vasodilatation under hyperglycaemic conditions depends on an adequate supply of L-arginine to maintain sufficient formation of nitric oxide.
Insulin resistance and membrane abnormalities.
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Severely depressed natural killer cell activity of patients with adrenoleukodystrophy under treatment with Lorenzo's oil.
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Effects of treadmill exercise protocol with constant and ascending grade on levelling-off O2 uptake and VO2 max.
In order to investigate the effect of an exercise protocol on the levelling-off O2 uptake and VO2 max values, ten male subjects aged 28 +/- 5 yrs, height 1.8 +/- 0.05 m, body mass 76 +/- 6 kg performed two treadmill exercise protocols: 1) constant grade (CG) of 5%, with increasing running speed starting at 6 km.h-1 and increments of 2 km.h-1 every 3 minutes. 2) ascending grade (AG) starting at 0% and increments of 5% every 3 minutes, with constant running speed of 5 km.h-1. During each protocol oxygen uptake (VO2), pulmonary ventilation (VE), tidal volume (Vt), and breathing rate (BR) as well as blood lactate concentration (La) and heart rate (HR) were measured. In CG a levelling-off phenomenon of VO2 in all cases was observed. Aerobic capacity expressed as VO2 max in CG was 46.2 +/- 6.0 ml.min-1.kg-1. In contrast, VO2 max was 35% higher in AG (62.6 +/- 7.2 ml.min-1.kg-1). The behaviour of VO2 indicates a lower efficiency with increasing work load in AG as compared to CG. Regarding maximum performance it can be concluded that VO2 in CG seems to be limited by a mechanical or neuromuscular constraint on the depth of breathing, which is confirmed by a distinct flattening of Vt. The levelling-off of the VO2 in CG, something which is not observed in AG, can be explained plausibly this way.
Elevation of D-glucose impairs coronary artery autoregulation after slight reduction of coronary flow.
Diabetes mellitus is thought to increase the susceptibility of tissue to hypoxic injury through D-glucose-induced alterations of intracellular metabolism. Therefore the effects of hyperglycaemia on coronary artery autoregulation under slight reduction of coronary flow were investigated in isolated perfused guinea-pig hearts. Under normal (10 mM) D-glucose concentrations coronary autoregulation was intact in response to a slight reduction of coronary flow (from 6 to 4.5 mL min-1) when L-arginine as a precursor of the endothelium-derived relaxing factor (EDRF/NO) was available and formation of prostaglandines was intact. Under high (44 mM) D-glucose concentrations on the other hand, a sustained vasodilatation dependent on the availability of L-arginine was observed, when formation of prostaglandins was blocked. This effect was partially reduced in the presence of prostaglandin synthesis. Furthermore, the effect of L-arginine under both conditions could be antagonized by the L-arginine-analogue NG-nitro-L-arginine-methyl-ester (100 microM). Our results suggest that hyperglycaemia impairs coronary artery autoregulation by reducing the threshold for hypoxic vasodilatation in an EDRF/NO-dependent manner. Concomitantly a shift from the formation of vasodilatatory to vasoconstrictive prostaglandines was observed. These results might be of particular interest in patients with diabetes mellitus and ischaemic heart disease.
[Increased prevalence of serum IgA Chlamydia antibodies in obesity].
Obesity is metabolically related to diabetes type II. We have previously shown that seroactive (IgG- and IgA-Chlamydia antibody positive) chlamydial infection of asymptomatic patients is more frequent in type II diabetic patients than in nondiabetics, independent from metabolic control. Thus we investigated 119 nondiabetic patients (66 +/- 9 years, HbA1c < 6%) of our department for seroactive chlamydia infection using an immunoperoxidase reaction and compared the results to the anthropometric data. The prevalence of seroactive chlamydial infection was significantly (p < 0.05) higher in the considerably overweight patients with a BMI > 30 kg/m2, both when compared to lean patients (BMI < 24 kg/m2) and when compared to all those with BMI < 30 kg/m2. For slight to moderate obesity the prevalences were slightly (but not significantly) increased. Due to the fact that similar data were obtained for type II diabetic patients, an unknown relation to insulin resistance might be the underlying cause and should be further investigated.
[Effect of dexfenfluramine on eating behavior and body weight of obese patients: results of a field study of Isomeride in Austrian general practice].
In a multicenter study by 243 practicing physicians in Austria 819 severely obese subjects of both sexes without overt disease were encouraged to keep a calorie-restricted diet to reduce weight. After a run-in period of more than two weeks of dieting patients started taking 15 mg dexfenfluramine (Isomeride) twice daily for three month. While their weight was fairly stable during the run-in period progressive weight loss occurred during taking dexfenfluramine due to obvious changes in eating habits and appetite allowing to keep the reducing diet more strictly. Females lost 7.7 +/- 3.9 kg while obese men lost 9.32 +/- 4.6 kg. Laboratory tests obtained before starting dexfenfluramine and after 3 months at termination of medication showed blood glucose, cholesterol, LDL and triglycerides to decrease while HDL-cholesterol increased moderately. Dexfenfluramine was well tolerated by the majority of patients. Side effects such as fatigue, sedation, flatulence or diarrhea occurred in only 7.9% of the probands initially and dropped to 2.1% during the third month of the medication. It is concluded that Dexfenfluramine modifies eating habits and appetite thus making weight reducing diets easier acceptable and resulting in weight loss. It is suggested that Dexfenfluramine has a role in treatment regimes for morbid and refractory obesity.
Endothelial dysfunction in hypertension.
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Endothelial dysfunction and diabetic angiopathy.
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Reduced stimulability of platelet surface adhesion molecules under treatment with Lorenzo's oil.
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Chondrodysplasia punctata with a mild clinical course.
We report a 7-year-old patient with chondrodysplasia punctata but without rhizomelia. He was born with typical clinical and radiological symptoms of this disease. He developed slowly with considerable psychomotor retardation but improved later, gaining some speech and psychosocial contacts. Joint contractures and bilateral cataracts are still major problems. De novo plasmalogen synthesis in fibroblasts was greatly reduced and DHAP-AT activity was at the lower limit of controls. Peroxisomal thiolase was present in its precursor form only. Membrane fluidity (measured by TMA-DPH fluorescence anisotropy) was increased in erythrocyte ghosts and in lymphocytes. Plasma phytanic acid concentration was elevated 5-fold. The patient represents a mild clinical course of chondrodysplasia punctata, resembling Conradi-Hünermann syndrome, but biochemically he has the typical peroxisomal dysfunction of rhizomelic chondrodysplasia punctata except for a high residual activity of DHAP-AT.
Influence of weight reduction on platelet volume: different effects of a hypocaloric diet and a very low calorie diet.
Since platelet volume reflects platelet activity, the mean platelet volume (MPV) is proposed to be a further independent risk factor for cardiovascular disease (CVD). Even if it is well established that weight reduction reduces some of the risk factors of CVD in obese patients, an increase of MPV occurs during periods of weight loss. We therefore prospectively investigated the effects of different weight reduction therapies on platelet mass, platelet volume, body weight and serum lipid profile in patients undergoing an 8 week weight reduction therapy either by a hypocaloric diet (HD) or a nutritionally completed very low calorie diet (VLCD) with a subsequent maintenance period of 40 weeks. In both groups, MPV transiently increased during the 8 week diet period. After 48 weeks the MPV was decreased to initial values. The change in MPV was significantly (P < 0.05) smaller in the VLCD group. We therefore suggest that fasting might alter the control of platelet size with a possible impact on platelet activity. This might result in an increased risk for thromboembolic ischaemic events in atherosclerotic patients. Thus, we conclude that the use of a VLCD is potentially superior for weight reduction in patients with pre-existing atherosclerosis.
Time course of endothelial dysfunction in diabetes mellitus.
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Intracellular mechanisms involved in D-glucose-mediated amplification of agonist-induced Ca2+ response and EDRF formation in vascular endothelial cells.
Prolonged treatment of vascular endothelial cells with pathologically high D-glucose amplifies autacoid-induced Ca2+ mobilization and thus formation of nitric oxide. This study investigated the Ca2+ source for the change in endothelial CA2+ response on agonist stimulation. Pretreatment with high D-glucose (44 vs. 5 mM) enhanced release of intracellular Ca2+ by bradykinin as a result of a 2.0-fold increased formation of inositol 1,4,5-trisphosphate. High D-glucose also amplified Ca2+ influx (2.0-fold). In high D-glucose preincubated cells, stimulation with bradykinin significantly increased transplasmalemmal 45Ca2+ flux (3.2-fold) and caused a 2.0-fold increase in permeability to Mn2+, a surrogate for endothelial plasma membrane Ca2+ channels. A significant 2.0-fold increase occurred in the maximal slope, suggesting a higher rate of Mn2+ (Ca2+) influx. Ca2+ influx, stimulated by an inositol phosphate-independent depletion of intracellular Ca2+ stores with 2,5-di-(tert-butyl)-hydroquinone was also significantly increased 2.4-fold by high D-glucose, with no effect on intracellular Ca2+ release. D-glucose failed to modulate resting or stimulated cAMP levels. We suggest that prolonged exposure to pathologically high D-glucose increases formation of inositol polyphosphates, thus increasing Ca2+ release. Ca2+ entry is increased by amplification of unknown signal transduction mechanisms triggered by Ca2+ store depletion.