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Biomedical subjects

E van Breda

Publications and source records attributed to E van Breda.

13 recordsLinked to original sources

Androgenic anabolic steroid use and severe hypothalamic-pituitary dysfunction: a case study.

The data of the present case demonstrate that the abuse of androgenic anabolic steroids (AAS) may lead to serious health effects. Although most clinical attention is usually directed towards peripheral side effects, the most serious central side effect, hypothalamic-pituitary-dysfunction, is often overlooked in severe cases. Although this latter central side-effect usually recovers spontaneously when AAS intake is discontinued, the present case shows that spontaneous recovery does not always take place. We suggest that hypothalamic-pituitary dysfunction should always be considered in the differential diagnosis in athletes seen with typical presentation of anabolic steroid use. In order to regain normal hypothalamic-pituitary function, supraphysiological doses of 200 microg LH-RH should be considered when the physiological challenge test with LH-RH (50 microg) fails to show an acceptable response.

Adult↗

Effect of testosterone and endurance training on glycogen metabolism in skeletal muscle of chronic hyperglycaemic female rats.

OBJECTIVES: To investigate in glycolytic and oxidative muscles of trained (nine weeks) and untrained hyperglycaemic female rats the effect of hyperandrogenicity and/or endurance training on energy metabolic properties. METHODS: Glycogen content and activity of muscle enzymes with regulatory functions in glycogen synthesis were examined. RESULTS: Testosterone treatment increased glycogen content of extensor digitorum longus (EDL) and soleus muscles of hyperglycaemic sedentary (18% and 84% respectively) and hyperglycaemic trained (7% and 16% respectively) rats. In both types of muscle of the hyperglycaemic testosterone treated exercised subgroup, less depletion of glycogen was found than in the untreated group (38% and 87% for EDL and soleus respectively). CONCLUSIONS: The mechanisms by which training and/or hyperandrogenism alone or in combination elicits their specific effects are complex. Differences in sex, surgery, levels of hormones administered, and exercise model used may be the main reasons for the observed discrepancies. Conclusions from the results: (a) hyperandrogenism is not a primary cause of the development of insulin resistance; (b) glycogen content of slow and fast twitch muscle is increased by training through increased glycogen synthase activity. The most plausible explanation for differences between different muscle fibre types is the different levels of expression of androgen receptors in these fibres. Hyperandrogenicity therefore acts on energy metabolic variables of hyperglycaemic animals by different mechanisms in glycolytic and oxidative muscle fibres.

Animals↗

Nebivolol: a third-generation beta-blocker that augments vascular nitric oxide release: endothelial beta(2)-adrenergic receptor-mediated nitric oxide production.

BACKGROUND: Nebivolol is a beta(1)-selective adrenergic receptor antagonist with proposed nitric oxide (NO)-mediated vasodilating properties in humans. In this study, we explored whether nebivolol indeed induces NO production and, if so, by what mechanism. We hypothesized that not nebivolol itself but rather its metabolites augment NO production. METHODS AND RESULTS: Mouse thoracic aorta segments were bathed in an organ chamber. Administration of nebivolol did not affect NO production. When nebivolol was allowed to metabolize in vivo in mice, addition of plasma of these mice caused a sustained 2-fold increase in NO release. Interestingly, coadministration of a selective beta(2)-adrenergic receptor antagonist (butoxamine) prevented the response. Immunohistochemistry and Western blot analysis demonstrated the presence of beta(2)- but not beta(1)-adrenergic receptors on endothelial cells. In the absence of calcium, metabolized nebivolol failed to increase NO production, suggesting a role for calcium-dependent NO synthase. With digital fluorescence imaging, a rapid and sustained rise in endothelial cytosolic free Ca(2+) concentration was observed after administration of metabolized nebivolol, which also was abrogated by butoxamine pretreatment. CONCLUSIONS: In vivo metabolized nebivolol increases vascular NO production. This phenomenon involves endothelial beta(2)-adrenergic receptor ligation, with a subsequent rise in endothelial free [Ca(2+)](i) and endothelial NO synthase-dependent NO production. This may be an important mechanism underlying the nebivolol-induced, NO-mediated arterial dilation in humans.

Adrenergic beta-Antagonists↗

The role of mast cells and histamine in leukocyte-endothelium interactions in four rat strains.

The objective of the present study was to determine the role of mast cells and histamine in leukocyte-endothelium interactions in mesenteric venules of four rat strains: Brown Norway, Lewis, Sprague-Dawley and Wistar. Intravital microscopy showed that the mast cell stabilizer cromoglycate (5 mg/kg i.v. just before exteriorization of the mesentery) did not affect the baseline level and velocity of leukocyte rolling in any of the four strains. This finding is in agreement with the observation that cromoglycate pretreatment only slightly influenced mast cell degranulation in all strains except the Brown Norway. After mast cell stabilization, only in Sprague-Dawley did topical administration of histamine (10(-4) M) result in a significant increase in the level of leukocyte rolling and a decrease in the rolling velocity compared with the time control. Histamine induced leukocyte adhesion only in the Brown Norway strain. In conclusion, the hypothesis presented in other studies, that degranulation of mast cells, and more specifically the release of histamine, is of major importance for the induction of leukocyte-endothelium interactions in rat mesenteric venules is not generally applicable; the present study shows a clear strain dependency.

Animals↗

Structural and functional analysis of the canine histamine H2 receptor by site-directed mutagenesis: N-glycosylation is not vital for its action.

G-protein-coupled receptors generally share a similar structure containing seven membrane-spanning domains and extracellular site(s) for N-glycosylation. The histamine H2 receptor is a member of the family of G-protein-coupled receptors, and has three extracellular potential sites for N-glycosylation (Asn-4, Asn-162 and Asn-168). To date, however, no information has been presented regarding N-glycosylation of the H2 receptor. To investigate the presence, location and functional roles of N-glycosylation of the H2 receptor, site-directed mutagenesis was performed to eliminate the potential site(s) for N-glycosylation singly and collectively. The wild-type and mutated H2 receptors were expressed stably in Chinese hamster ovary (CHO) cells or transiently in COS7 cells. Immunoblotting of the wild-type and mutated H2 receptors with an antiserum directed against the C-terminus of the H2 receptor showed that mutation at Asn-162, but not at Asn-168, resulted in a substantial decrease in the molecular mass. A mutation at Asn-4 led to a further decrease in the molecular mass. Tunicamycin treatment of the transfected cells yielded a sharp band with a molecular mass identical to that of the mutant devoid of all three potential sites for N-glycosylation. These findings indicate that the H2 receptor is N-glycosylated, and that N-glycosylation takes place mainly at two sites, Asn-4 and Asn-162. Neither the affinity for tiotidine nor that for histamine was affected by the mutagenesis. Immunocytochemistry and tiotidine binding showed that the mutated receptors were exclusively distributed on the cell surface in a fashion similar to that of the wild-type. In addition, the glycosylation-defective receptor was capable of activating adenylate cyclase and elevating the intracellular Ca2+ concentration in response to histamine in stable CHO cell lines. Thus N-glycosylation of the H2 receptor is not required for cell surface localization, ligand binding or functional coupling to G-protein(s).

1-Methyl-3-isobutylxanthine↗

Rat heart fatty acid-binding protein content is increased in experimental diabetes.

Cytoplasmic fatty acid-binding protein (FABP) was assayed immunochemically in hearts from rats with insulin-dependent (IDDM) or non-insulin-dependent diabetes mellitus (NIDDM). FABP contents were 34% higher in IDDM and 103% higher in NIDDM hearts than in respective age-matched controls. FABP levels returned to control values when islets of Langerhans were transplanted into diabetic IDDM animals. In the diabetic hearts the activity of fructose-6-phosphate kinase decreased (IDDM and NIDDM animals), while that of 3-hydroxyacyl-CoA dehydrogenase increased (NIDDM animals only). These data indicate that experimental diabetes induces a marked increase of the FABP content of rat heart and suggests that this protein is involved in the enhanced fatty acid utilization by the diabetic heart.

Animals↗

Modulation of glycogen metabolism of rat skeletal muscles by endurance training and testosterone treatment.

The effects of training and/or testosterone treatment on glycogen content and the activities of glycogen synthase, glycogen phosphorylase, and fructose-6-phosphate kinase were studied in extensor digitorum longus (EDL) and soleus muscles of intact adult female rats. One group of rats remained sedentary, whereas another group was trained for 7 weeks. Thereafter, both the sedentary and trained rats were subdivided into two control and four testosterone-treated subgroups. Testosterone was administered by a silastic implant. Training was continued for 2 weeks. On the final day of the experiment rats from one trained control and one trained testosterone-treated subgroup ran for 60 min submaximally. Upon testosterone treatment of sedentary rats the glycogen concentration was not changed. However, in the soleus, but not in the EDL, the glycogen content was increased by training (P < 0.05) which could, at least partly, be explained by a decrease in activity of active glycogen phosphorylase (P < 0.05). In the EDL of trained rats testosterone treatment increased glycogen content significantly by both an increase in activity of active glycogen synthase and a decrease in activity of active glycogen phosphorylase (P < 0.05). In the EDL and soleus of testosterone-treated animals from the exercised subgroup a significant sparing of glycogen was observed, which could be explained by an increase in activity of active glycogen synthase and, in the soleus, could also be explained by a concerted decrease in active glycogen phosphorylase (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Modulation of fatty-acid-binding protein content of rat heart and skeletal muscle by endurance training and testosterone treatment.

The effects of training and/or testosterone treatment and its aromatization to oestradiol on fatty-acid-binding protein (FABP) content and cytochrome c oxidase activity in heart, soleus and extensor digitorum longus (EDL) muscles were studied in intact adult female rats. One group of rats remained sedentary, whereas the others were trained for 7 weeks. Thereafter the trained rats were divided into control and testosterone-treated groups, with or without an aromatase inhibitor. Testosterone was administered by a silastic implant. Training was continued for 2 weeks. In untreated sedentary rats the immunochemically assayed FABP contents were 497 +/- 28, 255 +/- 49 and 58 +/- 17 micrograms/g wet weight for the heart, soleus, and EDL respectively. In the heart the FABP content was increased after training (29%), testosterone treatment (33%) or both manipulations (53%). In soleus muscle FABP increased only after testosterone treatment (16%), whereas in EDL no changes were found. Inhibiting the aromatase enzyme complex abolished the testosterone-induced effect on FABP content in soleus (suggesting an oestradiol effect) but not in heart muscle. Among the three muscles studied the FABP content was found to be related to the cytochrome c oxidase activity in a non-linear way. In conclusion, it is shown that the FABP contents and mitochondrial activities of heart and skeletal muscle are affected by training and sex hormones and that these effects are different for heart and skeletal muscles.

Animals↗

Use of the intact mouse skeletal-muscle preparation for metabolic studies. Evaluation of the model.

1. We examined the isolated mouse skeletal-muscle model in vitro, commonly used by many investigators, for its suitability for metabolic studies. 2. Despite the fact that pH, O2 saturation, osmolality and the release of the enzyme creatine kinase remained stable, histochemical studies showed large cores devoid of glycogen, suggesting that the incubated muscle had lost its viability. 3. This study indicates that caution should be exercised when interpreting the results of studies with intact isolated mouse muscles.

Animals↗

Effects of oral bovine colostrum supplementation on serum insulin-like growth factor-I levels.

OBJECTIVES: We investigated whether supplementation with 60 g/d of bovine colostrum affects blood levels of insulin-like growth factor-I (IGF-I) and IGF binding protein-3 in relation to doping testing. Nine endurance-trained men ingested 60 g/d of bovine colostrum for 4 wk. METHODS: Blood and urine were sampled before starting supplementation. After 4 wk urine and blood samples were taken after an overnight fast and 2 h after ingestion of the last portion to study possible acute effects. RESULTS: Blood IGF-I levels before supplementation were (mean +/- standard deviation) 31 +/- 13 nM/L, and no acute effects were observed after 4 wk of supplementation (33 +/- 9 nM/L). Levels of IGF-binding protein-3 were 136 +/- 11 nM/L before supplementation and 135 +/- 16 nM/L after 4 wk of supplementation. Two hours after ingestion of the last portion, the level of IGF binding protein-3 was 131 +/- 19 nM/L, which was not different from baseline values. Drug testing in a laboratory accredited by the International Olympic Committee did not show any forbidden substance before or after 4 wk of supplementation. CONCLUSIONS: Daily supplementation with 60 g of bovine colostrum for 4 wk does not change blood IGF-I or IGF binding protein-3 levels and does not elicit positive results on drug tests.

Adult↗

Physiological, biochemical and psychological markers of strenuous training-induced fatigue.

The purpose of the study was to investigate whether severe fatigue, possibly leading to overreaching, could be diagnosed at an early stage by a combination of parameters. Seven well-trained male subjects (age [mean +/- SD]: 25.3 +/- 4.7 yr; body mass: 76 +/- 6.6 kg; VO2max: 61.1 +/- 7 ml.kg(-1).min(-1)) increased their training load by doubling their training volume and increasing the intensity by 15 % over a period of two weeks. Before and after this intensified training period subjects underwent a series of tests including a maximal incremental cycle ergometer test (Wmax) with continuous ventilatory measurements and blood lactate values, time trial, basal blood parameter tests (red and white blood profile), hormones [growth hormone (GH), insulin-like growth factor 1(IGF-1), adreno-corticotropic hormone (ACTH), cortisol], neuro-endocrine stress test [short insulin tolerance test (SITT), combined anterior pituitary test (CAPT) and exercise], a shortened Profile of Mood State (POMS), the estimated rate of perceived exertion (RPE) and a cognitive reaction time test. The intensified training period resulted in a significant increase of the training load (p <0.01), training monotony (p <0.01) and training strain (p <0.01). The RPE during training increased significantly (p <0.01) during the intensified training period. Total mood score obtained from the POMS tended to increase (p=0.06), reflecting an increase in worse mood state. A novel finding was that reaction times increased significantly, indicating that overreaching might adversely affect speed of information processing by the brain, especially for the most difficult conditions. After the intensified training period, neither changes in exercise-induced plasma hormone values, nor SITT values were observed. During the CAPT only cortisol showed a significant decrease after the intensified training period. Hemoglobin showed a significant decrease after the intensified training period whereas hematocrit, red blood cell count (RBC) and MCV tended to decrease. The intensified training had no effect on physical performance (Wmax or time trial), maximal blood lactate, maximal heart rate and white blood cell profile. The most sensitive parameters for detecting overreaching are reaction time performance (indicative for cognitive brain functioning), RPE and to a lesser extend the shortened POMS. This strongly suggests, that central fatigue precedes peripheral fatigue. All other systems,including the neuro-endocrine, are more robust and react most likely at a later stage in exhaustive training periods.

Adult↗