Fysiologie als metafoor:Afscheidsrede van Ger J. van der Vusse

Rede uitgesproken ter gelegenheid van het bereiken van de pensioengerechtigde leeftijd door Ger J. van der Vusse, Hoogleraar Fysiologie aan de voormalige Faculteit der Geneeskunde, nu Faculty of Health, Medicine and Life Sciences, van de Universiteit Maastrich

The role of mitochondria in testicular steroid production

The testicular gland is the main androgen producing organ in male animals. The production of androgens is regulated by LH, secreted by the pituitary. The experimental work described in this thesis concerns the role of the rate-limiting step in overall testosterone formation in rat testis, that is the rnitochondrially localized production of pregnenolone. In order to properly characterize cellular and subcellular fractions used in this study, the presence and distribution of specific marker enzymes had to be established in these fractions. Carboxyl esterase has been used to characterize testicular interstitial tissue. Cytochrome £ oxidase and monoamine oxidase have been applied to identify mitochondrial fractions, whereas carboxyl esterase, rotenone-insensitive NADPH-cytochrome £ reductase and steroid sulfatase have been used as marker enzymes for microsomal fractions. Glucose-6-phosphate dehydrogenase and lactate dehydrogenase were assayed as reference enzymes for the particle-free supernatant fraction. In appendix paper I, however, it has been suggested that a small part of lactate dehydrogenase activity is localized in mitochondria of specific cell types in the seminiferous tubules

Cytochrome P450, peroxisome proliferation, and cytoplasmic fatty acid-binding protein content in liver, heart and kidney of the diabetic rat

Diabetes mellitus generally results in an increased systemic fatty acid mobilization which can be associated with an increase in mitochondrial and peroxisomal beta-oxidation of fatty acids in selected tissues. The latter is usually accompanied by a concomitant increase in the tissue content of cytoplasmic fatty acid-binding protein (FABP) which functions in the intracellular translocation of fatty acids. It was previously found that in liver clofibrate-induced proliferation of peroxisomes and increase in FABP expression each are dependent on the induction by cytochrome P4504A1 -mediated (CYP4A1) formation of dicarboxylic acids. We studied whether peroxisome proliferation and an increase of FABP contents in liver, heart and kidney of streptozotocin-induced diabetic rats are also accompanied by an increase of CYP4A1 activity, as this would indicate a possible regulatory role for dicarboxylic acids in peroxisome proliferation and FABP induction in diabetic organs other than liver. In livers of the diabetic rat, a concomitant increase was observed of the activities of CYP4A1 and the peroxisomal key enzyme fatty acyl-CoA oxidase (FACO) and of the FABP content. In the diabetic heart FACO activity and FABP content also increased, but there was no induction of CYP4A1 activity. Conversely, in diabetic kidney there was no increase in FACO activity nor FABP content in spite of a marked induction of CYP4A1 activity. It is concluded that streptozotocin-induced diabetes leads to increased peroxisome proliferation and increased levels of FABP in both liver and heart, which only in liver is accompanied by an induction of the cytochrome P450 system. Consequently, it is not likely that dicarboxylic acids are involved in the induction of peroxisome proliferation in the heart

Striking similarities in systemic factors contributing to decreased exercise capacity in patients with severe chronic heart failure or COPD

Striking similarities in systemic factors contributing to decreased exercise capacity in patients with severe chronic heart failure or COPD. Gosker HR, Lencer NH, Franssen FM, van der Vusse GJ, Wouters EF, Schols AM. Department of Pulmonology, University of Maastricht, the Netherlands. [email protected] AIMS: Chronic heart failure (CHF) and COPD are both characterized by muscular impairment. To assess whether the severity and functional consequences of muscular impairment are disease specific, we compared skeletal muscle function, body composition, and daily activity level relative to exercise capacity between these two disorders. METHODS: Twenty-five patients with CHF and 25 patients with COPD, and 36 healthy gender- and age-matched control subjects underwent measurement of fat-free mass (FFM) [by bioelectrical impedance analysis] as an index of muscle mass. Quadriceps and biceps functions were tested by isokinetic methods, and daily activity level was assessed by the Physical Activity Scale for Elderly (PASE) questionnaire. Peak oxygen consumption (O(2)peak) was measured by incremental cycle ergometry. RESULTS: PASE results were similar in patients with CHF and in patients with COPD, each group scoring lower than control subjects. FFM was also lower in patients than control subjects and correlated closely with quadriceps and biceps strength in all three subgroups, R values ranging from 0.63 to 0.78, with identical slopes. FFM also correlated significantly with O(2)peak (p < 0.05), but slopes were less steep in patients than in control subjects. The type and severity of muscle dysfunction were similar in each group of patients. There were no significant correlations between indexes of cardiopulmonary function and muscle function or exercise performance in patients with CHF or in patients with COPD. In both control subjects and patients, FFM was the most significant determinant of O(2)peak. CONCLUSION: Muscle dysfunction is not limited to the lower limbs, but generalized and comparable between patients with CHF and patients with COPD with similar exercise capacity. FFM is a strong predictor of peripheral muscle strength, to a lesser extent of O(2)peak, and not at all of peripheral muscle enduranc

Enzyme activity of rat tibialis anterior muscle differs between treatment with triamcinolone and prednisolone and nutritional deprivation.

Department of Pulmonology, Nutrition Toxicology and Environment Research Institute Maastricht, University Hospital Maastricht, The Netherlands. The maximal activity of a selection of enzymes involved in muscle carbohydrate handling, citric acid cycle and fatty acyl beta-oxidation were studied after treatment with the fluorinated corticosteroid triamcinolone and compared to a similar treatment of the non-fluorinated corticosteroid prednisolone in an equipotent anti-inflammatory dose. Furthermore, because triamcinolone causes loss of body mass and muscle wasting, the effects of triamcinolone were investigated relative to a control group, with the same loss of body mass, due to nutritional deprivation. The study was performed in male Wistar rats in the following treatment groups: TR, triamcinolone treatment (0.25 mg x kg(-1) x day(-1) for 2 weeks), which resulted in a reduction of body mass (24%); ND, nutritional deprivation (30% of normal daily food intake for 2 weeks) resulting in a similar (24%) decrease of body mass as TR; PR, prednisolone treatment (0.31 mg x kg(-1) x day(-1) for 2 weeks), with a 10% increase in body mass; FF, free-fed control group, with a 12% increase in body mass in 2 weeks. Compared to FF, TR induced an increase in phosphofructokinase (PFK) activity (P < 0.01), glycogen synthase [GS(i + d)] activity (P < 0.05) and glycogen content (P < 0.01) in the tibialis anterior muscle. The PR and ND caused no alterations in PFK or citrate synthase (CS) activity compared to FF. Compared to PR, TR induced an increase in PFK (P < 0.01), CS (P < 0.05) and GS(i + d) activity (P < 0.01). Both TR and PR caused an increased muscle glycogen content, being more pronounced in TR (P < 0.05). Compared to ND, TR induced an increased CS (P < 0.05) and GS(i + d) activity (P < 0.01) and glycogen content (P < 0.01). The ND resulted in a decreased glycogen content compared to FF (P < 0.05). None of the treatments affected the activity of glycogen phosphorylase, beta-hydroxyacyl coenzyme A dehydrogenase and lactate dehydrogenase. It was concluded that corticosteroids led to an increased muscle glycogen content; however, the changes in the enzymes of carbohydrate metabolism were corticosteroid type specific and did not relate to undernutrition, which accompanied the triamcinolone treatment

Altered antioxidant status in peripheral skeletal muscle of patients with COPD

AbstractDespite the growing field of interest in the role of pulmonary oxidative stress in chronic obstructive pulmonary disease (COPD), barely any data are available with respect to antioxidant capacity in the peripheral musculature of these patients. The main objective of this study was to assess in detail the antioxidant status in skeletal muscle of patients with COPD. Biopsies from the vastus lateralis of 21 patients with COPD and 12 healthy age-matched controls were analysed. Total antioxidant capacity, vitamin E, glutathione, and uric acid levels were determined and the enzyme activities of superoxide dismutase, glutathione reductase, glutathione peroxidase, and glutathione-S-transferase were measured. Malondialdehyde was measured as an index of lipid peroxidation. The total antioxidant capacity and the uric acid levels were markedly higher in COPD patients than in healthy controls (25%, P=0.006 and 24%, P=0.029, respectively). Glutathione-S-transferase activity was also increased (35%; P=0.044) in patients compared to healthy subjects. Vitamin E level was lower in patients than in controls (P<0.05). The malondialdehyde level was not different between the two groups. It can be concluded that the muscle total antioxidant capacity is increased in patients with COPD. Together with the reduced vitamin E levels, the increased glutathione-S-transferase activity and normal levels of lipid peroxidation products, these findings suggest that the antioxidant system may be exposed to and subsequently triggered by elevated levels of reactive oxygen species