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Biomedical subjects

M Krotkiewski

Publications and source records attributed to M Krotkiewski.

At least 19 recordsLinked to original sources

Upper motor neuron lesions: their effect on muscle performance and appearance in stroke patients with minor motor impairment.

OBJECTIVE: To evaluate muscular performance and appearance in patients with prior stroke who were ambulatory. DESIGN: Nonrandomized study. SETTING: University hospital laboratory. SUBJECTS: Sixteen persons (11 men, 5 women) with minor motor impairments, 6 to 24 months after stroke, were included. As reference, data were used from a population-based sample of 144 men and women. MAIN OUTCOME MEASUREMENTS: Muscle performance was evaluated using a Kin-Com dynamometer in both the affected and the nonaffected leg. Peak isometric strength was measured at a 60 degree angle in both extension and flexion. Maximal isokinetic strength was measured at 60 degrees/sec and at 180 degrees/sec. Endurance was evaluated during isometric and dynamic knee extensions. Muscle biopsies were taken on nine patients and muscle tissue areas were determined with computed tomography. RESULTS: The affected leg was weaker but not different in relative endurance compared with the nonaffected side. The performance of the nonaffected side was somewhat lower than that of a matched reference population. No major difference in fiber composition between the affected and nonaffected legs was noted, except for a lower degree of capillarization in the affected leg. CONCLUSION: In well-functioning stroke patients with good motor performance, further muscle training that includes resistance exercise might be indicated.

Adult

High blood pressure and muscle morphology/metabolism--causal relationship or only associated factors?

As muscle tissue constitutes a main target organ for glucose metabolism and is responsible for the development of insulin resistance, it seems plausible to elucidate the relationship between blood pressure and muscle morphology and metabolism. The association between blood pressure and capillarization/morphology of the vastus lateralis muscle and metabolic variables was evaluated in 24 perimenopausal obese women [body mass index (BMI) 34.9 +/- 1.1; waist-hip ratio (WHR) 0.90 +/- 0.02]. The muscle enzyme activity of lipoprotein lipase (LPL), citrate synthase and glycogen synthase was determined. There was a significant negative correlation between the percentage of type I fibres and relative fibre area of type I on the one hand and systolic and diastolic blood pressure on the other. There was a negative correlation between the capillary density (i.e. number of capillaries/muscle fibre) and a positive correlation between the diffusion distance (fibre area supplied by one capillary) and diastolic blood pressure. The activities of LPL and citrate synthase were positively correlated with the percentage of type I and negatively correlated with the percentage of type II muscle fibres. The activity of LPL was also negatively correlated with plasma glucose and the insulin/C-peptide ratio. The insulin/C-peptide ratio was positively correlated with the percentage of type II muscle fibres. In stepwise multiple regression analyses, 20-30% of the variation in systolic and diastolic blood pressure could be explained by the variables of muscle fibre distribution. Excluding muscle morphological variables from the regression model, the insulin/C-peptide ratio accounted for 13% of the variation in systolic and diastolic blood pressure. The results of the study show the close association between muscle morphology and blood pressure. It remains to be elucidated whether this association indicates a causal relationship.

Adult

Effects of two antiandrogen treatments on hirsutism and insulin sensitivity in women with polycystic ovary syndrome.

Thirty-two women with polycystic ovary syndrome (PCOS) were allocated to two antiandrogen treatment regimens; 28 women completed the trial. Twenty women were treated with ethinyloestradiol and cyproterone acetate (EO-CA) cyclically for 6 months and eight women were treated with the gonadotrophin releasing hormone (GnRH) analogue, goserelin for 6 months. Effects on hirsutism, insulin sensitivity (estimated by glucose clamp technique), blood lipids and hormones were measured. Women treated with EO-CA showed a reduction in hirsutism (P <0.05), and decreased serum androgen concentrations (P <0.001) as well as reduced insulin sensitivity (P <0.05). In women treated with goserelin, serum androgen concentrations also decreased (P <0.001), but there was no significant reduction of hirsutism. This group, however, showed an improved insulin sensitivity (P <0.05) despite an unchanged body mass index. Bone mineral density was unaltered in both treatment groups. The reduction in androgen concentrations caused by EO-CA was not paralleled by increased insulin sensitivity, most probably due to the effect of ethinyloestradiol per se. In contrast, the reduction in androgen concentrations by goserelin was accompanied by an improved insulin sensitivity.

Adult

Small doses of triiodothyronine can change some risk factors associated with abdominal obesity.

OBJECTIVE: To elucidate whether the administration of small doses of triidothyronine (T3) can increase concentrations of sex hormone binding globulin (SHBG) in obese women with different types of obesity and to evaluate the potential metabolic benefits of such treatment. DESIGN: Daily administration of 20 micrograms of T3 during six weeks while maintaining habitual food intake and physical activity. SUBJECTS: Seventy premenopausal obese women (age: 41.2 +/- 1.5 y mean +/- s.e.m., body mass index (BMI): 34.4 +/- 0.7). MEASUREMENTS: Plasma concentrations of SHBG, lipids, insulin, thyroid hormones, sex hormones, blood glucose and insulin sensitivity (by euglycemic insulin clamp in 12 patients) at base line after six weeks of treatment. RESULTS: Six weeks treatment with small doses of T3 resulted in a significant increase in plasma SHBG. The increase of SHBG was higher in abdominal obesity and not associated with a significant change in body weight, plasma insulin concentration, insulin/glucose ratio of plasma insulin sensitivity (glucose disposal during insulin clamp). In patients with initially high SHBG the significant increase of insulin removal (as judged from the increase of c-peptide/insulin ratio) was observed. Treatment resulted in a reciprocal increase of T3, decrease of thyroxine (T4), and a more than double increase of T3/T4 ratio. CONCLUSIONS: Administration of small doses of T3 can increase the concentration of SHBG without changing insulin concentrations or sensitivity. As there was a significant decrease (by 36%) of T4 and parallel increase of T3 with a clear increase of T3/T4 ratio it seems possible that rather than lack of thyroid hormones a lower peripheral deiodination of T4 might be a factor contributing to the low SHBG concentration in abdominal obesity. Treatment with small doses of T3 may be considered to ameliorate some of the risk factors associated with abdominal obesity, particularly in some subgroups of obese women with a relative resistance to thyroid hormones possibly dependent on decreased peripheral deiodination of thyroxine.

Abdomen

Lipid peroxides production after strenuous exercise and in relation to muscle morphology and capillarization.

The antioxidative capacity of slow twitch muscle fibers has been reported to be higher than that of fast twitch ones. The purpose of this study was to relate the production of lipid peroxides during exercise to the morphology and capillarization of human muscles. Twenty-seven healthy volunteers performed a strenuous 90-min exercise. The content of malonyldialdehyde (MDA) in the middle portion of vastus lateralis muscle was found positively correlated with percentage and the relative cross-sectional area of the type 1 of muscle fibers (r = 0.46, P < 0.05, r = 0.43, P < 0.05, respectively) but negatively with type II muscle fibers (r = -0.46, P < 0.05, r = -0.43, P < 0.05, respectively), especially type IIB. The content of MDA in the vastus lateralis muscle correlated positively with the number of capillaries around type II muscle fibers (r = 0.71, P < 0.001). It is suggested that the production of lipid peroxides parallels the exercise-induced increase of oxygen uptake in the muscle, being highest in more oxidative and better perfused, oxygen-consuming muscle fibers.

Adult

Effects on muscle of dieting with or without exercise in overweight postmenopausal women.

The main aim of this study was to investigate the effect of an energy-restrictive, high-protein diet with or without exercise on muscle morphology and biochemistry. Moderately overweight postmenopausal women (49-58 yr, body mass index: 25-42 kg/m2) were randomly assigned to three groups for 12 wk of intervention; namely, a control group, a group on a 4.2 MJ/day diet, and a group on 4.2 MJ/day diet combined with aerobic and anaerobic exercise. Muscle morphology and biochemistry analysis were performed in 69 and 58 women, respectively. In contrast to the diet-only group, the die-plus- exercise group significantly increased the muscle fiber areas by 20-25%, the number of capillaries per muscle fiber type I by approximately 20%, and the activities of citrate synthase by approximately 35% and hexokinase by approximately 20% (P < 0.05). There were no statistically significant changes in any other muscle variable (P < 0.05). The respiratory exchange ratio decreased in both intervention groups by 2-4% (P < 0.01). It is concluded that 12-wk period of an energy-restrictive high-protein diet was not associated with major changes in muscle morphology or biochemistry. The addition of exercise to the die led to an adaptive increase in muscle fiber areas and in the oxidative capacity of the muscles.

Diet

The concentrations of monoamine metabolites and neuropeptides in the cerebrospinal fluid of obese women with different body fat distribution.

DESIGN AND SUBJECTS: Several studies suggest neuroendocrine abnormalities in, particularly, abdominal, central obesity in humans, a condition with high morbidity and mortality. Therefore the concentrations of neuropeptides and catecholamines in cerebrospinal fluid (CSF) were analysed in 48 obese women, subdivided into groups with central, abdominal and gluteo-femoral distribution of body fat, utilising the waist-to-hip circumference ratio (WHR) for division. RESULTS: In comparisons with non-obese control women concentration of 5-hydroxyindol acetic acid (5-HIAA), methoxyhydroxyphenylglycol (MHPG), corticotropin releasing hormone (CRH), beta-endorphins (END) and neuropeptide Y (NPY) were lower, while homovanillic acid (HVA) was not different in obese women, HIAA, HVA and END correlated negatively with the WHR only in abdominally obese women, suggesting a threshold effect. HIAA vs HVA as well as CRF vs END correlated strongly in the total and both subgroups. An interrelationship between all these four substances was found in abdominal but not in gluteo-femoral obesity, suggesting a tighter functional coupling in the former group. Several correlations were found between CSF substance levels and appetite registrations, including END vs voracious eating, and for carbohydrate craving vs HIAA and vs HVA (negatively). This was also found only in abdominally obese women. CONCLUSION: Although the concentrations of monoamine metabolites and neuropeptides in the CSF sampled at the level of the lumber spine might not be representative for those at regulatory centers in the brain, the findings suggest that low 5-HIAA is characteristic of human obesity, and coupled to CRH as well as eating abnormalities, particularly in abdominal obesity. Since CRH is regulating the balance between the autonomic nervous systems, insulin secretion and thermogenesis in animals, corresponding anomalies in abdominal obesity in humans may have a central origin.

Adipose Tissue

Phosphate supplementation prevents a decrease of triiodothyronine and increases resting metabolic rate during low energy diet.

Thirty overweight women participated in 8 week slimming program consisting of a self-controlled low-energy diet (4.2 MJ/day) supplemented with highly viscous fibres and mineral tablets containing calcium, potassium and sodium phosphates (Redusan Combi, Biokraft Pharma AB, Sweden). Half of the patients received in double blind manner mineral tablets during first 4 weeks and placebo (without phosphates) during next 4 weeks (group 1) while the remaining patients were treated (cross-over) with placebo first and mineral tablets in the final period (group 2). The rate of weight loss was similar in groups 1 and 2 (4.7 vs 5.2 kg during the first 4 weeks and 2.7 vs 3.0 kg in the further 4 weeks). During periods of phosphate supplementation, the resting metabolic rate (RMR) increased by approx. 12% (p < 0.05) in group 1 and 19% (p < 0.05) in group 2. Phosphate supplementation ameliorated also a decrease in plasma triiodothyronine level and a decrease in thyroxine to triiodothyronine ratio. There were no differences between groups in the plasma insulin, catecholamine, growth hormone, cortisol and testosterone levels. Phosphate supplementation did not affect plasma lipids or blood glucose concentration. It is concluded that phosphate supplementation in obese patients on a low-energy diet enhances RMR irrespectively of the rate of weight loss. This effect seems to be, at least partly, due to an influence of phosphates on peripheral metabolism of thyroid hormones.

Adult

Role of muscle morphology in the development of insulin resistance and metabolic syndrome.

Type IIB muscle fibres are among the most insulin-insensitive muscle fibres and are not adapted to oxidation of fat during muscle work. The first characteristic of this type of muscle fibre most probably reflects or contributes to further development of insulin resistance contribute to further perpetuation of obesity and to the channeling of excess free fatty acids to the liver followed by secondary deterioration of its function. The impaired functioning of the liver is epitomized, among other changes, by impairment of insulin extraction. The increasing hyperinsulinaemia is followed by inhibition of synthesis of specific proteins such as carrier proteins for transporting testosterone (sex hormone binding globulin, SHBG). This results in an increased free testosterone concentration which induces androgenization in women and may further increase insulin insensitivity in abdominal obesity in women. The poor capillarization and changed muscle morphology in spite of great interindividual variety is observed in several pathological conditions characterised by insulin sensitivity (stroke, PCO, hypertension, diabetes, obesity). It is suggested that, in addition to the previous concept of the main role of intraabdominal adipose tissue, even muscles and liver are also important organs contributing to the pathogenesis and development of the metabolic syndrome.

Exercise

Muscle fiber composition and capillary density in women and men with NIDDM.

OBJECTIVE: To determine whether muscle fiber composition and capillary density differed between diabetic and nondiabetic subjects. RESEARCH DESIGN AND METHODS: Muscle fiber composition and capillary density were determined in biopsies from women and men with non-insulin-dependent diabetes mellitus (NIDDM) and compared with those of control subjects matched for gender, age, obesity, and the waist-to-hip ratio, which are all factors known to influence muscle morphology. RESULTS: Patients with NIDDM, as well as control subjects with abdominal obesity and insulin resistance, showed the same abnormalities in muscle morphology, namely, a low percentage of type I fibers, elevated type II (particularly type IIB) fibers, and a low capillary density. These changes correlated closely with insulin concentrations in both diabetic and nondiabetic groups. CONCLUSIONS: Recent information suggests that insulin may regulate myosin synthesis in muscle in the direction of the changes observed. Therefore, it is possible that muscle fiber composition abnormalities in insulin-resistant conditions are secondary to hyperinsulinemia. However, the low capillary density, hypothetically, may contribute to insulin resistance.

Biopsy

Effects of acute exercise on insulin and non-insulin-dependent glucose uptake in normal and moderately obese women.

OBJECTIVES: To investigate the effectiveness of exercise on the regulation of insulin sensitivity. METHODS: Eleven premenopausal women, with body fat mass from the normal range to moderate obesity, were examined with glucose clamp at 10 mmol/L glucose concentration to determine insulin-dependent and non-insulin-dependent (after somatostatin inhibition of endogenous insulin production) glucose uptake (= IDGU and NIDGU respectively) before and 24 hrs after a glycogen-decreasing exercise. RESULTS: IDGU, but not NIDGU, increased after exercise. The degree of increase of IDGU after exercise showed negative correlations with body mass index (borderline, significance), the waist to hip circumference ratio, fasting free testosterone and free fatty acid concentrations, as well as diastolic blood pressure (borderline significance), and a positive relationship to sex hormone binding globulin concentration and IDGU before exercise. CONCLUSION: It is concluded that only IDGU contributes to the augmentation of insulin sensitivity after a glycogen-decreasing exercise in women. Additionally, the increase of IDGU is less in abdominal obesity, and negatively dependent on free fatty acid concentrations, hyperandrogenism and hyperinsulinaemia, all putative pathogenetic factors for insulin resistance.

Adult

Uptake of glucose carbon in muscle glycogen and adipose tissue triglycerides in vivo in humans.

Glucose disposal into muscle glycogen has previously been directly studied after intravenous, but not after physiological, oral administration. In this study 100 g glucose, containing 50 microCi [U-14C]glucose, were taken orally by premenopausal women in the overnight fasting state or after a carbohydrate-rich meal. After 4 h, biopsies were taken from the vastus lateralis muscle and abdominal and femoral subcutaneous adipose tissue for determinations of label in isolated glycogen and triglycerides, respectively. Uptake of administered glucose carbon in muscle glycogen was estimated to be approximately 20 g in the fasting and approximately 9 g in the carbohydrate-fed groups, respectively. Total uptake in adipose tissue triglycerides was approximately 2 g. Glucose carbon uptake in muscle glycogen correlated positively with glucose infusion rates during euglycemic hyperinsulinemic glucose clamps, glycogen synthase activity in vitro, and type I muscle fiber distribution and fiber area. Negative correlations were found between glucose uptake in adipose tissue triglycerides, type II fiber distribution and fiber area, as well as the waist-to-hip circumference ratio and degree of obesity. It was concluded that muscle glycogen is probably not a major pathway for disposal of oral glucose carbon in the sedentary condition.

Adipose Tissue

Androgen treatment of middle-aged, obese men: effects on metabolism, muscle and adipose tissues.

OBJECTIVES: This pilot investigation was conducted to explore the relationship between androgens and glucose tolerance in obese men and to select an optimal mode for androgen treatment. METHODS: For exploratory purposes, testosterone (T) or dihydrotestosterone (DHT) were given in different doses and preparations for different periods of time to obese, middle-aged men. The administration forms were selected in order to by-pass the liver. In the first two studies T was given as a single intramuscular injection of 250 or 500 mg and the results evaluated after 1 week. In two subsequent studies testosterone was administered in moderate doses either as oral T undecanoate or a T and DHT in preparations applied on the skin for transdermal absorption for 6 weeks and 3 months respectively. Before and after treatment the following examinations were performed: glucose tolerance tests with insulin determinations or euglycemic clamps at submaximal insulin levels. Anthropometric measurements including the waist/hip circumference ratio and estimations of body fat and lean body mass (from measurements of whole body potassium content) were performed. Plasma triglyceride and cholesterol concentrations, liver function tests and blood pressure were followed. Physical examination including the prostate was performed before and after study. Muscle function, glycogen synthase and morphology were examined in the 3-month study. RESULTS: Administration of T was followed by moderate increases of circulating T concentrations in all studies, except after injection of 500 mg, where large increases were seen. Follicle stimulating hormone and luteinizing hormone levels decreased consistently. Injection of 500 mg T resulted in a decreased glucose tolerance. In the other treatment groups, plasma insulin decreased or glucose disappearance rate increased in clamp measurements, suggesting improved insulin sensitivity. This was most pronounced in men with relative hypogonadism from the outset. In the study of 3 months duration, a decrease in the waist/hip ratio, without a change in body fat mass, was also seen. Plasma lipids, liver function tests and blood pressure did not change. Muscle strength, the fractional velocity of glycogen synthase as well as the percentage and diameter of type IIB fibres increased after T treatment. No adverse effects were seen. 17 -beta oestradiol concentrations were unaltered and DHT administration was less effective than T, suggesting that T rather than derivatives of this hormone was mainly responsible for the effects observed. CONCLUSION: The results suggest that T administration to middle-aged, obese man may have beneficial effects.

Adipose Tissue

Hemorheological disturbances, metabolic parameters and blood pressure in different types of obesity.

Body fat distribution characterized by a high waist/hip ratio (WHR) has been described as a risk factor in the incidence of cardiovascular diseases and associated mortality. Hemorheological changes have been shown to accompany several risk factors. Gynoid and android obese women were compared in the present study with respect to hemorheological and metabolic variables and blood pressure. The android obese women had a significantly higher hematocrit and red blood cell count and showed higher blood viscosity at both high and low shear rates than women with the gynoid obesity type. Blood pressure was also higher in the android group. No significant differences were shown in concentration of cholesterol or triglycerides in serum nor in the microrheological properties of the red blood cells. The filterability index, which mirrors the number of rigid erythrocytes in the blood, was found to correlate with the plasma insulin concentration (r = 0.78, P less than 0.05) in the android but not in the gynoid obese women. It is concluded that the pathological changes in blood rheology observed in the android obese women may contribute to the high rate of cardiovascular events and associated mortality reported in this type of obesity.

Adipose Tissue

Effects of a sodium-potassium ion-exchanging seaweed preparation in mild hypertension.

A nonpharmacological approach in the treatment of mild hypertension is often advocated. In an attempt to decrease sodium and increase potassium intake, sixty-two middle-aged patients with mild hypertension were given a potassium loaded ion-exchanging sodium-adsorbing potassium-releasing seaweed preparation (seaweed fiber, SF). The mean blood pressure (MBP), evaluated in a double-blind crossover manner with four weeks familiarization and wash-out periods, showed a significant decrease after four weeks on 12 and 24 g/day SF but not on 6 g/day or placebo treatment. Systolic blood pressure during submaximal exercise decreased on all three SF doses. The decrease in MBP appeared to be significantly higher in sodium-sensitive (11.2 mm Hg, P less than .001) than in sodium-insensitive (5.7 mm Hg, P less than .05) patients and was in salt-sensitive patients significantly correlated to the increase in plasma renin activity (PRA). The urinary sodium excretion decreased, the urinary potassium increased and the sodium/potassium urinary excretion ratio decreased, indicating that the decrease of MBP was dependent on the decreased intestinal absorption of sodium and increased absorption of potassium released from the seaweed preparation. A sodium-potassium ion-exchanging seaweed preparation is an effective means of decreasing sodium and increasing potassium intake, and may be used for antihypertensive treatment in mild hypertension.

Adult