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Biomedical subjects

P Kaiser

Publications and source records attributed to P Kaiser.

At least 91 records · Page 5Linked to original sources

Decreased insulin secretory response of pancreatic islets during culture in the presence of low glucose is associated with diminished 45Ca2+ net uptake, NADPH/NADP+ and GSH/GSSG ratios.

In isolated rat pancreatic islets maintained at a physiologic glucose concentration (5.6 mM) the effect of glucose on parameters which are known to be involved in the insulin secretion coupling such as NADPH, reduced glutathione (GSH), 86Rb+ efflux, and 45Ca++ net uptake were investigated. The insulinotropic effect of 16.7 mM glucose was decreased with the period of culturing during the first 14 days being significant after 2 days though in control experiments both protein content and ATP levels per islet were not affected and insulin content was only slightly decreased. Both NADPH and GSH decreased with time of culture. 86Rb+ efflux which is decreased by enhancing the glucose concentration from 3 to 5.6 mM in freshly isolated islets was not affected by culturing whatsoever, even not after 14 days of culture when there was no longer any insulin responsiveness to glucose. The 45Ca++ net uptake was decreased during culturing. The data indicate (1) that the diminished glucose-stimulated release of insulin during culturing is not due to cell loss or simple energy disturbances, (2) that more likely it is the result of a diminished 45Ca++ net uptake as a consequence of the inability of islet cells to maintain proper NADPH and GSH levels, and (3) that potassium (86Rb+) efflux may not be related to changes of NADPH and GSH.

Adenosine Triphosphate↗

Synaptophysin: molecular organization and mRNA expression as determined from cloned cDNA.

Synaptophysin is a major glycoprotein of Mr approximately 38,000 (in deglycosylated form: Mr approximately 34,000) characteristic of a certain class of small (30-80 nm diameter) neurosecretory vesicles, including presynaptic vesicles, but also vesicles of various neuroendocrine cells of both neuronal and epithelial phenotype. Using synaptophysin-specific antibodies we have isolated cDNA clones from rat nervous tissue libraries, which identify an approximately 2.5-kb mRNA in rat and human cells, including neuroendocrine tumours, that contains a reading frame for a polypeptide of 307 amino acids with a total mol. wt of 33 312. The deduced amino acid sequence, which was partly confirmed by comparison with sequences of two tryptic peptides obtained from purified synaptophysin, revealed four hydrophobic regions of 24 amino acids each, which are characterized, according to conformation prediction analyses, by marked alpha-helicity. The sequence shows a single potential N-glycosylation site, which is assigned to the vesicle interior, and a carboxy-terminal tail of 89 amino acids which contains glycine-rich tetrapeptide repeats, the epitope of monoclonal antibody SY38, and a number of collagenase-sensitive sites accessible on the surface of the intact vesicles. These features suggest that the polypeptide spans the vesicle membrane four times, with both N and C termini located on the outer, i.e. cytoplasmic, surface of the vesicles.

Amino Acid Sequence↗

Muscle metabolism during intense, heavy-resistance exercise.

The objective of this study was to examine the muscle metabolic changes occurring during intense and prolonged, heavy-resistance exercise. Muscle biopsies were obtained from the vastus lateralis of 9 strength trained athletes before and 30 s after an exercise regimen comprising 5 sets each of front squats, back squats, leg presses and knee extensions using barbell or variable resistance machines. Each set was executed until muscle failure, which occurred within 6-12 muscle contractions. The exercise: rest ratio was approximately 1:2 and the total performance time was 30 min. Concentrations of adenosine triphosphate (ATP), creatine phosphate (CP), creatine, glycogen, glucose, glucose-6-phosphate (G-6-P), alpha-glycerophosphate (alpha-G-P) and lactate were determined on freeze-dried tissue samples using fluorometric assays. Blood samples were analyzed for lactate and glucose. The exercise produced significant reductions in ATP (p less than 0.01) and CP (p less than 0.001), while alpha-G-P more than doubled (p less than 0.05), glucose increased tenfold (p less than 0.001) and G-6-P fourfold (p less than 0.001). Muscle lactate concentration at cessation of exercise averaged 17.3 mmol X kg-1 w. w. Glycogen concentration decreased (p less than 0.001) from 160 to 118 mmol X kg-1 w. w. It is concluded that high intensity, heavy resistance exercise is associated with a high rate of energy utilization through phosphagen breakdown and activation of glycogenolysis.

Adult↗

Effect of beta 1-selective and non-selective beta-blockade on work capacity and muscle metabolism.

Six well-trained men were studied while performing a maximal bicycle exercise. The seven experiments included in this study were randomized in a double-blind cross-over fashion. On each occasion the subjects were given either placebo or 40, 80, or 160 mg propranolol (non-selective blockade) or 25,50, or 100 mg atenolol (beta 1-selective blockade). After completion of the study each subject had performed once under each of the seven treatments. Heart rate, maximal oxygen uptake (Vo2max), blood lactate and performance time to exhaustion were measured. A muscle biopsy from vastus lateralis was taken at exhaustion after placebo, 80 mg propranolol and 50 mg atenolol trials, for analysis of ATP, creatine phosphate (CP), glucose-6-phosphate (G-6-P), glucose and lactate. The performance time was reduced (P less than 0.05-0.001) with both blockers compared to placebo. At an equal heart rate reduction, Vo2max was equally reduced by both blockers. Performance time, on the other hand, was reduced to a greater extent (P less than 0.05) with propranolol. ATP and CP levels were decreased (P less than 0.05) by both drugs. G-6-P, however, was lower (P less than 0.05) with propranolol than with either placebo or atenolol. No difference was observed between placebo and atenolol. In conclusion, both beta1-selective and non-selective blockade reduced short-term maximal exercise capacity. The major limiting factor seems to be the reduction in oxygen transport. The finding that at an equivalent reduction in Vo2max propranolol reduced performance time to a greater extent than atenolol suggests that beta 2-blockade may reduce performance by mechanisms additional to those that affect oxygen transport.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

Effect of beta 1-selective and nonselective beta blockade on blood pressure relative to physical performance in men with systemic hypertension.

Eleven physically active men with systemic hypertension were studied after 5 weeks of treatment with placebo, atenolol or propranolol. A double-blind, crossover randomized design was used. Blood pressure (BP), heart rate (HR), physical performance capacity, rate of perceived exertion and blood lactate concentrations were measured during rest, exercise to exhaustion and postexercise, at 8 and 24 hours after intake of the last dose. Blood pressure at rest and during exercise was similarly decreased with both drugs (8 and 24 hours), and there was no difference between 8 and 24 hours with any of the treatments. Heart rate (8 hours) was decreased similarly by both drugs, but after 24 hours, HR at increased workloads (above 120 watts) was higher with atenolol compared with propranolol. Maximal HR was lower with propranolol than atenolol at both 8 and 24 hours. Maximal exercise loads (8 and 24 hours) were 231 and 232 watts with placebo, 211 and 212 with propranolol and 228 and 227 with atenolol. That is, maximal workload was decreased with propranolol compared with placebo and atenolol at both 8 and 24 hours. No difference was found between placebo and atenolol at either 8 or 24 hours. The rate of perceived exertion values were higher with propranolol than atenolol. Blood lactate concentrations did not differ according to treatments. The results indicate that atenolol, when given in a dose that decreases resting and exercise BP to the same extent as propranolol, limits physical performance less than propranolol.

Adult↗

Skeletal muscle glycolysis during submaximal exercise following acute beta-adrenergic blockade in man.

The present study describes the influence of beta-adrenergic blockade on glycogen utilization and lactate accumulation in skeletal muscle of exercising man. Twelve physically active men were examined during 25 min of continuous cycle exercise equivalent to 65% of their maximal oxygen uptake both with and without oral administration of 80 mg of propranolol (Inderal). Heart rate, oxygen uptake, rate of perceived exertion (RPE) and blood lactate concentration were measured during exercise. Muscle biopsies were obtained from m. vastus lateralis after 5 and 25 min of exercise. Beta-adrenergic blockade decreased steady state exercise heart rate by (mean +/- SD) 35 +/- 10 beats . min-1 (P less than 0.001) and oxygen uptake from 2.47 to 2.39 l . min-1 (P less than 0.01). Muscle glycogen decreased from the 5th to the 25th min of exercise, and beta-blockade had no significant effect on this decrease. In contrast to without drug, beta-blockade resulted in a decrease (P less than 0.05) in muscle lactate concentration from the 5th (6.9 mmol . kg-1 w./w.) to the 25th min (4.8 mmol . kg-1 w./w.). Similarly blood lactate levels were lower (P less than 0.05) with than without beta-blockade in the last but not the first 10 min of exercise. The alteration in muscle lactate concentration pattern following beta-blockade, may imply that adrenergic effects per se contribute to the stimulation of glycolysis during submaximal exercise, except in its earliest phase. Nevertheless, the effect is not great enough to produce substantial differences in glycogen utilization.

Adult↗

Pericentric inversions. Problems and significance for clinical genetics.

A review is given of the incidence, cytogenetics, and biologic relevance of pericentric inversions (pii). In 251 cases in the literature and our patients, 96 different inversion forms with different breakpoints are found. Eighteen of these cases have been observed several times in unrelated families; they are classified as types. The problem of pii in the heterochromatic regions of chromosomes 1 and 9 is especially emphasized and the investigations required are pointed out. The significance of the individual pii is checked with regard to their behavior in meiosis and their phenotypical relevance. An approximately 1:1 segregation is found. Fertility, stillbirth, and rates of abortion are not statistically altered. The gonadal findings available at present in man are reported and commented on. The occurrence of aneusomic recombinants among the live offspring of carriers shows a marked dependence on the length of the relative inversion segments. Since these are distinctly below average in inversion types, they only result in recombinants in exceptional cases. Certain pointers to an above-random common occurrence of other chromosomal aberrations are not found in families with pii. A correlation between pii and clinical symptoms likewise cannot be detected. However, in this connection it is pointed out that trisomic mosaics were observed jointly with pii(9) and pii(22). The review is completed by a brief examination of the literature concerning the significance of pii in evolution.

Animals↗

Therapeutic and metabolic effects of sotalol.

In a single-blind, randomized study, the cardiovascular and metabolic effects of sotalol, 40 to 160 mg/day, in six patients with mild essential hypertension were compared to those of placebo at rest and during submaximal dynamic exercise. Resting blood pressure was controlled by sotalol but not the pressor response to exercise, despite reduction of tachycardia. The major metabolic finding on sotalol was an approximately 40% decrease in lipid mobilization during exercise. Alterations in muscle lactate concentrations were much like those caused by other beta-blockers. Plasma concentrations of norepinephrine and epinephrine were doubled during exercise on sotalol, epinephrine disposition more so. No effects on serum lipoproteins were observed after 6 wk on sotalol in therapeutic doses. Despite its special electrophysiologic properties, sotalol appears to induce the same cardiovascular and metabolic changes during exercise as do other beta-blockers.

Adult↗

Isometric muscle endurance during acute beta-adrenergic blockade.

Isometric muscle endurance was measured in fourteen physically active men without (placebo) and after acute oral administration of 160 mg propranolol (Inderal). Quadriceps muscle contractions were sustained at 65% maximum voluntary contraction (MVC) to exhaustion. Muscle biopsies were obtained from m. vastus lateralis at rest for subsequent histochemical analysis for myofibrillar ATPase and amylase-PAS in order to determine fiber type composition and capillary density. The time to exhaustion was shorter (p less than 0.01) during beta-blockade (0.82 +/- 0.22) min than placebo (0.90 +/- 0.23) min. Changes in endurance time, induced by beta-blockade, were not correlated with any of the muscle morphological or histochemical variables examined. It is concluded that muscular performance is impaired as a result of beta-blockade on muscle tissue irrespective of any concomitant change in central circulation.

Adenosine Triphosphatases↗

Muscle capillary supply and fiber type characteristics in weight and power lifters.

Muscle tissue samples were obtained from vastus lateralis muscle of elite weight/power lifters (WL/PL, n = 8), endurance athletes (EA, n = 8), and nonathletes (NA, n = 8). Histochemical stainings for myofibrillar ATPase, NADH-tetrazolium reductase, and amylase-periodic acid-Schiff, respectively, were undertaken to assess relative distribution of fast-twitch (FT) and slow-twitch (ST) muscle fiber types, fiber size, and capillary supply [capillaries per fiber (cap X fib-1) and capillaries per mm2 (cap X mm-2)]. Fiber type distribution in WL/PL, EA, and NA averaged 59 +/- 6 (SD), 40 +/- 11, and 61 +/- 10% FT. Values for mean fiber area and FT/ST area were significantly greater in WL/PL compared with values obtained in EA and NA. Similar values for cap X fib-1 were observed WL/PL (2.06 +/- 0.74) and NA (2.16 +/- 0.34). EA exhibited greater cap X fib-1 (3.11 +/- 0.73) than WL/PL (NS) and NA (P less than 0.01). However, cap X mm-2 in WL/PL (199 +/- 29) was lower than in EA (401 +/- 61, P less than 0.001) and NA (306 +/- 29, P less than 0.01). It is suggested that heavy resistance training in contrast to endurance training does not result in increased capillary density. Instead, as a consequence of fiber hypertrophy induced by muscle overloading, capillary density is decreased.

Adult↗

Physical performance and muscle metabolism during beta-adrenergic blockade in man.

The major findings of the present study may be summarized as follows: Muscle strength, measured as maximal isokinetic torque and maximal dynamic muscle power, measured as the highest 5 s power output during a 30 s maximal cycle exercise test, were unaltered by beta-blockade. When maximal exercise was prolonged to 30-60 s, anaerobic endurance, measured both as average power during 30 s maximal cycle exercise and as static endurance time at 65% of maximal voluntary contraction force, was decreased by beta-blockade. On the other hand, anaerobic endurance measured as peak torque decline during 50 repeated maximal isokinetic contractions was unaffected by beta-blockade. Aerobic power, measured as maximal oxygen uptake (VO2max) during cycle exercise, was decreased by beta-blockade. In addition, aerobic endurance was decreased by beta-blockade when measured as both time to fatigue during 10 min cycling and as time for a 2000 m run. When comparing the effects of beta 1-selective and non-selective beta-blockade on work capacity, no differences were demonstrated with regard to muscle strength, muscle power, and aerobic power (VO2max). Aerobic endurance was decreased to a greater extent by non-selective than by beta 1-selective blockade, when similar reductions in heart rate and VO2 max were attained. The difference in aerobic endurance between the two types of blockers indicates that factors other than an effect on oxygen transport, are responsible for the further reduction in endurance induced by the non-selective blockade. These factors are most likely local metabolic factors. Similarly, work capacity was reduced to a greater extent by non-selective than beta 1-selective blockade when similar reduction in blood pressure were attained by both drugs in hypertensive patients. Muscle G-6-P concentration was reduced by non-selective, but not by beta 1-selective blockade, suggesting a beta 2-mediated retardation of glycolysis. The effects of beta-blockade on VO2max and work capacity shown during acute administration persisted during long-term treatment.

Adrenergic beta-Antagonists↗

Semi-automatic blood lactate assay: experiences from an exercise laboratory.

A semi-automatic system based on flow injection analysis (FIA) for the transportation of small sample aliquots has been combined with fluorometric, enzymatic methods for blood lactate determination and has been described earlier. In the present study duplicate blood samples were obtained from exercising subjects to enable a comparison of lactate concentrations between neutralized and non-neutralized samples. Duplicate samples were also obtained to enable FIA lactate values to be compared to those obtained with a manual enzymatic method, and with a colorimetric method. No significant change was observed if the sample was not neutralized, enabling a more rapid sample turnover. The FIA method was reliable, with a coefficient of variation of 4.9% between duplicate blood samples. FIA lactate values were valid when compared to two other manual assays. FIA has been shown to be a rapid (60 samples x h-1) means of accurately determining blood lactate concentrations with 25 microliter blood samples and is of particular relevance to the exercise laboratory.

Automation↗

Alpine skiing and acute beta-blockade.

The effect of acute unselective (propranolol) and beta 1-selective (atenolol) beta-adrenoceptor blockade was studied on alpine skiing in six leisure and seven elite skiers. Prior to the skiing tests a short time "all out" cycle ergometer test (Wingate muscle power test) was performed to confirm whether a beta-blocking effect (80 mg propranolol and 100 mg atenolol orally) was present or not. Peak and average power of the Wingate test showed an impairment in the order of 4%--6% (P less than 0.05--0.001). Peak blood lactate was only reduced after propranolol (0.05 greater than P greater than 0.01). During leisure skiing under submaximal exercise conditions peak blood lactate was increased (P less than 0.05) as compared to placebo, but rated perceived exertion (RPE) was unchanged as well as the estimated skiing technique. The elite skiers showed prolonged performance times (P less than 0.05) after beta-blockade and in the case of propranolol also reduced peak and mean blood lactates (P less than 0.05). It is suggested that during intense exercise propranolol reduced lactate formation, which is in line with previous reports. This might impair short time, "explosive" type muscular exercise. If there is a risk factor for injury during beta-blockade and alpine skiing, it might be connected to the impaired performance and metabolism in relation to intense exercise and propranolol treatment.

Adolescent↗

Effects of acute beta-adrenergic blockade on blood and muscle lactate concentration during submaximal exercise.

Heart rate and blood and muscle lactate concentrations were studied in 15 physically active males during submaximal exercise before and after oral administration of 80 mg propranolol (Inderal). First, a cycle exercise protocol, with a stepwise increased exercise intensity (30 W every 4 min until voluntary exhaustion) was performed before and after beta-blockade. Blood samples for lactate determination were obtained before each exercise intensity increase. In a second set of experiments, the procedure was repeated before and after beta-blockade, but exercise was terminated at the exercise corresponding to a blood lactate concentration of 4 mmol X l-1 l-1, as determined beforehand without beta-blockade (i.e., the same absolute work load was compared with and without beta-blockade), and a muscle biopsy was taken from m. vastus lateralis for subsequent lactate analyses. Following beta-blockade at low and high work loads, the heart rate decreased similarly by 22%-26%. Blood lactate concentration was unchanged at exercise intensities up to 150 W. At higher exercise intensities (180-240 W), a significant increase (P less than 0.05 - P less than 0.01) in blood lactate concentration occurred after beta-blockade. Muscle lactate concentration was unaffected by beta-blockade at a work load (130-230 W) where blood lactate was higher with than without blockade. Assuming a reduced blood flow to the exercising muscle, there are reasons to speculate that lactate production was diminished following beta-blockade even though blood lactate increased probably as a result of reduced lactate uptake by other organs.

Adrenergic beta-Antagonists↗