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Biomedical subjects

H Weicker

Publications and source records attributed to H Weicker.

At least 37 records · Page 2Linked to original sources

Influence of peripheral arterial occlusive disease on muscular metabolism. Part 1: Changes in lactate, ammonia, and hypoxanthine concentration in femoral blood.

The concentrations of lactate, ammonia and hypoxanthine were determined in blood from the femoral artery, femoral vein and cubital vein under resting conditions in 23 patients with stage II, 10 patients and 20 diabetics with stage IV peripheral arterial occlusive disease (PAOD) and in 19 healthy subjects. The metabolite concentrations were also measured immediately and 20 min after calf exercise in the patients with stage II PAOD and in the controls. At rest, there was a negative arteriovenous difference in femoral lactate level and a positive arteriovenous difference in the ammonia level in all groups. After exercise to the claudication limit, the femoral venous concentration and arteriovenous difference for lactate increased in the patient group significantly higher than in the controls, who were exercised three times as heavily. Furthermore, there was a significant rise in femoral venous ammonia concentration with inversion of the arteriovenous difference into the negative range and an increase in femoral venous hypoxanthine concentration only in the patients with PAOD and not in the controls. A significant correlation was found between the exercise-induced increases in lactate and ammonia. The results indicate activation of the purine nucleotide cycle in the muscles of limbs with impaired circulation, even for a short duration of load. This can be explained by activation of the AMP-deaminase in type I and type IIa muscle fibres by anoxaemia. The purine nucleotide cycle has an emergency metabolic function in ischaemia to maintain muscle contractility. Ammonia determination in femoral blood permits, in association with lactate and hypoxanthine determination, a precise quantitative assessment of the metabolic effects of PAOD.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

[Comparison of 3 latest-generation glucose micro-reflectometers].

Three glucose reflectance meters (Reflolux II = Accu-Chek II, Glucometer II and Hypocount GA) were tested for precision and accuracy when used by medical personnel of a diabetic outpatient department and for self-monitoring at home. In addition, the visual readability of the appropriate reagent strip was checked. All three systems were sufficiently valid for reflectometric reading, while visual evaluation showed a higher deviation. The precision of Accu-Chek II under optimal conditions in the outpatient department was comparable to the precision of laboratory examinations (CV 3.3%). When used by patients themselves, Accu-Chek II and Glucometer II were sufficiently precise (CV 4.8% [corrected] and 5.3% respectively). These devices are recommended for blood glucose self-monitoring.

Adult

Comparison of sympatho-adrenergic regulation at rest and of the adrenoceptor system in swimmers, long-distance runners, weight lifters, wrestlers and untrained men.

The effects of different physical training regimes on the plasma catecholamine values at rest and the density and responsiveness of adrenergic receptors at rest were investigated. The changes during well-defined training periods of swimmers, long-distance runners, weight lifters and wrestlers were compared with untrained male volunteers. The training of swimmers and long-distance runners, building up endurance, resulted in a significantly lower basal plasma norepinephrine (NE) concentration and a significantly or possibly lower ratio NE:EPI (epinephrine). Both values indicated reduced sympathetic activity and resulted also in a significantly lower beta-receptor density and a higher alpha 2-receptor sensitivity compared with the other groups investigated. However, swimming-specific characteristics provoked labile hypertensive blood pressure regulation with an unchanged heart rate in swimmers. Static training of weight lifters, building up power, also led to a lower NE concentration compared with untrained subjects, whereas beta-receptor density was unchanged and alpha 2-receptor density and sensitivity were decreased. Elevated blood pressure values were observed in weight lifters and swimmers due to a reduced baroreceptor sensitivity. The dynamic training of wrestlers affected only basal heart rate and alpha 2-receptor sensitivity, both of which were decreased. Different kinds of physical training caused various adaptations of the basal activity of the autonomic nervous system in which adrenergic receptors also became adapted. In this context, the stronger adrenergic circulatory component of overall sympathetic activity at rest in swimmers and long-distance runners resulted in lower beta-receptor density, and the reduced noradrenergic component sensitized alpha 2-receptors.

Adenylyl Cyclases

Syntheses of the sulfoconjugated isomers of norepinephrine and dopamine, controlled by HPLC with ultraviolet detection.

The physiological significance of sulfoconjugated catecholamines and their involvement in clinical disorders, e.g. hypertension and Parkinsonism, is poorly investigated. For this reason, the sulfoconjugated isomers of dopamine as well as of norepinephrine were synthesized by modified methods. All isomers and their intermediates could be detected by a reversed-phase high-performance liquid chromatography with ultraviolet detection (HPLC-UV) with short retention times and a good reproducibility. Ion-exchange chromatography with an extended column length improved the separation of the reaction products, and the immediate control by HPLC-UV enabled precise cutting of the fractions. The selection of the fractions with the optimum ratios of product/by-product resulted in improved yields and highest purity. All by-products, e.g. dopamine sulfonic acids, were less than 0.04%, as detected by HPLC-UV and, in addition, the contamination by free catecholamines was only 41 x 10(-4)-87 x 10(-4)%, as measured by HPLC with electrochemical detection (HPLC-ED). The purity was further demonstrated in two highly sensitive biological assays: cAMP production in human mononuclear leukocytes and aggregation of human platelets. The sulfoconjugated catecholamines were characterized by melting point, thin-layer chromatography, infrared spectrum, HPLC-UV, elemental analysis, and unequivocally identified by 1H-NMR.

Chemical Phenomena

3- and 4-O-sulfoconjugated and methylated dopamine: highly reduced binding affinity to dopamine D2 receptors in rat striatal membranes.

The binding properties of 3- and 4-O-sulfo-conjugated dopamine (DA-3-O-S, DA-4-O-S) as well as 3-O-methylated dopamine (MT) to rat striatal dopamine D2 receptors were investigated. 3H-spiperone was used as a radioligand in the binding studies. In saturation binding experiments (+)butaclamol, which has been reported to bind to dopaminergic D2 and serotoninergic 5HT2 receptors, was used in conjunction with ketanserin and sulpiride, which preferentially label 5HT2 and D2 receptors, respectively, in order to discriminate between 3H-spiperone binding to D2 and to 5HT2 receptors. Under our particular membrane preparation and assay conditions, 3H-spiperone binds to D2 and 5HT2 receptors with a maximal binding capacity (Bmax) of 340 fmol/mg protein in proportions of about 75%:25% with similar dissociation constants KD (35 pmol/l; 43 pmol/l). This result was verified by the biphasic competition curve of ketanserin, which revealed about 20% high (KD = 24 nmol/l) and 80% low (KD = 420 nmol/l) affinity binding sites corresponding to 5HT2 and D2 receptors, respectively. Therefore, all further competition experiments at a tracer concentration of 50 pmol/l were performed in the presence of 0.1 mumol/l ketanserin to mask the 5HT2 receptors. DA competition curves were best fitted assuming two binding sites, with high (KH = 0.12 mumol/l) and low (KL = 18 mumol/l) affinity, present in a ratio of 3:1. The high affinity binding sites were interconvertible by 100 mumol/l guanyl-5-yl imidodiphosphate [Gpp(NH)p], resulting in a homogenous affinity state of DA receptors (KD = 2.8 mumol/l).2+ off

Animals

[Rhabdomyolysis in a bodybuilder using anabolic steroids].

The clinical course and the laboratory findings of a massive rhabdomyolysis in a male bodybuilder is presented. Particularly spectacular are the light- and electron-microscopical pictures of the histological findings. The acute renal failure as the most important and major life-threatening complication of the rhabdomyolysis is considered and the successful therapeutic procedure is described. The probability of a causal relation between anabolic steroids and rhabdomyolysis is discussed as well as the resulting consequences for the care of athletes in sports medicine.

Adult

Determination of free and sulfoconjugated catecholamines in plasma and urine by high-performance liquid chromatography.

The determination of free and sulfoconjugated catecholamines (CA) in serum and urine with amperometric detection after HPLC separation is described. The reliability of this method has been extensively investigated. Since in men 69-90% of the total CA are sulfoconjugated, an enzymatic hydrolysis of these conjugates with arylsulfatase VI has been elaborated and optimized for a routine assay. The reproducibility with coefficients of variation between 1% and 3% for free and 5% and 10% for conjugated CA and recovery rates of 65%-75% for both were found. The calibration plots were linear between 10 and 5000 ng/l and the smallest detectable amount of CA was 0.1 nmol/l. The sample amount of 0.75 to 1.0 ml for free and 0.2 ml for conjugated CA was lower than with the extraction method (18) which needs 3 ml of serum. Using an automatic sampler, the sampling rate was 50-60 p.d. With the Al2O3 adsorption and the same buffer eluent system, L-dopa can also be detected at the same voltage of 700 mV. The values obtained for the HPLCA described method correlated well with those of the radio enzyme assays according to Da Prada et al. The HPLCA detection of free and sulfoconjugated CA in urine was carried out after an ion exchange column procedure on Biorex 70. The validity of the urine assay was at least as reliable as the determination of free and conjugated CA in plasma.

Catecholamines

Cardiocirculatory, hormonal, and metabolic reactions to various forms of ergometric tests.

The sympathoadrenergic reaction is not only dependent on the duration and intensity of work but also on the body position and the involvement of small or large muscle masses. This observation made in field tests comparing different sports disciplines such as swimming, running, or diving encouraged us to investigate this topic under the following laboratory conditions. Twelve healthy sport students participated in ergometric tests on a bicycle ergometer in a horizontal and vertical body position as well as on a treadmill and a swim bench ergometer. The changes of plasma catecholamines (CA) obtained in the different ergometric tests were compared with those cardiocirculatory, metabolic, and hormonal parameters which can be influenced by the sympathoadrenergic stimulation. In the horizontal body position we found a smaller increase of norepinephrine at submaximal and maximal work loads combined with a similar reaction of renin, whereas the diastolic blood pressure and the mean arterial blood pressure increased more. The substrates of lipolysis and aerobic and anaerobic glycolysis did not show obvious differences depending on the body position. In the swim bench test, however, the lactate increase started earlier and was comparatively higher than in the other ergometric tests in which the maximal work load and VO2max were higher. Although a smaller muscle mass was used and a lower maximal oxygen uptake was reached, we did not find statistically different CA values during the swim bench ergometric test compared with the bicycle ergometric test in a horizontal body position. In our ergometric tests, the venous CA levels (especially norepinephrine) were predominantly influenced by the body position.

Adult

Modified syntheses of dopamine-4-sulfate, epinephrine-3-sulfate, and norepinephrine-3-sulfate: determination of the position of the sulfate group by 1H-NMR spectroscopy.

With respect to the growing interest in sulfoconjugated catecholamines (CAS), reliable syntheses of those substances including high purification and unequivocal identification are required. For the syntheses of the 3-O-sulfates of norepinephrine (NE) and epinephrine (EPI), modifications of the methods of Stolz (12) and Arakawa et al. (1) were performed. Noradrenalone and adrenalone were prepared according to the method of Stolz (12) and sulfated by reaction with pyridine-sulfurtrioxide complex in dry pyridine at 60 degrees C. After reduction of these ketosulfates by sodium borohydride in dry pyridine, NE-3-O-S and EPI-3-O-S were obtained respectively. We synthesized dopamine-4-O-sulfate (DA-4-O-S) by reaction of DA hydrochloride with pyridine-sulfurtrioxide complex in dry dimethylformamide at 20 degrees C (Harbeson et al., 1983). The highly purified products (DA-4-O-S, NE-3-O-S, EPI-3-O-S) were characterized by their melting points (mp), infrared spectra (IR), thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), elemental analysis, and 1H-nuclear magnetic resonance spectroscopy (1H-NMR).

Dopamine

Restricted alpha- and beta-adrenoceptor affinity of sulfoconjugated catecholamines in human mononuclear leukocytes, platelets, and fat cells and reduction of the postreceptor mechanisms.

The physiologic significance of the racemic 3-O-sulfate esters of epinephrine (EPI-3-O-S) and norepinephrine (NE-3-O-S) as well as 4-O-sulfoconjugated dopamine (DA-4-O-S) was evaluated. For this purpose these conjugated catecholamines (CA) were synthesized and investigated with respect to their alpha 2- and beta 2-adrenoceptor affinities and their biological activity in three different human cell systems: in mononuclear leukocytes (MNL), platelets, and fat cells. The unequivocal identification and the minimal degree of contamination of the synthesized sulfoconjugates with free CA was proved by 1H-NMR and by high-performance liquid chromatography with amperometric detection (HPLCA) respectively. In isolated human MNL, beta-adrenoceptor affinities of these conjugated CA were determined in competition experiments with the lipophilic nonspecific radioligand (-) 125I-cyanopindolol (ICYP) and, in addition, with the hydrophilic ligand 3H-CGP12177. With both ligands the affinity constants (KD) of the sulfoconjugated CA under investigation were about 100- to 1000-fold higher when compared with the respective free amines. Moreover, these sulfoconjugated CA per se induced no intracellular production of cyclic adenosine monophosphate (cAMP) in MNL. In comparison with the free amines, metanephrine (MN) and normetanephrine (NMN) showed a highly reduced competitive potency on the MNL beta-adrenoceptors labelled with 3H-CGP or ICYP. The KD values for MN and NMN in competition studies with ICYP were 10- and 5-fold higher than in those with 3H-CGP respectively, indicating a restricted access of MN and NMN to intracellular receptors. The adenylate cyclase system was not stimulated at all by MN or by NMN. In human platelets EPI-3-O-S and NE-3-O-S neither competed with the specific alpha 2-adrenoceptor antagonist 3H-yohimbine nor elicited any aggregation response at all. MN and NMN exhibited an about 40-fold reduced affinity for alpha 2-adrenoceptors in platelets when compared with the respective free amines and elicited no aggregation response at all. However, in the presence of MN and NMN the EPI- and NE-induced platelet aggregation was dose-dependently attenuated. These findings reveal an alpha 2-adrenoceptor antagonistic potency of MN and NMN. In human adipocytes EPI-3-O-S and NE-3-O-S were 100- to 1000-fold less potent to inhibit lipid mobilization via alpha 2-adrenoceptors as well as to stimulate the beta-adrenoceptor mediated lipolysis when compared with free CA.

Adipose Tissue

Humoral regulation of the orthostatic reaction.

A tilt-table test was performed on 12 untrained subjects to evaluate the humoral adaptation to postural change. The observed peripheral reaction with a reversible short-term rise of norepinephrine (NE) and plasma renin activity (PRA) allowed us to divide the syndrome of the orthostatic dysregulation into a hyponoradrenergic and hypernoradrenergic type. This classification can be helpful for the clinical evaluation and therapy of orthostatic lability. The central excessive stimulation of the antidiuretic (ADH) and adrenocorticotropic hormone (ACTH) follow-ing orthostatic symptoms such as weakness or dizziness was not completely reversible within the observation period of 30 min. The ADH and ACTH increase was not different between the hypo- and the hypernoradrenergic type of dysregulation but was the most sensitive indicator of orthostatic lability: 41% of all subjects showed a hypernoradrenergic orthostatic dysregulation with pronounced NE response and alpha 2-adrenoceptor down-regulation. By use of antiembolism stockings (AES) or dihydroergotamine (DHE) this rate decreased to 16%. This was associated with a significantly reduced NE and PRA response and a diminished alpha 2-adrenoceptor number.

Adrenocorticotropic Hormone

Effects of temperature and water immersion on plasma catecholamines and circulation.

The effects of environmental air temperature of 6 degrees C and 26 degrees C on catecholamines (CA) and circulation were studied in eight male subjects during rest and during bicycle exercise at WOBLA for 45 min each. We found that resting at 6 degrees C increased the norepinephrine (NE) levels to the same levels as endurance exercises at 6 degrees C. The increase of CA levels was 2.5 to 3 times higher during work at 26 degrees C compared with 6 degrees C. During both rest and exercise at 6 degrees C we found a higher stroke volume of the heart and a reduced heart rate (HR) with no or only small effects on the oxygen uptake and blood lactate levels compared with 26 degrees C. Measurements of the skin temperatures showed large differences both at rest and during work; those of core temperature showed no changes at rest and a slightly more pronounced increase during work at 26 degrees C compared with 6 degrees C. The behavior of CA, plasma renin activity (PRA), plasma aldosterone (PA), and circulation were studied in 13 top class swimmers and 12 recreational swimmers during immersion into water of 27 degrees C for 10 min. The recreational swimmers were additionally immersed into water of 21 degrees C and 33 degrees C. Even immersion at 33 degrees C induced a small but significant increase of NE levels and of blood pressure (BP) values with no effect on the HR and blood lactate values. Epinephrine (EPI) showed a tendency to decrease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Differences in sympathoadrenal, hormonal, and metabolic adaptation to submaximal and maximal arm and leg work compared with whole stroke in breast-style swimming.

During work on land adaptational reactions of circulation and hormones are influenced by the body position, the activated muscle mass, and the working extremities. The aim of this study was to explore the additional effect of water immersion during swimming on cardiocirculatory, metabolic, and hormonal regulation under different working conditions. Twelve young men not specifically trained in swimming underwent swimming tests on 3 different days. They had to swim breast stroke in total as well as isolated with legs or arms only each for 10 min at submaximal intensity and 150 m or 100 m at maximal intensity. This study was focused on changes of catecholamines (CA), heart rate (HR), blood pressure (BP), glucose, lactate, plasma renin activity (PRA), and plasma aldosterone (PA). Additionally, parameters of the electrolyte-volume homeostasis were investigated. Norepinephrine (NE) and epinephrine (EPI) increased during swimming under submaximal and maximal conditions. The augmentation of CA and HR was the highest after swimming whole stroke and the lowest after swimming arm stroke only. They were related to intensity within one type of swimming and showed a dependence on muscle mass independent from lactate or glucose levels when the different types of swimming were compared, although a positive correlation between CA and lactate levels was found. The BP was higher after leg work than after arm work, contrary to observations done on land regarding the comparable submaximal work loads. We suppose that this is an effect of water immersion and the horizontal body position whereby the central hemodynamic circulation becomes stabilized.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological

Influence of exercise in water on hormonal, metabolic and adrenergic receptor changes in man.

We investigated hormonal, metabolic, and cardiovascular adaptations as well as changes of alpha 2- and beta 2-adrenergic receptors in response to three different exercise performances in water: 1000 m fin swimming with or without a neoprene suit and, additionally, 600 m diving with a breathing apparatus while performing several tasks. Eight male divers participated in the study. Blood samples were taken at rest on land, 10 min after water immersion, immediately after exercise, and after 20 min recovery. Both free and sulfoconjugated norepinephrine (NE) increased exercise-dependently. Moreover, heat loss in water caused elevation of plasma free NE. Free epinephrine (EPI) increases showed a highly significant correlation with NE except during fin swimming with a neoprene suit where EPI concentrations were constantly higher. ACTH and cortisol levels rose during exercise and paralleled those of plasma NE. Plasma aldosterone decreased in response to water immersion at rest. Blood volume regulating hormones such as plasma renin, aldosterone, and vasopressin were significantly higher during physical exercise. Moreover, increased pressure conditions during diving caused significantly higher secretion rates of all of these hormones, resulting in a higher systolic blood pressure. This clinical issue might be considered when examining diving ability. Lipolysis was elevated to the same degree after the three exercise schedules had been applied. As expected, plasma glucose also increased during physical activity. The lactate values observed after fin swimming, but not after diving with a breathing apparatus were closely related to NE. The lowest lactate levels were obtained during air-assisted diving.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone

Sympathoadrenergic regulation of metabolism and cardiocirculation during and following running exercises of different intensity and duration.

In three different field studies running loads of 2 X 200 m and 400 m, 3 X 1000 m and 3000 m, and finally 10,000 m were performed by respective groups of sprinters, middle-, and long-distance runners. We investigated the effects of exercise on the sympathoadrenal system by determining catecholamine (CA) concentrations in the venous blood and urine [free norepinephrine (NE), epinephrine (EPI)] and the respective sulfoconjugates in plasma and various hormonal, metabolic, and cardiocirculatory parameters. Endurance-trained athletes showed a lower heart rate (HR) and plasma renin activity (PRA) at rest in comparison with the sprinters. The concentrations of the plasma CA reflected the intensity more than the duration of exercise. At rest and following recovery the ratio of free NE/EPI in plasma was markedly higher in the group of sprinters in comparison with the long-distance runners. During exercise, however, an opposite movement occurred resulting in a higher ratio in the latter group. The pre-start ratios of NE/EPI in urine were similar to those in plasma. The sports disciplines' specific differences in NE/EPI both at rest and during exercise suggest that the overall sympathetic activity, reflected by NE and EPI, is regulated in a quite differentiated pattern. The sulfoconjugated CA, however, increased less clearly after the middle- and long-distance bouts than the respective free CA which caused the ratio sulfates/free CA to decline. There were strong relations between the levels of free plasma NE and EPI and that of blood lactate which, however, rather reflects a parallelism subsequent to the highly intensive stimulation.

Adaptation, Physiological

Sympathoadrenergic regulation in elite fencers in training and competition.

In ten fencers at the top national level the adrenergic regulation was investigated by determining the free and sulfoconjugated catecholamines (CA) in a training fight and a competition for the national championship to evaluate the influence of emotional strain in this discipline. In the training fight which is physically more strenuous, norepinephrine (NE) was significantly higher (+27%) than in the championship contest after which the epinephrine (EPI) level was more increased (+76.5%). Accordingly, the systolic blood pressure (SBP) was higher during competition and correlated with EPI. The share of the sulfated CA in their total amount was reduced in both loads. Since energy production in fencing is predominantly alactacitic during maximal loads of short duration and aerobic during submaximal load intensities, the lactate level in the training fight was below the anaerobic/aerobic threshold. The significantly higher lactate, glucose, and alanine levels during the fight for the national championship, presumably induced by the additional stimulation of the anaerobic muscular and hepatic glycogenolysis as well as muscular glycolysis, may be accounted to the fortified EPI secretion caused by emotional strain. The higher cortisol and renin levels may be explained by the strong central stimulation and the direct peripheral effect of EPI respectively.

Adult

Influence of different experimental recreation treatments on sympathoadrenergic and metabolic regulation mechanisms in repeated exercises.

The influence of different recreation treatments on the sympathoadrenergic regulation, heart rate, mean blood pressure, plasma lactate, and glucose levels was investigated in a study in which the 1000 m distance was performed twice by top middle- and long-distance runners. Between the two runs, executed three times in an interval of 1 week, different regeneration strategies such as active or passive recreation as well as progressive muscle relaxation (PMR) with cognitive skill (Cl) were applied. The best running times in the second run were achieved after the PMR with Cl. After this treatment heart rate (HR) and mean arterial blood pressure (MBP) were not higher than in the other forms of regeneration, although the norepinephrine (NE) and epinephrine (EPI) increase was significantly higher after the second run compared with other treatments. The lactate and glucose levels in plasma were significantly higher after PMR with Cl than after active and passive regeneration. After the recovery period both metabolites decreased faster after PMR with Cl. The percentage of catecholamine sulfates of the total amount decreased after the first and the second run without significant differences between the three recreation treatments.

Blood Glucose

Sulfoconjugated catecholamines: lack of beta-adrenoceptor binding and adenylate cyclase stimulation in human mononuclear leukocytes.

The racemic 3-O-sulfates of epinephrine and norepinephrine as well as 4-O-sulfoconjugated dopamine were synthesized, highly purified and investigated with respect to their beta-adrenoceptor affinities and relative potencies in the receptor-coupled adenylate cyclase system in isolated human mononuclear leukocytes. The receptor affinities of all catecholamine sulfates were reduced at least 1,000-fold when compared to those of the free catecholamines. Furthermore, catecholamine sulfoconjugates did not produce intracellular cAMP signals. In contrast to the sulfated catecholamine metabolites, the 3-O-methylated catecholamines metanephrine and normetanephrine were found to behave as endogenous beta-adrenoceptor-competing agents with lower beta-receptor affinities than the corresponding free catecholamines. No beta-receptor agonist activity in the adenylate cyclase system was found with metanephrine and normetanephrine. Our data provide direct evidence that sulfoconjugation renders catecholamines inactive as beta-receptor ligands and must thus be regarded as a mechanism to control adrenergic action at the prereceptor level by a buffering of the concentration of free catecholamines. The physiological significance of a potential role of 3-O-methylated catecholamines as endogenous beta-receptor antagonists has to be further clarified.

Adenylyl Cyclases