Biomedical subjects

H Weicker

Publications and source records attributed to H Weicker.

At least 37 records · Page 2Linked to original sources

PubMed1990

Comparison of alanine production after L-leucine and AMP deamination in an enzymatic model and in muscle specimens.

The amination of 2-oxoglutarate to glutamate by the deamination of leucine followed by the transamination of pyruvate to alanine in skeletal muscle is generally accepted. However, alanine formation following AMP deamination by AMP deaminase is still questionable even though it is theoretically possible. For this reason, we investigated in an enzymatic model the dependence of alanine yield both on the increasing concentration of AMP and leucine as amino group donors as well as on AMP deaminase and leucine dehydrogenase augmentation. Up to a concentration of 375 microM neither of the amino group donors produced a difference in the glutamate nor alanine yield. At a concentration of 500 microM ammonia formation was less, but alanine production was higher when leucine was present as a starting material. However, in muscle samples obtained from trained or untrained rats we did not find an increase in alanine yield when AMP was added to the muscle sample, even though NH3 production was significantly higher in samples with than in those without AMP. This discrepancy might be further elucidated by hindquarter perfusion experiments, in which alanine release would be determined after AMP deamination enhanced by electrostimulation of these muscle groups.

AMP Deaminase↗

PubMed1990

Sympathoadrenergic regulation and the adrenoceptor system.

We investigated the effects of endurance and high-intensity training periods on the plasma catecholamine (CA) concentration at rest; on the basal alpha- and beta-adrenoceptor density, regulation, and function on circulating cells; and on the cardiovascular adaptation in long-distance runners and swimmers. The findings of each period were compared with those of untrained men. Endurance training of the long-distance runners and the swimmers led both to a reduced sympathetic activity at rest, indicated by lower CA values, and to a lower beta-receptor density and responsiveness on circulating lymphocytes and an increased alpha 2-receptor sensitivity on circulating platelets. During the high-intensity training period beta-receptor density and responsiveness increased, alpha 2-receptor sensitivity normalized, and heart rate as well as blood pressure values increased in both trained groups. The basal sympathetic activity remained reduced, but the norepinephrine-to-epinephrine (NE/EPI) ratio increased. The NE/EPI ratio might play an important part in the regulation of adrenoceptor density during these different training periods. Swimming-specific characteristics caused different physiological impacts compared with running training, but an attenuated baroreceptor sensitivity might be indicated in both intensively trained groups.

Adenylyl Cyclases↗

PubMed1990

Isomer specific kinetics of dopamine beta-hydroxylase and arylsulfatase towards catecholamine sulfates.

Both isomers of epinephrine sulfate were synthesized, unequivocally identified by 1H-NMR and highly purified from catecholamines (less than 90 ppm). Bacterial as well as pig liver arylsulfatase A and B demonstrated a higher substrate turnover of epinephrine-4-sulfate, norepinephrine-4-sulfate and dopamine-4-sulfate as compared to the 3-sulfate isomers. The arylsulfatase B however, is less important for the deconjugation of these sulfoconjugates than arylsulfatase A. Since arylsulfatase A occurs in most human tissues, it might be of physiological significance in the deconjugation of the catecholamine sulfate isomers. Furthermore the kinetic data at pH 7.4 and 6.9 suggest the increased cleavage of the sulfate group, e.g. during exercise-induced acidosis. In contrast to results reported in the literature, dopamine sulfates were no substrates of dopamine beta-hydroxylase.

Animals↗

PubMed1989

Assessment of muscular metabolism in peripheral arterial occlusive disease using 31P nuclear magnetic resonance spectroscopy. Comparison with metabolite concentrations in femoral blood.

The behaviour of muscular metabolism was investigated in 10 patients with peripheral arterial occlusive disease stage II at rest and after maximum ergometric calf exercise. The intracellular concentrations of phosphocreatine, inorganic phosphate and adenosine triphosphate as well as muscle pH were measured by means of 31P magnetic resonance spectroscopy and compared with those from a control group. In addition, arteriovenous differences in concentrations of lactate, pyruvate, ammonia, hypoxanthine and alanine in the femoral blood were determined. The fall in intracellular phosphocreatine concentration during exercise was significantly greater in the calf muscles of patients with arterial occlusion than in controls and correlated linearly with the increase in femoral arteriovenous differences in lactate, ammonia and alanine. A significant fall in intracellular pH occurred during muscular activity only in the patient group, but not in the identically exercised control group. The fall in pH correlated closely with the rise in arteriovenous lactate difference in the femoral blood. The intramuscular ATP concentration remained constant throughout the exercise procedure. The behaviour of both the directly and indirectly measured metabolites permits the deduction of activation of the creatine kinase reaction, glycolysis, myokinase reaction and the purine nucleotide cycle during exercise-induced hypoxia in the presence of arterial occlusive disease. The anaerobic production of energy is sufficient to maintain the ATP concentration even during claudication pain.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗

PubMed1989

Influence of peripheral arterial occlusive disease on muscular metabolism. Part 2: Changes in pyruvate, alanine, and urea concentration in femoral blood.

The metabolites pyruvate, alanine and urea were determined under resting conditions in blood from the femoral artery, femoral vein and cubital vein of 23 patients with stage II, 10 patients and 20 diabetics with stage IV PAOD as well as 19 healthy volunteers. Measurements were also carried out immediately and 20 min after ergometric calf exercise in the patients with stage II PAOD and the controls. In both patient groups with stage IV PAOD, there were lower arterial and venous alanine levels and higher urea concentrations at rest than in patients with adequate resting circulation, which is evidence for increased hepatic alanine extraction. After exercise, a significantly higher increase in the arteriovenous difference of pyruvate concentration was to be found in the patient group with stage II PAOD than in the control group. Moreover, there was a significant increase in femoral venous concentration and a rise in the arteriovenous difference of alanine, indicating muscular release, only in the PAOD patients and not in the volunteers in spite of a three times higher exercise load. The exercise-induced rise in femoral venous alanine correlated closely with those of pyruvate and ammonia. Alanine formation fulfills the function of a non-toxic carrier of muscularly produced amino groups and represents in PAOD a compensating mechanism that delays the limitation of muscular contractility. Alanine determination, especially in association with an exercise test, appears to be suitable for assessing the extent of anaerobic energy production in muscles of limbs affected by PAOD.

Alanine↗

PubMed1989

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↗

PubMed1989

[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↗

PubMed1989

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↗

PubMed1988

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↗

PubMed1988

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↗

PubMed1988

[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↗

PubMed1988

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↗

PubMed1988

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↗

PubMed1988

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↗

PubMed1988

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↗

PubMed1988

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↗

PubMed1988

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↗

PubMed1988

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↗