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H Koch

Publications and source records attributed to H Koch.

At least 181 records · Page 10Linked to original sources

P2-receptor-mediated inhibition of noradrenaline release in the rat pancreas.

The aim of the study was to find out whether, and if so through which receptors, nucleotides modulate the release of noradrenaline in the rat pancreas. Segments of the pancreas were preincubated with [3H]-noradrenaline, superfused with medium containing desipramine (1 microM) and yohimbine (1 microM), and stimulated electrically, in most experiments by 60 pulses/l Hz. The adenosine A1-receptor agonist N6-cyclopentyl-adenosine (CPA; EC50 32 nM), the non-subtype-selective adenosine receptor agonists adenosine (EC50 15 microM) and 5'-N-ethylcarboxamidoadenosine (NECA; EC50 135 nM), and the nucleotides ATP (EC50 13 microM), adenosine-5'-O-(3-thiotriphosphate) (ATPgammaS; EC50 19 microM) and adenosine-5'-O-(2-thiodiphosphate) (ADPbetaS; EC50 16 microM) decreased the evoked overflow of tritium. The adenosine A2A-agonist 2-p-(2-carboxyethyl)-phenethylamino-5 '-N-ethylcarboxamido-adenosine (CGS 21680) caused no change. The concentration-response curve of CPA was shifted to the right by the A -antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX 10 nM; pKd 9.1) but, like the concentration-response curve of adenosine, hardly affected by the P2-receptor antagonist cibacron blue 3GA (30 microM). Combined administration of a high concentration of DPCPX (1 microM) and 8-phenyltheophylline (10 microM) abolished the effects of CPA and NECA. The concentration-response curves of ATP and ADPbetaS were shifted to the right by both DPCPX (10 nM; pKd 8.7 and 8.9, respectively) and cibacron blue 3GA (30 microM; pKd 5.0 and 5.2, respectively). The antagonist effects of DPCPX (10 nM) and cibacron blue 3GA (30 microM) against ATP were additive in a manner compatible with the blockade of two separate receptors for ATP. In the presence of the high concentration of DPCPX (1 microM) and 8-phenyltheophylline (10 microM), ATP and ADPbetaS still decreased evoked tritium overflow, and this decrease was attenuated by additional administration of cibacron blue 3GA (30 microM). The P2-antagonists cibacron blue 3GA, reactive blue 2, reactive red 2, and to a limited extent also suramin and 8-(3,5-dinitro-phenylenecarbonylimino)- 1,3,5-naphthalenetrisulphonate (XAMR0721), increased the evoked overflow of tritium by up to 114%. Pyridoxalphosphate-6-azophenyl-2',4'-disulphonate (PPADS) caused no change. The results indicate that the postganglionic sympathetic axons of the rat pancreas possess A1-adenosine and P2-receptors. Both receptors mediate an inhibition of noradrenaline release. The presynaptic P2-receptors are activated by an endogenous ligand, presumably ATP, during appropriate trains of action potentials. This is the first demonstration of presynaptic P2-receptors at postganglionic sympathetic neurons that are located in prevertebral ganglia.

Animals↗

Left ventricular diastolic function in infants, children, and adolescents. Reference values and analysis of morphologic and physiologic determinants of echocardiographic Doppler flow signals during growth and maturation.

OBJECTIVES: The aim of this study was to set up reference values for Doppler flow-derived left ventricular filling parameters and to evaluate physiologic determinants of changes in signal expression related to maturation. BACKGROUND: In left ventricular diastolic function studies, age-related modulations in signal expression are observed. Assuming degenerative myocardial changes to be absent during childhood and adolescence, the determinants of these modulations must be different from those suspected in adults. METHODS: Pulsed wave Doppler signals from the mitral valve tip region were recorded in 329 healthy subjects aged 2 months to 39 years. Multiple linear regression was used to evaluate statistical relations between Doppler flow signals and stroke volume in the mitral valve area. RESULTS: Increasing early filling time velocity integral throughout maturation caused a decrease in atrial filling fraction from 0.34+/-0.06 to 0.24+/-0.04 (p < 0.005). Peak flow velocities during atrial systole decreased from infancy to adolescence (66+/-15 to 41+/-10 cm/s). Main effects on signal modulation were caused by heart rate, stroke volume and mitral ring area with a linear model fit (R2) of 0.79 for early filling phase (E)-time velocity integral, 0.6 for atrial filling phase peak velocity 0.84 for total E duration and 0.73 for E deceleration time. Atrial filling phase-time velocity integral, albeit significantly dependent on heart rate, was stable throughout growth. CONCLUSIONS: During infancy and childhood, the stroke volume crossing the mitral valve is a main modulator for early filling phase (E)-time velocity integral and diastolic time intervals during early filling, whereas atrial filling phase parameters are mainly dependent on heart rate. This results in a more pronounced atrial filling during infancy and childhood.

Adolescent↗

The excitation of NMR transitions by the current in a sample and the proposals for its detection.

A new magnetic resonance technique for investigating conducting samples is described. NMR transitions are excited by the magnetic field of alternating current which flows across the sample. The dissipation of the energy caused by NMR transitions results in a change of the impedance of the sample. The NMR signal is detected as an associated change of the voltage drop across a sample while passing through the resonance region. It is predicted that the resonance can be detected by state-of-the-art low-noise superconducting quantum interference device (SQUID)-based NMR spectrometers. The method is believed to be useful for investigations of small-volume samples which are inaccessible by other NMR techniques.

Electric Impedance↗

Pantoprazole does not interact with the pharmacokinetics of carbamazepine.

OBJECTIVE: Pantoprazole is a H+/K+-ATPase inhibitor with a minimized potential of interaction with the cytochrome P450 system. Imidazole derivatives such as cimetidine and omeprazole have been shown to markedly interact with carbamazepine, a major anticonvulsant with a narrow therapeutic range. Therefore, the influence of steady-state pantoprazole on the pharmacokinetics of carbamazepine was investigated. SUBJECTS AND METHODS: N = 20 healthy volunteers (12 male/8 female) completed a double-blind, placebo-controlled, randomized crossover study. During the test period they received 40 mg pantoprazole p.o. once daily for 11 days and concomitantly a single oral dose of 400 mg carbamazepine on day 5. In the reference period placebo was administered instead of pantoprazole. RESULTS: Serum concentrations of carbamazepine and its active metabolite carbamazepine-10,11-epoxide were measured until day 11. Geometric means of AUC (extent characteristic) and Cmax/AUC (rate characteristic) of carbamazepine were 292 and 287 mgxh/l, and 0.0150 and 0.0144 l/h (reference and test), respectively. Point estimates and 90% confidence intervals of the ratios were 0.98 (0.95, 1.01) for AUC, and 0.96 (0.92, 1.00) for Cmax/AUC, respectively. Since the 90% confidence intervals of the primary characteristics, AUC and Cmax/AUC were entirely within the predefined equivalence range of 0.80 - 1.25, lack of interaction of pantoprazole with the pharmacokinetics of carbamazepine was demonstrated. Equivalence was also demonstrated for carbamazepine-10,11-epoxide using the characteristics AUC and Cmax. CONCLUSION: No dose adjustment of carbamazepine is therefore required during concomitant treatment with pantoprazole.

2-Pyridinylmethylsulfinylbenzimidazoles↗

P2-receptor-mediated inhibition of noradrenaline release in the rat hippocampus.

Experiments on hippocampal slices were carried out in order to find out whether the release of noradrenaline in the hippocampus can be modulated through P2-receptors. The slices were preincubated with [3H]-noradrenaline, superfused with medium containing desipramine (1 microM), and stimulated electrically, in most experiments by 4 pulses/100 Hz. The adenosine A1-receptor agonist N6-cyclopentyl-adenosine (CPA) and the nucleotides ATP, adenosine-5'-O-(3-thiotriphosphate) (ATP gamma S) and adenosine-5'-O-(2-thiodiphosphate) (ADP beta S) decreased the evoked overflow of tritium by up to 55%. The adenosine A2a-agonist 2-p-(2-carboxyethyl)-phenethylamino-5'-N-ethylcarboxamido-adenosin e (CGS 21680; 0.003-0.3 microM) caused no change. The concentration-response curve of CPA was shifted to the right by the A1-antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 3 nM) but not by the P2-receptor antagonists cibacron blue 3GA (30 microM) and reactive blue 2 (30 microM); the apparent pKB value of DPCPX against CPA was 9.0. In contrast, the concentration-response curve of ATP was shifted to the right by DPCPX (3 nM), apparent pKB 8.7, as well as by cibacron blue 3GA (30 microM), apparent pKB 5.2, and reactive blue 2 (30 microM), apparent pKB 5.6; the antagonist effects of DPCPX and cibacron blue 3GA were additive in a manner compatible with the blockade of two separate receptors for ATP. The same pattern was obtained with ATP gamma S: its concentration-response curve was shifted to the right by DPCPX as well as by cibacron blue 3GA and reactive blue 2. Suramin (300 microM) antagonized neither the effect of ATP nor that of ATP gamma S. The 5'-nucleotidase inhibitor alpha, beta-methylene-ADP (100 microM) did not change the effect of ATP. Only cibacron blue 3GA (30 microM) but not reactive blue 2 (30 microM), given alone, consistently caused a small increase of the evoked overflow of tritium. Hippocampal slices degraded exogenous ATP, and this degradation was reduced by cibacron blue 3GA (30 microM), reactive blue 2 (30 microM) and suramin (300 microM). The results indicate that the noradrenergic terminal axons of the rat hippocampus possess P2-receptors in addition to the known A1-adenosine receptors. The presynaptic P2-receptors mediate an inhibition of noradrenaline release, are activated by nucleotides but not nucleosides, and are blocked by cibacron blue 3GA and reactive blue 2. ATP and ATP gamma S act at both the A1- and the P2-receptors. An autoreceptor function of cerebral presynaptic P2-receptors remains doubtful.

Adenosine↗

P2-receptor-mediated inhibition of serotonin release in the rat brain cortex.

The possibility of a P2-receptor-mediated modulation of the release of serotonin in the rat brain cortex was investigated in occipito-parietal slices preincubated with [3H]serotonin and then superfused and stimulated electrically (10 pulses, 1 Hz). Adenosine receptor agonists decreased the stimulation-evoked overflow of tritium at best slightly; the selective A1 agonist N6-cyclopentyl-adenosine caused no change. Several nucleotides had more marked effects: ATP (3-1000 microM), adenosine-5'-O-(3-thiotriphosphate) (3-300 microM) and P1,P5-di(adenosine-5')-pentaphosphate (3-300 microM) decreased the evoked overflow by up to ca 35%. AMP, alpha,beta-methylene-ATP and UTP produced smaller decreases and 2-methylthio-ATP and UMP caused no change. The inhibition by ATP was attenuated both by the P1-receptor antagonist 8-(p-sulphophenyl)-theophylline (100 microM) and by the P2-receptor antagonist suramin (300 microM) but was not changed by indomethacin (10 microM) and NG-nitro-L-arginine (10 microM). We conclude that the release of serotonin in the rat brain cortex is inhibited through presynaptic P1-receptors (which are not A1) as well as P2-receptors. Inhibition of release via P2-receptors has been previously shown for noradrenaline (brain cortex and hippocampus) and dopamine (neostriatum) and, hence, may be widespread. Differences between transmitter systems exist, however, in the degree of their sensitivity to presynaptic P2-receptor-mediated modulation.

2-Chloroadenosine↗

Identification of 2,5-dimethyl-4-hydroxy-3[2H]-furanone beta-D-glucuronide as the major metabolite of a strawberry flavour constituent in humans.

2,5-Dimethyl-4-hydroxy-3[2H]furanone (Furaneol, DMHF) [3658-77-3], an important flavour constituent of strawberry fruit, was administered to four male and two female volunteers using fresh strawberries as a natural DMHF source. The amount excreted was determined by measuring urinary levels of DMHF and DMHF glucuronide. DMHF glucuronide was synthesized and the structure elucidated by mens of 1H, 13C and two dimensional nuclear magnetic resonance, as well as mass spectral data. Identification and quantification of DMHF glucuronide in human urine were achieved after solid phase extraction on XAD-2 using reverse-phase reverse-phase HPLC with either on-line UV/VIS or electrospray tandem mass spectrometry detection. Male and female volunteers excreted 59-69% and 81-94%, respectively, of the DMHF dose (total of free and glycosidically bound DMHF in strawberries) as DMHF glucuronide in urine within 24 hr. The amount of DMHF excretion was independent of the dose size and the ratio of free to glycosidically bound forms of DMHF in strawberry fruit. DMHF, DMHF glucoside and its 6'-O-malonyl derivative, naturally occurring in strawberries, were not detected in human urine.

Adult↗

Importance of the serovar-specific plasmid for virulence of salmonella strains in calves.

To evaluate the influence of serovar-specific plasmids on salmonella virulence in calves, experiments were performed involving infection, by the oral route, with mixtures of strains containing equal counts of a plasmid-carrying and a plasmid-free strain of the same serovar. The concentration ratio between the plasmid-carrying and the plasmid-free strain which had developed in the organs of the infected animals was used for a comparative evaluation of virulence and pathogenetic behaviour of the strains. While in the S. typhimurium strains studied, the presence of the plasmid was accompanied by a significantly increased colonization and multiplication of the agent in the host's body, examination of S. enteritidis and S. dublin revealed that the plasmid-free strains exhibited identical or even significantly higher bacterial counts than the plasmid-carrying strains in organs. The fact that plasmid-free salmonella strains with a high virulence for calves have been found demonstrates that the presence of a serovar-specific plasmid is not an indispensable requirement for the development of salmonellosis in calves.

Animals↗

Magnetocardiography and 32-lead potential mapping: repolarization in normal subjects during pharmacologically induced stress.

Signals from 37 magnetocardiographic sensors and simultaneously recorded 32 ECG leads were obtained in three healthy male subjects (including two reinvestigations). After recordings at rest, the heart rate was increased by pharmacologic stress (117 to 142 beats/min). Comparison of the repolarization of rest and stress showed substantial changes in the magnetocardiogram (MCG) up to T wave inversions during stress. In the ECG only junctional ST-T segment shifts were present. For quantification, correlation coefficients between pairs of rest and stress MCG and rest and stress ECG distributions were calculated for the same time instant at the beginning of T wave under rest and stress conditions. In addition, equivalent electrical current dipole moment and magnetic dipole moment vectors were calculated from the MCG, and their change from rest to stress evaluated. Correlation coefficients for MCG comparison ranged from 0.3 to 0.5; ECG comparison suggested much less change from stress, ranging from 0.7 to 1.0. Current dipole moment changes at T wave onset were marginal; in contrast, the magnetic dipole moment changed substantially. Since the magnetic dipole reflects vortex currents, changes in its intensity and/or orientation during repolarization suggest this as the biophysical basis of the striking difference in the response of the MCG and ECG to pharmacologic stress. Normal ECG findings at rest and under stress in healthy subjects support the conclusion that the repolarization changes in the MCG were of nonpathologic origin.

Adult↗

Magnetometry of evoked fields from human peripheral nerve, brachial plexus and primary somatosensory cortex using a liquid nitrogen cooled superconducting quantum interference device.

Superconducting Quantum Interference Devices (SQUIDs) can be used to detect neuromagnetic fields evoked in the peripheral and central nervous system. Up to now, such measurements had to be based on SQUIDs with a low critical temperature (Tc) requiring liquid helium cooling. Recent improvements in high-Tc SQUID technology relying on liquid nitrogen cooling led to a significant reduction in the system's noise level. Hare, first high-Tc recordings of weak neuromagnetic fields are demonstrated. In particular, along the entire somatosensory afferent pathway including peripheral nerves, brachial plexus and primary somatosensory neocortex evoked neuromagnetic activities were detected using conventional recording parameters for bandwidth and number of averages. This opens up a wide perspective for cost-effective high-Tc magnetometry in clinical neuroscience.

Brachial Plexus↗

Influence of prior infection on the dynamics of bacterial counts in calves experimentally infected with Salmonella dublin.

The aim of this investigation was to obtain information on the influence of immunity gained from a previous infection in calves on the dynamics of a subsequent salmonella infection. Immune and non-immune animals were orally infected with virulent S. dublin. After infection clinical symptoms and the development of bacterial counts in intestinal contents and intestinal mucosa, as well as in intestinal lymph nodes, spleen and liver were compared. The protection of the immune animals became evident as milder courses of infection and in lower bacterial counts in all examined organs. The greatest absolute and relative difference between the counts of immune animals and controls was in the intestinal mucosa. While absolute counts were lower, the proportion of bacteria was higher in the lymph nodes of immune animals. This apparently more intensive penetration in immune animals was feigned by a general and immunity independent negative correlation between concentration of salmonella in the mucosa and of salmonella found in the intestinal lymph nodes. This time course of counts provided evidence that enhanced defence of immune calves was particularly pronounced 3 and 4 days after the onset of infection.

Animals↗

Development of pathological lumbar kyphosis in myelomeningocele.

We analysed the cases of lumbar kyphosis in 151 (21%) of a series of 719 patients with myelomeningocele. Three different types were distinguished: paralytic, sharp-angled and congenital. In a cross-sectional and partly longitudinal study the size and magnitude of the kyphosis, the apex of the curve and the level of paralysis of each group were recorded and statistically analysed. Paralytic kyphosis (less than 90 degrees at birth) occurred in 44.4% and increased linearly during further development. Sharp-angled kyphosis (90 degrees or more at birth) was present in 38.4% and also showed a linear progression. In both types, progression seemed to depend also on the level of paralysis. Congenital kyphosis occurred in 13.9% and we could find no significant factor which correlated with progression.

Cross-Sectional Studies↗

[Gunshot wounds--ballistics, physiopathology, surgical treatment].

The form and size of gunshot wounds depend on the projectile type (bird shot, deforming projectiles, non-deforming projectiles), its velocity at impact (high or low velocity projectiles) and the type of tissue affected by the projectile (soft tissues, bones). Gunshot wounds are always contaminated. While low velocity projectiles usually cause minimal wounds, high velocity projectiles can cause large, devastating wounds. All projectiles fired from firearms have a high velocity on impact and may cause death by traumatic shock instantaneously. Ballistics, pathophysiology and clinical findings of gunshot wounds are discussed, forensic aspects are mentioned. Gunshot wounds are often emergencies. Lifesaving and -stabilizing treatment is most important. A treatment plan aiming at preventing possible complications such as infections and functional disturbances is given for different types of gunshot wounds. Systemic lead poisoning has not been investigated sufficiently. Projectiles usually become encapsulated. The search for projectiles is associated with an additional surgical trauma and usually indicated only for joint wounds (lead arthropathy).

Animals↗

The effect of season and latitude on in vitro vitamin D formation by sunlight in South Africa.

AIMS: To assess the effect of season and latitude on the in vitro formation of previtamin D3 and vitamin D3 from 7-dehydrocholesterol (7-DHC) by sunlight in two cities in South Africa, Cape Town and Johannesburg. METHODS: An in vitro study utilising vials containing 7-DHC, which were exposed to sunlight for a period of 1 hour between 8:00 and 17:00 on 1 day a month for a year. Previtamin D3 and vitamin D3 were separated from 7-DHC by high-performance liquid chromatography, and the amounts formed were calculated with the use of external standards. RESULTS: A marked seasonal variation in vitamin D3 production was noted in Cape Town, with very little being formed during the winter months of April through September. In Johannesburg, in vitro formation changed little throughout the year, and was similar to that found in Cape Town during the summer. During sunlit hours, vitamin D3 production was maximal at midday and small quantities were still being formed between 8:00 and 9:00, and between 16:00 and 17:00 during the summer. During winter in Cape Town, peak formation at midday was less than one-third of that in Johannesburg, and negligible amounts were formed before 10:00 and after 15:00. CONCLUSIONS: The previously documented seasonal variation in serum 25-hydroxyvitamin D recorded in patients in Johannesburg is probably a consequence of the increased clothing worn and the decreased time spent out of doors during winter, rather than decreased ultraviolet radiation reaching the earth. The limited in vitro formation of vitamin D3 during winter in Cape Town may have clinical implications insofar as the management of metabolic bone diseases like rickets and osteoporosis is concerned. Breast-fed infants resident in the area are likely to suffer from vitamin D deficiency rickets unless vitamin D supplements are provided, or the mothers are encouraged to take their children out of doors.

Breast Feeding↗

Nemaline myopathy: two autopsy reports.

Nemaline myopathy belongs to the group of congenital non-progressive myopathies; however, in rare cases death occurs in early infancy. We report two cases of rapidly fatal nemaline myopathy. The first patient, who died at the age of 26 months, showed atrophy of type 1 fibers containing numerous rods in biopsy sections. Biopsy of the second patient, who had died at the age of 5 months, revealed severe maturational arrest and myopathy, but rods were so rare that diagnosis could only be made at the ultrastructural level. Autopsy of both patients showed that atrophy of type 1 fibers and maturational arrest had disappeared in the very same muscles; rods had moved to a central position in the first and significantly increased in number in the second case. Diaphragma muscles contained abundant amounts of rods in both cases. The cardiac musculature showed a few rods only in the first patient, who had developed heart insufficiency 11 months prior to death. Immunohistochemical analysis showed that rods did not contain desmin or ubiquitin.

Biopsy↗