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Biomedical subjects

C Braun

Publications and source records attributed to C Braun.

At least 91 records · Page 5Linked to original sources
PubMed1997

Suppression of type II collagen-induced arthritis by N-acetyl-L-cysteine in mice.

1. The antiarthritic and anti-inflammatory efficacy of N-acetyl-L-cysteine (NAC) was tested in male DBA/1 hybrid mice suffering from type II collagen-induced arthritis. Parameters including the arthritis index and the phagocytic responses recorded by chemiluminescence in unseparated blood were used for the assessment of disease activity. 2. Mice were immunized by subdermal injection of bovine type II collagen in Freund's complete adjuvant. The treatment with NAC started at day 42 after immunization and was continued over a period of six weeks: in doses ranging up to 50 mg/kg, a dose-dependent suppression of arthritis was noted; between 50 and 200 mg/kg, the inhibition curve had a plateau [ED50 = 50 mg/(kg x day)]. 3. The arthritis index correlated positively with the generation of chemiluminescence by reactive oxygen species (ROS) produced in neutrophils and monocytes activated by 12-O-tetradecanoylphorbol 13-acetate. 4. After treatment with 100 mg/kg of NAC from day 42 after immunization over a period of six weeks, the ROS production was reduced to levels occurring in whole blood of healthy animals. 5. It is concluded that low-molecular-weight antioxidants such as NAC may be adequate for controlling oxidative stress-derived damage in rheumatic diseases by modulation of ROS-dependent signal transduction pathways.

Acetylcysteine↗
PubMed1997

Confidence interval of single dipole locations based on EEG data.

Noise in EEG and MEG measurements leads to inaccurate localizations of the sources. A confidence volume is used to describe the amount of localization error. Previous methods to estimate the confidence volume proved insufficient. Thus a new procedure was introduced and compared with previous ones. As one procedure, Monte Carlo simulations (MCS) were performed. The confidence volume was also estimated using two methods with different assumptions about a linear transfer function between source location and the distribution of the potential. One method used variable (LVM) and the other fixed dipole orientations (LFM). Finally, the confidence volume was estimated through a procedure in which there was no linearization of the transfer function. This procedure scans the confidence volume by varying the dipole location in multiple directions. Confidence volumes were calculated for simulated distributions of the electrical potential and for experimental data including somatosensory evoked responses to stimulation of lower lip, thumb, and little finger. Results from simulated data indicated that confidence volumes calculated with the MCS method were largest, and those calculated with the LFM method were smallest. For dipole locations close to the brain surface, the confidence volume was smaller than for a central deeper source. An increase in electrode density resulted in smaller confidence volumes. When the noise was correlated, only the method using the MCS produced acceptable results. Since the noise in experimental data is highly correlated, only the MCS method would appear to be useful in estimating the size of the confidence volume of the dipole locations. Thus, using real data with the MCS method, we easily distinguished separate and distinct representations of the thumb, little finger, and lower lip in the somatosensory cortex (SI). It was concluded that adequate estimation of confidence volumes is useful for localizing neural activity. On a practical level, this information can be used prior to an experiment for determining the conditions necessary to distinguish between different dipole sources, including the required signal to noise ratio and the minimum electrode density.

Brain↗
PubMed1997

Effects of bradykinin and icatibant on renal hemodynamics in conscious spontaneously hypertensive and normotensive rats.

We investigated the effects of bradykinin (BK) and icatibant (HOE 140), a highly selective bradykinin-B2-receptor antagonist, on mean arterial blood pressure (MAP), heart rate (HR), renal blood flow (RBF), and renal vascular resistance (RVR) in conscious Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). Experiments were performed in conscious male WKY rats and SHRs instrumented over the long term with arterial and venous catheters and a transit-time flow probe for measurement of RBF. In WKY rats (n = 16), intraaortic (i.a.) bolus injections of BK (0.1, 1.0, and 10 microg) produced dose-dependent decreases in MAP and RBF with reciprocal increases in RVR. Intrarenal (i.r.) injections of BK (10 microg; n = 6) induced the same hemodynamic response pattern, although the increase in RVR was higher compared with i.a. injections (p < 0.05). Neither vasopressin V1-receptor nor alpha1-adrenoceptor blockade had an effect on the renal vasoconstrictor responses on i.a. BK. The i.a. injections of icatibant (0.1, 1.0, 5.0, and 10 microg; n = 6-10 for each dose) led to a dose-dependent blockade of the hemodynamic responses to BK (10 microg, i.a.). Icatibant (10 microg, i.a) had no effect on resting MAP and HR but induced a biphasic response in RBF and RVR with significant changes compared with basal values (p < 0.05). In SHRs (n = 9), after injection of increasing i.a. doses of BK (0.1, 1.0, and 10 microg), dose-dependent decreases in MAP were proportionately greater compared with those in WKY rats. In contrast to WKY rats, RBF and RVR exhibited a biphasic response pattern on BK in SHRs. Neither vasopressin V1-receptor nor alpha1-adrenoceptor blockade had an effect on the renal vasoconstrictor responses on i.a. BK. The i.a. injections of icatibant (10 microg) almost completely blocked the hemodynamic responses on BK in SHRs (n = 13). Icatibant (10 microg, i.a.) itself induced an increase in resting MAP and HR (p < 0.05) and a biphasic response in RBF and RVR with significant changes of basal values (p < 0.05). Our results provide evidence that BK exhibits renal vasoconstrictor and vasodilator properties in vivo, both mediated by B2-receptors. Furthermore, we demonstrated that SHRs display an increased B2-receptor-mediated vasodilatory responsiveness to BK. Finally we showed that blockade of B2 receptors leads to an increase of MAP in SHRs in contrast to WKY rats, suggesting an important role of the kallikrein/kinin system in the regulation of high blood pressure in SHRs.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1997

Cerebral processing of words and the development of chronic pain.

The processing of pain-related, body-related, and neutral words was assessed in individuals with prechronic pain and matched healthy controls. Integrated surface electromyogram, heart rate, skin conductance level, and visual event-related potentials from 11 electrode sites were recorded during the presentation of three word types at perception threshold. Startle responses were recorded from words presented above perception threshold. The patient and control groups did not differ in recognition performance. Pain-related words evoked an enhanced early component (N100) of the visual event-related potential only in the prechronic pain group. In both groups the late slow wave and the startle response were enhanced for body- and pain-related words compared with those for neutral words. All word types elicited larger late positivities in the prechronic pain group and in the right compared with the left hemisphere. These data suggest differential cortical processing of pain-related material in persons at a prechronic pain stage.

Adult↗
PubMed1997

Influence of the renal endothelin system on the autoregulation of renal blood flow in spontaneously hypertensive rats.

The renal endothelin (ET) system has been claimed to play an important role in the regulation of renal blood flow (RBF) and sodium excretion in primary hypertension. The aim of the present study was to investigate the contribution of the endogenous ET system in the autoregulation of total RBF, cortical blood flow (CBF), pressure-dependent plasma renin activity (PRA) and pressure natriuresis in spontaneously hypertensive rats (SHR) by means of the combined (A/B) ET-receptor antagonist, bosentan. In anesthetized rats, RBF was measured by transit-time flow probes and CBF by laser flow probes. During the experiments, the rats received an intrarenal infusion of either bosentan (1 mg/kg/h) or vehicle. Renal perfusion pressure (RPP) was lowered in pressure steps of 5 mm Hg with a servo-controlled electropneumatic device via an inflatable suprarenal cuff. Bosentan had no effect on resting RPP, CBF, PRA and renal sodium excretion, whereas RBF was lowered by 30% (p < 0.05). Furthermore after bosentan the rats revealed a complete loss of RBF autoregulation. In contrast no changes in autoregulation of CBF, pressure-dependent PRA and pressure natriuresis were observed. Our findings demonstrate a significant impairment in total RBF autoregulatory ability during renal ET-receptor blockade which is not confined to the cortical vessels. These data suggest that the renal ET system plays an important role in the dynamic regulation of renal blood flow in SHR.

Animals↗
PubMed1997

Cyclic nucleotides in glutamate chemosensory signal transduction of Paramecium.

Glutamate is an attractant stimulus to Paramecium tetraurelia. It causes a hyperpolarization of the cell and smooth, relatively fast swimming that is characteristic of hyperpolarizing stimuli. We show here that by 1-30 seconds of stimulation, glutamate increases intracellular cAMP. Interestingly, other attractant stimuli, such as acetate and NH4Cl, that similarly hyperpolarize the cell do not induce an increase in cyclic AMP observable at 30 seconds. In order to determine whether the changes in cyclic AMP could be rapid enough to participate in stimulation as compared to slower processes such as adaptation, rapid kinetic measurements of cyclic AMP were made on whole cells by quenched-flow. We found that, in cells stimulated with glutamate, intracellular cyclic AMP increases by 30 mseconds and peaks at about sevenfold over basal levels by 200 mseconds. Cyclic GMP does not change relative to basal levels over rapid or slower time courses of glutamate stimulation. An antagonist of glutamate, IMP, depolarizes the cells and decreases intracellular cyclic AMP by approx. 50% and slightly increases cyclic GMP. Results of behavioral tests of cells treated with protein kinase inhibitors also suggest that cyclic AMP is part of the signal transduction pathway for glutamate, but not for other attractant stimuli. These studies are the first demonstration of a possible role for cyclic nucleotide second messengers in an attractant chemosensory transduction pathway in Paramecium.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1996

Bilateral vertebral artery lesion after dislocating cervical spine trauma. A case report.

STUDY DESIGN: This case report illustrates the problems associated with diagnosis and management of vertebral artery injuries resulting from dislocating cervical spine trauma. OBJECTIVES: Treatment involved the principles of anterior stabilization of dislocating cervical spine fracture as well as the diagnostic procedures and therapeutic modalities appropriate for vertebral artery lesions. SUMMARY OF BACKGROUND DATA: Because vertebral artery injuries with cervical spine trauma are rarely symptomatic, they can easily be overlooked. Bilateral or dominant vertebral artery occlusion, however, may cause fatal ischemic damage to the brain stem and cerebellum. METHODS: Cervical spine dislocation was stabilized immediately after admission using internal fixation by ventral plate and corticocancellous bone graft. Immediate angiography was performed when brain stem neurologic dysfunction manifested 36 hours after surgery. The patient was treated with anticoagulation, osmotherapy, and controlled hypertension. RESULTS: A fatal outcome resulted in this case of dominant left vertebral artery occlusion. Necropsy even revealed bilateral vertebral artery damage at the level of the osseous lesion. CONCLUSIONS: The possibility of the complication of a vertebral artery lesion should be kept in mind when examining patients with cervical spine trauma, especially in patients with fracture-dislocation. Immediate identification by vertebral angiography, magnetic resonance imaging, or thin-slice computed tomography scan is necessary for optimal management of this injury.

Adult↗
PubMed1996

[Chronic recurrent subileus due to Strongyloides stercoralis infection under immunosuppressive therapy].

HISTORY AND CLINICAL FINDINGS: A 33-year-old woman from Laos was admitted due to recurrent vomiting and weight loss. Since one year, she was receiving immunosuppressive therapy (azathioprine 50 mg/d and methylprednisolone 18 mg/d) for a mixed connective tissue disease. Because of a drug induced Stevens-Johnson-Syndrome one month earlier high doses of methylprednisolone (100 mg/d intravenously) had been administered. The patient's general condition was reduced. Examination elicited a mild pain in the middle abdomen on palpation but no resistance or tumour. The differential diagnosis included obstructive and (or) inflammatory disease of the gastrointestinal tract. INVESTIGATIONS: Elevated IgE-levels (1111 IU/ml; normal up to 100 IU/ml) and eosinophilia (8%) lead to the suspicion of a helminthiasis. Oesophagogastroduodenoscopy showed a significant duodenal stenosis. Duodenal biopsy revealed a severe infestation with Strongyloides stercoralis. Stool examinations were negative though. TREATMENT AND COURSE: With administration of thiabendazole (2 g/d) a rapid recovery was noted. A second oesophagogastroduodenoscopy one week after the onset of therapy revealed no further stenosis. Since there was no activity of the mixed connective tissue disease the methylprednisolone dosage was reduced and the administration of azathioprine was ceased. 3 weeks after beginning of treatment the patient was discharged in improved condition. CONCLUSION: In immunocompromised patients suffering from gastrointestinal complaints who have been in endemic areas an infection with Strongyloides stercoralis should be excluded. Without treatment, this helminthiasis may be fatal.

Adult↗
PubMed1996

Identification of Asp 549 as the catalytic nucleophile of glycogen-debranching enzyme via trapping of the glycosyl-enzyme intermediate.

Glycogen-debranching enzyme catalyzes the removal of branching from glycogen via a two-step process involving first the transfer of a maltotriosyl unit from the branch to the main chain and second the hydrolysis of the residual alpha-(1,6)-linked glucose moiety. Since the transfer occurs with retention of anomeric configuration, a mechanism involving a maltotriosyl-enzyme species is presumed. 4-Deoxy-alpha-maltotriosyl fluoride functions as an incompetent substrate for this transferase activity since a glycosyl-enzyme species in formed, as witnessed by a "burst" of fluoride release, but turned over only very slowly unless a suitable acceptor such as maltotriose is added, at which point 4-deoxymaltohexaose is released. Peptic proteolysis of this trapped enzyme generated a mixture of peptides which was separated by reverse phase high-performance liquid chromatography, and the glycosylated peptide was located by use of tandem mass spectrometry in the neutral loss mode. Subsequent tandem mass spectrometric experiments on this peptide identified it as one surrounding Asp 549. This amino acid is completely conserved in all alpha-glucanotransferases and alpha-glucosidases belonging to this sequence -related family and is hereby identified as the catalytic nucleophile.

Amino Acid Sequence↗
PubMed1996

No attenuation of ischaemic preconditioning by the calcium antagonist nisoldipine.

In anaesthetized dogs, intracoronary infusion of calcium prior to a prolonged ischaemic period reduced infarct size, thereby mimicking the protective effects of ischaemic preconditioning and suggesting that an increase in the intracellular calcium concentration might be an important mechanism underlying this phenomenon. The aim was to determine whether pretreatment with the calcium antagonist nisoldipine attenuates the reduction in infarct size achieved by ischaemic preconditioning. In 10 enflurane-anaesthetized pigs serving as controls (group 1), the inflow into the cannulated left anterior descending coronary artery was reduced (low-flow ischaemia) to achieve a 90% reduction in an anterior myocardial work index (sonomicrometry) for 90 min. In 11 pigs (group 2), a cycle of 10 min of low-flow ischaemia and 15 min of reperfusion (preconditioning) preceded the prolonged ischaemia. In groups 3 (n = 9) and 4 (n = 7), nisoldipine was administered by intravenous infusion (500 ng/kg/min) starting 40 min prior to and then throughout a protocol identical to that of groups 1 and 2, respectively. Subendocardial blood flow was measured with radiolabelled microspheres. Infarct size (% area at risk) was determined by triphenyltetrazolium staining in all pigs after 120 min of reperfusion. Subendocardial blood flow in the area at risk was similar in all four groups (group 1: 0.09 +/- 0.04 ml/min/g; group 2: 0.05 +/- 0.03; group 3: 0.09 +/- 0.03; group 4: 0.07 +/- 0.03). Group 2 had reduced infarct size when compared with group 1 (2.6 +/- 3.0% v 12.4 +/- 8.7%, P = 0.004), and there was a trend for a reduction in infarct size following nisoldipine treatment (group 3: 10.2 +/- 7.1%, group 4: 1.6 +/- 2.8%, P = 0.01). Thus administration of nisoldipine in pigs tended to decrease infarct size, and did not abolish the cardioprotection afforded by ischaemic preconditioning.

Analysis of Variance↗
PubMed1996

[Defect fractures of the tibia--various forms of bone replacement].

Different bone substitutes exist for reconstruction of segmental tibial bone defects. The choice of bone substitute is limited by the quality of the surrounding tissue and the size of the bone defect. Especially in large bone defects, the freely or microvascularly transferred autogenic graft should be preferred. Allogenic transplants or artificial bone substitutes, such as spongy calcium phosphate materials, are suitable only for implantation in smaller, well-vascularized bone defects or as an additional procedure in large bone defects. In infected cases, allogenic and artificial, especially slowly resorbable implants, have to be avoided. The prerequisite for defect reconstruction is stable internal fixation.

Bone Substitutes↗
PubMed1996

Left and right visual field advantages are a function of scotopic and photopic retinal adaptation, respectively, in simple reaction time to near-threshold targets.

Modulation of stimulus luminance in a tachistoscopic face discrimination task has been found to significantly invert visual hemifield advantage in reaction time (RT) (Sergent, 1982a, Sergent, 1982b). However, there is no more physiological rationale for that than for a similar effect, say, of retinal adaptation, and it is even conceivable that the latter may have confounded the former in past experiments. The experiments reported here were therefore designed to tease out the relative contributions of stimulus luminance and of background illumination (i.e., retinal adaptation) in a simple RT task. Two equally difficult conditions of dim targets were set up, one with light-adapted subjects and one with dark-adapted subjects. Similarly, two equally difficult conditions of bright targets were set up with light and dark-adapted subjects. It was found that dim targets (near detection threshold) yielded a significant right visual field RT advantage in light-adapted subjects and that dim targets (equally near detection threshold) yielded a significant left visual field RT advantage in dark-adapted subjects. Future experiments will determine whether cone-mediated RT to detection is left hemisphere dominant and whether rod-mediated RT to detection is right hemisphere dominant.

Adaptation, Ocular↗
PubMed1996

Autoregulation of renal blood flow and pressure-dependent renin release in autosomal dominant polycystic kidney disease of rats.

The Han:SPRD (PKD) rat is a new animal model of autosomal dominant polycystic kidney disease (ADPKD) which resembles many clinical and pathoanatomical features of human ADPKD. The aim of the present study was to analyse age-dependent changes in renal haemodynamics and renal renin secretion which could be of pathophysiological importance in the course of the disease. We investigated glomerular filtration rate (GFR), renal blood flow (RBF), renal vascular resistance (RVR), plasma renin activity (PRA), the autoregulatory behaviour of RBF and the pressure-dependent plasma renin activity in conscious PKD rats compared with age-matched controls. Experiments were performed in conscious chronically instrumented PKD rats (age: 3 and 9 months) and their age-matched genetic controls. GFR in 3-(0.52 +/- 0.07 ml/min/100 g; n = 9) and 9-month-old (0.42 +/- 0.03 ml/min/100 g; n = 21) PKD rats were significantly lower (P < 0.05) than 3- (0.92 +/- 0.07 ml/min/100 g; n = 17) and 9-month-old (0.67 +/- 0.05 ml/min/100 g; n = 17) controls. Nine-month-old PKD revealed a significant (P < 0.005) resetting of the breakpoint of RBF autoregulation towards lower pressures (85.5 +/- 4.4 mmHg; n = 10) than either age-matched controls (102.8 +/- 2.5 mmHg; n = 11) or young PKD (107.5 +/- 4.4 mmHg; n = 6). The basal plasma renin activity was significantly (P < 0.05) lower in 3-month-old PKD than in old PKD and age-matched controls. A significant shift of threshold pressure for pressure-dependent renin release to lower pressures was observed in PKD rats. The observed improvement of autoregulatory reserve, at least in the low pressure range, could be of pathophysiological importance in delaying the progression of chronic renal failure in ADPKD. The suppression of the renin angiotensin system in young PKD could explain the fact that we did not observe hypertension in PKD rats, which is a major difference between this animal model and human ADPKD.

Aging↗
PubMed1995

Mechanism-based inhibition of yeast alpha-glucosidase and human pancreatic alpha-amylase by a new class of inhibitors. 2-Deoxy-2,2-difluoro-alpha-glycosides.

2-Deoxy-2,2-difluoroglycosides are a new class of mechanism-based inhibitors of alpha-glycosidases, which function via the accumulation of a stable difluoroglycosyl-enzyme intermediate. Two members of this new class of inhibitor have been synthesized and kinetic studies performed with their target glycosidases. Thus 2,4,6-trinitrophenyl 2-deoxy-2,2-difluoro-alpha-glucoside is shown to inactivate yeast alpha-glucosidase with a second order rate constant of ki/Ki = 0.25 min-1 mM-1. The equivalent difluoromaltoside inactivates human pancreatic alpha-amylase with ki/Ki = 0.0073 min-1 mM-1. Competitive inhibitors protect the enzyme against inactivation in each case, showing reaction to occur at the active site. A burst of release of one equivalent of trinitrophenolate observed upon inactivation of human pancreatic alpha-amylase proves the required 1:1 stoichiometry. These are the first mechanism-based inhibitors of this class to be described, and the first mechanism-based inhibitors of any sort for the medically important alpha-amylase. In addition to having potential as therapeutics, compounds of this class should prove useful in subsequent structural and mechanistic studies of these enzymes.

Carbohydrate Sequence↗
PubMed1995

Pain-related cerebral potentials in patients with frontal or parietal lobe lesions.

The present study investigated the processing of painful electrical stimuli in patients with unilateral frontal or parietal lobe damage and matched control subjects. Patients with frontal lesions showed increased pain thresholds when the stimuli were administered contralateral to the lesion. While the peak-to-peak amplitudes of the N150/P250 components of the somatosensory potentials increased linearly with stimulus intensity in the control subjects, the responses in the frontal group did not change significantly between stimulation at pain and tolerance threshold. There was no evidence for altered pain processing in patients with parietal lobe lesions. The findings of the present study support the hypothesis of an involvement of the frontal cortex in pain perception in humans.

Adult↗