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M Weih

Publications and source records attributed to M Weih.

34 records · Page 2Linked to original sources
PubMed1999

Short-term block of Na+/K+-ATPase in neuro-glial cell cultures of cerebellum induces glutamate dependent damage of granule cells.

Granule cells in a dissociated neuro-glial cell culture of cerebellum when exposed to ouabain (10(-3) M) for 25 min apparently swell, increase their [Ca2+]i with obvious depolarization of the mitochondrial membrane. In 3 h after ouabain was omitted from the solution, 62 +/- 3% of granule cells had pycnotic nuclei. The supplement of a solution with competitive specific antagonist of NMDA receptors, L-2-amino-7-phosphonoheptanoate (10(-4) M, APH) together with ouabain prevented cells from swelling, mitochondrial deenergization, neuronal death and increase of [Ca2+]i. These data suggest that cellular Na+/K+-ATPase inactivation in neuro-glial cell cultures of cerebellum leads to glutamate (Glu) accumulation, hyperstimulation of glutamate receptors, higher Ca2+ and Na+ influxes into the cells through the channels activated by Glu. This process leads to cell swelling, mitochondrial deenergization and death of granule cells. Possibly, the decrease of Na+/K+-ATPase activity in brain cells can lead to the onset of at least some chronic neurological disorders.

2-Amino-5-phosphonovalerate↗
PubMed1999

Monitoring of venous hemodynamics in patients with cerebral venous thrombosis by transcranial Doppler ultrasound.

OBJECTIVES: To test the assumption that transcranial Doppler ultrasound (TCD) is able to detect and to monitor intracranial venous blood flow velocities in patients with confirmed cerebral venous thrombosis (CVT). DESIGN: Prospective case study in 18 patients. SETTING: Inpatient neurologic service in a university hospital. SUBJECTS AND METHODS: Serial TCD examinations were performed in 18 consecutive patients with CVT (14 females, 4 males) aged 16 to 64 years (mean+/-SD, 36.8+/-13.1 years) during a mean follow-up ranging from 34 to 783 days (mean+/-SD, 201+/-185 days) between 1993 and 1997. Venous TCD was performed with a 2-MHz range-gated transducer. RESULTS: Venous blood flow velocities were successfully measured in all patients. The highest measured velocities in the monitored intracranial venous vessels ranged from 20 to 150 cm/s (mean+/-SD, 58.9+/-38.8 cm/s), and the lowest were from 9 to 84 cm/s (mean+/-SD, 27.9+/-17.0 cm/s). Fifteen patients (83%) showed a decrease of velocities-2 of them after a transient increase during cessation of heparin therapy. The percentage of velocity decrease ranged from 34% to 73% (mean+/-SD, 56.4%+/-10.9%). A plateau phase, defined as no further decrease in velocities, was reached in these patients within 4 to 314 days (mean+/-SD, 59.9+/-73.7 days). Three patients (17%) showed no changes in velocities as defined by a limit of velocity variation of 30% during the course of CVT. High venous velocities were significantly associated with altered consciousness (P = .001). A nonsignificant relationship was observed with affliction of the superior sagittal sinus. No correlations were noted for onset of disease, initial motor deficits, and presence of bleeding. No predictive value was gained from analyzing the outcome in relation to absolute velocities or their decrease. CONCLUSIONS: Serial TCD studies allow monitoring of venous hemodynamics and collateral pathways in patients with CVT. Normal venous velocities in serial measurements, however, do not exclude a diagnosis of CVT.

Adolescent↗
PubMed1999

Blood flow velocities in the vertebral veins of healthy subjects: a duplex sonographic study.

Along with the jugular veins, the vertebral veins serve as an important pathway for venous blood returning from the brain. In this study, the authors report duplex sonographic findings in 138 healthy subjects without central nervous disease. Successful insonation was possible in 70.7% of all examined vessels. Bilateral insonation was achieved in 86 subjects (62.3%). Only 1 vertebral vein was detected in 23 persons (16.7%), whereas no vein was found in 29 persons (21%). The authors observed a marked variation of peak flow velocities ranged (5-81 cm/s, mean +/- standard deviation, 23.9 +/- 12.3 cm/s). No significant gender-related or side-to-side differences or age influences on flow velocities were detected. The authors' findings may be of relevance when discussing flow velocities in the vertebral veins in cases of cerebrovenous disorders (e.g., dural sinus thrombosis) or in patients after neck dissection.

Adolescent↗
PubMed1999

Attenuated stroke severity after prodromal TIA: a role for ischemic tolerance in the brain?

BACKGROUND AND PURPOSE: Ischemic tolerance has been extensively studied in experimental models of heart and brain ischemia. While there is some clinical evidence of ischemic tolerance in the heart, it is not known whether the same is true for the human brain. METHODS: We conducted a retrospective case-control study in 148 stroke patients with and without antecedent TIA. RESULTS: Despite no significant differences in baseline characteristics, independence (Rankin scale score of 0 to 1) and favorable outcome (Glasgow Coma Scale score of 5) were significantly associated with prior TIA in univariate analysis. After correction for other cardiovascular risk factors, TIA before stroke also was an independent predictor of mild stroke (Canadian Neurological Scale score of > or= 6.5) in multivariate models (absolute difference 21.6%; P=0.01). CONCLUSIONS: Assuming that a TIA represents an adequate stimulus to elicit ischemic tolerance, our results suggest that ischemic tolerance might occur in the human brain.

Adaptation, Physiological↗
PubMed1998

Induction of hypoxia inducible factor 1 by oxygen glucose deprivation is attenuated by hypoxic preconditioning in rat cultured neurons.

Hypoxia-inducible factor 1 (HIF-1) is a posttranscriptionally regulated transcription factor, controlling several hypoxia-inducible genes. Here we show a rapid and transient increase of HIF-1 DNA binding activity in a dose dependent manner in primary cortical neurons of rats exposed to oxygen glucose deprivation (OGD) for 30, 60, 90, or 120 min. A reduced induction of binding activity was observed when neurons were preconditioned by a non-lethal OGD interval (60 min) 48 h prior to the 90 min OGD. Thus, hypoxic preconditioning reduces activation of HIF-1 binding activity. The molecular mechanism of HIF-1 activation, its target genes, and its role in tolerance induction and/or ischemia induced damage remain to be elucidated.

Animals↗
PubMed1998

Characterization of the pulse signal over the human head by near infrared spectroscopy.

In this study we examine and describe the changes in the hemoglobin oxygenation and the Cytochrome-C-Oxidase redox state that are caused by the pulsatile character of the blood flow in the human head. We used near-infrared spectroscopy (NIRS) in combination with simultaneously recorded ECG and Transcranial Doppler sonography of arteries and veins and show that there is a distinct time lag between heart activity, arterial blood flow, hemoglobin concentration as measured by NIRS and venous blood flow. NIRS has intensively been used to measure functional activation of the brain. When measuring cortical activation by functional stimulation, the pulse signal interferes with the acquired activation signal. We demonstrate that a filter algorithm can remove the pulse artifact and therefore improves the data acquired during visual stimulation.

Adult↗
PubMed1998

Increased rate of factor V Leiden mutation in patients with cerebral venous thrombosis.

We investigated the association between cerebral venous thrombosis and hereditary resistance to activated protein C (APC) in 12 consecutive German patients with non-fatal cerebral venous thrombosis and in 187 controls without a history of thrombotic disorder. Three patients (25%) had a mutation in the factor V Leiden gene against only one subject in the control group. This difference was significant (P < 0.05), with an odds ratio of 11.7 (1.5-87; 95% confidence interval). Two patients carrying the mutation had additional common risk factors for thrombosis, and 2 had a positive family history of thromboembolism. We conclude that inherited APC resistance by a mutation in factor V Leiden is an important risk factor in non-fatal cerebral venous thrombosis. We recommend testing for APC resistance and, if abnormal for factor V Leiden mutation in patients with cerebral venous thrombosis.

Adult↗
PubMed1997

Rapid Ca2+-dependent NO-production from central nervous system cells in culture measured by NO-nitrite/ozone chemoluminescence.

We have established simple and reliable measurement of constitutive nitric oxide (NO) synthase-dependent nitrite formation in supernatants from primary central nervous system (CNS) cells in culture using NO-ozone chemoluminescence. We found that: (1) astrocytes, endothelial cells and cerebellar granule cells produce NO upon stimulation with the calcium ionophore A23187 (1 microM); (2) application of 100 microM glutamate for 2 min results in NO-production in cerebellar granule cells and cortical neurons. NO-formation upon application of 50 mM KCl was found in cortical neurons; (3) in cultivated cerebral endothelial cells, an inducible form of NO-synthase (iNOS) is found under standard culture conditions. This induction was blocked by dexamethasone applied for at least 48 h and stimulation of constitutive NOS was detectable while iNOS was inhibited. The activity of iNOS was selectively inhibited by application of aminoguanidine for 48 h. Our results suggest that all major CNS cells implied in cerebral blood flow regulation and neurovascular coupling are capable of rapidly producing the vasodilator NO upon intracellular increases of the universal second messenger calcium.

Animals↗
PubMed1996

Pneumococcal cell wall components induce nitric oxide synthase and TNF-alpha in astroglial-enriched cultures.

Astroglia and microglia, the most numerous cells in the central nervous system (CNS), have been shown to produce the inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-alpha) upon stimulation with the cytokines IFN-gamma, IL-1-beta, or bacterial lipopolysaccharides (LPS). However, it is not known whether gram-positive bacteria like Streptococcus pneumoniae cause astroglial cells to release nitric oxide (NO) and TNF-alpha. S. pneumoniae meningitis still has a high incidence and mortality in spite of antibiotic therapy. Cell wall components from S. pneumoniae (pneumococcal cell-wall components, PCW) and TNF-alpha have been shown to cause meningeal inflammation and cerebrovascular changes in experimental meningitis. Addition of PCW to cultured rat astroglial cells increased nitrite in the supernatant significantly after 24 h, from 17 +/- 21 to 133 +/- 62 nM/micrograms protein. Nitrite release was dose-dependent in a range shown to cause meningeal inflammation in vivo and was inhibited by the competitive NO synthase inhibitor NW-nitro-L-arginine (L-NA 10(-4 M)) and dexamethasone (10(-6 M)), with transcriptional and translational inhibition by actinomycin D and cycloheximide, respectively. PCW caused a significant increase in the release of TNF-alpha from astroglial cells after 4 h, from 2 +/- 3.5 pg/ml to 102 +/- 13.5 pg/ml, which was inhibited by dexamethasone (10(-6 M)). Our results suggest a role for astroglial-derived NO and TNF-alpha as mediators of vascular and inflammatory response in the early phase of experimental pneumococcal meningitis.

Animals↗
PubMed1995

Fucoidin, a polysaccharide inhibiting leukocyte rolling, attenuates inflammatory responses in experimental pneumococcal meningitis in rats.

It is presumed that adjuvant therapy rather than new antibiotics will improve the prognosis of pneumococcal meningitis. We investigated the effect of fucoidin, a polysaccharide inhibiting leukocyte rolling, on inflammatory changes in experimental meningitis in rats. After induction of meningitis by pneumococcal cell wall components, regional cerebral blood flow and intracranial pressure increased over the observation period of 6 h. At the end of the experiments, cerebrospinal fluid pleocytosis and brain water content were higher in animals with meningitis than without. Fucoidin treatment in the meningitis group reduced all inflammatory changes, whereas fucoidin treatment of animals without meningitis increased blood white cell count, but had no effect on any other parameter. Our results confirm that selectins are involved in the early phase of pneumococcal meningitis and possibly are a target for adjunctive therapy.

Animals↗
PubMed1995

Nitric oxide modulates the CBF response to increased extracellular potassium.

The response of the regional cerebral blood flow (rCBF) to brain topical superfusion of 20 mM K+ was characterized in a closed cranial window preparation in barbiturate anesthetized and ventilated rats: Increasing K+ in the artificial cerebrospinal fluid (ACSF) induced a rCBF elevation (measured by laser-Doppler flowmetry) of +85 +/- 37% above baseline (n = 19). This elevation was stable for > 3 h with continuous superfusion of increased K+ (n = 5) and partially reversible to a level of +18 +/- 19% above baseline when returning to a physiological K+ concentration. Nitric oxide synthase (NOS) inhibition by brain topical superfusion with N omega-nitro-L-arginine (L-NA) revealed (a) Addition of L-NA to high-potassium ACSF reduced the rCBF increase from +94 +/- 36% to +21 +/- 18% (p < or = 0.01, n = 7). (b) When L-NA was superfused for 60 min before increasing K+, rCBF decreased to -17 +/- 7% below baseline. Subsequent coapplication of L-NA and increased K+ induced only an elevation of +7 +/- 4% above baseline (n = 4). (c) When the NO donor S-nitroso-N-acetylpenicillamine (SNAP) was added during NOS inhibition to restore basal tissue NO levels, the resultant level of rCBF was +28 +/- 54% above baseline. Subsequent increase of K+ in the presence of NOS inhibition and SNAP elevated rCBF to +137 +/- 89% above baseline (n = 4).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Inhibition of growth by calcitriol in a proximal tubular cell line (OK).

Calcitriol has been shown to inhibit (i) cell proliferation of renal carcinoma cell lines and of cultured adult human mesangial cells in vitro, and (ii) renal compensatory growth in vivo. In the present study we examined the effects of calcitriol on DNA synthesis and cell replication in an immortalized cell line showing the phenotypic characteristics of proximal tubular cells (opossum kidney, OK cells). The viability of OK cells was not affected by calcitriol (Trypan-blue exclusion, LDH and K+ release), but the cells did not convert 3H-25(OH)2D3 to 3H-1,25(OH)2D3. In the log growth phase, calcitriol (but not alternative vitamin D metabolites) caused dose-dependent (10(-12) to 10(-6) M) inhibition of radiothymidine incorporation. Inhibition was calcium dependent, i.e. it was more pronounced at the lower nominal calcium concentration in tissue culture media (0.9 versus 1.8 mmol/l) and amplified by coincubation with nifedipine (1 microM). Inhibition of DNA synthesis was paralleled by inhibition of cell replication (growth curve) under basal conditions and after stimulation with EGF (10 ng/ml). In conclusion, calcitriol inhibits proliferation of proximal tubular cells which normally express 1-alpha-hydroxylase activity.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMedDate not supplied

Measurement of cerebral circulation time by contrast-enhanced Doppler sonography.

We present a new, non-invasive ultrasound method for the measurement of cerebral circulation time. After injection of a galactose-based echo-contrast agent (Levovist) into an antecubital vein, cerebral circulation time is measured as the interval between the beginning of a stable signal enhancement of at least 5 dB in the internal carotid artery and in the ipsilateral internal jugular vein. Both vessels are insonated simultaneously at the mandibular angle using a single 2-MHz range-gated transducer. For this study, 25 healthy volunteers ranging in age from 23 to 55 years (30.1 +/- 7.5 years; mean +/- SD) were examined. Cerebral circulation time was 5.6 +/- 1.7 s without significant side-to-side or sex-related differences. Measurement of circulation times offers a new possibility for the employment of echo-contrast agents in functional ultrasound.

Adult↗
PubMedDate not supplied

Angiotensin II induces hypertrophy and hyperplasia in adult human mesangial cells.

Several experimental studies point to a potential role of angiotensin II (Ang II) in the progression of glomerulosclerosis even in the absence of glomerular hypertension. We tested the hypothesis that Ang II acts as a growth factor for adult human mesangial cells (AHMC). AHMC were isolated from noninvolved parts of tumor nephrectomy specimens and grown in RPMI medium with the addition of fetal calf serum (FCS). All studies were performed with growth-arrested cells. Proliferation studies were done in serum-free standard growth medium (SF) with the addition of either various concentrations of insulin, plasma-derived serum, or FCS. Ang II (10(-10) to 10(-6) M) dose dependently increased the 3H-thymidine uptake of AHMC up to 57 +/- 13% over solvent controls (p < 0.01). In parallel, the DNA content was 36 +/- 10% higher (p < 0.05) than in solvent controls after 2 days of culture. The cell numbers were higher up to 47 +/- 8% in Ang II (10(-6) M) stimulated cultures after 4 days of incubation (p < 0.01). The effect of Ang II was specific, since it was almost completely obliterated by the AT1 receptor antagonist DuP753. The effect of Ang II was particularly marked when cultures were incubated with SF plus high concentrations (1.7 x 10(-6) M) of insulin or SF plus 10% plasma-derived serum. In contrast, the effect was not significant when cultures were incubated with SF plus 10% FCS. Ang II, when added to platelet-derived growth factor at various concentrations, did not further increase the proliferation. The effect on protein synthesis was assessed in growth-arrested AHMC by 3H-methionine uptake and protein/DNA ratio in cell lysates. Ang II (10(-10) to 10(-6) M) dose dependently increased the 3H-methionine uptake of AHMC up to 47 +/- 10% over solvent controls (p < 0.01). In parallel Ang II (10(-8) to 10(-6) M) dose dependently increased the 3H-methionine uptake of the protein/DNA ratio by 24 +/- 6% after 48 h of incubation. DuP753 obliterated the stimulatory effect of Ang II. Ang II (10(-6) M) also increased the mRNA of the immediate-early growth-related gene Egr-1. We conclude that Ang II induces hypertrophy and proliferation in adult human mesangial cells. This result is of interest with respect to a potential role of Ang II in the pathogenesis of glomerulosclerosis in humans.

Adult↗