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Biomedical subjects

B Schubert

Publications and source records attributed to B Schubert.

At least 55 records · Page 3Linked to original sources

Beta-adrenergic inhibition of cardiac sodium channels by dual G-protein pathways.

The signaling pathways by which beta-adrenergic agonists modulate voltage-dependent cardiac sodium currents are unknown, although it is likely that adenosine 3'5'-monophosphate (cAMP) is involved. Single-channel and whole-cell sodium currents were measured in cardiac myocytes and the signal transducing G protein Gs was found to couple beta-adrenergic receptors to sodium channels by both cytoplasmic (indirect) and membrane-delimited (direct) pathways. Hence, Gs can act on at least three effectors in the heart: sodium channels, calcium channels, and adenylyl cyclase. The effect on sodium currents was inhibitory and was enhanced by membrane depolarization. During myocardial ischemia the sodium currents of depolarized cells may be further inhibited by the accompanying increase in catecholamine levels.

8-Bromo Cyclic Adenosine Monophosphate↗

Fusarium moniliforme Sheld. A fungus producing a broad spectrum of bioactive metabolites.

Fusarium moniliforme Sheldon (perfect stage Gibberella fujikuroi (SAW. Wollenweber), an ubiquitous fungus belonging to the section Liseola (Booth), is one of the widespread, phytopathogenic fungi. This field fungus common on many crops, including rice, oats, wheat, maize, barley and soybeans was well known because of the ability to produce gibberellins in high quantities. Today beside of the very important gibberellic acid (GA3) other gibberellins such as GA4 and GA7 are of significance for agriculture and horticulture. Moreover, this fungus produces further biologically active metabolites, e.g. pigments, mycotoxins, phytotoxins, oestrogens and extracellular enzymes. Fusarium moniliforme strains are able to produce 2 pigment groups - the karotenoids and the bikaverins, the last of which has antibiotical activity against Leishmania brasiliensis. The biosynthesis of some mycotoxic substances, such as moniliformin, fusaric acid, fusarin C and fusariocin C, is described. From enzymes the milk-clotting rennin, cellulolytic and amylolytic enzymes, pectinases and phenol-degrading enzymes are of economical interest. Therefore, Fusarium moniliforme is a source of different bioactive metabolites. The production is dependent on the conditions and strain specifity.

Chemical Phenomena↗

[Myocardial damage following lightning injury].

In a 27-year-old woman, struck by lightning behind the left ear, the ECG showed signs of an acute posterior-lateral myocardial infarction after 1 h of unconsciousness and loss of memory. Her serum enzymes were increased as is typical of myocardial infarction, but the patient did not complain of cardiac symptoms. Besides clear signs of lightning injury, the patient showed a hemorrhage throughout the left breast and transient pericardial effusion was observed by echocardiography. In the course of two months, the ECG revealed a regression to unspecific ST-T-deviations and serum enzymes became normal. TI-201-myocardial-scintigraphy (SPECT), done six days and two months after lightning injury, excluded reversible and irreversible perfusion defects.

Adult↗

[Acute renal failure--clinical aspects and morphology].

This study reports the pathological-anatomical diagnoses in 180 cases in which a diagnosis of acute renal failure (ARF) had been made on clinical grounds. The clinical and pathological diagnoses were in agreement in 43.3% of the cases. In 56.7%, the pathological-anatomical diagnosis differed from the clinical diagnosis. Glomerulonephritis (GN) was particularly often concealed behind ARF, in particular rapidly progressive GN, but also acute interstitial nephritis or hemolyticuremic syndrome. In addition, the clinical diagnoses in cases with a pathological-anatomical diagnosis of ARF are presented. Finally, the clinical diagnoses made in cases with a pathological-anatomical diagnosis of GN with ARF are reported. It is thus shown that the pathologist is in a position to distinguish GN with true compensated retention from GN with transient ARF simulating compensated retention.

Acute Kidney Injury↗

Transmission and scanning electron microscopy investigations on the structure of the ultrafilter of glomeruli in human acute renal failure.

In 4 cases of human acute renal failure (ARF) with oligo-anuria, normuria and polyuria the following findings were made. (1) The diameter of endothelial cell fenestrae is on average larger than that of the control values, but not significantly. (2) In ARF the ratio of the endothelial cell fenestral area to the total endothelial area is not significantly lower than in control kidneys. (3) In ARF the average density of fenestrae per unit of area is not significantly lower than in control kidneys. (4) The structure of the podocytes does not differ from that of control kidneys.

Acute Kidney Injury↗

Cell-attached patch clamp measurement of macroscopic rapid inward sodium current in cultured heart cell reaggregates.

A megaohm seal, cell-attached patch clamp technique utilizing plastic suction pipettes for measuring macroscopic rapid inward sodium current (INa) was applied to cell membrane patches 30 to 100 micron2 in area at the periphery of reaggregates of myocardial cells from newborn rats cultured for 3 to 7 days. The reaggregates were composed of about 20 to several thousand of electrically well-coupled cells, the latter forming spheroidal reaggregates with a diameter of maximally 300 microns. This system was shown to guarantee satisfactory voltage-clamp control during ionic current measurements. The time and voltage dependence of the INa recorded during periods of up to 90 min was similar to that observed in single cardiac cell preparations from adult rats. INa inactivation was described by two time constants (tau h1, and tau h2). For maximal INa tau h1 and tau h2 had values of 1.5 +/- 0.25 ms and 8.7 +/- 3.9 ms (n = 4), respectively. The time course for recovery of INa from inactivation at the reaggregate resting potential exhibited also two time constants (tau re1 = 9.8 +/- 3 ms, tau re2 = 193 +/- 50 ms, n = 5). Estimated current density was about 10 pA/micron2. The concentration of tetrodotoxin needed to reduce maximal INa by 75% was 85 times lower in the reaggregates than it was in freshly isolated heart muscle cells from adult rats. The present system offers a combination of features that should make it well-suited for the study of both short- and long-term effects on the sodium channels in neonatal heart cells: Easy handling of the object, great electric stability, high time and amplitude resolution during ionic current measurements, and viability for at least one week.

Animals↗

Increased visualization of antral gastrin-producing G-cells after acute stimulation of gastrin release in the rat.

The effect of acute stimulation of gastrin release on the number of antral gastrin-producing G-cells stained by conventional immunohistology was investigated in two experimental models. The substituted benzimidazole derivate BY 308 was administered at a dosage that induces complete achlorhydria and thereby led to marked hypergastrinaemia. Two hours after drug administration, antral G-cell density was increased by 14% and 35% in 12-h and 48-h fasted rats, respectively. Both serum gastrin levels and G-cell density further increased after 3 and 8 days' treatment with BY 308 whereas the somatostatin (D)-cell count did not change prior to 8 days' administration. In the isolated, vascularly perfused rat stomach, acetylcholine was perfused for 36 min; this regimen increased gastrin release four-fold and enhanced the G-cell count by 24% whereas 8 min acetylcholine perfusion did not alter G-cell density significantly but stimulated gastrin output. The results of this study suggest that acute changes in the secretory activity of the gastrin cell are accompanied by an alteration of the staining characteristics thus indicating that an increase in the antral G-cell count does not solely depend upon formation of new cells.

Acetylcholine↗

A patch clamp study of the action of ethacyzine on the rapid inward sodium current in single rat heart muscle cells.

The effect of ethacyzine (a diethylamine analogue of ethmozine) on the rapid inward sodium current (INa) was studied in single rat ventricular muscle cells by a patch clamp technique. Extracellular application of 3 microM ethacyzine depressed the INa in a use-dependent fashion. Rest recovery from the use-dependent block by ethacyzine followed an exponential time course with a time constant of about 215 +/- 40 s (n = 4, mean +/- S.E.).

Animals↗

Isolation of meclofenamic acid and two metabolites from equine urine--a comparison between horse and man.

Two metabolites of meclofenamic acid have been isolated from equine urine. Both metabolites are found to be monohydroxylated forms of meclofenamic acid by gas chromatography-mass spectrometry after extractive alkylation. The parent drug and the metabolites are separated by reversed-phase liquid chromatography on a Spherisorb ODS column, using methanol-phosphate buffer eluents and UV detection at 280 nm. The structure of the metabolites is discussed on the basis of LC, TLC and GC-MS data.

Journal Article↗

[Frequency-dependent blockade of sodium channels in isolated rat myocardial cells by the anti-arrhythmia agent ethmozine].

A patch-clamp method was used to study the effects of the phenotiazine antiarrhythmic drug ethmozine (E) on the fast sodium inward current (INa) in freshly isolated heart muscle cells of adult rats. At a concentration of 10(-5) M E caused INa inhibition that could be enhanced by increasing the frequency of depolarization. This inhibition was reversible. After the termination of repetitive depolarization the amplitude of INa recovered with a time constant of about 10 sec. These findings may help to explain the therapeutic efficiency of E in high frequency cardiac rhythm disturbances.

Animals↗

[The role of disturbed DNA synthesis in the genesis of cervical carcinomas. Results of histoautoradiographic studies].

Histoautoradiographic and histopathologic studies are presented for normal and atypical cervical squamous epithelium from biopsies in 129 women. Labelling indices were obtained using in vitro labelling of biopsy specimens with H3-thymidine. In 38 cases with normal squamous epithelium, different indices were observed depending on the indication for operation. The index for normal epithelium with nearby preneoplastic changes was 5.3 +/- 1.8; for normal epithelium of patients with other diseases (uterus myomatosus, descensus uteri) it was 2.8 +/- 1.3. The index for virus-induced koilocytic dysplasias (6.3 +/- 2.9) lay between those of mild (5.3 +/- 1.4) and moderate dysplasias (7.2 +/- 1.8) without histopathological signs of virus infection. Carcinoma-in-situ (11.7 +/- 4.0) and microcarcinomas (12.6 +/- 4.2) showed higher values. There were no significant differences between the labelling indices of the microcarcinomas and preneoplastic lesions. Early stages of tumor development may histoautoradiographically offer hints of proliferative activity. In later stages the proliferative heterogeneity of the tumors limits the interpretability of the indices. The results are discussed in light of the possible role played by papilloma virus in the genesis of cervical cancer.

Autoradiography↗

Sodium and calcium currents in neuroblastoma x glioma hybrid cells before and after morphological differentiation by dibutyryl cyclic AMP.

Sodium and calcium inward currents (INa and ICa) were measured in neuroblastoma X glioma hybrid cells of clones 108CC5 and 108CC15 by a single suction pipette method for internal perfusion and voltage clamp. Morphologically undifferentiated, exponentially growing cells were compared with cells differentiated by cultivation with 1 mmol/l dibutyryl cyclic AMP. Outward currents were eliminated by perfusing the cells with a K+-free solution. Voltage dependence and ion selectivity as well as steady state inactivation characteristics of INa and ICa resembled those of differentiated mouse neuroblastoma cells, clone N1E-115 (Moolenaar and Spector 1978, 1979). These parameters were identical in undifferentiated and differentiated cells of both clones. After differentiation the average density of the peak sodium and calcium currents was increased two and four-fold, respectively, in both cell lines. Our data indicate that exponentially growing, morphologically undifferentiated 108CC5 and 108CC15 neuroblastoma X glioma hybrid cells possess functional Na+ and Ca2+ channels undistinguishable from those of non-proliferating cells of these clones differentiated morphologically by treatment with dibutyryl cyclic AMP. That Na+ and Ca2+ spikes were not detected by other authors in these cells prior to morphological differentiation by dibutyryl cyclic AMP may be attributed to the fact that at the low resting membrane potential measured the Na+ and Ca2+ channels are inactivated.

Animals↗

A kinetic analysis of the inward calcium current in 108CC15 neuroblastoma x glioma hybrid cells.

The kinetics of activation and inactivation of the inward calcium current (ICa) in morphologically undifferentiated and differentiated neuroblastoma X glioma hybrid cells of the clone 108CC15 were studied by the suction pipette technique for internal perfusion and voltage clamping. Potassium currents were eliminated by internal perfusion of the cells with a K+-free solution. Activation of ICa followed a sigmoidal time course and could reasonably be fitted by a m2 relation. The kinetics of ICa inactivation were studied by analyzing the current inactivation during long depolarizing steps and by measuring the peak ICa as a function of the length of a prepulse. Both methods gave comparable results indicating that the ICa inactivation cannot be fitted by a single exponential. The ICa inactivation was fitted by a biexponential function. Neither the activation nor the inactivation of ICa were changed after morphological cell differentiation induced by treatment with dibutyryl cyclic AMP.

Animals↗

Trapidil and other 5-triazolo-(1, 5-alpha)-pyrimidine derivatives as calcium channel blockers in 108CC5 cells.

The action of trapidil (RocornalR) and its derivatives AR 12-456 and AR 12-160 on the inward calcium current (ICa) was studied in mouse neuroblastoma x rat glioma hybrid cells of the line 108CC5 under voltage clamp conditions by means of a suction pipette method. A dissociation constant of the calcium channel-trapidil complex of 277 microM was estimated for the initial inhibition of ICa by trapidil. Half maximal block of ICa was produced by 80 +/- 20 microM AR 12-456 and 500 +/- 150 microM AR 12-160.

Animals↗

Calcium channel block by phenytoin in neuroblastoma x glioma hybrid cells.

The action of phenytoin on the inward calcium current (ICa) was studied in cells of the clonal mouse neuroblastoma X rat glioma hybrid line 108CC5 by the suction pipette technique for internal perfusion and voltage clamp. The ICa was recorded after suppression of Na+ and K+ currents. Phenytoin, applied externally in concentrations of 50 to 500 microM, depressed the ICa in the investigated potential range of -60 to +30 mV in a concentration-dependent manner. When the cells were stimulated by depolarizing clamp steps, the extent of the ICa depression increased with the frequency and duration of the activating pulses. ICa was also inhibited on intracellular application of phenytoin.

Action Potentials↗

Determination of flunixin in equine plasma by reversed-phase liquid chromatography.

Flunixin is determined in equine plasma by liquid chromatography on LiChrosorb RP-18 with 70% methanol in phosphate buffer pH 3.1 as the eluent, with detection at 284 nm. Plasma is deproteinized with methanol and the supernatant is then injected directly into the system. With a short pre-column (5 x 3 mm i.d.), which is replaced after 25-40 injections of sample, 420 plasma samples could be analysed on one analytical column. The detection limit in plasma is 0.30 micromol/l (89 ng/ml) and the method can be used in pharmacokinetic studies.

Journal Article↗