Biomedical subjects
Publications and source records attributed to J Schmidt.
The development of ethanol preference behaviour in rats is connected with a decrease of dopamine release from striatum slices seen after alcohol cessation. The inhibition of dopamine release vanishes spontaneously within a few days. Restitution is highly accelerated by piracetam, exhibiting similarities to posthypoxic membrane damages.
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Ventricular arrhythmias, especially ventricular fibrillation, are assumed to be a main cause of sudden death during the first 24 h of acute myocardial infarction. Effective prophylaxis and acute suppression of these life-threatening rhythm disturbances are a major therapeutic problem. The present study was undertaken to investigate the efficacy of the new antiarrhythmic compound stirocainide (2-(1-benzylidene)cycloheptenimino-oxyethyl-diisopropylamine -2-butenedionate, Th 494) in suppressing "2nd phase arrhythmias" arising from large anteroseptal myocardial infarctions using a standardized experimental canine preparation. Our results demonstrate that "2nd phase arrhythmias"--i.e. frequent ventricular ectopics, tachycardias, salvos, and R-on-T phenomena--are reduced by 80-90% (sometimes even completely abolished) by stirocainide (dose: 4 mg/kg within 3 min, followed by 300 micrograms/kg X min over a 20-min period). The administration of the drug at the dose used does not produce severe cardiodepression, but intraventricular conduction time is significantly prolonged. Thus, Th 494 is a highly effective antiarrhythmic agent in acute myocardial infarction, and further experimental and clinical investigations on its antiarrhythmic and antifibrillatory properties may lead to beneficial therapeutic results.
This study anhidrotic ectodermal dysplasia in quadruplets, allows the authors to recall the principal signs of this affliction, which are anhidrosis, or hypohidrosis, hypotrichosis and anodontia or hypodontia.
The effects of rapid-eye-movement (REM) sleep deprivation for 72 h on motor behaviour of rats have been studied. It has been shown both an increased spontaneous locomotor activity and an enhanced rotational behaviour after unilateral intrastriatal injection of dopamine 24 h and 48 h after the end of REM sleep deprivation. The enhancement of motor activity after REM sleep deprivation points to changes in the dopaminergic transmission system. But it is not yet clear, if the main cause of these effects is the development of a super-sensitivity of postsynaptic dopaminergic receptors. In the same way interactions between the dopaminergic system and other inhibitory transmission systems may play an important role, explaining effects of REM sleep deprivation.
The detection and characterization of oncogenes via RNA tumor viruses (or retroviruses) and the recognition of their location at breakpoints of chromosomal translocations which are frequently found in certain human neoplasms has promoted present understanding of molecular mechanisms underlying carcinogenesis. Oncogenes are cellular genes which can be transduced by RNA tumorviruses and induce malignant transformation under experimental conditions in vivo and in vitro. A role of retroviruses in human leukemogenesis is suggested by epidemiological observations and by the isolation of such viruses from several human T-cell leukemias and lymphomas (human T-cell leukemia/lymphoma virus or HTLV) as well as by biochemical association of retroviral markers with human leukemias. A role of HTLV has been suggested also in a human immune deficiency syndrome (AIDS). In view of the well known role of many factors in carcinogenesis the concept of carcinogenesis as a multistep process as well as the concept of cocarcinogenesis and the role of cofactors other than viruses, such as radiation and chemicals, aging, hormones, graft vs host reaction, environmental factors etc., will have to be carefully considered.
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ETF Dehydrogenase is an iron sulfur flavoprotein responsible for the transfer of electrons between electron transfer flavoprotein (ETF) and CoQ of the electron transport chain. We have determined the resonance Raman spectrum of this enzyme observing in the process at least seven of thirteen flavin bands in the 1100cm-1-1600 cm-1 region of the Raman spectrum. The positions of three of these bands, II, IX, and X (see Figure I and Table I for band numbering system) in ETF dehydrogenase is very similar to their positions in aqueous solution of flavins in which water is hydrogen bonded to N-1, N-5, C=0(2), C=0(4), and N-H(3) of flavin. Conversely the positions of the flavin Raman bands are considerably shifted from those of flavin in nonhydrogen bonding solvent. The positions of bands II, IX, and X are nearly identical to those in the flavoprotein glutathione reductase; x-ray structural investigations on this enzyme indicate that there is extensive hydrogen bonding between FAD and protein in this molecule. A previous study in our laboratory has demonstrated that metal complexation at N-5 and C=0(4) with either Ru or Ag produces large shifts in the positions of Raman bands II, VI, IX, and X. None of these shifts are observed in ETF dehydrogenase indicating that there is no direct inner sphere coordination of Fe to flavin. In addition to the Raman bands of flavin observed in our spectrum, we also observe one band that is in the Fe-S stretching region observed for a variety of Fe-S proteins. This band is located at 331 cm-1. The frequency of the band corresponds to the 335 cm-1 band associated with the strongest Fe-S stretching mode in the 4Fe-4S protein ferrodoxin from C. pasterianum. The observed frequency is quite different from that of the 3Fe-3S proteins such as ferrodoxin(II) from D. gigas. Finally, ETF dehydrogenase shows no loss of activity or visual evidence of photodegradation in the laser beam as most other FeS proteins do.
Orthograde intestinal lavage was successfully used in the treatment of eight patients with acute poisoning. Three had mushroom (Amanita pantherina) poisoning, five acute drug intoxication (attempted suicide: diazepam, dihydropyridine, crotylbarbital, phenobarbital, amitriptyline and glibenclamide). Within 5-18 hours the clinical signs of poisoning regressed in four patient in stage IV (after Reed), so that the patients became responsive. Detoxication by orthograde intestinal lavage is achieved by mechanical removal of nonabsorbed compounds from the gastro-intestinal tract and via intestinal dialysis across the intestinal mucosa.
The effect of elevated extracellular potassium on acetylcholine receptor synthesis was studied in chick embryonic muscle cultures. At physiological ionic strength, potassium chloride, in the 3.3 to 50 mM range, gave rise to a complex dose-response curve whose prominent features are a considerable reduction of receptor appearance rate at 20 mM and a more than 2-fold increase at higher concentrations. The effect of potassium chloride on receptor synthesis appears to be fairly specific: neither was there a duplication of its effect by other electrolytes or solutes, nor did it alter total protein synthesis or receptor stability by more than 30% at any concentration tested; cellular acetylcholinesterase levels actually declined with increasing KCl concentrations. In order to explore the mechanism of the potassium effect, tetrodotoxin (10(-6) M), veratridine (3 X 10(-6) M), D-600 (1.6 X 10(-5) M), and ryanodine (3 X 10(-7) M) were tested in the presence of various concentrations of potassium. Sodium channel toxins as well as calcium effectors modified the potassium response. Based on these findings we propose that the effects of potassium are due to: (a) cessation of spontaneous muscle activity upon raising KCl from 3 to 10 mM; (b) depolarization of the muscle membrane and persistent activation of a calcium channel as concentration is raised from 10 to 20 mM; (c) finally, inactivation or desensitization of the calcium channel, or some other signaling element proximal to the sarcoplasmic reticulum, upon further depolarization.
Extracts of calf brain were analyzed for substances capable of blocking the binding of [125I]-alpha-bungarotoxin to chick brain membrane preparations, and shown to contain blocking activity that was insensitive to heating and trypsin. Fractionation on Sephadex G-25 yielded two components, one representing nonspecific inhibition by inorganic cations, the other identified as choline by co-chromatography experiments and analysis of the purified inhibitor using thin layer chromatography and mass spectrometry. These results support the notion that the alpha-bungarotoxin binding macromolecule in the central nervous system is an acetylcholine receptor.
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A new non-invasive method for investigating total coronary blood supply is presented. This method is based on the principle of indicator dilution of a radio-nuclide bolus (99Tc), requiring a scintillation camera with high sensitivity and high picture resolution. The first findings obtained from 83 patients are shown. With 4.61 +/- 1.19% of cardiac output the mean values of the rates of coronary perfusion obtained at rest in subjects with a normal heart differed significantly from those obtained for patients with certain coronary occlusions (8.18 +/- 3.99% of cardiac output) and from those obtained for hypertensive patients (Stages I-III). Double examinations carried out on 20 patients yielded an adequate reproducibility. The mean deviation of the double examinations from one another was 16%.
13 ,14 -Dihydro-15-keto-PGF2 alpha (PGFM) serum levels were determined by radioimmunoassay in 101 postpartum women who were treated with 200 micrograms methergin, 5 I.U. oxytocin and 500 micrograms sulprostone, respectively, 30 min after expulsion of placenta. All patients had normal deliveries. The present radioimmunoassay system did not show cross-reactivity with sulprostone. In addition, radioimmunoassayable sulprostone serum levels were monitored. Covariance analysis of area under PGFM serum levels between time zero and 180 min after application of oxytocics was performed. A higher but statistically not significantly PGFM serum level was maintained in subjects treated with sulprostone. Sulprostone serum levels are rapidly attained after application. Decrease of radioimmunoassayable sulprostone indicates a half-life of 75 min. These data corroborate clinical findings of an accompanying paper and combine to suggest that sulprostone may be a useful alternative therapy in high-risk patients with severe postpartum atony and hemorrhage in whom prior preventive measures have failed.
UNLABELLED: With the introduction of prostaglandins to obstetrics another group of substances was known to influence uterine motility also post partum. It was interesting to study the effect of equal doses of synthetic prostaglandin E2 (sulprostone), methergin and synthetic oxytocin on the so-called puerperal model in humans. By transcervically introduced twin-catheters uterine motility was recorded after uncomplicated pregnancy and delivery in 101 volunteers. Uterine motility was recorded and evaluated according to the onset of the effect, its duration, motility pattern and uterine activity. Maternal heart-rate was additionally recorded similarly to the feto-maternal cardiotocogram. All substances were applied by intramuscular injection. The following observations could be made: 1. Onset: sulprostone is effective in the shortest time, followed by oxytocin and methergin. 2. DURATION: the most prolonged effect is noticed with methergin, followed by sulprostone and syntocinon. 3. Motility pattern: the strongest effect can be seen with sulprostone, followed by methergin and syntocinon. 4. Increase of uterine motility was highest with sulprostone, followed by methergin and oxytocin. 5. No side-effects on the maternal heart-rate could be found with any of the tested substances. As a conclusion, sulprostone is recommended in the treatment of severe bleeding post partum when an immediate and long-lasting effect is to be achieved with one single substance.
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The alcohol preference has been used as a model of drug habituation in animal experiments in order to examine the influence of altered synaptic efficiency of central transmission systems following acute receptor reactions with agonists or antagonists as well as by alterations of receptor sensitivity in mice. Ethanol in 10 per cent solution as the only beverage over 4 weeks produces an ethanol preference quotient 1 in the free choice of ethanol solution and water. Control animals without ethanol exposure before the preference test are only drinking water and refuse ethanol. A single injection of haloperidol increases the preference, apomorphine as well as a long term haloperidol administration producing a dopaminergic supersensitivity diminishes the preference. Moreover the preference is enhanced by atropine, isoprenaline and pholedrine and is decreased by arecoline, propranolol and phenoxybenzamine. Cyproheptadine and picrotoxine do not influence the preference. The results point to a preference promoting influence of the alpha- and beta-adrenergic transmission and to an inhibition by dopaminergic and cholinergic activity. An influence by the 5-HT and GABA system could not be observed. Additionally the paper describes the decrease of the ethanol preference by the nootropics piracetam, meclofenoxane, methylglucamine orotate and nicergoline.