Acute effects of dichloromethane on arrhythmia development during the early phase of myocardial ischemia and reperfusion in the rat.
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Biomedical subjects
Publications and source records attributed to M Weise.
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Acute methanol intoxications are infrequent among accidental or suicidal intoxications today. The characteristic findings are illustrated by a review. Mainly, the methanol metabolites formaldehyde and formic acid are of toxicologic importance and cause the dominant central nervous and ocular symptoms. The principal therapeutic procedures include gastric lavage, induced vomiting, titrated correction of acidosis with sodium bicarbonate, administration of ethanol, folic acid and, especially, the secondary detoxication with peritoneal--or better--haemodialysis. The therapeutic measures must be started quickly and carried out consequently to improve the prognosis of methanol intoxication and to decrease the frequency of serious late complications like ophthalmologic and neurologic lesions. Our own medical management is described by a case report treated successfully.
Dichloromethane sensitizes the myocardium to arrhythmia development in response to catecholamines. The effects of acute dichloromethane exposure (3.1, 6.2 or 12.4 mmol/kg) on cardiovascular actions of epinephrine (1 or 4 micrograms/kg iv) and norepinephrine (2 or 10 micrograms/kg iv) in the urethane-anaesthetized rat model was investigated. Hypertensive epinephrine effects as well as reflex bradycardia after epinephrine and norepinephrine injections were augmented in dichloromethane-exposed rats. Moreover we observed an enhanced negative dromotropic epinephrine action. The transient T-wave elevation after catecholamine injection was markedly increased in animals treated with 12.4 mmol/kg dichloromethane. The results show that dichloromethane exposure modifies cardiovascular actions after catecholamine administration. The release by dichloromethane of endogenous catecholamines could play a role in the manifestation of these effects.
The development and establishment of intensive care units for adult patients requires a far-reaching subdivision into surgical and conservatively oriented intensive care for qualitative and quantitative reasons. Insufficiently substantiated claims to monopolization of intensive care techniques that are polemically asserted have to be strongly contradicted. The present paper is concerned with approved structural concepts of intensive care developed by Deutsche Krankenhausgesellschaft and various medical societies. They are supplemented by personal experience in the field of internal intensive care.
The concentration of 18 alpha-amino acids (AAs) in plasma and renal cortical cell water were measured 3 or 24 hr after 1 hr of unilateral renal artery clamping or 24 or 48 hr after 15 mg/kg body weight HgCl2 injection sc as a test of epithelial integrity. Cellular glycine (Gly), hydroxyproline (Hpr), ornithine (Orn), phenylalanine (Phe), serine (Ser), and tryptophan (Trp) concentrations were depressed 24 hr after HgCl2 (p less than 0.05), but the remaining 12 AAs were not distinguishable from control despite the presence of severe renal failure. ARginine (Arg), glutamic acid (Glu), and valine (Val) also were decreased (P less than 0.05) 24 hr later, but concentrations of half of all measured AAs were still normal. Cellular alanine (Ala), Arg, Glu, Gly, Phe, and Ser concentrations were decreased 3 hr after ischemia, p less than 0.05, but 12 AAs were unchanged and only Arg, Phe, Ser, and threonine (Thr) were reduced 24 hr after ischemia was reversed. Concentrations of even the most affected AAs remained notably higher than in plasma in both forms of acute renal failure (ARF). Total loss of AAs from a small proportion of tubular cells would be hidden by essentially normal concentrations in the rest, and such losses may well have occurred. Unless cellular AAs in ARF are almost completely bound, however, the well-maintained cell:plasma AA concentration ratios indicate that cellular energetics were adequate for AA uptake and that epithelial permeability to AAs in the vast majority of cells was not greatly disturbed. Such findings suggest that most of the epithelium, although seriously damaged, had remained viable.
The acyl-CoA ligases convert free fatty acids to acyl-CoA derivatives, and these enzymes have been shown to be present in mitochondria, peroxisomes, and endoplasmic reticulum. Because their activity is obligatory for fatty acid metabolism, it is important to identify their substrate specificities and subcellular distributions to further understand the cellular regulation of these pathways. To define the role of the enzymes and organelles involved in the metabolism of very long chain (VLC) fatty acids, we studied human genetic cell mutants impaired for the metabolism of these molecules. Fibroblast cell lines were derived from patients with X-linked adrenoleukodystrophy (X-ALD) and Zellweger's cerebro-hepato-renal syndrome (CHRS). While peroxisomes are present and morphologically normal in X-ALD, they are either greatly reduced in number or absent in CHRS. Palmitoyl-CoA ligase is known to be present in mitochondria, peroxisomes, and endoplasmic reticulum (microsomes). We found enzyme-dependent formation of lignoceroyl-CoA in these same organelles (specific activities were 0.32 +/- 0.12, 0.86 +/- 0.12, and 0.78 +/- 0.07 nmol/h per mg protein, respectively). However, lignoceroyl-CoA synthesis was inhibited by an antibody to palmitoyl-CoA ligase in isolated mitochondria while it was not inhibited in peroxisomes or endoplasmic reticulum (ER). This suggests that palmitoyl-CoA ligase and lignoceroyl-CoA are different enzymes and that mitochondria lack lignoceroyl-CoA ligase. This conclusion is further supported by data showing that oxidation of lignoceric acid was found almost exclusively in peroxisomes (0.17 nmol/h per mg protein) but was largely absent from mitochondria and the finding that monolayers of CHRS fibroblasts lacking peroxisomes showed a pronounced deficiency in lignoceric acid oxidation in situ (1.8% of control). In spite of the observation that lignoceroyl-CoA ligase activity is present on the cytoplasmic surface of ER, our data indicate that lignoceroyl-CoA synthesized by ER is not available for oxidation in mitochondria. This organelle plays no physiological role in the beta-oxidation of VLC fatty acids. Furthermore, the normal peroxisomal oxidation of lignoceroyl-CoA but deficient oxidation of lignoceric acid in X-ALD cells indicates that cellular VLC fatty acid oxidation is dependent on peroxisomal lignoceroyl-CoA ligase. These studies allow us to propose a model for the subcellular localization of various acyl-CoA ligases and to describe how these enzymes control cellular fatty acid metabolism.
The bovine P2 protein is known to produce experimental allergic neuritis (EAN) in Lewis rats. The longest region of amphipathic alpha-helix within the bovine P2 protein was identified as residues 61-72. A synthetic peptide representing this sequence was synthesized and shown to have the ability to (1) produce EAN in Lewis rats by direct sensitization, (2) produce a lymphoproliferative response in a P2-specific T cell line, and (3) stimulate a P2 protein-specific T cell line sufficiently to transfer EAN to naive recipient Lewis rats. Residues 61-72 is the shortest sequence thus far identified that will produce EAN in the Lewis rat and supports the contention that T cell determinants tend to be amphipathic alpha-helices.
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P2 protein is a minor component of the myelin membrane. We have crystallized this protein for high-resolution crystallographic study. Three crystal morphologies are available. Two of them are from ammonium sulfate, and one is from polyethyleneglycol (PEG). The unit cell of the most suitable crystals from PEG 4000 has the dimensions a = 91.3 A, b = 99.8 A, c = 56.0 A; is of space group P2(1)2(1)2(1); and contains up to four molecules per asymmetric unit. The limit of resolution is 2.7 A.
Single crystals of bovine P2 myelin protein have been grown in polyethylene glycol 4000 by the hanging-drop vapor diffusion method. Crystals belonging to space group P2(1)2(1)2(1) with cell dimensions a = 91.8 A, b = 99.5 A, c = 56.5 A (1 A = 0.1 nm). The diffraction pattern extends to better than 2.3 A resolution.
It is reported on the malignant course of a case of rheumatoid arthritis, in which the participation of the heart became the cause of death. Here it is stated that we certainly enlarge our knowledge on the participation of the heart by modern cardiological diagnostics, but therapeutically are not yet able to engage decisively in the fateful course of the systemic rheumatoid basic disease. Therefore, efforts about an early cardiologic diagnosis are at present not yet of therapeutic consequences.
Serum magnesium concentrations were followed during the course of coronary infarction and were correlated to the event on the basis of the creatinine kinase activity E.C. no. 2.7.3.2. Those patients admitted to the hospital at a very early stage of the infarction showed initial high serum magnesium concentrations which fell during the event to subnormal values and then normalized later. In the case of severe coronary infarction (maximum CK activity greater than 700 U/1) the subsequent decrease in serum magnesium concentration was more pronounced than in subjects with lower CK activity. Patients suffering from angina pectoris had normal serum magnesium values which did not show any concentration change during a clinical follow-up. The previously postulated correlation between low serum magnesium and high risk for myocardial infarction may be questioned in the light of our observations.
We describe the group-selective separation and quantification of unmodified, modified and hypermodified ribonucleosides in physiological fluids (urine, serum) by on-line multidimensional high-performance affinity chromatography (HPAC)-reversed-phase liquid chromatography (RPLC). The excretion levels and patterns of ribonucleosides such as N1-methyladenosine, N1-methylinosine, N2-methylguanosine, N2-dimethylguanosine, N6-carbamoylthreonyladenosine and 2-pyridone-5-carboxamido-N-ribofuranoside were determined in urines from a control group and from patients with different diseases. The HPAC-RPLC method applied represents a powerful tool, e.g. as a non-invasive screening test, a method to investigate disorders in ribonucleoside and/or RNA metabolism, a method for drug monitoring during nucleoside chemotherapy, and a method to study renal ribonucleoside reutilization.
157 EDTA blood samples from thrombocytopenic patients (platelets less than 100 X 10(9)/1) were measured and the platelet counts compared using the various blood cell counters of the central laboratory, University Clinic, Göttingen. Using the H 6000, Hemalog 8 (both Technicon) and ELT-8 (Ortho Instruments), product-moment correlation coefficients (r) ranging from 0.88 to 0.92 were obtained between the different counters. The correlation coefficients of the thrombocounter (Coulter) to the other instruments were only 0.84 and 0.85. Discrepant platelet counts (difference greater than 40 X 10(9)/1) were reinvestigated using the Neubauer chamber. From a total of 354 platelet measurements, falsely high concentrations were observed only in three cases and falsely low concentrations in seven cases.
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Report on an extended thrombosis of the lower leg and the femur in which after a successless ambulatory treatment of one year an arthrocele of the knee-joint of the size of a fist could be proved. After operative removal of it a clinical regression of all symptoms of phlebothrombosis over a period of 2 years was observed. It is recommended to observe increasingly the in no case rare arthroceles in the thromboses of the lower extremities and if the occasion arises to include their operative treatment in the therapeutic considerations.
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