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Biomedical subjects

S Marklund

Publications and source records attributed to S Marklund.

At least 19 recordsLinked to original sources

Enzyme and immunohistochemical assessment of myocardial damage after ischaemia and reperfusion in a closed-chest pig model.

The usefulness of different enzyme and immunohistochemical stains to distinguish reversible and irreversible myocardial cell injury after experimental coronary artery occlusion of varying duration and reperfusion with or without superoxide dismutase as adjunct was investigated. Biopsies or parts of the infarcted and non-infarcted area were rapidly frozen and sectioned in series for enzyme and immunohistochemical evaluation. Sections were stained for the demonstration of phosphorylase, myofibrillar ATPase and mitochondrial oxidative enzymes and also with periodic acid-Schiff, alizarin red S and routine histological stains. Other sections in series were stained with antibodies against fibronectin and the intermediate filament proteins desmin and vimentin. In 49 biopsies a blind quantitative estimation of the area stained for fibronectin, phosphorylase and alizarin red S was performed and evaluated statistically. Phosphorylase, periodic acid-Schiff, fibronectin and alizarin red S allowed delineation of affected myocardium after 30 min of ischaemia followed by reperfusion whereas with the other stains, affected myocardium was readily detectable only after 60 or 90 min of ischaemia followed by reperfusion as well as after 24 h of ischaemia without reperfusion. The immunostaining for fibronectin was very distinct and inversely related to the phosphorylase activity. We show that fibronectin is an excellent marker for damaged cells and that these positively stained myocytes are necrotic as confirmed ultrastructurally. Using alizarin red S as a marker of calcium accumulation in myocytes, a marked discrepancy was observed between the area of fibronectin-containing myocytes and that of myocytes stained by alizarin red S. Calcium accumulation in mitochondria is thus not a prerequisite for myocyte necrosis but does occur only in some of the irreversibly damaged cells. Of special interest is the finding that there was a significant reduction of intracellular calcium in pigs where superoxide dismutase had been used as an adjunct at reperfusion, thus supporting the theory that free radicals do play a role during reperfusion of ischaemic myocardium.

Adenosine Triphosphatases

Factors affecting work-time allocation among physiotherapists. A multiple classification analysis.

As part of a time budget study among 149 physiotherapists in Västerbotten County, northern Sweden, a Multiple Classification Analysis was completed. The aims were to evaluate the relative importance of some factors for the allocation of working hours, and to devise comparable measures of the ability of the particular set of variables to account for the variations in time utilisation. Occupational area was the most important factor in explaining the distribution of working hours, when the other factors were kept constant. Time utilisation was slightly affected by professional post and sex, but not by working hours. The explained variance, R2, was 0.37 for patient treatment and 0.30 for transport, indicating a fair degree of explained variance in these models. The R2 coefficients for the other tasks were low, indicating that factors, not included in the study, were more important in explaining the allocation of working hours for those tasks.

Adult

Interaction between benzylpenicillin and thiopental in the central nervous system of the male rat.

The effect of benzylpenicillin (BPC) pretreatment on the kinetics and brain sensitivity for thiopental was studied in male rats using a previously developed electroencephalgrafic (EEG) threshold method. Thiopental was infused intravenously with constant infusion rate. The rats were killed by decapitation immediately after the first burst suppression of 1 sec. or more (the silent second) which was observed in the EEG-record during the infusion. Thiopental concentration in serum and in different brain regions was determined by a high pressure liquid chromatografic method. After pretreatment with 0.9 g/kg of BPC the dose of thiopental needed to induce the silent second was significantly reduced (-20 per cent) when compared with saline treated controls. The serum concentration was also reduced (-30 per cent) after this BPC pretreatment but the concentrations in the different brain regions were the same in both groups. After pretreatment with 1.2 g/kg of BPC almost all animals had convulsions, the dose needed to obtain the silent second was very much reduced and there were reduced concentrations of thiopental in the different brain regions. After both doses of BPC high negative correlations were found between BPC concentrations in brain tissue and thiopental concentrations in hippocampus and brainstem indicating an interaction between the drugs. The most probable site of this interaction is the organic acid transport system out of the CNS which could be used by both substances. Lipid solubility is not the only factor involved in the distribution of thiopental in the rat brain.

Animals

Plasma-selenium, glutathione peroxidase in erythrocytes and mercury in plasma in patients allegedly subject to oral galvanism.

Twelve patients with subjective symptoms, ascribed by the patients themselves to mercury released from dental restorations, were investigated. In addition to a general dental examination the following parameters were registered: the total number of amalgam surfaces in the mouth; potential and polarization of existing and accessible dental metallic restorations for calculation of intraoral currents. As regards the highest calculated intraoral current for each individual there was a statistically significant difference between the patient group and a control group consisting of 12 persons. An analysis of the amount of selenium, glutathione-peroxidase and mercury in the blood showed no differences between the patient and the control group. However, a statistically significant positive correlation could be seen between the total number of amalgam surfaces and the plasma-mercury level for patients and controls pooled together. The numerous other blood parameters analyzed did not reveal any differences between the groups.

Adult

Enhanced breakdown in vitro of bovine articular cartilage proteoglycans by conditional synovial medium. The effect of superoxide dismutase and catalase.

We have previously reported that addition of conditioned medium derived from fragment cultures of synovial tissue dissected from bovine knee-joints (SM) to cultures of articular cartilage derived from the same knee-joint resulted in enhanced breakdown of cartilage proteoglycans, measured as the release of [35S]sulphate from pieces of prelabelled cartilage. It has also been reported that oxygen-centered free radicals can degrade cartilage proteoglycans and that superoxide dismutase and catalase can reduce such degradation. Here we report that superoxide dismutase and catalase do not significantly affect the degradation of articular cartilage proteoglycans enhanced by conditioned synovial medium. It therefore appears that oxygen-centered free radicals are of at most minor importance for the degradation of cartilage enhanced by conditioned synovial medium.

Animals

Strategies and techniques for sample collection and analysis: experience from the Swedish PCB accidents.

A series of polychlorinated biphenyl (PCB) fires and explosion in PCB-filled capacitors and transformers is discussed. A sampling program followed by isomer specific determination of trace levels of polychlorinated dibenzofurans (PCDFs) and polychlorinated dibenzo-p-dioxins (PCDDs) is described. Data from a series of Swedish PCB accidents are given. In addition to PCDFs and PCDDs, we have also found a series of polychlorinated biphenylenes (PCBPs). Cleaning of contaminated areas was done by vacuum cleaning followed by high pressure washing.

Accidents, Occupational

Assessment of human exposure to polychlorinated dibenzofurans and dioxins.

Fires, explosions and other accidents in polychlorinated biphenyl (PCB)-filled equipment can result in possible exposure of firemen, cleaning personnel and regular workers. Inhalation, dermal exposure and ingestion are the possible routes of exposure. An indirect assessment of the exposure can be made by analyses of wipes, air and water samples and clothes. A direct assessment of exposure can be made by analyses of blood samples, adipose and other tissue samples, feces and bile.

Adipose Tissue

Role of free oxygen radicals in the development of gastrointestinal mucosal damage in Escherichia coli sepsis.

Live Escherichia coli were infused into anesthetized cats given 0.6 ml bile/kg and 80 mM HCl into the stomach. Systemic and pulmonary arterial blood pressures, cardiac output, and gastric blood flow were monitored. Gastrointestinal total wall and mucosal blood flow were measured by microspheres. The microscopic mucosal damage was graded 0-4 (stomach) or 0-5 (intestine). One group of cats (N = 8) received 5 mg yeast CuZn superoxide dismutase (SOD) as a bolus before bacteria followed by infusion 50 mg/3 hr. Four of these cats were also given catalase in the same dose. Controls (N = 8) had no treatment. After 3 hr gastric ulceration (grades 2-4) was found in controls but only in 50% of treated cats (P less than 0.1). About 50% and 25% of the cats in both groups developed significant small intestinal and colonic mucosal damage, respectively. SOD or SOD/catalase had no effect on late systemic hypotension, decrease in cardiac output, or transient increase in pulmonary pressure. Total gastric blood flow did not change, while at late sepsis gastric mucosal flow was decreased in the treated group. Small intestinal mucosal flow decreased in both series. It is concluded that free oxygen radicals may be of partial importance in the development of sepsis-induced gastric, but not intestinal, mucosal damage.

Animals

Superoxide dismutase, catalase and scavengers of hydroxyl radical protect against the toxic action of alloxan on pancreatic islet cells in vitro.

Experiments with isolated pancreatic islets or dispersed islet cells from non-inbred ob/ob mice were performed to test the hypothesis that free radicals, notably OH., mediate the diabetogenic toxicity of alloxan. Accumulation of 86Rb+ by whole islets and exclusion of Trypan Blue by dispersed cells were used as previously validated criteria of islet-cell viability. Alloxan alone drastically inhibited the Rb+ accumulation and significantly decreased the frequency of cells excluding Trypan Blue. Enzymic scavengers of O2.- and H2O2 or non-enzymic scavengers of OH. or singlet oxygen were added to the incubation medium and tested for their ability to protect against these effects of alloxan. Superoxide dismutase, catalase, dimethyl sulphoxide, benzoate, and mannitol counteracted the effects of alloxan in both cytotoxicity assays. Significant protection of the Rb+-accumulating capacity was also afforded by butanol, caffeine, theophylline, NADH, NADPH and, to a small extent, NAD+. Urea has a poor affinity for OH. and did not protect against alloxan. No effect was obtained with the singlet-oxygen scavenger, histidine. Except for the protection by NADH and NADPH, which may be due to a direct reaction with alloxan in the medium, the results strongly support the hypothesis. beta-Cells may be particularly vulnerable to alloxan because their metabolic specialization facilitates reduction of the drug and perhaps of other substrates for O2.--yielding redox cycles.

Alloxan

A simple specific method for the determination of the hemoglobin content of tissue homogenates.

A simple, inexpensive and specific method for the determination of hemoglobin in tissue homogenates is described. It is based on the specific binding of hemoglobin by haptoglobin and the stabilizing effect of this binding on the peroxidase activity of hemoglobin. The haptoglobin is added as serum and no purification is needed. The method gives reliable estimates of hemoglobin contents above 10 mg/l.

Haptoglobins

Hepatomas and other neoplasms in the atlantic hagfish (Myxine glutinosa): a histopathologic and chemical study.

M. glutinosa is a cyclostome, living in the mud in seawater of high salinity. It probably is a stationary scavenger feeder. About 28,000 hagfish from the Gullmar Fjord were examined during a 5-year period for the occurrence of tumors. Hepatomas were found to be predominant neoplasm, observed at a frequency that decreased from 5.8% in 1972 to 2.9% in 1973 and finally to 0.6% in 1974--76. Islet cell hamartomas and frank neoplasms decreased from 0.5% in 1972 to less than 0.1% in 1973--76. Occasional subcutaneous and mesenterial neoplasms were also observed during 1972--74. In hagfish caught 12 km out in the open sea, the hepatoma incidence decreased from 2.8% in 1972 to 0.9% in 1974. Given this background, it is possible that pollution of the Gullmar Fjord by carcinogenic substances with low biodegradability has occurred until 1972, and this pollution could be of etiologic significance for these hagfish tumors. In fact, the use of PCBs became prohibited by law in Sweden in 1971--72. Severe restrictions were also introduced for the use of chlorinated pesticides, notably DDT, and associated substances (DDD, DDE). Preliminary analyses for the presence of PCBs, DDT (and its metabolites), and aflatoxins (the notorious hepatocarcinogen) were performed by gas chromatography and thin-layer chromatography. Livers (with and without neoplasms) from hagfish caught inside the threshold of the fjord contained about 5 mg/kg of wet weight of PCBs and about 0.1--0.4 mg/kg of dry weight of DDT, DDD, or DDE, whereas those from hagfish caught in the open sea had a much lower PCB concentration (about 0.2 mg/kg of wet weight). No PCBs and no chlorinated pesticides were found in analyses of the mud at the catching site. High PCB concentrations (3 mg/kg of wet weight) were, however, observed in livers from cod living in the Gullmar Fjord, and it was proposed that bony fish may be the source of hagfish liver PCBs. PCB chromatograms of hagfish livers differed from those of PCB standards and cod liver. This strange pattern, which was not seen in livers from hagfish caught in the open sea, might be explained by an unusual mode of metabolization. The assays for aflatoxins gave completely negative results.

Adenoma, Bile Duct

Determination of plasma or serum haemoglobin by peroxidase activity employing 2,2'-azino-di-(3-ethyl-benzthiazolinsulphonate-6) as chromogen.

A procedure is described for the determination of plasma or serum haemoglobin employing the peroxidase activity of the haemoprotein using 2,2'-azino-di-(3-ethyl-benzthiazolinsulphonate-6) as chromogen. The method gives equal results for free haemoglobin, methaemoglobin and haemoglobin complexed to haptoglobin. It is designed to measure haemoglobin in the range 0--12 mumol/l. The peroxidase activity of myoglobin is similar to that of haemoglobin, whereas haemin in free solution, bound to haemopexin or to albumin (methaemalbumin) shows much lower activity. The precision within run is satisfactory, +/- 5%.

Hemin

A comparison between the common type and a rare genetic variant of human cupro-zinc superoxide dismutase.

Human cupro-zinc superoxide dismutase is polymorphic in northern Sweden. The genetic variant type has a lower mobility at electrophoresis in alkaline buffer. The enzyme was isolated from erythrocytes from one of the rare homozygotes and its properties compared to those of the common type. The isoelectric point of the variant was higher (4.85) than that of the common type (4.7). Small differences in amino acid composition were found but no definite amino acid substitutions could be pointed out. The molecular weights were equal as judged from electrophoreses in polyacrylamide gels in the presence of dodecylsulphate. The ultraviolet spectra were similar. Parameters related to the active site of the enzyme were very similar; i.e. specific activity and sensitivity to inhibition by cyanide and by H2O2. These parameters, especially the latter two, differ widely between species. Both enzymes were stable for weeks at neutral pH at 37 degrees C, whereas the common type was significantly more stable at pH 4 and pH 11 and also at incubation in neutral buffer at 70 degrees C. It appears that the active site of the variant is conserved whereas the stability of the enzyme is affected.

Amino Acids