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Biomedical subjects

S Marklund

Publications and source records attributed to S Marklund.

At least 55 records · Page 3Linked to original sources

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↗

Enzymes of leukocyte oxidative metabolism in Down's syndrome.

Enzymes of importance for oxygen dependent leukocyte killing of microorganisms were studied in 14 patients with Down's Syndrome (DS) and 10 controls. As has been reported previously for other cell types, the level of CuZn superoxide dismutase (SOD) was 50% higher in polymorphonuclear leukocytes (PMN) from DS patients than from the controls. The amount of SOD was extremely low in the PMNs from controls, i.e. only about 6% of the levels in other human tissues. The levels of catalase and of the Mn dependent SOD were normal. The myeloperoxidase (MPO) activity of DS PMNs was only 59% of that of the control cells. Previously reported increased levels of CuZnSOD and GSH peroxidase in erythrocytes and CuZnSOD in lymphocytes were confirmed. The increased levels of SOD in DS phagocytes provide a possible partial explanation for previous reports of defective killing of S. aureus in DS. In addition, the MPO deficiency impairs the H2O2-halide-MPO system, which is of particular importance for fungal killing, e.g. of C. albicans, which has also been reported to be deficient in DS. The findings may thus explain some of the mechanisms underlying the increased susceptibility to certain infections in DS.

Adolescent↗

Blood components in an elderly population.

The reference intervals of 18 blood components were established for an elderly population in the 8th decade of life. The most significant findings were a broader range of values for most of the components, lower values of plasma folate and plasma potassium and higher values of erythrocyte sedimentation rate, plasma creatinine and serum cholesterol, the lattermost in women only, compared to younger people.

Aged↗

Partial protection against streptozotocin-induced hyperglycaemia by superoxide dismutase linked to polyethylene glycol.

To test the possible role of superoxide radicals in the diabetogenic action of streptozotocin, blood glucose levels were measured in mice after a single high-dose (150 mg/kg body weight) or multiple low-dose (40 mg/kg for 5 days) injections of streptozotocin. Pretreatment 6 h before streptozotocin with 250-300 mg/kg superoxide dismutase coupled to polyethylene glycol reduced the hyperglycaemic response in mice injected with a single dose of streptozotocin. The blood glucose levels after multiple low doses of streptozotocin were not affected by superoxide dismutase-polyethylene glycol. Enzymatically inactive superoxide dismutase did not affect the development of hyperglycaemia. The results suggest that superoxide radicals may play a role in the diabetogenic action of streptozotocin injected as a high-dose single bolus.

Animals↗

Normal CuZn superoxide dismutase, Mn superoxide dismutase, catalase and glutathione peroxidase in Werner's syndrome.

Werner's syndrome is often regarded as a segmental progeroid syndrome. It has been suggested that free radical damage involving oxygen contributes to aging. Furthermore, lymphocytes from Werner's syndrome patients show in vitro increased chromosome breakage and are protected by exogenous superoxide dismutase and catalase. We prepared erythrocytes and lymphocytes from three patients with Werner's syndrome and determined four important enzymes protecting against oxygen toxicity; CuZn superoxide dismutase, Mn superoxide dismutase, catalase and glutathione peroxidase. All enzymic activities were found to be normal.

Catalase↗

Distribution of CuZn superoxide dismutase and Mn superoxide dismutase in human tissues and extracellular fluids.

Among various human tissues liver had the highest content of both CuZn superoxide dismutase and Mn superoxide dismutase. There were comparatively small differences in CuZn superoxide dismutase among other organs. The Mn superoxide dismutase contents were roughly half as large as the CuZn superoxide dismutase contents. The total amount of CuZn superoxide dismutase in the body was estimated to be 3900 mg. The superoxide dismutase activities of serum and cerebrospinal fluid corresponded to between 0.2-0.3 mg CuZn superoxide dismutase per liter. CuZn superoxide dismutase was apparently the source of the superoxide dismutase activity in cerebrospinal fluid, whereas this enzyme only accounted for about 15% of the serum activity. The superoxide dismutase activities of ceruloplasmin, transferrin and ferritin were very low, 40 000, 350 000 and 330 000 times lower than that of human CuZn superoxide dismutase. These factors contributed very little to serum superoxide dismutase activity. The activity of lymph was more than twice that of serum. Sera from patients with severely impaired renal function or bilaterally nephrectomized had a very high superoxide dismutase activity.

Female↗

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↗