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Biomedical subjects

O Eriksson

Publications and source records attributed to O Eriksson.

At least 19 recordsLinked to original sources

Inhibition of lipid peroxidation in isolated rat liver mitochondria by the general anaesthetic propofol.

The effect of the general anaesthetic propofol (2,6-diisopropylphenol) on lipid peroxidation in rat liver mitochondria was assessed with the thiobarbituric acid (TBA) assay. Propofol was shown to inhibit the accumulation of TBA-reactive compounds after initiation of radical production by the addition of the ADP-Fe2+ complex. Analysis of kinetics showed that propofol caused a concentration-dependent delay as well as a decrease in the rate of the peroxidation process. 1H-NMR spectra of mitochondrial lipid extracts indicated that 95% of the added propofol remained intact after 30 min incubation under conditions of low oxidative stress. The ESR spectrum of propofol incubated in the presence of EDTA-Fe2+ and H2O2 as initiators of radical production showed a radical that was most likely a decomposition product of the primary phenoxy radical of propofol. It is concluded that (a) propofol acts as a chain reaction-breaking antioxidant by forming a stable radical and (b) propofol does not seem to be metabolized in mitochondria in vitro.

Adenosine Diphosphate

The role of endotoxins in induced ruminal acidosis in calves.

Experimentally induced ruminal acidosis was carried out in 4 calves to investigate the possibility of resorption of endotoxins from Gram negative bacteria originating from the gastro-intestinal tract. The ruminal acidosis was induced by overfeeding of oats and the effect was evaluated by clinical and blood biochemical changes. Blood samples were collected every 2 h for 60 h before and after experimental feeding. The animals showed signs of ruminal acidosis and also the clinical and blood biochemical changes were similar to those seen after experimental endotoxaemia. However, although being less dramatic the changes in many relevant parameters such as an increase in prostaglandin F metabolite levels, body temperature, endotoxins and a decrease in iron indicate that an endotoxaemic state had occurred. The results of the present study show that ruminal acidosis/stasis is linked to resorption of endotoxins from the gastro-intestinal tract causing endotoxaemia/endotoxicosis.

Acidosis

Effects of the membrane potential upon the Ca(2+)- and cumene hydroperoxide-induced permeabilization of the inner mitochondrial membrane.

A protonophore-induced delta psi decrease in a 180-140 mV range causes an increase in the lag-period of Ca(2+)-induced mitochondrial permeabilization but has little effect on the cumene hydroperoxide-induced permeability transition of mitochondria. Suppression of the non-specific permeability induction seems to be mediated by an increase in [ADP] in the mitochondrial matrix. A further decrease in delta psi leads to additional suppression of the non-specific permeability as a result of a partial ruthenium red-sensitive efflux of the previously accumulated Ca2+. On the other hand, complete dissipation of delta psi causes immediate induction of the non-specific permeability. It is concluded that only complete dissipation of delta psi caused by H+ leakages may act as a trigger for non-specific permeability induction.

Animals

1H-NMR studies of lipid extracts of rat liver mitochondria.

Lipid extracts of rat liver mitochondria were studied by 1H-NMR at 200 MHz. Each spectrum, obtained in 6 min with routine acquisition parameters, allowed the estimation of the phosphatidylcholine/phosphatidylethanolamine ratio, the cholesterol/total lipid molar ratio, the average fatty acid length, the unsaturation ratio and the oxidation state of the ubiquinone/ubiquinol couple. 1H-NMR spectroscopy was also used to analyze structural changes of the lipids following peroxidation. In model liposomes subjected to enzymatic peroxidation the appearance of hydroperoxides and conjugated double bonds were detected, whereas in mitochondria no such changes were seen even after a period of relatively high oxidative stress. This suggests that the systems for protection against oxidative damage in mitochondria are able to keep the amount of peroxidation products below the detection limit of the technique.

Animals

Effects of the general anaesthetic Propofol on the Ca2(+)-induced permeabilization of rat liver mitochondria.

The molecular mechanism of the Ca2(+)-induced permeabilization of rat liver mitochondria was evaluated by studying a new effect of the commonly used general anaesthetic Propofol (2,6-diisopropylphenol). The compound was found to induce an apparent uptake of Ca2+ at steady-state in the Ca2(+)-distribution between the medium and the mitochondria, and to inhibit swelling and release of accumulated Ca2+ induced by inorganic phosphate, t-butyl hydroperoxide, diamide or FCCP plus Ruthenium red. The compound did not stimulate the activity of the Ca2(+)-uniporter and it is concluded that the effects seen are due to the inhibition of the Ca2(+)-dependent, unspecific permeability increase. The results suggest two mechanisms whereby Propofol stabilizes the mitochondrial membrane in the presence of Ca2+: (i) by interaction with the putative pore, thus causing its closure; and (ii) by scavenging of free radicals thus inhibiting its opening during oxidative stress.

Animals

Vaginal immunoglobulin A (IgA) levels in post-menopausal women: influence of oestriol therapy.

The concentration of secretory immunoglobulin A (IgA) in the vaginal fluid of 20 untreated post-menopausal women (aged 75.4 +/- 1.4 years) was compared with the levels in a group of 20 post-menopausal women (aged 73.2 +/- 1.5 years) treated with oral oestriol (E3) (2 mg/day) and a further group of 20 healthy, non-pregnant, fertile women (aged 28.2 +/- 1.8 years). Secretory IgA was determined using a paper disc modification of the single radial immunodiffusion technique. The vaginal concentration of IgA in the untreated women was 41.5 +/- 5.7 mg/l, which was higher than that recorded in those treated with E3 (20.8 +/- 5.7 mg/l, P less than 0.05) and in the fertile women (16.4 +/- 3.7 mg/l, P less than 0.01). Epithelial cells predominated in the wet smear preparations obtained from the women who received E3 and the fertile women, while a predominance of leucocytes was observed in the untreated women. Lactobacilli were found more frequently in the vaginal flora of the women in the E3 group (P less than 0.001) and the fertile women (P less than 0.001) than the untreated group. Faecal-type bacteria were seen more frequently in the vaginal flora of the untreated women than the E3 group (P less than 0.01) or the fertile women (P less than 0.001). The possible implications of the present findings with regard to the individual variation in the intensity of symptoms experienced by women suffering from the oestrogen deficiency syndrome are discussed.

Adult

A health care program for the investigation and treatment of elderly women with urinary incontinence and related urogenital symptoms.

The assessment and treatment of urinary incontinence and related urogenital symptoms using an algorithm model was evaluated in 364 elderly women complaining of urinary incontinence. The women (age 72.1 +/- 1.5 years, range 65-84 years) were assessed by a 48-hour pad test, a cough provocation test, micturition lists and a gynecological examination which included a smear test, measurement of vaginal pH and bacterial cultures. The diagnosis of urinary incontinence was confirmed in 346 women (stress 26.3%; urge: 32.7%; mixed: 41.0%). Women suffering from stress incontinence were younger (p less than 0.05) and had experienced a larger number of deliveries (p less than 0.05) than women with urge incontinence. All the women were treated with oral estriol, 3 mg daily for 4 weeks followed by 1-2 mg daily. The total urinary leakage per 48 hours (p less than 0.01) and maximum single leakage (p less than 0.05) were reduced in women with mixed incontinence, while the frequency of micturition decreased (p less than 0.05) in women with urge incontinence after 12 weeks treatment with oral estriol. There were no significant changes in any of the objective micturition parameters in women with stress incontinence following treatment. Karyopyknotic index and the presence of lactobacilli were increased (p less than 0.001), and vaginal pH decreased (p less than 0.001) following treatment in women with all types of incontinence. More than 70% of all the women treated in this algorithm model judged themselves to be improved, much improved or cured.

Aged

Effects of vitamin A on endotoxaemia in rats.

OBJECTIVES: To find out if survival after peritonitis induced by caecal puncture and injection of endotoxin is correlated with serum endotoxin concentrations in rats; whether this study could be carried out by studying the effects of vitamin A in rats with peritonitis; and if it was possible to differentiate between local and systemic effects of vitamin A on endotoxaemia in rats. DESIGN: Prospective randomised study. MATERIAL: Sixty adult male Sprague-Dawley rats. INTERVENTIONS: Rats were kept on a diet containing no vitamin A for six days; 30 were given vitamin A 1,380 IU/kg/day intramuscularly and 30 were given peanut oil. Peritonitis was then induced in 16 rats by caecal puncture (treated n = 10, untreated n = 6) and the remainder received intraperitoneal injections of either 0.5 mg/kg endotoxin, or 2.0 mg/kg endotoxin. MAIN OUTCOME MEASURES: Plasma concentrations of vitamin A, vitamin E, and serum concentrations of endotoxin, estimation of erythrocyte volume fraction and leucocyte particle concentrations, and survival. RESULTS: Rats that were given 2 mg of endotoxin had higher mortality and did generally less well than others. Serum endotoxin concentrations were lower in those groups that had been pretreated with vitamin A. No animal developed vitamin A deficiency and there were no differences in erythrocyte volume fraction or leucocyte particle concentration between those that did and did not receive vitamin A. CONCLUSION: Vitamin A lowered the concentration of endotoxin in the circulation, it has a central function in the host's defence against endotoxin, and the experimental model seems suitable for the study of the effect of vitamin A or endotoxemia and peritonitis.

Animals

Low doses of quinine during a short time period are effective for clearance of Plasmodium falciparum in asymptomatic children in Guinea Bissau.

Asymptomatic children in Guinea Bissau were given 5 mg quinine per kg body weight two times daily for 5 days (n = 18) or 3 days (n = 20) for treatment of Plasmodium falciparum. Parasites disappeared within four days after initiation of treatment and remained absent during the first week afterwards. Six children reported adverse reactions, mainly mild tinnitus which disappeared after termination of treatment. Reduced doses of quinine for shorter treatment periods was effective in this study. Further studies in symptomatic patients are needed to elucidate whether this low-dose regimen could be an alternative to chloro-quine in the treatment of P. falciparum in Africa.

Adolescent

Quantitative determination of endotoxins on surgical gloves.

The amount of endotoxin on surgical gloves was investigated by the limulus chromogenic substrate method. Heavy endotoxin contamination was observed on the outside of certain surgical gloves sold in Sweden. Given an endotoxin absorption of 10% to the patients, one of the types of gloves studied would cause fever, chills, headache and muscle pain. The amount of endotoxin on the gloves could be minimized by rinsing in endotoxin-free water. We conclude that the manufacturing process of latex gloves should be checked microbiologically for Gram-negative bacteria before sterilization. Alternatively, the amount of endotoxin should be checked on the product by the limulus ameobocyte lysate test before release.

Endotoxins

Effect of oral oestriol on vaginal flora and cytology and urogenital symptoms in the post-menopause.

The effect of oral oestriol (3 mg/day for 4 weeks followed by 2 mg/day for a further 6 weeks) on the vaginal bacterial flora, vaginal cytology and urogenital symptoms was assessed in a double-blind, placebo-controlled study in 35 women with symptoms of the urogenital oestrogen deficiency syndrome. No significant differences were observed with regard to the occurrence or severity of urogenital symptoms, vaginal pH, karyopyknotic index (KPI) or the baseline results of vaginal bacterial cultures in the 18 patients (mean age 71.6 +/- 1.0 years) treated with oestriol and the 17 women (mean age 72.6 +/- 1.4 years) who received placebo tablets. A decrease in both vaginal pH (P less than 0.001) and the proportion of faecal-type bacteria (P less than 0.05), and an increase in the KPI (P less than 0.01) and the proportion of lactobacilli (P less than 0.001) were recorded after 10 weeks of treatment with oral oestriol. At the end of the following 10 medication-free weeks all of these parameters except vaginal pH had returned to values that were not significantly altered from the corresponding baseline levels. In the patients treated with placebo no significant changes occurred in vaginal pH, KPI or the proportion of lactobacilli in vaginal cultures during the course of this study. Urogenital symptoms improved in both groups after medication (and even after the medication-free period) in relation to the baseline assessment, which reflects the latter's subjective nature.

Administration, Oral

Endotoxin concentrations in the blood following intravenous injection and effect on prostaglandin F2 alpha release, calcium and bile acids in goats.

Injection of endotoxin from Salmonella typhimurium in male goats resulted in a biphasic release pattern of PGF2 alpha, as determined by 15-ketodihydro-PGF2 alpha concentrations in plasma. A small initial peak at 30 minutes was followed by a second peak one hour after injection. The rectal temperature increased three to five hours after endotoxin injection and calcium concentrations started to decrease soon after injection; a significant decrease was seen from 105 minutes. Endotoxin concentrations varied among the animals but had a tendency to increase three hours after injection, simultaneously with a decrease in bile acid concentrations three hours after injection. The decrease in bile acids indicated alimentary stasis. Therefore, the raised endotoxin levels could be of endogenous origin. This study also shows that the prostaglandin metabolite is a very reliable parameter for estimating the effect of endotoxin.

Animals

Endotoxins in cardiopulmonary bypass.

Endotoxins are biologically active substances derived from the cell wall of degraded gram-negative bacteria. Since sterile water may also contain large amounts of endotoxins, these are easily introduced into the manufacturing processes of technical medical material, such as the extracorporeal components used in cardiopulmonary bypass. In hemodialysis, the presence of endotoxins has been related to untoward effects in patients. Using the limulus amebocyte lysate test, we determined the serum concentration of endotoxin in 42 patients undergoing coronary bypass operations. The values increased during cardiopulmonary bypass, exceeding the normal range of 0 to 20 ng/L in 10 patients with a maximum of 82 ng/L, which probably indicates endotoxin release from the extracorporeal equipment. We found no obvious relation to postoperative morbidity. The endotoxin levels of this study are considerably lower than those reported in two other studies of patients having cardiopulmonary bypass. This might be due to less intraoperative contamination but possibly also to differences in analytic methods.

Adult

Radiocesium uptake in reindeer on natural pasture.

In an experiment initiated after the Chernobyl accident, a herd of reindeer was followed before and after a temporary move from a highly contaminated area (greater than 20 kBq 137 Cs/m2) to a less contaminated area (less than 3 kBq 137Cs/m2) of natural pasture. The animals grazed in a highly contaminated area until they were moved to the low contaminated area where they grazed from late November to late April. The level of 137Cs in meat was about 12 kBq/kg at the time when the animals were moved (Nov.) to the low contaminated area and it decreased to about 3 kBq/kg with an effective half-time of about 1 month, after the animals were moved. In the low contaminated area the fractional transfer, fm, of 137Cs was determined to be 0.65 d/kg during winter pasture, mainly on lichens, and 0.30 d/kg during summer pasture, in the fields. The actual intake of radiocesium was determined by measurement of ruminal samples from slaughtered animals. The maximal radiation dose to reindeer in Sweden after the Chernobyl accident was estimated to less than 200 mSv/a with a dose rate of less than 1mSv/d during the winter period of maximum tissue concentration of radiocesium.

Accidents

Vaginal administration of low-dose oestradiol--effects on the endometrium and vaginal cytology.

Twenty (20) post-menopausal women, mean age 62.4 yr, presenting with symptoms associated with urogenital atrophy were treated intravaginally with daily doses of 25 and 50 micrograms oestradiol (E2) in a double-blind, cross-over study. After randomization, the patients started daily treatment with pessaries containing either 25 or 50 micrograms E2 for 3 wk, followed by a maintenance period of 6 wk during which the pessaries were used only twice a week. A 4-wk wash-out period was followed by another treatment period of 9 wk. The effects on the karyopyknotic index (KPI) and on endometrial histopathology were assessed before and after 3, 9, 16 and 22 wk of treatment. In the case of the 25 micrograms dose the mean KPI values were 34.7 and 20.9% after 3 and 9 weeks of treatment, respectively, the corresponding figures after treatment with 50 micrograms E2 being 39.2 and 22.7%. No dose-effect relationship was apparent from the vaginal cytology findings. Endometrial biopsies could not be taken systematically in all patients. Weak proliferation of the endometrium was observed in 1 woman after 3 wk of daily treatment with the 50 micrograms dose. No endometrial stimulation was detected in any of the patients after treatment with 25 micrograms daily. Beneficial clinical and cytological effects were obtained with both dosage regimens. Daily intravaginal administration of 25 micrograms E2 can accordingly be advocated for the treatment of urogenital symptoms attributable to oestrogen deficiency in post-menopausal women.

Administration, Intravaginal

The phospholipase A2-induced increase in the permeability of phospholipid membranes to Ca2+ and H+ ions.

The permeability of liposomes prepared from beef heart mitochondrial phospholipids was studied after treatment with phospholipase A2. The permeability to H+ ions was measured by recording the rate of change of pH in the external medium following an addition of an aliquot of alkali to liposomes with a highly buffered inner medium, while the penetration of Ca2+ ions into liposomes was measured in liposomes loaded with arsenazo III. There was a doubling of H+ permeability when the lysophospholipid content was increased to 2% by treatment with phospholipase A2, and a tripling at 4%. Entrapped sucrose leakage from liposomes became apparent at above 6% lysophospholipid. Treatment with phospholipase A2 stimulated Ca2+ penetration into liposomes driven by a valinomycin-induced diffusion potential or a nigericin-induced H+ gradient. The data are discussed in relation to the mechanism of damage to mitochondria occurring in Ca2+ overload as well as in phospholipase A2-induced cellular damage.

Animals

Response of Plasmodium falciparum to chloroquine treatment: relation to whole blood concentrations of chloroquine and desethylchloroquine.

A standard treatment with 25 mg chloroquine base per kilogram body weight was given to 39 semi-immune asymptomatic Tanzanian schoolchildren with Plasmodium falciparum parasitaemia. Whole blood chloroquine and desethylchloroquine concentrations were monitored 12 times during 30 days of follow-up using 100 microliters capillary blood dried on filter-paper. All but three children had detectable amounts of chloroquine (greater than or equal to 10 nmol/l) in their blood before treatment. The interindividual variations in concentrations during the first week were 3.3 to 5.1-fold for chloroquine and 3.5 to 6.3-fold for desethylchloroquine. In seven children with RII response in vivo, the highest determined chloroquine concentration was lower (P = 0.029) than in the others. After treatment, a rough approximation of the minimum inhibitory concentration in vivo was made by calculating the average of the chloroquine concentrations before and after the time when parasites increased or reappeared again. RII-resistant parasites increased in number when the median residual whole blood concentration in the children was approximately 790 (range, 444-869) nmol/l. Parasites reappeared when the median residual whole blood concentrations was approximately 147 (range, 44-673) nmol/l. We conclude that interindividual variations of chloroquine concentrations have an impact on the outcome of treatment and the classification of resistance in vivo.

Adolescent