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Biomedical subjects

K Andersson

Publications and source records attributed to K Andersson.

At least 19 recordsLinked to original sources

The involvement of selenium in peroxisome proliferation caused by dietary administration of clofibrate to rats.

The effects of dietary treatment with clofibrate (0.5% w/w for 10 days) on the livers of selenium-deficient male rats were examined. The peroxisome proliferation (as determined by electron microscopy) in the livers of selenium-deficient animals was much less pronounced than in the case of selenium-adequate rats and no increase in peroxisomal fatty acid beta-oxidation (assayed both as antimycin-insensitive palmitoyl-CoA oxidation and lauroyl-CoA oxidase activity) was observed in the deficient animals. On the other hand, in selenium-deficient rats clofibrate caused increases in the specific activity of microsomal lauric acid omega- and omega-1-hydroxylation and an apparent change in mitochondrial size, seen as a redistribution of mitochondria from the 600 x g(av) pellet to the 10,000 x g(av) pellet, which were approximately 50% as great as the corresponding effects on control animals. Obviously, then, these three different effects of clofibrate are not strictly coupled and may involve at least partially distinct underlying mechanisms. Initial experiments demonstrated that peroxisome proliferation could be obtained by exposing primary hepatocyte cultures derived from selenium-deficient rats to clofibric acid (an in vivo hydrolysis product of clofibrate which is the proximate peroxisome proliferator), nafenopin or mono(2-ethylhexyl)phthalate. This finding suggests that selenium deficiency does not have a direct influence on the basic process(es) underlying peroxisome proliferation, but rather has indirect effects, influencing, for example, the pharmacokinetics of clofibrate and/or hormonal factors.

Animals

Effects of perfluoro fatty acids on xenobiotic-metabolizing enzymes, enzymes which detoxify reactive forms of oxygen and lipid peroxidation in mouse liver.

Male mice were exposed via their diet to perfluoro fatty acids of various chain-lengths (2-10 carbon atoms) at different doses (0.02 and 0.1% weight) and for different periods of time (2-10 days). Thereafter, we monitored effects on liver and body weights and a number of hepatic parameters, including mitochondrial protein content, microsomal contents of cytochromes P450 and b5, NADPH-cytochrome P450 reductase activity [measured as NADPH-cytochrome c reductase (EC 1.6.2.3)], microsomal and cytosolic epoxide hydrolase (EC 3.3.2.3) activities, cytosolic DT-diaphorase (EC 1.6.99.2), glutathione transferase (EC 2.5.1.18), glutathione peroxidase (EC 1.11.1.9) and superoxide dismutase (EC 1.15.1.1) activities, and levels of thiobarbituric acid-reactive material (as an indicator of lipid peroxidation) in the mitochondrial subfraction. The most dramatic changes observed were a 5-9-fold increase in mitochondrial protein, a 3-6-fold increase in the microsomal content of cytochrome P450, a 3-10-fold increase in cytosolic DT-diaphorase activity, an approximately 2-fold increase in cytosolic epoxide hydrolase activity and as much as a 60% decrease in the level of thiobarbituric acid-reactive compounds in the mitochondrial fraction. Smaller increases in microsomal epoxide hydrolase activity and decreases in cytosolic glutathione peroxidase activity were also observed. Of the perfluoro fatty acids tested, perfluorooctanoic acid caused the largest changes in the parameters examined here. Dietary exposure of mice to a 0.02% dose of this substance for 10 days results in a maximal or near-maximal effect in most cases.

Animals

Is the cytosolic catalase induced by peroxisome proliferators in mouse liver on its way to the peroxisomes?

Dietary treatment of male C57B1/6 mice with clofibrate, nafenopin or WY-14.643 resulted in a modest (at most 2-fold) increase in the total catalase activity in the whole homogenate and mitochondrial fraction prepared from the livers of these animals. On the other hand, the catalase activity recovered in the cytosolic fraction was increased 12- to 18-fold, i.e. 30-35% of the total catalase activity in the hepatic homogenate was present in the high-speed supernatant fraction after treatment with these peroxisome proliferators. A study of the time course of the changes in peroxisomal and cytosolic catalase activities demonstrated that the peroxisomal activity both increased upon initiation of exposure and decreased after termination of treatment several days after the increase and decrease, respectively, in the corresponding cytosolic activity. This finding suggests that the cytosolic catalase may be on its way to incorporation into peroxisomes.

Animals

The effects of perfluoro-octanoic acid on hepatic peroxisome proliferation and related parameters show no sex-related differences in mice.

Male and female C57Bl/6 mice were administered perfluor-octanoic acid PFOA; 0.02-0.05% w/w; 5-10 days) in their diet. This treatment resulted in a several-fold induction of hepatic peroxisomal fatty acid beta-oxidation (monitored as increases in cyanide-insensitive palmitoyl-CoA oxidation, lauroyl-CoA oxidase and catalase activity) in all animals. The protein content of the hepatic mitochondrial fraction was also increased in all mice exposed to PFOA. Furthermore, studies on xenobiotic-metabolizing enzymes revealed no sex-related difference in the response to PFOA. All mice demonstrated a dramatic increase in omega-hydroxylation of lauric acid. Cytosolic epoxide hydrolase, glutathione transferase and DT-diaphorase activities were increased about 2-5-fold. These results with mice differ dramatically from previous studies and our own experiments here with Wistar rats, in which exposure to PFOA causes hepatic peroxisome proliferation in male animals, whereas females are unaffected.

Animals

Effects of dietary treatment with 11 dicarboxylic acids, diethylcarboxylic esters and fatty acids on peroxisomal fatty acid beta-oxidation, epoxide hydrolases and lauric acid omega-hydroxylation in mouse liver.

C57B1/6 male mice were exposed through their diet to 11 dicarboxylic acids, carboxylic acids and diethyldicarboxylesters for 10 days. For the diacids and diethylesters this treatment resulted in a chain length-dependent induction of lauryl-CoA oxidase and cyanide-insensitive palmitoyl-CoA oxidation activities. A chain length of 12 carbon atoms or more seemed to be necessary for induction of these two activities. In addition, the same chain length dependence was observed for induction of lauric acid omega + omega-1 hydroxylase activity and increase in the protein content of the mitochondrial fraction. Treatment with two "natural" fatty acids, i.e. lauric and palmitic acid gave no effect at all on these various parameters. In no case was induction of cytosolic and mitochondrial epoxide hydrolase activities observed. Instead, a slight decrease in these activities was observed after administration of diacids with a chain length of 4-8 carbon atoms, whereas microsomal epoxide hydrolase activity was concurrently induced.

Animals

Enterochromaffin-like cells in the rat stomach: effect of alpha-fluoromethylhistidine-evoked histamine depletion. A chemical, histochemical and electron-microscopic study.

In the rat, gastric histamine is stored predominantly in the enterochromaffin-like (ECL) cells, which are located basally in the oxyntic mucosa. The functional significance of histamine in the ECL cells is a matter of speculation. In this study the effect of depletion of histamine on the properties and ultrastructure of the ECL cells was examined. Histamine synthesis was inhibited with alpha-fluoromethylhistidine (3 mg.kg-1.h-1) given via osmotic minipumps over a period of 24 h. The treatment reduced the histidine decarboxylase activity (approximately 20% remaining) and histamine concentration (less than 20% remaining) in the oxyntic mucosa, as well as the intensity of histamine- and chromogranin A-immunostaining in the ECL cells, compared to control rats. The cytoplasmic (secretory) granules/vesicles were greatly reduced in number and size following alpha-fluoromethylhistidine administration. The histamine immunostaining of the mast cells, which occurs at the mucosal surface and in the submucosa, appeared unaffected. We conclude that ECL cell histamine accounts for at least 80% of the total oxyntic mucosal histamine in the rat and that it represents a more mobile pool than mast cell histamine. The reduction in the number and size of the ECL cell granules/vesicles following histamine depletion is in accord with the idea that they represent the storage site for histamine.

Animals

Carbamazepine kinetics and adverse effects during and after ethanol exposure in alcoholics and in healthy volunteers.

The influence of ethanol on the single-dose kinetics of carbamazepine (400 mg syrup) was assessed in 7 alcoholics after a debauche (mean daily consumption 240 g ethanol) and after 9 days of controlled abstinence, and in 8 healthy volunteers after intake of the drug with and without a single dose of ethanol (25 g). Twelve h after the first test dose of carbamazepine the alcoholics were treated with the drug for 4 days (200 mg tablet b.d.). Carbamazepine was then withheld until a single test dose was given on day 9. Serum levels of carbamazepine and its 10,11-epoxide metabolite were measured by liquid chromatography. Carbamazepine absorption appeared to be delayed in alcoholics, both after debauche and withdrawal, but its bioavailability did not seem to be reduced. Carbamazepine levels were higher and those of its metabolite lower in alcoholics after a debauche than after 9 days of controlled abstinence, but neither was changed in healthy volunteers after the ingestion of carbamazepine together with a single dose of ethanol. The difference may have been due to inhibition of carbamazepine metabolism by ethanol at the high levels attained in alcoholics but not in volunteers. However, it could also be an expression of the unmasking of enzyme induction after ethanol withdrawal. None of the alcoholics had any withdrawal seizures. Despite similar carbamazepine levels, side effects occurred in all volunteers but in none of the alcoholics, indicating that long-term ethanol exposure may promote central nervous adaptation to the acute untoward effects of carbamazepine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Return to fertility after removal of a levonorgestrel-releasing intrauterine device and Nova-T.

In a European randomized multicenter study, the efficacy and safety of an intrauterine contraceptive device releasing 20 microgram levonorgestrel/24 hours (LNG-IUD) have been evaluated and compared to the Nova-T. Because the LNG-IUD has a strongly suppressive effect on the endometrium and in some women affects ovarian function, the return to fertility after removal of the IUD was studied. Two-hundred-nine women (71 in the Nova-T and 138 in the LNG-IUD group), who had their IUDs removed because of planning pregnancy, were followed at least 24 months or until termination of pregnancy. For the Nova-T, the cumulative conception gross rate was 71.2/100 women after 12 months (79.7 after 24 months) and for the LNG-IUD 79.1 (86.6 after 24 months). The difference between the devices is not statistically significant, and in spite of the endometrial suppression during use of LNG-IUD, there is no delay of return to fertility and in both groups 96% of the pregnancies occurred during the first year after removal of the device. Eighty-four % of the pregnancies in the Nova-T group and eighty-six % in the LNG-IUD group ended in live births. The results suggest that the endometrium recovers quickly, normal ovulations are established and the fertility seems to be unaffected after use of an LNG-IUD.

Female

Hyperplasia of histamine-depleted enterochromaffinlike cells in rat stomach using omeprazole and alpha-fluoromethylhistidine.

In the rat, gastric histamine is stored mainly in the enterochromaffinlike cells. Gastrin releases histamine from these cells, and long-term hypergastrinemia results in hyperplasia. The effect of sustained hypergastrinemia on histamine-depleted enterochromaffinlike cells was studied by measuring histidine decarboxylase activity and histamine concentrations and by using quantitative histology. Hypergastrinemia maintained for 6 weeks was induced by inhibition of gastric acid secretion with omeprazole (400 mumol.kg-1.day-1) given orally, and histamine synthesis was inhibited for the same length of time with alpha-fluoromethylhistidine (3 mg.kg-1.h-1) given via osmotic minipumps. In rats given omeprazole alone, the effects of the resulting hypergastrinemia on the enterochromaffinlike cells was reflected in increased histidine decarboxylase activity, increased histamine concentration, and increased number of enterochromaffinlike cells. The general trophic effects on the stomach were seen as increased stomach and oxyntic mucosal weight and increased mucosal thickness. Treatment with alpha-fluoromethylhistidine plus omeprazole markedly reduced the histidine decarboxylase activity and histamine concentration, but the weight of the stomach and oxyntic mucosa, the enterochromaffinlike cell density, and intensity of histidine decarboxylase immunostaining were increased to at least the same extent as after omeprazole alone. These observations indicate that enterochromaffinlike cell histamine is not important for a full expression of gastrin-evoked trophic effects in the stomach.

Animals

The gene for dominant white color in the pig is closely linked to ALB and PDGRFRA on chromosome 8.

White is a widespread coat color among domestic pig breeds and is controlled by an autosomal dominant gene I. The segregation of this gene was analyzed in a reference pedigree for gene mapping developed by crossing the European wild pig and a Large White domestic breed. The gene for dominant white color was shown to be closely linked to the genes for albumin (ALB) and platelet-derived growth factor receptor alpha (PDGFRA) on chromosome 8. An unexpected phenotype with patches of colored and white coat was observed among the F1 and F2 animals. The segregation data indicated that the phenotype was controlled by a third allele, denoted patch (Ip), most likely transmitted by one of the Large White founder animals. It is shown that the ALB, PDGFRA, I linkage group shares homologies with parts of mouse chromosome 5, human chromosome 4, and horse linkage group II, all of which contain dominant genes for white or white spotting. Candidate genes for the dominant white and patch mutations in the pig are proposed on the basis on these linkage homologies and the recent molecular definition of the dominant white spotting (W) and patch (Ph) mutations in the mouse.

Albumins

Differential diagnosis and treatment of psychogenic voice disorder.

Forty consecutive patients with psychogenic voice disorder were studied prospectively to shed light on some problems of differential diagnosis met by the otolaryngologist. The females (n = 35) were on average younger than males (n = 5) (mean age 34.5 vs 51.8 years, respectively). Although an upper respiratory tract infection preceding the voice disorder was reported by no more than 25% of the patients, as many as 40% had been treated with antibiotics on one or more occasions. Other treatment and voice rest had been prescribed to a further 20% of the patients. The frequency rate of reported asthma/allergy-like symptoms (37.5) exceeded the incidence of asthma/allergy in the normal Swedish adult population. Minor laryngeal abnormalities found in 10 patients could be rejected as causative since they were inconsistent with the voice disturbance. In most of the patients (n = 27), vocal function returned to normal or improved after voice therapy combined with counselling. Vocal abnormalities remained unchanged in three patients. The patients who required multiple therapy sessions (n = 10) were older (mean age 48.8 years) and seemed to have more profound personal problems than the average. The findings suggest that psychogenic voice disorder may often be misdiagnosed as acute laryngitis or asthma/allergy. Restricted use of antibiotics and other drugs is to be recommended in the treatment of benign voice disorders.

Adult

The effect of non-immune IgG on antigen-antibody complexation.

Two preparations of human IgG, one acylated with beta-propiolactone (acylated IgG) and one treated at pH 4 with traces of pepsin (pH 4-IgG), were used to study the effect of non-immune IgG on antigen-antibody interactions in the antigen excess zone. Employing two immunological methods together with size-exclusion chromatography, we found that the formation of human albumin-rabbit anti-human albumin complexes was inhibited in the presence of human IgG. In addition, IgG seemed to promote the aggregation of already formed complexes. Thus, non-immune IgG may modulate immune complexation by direct molecular interactions. The effect was dependent on the size and composition of the immune complexes as well as on the conformation of the IgG molecules with respect to their shape, isotype, charge, and other surface properties. Some possible mechanisms for the reactions are discussed.

Acylation

Effects of a postnatal exposure to cigarette smoke on hypothalamic catecholamine nerve terminal systems and on neuroendocrine function in the postnatal and adult male rat. Evidence for long-term modulation of anterior pituitary function.

The purpose of this paper was to study the possible long-term effects of postnatal exposure to cigarette smoke. Male Sprague-Dawley rats were exposed to the smoke from 2 cigarettes (Kentucky reference IR-1 type) every morning from day 1 after birth for a period of 5, 10 or 20 days. The rats were decapitated 24 hours (5, 10 and 20 days of exposure), 1 week (20 days of exposure) or 7 months (20 days of exposure) after the last exposure. Using the Falck-Hillarp methodology in combination with quantitative histofluorimetry catecholamine levels and changes in catecholamine utilization (alpha MT-induced CA fluorescence disappearance) in discrete hypothalamic catecholamine nerve terminal systems were analysed. Serum prolactin, LH, TSH and corticosterone levels were determined by means of radioimmunoassay procedures. In the postnatal period serum LH levels were significantly increased 24 hours after a 10 and 20 day exposure to cigarette smoke. In adult life after a 20-day postnatal exposure to cigarette smoke a highly significant increase was observed in serum prolactin levels, which were unaltered by this exposure when measured in the postnatal period. Twenty-four hours following a 20-day postnatal exposure, catecholamine utilization was increased in the medial palisade zone of the median eminence and substantially reduced in the parvocellular and magnocellular parts of the paraventricular hypothalamic nucleus. One week and 7 months following a 20-day postnatal exposure to cigarette smoke no alterations were observed in catecholamine levels or utilization in various hypothalamic areas including the median eminence. All the above changes were observed in the presence of an unaltered development of body weight. The results indicate that marked but temporary increases in LH secretion occur 24 hours after a postnatal exposure to cigarette smoke, while increase in prolactin secretion only develop in adult life, when the maturational processes of the brain and/or the anterior pituitary gland are completed. Changes in catecholamine levels and utilization are found in discrete hypothalamic nerve terminal networks but do not play a major role in mediating the above changes in anterior pituitary function and are probably the result of a withdrawal phenomenon.

Animals

Risk of developing atopic disease after early feeding with cows' milk based formula.

A follow up of a cohort of 736 healthy full term children with exposure to cows' milk based formula and breast milk from donors on the maternity ward was performed. The children were divided into three exposure groups according to the feeding patterns on the maternity ward. Group 1 received only mother's milk, group 2 mother's milk and human donors' milk, and group 3 received mother's milk, donors' milk and cows' milk based formula. The children were investigated at 7 years of age, by examining their medical files, and at 11 and 14 years, by questionnaires regarding symptoms of atopic disease. No significant differences between the three groups at follow up were found in the cumulative incidences of atopic diseases. The amount of formula given did not affect the risk of developing atopic disease. Children with a family history of such diseases ran the same risk of subsequent atopic disease whether they were fed formula or breast milk alone. Cows' milk based formula given on the maternity ward does not seem to increase the risk of developing atopic disease.

Animals

Diagnosis of psychogenic dysphonia.

Background factors, symptoms and signs were analysed in 40 consecutive patients with psychogenic dysphonia. Their voice profile was compared with that of 40 patients with infectious laryngitis. The majority of the patients were young females, non-smokers, who were not professional voice users. Criteria for acute infectious laryngitis prior the voice disorder were met in no more than 10% of the patients. Nevertheless as many as 40% of the patients had been treated with various antibiotics. The prevalence of reported asthma/allergy-like symptoms was high, 37.5%. Perceptual analysis of voice profiles demonstrated similarity of aberrancies in psychogenic dysphonia and in acute laryngitis. Since it may be difficult to distinguish psychogenic dysphonia from acute laryngitis, careful analysis of anamnestic data may be helpful for a correct diagnosis.

Acute Disease

Interaction of phospholipids with rhodamine 6G in toluene.

Upon interaction of various glycerophospholipids with Rhodamine 6G in toluene, a typical difference spectrum with an absorption maximum at approximately 515 nm is obtained . This spectrum is obtained with phosphatidylcholine only after treatment with NaCl, which presumably weakens intra- and/or inter-molecular electrostatic binding between the negatively charged phosphate moiety and the protonated nitrogen in this molecule. Absorption at 515 nm was linear for all of the phospholipids investigated from a concentration of approximately 1.2 microM up to at least 50 microM. The highest extinction coefficient was obtained for diphosphatidylglycerol (251 mM-1 cm-1) and all of the compounds tested, with the exception of phosphatidylethanolamine, demonstrated extinction coefficients higher than that of palmitic acid. Thus, the absorption spectrum which results from the interaction of purified glycerophospholipids with Rhodamine 6G in organic solvent is a sensitive measure of the amount of phospholipid present.

Coloring Agents

A randomized study of long-term out-patient treatment in alcoholics. Psychiatric treatment versus multimodal behavioural therapy, during 1 versus 2 years of treatment.

Seventy-two alcoholic patients (60 men and 12 women) were randomized into four groups who received psychiatric treatment (PT) or multimodal behavioural therapy (MBT), for either 1 or 2 years. PT was based on psychodynamic principles, and MBT is a cognitive-behavioural treatment. The patients accepting treatment had a mean age of 37 +/- 9 years, and they were socially stable. There was no difference in attrition rate (35%) in relation to therapy and length of treatment. The rate of favourable drinking outcome during the third year was similar in all four alternatives, at 40-44%. A favourable drinking outcome was predicted by a better initial psychic status and few psychiatric symptoms at intake. In PT patients a favourable outcome was more strongly related to a better psychic status than in MBT patients (P = 0.58). The mean number of sessions, 23, did not differ in relation to outcome. The main conclusion from this study is that there were only small and inconclusive differences between the therapies of different types and different duration.

Alcoholism