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Biomedical subjects

K Andersson

Publications and source records attributed to K Andersson.

At least 163 records · Page 9Linked to original sources

Nicotine treatment counteracts perinatal asphyxia-induced changes in the mesostriatal/limbic dopamine systems and in motor behaviour in the four-week-old male rat.

In the present study, the effects of nicotine treatment on the changes induced by perinatal asphyxia in exploratory and D-amphetamine-induced behaviour, and in the number of brain tyrosine hydroxylase-immunoreactive nerve cell bodies were investigated in four-week-old male rats. Asphyxia was induced in pups by placing the fetuses, still in their uterus horns removed by hysterectomy from full-term pregnant rats, in a 37 degrees C water bath for 15-16 min or 19-20 min. Surviving male pups were treated with nicotine via suckling from surrogate mothers implanted subcutaneously with Alzet minipumps containing nicotine (0.2 mumol/kg per h) for four weeks. The minipumps implanted in the mothers of sham-treated animals contained saline only. After treatment, exploratory behaviour and D-amphetamine-induced behaviour was analysed in a computerized "activity" box. After the behavioural experiments, the rats were taken for tyrosine hydroxylase immunohistochemistry, and the total number of tyrosine hydroxylase immunoreactive cell bodies were counted in the A9 and A10 regions of the substantia nigra and the ventral tegmental area, respectively. Nicotine serum levels were measured using gas chromatography in selected asphyctic and control pups at different periods after delivery. During the exploratory phase, in saline-nurtured rats, 15-16 min of asphyxia slightly increased (approximately 25%) locomotion, motility and rearing. In contrast, 19-20 min of asphyxia reduced the locomotion and rearing by approximately 50%, as compared to controls. An increase in amphetamine-induced behaviours was observed after 15-16 min, but not after 19-20 min of asphyxia, as compared to controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Intrauterine administration of levonorgestrel in two low doses in HRT. A randomized clinical trial during one year: effects on lipid and lipoprotein metabolism.

OBJECTIVE: To investigate the effects on lipid and lipoprotein metabolism of two doses (5- or 10 micrograms/24 h) of levonorgestrel released from an intrauterine device (IUD) in combination with orally administered estradiol (2 mg estradiol valerate) in perimenopausal women. DESIGN: A 1-year prospective randomized single blind clinical trial. SETTING: Department of Obstetrics and Gynaecology, Ostra Hospital, Göteborg, Sweden. SUBJECTS: Fifty-one perimenopausal women with climacteric symptoms. OUTCOME MEASURES: Cholesterol in serum and in lipoprotein fractions; high-density lipoprotein (HDL), low-density lipoprotein (LDL). Triglycerides in serum and in very low-density lipoprotein. RESULTS: In both treatment groups significant elevations in HDL-cholesterol of similar magnitude were observed after 1 month and these changes were maintained during the 12 month observation period. In both treatment groups an initial significant decrease of LDL-cholesterol was observed and the decrement was maintained after 12 months. Serum levels of cholesterol decreased significantly in both groups after 1 month and were maintained after 12 months in the levonorgestrel-IUD (LNG-IUD) 5 micrograms group. However, the initial reduction of serum cholesterol in the LNG-IUD 10 micrograms group did not differ from baseline after 12 months. Serum triglyceride levels fluctuated during the observation period. No significant changes occurred. CONCLUSION: Continuous combined HRT with intrauterine administration of levonorgestrel, 5- or 10 micrograms/24 h, in perimenopausal women was observed to increase HDL-cholesterol and to decrease LDL-cholesterol compared with pretreatment values. The low doses of levonorgestrel did not reverse the beneficial effects on lipid metabolism usually seen after estradiol administration.

Administration, Oral↗

Human skeletal muscle protein: effect of malnutrition, elective surgery and total parenteral nutrition.

1. The concentration of alkali-soluble protein, DNA and RNA in percutaneous muscle biopsy specimens was analysed. Tissue alkali-soluble protein/DNA ratio is a measure of muscle protein concentration, while tissue RNA/DNA ratio may reflect the capacity for protein synthesis. 2. Patients with weight loss due to cancer (n = 6) were compared with metabolically healthy patients before elective surgery (n = 7). Alkali-soluble protein/DNA and RNA/DNA ratios in the weight loss group were 248 (14) g/g and 1.3 (0.1) g/g respectively as compared with 404 (13) g/g and 2.1 (0.1) g/g in otherwise healthy patients. All of the alkali-soluble protein/DNA ratios and 5/6 of the RNA/DNA ratios in the weight loss group were below the 95% confidence interval for the healthy control subjects. 3. Patients undergoing elective open cholecystectomy (n = 7) were studied preoperatively and on days 3, 10, 20 and 30 post-operatively. The alkali-soluble protein/DNA ratio remained unchanged on post-operative day 3 but decreased by 8.7% (P < 0.01), 9.6% (P < 0.05) and 20.4% (P < 0.01) on days 10, 20 and 30 respectively in patients eating at will after the operation. No significant post-operative changes in alkali-soluble protein/DNA ratio were seen in patients given post-operative total parenteral nutrition with (n = 9) or without (n = 7) glycyl-glutamine supplementation for 3 days after surgery. 4. In conclusion, patients with weight loss due to malignant disease have a low muscle protein concentration. Elective surgery of medium magnitude results in a decrease in muscle protein lasting for more than 30 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Modulation of antigen-antibody complexations by immunoglobulins.

In this investigation, the modulating effects of non-immune human IgG and rheumatoid factors (RFs) on antigen-antibody complexations were studied. Non-immune human IgG, as well as RF, were found to inhibit the binding of antigen to specific antibodies of both human and rabbit origin. In addition, human immunoglobulins were also able to modify the composition of preformed antigen-antibody complexes. The effects were detected by immunological methods in two different antigen-antibody systems (human serum albumin-rabbit anti-HSA and tetanus toxoid-human anti-TT). Changes in biological activities could be followed by employing enzymes (glucose-6-phosphate dehydrogenase and human placental alkaline phosphatase) as antigens. The outcome of the effects was found to be dependent on the ratio of antigen to antibody, the antigen-binding properties of the antibody and its origin, and on the properties of the immunoglobulins added. The observed changes could not be explained only by the presence of specific antibodies in the immunoglobulin preparations. The ability of immunoglobulins to modulate antigen-antibody complexations may provide a rationale for the large amounts of non-specific immunoglobulins in the circulation by preventing premature precipitation and promoting the elimination of antigenic molecules.

Albumins↗

Reduction of menstrual blood loss in women suffering from idiopathic menorrhagia with a novel antifibrinolytic drug (Kabi 2161).

OBJECTIVE: To compare the effect of Kabi 2161 (a prodrug of tranexamic acid) and placebo on the reduction of menstrual blood loss in women suffering from idiopathic menorrhagia and to evaluate tolerance and effectiveness in a two-dose regimen. DESIGN: A randomised, double blind parallel group study using double dummy technique. SETTING: The departments of gynaecology at three medical centres in Sweden. SUBJECTS: Ninety-one outpatients visiting the gynaecological clinics from March 1991 to May 1992 were randomised into the study; 68 women fulfilled the study. INTERVENTIONS: Two run-in cycles, followed by administrations of Kabi 2161 (600 mg) tablets (1 four times daily or 2 twice daily) or placebo for the first five days of three menstrual cycles. MAIN OUTCOME MEASURES: Objective measurement of the change in menstrual blood loss during the treatment periods compared with menstrual blood loss during the run-in periods. RESULTS: A statistically significant reduction of menstrual blood loss was found for each treatment group, compared with the placebo group (P < 0.001). The mean reduction with 95% confidence interval (CI) was 33% (24-40) in the group treated with 1 four times daily and 41% (33-49) in the group treated 2 twice daily. The difference between the treated groups in reduction of menstrual blood loss is not significant. No significant differences were found in the frequencies of reported unwanted events during run-in and during treatment between the different treatment groups. There were also no significant differences between the treatment groups and the placebo group. CONCLUSION: Kabi 2161 in a dosage of 2.4 g per day gave a statistically significant reduction in objectively measured menstrual blood loss in a two (41%) as well as in a four (33%) dosage regimen compared with placebo. Frequency of unwanted events did not differ from those during run-in or from those in the placebo group. The optimal daily dosage needs to be further evaluated in a dose titration study.

Adult↗

Cholinoceptor-mediated effects on glycerol output from human adipose tissue using in situ microdialysis.

1. Possible cholinoceptor-mediated effects on lipolysis were investigated in vivo in human subcutaneous adipose tissue of non-obese, non-smoking, healthy subjects, by use of microdialysis. Cholinomimetic and sympathomimetic agents were added to the in going dialysate solvent. 2. Addition of nicotine to the perfusion solvent caused a concentration-dependent reversible increase in the levels of glycerol in the dialysate (lipolysis index). The opposite effect (also concentration-dependent and reversible) was caused by the addition of carbachol. The maximum effects were 100% stimulation and 50% inhibition, respectively, by nicotine and carbachol. Neither nicotine nor carbachol stimulated nutritive blood flow in adipose tissue (as measured with an ethanol escape technique). 3. The nicotine effect in situ was concentration-dependently counteracted by the nicotinic cholinoceptor antagonist, mecamylamine. Likewise, the carbachol effect was concentration-dependently counteracted by the muscarinic cholinoceptor antagonist, atropine. 4. When adipose tissue was pretreated with phentolamine plus propranolol in order to obtain a complete alpha and beta-adrenoceptor blockade, the subsequent addition of nicotine or carbachol still induced an increase and decrease in dialysate glycerol levels (lipolytic or antilipolytic effects), respectively. When adipose tissue was pretreated with mecamylamine or atropine, the subsequent addition of acetylcholine caused a reversible decrease and increase, respectively, of the dialysate glycerol levels. 5. Nicotine and carbachol had no effects on glycerol release from human isolated subcutaneous fat cells that were incubated in vivo. 6. In conclusion, the data demonstrate a dual effect of the cholinoceptor system on glycerol output inhuman adipose tissue: stimulation through nicotinic receptors and inhibition through muscarinic receptors. These effects, which are not observed in vitro, are independent of the adrenergic system and the local blood flow and seem not to be mediated by a direct action on the fat cell.

Adipose Tissue↗

Yersinia pseudotuberculosis inhibits Fc receptor-mediated phagocytosis in J774 cells.

Nonopsonized as well as immunoglobulin-G (IgG)-opsonized Yersinia pseudotuberculosis resists phagocytic uptake by the macrophage-like cell line J774 by a mechanism involving the plasmid-encoded proteins Yops. The tyrosine phosphatase YopH was of great importance for the antiphagocytic effect of the bacteria. YopH-negative mutants did not induce antiphagocytosis; instead, they were readily ingested, almost to the same extent as that of the translocation mutants YopB and YopD and the plasmid-cured strain. The bacterial determinant invasin was demonstrated to mediate phagocytosis of nonopsonized bacteria by these cells. In addition to inhibiting uptake of itself, Y. pseudotuberculosis also interfered with the phagocytic uptake of other types of prey: J774 cells that had been exposed to virulent Y. pseudotuberculosis exhibited a reduced capacity to ingest IgG-opsonized yeast particles. This effect was impaired when the bacterium-phagocyte interaction occurred in the presence of gentamicin, indicating a requirement for in situ bacterial protein synthesis. The Yersinia-mediated antiphagocytic effect on J774 cells was reversible: after 18 h in the presence of gentamicin, the phagocytic capacity of Yersinia-exposed J774 cells was completely restored. Inhibition of the uptake of IgG-opsonized yeast particles was dependent on the Yops in a manner similar to that seen for blockage of Yersinia phagocytosis. This similarity suggests that the pathogen affected a general phagocytic mechanism. Despite a marked reduction in the capacity to ingest IgG-opsonized yeast particles, no effect was observed on the binding of the prey. Taken together, these results demonstrate that Yop-mediated antiphagocytosis by Y. pseudotuberculosis affects regulatory functions downstream of the phagocytic receptor and thereby extends to other types of phagocytosis.

Animals↗

Administration of omeprazole to rats for one year produces reciprocal effects on antral gastrin and somatostatin cells and no effect on endocrine cells in the colon.

Inhibition of acid secretion with high doses of antisecretagogues, such as omeprazole, is known to raise the plasma gastrin levels. In the present study, we examined the effect of long-term (1-year) treatment of female rats with high doses of omeprazole on the density of antral gastrin and somatostatin cells. A possible effect on the endocrine cell density (chromogranin A as marker) and mucosal thickness of the colon was also examined. The plasma gastrin level in the omeprazole-treated rats was increased 15-fold compared with the level in the controls. The gastrin cell density, on the other hand, showed only a 2-fold increase. The somatostatin cell density in the omeprazole-treated rats was half that in the controls, indicating an inverse relationship between antral gastrin and somatostatin. In the colonic mucosa, neither the mucosal thickness nor the number of chromogranin-A-containing endocrine cells were affected by the omeprazole-induced hypergastrinemia. The results indicate that long-term acid inhibition results in a sustained hypergastrinemia, a modest and stable antral gastrin cell hyperplasia, antral somatostatin cell hypoplasia and lack of trophic effects in the colon.

Animals↗

Elective abdominal operations alter the free amino acid content of the human intestinal mucosa.

OBJECTIVE: To assess the impact of a standard moderately severe surgical operation on the mucosal amino acid content of the duodenum and the colon. DESIGN: Open study. SETTING: University hospital, Sweden. SUBJECTS: Nine patients who were to undergo elective open cholecystectomy. INTERVENTIONS: Endoscopically obtained biopsy specimens from the intestinal mucosa. MAIN OUTCOME MEASURES: Changes in the content of free amino acids in the duodenum and colon at three days postoperatively. RESULTS: The concentration of glutamine in the duodenum increased by 27% and that of glutamic acid by 34% after operation, whereas their content in colon remained unaltered. The concentration of branched chain amino acids increased by 26% in the duodenal mucosa after operation and by 24% in the colonic mucosa. The total concentration of amino acids (excluding taurine) increased by 9% in the duodenum, but remained unaltered in the colon. CONCLUSION: This study shows characteristic and consistent alterations in the free amino acid content of the intestinal tract after a moderately severe operation.

Amino Acids↗

Long-term effects of perinatal asphyxia on basal ganglia neurotransmitter systems studied with microdialysis in rat.

Asphyxia was induced in pups delivered by caesarean section on pregnant Sprague-Dawley rats. Rats within the last day of gestation were anaesthetised and hysterectomized. The uterus horns including the foetuses were placed in a water bath for various periods of time. Following asphyxia the uterus horns were opened. The pups were removed, stimulated to breathe, left to recover and given to surrogate mothers. Control and asphyctic pups were obtained from each mother. Rats surviving asphyctic periods longer than 20 min at 37 degrees C showed chronic deficits in the release of neurotransmitters monitored with microdialysis in the basal ganglia. The main change observed in 6-month-old male rats that underwent severe perinatal asphyxia was a marked decrease in striatal dopamine release, monitored under basal and D-amphetamine stimulated conditions, as compared with control (normal- or caesarean-delivered) rats. Striatal glutamate and aspartate levels were also decreased following asphyxia. In the substantia nigra, the main effect of asphyxia was a decrease of both gamma-aminobutyric acid (GABA) and aspartate levels. Thus, this study provides evidence that perinatal asphyxia leads to chronic deficits in neurotransmission in the basal ganglia.

3,4-Dihydroxyphenylacetic Acid↗

Effects of perfluorooctanoic acid--a potent peroxisome proliferator in rat--on Morris hepatoma 7800C1 cells, a rat cell line.

In this study, Morris hepatoma 7800C1 cells (from rat) were exposed to 500 microM perfluorooctanoic acid (PFOA) in the culture medium for 7 days. This treatment resulted in inductions of catalase, lauroyl-CoA oxidase (which catalyzes the first step in peroxisomal beta-oxidation) and of cytochrome P-450IVA (specialized for omega- and omega-1 hydroxylation of fatty acids). Northern blot analysis revealed that the level of mRNA for peroxisomal fatty acyl-CoA oxidase was enhanced in cells treated with PFOA. Inductions of the enzymes mentioned above are generally connected with peroxisome proliferation in vivo. This work also includes a comparison between the activities of catalase, lauroyl-CoA oxidase, DT-diaphorase and glutathione transferase in rat liver homogenate and 7800C1 cells in order to investigate to what extent this cell line differs from the situation in vivo. The findings suggest that the cells selectively lost most of their peroxisomes during transformation into a cell line and subsequent propagation. The control activities of catalase and lauroyl-CoA oxidase (marker enzymes for peroxisomes) were only about 2% of the corresponding enzyme activities in rat liver. In addition, a morphological study revealed that the frequency of peroxisomes in 7800C1 cells is very low. The control activity of glutathione transferase in 7800C1 cells was 11% of the corresponding activity in rat liver homogenate, whereas the level of DT-diaphorase was virtually the same in 7800C1 cells as in rat liver. Electron microscopic investigation of the control cultures revealed all signs of viable cells, with well-developed cell organelles. Treatment of 7800C1 cells with 500 microM PFOA has little effect on cellular morphology.

Acyl-CoA Oxidase↗

Determination of aflatoxin Q1 in urine by automated immunoaffinity column clean-up and liquid chromatography.

A liquid chromatographic system with an automated clean-up procedure for aflatoxin Q1 in human urine is described. The samples were cleaned up by using immunoaffinity columns originally designed for aflatoxin M1. The chromatographic system was a C18 column with an acidic mobile phase of acetonitrile-water containing potassium bromide. Fluorescence detection (365/440 nm) of aflatoxin Q1 was enhanced by addition of bromine, using post-column derivatization, which was studied by factorial designs. Average recovery of aflatoxin Q1 in spiked 10-ml urine samples was 88% (R.S.D. = 6.4%) at a level of 50 pg/ml. The determination limit was 49.5 pg/ml urine.

Aflatoxin M1↗

Effects of acetylsalicylic acid on parameters related to peroxisome proliferation in mouse liver.

Male C57 BL/6 mice were exposed to 1.0% (w/w) acetylsalicylic acid (ASA) in their diet for 10 days and effects related to peroxisome proliferation were subsequently examined. A 2.2-fold increase in mitochondrial protein content was obtained. The activities of the peroxisomal enzymes, lauroyl-CoA oxidase, palmitoyl-CoA oxidation and catalase, were enhanced 4.5-, 4.0- and 2.1-fold, respectively. There was a dramatic increase (9.1-fold) in microsomal cytochrome P450 IVA-catalysed activity, a 1.6-fold induction of total microsomal P450 content and a 2-fold induction of microsomal cytochrome P450 reductase activity (measured as NADPH-cytochrome c reductase). Catalase activity in the cytosol was induced 5.2-fold and DT-diaphorase activity was increased 3.5- and 3.2-fold in the cytosol and mitochondria, respectively. There was a significant increase in the susceptibility of microsomes to lipid peroxidation. Smaller increases in superoxide dismutase, glutathione transferase and glutathione peroxidase activities were also observed. The possible relevance of these effects to the pharmacology of ASA is discussed.

Animals↗

Left hemisphere dominance for processing vocalizations in adult, but not infant, rhesus monkeys: field experiments.

In humans, the left hemisphere of the brain is dominant for processing language. To assess the evolutionary origins of this neuropsychological mechanism, playback experiments were conducted on a large population of free-ranging rhesus monkeys (Macaca mulatta). Playbacks provided an equal opportunity to orient the right or left ear toward the speaker. Results revealed that 61 of 80 adult rhesus favored the right ear (left hemisphere) when vocalizations from their own repertoire were heard but favored the left ear when listening to heterospecific vocalizations. In contrast, infants less than a year old showed no perceptual asymmetry for conspecific or heterospecific calls. Thus, like humans, adult rhesus monkeys also evidence left hemisphere dominance for processing species-specific vocalizations. The emergence of such asymmetry, however, may depend on both differential maturation of the two hemispheres and experience with the species-typical vocal repertoire.

Age Factors↗

Genetic mapping of quantitative trait loci for growth and fatness in pigs.

The European wild boar was crossed with the domesticated Large White pig to genetically dissect phenotypic differences between these populations for growth and fat deposition. The most important effects were clustered on chromosome 4, with a single region accounting for a large part of the breed difference in growth rate, fatness, and length of the small intestine. The study is an advance in genome analyses and documents the usefulness of crosses between divergent outbred populations for the detection and characterization of quantitative trait loci. The genetic mapping of a major locus for fat deposition in the pig could have implications for understanding human obesity.

Adipose Tissue↗

Levonorgestrel-releasing and copper-releasing (Nova T) IUDs during five years of use: a randomized comparative trial.

A 20 micrograms/24 hours levonorgestrel-releasing intrauterine contraceptive device (LNG-IUD) has, in an open randomized multicenter study, been compared to the copper-releasing device Nova T during 5 years of use; 1821 women had the LNG-IUD and 937 women had the Nova T inserted. The 5-year cumulative gross pregnancy rate was 5.9% for Nova T and 0.5% for the LNG-IUD. The local effect of levonorgestrel in the uterine cavity causes reduction of menstrual blood loss and development of oligo-amenorrhea, and the termination rates because of heavy and/or prolonged menstrual flow were significantly (P < 0.001) lower among LNG-IUD users. However, the gross termination rate because of amenorrhea was 6.0 in this group. Hb increased during use of the LNG-IUD and decreased during Nova T use, and the difference between the devices was statistically significant. The incidence of pelvic inflammatory disease (PID) was low in LNG-IUD users regardless of age, whereas in the Nova T group, the PID rate was increased among the youngest women, which makes the difference between the devices significant (P < 0.01). The gross termination rate for reasons considered to be hormonal was 12.1 in the LNG-IUD group compared to 2.0 in the Nova T group (P < 0.001). The LNG-IUD is a long-acting reversible contraceptive method for 5 years with a pregnancy rate comparable to female sterilization. The incidence of PID is low even in young women. In addition, the positive health effects such as decreased menstrual blood loss and increased blood haemoglobin concentration make the LNG-IUD a favorable combination of hormonal and intrauterine contraception.

Adult↗

Cerebrospinal fluid levels of monoamine metabolites. A preliminary study of their relation to menstrual cycle phase, sex steroids, and pituitary hormones in healthy women and in women with premenstrual syndrome.

The cerebrospinal fluid (CSF) levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), the noradrenaline metabolite 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), and the dopamine metabolite homovanillic acid (HVA) were measured in a group of drug-free non-depressed women with premenstrual syndrome (PMS) (late luteal phase dysphoric disorder) (n = 13) and in controls with no premenstrual complaints (n = 13). In six patients and eight controls, CSF samples from both the luteal and the follicular phase were obtained, whereas in the remainder of the subjects, samples from either the follicular phase (patients: 4, controls: 2) or the luteal phase (patients: 3, controls: 3) were taken. The following observations were made: (1) Neither in the follicular phase nor in the luteal phase did the mean concentrations of CSF monoamine metabolites in the PMS group differ from the corresponding values in the control group. (2) Neither in the PMS group nor in the control group did the mean concentrations of monoamine metabolites in CSF samples obtained in the luteal phase differ from the corresponding values obtained in the follicular phase. (3) The intraindividual, intersample variations of CSF HVA and 5-HIAA concentrations were significantly smaller in the PMS group than in the control group. (4) CSF HVA correlated strongly to CSF 5-HIAA in the luteal phase of both patients and controls whereas in the follicular phase, particularly in controls, this correlation was much weaker. (5) In the luteal phase, the CSF HVA/5-HIAA ratio correlated negatively to serum levels of estradiol, progesterone, and testosterone. (6) The CSF HVA/5-HIAA ratio was significantly lower in PMS patients than in controls. (7) A positive correlation between CSF MHPG and serum luteinizing hormone was observed in the follicular phase. (8) A positive correlation between CSF HVA and serum prolactin was observed in the luteal phase. Because the study was comprised of a small number of subjects, the reported findings until replicated should be interpreted with caution.

Adult↗