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Biomedical subjects

Agneta Andersson

Publications and source records attributed to Agneta Andersson.

12 recordsLinked to original sources

A Vibrio cholerae protease needed for killing of Caenorhabditis elegans has a role in protection from natural predator grazing.

Vibrio cholerae is the causal bacterium of the diarrheal disease cholera, and its growth and survival are thought to be curtailed by bacteriovorous predators, e.g., ciliates and flagellates. We explored Caenorhabditis elegans as a test organism after finding that V. cholerae can cause lethal infection of this nematode. By reverse genetics we identified an extracellular protease, the previously uncharacterized PrtV protein, as being necessary for killing. The killing effect is associated with the colonization of bacteria within the Caenorhabditis elegans intestine. We also show that PrtV is essential for V. cholerae in the bacterial survival from grazing by the flagellate Cafeteria roenbergensis and the ciliate Tetrahymena pyriformis. The PrtV protein appears to have an indirect role in the interaction of V. cholerae with mammalian host cells as judged from tests with tight monolayers of human intestinal epithelial cells. Our results demonstrate a key role for PrtV in V. cholerae interaction with grazing predators, and we establish Caenorhabditis elegans as a convenient organism for identification of V. cholerae factors involved in host interactions and environmental persistence.

Animals↗

Human embryonic stem cells are immunogenic in allogeneic and xenogeneic settings.

Recent studies have suggested that human embryonic stem cells (HESC) are immune-privileged and may thereby circumvent rejection. The expression of immunologically active molecules was studied by DNA microarray analysis and by flow cytometry. HESC were transplanted into immunologically competent mice and traced by fluorescence in-situ hybridization (FISH) and immunohistochemistry. The ability of HESC to directly and indirectly induce immune responses in CD4+ T-cells from naive and transplanted mice was studied. Their ability to induce immune responses of human CD4+ T-cells, when cultured in the presence of dendritic cells (DC) syngeneic to responder T-cells, was also analysed. HESC demonstrated expression of HLA class I and HLA class II genes, but the cell surface expression of HLA class II molecules was low even after incubation with IFNgamma. In wild-type mice, HESC could be demonstrated by FISH until 3 days after transplantation and were surrounded by heavy infiltrates of T-cells and macrophages. HESC induced a similar immune response as human fibroblast cells (HFib) on naive and immunized T-cells, both directly and in the presence of syngeneic DC. A similar response was observed in the allogeneic setting. It is concluded that HESC are immunologically inert and do not inhibit immune responses during direct or indirect antigen presentation, and they were acutely rejected in a xenogeneic setting.

Animals↗

Pharmacokinetic and behavioral effects of allopregnanolone in healthy women.

RATIONALE: The behavioral effects of allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one) in women are not known. OBJECTIVE: Allopregnanolone, a neuroactive steroid secreted by the mammalian ovary, exerts its anesthetic, anxiolytic, and sedative/hypnotic effects through potentiation of GABAA receptors. The purpose of this study was to evaluate the behavioral effects of allopregnanolone in healthy women. METHODS: Ten healthy women were given three increasing intravenous doses of allopregnanolone in the follicular phase of the menstrual cycle. Saccadic eye movement parameters and visual analogue scales of sedation were used to evaluate the behavioral response of allopregnanolone. Repeated blood samples for analyses of allopregnanolone were drawn throughout the study day. RESULTS: Exogenously administered allopregnanolone decreases saccadic eye movement parameters and increases subjective ratings of sedation that correlate with increased serum concentrations of this neuroactive steroid. CONCLUSION: The behavioral effects of allopregnanolone are similar to that of its 5beta-stereoisomer, pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one). Apart from fatigue and mild nausea, allopregnanolone given in a cumulative dose of 0.09 mg/kg did not have any adverse effects.

Adult↗

Relationship between allopregnanolone and negative mood in postmenopausal women taking sequential hormone replacement therapy with vaginal progesterone.

OBJECTIVE: To compare severity of negative mood and physical symptoms between women with different progesterone, allopregnanolone, and pregnanolone plasma concentrations during sequential Hormone Replacement Therapy (HRT) with vaginal progesterone suppositories. DESIGN: A randomized, placebo-controlled, double-blind, crossover study. METHOD: Postmenopausal women (n=36) with climacteric symptoms were treated with 2mg estradiol daily during three 28-day cycles. Vaginal progesterone suppositories with 400, 800 mg/day or placebo were added sequentially for 14 days per cycle. Daily symptom ratings using a validated rating scale were kept. Blood samples for progesterone, allopregnanolone, and pregnanolone radioimmunoassays were collected during each treatment cycle. RESULTS: Women were divided into three groups (low, medium, and high) based on plasma allopregnanolone concentration during progesterone treatment. The concentration of allopregnanolone in the medium group corresponds to the concentration seen during the mid luteal phase of the menstrual cycle. Within women with medium allopregnanolone concentration significantly more negative mood and physical symptoms were rated during progesterone treatment compared to treatment with unopposed estrogen or placebo. Between women significantly more negative mood symptoms were seen during progesterone treatment cycles with medium allopregnanolone concentration compared to cycles with low concentration. Plasma progesterone, allopregnanolone, and pregnanolone concentrations increased with increasing progesterone dose. Progesterone and allopregnanolone plasma concentrations increased 2h after vaginal administration of progesterone at 400 and 800 mg/day. CONCLUSION: Vaginal progesterone in sequential HRT causes negative mood, most likely mediated via allopregnanolone.

Administration, Intravaginal↗

The effect of a low dose of alcohol on allopregnanolone serum concentrations across the menstrual cycle in women with severe premenstrual syndrome and controls.

BACKGROUND: Neurosteroids have been proposed to play an important role in the interaction between alcohol and GABA(A) receptors and for the symptomatology of premenstrual dysphoric disorder (PMDD). The primary aim of this study was to investigate possible alcohol-induced changes in allopregnanolone serum concentrations across different menstrual cycle phases in women with severe premenstrual syndrome (PMS) and controls. METHODS: The allopregnanolone and cortisol responses to a low-dose of alcohol were evaluated in 14 women with and 12 women without severe premenstrual syndrome in the follicular and late luteal phases. The effect of a 30-min intravenous alcohol infusion (0.2 g/kg) on allopregnanolone and cortisol serum concentrations was compared to placebo, and compared between cycle phases and groups. Blood samples for measuring allopregnanolone were taken at baseline 25, 55, and 75 min after the start of the alcohol infusion. RESULTS: In the late luteal phase, the alcohol infusion decreased allopregnanolone levels, compared to baseline levels as well as to placebo. The difference in allopregnanolone levels between alcohol and placebo was evident 25 min (P < 0.01), 55 min (P < 0.01), and 75 min (P < 0.05) after start of the infusion. There was no change in allopregnanolone levels during the alcohol infusion in the follicular phase. Also, no difference in alcohol-induced allopregnanolone response between PMS patients and control subjects was detected. Cortisol levels declined during both the placebo and alcohol infusion, but did not differ with respect to which infusion had been given. CONCLUSION: During the late luteal phase, independent of PMS diagnosis, the low-dose alcohol infusion resulted in decreasing peripheral allopregnanolone levels.

Adult↗

Costs of informal care for patients in advanced home care: a population-based study.

OBJECTIVES: Several studies have sought to analyze the cost-effectiveness of advanced home care and home rehabilitation. However, the costs of informal care are rarely included in economic appraisals of home care. This study estimates the cost of informal care for patients treated in advanced home care and analyses some patient characteristics that influence informal care costs. METHODS: During one week in October 1995, data were collected on all 451 patients in advanced home care in the Swedish county of Ostergötland. Costs were calculated by using two models: one including leisure time, and one excluding leisure time. Multiple regression analysis was used to analyze factors associated with costs of informal care. RESULTS: Severity percent of the patients in the study had informal care around the clock during the week investigated. The patients had, on average, five formal care visits per week, each of which lasted for almost half an hour. Thus, the cost of informal care constituted a considerable part of the cost of advanced home care. When the cost of leisure time was included, the cost of informal care was estimated at SEK 5,880 per week per patient, or twice as high as total formal caregiver costs. When leisure time was excluded, the cost of informal care was estimated at SEK 3,410 per week per patient, which is still 1.2 times higher than formal caregiver costs (estimated at SEK 2,810 per week per patient). Informal care costs were higher among patients who were men, who were younger, who had their own housing, and who were diagnosed with cancer. CONCLUSIONS: Studies of advanced home care that exclude the cost of informal care substantially underestimate the costs to society, regardless of whether or not the leisure time of the caregiver is included in the calculations.

Activities of Daily Living↗

Pathogenesis in menstrual cycle-linked CNS disorders.

That 3alpha-hydroxy-5alpha/beta-pregnane steroids (GABA steroids) have modulatory effects on the GABA-A receptor is well known. In behavioral studies in animals high exogenous dosages give concentrations not usually reached in the brain under physiological conditions. Animal and human studies show that GABA-A receptor-positive modulators like barbiturates, benzodiazepines, alcohol, and allopregnanolone have a bimodal effect. In pharmacological concentrations they are CNS depressants, anesthetic, antiepileptic, and anxiolytic. In low dosages and concentrations, reached endogenously, they can induce adverse emotional reactions in up to 20% of individuals. GABA steroids can also induce tolerance to themselves and similar substances, and rebound occurs at withdrawal. Menstrual cycle-linked disorders can be understood by the concept that they are caused by the action of endogenously produced GABA-steroids through three mechanisms: (a) direct action, (b) tolerance induction, and (c) withdrawal effect. Examples of symptoms and disorders caused by the direct action of GABA steroids are sedation, memory and learning disturbance, clumsiness, increased appetite, worsening of petit mal epilepsy, negative mood as tension, irritability and depression during hormone treatments, and the premenstrual dysphoric disorder (PMDD). A continuous exposure to GABA steroids causes tolerance, and women with PMDD are less sensitive to GABA-A modulators. A malfunctioning GABA-A receptor system is related to stress sensitivity, concentration difficulties, loss of impulse control, irritability, anxiety, and depression. An example of withdrawal effect is "catamenial epilepsy," when seizures increase during menstruation after the withdrawal of GABA steroids. Similar phenomena occur at stress since the adrenals produce GABA steroids during stress.

Affect↗

Health care and social welfare costs in home-based and hospital-based rehabilitation after stroke.

During the 1990s most western European and Organization of Economic Cooperation and Development (OECD) countries experienced financial difficulties and were forced to cut back on or restrain health care expenditures. Home rehabilitation has received attention in recent years because of its potential for cost containment. Often forgotten, however, is the redistribution of costs from one caregiver to another. The aim of this study was to analyse whether a redistribution of costs occurs between health care providers (the County councils) and social welfare providers (the municipalities) in a comparison of home-based rehabilitation and hospital-based rehabilitation after stroke. The study population included 123 patients, 53 in the home-based rehabilitation group and 68 in the hospital-based rehabilitation group. The patients were followed up at 6 and 12 months after onset of stroke. Resource use over a 12-month period included acute hospital care, in-hospital rehabilitation, home rehabilitation and use of home-help service as well as nursing home living. The hospital-based rehabilitation group had significantly fewer hospitalization days after a decision was made about rehabilitation at the acute care ward and consequently the cost for the acute care period was significantly lower. The cost for the rehabilitation period was significantly lower in the home-based rehabilitation group. However, the cost for home help service was significantly higher in the home-based rehabilitation group. The total costs for the care episode did not differ between the two groups. The main finding of this study is that there seems to occur a redistribution of costs between health care providers and social welfare providers in home rehabilitation after stroke in a group of patients with mixed degree of impairment.

Activities of Daily Living↗

Fatty acid composition of skeletal muscle reflects dietary fat composition in humans.

BACKGROUND: It is still unknown whether the fatty acid composition of human skeletal muscle lipids is directly influenced by the fat composition of the diet. OBJECTIVE: We investigated whether the fatty acid composition of the diet is reflected in the fatty acid profile of skeletal muscle phospholipids and triacylglycerols. DESIGN: Thirty-two healthy adults (25 men and 7 women) included in a larger controlled, multicenter dietary study were randomly assigned to diets containing a high proportion of either saturated fatty acids (SFAs) [total fat, 36% of energy; SFAs, 18% of energy; monounsaturated fatty acids (MUFAs), 10% of energy] or MUFAs (total fat, 35% of energy; SFAs, 9% of energy; MUFAs, 19% of energy) for 3 mo. Within each diet group, there was a second random assignment to supplementation with fish oil capsules [containing 3.6 g n-3 fatty acids/d; 2.4 g eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3)] or placebo. A muscle biopsy sample was taken from the vastus lateralis muscle after the diet period. Parallel analyses of diet and supplementation effects were performed. RESULTS: The proportions of myristic (14:0), pentadecanoic (15:0), heptadecanoic (17:0), and palmitoleic (16:1n-7) acids in the skeletal muscle phospholipids were higher and the proportion of oleic acid (18:1n-9) was lower in the SFA group than in the MUFA group. The proportion of total n-3 fatty acids in the muscle phospholipids was approximately 2.5 times higher, with a 5 times higher proportion of eicosapentaenoic acid (20:5n-3), in subjects supplemented with n-3 fatty acids than in those given placebo. Similar differences were observed in the skeletal muscle triacylglycerols. CONCLUSION: The fatty acid composition of skeletal muscle lipids reflects the fatty acid composition of the diet in healthy men and women.

Adult↗

The economic burden of informal care.

OBJECTIVES: The great interest focused on home care technologies during the last decade resulted from its potential to cut costs. However, the reallocation of costs between healthcare providers and social welfare providers, and the indirect costs of informal care, are not as frequent topics of discussion. The aim of this paper is to discuss different models for estimating the costs of informal care in the home care setting in economic appraisals. METHODS: The outcome of using different models for estimating indirect costs was illustrated using empirical data regarding the time spent by informal caregivers in providing care in a group of home care patients (n = 59). The models used comprise different interpretations of the traditional human capital approach and the friction cost model. RESULTS AND CONCLUSIONS: Informal care is an important component in home care. The inclusion of indirect costs of informal care in economic appraisals will have implications for the cost-effectiveness of home care, since it will raise costs depending on the model used for estimating indirect costs. In this study we have shown that indirect costs estimated by the friction cost model only amount to 18% to 44% of the cost when the human capital approach is used. The results indicate that, regardless of the method used to estimate indirect costs, the cost of informal care in evaluations of home care programs is often underestimated due to the exclusion of indirect costs.

Aged↗

Oligohydramnios in uncomplicated pregnancies beyond 40 completed weeks. A prospective, randomised, pilot study on maternal and neonatal outcomes.

OBJECTIVES: In low-risk pregnancies, the management of oligohydramnios is not clear. The aim of this study was to compare maternal and neonatal outcomes in cases of isolated oligohydramnios randomised to either induction of labour or expectant management. METHODS: 87 women pregnant beyond 40 completed weeks were asked to participate in the study. Fifty-four accepted and were randomised at 288 days of pregnancy. Twenty-six were randomised to expectant management and 28 to induction of labour. The primary maternal outcome was the mode of delivery and the primary neonatal outcomes were cord blood pH and Apgar score at delivery. RESULTS: No significant differences were found for any important maternal or neonatal outcome. CONCLUSION: Based on these results, the decisions about management could be individualised. Even though the number of patients included was small, these results are well in concordance with others.

Apgar Score↗