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51.
52.
Background
Following our previous publication we have received critical comments to our conclusions as well as new data that are strengthening our findings.Results
With the new data, 11 suicide attempts among patients on paroxetine against 1 among patients on placebo, we found with a Bayesian technique that the posterior probability that medication with paroxetine is associated with an increased intensity per year of a suicide attempt is from 0.98 to 0.99, depending on the prior. We found that the comment to our article by GSK representatives contained errors, misunderstanding and unwillingness to accept Bayesian principles in the analysis of clinical trials.Conclusion
We were in our previous publication, with preliminary data and a Bayesian approach, able to raise a concern that suicide attempts might be connected with the use of paroxetine. This suspicion has now been confirmed. 相似文献53.
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56.
Immunosuppression by CD4+ regulatory T cells induced by chronic retroviral infection 总被引:7,自引:0,他引:7 下载免费PDF全文
Michihiro Iwashiro Ronald J. Messer Karin E. Peterson Ingunn M. Stromnes Tomoharu Sugie Kim J. Hasenkrug 《Proceedings of the National Academy of Sciences of the United States of America》2001,98(16):9226-9230
Normal levels of CD4(+) regulatory T cells are critical for the maintenance of immunological homeostasis and the prevention of autoimmune diseases. However, we now show that the expansion of CD4(+) regulatory T cells in response to a chronic viral infection can lead to immunosuppression. Mice persistently infected with Friend retrovirus develop approximately twice the normal percentage of splenic CD4(+) regulatory T cells and lose their ability to reject certain tumor transplants. The role of CD4(+) regulatory T cells was demonstrated by the transmission of immunosuppression to uninfected mice by adoptive transfers of CD4(+) T cells. CD4(+) T cells from chronically infected mice were also immunosuppressive in vitro, inhibiting the generation of cytolytic T lymphocytes in mixed lymphocyte cultures. Inhibition occurred at the level of blast-cell formation through a mechanism or mechanisms involving transforming growth factor-beta and the cell surface molecule CTLA-4 (CD152). These results suggest a possible explanation for HIV- and human T cell leukemia virus-I-induced immunosuppression in the absence of T cell depletion. 相似文献
57.
We have shown previously that neonatal exposure to the cannabinoid CB1 receptor antagonist/inverse agonist rimonabant (SR141716) interfered with suckling and development. However, it was not clear whether the developmental deficiencies were induced by neutral CB1 receptor blockade, thereby inhibiting endogenous cannabinoid "tone," or by inverse agonist reduction of constitutive CB1 receptors. CB1 receptor blockade supports our hypothesis that low CB1 receptor concentrations and/or reduced endocannabinoid levels underlie infant nonorganic failure to thrive (NOFTT). Inverse agonism implies that lower constitutive CB1 receptor activity may be responsible for impaired food intake in newborns. In the present study, we injected the neutral CB1 receptor antagonist 5-(4-chlorophenyl)-3-[(E)-2-cyclohexylethenyl]-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole (VCHSR1) to 1-d-old mouse pups and recorded weight gain, gastric milk contents (milkbands), axillary temperature, and survival between age 1 and 10 d. The results showed a dose-related interference with all measures. These data show that (1) growth failure induced by rimonabant is generalized to another CB1 antagonist and (2) cannabinoid CB1 receptor activation by endocannabinoids is essential for normal milk ingestion and development in mice. This supports our hypothesis that endocannabinoid deficiency and perhaps CB1 receptor dysfunction represents the uncharacterized biologic vulnerability, which underlies NOFTT. 相似文献
58.
E Fride Y Ginzburg A Breuer T Bisogno V Di Marzo R Mechoulam 《European journal of pharmacology》2001,419(2-3):207-214
Delta9-tetrahydrocannabinol, the active principle in marijuana, is a cannabinoid receptor agonist. Both the crude drug and delta9-tetrahydrocannabinol have been used as appetite promoters. The endogenous cannabinoid, arachidonoyl ethanolamide (anandamide), likewise a cannabinoid receptor agonist, has been shown to have the same effect. In contrast, the cannabinoid CB1 receptor antagonist N-(piperidin-1-yl)-5(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1-H-pyrazole-3-carboxamide (SR141716A) reduces food intake. Here, we report that administration of SR141716A to newly born mouse pups (either a single administration on postnatal day 1, or daily for a week as of postnatal day 2) had a devastating effect on milk ingestion and growth. The first 24 h after birth appeared the most critical for the growth stunting effect of SR141716A. Death followed within 4-8 days. Co-administration of delta9-tetrahydrocannabinol almost fully reversed the effect of the antagonist in the week-long regimen. Co-administration of 2-arachidonoyl glycerol, an endocannabinoid, with 2-palmitoyl glycerol and 2-linoleoyl glycerol, which enhance 2-arachidonoyl glycerol potency, resulted in a significant delay in mortality rates caused by the antagonist. We conclude that the endocannabinoid system plays a vital role in milk suckling, and hence in growth and development during the early stages of mouse life. 相似文献
59.
Ingunn Marie S Engebretsen Henry Wamani Charles Karamagi Nulu Semiyaga James Tumwine Thorkild Tylleskär 《BMC pediatrics》2007,7(1):10
Background
Exclusive breastfeeding is recommended as the best feeding alternative for infants up to six months and has a protective effect against mortality and morbidity. It also seems to lower HIV-1 transmission compared to mixed feeding. We studied infant feeding practices comparing dietary recall since birth with 24-hour dietary recall. 相似文献60.
Branly Kilola Mbunga Mala Ali Mapatano Tor A. Strand Elin Lovise F. Gjengedal Pierre Zalagile Akilimali Ingunn Marie S. Engebretsen 《Nutrients》2021,13(3)
Iron deficiency (ID), the leading cause of anemia and the most common nutritional deficiency globally, is not well reported among children in malaria-endemic settings, and little is known about its contribution to anemia in these settings. We aimed to assess the prevalence of anemia, the role of ID using multiple parameters, and the factors associated with anemia in a malaria-endemic rural area. We conducted a community-based cross-sectional study of 432 children aged 1–5 years from the Popokabaka Health Zone, Democratic Republic of Congo. Sociodemographic characteristics, medical history, anthropometric parameters, and biochemical parameters were considered. Hemoglobin and malaria prevalence were assessed using rapid finger-prick capillary blood testing in the field. Venous blood samples were analyzed for serum ferritin, serum iron, total iron-binding capacity, and C-reactive protein (CRP) in a laboratory. Anemia was found in 294 out of 432 (68%) patients. Malaria was found in 375 out of 432 (87%), and ID in 1.8% according to diagnosis by adjusted ferritin only and in 12.9% according to transferrin saturation. ID indicators were not significantly correlated with low hemoglobin levels. Malaria, fever, and CRP > 5 mg/L were major factors associated with anemia in Popokabaka. Anemia control should focus on treating inflammatory conditions and infectious diseases among children in such settings. 相似文献