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81.
Hatem M Abuohashish Mohammed M Ahmed Salim S Al-Rejaie Kamal EH Eltahir 《Acta pharmacologica Sinica》2015,36(2):209-220
Aim:
Depression is a risk factor for impaired bone mass and micro-architecture, but several antidepressants were found to increase the incidence of osteoporotic fractures. In the present study we used ovariectomized (OVX) rats as a model of osteoporosis to investigate the effects of the antidepressant bupropion on the femoral bones.Methods:
OVX animals were treated with bupropion (30, 60 mg·kg−1·d−1) for six weeks. Bone turnover biomarkers (urinary DPD/Cr ratio, serum BALP, OC, TRAcP 5b, CTX and sRANKL levels) and inflammatory cytokines (TNF-α, IL-1β and IL-6) were determined using ELISA. Inductively coupled plasma mass spectroscopy (ICP-MS) was used to determine the femoral bone mineral concentrations. The cortical and trabecular morphometric parameters of femoral bones were determined using micro-CT scan and histopathology.Results:
In OVX rats, the levels of bone turnover biomarkers and inflammatory cytokines were significantly elevated and femoral bone Ca2+ and PO43− concentrations were significantly reduced. Moreover, cortical and trabecular morphometric parameters and histopathology of femoral bones were severely altered by ovariectomy. Bupropion dose-dependently inhibited the increases in bone turnover biomarkers and inflammatory cytokines. OVX rats treated with the high dose of bupropion showed normal mineral concentrations in femoral bones. The altered morphometric parameters and histopathology of femoral bones were markedly attenuated by the treatment.Conclusion:
Bupropion exerts osteo-protective action in OVX rats through suppressing osteoclastogenesis-inducing factors and inflammation, which stabilize the osteoclasts and decrease bone matrix degradation or resorption. 相似文献82.
83.
84.
A randomized controlled trial of single‐class maintenance therapy with abacavir/lamivudine/zidovudine after standard triple antiretroviral induction therapy: final 96‐week results from the FREE study 下载免费PDF全文
85.
Ingeborg Barisic Ljubica Boban Maria Loane Ester Garne Diana Wellesley Elisa Calzolari Helen Dolk Marie-Claude Addor Jorieke EH Bergman Paula Braz Elizabeth S Draper Martin Haeusler Babak Khoshnood Kari Klungsoyr Anna Pierini Annette Queisser-Luft Judith Rankin Anke Rissmann Christine Verellen-Dumoulin 《European journal of human genetics : EJHG》2015,23(6):746-752
Meckel–Gruber Syndrome is a rare autosomal recessive lethal ciliopathy characterized by the triad of cystic renal dysplasia, occipital encephalocele and postaxial polydactyly. We present the largest population-based epidemiological study to date using data provided by the European Surveillance of Congenital Anomalies (EUROCAT) network. The study population consisted of 191 cases of MKS identified between January 1990 and December 2011 in 34 European registries. The mean prevalence was 2.6 per 100 000 births in a subset of registries with good ascertainment. The prevalence was stable over time, but regional differences were observed. There were 145 (75.9%) terminations of pregnancy after prenatal diagnosis, 13 (6.8%) fetal deaths, 33 (17.3%) live births. In addition to cystic kidneys (97.7%), encephalocele (83.8%) and polydactyly (87.3%), frequent features include other central nervous system anomalies (51.4%), fibrotic/cystic changes of the liver (65.5% of cases with post mortem examination) and orofacial clefts (31.8%). Various other anomalies were present in 64 (37%) patients. As nowadays most patients are detected very early in pregnancy when liver or kidney changes may not yet be developed or may be difficult to assess, none of the anomalies should be considered obligatory for the diagnosis. Most cases (90.2%) are diagnosed prenatally at 14.3±2.6 (range 11–36) gestational weeks and pregnancies are mainly terminated, reducing the number of LB to one-fifth of the total prevalence rate. Early diagnosis is important for timely counseling of affected couples regarding the option of pregnancy termination and prenatal genetic testing in future pregnancies. 相似文献
86.
Overexpression of adenosine deaminase (ADA) in red blood cells is characterized by a marked, tissue-specific increase in levels of structurally normal ADA mRNA and enzymatic activity in the erythrocytes of affected individuals, leading to adenosine triphosphate (ATP) depletion and hemolytic anemia. This autosomal dominant trait is linked to the ADA gene. To investigate the molecular mechanism responsible for this disorder, we examined relative reporter gene activity using constructs containing 10.6 kb of 5' flanking sequence and 12.3 kb of the first intron of the ADA gene from the normal and mutant alleles. No differences in chloramphenicol acetyltransferase (CAT) activity were found in transient transfection experiments using erythroleukemia cell lines. Transgenic mice containing the ADA constructs expressed CAT in the appropriate tissue-specific fashion, with 10(2)- to 10(4)-fold higher activity in the thymus. However, CAT activities in erythrocytes and bone marrow of mice containing high transgene copy numbers did not differ between the normal and mutant alleles. These results indicate that the mutation responsible for ADA overexpression is unlikely to reside in the 5' and promoter regions or in the regulatory regions of the first intron. It is possible that the erythroid-specific overexpression of ADA results from a mutation at some distance from the gene or requires an interaction of a proximal mutation with more distal DNA elements. 相似文献
87.
Monoclonal antibody therapy in rheumatoid arthritis 总被引:1,自引:0,他引:1
Monoclonal antibodies bind to their targets with high specificity and
therefore have excellent potential as therapeutic agents. Biotechnological
advances have allowed the production of large quantities of engineered
monoclonal antibodies for therapeutic use. Recent research in rheumatoid
arthritis has identified important mediators of synovitis. Monoclonal
antibodies targeting these have been tested in clinical trials over the
last decade. Anti-cytokine therapies, in particular anti-tumour necrosis
factor alpha monoclonal antibodies, suppressed inflammation and produced
rapid symptomatic improvement. Anti-lymphocyte monoclonal antibodies
produced long- lasting disease suppression in animal models of rheumatoid
arthritis. The use of depleting anti-lymphocyte monoclonal antibodies in
rheumatoid arthritis had been disappointing as they did not penetrate the
synovial joint in sufficient quantity to suppress disease without producing
severe and protracted peripheral blood lymphopenia. Consequently, their use
in rheumatoid arthritis had been abandoned. In contrast, clinical trials of
non-depleting anti-CD4 monoclonal antibodies in rheumatoid arthritis showed
that they could suppress synovitis. However, it remains unclear whether
they could lead to prolonged disease improvement.
相似文献
88.
HJ Ng M Yule M Twoon NR Binnie EH Aly 《Annals of the Royal College of Surgeons of England》2015,97(2):151-156
Introduction
Emergency large bowel surgery (ELBS) is known to carry an increased risk of morbidity and mortality. Previous studies have reported morbidity and mortality rates up to 14.3%. However, there has not been a recent study to document the outcomes of ELBS following several major changes in surgical training and provision of emergency surgery. The aim of this study was therefore to explore the current outcomes of ELBS.Methods
A retrospective review was performed of a prospectively maintained database of the clinical records of all patients who had ELBS between 2006 and 2013. Data pertaining to patient demographics, ASA (American Society of Anesthesiologists) grade, diagnosis, surgical procedure performed, grade of operating surgeon and assistant, length of hospital stay, postoperative complications and in-hospital mortality were analysed.Results
A total of 202 patients underwent ELBS during the study period. The mean patient age was 62 years and the most common cause was colonic carcinoma (n=67, 33%). There were 32 patients (15.8%) who presented with obstruction and 64 (31.7%) had bowel perforation. The overall in-hospital mortality rate was 14.8% (n=30). A consultant surgeon was involved in 187 cases (92.6%) as either first operator, assistant or available in theatre.Conclusions
ELBS continues to carry a high risk despite several major changes in the provision of emergency surgery. Further developments are needed to improve postoperative outcomes in these patients. 相似文献89.