Objective To investigate the possible effects of phosphorylated signal transduction and activator of transcription3 (STAT3) in the formation of choroidal neovascuarization (CNV) induced by photocoagulation in rats. Methods The CNV model in rats induced by photocoagulation was established, and the expression of phosphorylated STAT3 at the early stage in CNV were observed by immunofluorescence. To set up the hypoxia model, the specific inhibitor of Janus kinase 2 (JAK2), AG490 was mixed into cell culture fluid and then cultured for 0,1 hour,3,6,12,and 24 hours.Retinal pigment epithelial (RPE) cells proliferation activity were detected by flow cytometry (FCM).the expression of hypoxiainducible factor (HIF)1α and vascular endothelial grow factor (VEGF) mRNA were detected by reverse transcriptase polymerase chain reaction (RT-PCR); the expression of HIF1α protein was detected by Western blot; the content of VEGF in the supernatant of cell culture fluid was measured by enzyme linked immunosorbent assay (ELISA). Results Phosphorylated STAT3 highly expressed in CNV areas in rats 3 days after the photocoagulation. The proliferation activity of human RPE cells under hypoxia condition significantly decreased after inhibition of JAK2/STAT3 signal transduction pathway (t=1.472, 3.566,2.391,6.420; P=0.054,0.038,0.042,0.016). The expression of HIF-1α and VEGF mRNA increased gradually with increasing time of hypoxia;while the expression of HIF1α and VEGF mRNA and the activation of HIF1α protein in cultured human RPE cells with the JAK/STAT3 signal transduction pathway blocked by AG490 were suppressed obviously under hypoxia condition (t=0.07,0.02,0.01, P<0.05); the content of VEGF in RPE cells supernatant decreased significantly (t=1.330,1.106,2.828,7.742,5.610,6.894; P=0.082,0.063,0.014,0.002,0.016,0.011). Conclusion STAT3 may be involved in CNV formation, which may partly dependent on JAK2/STAT3 signal transduction pathway regulating the expression of HIF-1α and VEGF in RPE cells.
Background In the latter of 20th century, a global growth in allergic diseases has been witnessed, accompanying with spring-out of therapeutic drugs. However, trials did not clarify the comparative effectiveness and pharmaceutical economics of these agents. Severe adverse drug effects have been reported increasingly in the last few years. These made it difficult for clinical practice and selection of national essential drugs. Objective To assess astemizole, loratadine, cetirizine and tefenadine for allergic rhinitis (AR) and urticaria in terms of effectiveness, heart-related drug adverse effects and pharmaceutical economics. Search strategy Cochrane Library, Medline, Embase and Chinese Biomedical Database will be searched. Additional database should be searched for safety and economic studies. Selection Criteria The publication languages are restrained to English and Chinese. 1) Effectiveness: high-quality randomized controlled trials (RCTs) and systematic Reviews (SRs)/ meta-analysis for AR and uritcaria are included, with comparisons restrained to among these four drugs; 2) Safety: a hierarchy of evidences of these four drugs for allergic diseases are included. 3) Economical evaluation: cost-effectiveness and cost-utility assessment of these four drugs for AR and urticaria should be included. Methods of review data extraction sheet and quality appraisal table are separately designed. QUOROM STATEMENT and Jadad Scale are applied, respectively, to SRs and RCTs. Two reviewers independently select the studies, appraise the quality and extract the data. Any disagreement is solved by discussion. Data analysis Fixed effect model is first applied. Sensitivity analysis is employed to study the heterogeneity between trials. Randomized effect model is alternatively used when compromised.
Objectives Re-evaluation the clinical evidence of. anti-virus medicines for virosis communicable respiratory disease on the effectiveness, safety and health economy. Methods To search CL (2003 Issue 1), Medline (1966-2003.5), CCOHTA, SBU, NICE and NCCHTA and collect all CSRs and HTA with computer . The quality of evaluation partly based on QUOROM will be done before results analysed. If heterogeneity does not exist in CSRs and HTA, a Meta-analysis will be re-conducted. Results 4 CSRs (38 RC, n=22 835) and 5 HTA (28 RCT, n=139 281) were included. Due to the significant heterogeneity between these studies, further Meta-analysis could not be conducted, and descri ptive conclusions were conducted only. Conclusions Neuraminidase inhibitors (zanamivir and oseltamivir) are more effective than placebo in reducing the duration of symptoms of patients with basic disease, and have limited effectiveness in health adults. But, both are well tolerated and reduce the rate of contracting influenza in all individuals. For prevention, neuraminidase inhibitors cost more and are not suitable as first-line drug. 2. Diamantane is more effective than placebo in reducing the duration of having fever, and effectively prevents the influenza A. Amantadine and rimantadine have comparable effectiveness in the prevention, although rimantadine induces fewer adverse effects than amantadine. 3. The number of the childrenpatients of upper respiratory tract infection prevented and treated by ribavirin is too small to draw any conculsion now.
Objective This review compared clinical effectiveness, cardiac safety and economics of astemizole, loratadine, cetirizine and terfenadine to provide evidence for adjustment of Essential Drug List in China. Search strategy We searched Medline, Cochrane Library, Embase and Chinese Biomedical Database. Fourteen databases for drug safety and pharmaceutical economics were additionally searched. Selection Criteria Randomized controlled trials and systematic reviews, published in English and Chinese and comparing two or more of these four antihistamines for allergic rhinitis and urticaria were included for study of effectiveness. Non-randomized clinical trials were additionally included for economic evaluation. Cardiac safety studies of antihistamines for allergic diseases of any type were included. Quality Appraisal Jadad scale was primarily applied to randomized controlled trials. Allocation concealment and intention-to-treat analysis were also appraised. The QUOROM statement was applied to systematic reviews and meta-analysis. Data extraction and analyses For the study of effectiveness, composite data were primarily extracted and analyzed by fixed effect model. Sensitivity analysis was done to explore the heterogeneity. For the study of cardiac safety, cases of adverse drug reactions and death were summarized. Difference of occurrence rate in sex and age were analyzed if possible.Electrocardiography and clinical symptoms were summarized. Results No studies on economic evaluation were identified. 27 and 6 randomized controlled trials, including 3 227 participants, for allergic rhinitis and urticaria were identified. Cetirizine was superior to loratadine (n=709) in symptom score and onset of action, superior to terfenadine (n=645) in Quality of Life and superior to astemizole (n=498) in patient satisfaction and onset of action. 73 h-ADR cases were identified in astemizole, 27 cases in terfenadine, 1 case in loratadine and none in cetirizine. No deaths were identified. Combination of terfenadine plus grapefruit juice (n=l8), itraconazole (n=6), nefazodone (n=67), and loratadine administration concomitant with cemitidine (n=30) significantly prolonged QTc interval. Conclusions Cetirizine was superior to other three antihistamines in terms of clinical effectiveness and drug safety. Astemizole and terfenadine could cause significantly more cardiac-related adverse reactions than cetirizine and loratadine.