siRNA, miRNA and HIV: promises and challenges

INTRODUCTION The recent discovery of small interfering RNA (siRNA) revealed an important role for small RNAs in regulating gene expression. First described in plants, as “post- trancriptional gene silencing” (PTGS) [1], RNA interfer- ence (RNAi) is a nucleic-acid based immune defense against viruses, transgenes and transposons [2]. Triggered by double-stranded RNA (dsRNA), RNAi leads to the se- quence specific degradation of a target mRNA [3]. In eukaryotic cells, long dsRN…     

Fish-oil supplementation in patients with implantable cardioverter defibrillators: a meta-analysis

Background

A recent Cochrane meta-analysis did not confirm the benefits of fish and fish oil in the secondary prevention of cardiac death and myocardial infarction. We performed a meta-analysis of randomized controlled trials that examined the effect of fish-oil supplementation on ventricular fibrillation and ventricular tachycardia to determine the overall effect and to assess whether heterogeneity exists between trials.

Methods

We searched electronic databases (MEDLINE, EMBASE, The Cochrane Central Register of Controlled Trials, CINAHL) from inception to May 2007. We included randomized controlled trials of fish-oil supplementation on ventricular fibrillation or ventricular tachycardia in patients with implantable cardioverter defibrillators. The primary outcome was implantable cardioverter defibrillator discharge. We calculated relative risk [RR] for outcomes at 1-year follow-up for each study. We used the DerSimonian and Laird random-effects methods when there was significant heterogeneity between trials and the Mantel-Hanzel fixed-effects method when heterogeneity was negligible.

Results

We identified 3 trials of 1–2 years'' duration. These trials included a total of 573 patients who received fish oil and 575 patients who received a control. Meta-analysis of data collected at 1 year showed no overall effect of fish oil on the relative risk of implantable cardioverter defibrillator discharge. There was significant heterogeneity between trials. The second largest study showed a significant benefit of fish oil (relative risk [RR] 0.74, 95% confidence interval [CI] 0.56–0.98). The smallest showed an adverse tendency at 1 year (RR 1.23, 95% CI 0.92–1.65) and significantly worse outcome at 2 years among patients with ventricular tachycardia at study entry (log rank p = 0.007).

Conclusion

These data indicate that there is heterogeneity in the response of patients to fish-oil supplementation. Caution should be used when prescribing fish-oil supplementation for patients with ventricular tachycardia.There is a public perception that fish and fish oil can be recommended uniformly for the prevention of coronary artery disease.^1–3 However, the scientific evidence is divided^4,5 and official agencies have called for more research.⁶It is estimated that 0.5% of patients with coronary heart disease, 1% of patients with diabetes or hypertension and 2% of the general population at low risk of coronary heart disease take fish-oil supplements.⁷ In 2004, the price of fish oils overtook that of vegetable oils, and in 2006, the price rose to US$750 per ton.⁸ The value of fish oil as a nutraceutical in the European market was US$194 million in 2004, and it is anticipated that the price will continue to rise as availability declines.⁸ Canada is both a consumer and an exporter of fish oil, and it exported 15 000 tons in 2006.⁹The scientific debate over the clinical value of fish oil is highlighted by a recent Cochrane review, which concluded that long-chain omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) had no clear effect on total mortality, combined cardiovascular events or cancer.⁴ Furthermore, another recent meta-analysis¹⁰ only showed a significant positive association between fish-oil consumption and prevention of restenosis after coronary angioplasty in a select subgroup after excluding key negative papers.¹¹ Finally, the antiarrhythmic effect, which is proposed to be the principal mechanism of their benefit in cardiovascular disease, has not been demonstrated clearly in clinical trials.^12–14We therefore performed a meta-analysis of randomized controlled trials that examined the effect of fish-oil supplementation in patients with implantable cardioverter defibrillators who are at risk of ventricular arrhythmia to determine the overall effect of fish oils. We also sought to investigate whether there was significant heterogeneity between trials.     

Debate: "How low should LDL cholesterol be lowered for optimum prevention of vascular disease?" Viewpoint: "Below 100 mg/dl"

Arteriosclerotic vascular disease manifests as heart disease, stroke, aortic aneurysms, and peripheral vascular disease, and is a growing problem world-wide. The preventive efforts made so far have demonstrated that lowering LDL-C is one action that individuals and populations can do with significant success in delaying the onset of clinical events. Epidemiological studies and small clinical trials suggest that more aggressive and sustained lowering to LDL-C below 100 mg/dl could result in 50 to 70% reductions in vascular death. The full benefit of reducing LDL-C is only now being tested in adequate clinical trials.     

A Review of the Adverse Effects of Peripheral Alpha-1 Antagonists in Hypertension Therapy

Background  

Doxazosin and its role as an antihypertensive agent have come under recent scrutiny as a result of the early termination of that treatment arm in ALLHAT. It is unclear why the cardiovascular (CV) event rate in this randomized, controlled trial (RCT), especially heart failure, is higher in those treated with a doxazosin-based regimen than with a chlorthalidone based-regimen. There has been little work in the past to summarize information on peripheral alpha-1 antagonists that may be helpful in evaluating the results of this randomized controlled trial.     

两株采自惠州的细鞘丝藻亚科(Leptolyngbyaceae)嗜热蓝细菌的分离鉴定及细胞组分分析

【背景】随着CO_2排放增加,全球变暖愈发严峻,嗜热蓝细菌作为能够在45°C及以上环境中生长并实现生物固碳的微生物,具有重要的研究意义。【目的】对从广东惠州地区采集的藻种进行分离鉴定,并筛选出2株嗜热蓝细菌,研究其生长特性,为嗜热蓝细菌的后续应用提供依据。【方法】通过16SrRNA基因、藻蓝蛋白链A基因(PhycoA)序列分析确定从惠州地区采集到的菌株的分类学位置。对PKUAC-GDTS1-24和PKUAC-GDTS1-29两株嗜热蓝细菌进行形态观察和主要细胞成分(灰分、糖类、脂质、蛋白质和色素)分析。【结果】共分离出12株嗜热蓝细菌,其中PKUAC-GDTS1-24和PKUAC-GDTS1-29菌株,形态上呈蓝绿色球形毛状体,是由细胞形成密集的簇,彼此附着形成的。两株嗜热蓝细菌的主要细胞成分是糖类,分别占细胞干重的36.42%和28.46%。PKUAC-GDTS1-24的灰分、脂质和蛋白质含量分别为24.41%、21.40%和26.64%。PKUAC-GDTS1-29的细胞中,灰分、脂质和蛋白质含量分别为24.72%、23.92%和12.93%。藻蓝蛋白(Phycocyanin,PC)在PKUAC-GDTS1-24和PKUAC-GDTS1-29中的含量分别为157.29 mg/g DW和374.86 mg/g DW,类胡萝卜素分别为65.13 mg/g DW和18.87 mg/g DW。【结论】基于系统发育树研究,本实验的2个分离株属于细鞘丝藻亚科(Leptolyngbyaceae),与研究较少的纤发鞘丝蓝细菌属(Leptolyngbya)菌株相近,可能是广东和四川温泉中存在的一种新型丝状轻度嗜热蓝细菌属或Leptolyngbya新种。嗜热菌株PKUAC-GDTS1-24和PKUAC-GDTS1-29的形态和细胞组成相似,通过比较,2个菌株的藻胆蛋白含量远远高于其他研究报道的Leptolyngbya蓝细菌,尤其是PKUAC-GDTS1-29可以作为藻蓝蛋白生产的潜在菌株。     

Immunohistochemical characterization of mononuclear cells in delayed hypersensitivity reactions toParacoccidiodes brasiliensis (paracoccidioidin test)

The density and distribution of T cells, T helper cells, macrophages and B cells at the site of skin tests with a cytoplasmicParacoccidioides brasiliensis antigen (paracoccidioidin) was studied at 24 and 48 h post-challenge in 10 patients with the chronic form of paracoccidioidomycosis and in 5 non-infected individuals. The in situ study was carried out using immunoperoxidase techniques and monoclonal antibodies. The controls showed negative skin test. In the patients, the great majority of the cells in the perivascular foci were T cells (CD43-positive cells) making up 47% and 48.6% of the total number of cells at 24 and 48 h respectively. Most of the T cells showed a T helper phenotype (CD45RO-positive cells). Approximately 25% of the cells were macrophages (CD68-positive cells) and there were very few B lymphocytes (CD20-positive cells). The present data on the microanatomy of paracoccidioidin skin test sites were consistent with a delayed type hypersensitivity pattern. Our results were comparable to those reported on skin tests for other granulomatous chronic diseases.     

Corticosteroid reduces blood flow to femoral heads in rabbits

Avascular necrosis of the femoral head is one of the common problems in orthopedic practice in Taiwan. The subchondral bone loses its blood supply which weakens its biomechanical support. Steroid overuse is one of many possible etiologies in reducing blood flow to the femoral head. Laser Doppler velocimeter is a precise monitor of regional blood flow of bone which is expressed in perfusion units (PU). In the control group the rabbits were injected with normal saline and there were no statistical differences between blood flow to the right hip (39.26±5.64 PU) and left hip (38.58±4.35 PU). In group B a weekly injection of methylprednisolone into rabbits for 6 weeks demonstrated the reduction of blood flow of femoral head (24.74±3.13 PU) by the laser Doppler velocimeter. The flow decreased further (15.93±2.33 PU) by 12 weeks of steroid treatment. In group C after a weekly injection of steroid for 6 weeks the flow became 31.63±4.79 PU. The steroid was then discontinued for 3 weeks and the flow was 34.6±1.34 PU. In group D the blood flow was 25.89±4.01 PU after 6 weeks of steroid treatment and we stopped the steroid for 6 weeks, the blood flow became 29.86±2.59 PU. The merit of our experiment established a model of study in avascular necrosis of the femoral head in rabbits.     

Improvement of long-term prognosis in patients with ovarian cancers by adjuvant sizofiran immunotherapy: a prospective randomized controlled study

The effect of immunotherapy using sizofiran (SPG) on the prognosis of patients with ovarian cancers was prospectively studied in a total of 68 patients, who were randomly assigned to either a cisplatin, adriamycin and cyclophosphamide (PAC) therapy group or a PAC plus SPG combination therapy group.The survival rate was significantly higher in patients with stage Ic, II or III cancers treated with the PAC plus SPG combination, compared with the patients treated with PAC alone. In the SPG-receiving patients with stage Ic or more advanced cancers who were treated with four cycles or more of PAC, the outcome was improved (Cox-Mantel, p=0.074; generalized Kruskal-Wallis, p=0.032). Similar improvement was also observed in the patients with non-serous adenocarcinomas (Cox-Mantel, p-0.076; generalized Krukal-Wallis, p=0.045). No side effects attributable to SPG were recorded.The present results suggest that the use of SPG in combination with long-term chemotherapy improves the postoperative prognosis in ovarian cancer patients.Abbreviations SPG sizofiran