Antihypertensive efficacy of metoprolol XL/Low dose chlorthalidone (6.25 mg) combination: a randomized,comparative study in Indian patients with mild-to-moderate essential hypertension

Objective

High blood pressure is one of the most important risk factors, directly responsible for increasing the cardiovascular morbidity and mortality. The primary objective was to evaluate the efficacy of metoprolol XL/chlorthalidone against metoprolol XL/hydrochlorothiazide with respect to mean fall in systolic and diastolic blood pressure. The secondary objective was to compare the response rates and to evaluate the tolerability of study medications in patients with mild-tomoderate essential hypertension.

Methods

Total 130 eligible patients (65: metoprolol XL 25 mg/chlorthalidone 6.25 mg; 65: metoprolol XL 25 mg/HCTZ 12.5 mg) were enrolled in this randomized, comparative, multicentric, 12-weeks study. Sixty-two patients from each group completed the study. After 4-weeks of treatment, non-responders from chlorthalidone 6.25 mg combination group were shifted to metoprolol XL 50 mg/chlorthalidone 12.5 mg and non-responders from HCTZ 12.5 mg combination group were escalated to metoprolol XL 50 mg/HCTZ 12.5 mg.

Results

The study treatment groups were comparable with respect to demography and baseline disease characteristics. Both the starting therapies were comparable with respect to mean fall in SBP (p = 0.788) and DBP (p = 0.939), and response rates (p = 1.0) after 4-weeks of therapy. Also both the step-up therapies showed similar mean fall in SBP (p = 0.277) and DBP (p = 0.507) at the end of 12-weeks. However, significantly more number of patients from chlorthalidone 12.5 mg/metoprolol XL 50 mg group responded to therapy as compared to that from HCTZ 12.5 mg/metoprolol XL 50 mg group (p = 0.045). All the reported adverse events were of mild-to-moderate intensity. There were no clinically significant trends in electrolytes (Na⁺, K⁺, Cl^-)and fasting blood sugar, evident across the treatment groups.

Conclusion

Chlorthalidone in combination with metoprolol XL is as effective and well tolerated as widely used combination of metoprolol XL/HCTZ, thus providing an alternative therapeutic option.     

Is growth hormone a radioprotective agent?

There is currently substantial clinical interest in growth hormone (GH) as a protective agent against radiation-related normal tissue injury. To further assess the potential radiation injury-preventive effects of GH, these effects were studied in rats by using a radiation-induced skin injury model. Group 1 received neither GH nor irradiation (control group). Group 2 received 30 Gy of gamma irradiation as a single dose to the right hind legs of the rats (radiation group). Group 3 and 4 received the same irradiation plus either 0.01 U/kg/day GH (RT + 0.01 GH group) or 0.02 U/kg/day GH (RT + 0.02 GH group) subcutaneously. Clinically and histopathologically, acute skin reactions were assessed by two independent experts in radiation oncology and pathology, respectively. Irradiation increased dermatitis in rats when compared with the control group. The severity of radiodermatitis in the rats in the RT + 0.01 GH and RT + 0.02 GH groups was significantly lower than that in the RT group; radiodermatitis developed earlier in the RT group than in the other groups. GH was efficacious in preventing epidermal atrophy, dermal degeneration such as oedema and collagen fibre loss, and hair follicle atrophy, but not better than in the control group. These results are preliminary to studies that will be performed with higher doses of GH in radiation-treated cancer patients, with the aim of reducing radiation-induced toxicity.     

人白血病HL60细胞的分化状态对细胞凋亡的影响

用细胞培养和流式细胞术等方法,研究人白血病HL60细胞诱导分化后,对三尖杉酯碱(Har)和喜树碱(Cam)诱导细胞凋亡的影响。结果表明,12-豆蔻酰及13-乙酸佛波酯以16nmol·L^-1浓度处理HL60细胞24h,细胞向单核/巨噬细胞方向分化,阻断于G_{1期;分化细胞抗Har和Cam诱导的细胞凋亡,但其c-myc基因的表达无变化。1.4%二甲基亚砜处理HL60细胞48h,细胞向粒细胞方向分化,阻断于G1期;分化细胞抗Cam,而不抗Har诱导的细胞凋亡;分化细胞的c-myc基因表达明显下降。结果提示,人白血病HL60细胞的分化状态,明显影响三尖杉酯碱和喜树碱诱导的细胞凋亡,但可能与c-myc基因的表达变化无关。}     

维甲酸与二甲基亚砜诱导HL-60细胞及其抗性亚型MDR 1的表达和对Rhodamine-123外排的影响

利用Dot blot 和流式细胞术，研究了分化诱导剂维甲酸，DMSO对HL-60细胞及其抗性亚型抗药性程度的影响，表明1μmol·ml^-1 RA 作用H-60及其亚型24h， MDR 1 mRNA 明显增高，但流式检测多药抗性细胞系对Rho-123的外排有所下降。2%DMSO作用HL-60及其亚型 24h，流式细胞术检测显示各细胞系对Rho-123 的外排明显增强，提示RA 虽然提高MDR 1基因的表达，但可能通过磷酸化/脱磷酸化方式抑制Pgp-170功能的表达，而DMSO能诱导完整功能的Pgp表达。     

Blockade of clearance of immune complexes by an anti-F(cγ) receptor monoclonal antibody

Clearance of immune complexes by the mononuclear phagocyte system is important for maintaining normal host defenses against bacterial and viral assault (1), but also contributes to the pathogenesis of a variety of immune- mediated diseases . For example, removal from the circulation of IgG-coated erythrocytes and platelets by the MPS is the sine qua non of immune-mediated cytopenias (2, 3). On the other hand, abnormally decreased removal by the MPS of smaller, soluble immune complexes may play a role in the pathogenesis of immune complex-mediated tissue damage found in such autoimmune diseases as SLE (4). Although the physicochemical nature and the size of immune complexes can influence rates of clearance and sites of deposition (reviewed in 5), interactions between immune complexes and the MPS in vivo are poorly understood. The inability to directly measure binding or internalization of immune complexes by cells in the liver and spleen has made the analysis of the molecular basis of immune complex clearance very difficult . Receptors for the Fc portion of IgG (FcγR) and for complement (CR) undoubtedly play a role in the removal of immune complexes, but the relative importance of these receptors is not known.     

中药葛根及其同属植物的资源利用和评价

对我国葛属（ＰｕｅｒａｒｉａＤＣ，）９种和１变种植物进行了调查研究，认为目前国内市售中药葛根的主流品种为野葛Ｐ，ｌｏｂａｔａ（Ｗｉｌｌｄ．）Ｏｈｗｉ和粉葛Ｐ．ｔｈｏｍｓｏｎｉｉ）Ｂｅｎｔｈ．。野葛在我国大部份省区都有分布，资源最为丰富；粉葛在广西载培历史悠久；其他种主要分布在西南地区，并有少数种在当地作中药葛根用。从成分分析结果看，野葛的葛根素（ｐｕｅｒａｒｉｎ）及总黄酮含量显著高于本属其它植物，粉葛次之。除野葛和粉葛外其他种均不宜作葛根药用。峨嵋葛Ｐ．ｏｍｅｉｅｎｓｉｓＷａｎｇｅｔＴａｎｇ是个有争议的种，我们比较了化学成分的含量，其结果与粉葛相近，而与山葛藤有所区别，有待进一步研究。