补肾方药归经与实验性骨质疏松靶器官信号转导分子Smad2的表达

目的:观察补肾方药归经与实验性骨质疏松靶器官信号转导分子Smad2的基因表达,从基因水平研究中医归经理论,为靶向给药提供依据。方法:实验于2004-06/2006-11在河北医科大学中西医结合基础实验室完成。实验分组:选择3个月龄健康雌性SD大鼠(未曾交配)90只,体质量(300±20)g。常规喂养1周后,随机数字表法分成7组:正常对照组、骨质疏松模型组、补肾方药口服组、肾经外贴组、膀胱经外贴组、依普拉封口服组、非经非穴位外贴组,其中正常对照组和骨质疏松模型组每组20只,其余每组各10只。实验处理:除正常对照组喂正常饲料,自由饮水外,其余各组均喂食低钙饲料,饮用蒸馏水,每周2次在大鼠大腿内侧肌肉注射地塞米松1mg/kg体质量,5周后建立骨质疏松模型。实验评估:造模后,用抗骨松穴位贴剂分别外贴肾经和膀胱经穴位、非经非穴位、并与口服补肾方药比较治疗骨质疏松,以双能X线骨密度仪检测连续给药16周后大鼠离体股骨骨密度,采用逆转录-聚合酶链反应、蛋白免疫印迹杂交方法分别检测Smad2的mRNA、蛋白表达,观察其治疗效果。结果:纳入90只大鼠,在实验第5周时,正常对照组、骨质疏松模型组分别取10只,用于验证造模成功,70只进入结果分析。①给药16周后,与骨质疏松模型组比较,补肾方药口服组、肾经外贴组、膀胱经外贴组、依普拉封口服组的股骨骨密度明显增加[(0.161±0.016),(0.206±0.028),(0.196±0.023),(0.202±0.015),(0.205±0.023)g/cm2,P均<0.01]。②应用补肾中药防治16周后,与骨质疏松模型组比较,补肾方药口服组、肾经外贴组、膀胱经外贴组、依普拉封口服组Smad2mRNA的表达明显上调(0.517±0.031,0.524±0.033,0.596±0.033,0.592±0.021,0.583±0.032,P<0.01);Smad2蛋白表达亦明显增强,差异显著(50.901±2.205,71.802±2.100,72.352±2.306,74.012±2.145,73.802±2.203,P<0.01)。结论:①补肾方药通过口服和外贴穴位两种不同途径均发挥“归经”作用,引起靶器官骨组织上调Smad2的表达而有效改善骨密度。②Smad2mRNA表达及蛋白水平的下调可能是原发性骨质疏松症发生的重要机制之一。     

不同结构松质骨填充植入股骨头负重区缺损的有限元分析

目的:应用三维有限元分析法比较松质骨粒和结构性松质骨块植骨重建股骨头负重区缺损对股骨近段应力分布的影响。方法:实验于2005-06/2006-03在解放军总医院骨科研究所完成。采用Taddei的基于连续CT断层构建的人股骨三维有限元模型,在ANSYS5.7分析软件中划分52350个四面体单元,模拟单腿站立时髋臼在股骨头表面负重区施加的面载荷,合力指向股骨头形心,与股骨干长轴的夹角成25°,大小2100N,分别在正常状态时、股骨头负重区缺损时及原位松质骨植入、异位松质骨植入和松质骨粒植入时计算股骨近段的应力分布。结果:①正常股骨近段的应力峰值集中在股骨颈上下方,股骨头表面的应力峰值为2.12MPa,深部应力高于表面应力峰值为6.37MPa。②负重区缺损模型下,股骨头表面应力增高,峰值达10.39MPa,股骨头内部应力低于表面。③在松质骨粒植入后,表面应力有所下降,但仍然高于内部,应力峰值达8.55MPa。④异位结构性松质骨植入后表面应力峰值为2.43MPa,与正常时差别不大;而原位松质骨块植入后的应力曲线几乎与正常应力曲线重合。结论:结构性松质骨块的植入对恢复股骨头表面及内部的应力水平要优于松质骨粒。     

补肾方药归经与实验性骨质疏松靶器官信号转导分子Smad4的表达

目的:观察补肾方药归经与实验性骨质疏松靶器官信号转导分子Smad4的基因表达,从基因水平研究中医归经理论,为靶向给药提供依据。方法:实验于2004-06/2007-05在河北医科大学中西医结合基础实验室完成。①实验分组:选择3月龄健康雌性SD大鼠(未曾交配)70只,体质量(300±20)g。常规喂养1周后,随机数字表法分成7组:正常对照组、病理模型组、补肾方药口服组、肾经外贴组、膀胱经外贴组、依普拉封口服组、非经非穴位外贴组,每组10只。②实验处理:除正常对照组喂正常饲料,自由饮水外,其余各组均喂食低钙饲料,饮用蒸馏水,每周2次在大鼠大腿内侧肌肉注射地塞米松1mg/kg体质量,5周后建立骨质疏松模型。造模后,补肾方药口服组将补肾方药总成分按8g/kg体质量灌喂给药;依普拉封口服组按10mg/kg体质量灌喂给药;正常对照组、模型组每天灌胃等体积的生理盐水,每天上午给药;膀胱经外贴组大鼠在膀胱经取肾俞、飞扬穴;肾经外贴组大鼠在肾经选太溪、大钟穴;非经非穴位外贴组大鼠在大腿内侧肌肉丰厚处选非经非穴位;于脱毛区贴上相应的膏剂,左右交替进行,1次/d。③实验评估:检测连续给药16周后的血清钙、磷、碱性磷酸酶、雌二醇、睾酮,以双能X线骨密度仪检测腰椎骨密度,采用反转录-聚合酶链反应、蛋白免疫印迹杂交方法分别检测Smad4的mRNA、蛋白表达。结果:70只大鼠均进入结果分析。①血清碱性磷酸酶、雌二醇、睾酮、骨密度:给药16周后,与病理模型组比较,补肾方药口服组、肾经外贴组、膀胱经外贴组、依普拉封口服组的血清碱性磷酸酶、雌二醇、睾酮、骨密度明显增加(P均<0.01)。②Smad4mRNA和Smad4蛋白的表达:应用补肾中药防治16周后,与病理模型组比较,补肾方药口服组、肾经外贴组、膀胱经外贴组、依普拉封口服组Smad4mRNA的表达明显上调(P<0.01);Smad4蛋白表达亦明显增强,差异有显著性(P<0.01)。结论:①补肾方药通过口服和外贴穴位两种不同途径给药均发挥"归经"作用,使靶器官骨组织上调Smad4的表达而有效改善骨密度。②Smad4mRNA表达及蛋白水平的下调可能是原发性骨质疏松症发生的重要机制之一。     

High platelet count associated with venous thromboembolism in cancer patients: results from the Vienna Cancer and Thrombosis Study (CATS)

Summary.  Background:  In cancer patients, laboratory parameters that predict venous thromboembolism (VTE) are scarce. Increased platelet count has been found to be a risk factor for VTE in cancer patients receiving chemotherapy (CHT). We have assessed high platelet count as a risk predictor for VTE in patients with cancer undergoing discriminative anti-cancer treatments and investigated whether platelet count correlates with thrombopoietin (TPO) levels. Design and methods:  The Cancer and Thrombosis Study (CATS) is an ongoing prospective observational study of patients with newly diagnosed cancer or progression of disease, which started in October 2003. Occurrence of VTE and information on the patients' anti-cancer treatment during follow-up were recorded. Results: Between October 2003 and February 2008, 665 patients with solid tumors were included (314 female/351 male, mean age 62 years). VTE occurred in 44 patients (18 female/26 male, mean age 62 years). The cumulative probability of VTE after 1 year was 34.3% in patients with a platelet count (PC) above the 95th percentile representing 443 × 10⁹/L compared with 5.9% in those below 443 × 10⁹/L. High platelet count [hazard ratio (HR): 3.50, 95% confidence interval (CI): 1.52–8.06, P  = 0.0032], soluble P-selectin [HR: 2.66, 95% CI: 1.42–4.96, P  = 0.0021] and surgery [HR: 4.05, 95% CI: 1.74–9.46, P  = 0.0012] were statistically significant risk factors for VTE in multivariable analysis along with leucocyte count, age, gender, radio- and CHT. We found no correlation between platelet count and TPO levels. Conclusions:  High PC is a clinically important, independent risk predictor for VTE in cancer patients. PC was not found to be associated with TPO levels.     

Ultrasound-enhanced thrombolysis using Definity as a cavitation nucleation agent

Ultrasound has been shown previously to act synergistically with a thrombolytic agent, such as recombinant tissue plasminogen activator (rt-PA) to accelerate thrombolysis. In this in vitro study, a commercial contrast agent, Definity((R)), was used to promote and sustain the nucleation of cavitation during pulsed ultrasound exposure at 120 kHz. Ultraharmonic signals, broadband emissions and harmonics of the fundamental were measured acoustically by using a focused hydrophone as a passive cavitation detector and used to quantify the level of cavitation activity. Human whole blood clots suspended in human plasma were exposed to a combination of rt-PA, Definity((R)) and ultrasound at a range of ultrasound peak-to-peak pressure amplitudes, which were selected to expose clots to various degrees of cavitation activity. Thrombolytic efficacy was determined by measuring clot mass loss before and after the treatment and correlated with the degree of cavitation activity. The penetration depth of rt-PA and plasminogen was also evaluated in the presence of cavitating microbubbles using a dual-antibody fluorescence imaging technique. The largest mass loss (26.2%) was observed for clots treated with 120-kHz ultrasound (0.32-MPa peak-to-peak pressure amplitude), rt-PA and stable cavitation nucleated by Definity((R)). A significant correlation was observed between mass loss and ultraharmonic signals (r = 0.85, p < 0.0001, n = 24). The largest mean penetration depth of rt-PA (222 mum) and plasminogen (241 mum) was observed in the presence of stable cavitation activity. Stable cavitation activity plays an important role in enhancement of thrombolysis and can be monitored to evaluate the efficacy of thrombolytic treatment. (E-mail: Christy.Holland@uc.edu).     

Dangers of injections overuse in developing countries with a high HIV/AIDS prevalence: a review on HIV risk hazards,traumatic effects and other blood borne infections

Use of injections is commonly practiced in both developed and developing countries. However, in developing countries like Tanzania, both public and private health care providers prescribe and administer injections to clients/patients. The private sector in developing countries is on the leading side for several reasons and becomes the main one being economic or financial gains through charging patients who demand or request or need an injection. Injections in Tanzania are believed by clients/patients or consumers to work fast or better or more effective than oral medications/tablets. This belief is based on the pharmacological advantage of the pharmacokinetics and pharmacodynamics of injectables versus oral medications/tablets. Despite the curative advantage injections have in a human body, these injections must be administered by qualified personnel in our health facilities applying both aseptic and sterile techniques in order to minimize/prevent trauma which may lead to paralysis after damaging sciatic nerve to gluteal muscle, nerve to deltoid muscle, continuous bleeding in individuals with bleeding disorders such as haemophilia, or thrombocytopenia, and spread of infections such as HIV, hepatitis B, C, poliomyelitis, osteomyelitis and other abscesses. Thus, there is a need to institute educational interventions targeting all the three levels i.e. health care providers (clinicians and nurses) in public and private facilities, clients/patients or consumers of care who attend in these facilities and not forgetting injection drug users and traditional healers/practitioners from the informal health sector in our society.