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。     

Treatment of sympathomimetic induced intraventricular hemorrhage with intraventricular urokinase

Intraventricular hemorrhage (IVH) occurred in a 32-year-old man following the use of both ephedrine and pseudoephedrine. Cerebral angiography and transcranial Doppler studies showed changes suggestive of vasculitis. We describe the management and investigations of a unique case of IVH. This patient was treated with ventriculostomy and intraventricular urokinase (UK). A favorable outcome was obtained with independent function at 10 weeks post hemorrhage. The use of intraventricular thrombolysis for drug-induced IVH has not previously been reported, although it has been shown to be a safe and potentially beneficial intervention.     

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.     

A single centre experience in circumcision of haemophilia patients: Izmir protocol

Summary. Haemophiliacs and their families consider that circumcision is a very important step to become a member of society and it is a social obligation for men in Turkey. Although bleeding risk is high, almost all haemophiliacs would like to be circumcised in Turkish society. The aim of this study was to evaluate our experience in circumcision of haemophilia patients and define efficacy, safety and complication rates of our protocol, called ‘Izmir protocol’. In this study, we retrospectively reviewed medical records of 50 patients with haemophilia who underwent circumcision at our hospital according to Izmir protocol between 1996 and 2009. Oral tranexamic acid and fibrin glue were used in all children. One hour before the operation, first dose of factor concentrate was given. After reaching a plasma factor level of around 90–100%, the prepuce was incised circumferentially and excised using Gomco clamp or open technique under general anaesthesia. Intermittent injections of factor concentrate were given every 12 for 48 h. While the first two doses were given at higher amount to achieve or continue plasma factor level at 90–100%, in the last three doses, the aim was to maintain the plasma factor level at 50–60%. Forty‐eight hours after the circumcision, patients were discharged. Three patients (6%) showed bleeding complication and all were resolved easily. All had at least one excuse from the protocol (Lower doses of factor concentrates was used in 2, tranexamic acid was not used in 2). Izmir protocol is safe, cheap and easy to carry out.     

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.     

Determinants of factor VIII plasma levels in carriers of haemophilia A and in control women

Summary.  Factor VIII (FVIII) levels show a considerable variability in female carriers of haemophilia A. Presently, the reasons for this are poorly understood. The aim of the study was to elucidate the influence of genetic and non-genetic parameters on FVIII plasma levels in carriers ( n  = 42). Results were compared with age-matched healthy women without carriership of haemophilia A ( n  = 42). Each carrier was tested for the family-specific mutation, ABO blood group, FVIII level, von Willebrand factor (VWF) antigen and activity and C-reactive protein (CRP). FVIII levels were lower in carriers compared to non-carriers [74% (51–103) vs. 142% (109–169), P  < 0.001]. No statistically significant differences were observed between the two groups with respect to VWF activity, prothrombin–time, hs-CRP, fibrinogen, body mass index (BMI), age and smoking status as well as the distribution of ABO blood groups. In non-carriers, FVIII was statistically significantly correlated with BMI, activated partial thromboplastin time (APTT), VWF antigen, hs-CRP and fibrinogen. In carriers, significant correlations between FVIII and APTT, VWF antigen and activity were found, whereas BMI, hs-CRP or fibrinogen did not correlate with FVIII. In non-carriers, the association of FVIII with ABO blood groups was statistically significant ( P  = 0.006), but not in carriers of haemophilia A ( P  = 0.234). The type of FVIII gene mutation did not influence FVIII levels. Carrier status is the major determinant of a carrier`s FVIII plasma level. Factors known to influence FVIII levels in the general population do not significantly affect FVIII activity in carriers, neither does the type of mutation influence FVIII levels.     

A sensitive indicator for the severity of COVID-19: thiol

Background/aimThiol status is a good reflector of the cellular redox and have vital roles in various cellular signaling pathways. The purpose of the study was to investigate thiol status in patients with SARS-CoV-2 infection. Materials and methods A total of 587 subjects (517 patients/70 healthy controls) were enrolled in the study.The patients were categorized into the groups regarding to the severity of disease (mild, moderate, severe, and critical).Thiol status of all groups were compared.ResultsThe patients had significantly diminished thiol levels compared to controls. Thiol levels were gradually decreased as the severity of the disease increased. Logistic regression analyses identified that thiol concentrations were an independent risk factor for the disease severity in each phase (mild group OR 0.975, 95%CI 0.965-0.986; moderate group, OR 0.964, 95%CI 0.953-0.976; severe group OR 0.953, 95%CI 0.941-0.965; critical group OR 0.947, 95%CI 0.935-0.960).Thiol test exhibited the largest area under the curve at 0.949, with the highest sensitivity (98.6%) and specificity (80.4%).ConclusionsDepleted thiol status was observed in SARS-CoV-2 infection. Decline of the thiol levels by degrees while the severity of infection increased was closely related to the progression of the disease. This outcome highlights that thiols could be an impressible biomarker for predicting of the severity of COVID-19.     

高效液相法测定排毒养颜胶囊中大黄素的含量

目的：建立排毒养颜胶囊中大黄素含量测定方法。方法：用高效液相法测定,选定YWG－C18分析柱（4．6mm*250mm,5um),流动相：甲醇－0．25％磷酸（80：20）,检测波长：436nm,流速：1．1ml/min,柱温：室温。结果：本法简便,灵敏,准确,生理性好,线性范围0．36－1．80ug(r=0.9999),平均回收率99．14％,RSD．0．81％,结论：建立的定量可用于排毒养颜胶囊的质量控制标准。     

Differentiating Vascular Pathophysiological States by Objective Analysis of Flow Dynamics

BACKGROUND AND PURPOSE: There is an unmet need to classify cerebrovascular conditions physiologically and to assess cerebrovascular system performance. The authors hypothesized that by simultaneously considering the dynamic parameters of flow velocity, acceleration, and pulsatility index (PI) (impedance) in individual Doppler spectrum waveforms, they could develop an objective method to elucidate the pathophysiology of vascular conditions and classify cerebrovascular disorders. This method, dynamic vascular analysis (DVA), is described. METHODS: First, a theoretical model was developed to determine how any vascular segment and the ensemble of intracranial vascular segments could be defined according to its dynamic physiological characteristics. Next, the DVA method was applied to 847 anonymous serial complete clinical transcranial Doppler (TCD) studies of patients without regard for their diagnosis to ascertain actual reference ranges and the normality of the distribution curves for each dimension of the 3-parameter nomogram. The authors applied DVA to 2 clinical cases to see if they could track the changes in vascular performance of 2 known progressive diseases. RESULTS: The theoretical analysis identified 295,245 possible vascular states for the ensemble of vascular segments in the cerebral circulation. When applied to clinical TCD data, DVA revealed continuous, normally distributed data for the velocity, PI, and logarithm of the acceleration. CONCLUSIONS: DVA is proposed as a method for monitoring the physiological state of each cerebral artery segment individually and in ensemble. DVA evaluates the relationship among acceleration (force or pressure), velocity, and PI and provides an objective means to evaluate intracranial vascular segments using the paradigm of the well-described pressure-perfusion autoregulation relationship. DVA may be used to study cerebrovascular pathophysiology and to classify, evaluate, and monitor cerebrovascular disorders or systemic disorders with cerebrovascular effects.