Relationship between oxidative stress and essential hypertension.

This study investigated the association of blood pressure with blood oxidative stress-related parameters in normotensive and hypertensive subjects. A cross-sectional design was applied to 31 hypertensive patients and 35 healthy normotensive subjects. All subjects were men between the ages of 35 and 60 years. Exclusion criteria were obesity, dyslipidemia, diabetes mellitus, smoking and current use of any medication. All patients underwent 24-h ambulatory blood pressure monitoring and sampling of blood and urine. Antioxidant enzymes activity, reduced/oxidized glutathione ratio (GSH/GSSG), and lipid peroxidation (malondialdehyde) were determined in erythrocytes. Parameters measured in the plasma of test subjects were plasma antioxidant status, lipid peroxidation (8-isoprostane), plasma vitamin C and E, and the blood pressure modulators renin, aldosterone, endothelin-1 and homocysteine. Daytime systolic and diastolic blood pressures of hypertensives were negatively correlated with plasma antioxidant capacity (r=-0.46, p<0.009 and r=-0.48, p<0.007), plasma vitamin C levels (r=-0.53, p<0.003 and r=-0.44, p<0.02), erythrocyte activity of antioxidant enzymes, and erythrocyte GSH/GSSG ratio, with hypertensives showing higher levels of oxidative stress. Blood pressures showed a positive correlation with both plasma and urine 8-isoprostane. Neither plasma vitamin E nor the assessed blood pressure modulator levels showed significant differences between the groups or correlation with blood pressures. These findings demonstrate a strong association between blood pressure and some oxidative stress-related parameters and suggest a possible role of oxidative stress in the pathophysiology of essential hypertension.     

Parkinson's disease in Africa: A systematic review of epidemiologic and genetic studies.

Parkinson's disease (PD) occurs worldwide, but little is known about PD in Africa. We systematically reviewed publications on PD in Africa, with emphasis on epidemiologic and genetic studies. Articles published between 1944 and December 2004 were identified using several strategies. The studies emanated from 13 African countries (Kenya, Uganda, Tanzania, Ethiopia, Nigeria, Senegal, Ghana, Togo, Libya, Tunisia, Algeria, Zimbabwe, and South Africa). The publications fell into four categories: clinical series (n = 17), prevalence studies (n = 7), incidence studies (n = 1), and genetic studies (n = 3). The clinical series documented the occurrence of PD in Africa and described its clinical characteristics. The prevalence studies suggested some intracontinental geographic variation in PD prevalence. Overall, the prevalence figures and the incidence rates of PD in Africa appeared lower than those reported for European and North American populations. Few genetic studies of PD have been reported from Africa, and none in blacks. There are no case-control or cohort studies of PD reported from Africa. This review provides a summary of PD research in Africa over the past 60 years and highlights the information gaps and potential areas for future research.     

C4d in Acute Rejection After Liver Transplantation—A Valuable Tool in Differential Diagnosis to Hepatitis C Recurrence

Hepatitis C is the most common indication for liver transplantation. Recurrence of HCV is universal leading to graft failure in up to 40% of all patients. The differentiation between acute rejection and recurrent hepatitis C is crucial as rejection treatments are likely to aggravate HCV recurrence. Histological examination of liver biopsy remains the gold standard for diagnosis of acute rejection but has failed in the past to distinguish between acute rejection and recurrent hepatitis C. We have recently reported that C4d as a marker of the activated complement cascade is detectable in hepatic specimen in acute rejection after liver transplantation. In this study, we investigate whether C4d may serve as a specific marker for differential diagnosis in hepatitis C reinfection cases. Immunohistochemical analysis of 97 patients was performed. A total of 67.7% of patients with acute cellular rejection displayed C4d-positive staining in liver biopsy whereas 11.8% of patients with hepatitis C reinfection tested positive for C4d. In the control group, 6.9% showed C4d positivity. For the first time we were able to clearly demonstrate that humoral components, represented by C4d deposition, play a role in acute cellular rejection after LTX. Consequently C4d may be helpful to distinguish between acute rejection and reinfection after LTX for HCV.     

Cyclooxygenase-2 inhibitors enhance shear stress-induced platelet aggregation.

OBJECTIVES: We aimed to investigate the effect of parecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, on in vivo shear stress-induced platelet aggregation in a rat model of arterial bypass with focal narrowing. BACKGROUND: Long-term use of COX-2 inhibitors is associated with increased incidence of adverse cardiovascular events, especially in patients with a history of cardiovascular disease. These patients are at risk for thrombotic occlusion of arterial stenoses initiated by shear stress-induced platelet aggregation. METHODS: To mimic the combination of a tight arterial stenosis and high shear stress in rats, an extracorporeal shunt from carotid to femoral artery was compressed by the rollers of a pump. Platelet aggregation was continuously measured by a photometric detector in the shunt. RESULTS: Pretreatment with parecoxib (20 mg/kg) almost doubled shear stress-induced platelet aggregation (188% vs. 100% in control subjects, p = 0.0003). This was accompanied by a fall in plasma 6-keto-prostaglandin F(1alpha) from 100 +/- 25 pg/ml to 36 +/- 11 pg/ml (p < 0.0001). Enhanced platelet aggregation was also observed with high-dose aspirin (150 mg/kg) (146%; p = 0.02) but not with low-dose aspirin (25 mg/kg), which reduced aggregation (68%; p = 0.01). The effect of parecoxib was neutralized by low-dose (1 mg/kg) clopidogrel (from 188% to 92%; p = 0.0001), but not by low-dose aspirin (from 188% to 177%; p = NS). CONCLUSIONS: In the presence of an arterial stenosis, COX-2 inhibitors enhance shear stress-induced platelet aggregation. This enhancement was prevented by low-dose clopidogrel but not by low-dose aspirin. Clopidogrel might therefore allow COX-2 inhibitors to be used without raising risk of thrombotic occlusion.     

Tissue-engineered trachea: History, problems and the future.

This review tries to summarize the efforts over the past 20 years to construct a tissue-engineered trachea. After illustrating the main technical bottlenecks faced nowadays, we discuss what might be the solutions to these bottlenecks. You may find out why the focus in this research field shifts dramatically from the construction of a tubular cartilage tissue to reepithelialization and revascularization of the prosthesis. In the end we propose a novel concept of 'in vivo bioreactor', defined as the design of a perfusion system inside the scaffold, and explain its potential application in the construction of a tissue-engineered trachea.     

The analysis of regional patterns in health data. I. Distributional considerations.

Regional patterns of health data such as cancer incidence rates are often examined for evidence of environmental effects. In this paper, three measures of spatial clustering are evaluated for use with epidemiologic data. In particular, the effects of variation in regional population structure on the distribution of these measures is considered. It is shown that substantial bias occurs if variation in regional population size is ignored (as has occurred in previous analyses). On the other hand, the methods are robust to small case frequencies and to variation in the regional age distribution. It is recommended that these regional differences be routinely taken into account, which can be done with relatively little additional computation. A companion paper (Walter SD. The analysis of regional patterns in health data. II. The power to detect environmental effects.     

Treatment of severe acute lung allograft rejection with OKT3 and temporary extracorporeal membrane oxygenation bridging.

OBJECTIVES: The use of OKT3 for treatment of advanced high-grade acute rejection episodes eventually can result in cytokine release and consecutive pulmonary edema. Temporary extracorporeal membrane oxygenation (ECMO) bridging can be used to overcome this crucial period before the beneficial effects of OKT3 can be observed. METHODS: We summarize our experience with three patients, who underwent lung transplantation and presented with severe acute rejection episodes. OKT3 had to be initiated due to insufficient response to standard rejection therapy with corticosteroids. Upon initiation of OKT3 treatment, a massive life-threatening deterioration of lung function in spite of heavily invasive respirator treatment was seen and temporary ECMO support was imperative to support graft function. Results of this treatment were retrospectively reviewed. RESULTS: In all cases femoro-femoral veno-arterial ECMO was used for support of the impaired graft and after a period of 4-5 days led to a massive improvement of graft function. In the further course two patients could be discharged from hospital and are still alive 30 and 36 months, respectively, after the described incident. One patient died 4 months later due to liver failure. CONCLUSIONS: We conclude that the use of ECMO support in patients experiencing significant side effects from OKT3 therapy is a useful and effective therapeutic tool to overcome the initial critical period until the lung has sufficiently recovered.