Objectives— The concept of neovascularization in response to tissue ischemia has been extended by the finding of postnatal vasculogenesis initiated by endothelial progenitor cells (EPCs). The aim of this study was to analyze whether a maximal stress test in patients with coronary artery disease (CAD) increases the number of circulating EPCs. Methods and Results— Blood concentration of EPCs was analyzed by FACS and cell culture assay in CAD patients with (n=16) or without (n=12) exercise-induced myocardial ischemia and in healthy subjects (n=11) for up to 144 hours after maximal stress test. Plasma concentrations of vascular endothelial growth factor (VEGF), basic fibroblast growth factor, tumor necrosis factor-α, and granulocyte macrophage-colony stimulating factor were determined by ELISA. EPCs increased significantly in ischemic patients, with a maximum after 24 to 48 hours (cell culture: 3.3±0.5-fold increase; FACS: 3.1±0.6-fold increase) and returned to baseline within 72 hour. In nonischemic patients and healthy subjects, no EPC increase was detectable. VEGF levels in ischemic patients increased significantly after 2 to 6 hours (maximum after 2 hours; 4.0±1.1-fold increase) and no change was observed in nonischemic patients and healthy subjects; ΔVEGF and ΔEPC correlated significantly ( r =0.66). Conclusions— Patients with symptomatic CAD respond to a single episode of exercise-induced myocardial ischemia with a time-dependent increase in circulating EPCs. This increase may be related to and preceded by an increase in plasma VEGF.

Background: Transfusion-transmissible infectious agents such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and syphilis are among the greatest threats to blood safety for the recipient. This study aimed to determine the seroprevalence, risk factors and trends of HIV, HBV, HCV and syphilis infections among blood donors over a period of five years at Gondar University Teaching Hospital, Northwest Ethiopia. Methods: A retrospective analysis of consecutive blood donors' records covering the period between January 2003 and December 2007 was conducted. Logistic regression analysis was used to determine risk factors associated with HIV, HBV, HCV and syphilis infections.Results: From the total of 6361 consecutive blood donors, 607 (9.5%) had serological evidence of infection with at least one pathogen and 50 (0.8%) had multiple infections. The overall seroprevalence of HIV, HBV, HCV and syphilis was 3.8%, 4.7%, 0.7%, and 1.3% respectively. Among those with multiple infections, the most common combinations were HIV -syphilis 19 (38%) and HIV -HBV 17 (34%). The seropositivity of HIV was significantly increased among female blood donors, first time donors, housewives, merchants, soldiers, drivers and construction workers. Significantly increased HBV seropositivity was observed among farmers, first time donors and age groups of 26 -35 and 36 -45 years. Similarly, the seroprevalence of syphilis was significantly increased among daily labourers and construction workers. Statistically significant association was observed between syphilis and HIV infections, and HCV and HIV infections. Moreover, significantly declining trends of HIV, HCV and syphilis seropositivity were observed over the study period. Conclusions: A substantial percentage of the blood donors harbour HIV, HBV, HCV and syphilis infections. Strict selection of blood donors and comprehensive screening of donors' blood using standard methods are highly recommended to ensure the safety of blood for recipient.

Abstract

Background

In Gondar University Teaching Hospital standardized tuberculosis prevention and control programme, incorporating Directly Observed Treatment, Short Course (DOTS) started in 2000. According to the proposal of World Health Organization (WHO), treatment outcome is an important indicator of tuberculosis control programs. This study investigated the outcome of tuberculosis treatment at Gondar University Teaching Hospital in Northwest Ethiopia.

Methods

We analyzed the records of 4000 tuberculosis patients registered at Gondar University Teaching Hospital from September 2003 to May 2008. Treatment outcome and tuberculosis type were categorized according to the national tuberculosis control program guideline. Multivariate analysis using logistic regression model was used to analyse the association between treatment outcome and potential predictor variables.

Results

From the total of 4000 patients, tuberculosis type was categorized as extrapulmonary in 1133 (28.3%), smear negative pulmonary tuberculosis in 2196 (54.9%) and smear positive pulmonary tuberculosis in 671 (16.8%) cases. Of all patients, treatment outcome was classified as successfully treated in 1181(29.5%), defaulted in 730 (18.3%), died in 403 (10.1%), treatment failed in six (0.2%) and transferred out in 1680 (42.0%) patients. Males had the trend to be more likely to experience death or default than females, and the elderly were more likely to die than younger. The proportion of default rate was increased across the years from 97(9.2%) to 228(42.9%). Being female, age group 15-24 years, smear positive pulmonary tuberculosis and being urban resident were associated with higher treatment success rate.

Conclusion

The treatment success rate of tuberculosis patients was unsatisfactorily low (29.5%). A high proportion of patients died (10.1%) or defaulted (18.3%), which is a serious public health concern that needs to be addressed urgently.

Lately certain cytotoxicity of quantum dots (QDs) and some deleterious effects of labeling procedure on stem cells differentiation abilities were shown. In the present study we compared cytotoxicity and intracellular processing of two different-sized protein-conjugated QDs after labeling of the human mesenchymal stem cells (hMSC). An asymmetrical intracellular uptake of red (605 nm) and green (525 nm) quantum dots was observed. We describe for the first time a size-dependent activation of autophagy, caused by nanoparticles.

Our data demonstrate that IL-21R is expressed in RA synovium by RASFs and synovial macrophages. IL-21R is associated with the activated phenotype of RASFs independently of the major proinflammatory cytokines IL-1beta and TNFalpha, but correlates negatively with the destruction of articular cartilage and bone.

Abstract-Transplantation of blood-derived circulating progenitor cells (CPC) has been shown to improve myocardial regeneration after myocardial infarction. It remains unclear whether CPC transplantation exerts beneficial effects also in patients with chronic myocardial ischemia. We initiated a randomized, double-blind, placebo-controlled study evaluating the impact of intracoronary infusion of CPCs on coronary vasomotion and left ventricular (LV) function in patients after recanalization of chronic coronary total occlusion (CTO). After recanalization of CTO, 26 patients (age, 63Ϯ2 years; LV ejection fraction, 53Ϯ2%) were randomly assigned to the treatment (intracoronary transplantation of CPCs) or control group. Coronary flow reserve in response to adenosine (2.4 mg/min) was measured in the target vessel at the beginning of the study and after 3 months. LV function and infarct size were assessed by MRI and metabolism by 18 F deoxyglucose positron emission tomography. CPC application resulted in an increase in coronary flow reserve by 43% from 2.3Ϯ0.3 to 3.3Ϯ0.5 (PϽ0.05 versus beginning and control). At 3 months, the number of hibernating segments in the target region (from 2.9Ϯ0.6 to 2.0Ϯ0.6 segments, PϽ0.05 versus beginning and control) had declined in the treatment group, whereas no significant changes were observed in the control group. MRI revealed a reduction in infarct size by 16% and an increase in LV ejection fraction by 14% in the treatment group (from 51.7Ϯ3.7 to 58.9Ϯ3.2%; PϽ0.05 versus beginning and control) because of an augmented wall motion in the target region. Hence, intracoronary transplantation of CPCs after recanalization of CTO results in an improvement of macro-and microvascular function and contributes to the recruitment of hibernating myocardium. Key Words: ischemic heart disease Ⅲ endothelial dysfunction Ⅲ progenitor cells Ⅲ hibernating myocardium Ⅲ reperfusion R ecently, bone marrow-derived circulating progenitor cells (CPCs) have been shown to promote formation of entirely new vessels into ischemic tissues by a process termed vasculogenesis. 1-3 The CPC-mediated augmentation in myocardial neoangiogenesis in animal experiments prompted researchers to conduct pioneer clinical trials. [3][4][5][6][7][8][9][10] In the TOPCARE-AMI (Transplantation Of Progenitor Cells And Regeneration Enhancement in Acute Myocardial Infarction) study, bone marrow-derived and progenitor cells from peripheral blood administered after successful recanalization in acute myocardial infarction were shown to improve myocardial perfusion, increase left ventricular (LV) contractility, and attenuate LV remodeling equally effective. 9 Perin et al were able to extend the knowledge with regard to bone marrowderived stem cell therapy in patients with severe ischemic heart failure: intramyocardial injection of these cells at the site of ischemia was elucidated to increase blood flow and improve regional and global ventricular function. 5 Additional evidence is emerging from the first randomized study, BOOST (BOne marrOw tr...

Subgroup C strains of Herpesvirus saimiri, a leukemogenic virus of non-human primates, transform human T cells to permanent growth in culture. These cell retain their antigen specificity, and they are becoming widely used as a model for activated human T cells. Though a variety of human cell types can be infected by H. saimiri, transformation appears to be specific for CD4+ and CD8+ T cells. Our investigation of early signaling events in H. saimiri-transformed T cells revealed a novel 40-kDa phosphoprotein complexed with the T cell-specific tyrosine protein kinase p56lck. This protein, termed Tip (tyrosine kinase interacting protein), is identified as a viral protein encoded by the open reading frame 1 (ORF1). In the transformed cells Tip is expressed together with the gene product of ORF2, the viral oncoprotein StpC, which acts on epithelial cells. The H. saimiri genome has 75 ORFs, but only ORF1 and ORF2 are transcribed in transformed human cells. Tip is phosphorylated on tyrosine in cell-free systems containing Lck, indicating that the viral protein is a substrate for this T cell-specific kinase. Alteration of T cell signaling pathways by Tip may be the second event complementing the action of StpC in a new mechanism of T cell transformation.

Jurkat T-lymphocytes comprise at least four intracellular Ca2+ pools. Pool I was agonist-sensitive and contained 23 +/- 8% (n = 18) of the total Ca(2+)-storage capacity, as shown in intact cells in the presence of EGTA. The time courses of the agonist-induced formation of Ins(1,4,5)P3 and of the Ca2+ release from pool I were nearly superimposable, indicating that the agonist-sensitive pool I is emptied by Ins(1,4,5)P3. Likewise, in permeabilized cells, the size of the Ins(1,4,5)P3-sensitive Ca2+ pool I was 27 +/- 11% (n = 14). Pool II contained 26 +/- 5% (n = 9) of intracellularly stored Ca2+ and was liberated by thapsigargin, an inhibitor of the endoplasmic-reticulum (ER) Ca(2+)-ATPase. Addition of thapsigargin before addition of agonist abolished the agonist-induced Ca2+ release in both intact and permeabilized cells, indicating that pool I is a subcompartment of the ER Ca2+ pool. The content of this ER Ca2+ pool (pools I and II) amounted to 51 +/- 15% (n = 9) in intact cells and 49 +/- 16% (n = 16) in permeabilized cells. Caffeine released Ca2+ even when the ER pool (pools I and II) was emptied by previous addition of thapsigargin, indicating the presence of a third pool independent of pools I and II. Pool III contained 23 +/- 6% (n = 8) in intact cells, but 41 +/- 8% (n = 5) in permeabilized cells. The remaining intracellularly stored Ca2+ was released by addition of the Ca2+ ionophore ionomycin. This fourth pool contained 27 +/- 8% (n = 9) in intact cells, but less than 10% in permeabilized cells. The size of pool III was increased when pools I and II were emptied before addition of caffeine, whereas the size of pool IV was decreased under such conditions. In conclusion, this first comprehensive description of intracellular Ca2+ pools in Jurkat T-lymphocytes demonstrates the presence of four different Ca2+ pools, provides estimates of their sizes and describes relationships between each other. Release of Ca2+ from pool I [Ins(1,4,5)P3-sensitive] has previously been shown to play a major role in T-cell activation, whereas the physiological role of pools II-IV remains to be established.