Nef interference with HIV-1-specific CTL antiviral activity is epitope specific

HIV-1 Nef and HIV-1-specific cytotoxic T lymphocytes (CTLs) have important and opposing roles in the immunopathogenesis of HIV-1 infection. Nef-mediated down-modulation of HLA class I on infected cells can confer resistance to CTL clearance, but the factors determining the efficiency of this process are unknown. This study examines the impact of Nef on the antiviral activity of several CTL clones recognizing epitopes from early and late HIV-1 proteins, restricted by HLA-A, -B, and -C molecules. CTL-targeting epitopes in early proteins remained susceptible to the effects of Nef, although possibly to a lesser degree than CTL-targeting late protein epitopes, indicating that significant Nef-mediated HLA down-regulation can precede even the presentation of early protein-derived epitopes. However, HLA-C-restricted CTLs were unaffected by Nef, consistent with down-regulation of cell-surface HLA-A and -B but not HLA-C molecules. Thus, CTLs vary dramatically in their susceptibility to Nef interference, suggesting differences in the relative importance of HLA-A- and HLA-B- versus HLA-C-restricted CTLs in vivo. The data thus indicate that HLA-C-restricted CTLs may have an under-appreciated antiviral role in the setting of Nef in vivo and suggest a benefit of promoting HLA-C-restricted CTLs for immunotherapy or vaccine development.     

C-reactive protein and prognosis in women and men with coronary artery disease after percutaneous coronary intervention

BackgroundSex-based differences in the association between C-reactive protein (CRP) and cardiovascular events in patients with coronary artery disease (CAD) are incompletely investigated. We investigated whether there are gender differences in the association between CRP and outcome in patients with CAD after percutaneous coronary intervention (PCI).MethodsThis study included 13,170 consecutive patients with CAD: 10,098 men and 3072 women. CRP was measured on admission in all patients. The primary outcome was 1-year mortality.ResultsCRP level (median [25th–75th percentiles]) was higher in women than in men (3.08 [1.30–8.37] mg/L vs 2.30 [0.92–6.47] mg/L; P < 0.001). CRP was > 3 mg/L in 4250 men (42.1%) and 1554 women (50.6%; P < 0.001). One-year mortality was 4.9% (n = 641 deaths). Deaths occurred in 318 men with CRP > 3 mg/L and 122 men with CRP ≤ 3 mg/L (mortality estimates 7.7% and 2.1%, P < 0.001) and in 154 women with CRP > 3 mg/L and 47 women with CRP ≤ 3 mg/L (mortality estimates 10.1% and 3.2%, P < 0.001). After adjustment in the Cox model, CRP was associated with increased risk of mortality in women (adjusted hazard ratio [HR] = 1.03, 95% confidence interval [CI] 1.01–1.04, P < 0.001 for each 5 mg/L increase) and in men (adjusted HR = 1.02 [1.01–1.03], P < 0.001, for each 5 mg/L increase). CRP predicted mortality with an area under the receiver-operating characteristic curve = 0.721, [0.683–0.760] in women and 0.732, [0.707–0.757] in men (P = 0.659).ConclusionsElevated CRP levels provide similar prognostic information in men and women with CAD after PCI which is independent and supplementary to that provided by conventional cardiovascular risk factors.     

Drug-eluting stents in acute myocardial infarction: updated meta-analysis of randomized trials

Background

Use of drug-eluting stents in patients with acute myocardial infarction (AMI) remains an “off label” indication due to concerns regarding their performance in this patient subset.

Methods

We searched Medline, the Cochrane Central Register of Controlled Trials, and Internet-based sources of information on clinical trials in cardiology for randomized trials comparing drug-eluting stents with bare-metal stents in patients with AMI. Hazard ratios for the composite of death or recurrent myocardial infarction, (primary safety endpoint), reintervention (primary efficacy endpoint), death, recurrent myocardial infarction, and stent thrombosis were calculated performing a meta-analysis of 14 randomized trials with 7,781 patients.

Results

There was no difference in the hazard of death or recurrent myocardial infarction (hazard ratio, 0.91; [95% CI 0.75–1.09]) between patients treated with drug-eluting stents versus patients treated with bare-metal stents. Treatment with drug-eluting stents resulted in a significant reduction in the hazard of reintervention (0.41 [95% CI 0.32–0.52]). The hazards of death (0.90 [95% CI 0.71–1.15]), myocardial infarction (0.81 [95% CI 0.63–1.04]), and stent thrombosis (0.84 [95% CI 0.61–1.17]) were not significantly different between patients treated with drug-eluting stents versus patients treated with bare-metal stents.

Conclusions

Use of drug-eluting stents in patients with AMI is safe and markedly reduces the need for reintervention as compared to bare-metal stents.     

Coronary sinus dilatation is associated with left ventricular systolic dysfunction and poor functional status ın subjects with chronic heart failure

Background and aims: Reliable echocardiographic markers additional to plasma biomarkers that would establish prognosis of chronic heart failure and guide therapeutic approach would be beneficial. In our hypothesis, echocardiographic assesment of coronary sinus anatomic alteration, which has been ignored, may be part of remodeling process in heart failure. We also aimed to evaluate relationship between coronary sinus anatomic alteration and left ventricular systolic dysfunction. We echocardiographically analysed 112 patients with heart failure and 61 normal subjects. Left/right ventricular volumes, left atrial area and mean coronary sinus were measured. Coronary sinus diameter was significantly higher in patients than in control group. Statisticallly positive correlation were present between coronary sinus measurements and left/right ventricular volumes (R = 0.5, P < 0.001; R = 0.4, P < 001, respectively), left atrial area (R = 0.6, P < 0.001), NYHA class (R = 0.3, P < 0.001), mitral regurgitation (R = 0.329, P < 0.001), tricuspid regurgitation (R = 0.215, P < 0.02) and left ventricular mass (R = 0.482, P < 0.001). Statistically negative correlation were present between coronary sinus measurements and left ventricle ejection fraction (R = ?0.4, P < 0.001). However, coronary sinus diameter was not correlated with body surface area and pulmonary artery pressure. Tricuspid and mitral regurgitation, left ventricular mass, ejection fraction and functional classs were included in multivariate analysis and only ejection fraction was independent predictor of coronary sinus diameter (P = 0.012). We demonstrated that, dilated coronary sinus is possibly a part of entire process of cardiac remodeling and echocardiographic assessment of dilated coronary sinus may provide useful additional information, predicting the severity of chronic heart failure and poor functional class.     

Phoenix dactylifera L. spathe essential oil: Chemical composition and repellent activity against the yellow fever mosquito

Date palm, Phoenix dactylifera L. (Arecaceae), grows commonly in the Arabian Peninsula and is traditionally used to treat various diseases. The aim of the present study was to identify chemical composition of the essential oil and to investigate the repellent activity. The essential oil of P. dactylifera was obtained by hydrodistillation from the spathe, a specialized leaf structure that surrounds the pollinating organs of the palm. The oil was subsequently analyzed by GC–FID and GC–MS. The oil showed promising repellent activity against yellow fever mosquito – Aedes aegypti. Sixteen components were characterized, constituting 99% of the oil. The main components were 3,4-dimethoxytoluene (73.5%), 2,4-dimethoxytoluene (9.5%), β-caryophyllene (5.5%), p-cresyl methyl ether (3.8%), and caryophyllene oxide (2.4%). The minimum effective dosage (MED) for repellency for the P. dactylifera oil was 0.051 mg/cm², which had moderately lower potency compared to reference standard N,N-diethyl-3-methylbenzamide, DEET (0.018 mg/cm²) in the “cloth patch assay”. The five major compounds were individually assayed for repellency to determine to what extent each is responsible for repellency from the oil. 3,4-Dimethoxytoluene and 2,4-dimethoxytoluene showed the best repellent activity with the same MED value of 0.063 mg/cm², respectively. The results indicate that these two constituents which comprise a large proportion of the P. dactylifera oil (83%) are likely responsible for the observed repellent activity. In this aspect, the P. dactylifera spathe oil is a sustainable, promising new source of natural repellents.     

Impact of body mass index on platelet aggregation after administration of a high loading dose of 600 mg of clopidogrel before percutaneous coronary intervention

This study assessed the effect of body mass index (BMI) on platelet aggregation after administration of a high loading dose of clopidogrel 600 mg. Blood samples of 402 patients before percutaneous coronary intervention were collected >or=2 hours after administration of clopidogrel 600 mg. Platelet aggregation was measured in response to adenosine diphosphate (ADP; 5 and 20 microM). Patients were categorized as normal weight (BMI <25 kg/m(2)) or overweight (BMI >or=25 kg/m(2)). ADP-induced platelet aggregation was significantly higher in overweight patients than in normal-weight patients (46.0 +/- 21.8% vs 38.2 +/- 19.3% for ADP 5 microM, p = 0.0007; 55.1 +/- 22.7% vs 45.2 +/- 21.7% for ADP 20 microM, p <0.0001). Multivariate analyses demonstrated high BMI as the only independent predictor for increased ADP-induced platelet aggregation (p 相似文献   

Human papillomavirus subtype 16 is common in Pakistani women with cervical carcinoma.

INTRODUCTION: Human papillomavirus (HPV) is recognized as a major causative agent for cervical carcinomas. Based on their oncogenic potential, HPV subtypes have been divided into high- and low-risk. In Pakistan, screening for HPV in female patients is not commonly practiced, and as a consequence, the degree of HPV prevalence and its correlation with cervical cancer is unknown. OBJECTIVE: In this study, we have attempted to estimate the prevalence of HPV infection, and also the HPV subtype profile, among Pakistani women with cervical cancer from varied geographical, racial, and social backgrounds within Pakistan. METHODOLOGY: Women visiting two tertiary care hospitals in Karachi, diagnosed with carcinoma of the cervix within the past 15 years, were analyzed for HPV subtypes in their cancer specimens. Retrospectively, 60 paraffin-embedded cervical cancer biopsies were examined for the presence of HPV DNA. After DNA extraction from these samples, polymerase chain reaction (PCR) was used to amplify the HPV L1 gene using the consensus (general) primers, and primers specific for subtypes 16 and 18. RESULTS: Of the 60 samples analyzed, only one sample was HPV negative; the rest of the samples were positive for the presence of HPV. Of the 59 HPV positive samples, 56 showed the presence of HPV16 and one sample was positive for HPV18; HPV subtype could not be determined in two samples. CONCLUSION: Our results show a strong relationship between HPV infection and cervical cancer among Pakistani women. These results underscore the need to implement regular HPV screening for Pakistani women. An early diagnosis of HPV infection will allow better health management to reduce the risk of developing cervical cancer.     

Association of polymorphisms in IL-12/IFN-gamma pathway genes with susceptibility to pulmonary tuberculosis in Indonesia

Upon infection with mycobacteria the IL-12/IFN-gamma axis plays an essential role in the activation of cell-mediated immunity required for the elimination of pathogens. Mutations in genes of the IL-12/IFN-gamma axis are known to cause extreme susceptibility to infection with environmental mycobacteria, and subtle variations in these genes may influence susceptibility to more virulent mycobacteria. We analyzed the distribution of polymorphisms in four essential genes from the IL-12/IFN-gamma axis, IL12B, IL12RB1, IFNG and IFNGR1, in 382 pulmonary tuberculosis patients and 437 healthy controls from an endemic region in Jakarta, Indonesia. The IL12RB1 gene was sequenced in a subset of individuals. Nine known single nucleotide polymorphisms (SNPs) and two new silent variations, 135G>A and 1056C>T, were detected in IL12RB1. Six functional SNPs (-2C>T, 467G>A, 641A>G, 1312C>T, 1573G>A, 1781G>A) in IL12RB1, an IL12B promoter insertion/deletion polymorphism and CA repeats in IFNG and IFNGR1 were analyzed in the cohort. The IFNGR1 allele CA(12) (p=0.004) and genotype CA(12)/CA(12) (p=0.01; OR 0.5) were associated with protection from pulmonary tuberculosis. Interestingly, IL12B promoter heterozygosity was associated with protection from tuberculosis in BCG-vaccinated individuals (p=0.03; OR=0.6). This new finding supports the role that IL-23-of which IL12B encodes a subunit--plays in generation of memory T cells.     

Histopathological and functional effects of antimony on the renal cortex of growing albino rat

Contamination of the environment with antimony compounds may affect human health through the persistent exposure to small doses over a long period. Sixty growing male albino rats, weighing 43-57 grams, utilized in this study. The animals were divided into 3 groups; each of 20 rats: animals of group I served as control, animals of group II received 6 mg/kg body weight antimony trisulfide daily for 8 weeks with drinking water, and those of group III received the same dose by the same route for 12 weeks. The Malpighian renal corpuscles showed distortion, destruction and congestion of glomerular tuft, vacuoles in the glomeruli, peritubular haemorrhage, obliteration of Bowman’s space, and thickening with irregularity of Bowman’s membrane. The proximal convoluted tubules demonstrated patchy loss of their brush border, thickening of the basement membrane with loss of its basal infoldings, disarrangement of the mitochondria, pleomorphic vacuoles in the cytoplasm, apical destruction of the cells, apical migration of the nuclei, and absence of microvilli. On the other hand, peri-tubular hemorrhage, apical vacuolation, small atrophic nuclei, swelling of mitochondria, obliteration of the lumina, destruction of cells, and presence of tissue debris in the lumina, were observed in the distal convoluted tubules. The present work demonstrated the hazardous effect of antimony on the renal function as evidenced by the significant increase of the level of blood urea, serum creatinine, and serum sodium and potassium. In conclusion, this study proposed that continuous oral administration of antimony for 8 and 12 weeks has hazardous toxic effect on the structure and function of the kidney in growing albino rat. Based on the results of the present study, it is recommended to avoid the use of any drinking water contaminated with antimony compounds and forbidden its use in infants and children foods.