Usefulness of C-Reactive Protein as a Marker for Prediction of Future Coronary Events in the Asian Indian Population: Indian Atherosclerosis Research Study

Inflammation plays a pivotal role in all stages of atherosclerosis. Numerous inflammatory, lipid, and cytokines markers have been associated with coronary artery disease (CAD) risk but data directly comparing their predictive value are limited. Studies were carried to elucidate the role of high-sensitivity C-reactive protein (hsCRP), other inflammatory as well as lipid markers and their associations. Among 1021 subjects, comprising 774 CAD affected members from Indian Atherosclerosis Research Study (IARS), plasma hsCRP levels showed strong correlation with inflammatory markers, namely, IL6 (r = .373; P = <.0001), sPLA2 (r = .544; P = <.0001) as also with fibrinogen (r = .579; P = <.0001). Levels of hsCRP were higher among subjects affected by CAD who suffered a repeat coronary event as compared to those who remained event free and subjects in the top quartile of hsCRP (>3.58 mg/L) were found to have a fourfold higher risk. In conclusion, hsCRP appears to be an independent predictor of recurrent CAD events in Asian Indian population

Fuzzy Based Packet Dropping Scheme in Wireless Cellular Networks

Wireless multimedia networks are becoming very popular owing to the user demands for multimedia services. Packet dropping in the event of buffer congestion is one of the important issue in wireless multimedia networks. A packet dropping scheme has to be flexible and adaptive such that acceptable quality of an application is maintained. The paper presents a fuzzy based packet dropping scheme for wireless multimedia networks. A buffer manager placed at the base station performs packet dropping depending upon the traffic conditions and type of an application. Packet dropping is performed by computing dropping factor by considering packet priority, queue length and adaptive queue length threshold. The adaptive queue length threshold is used to dynamically adjust the dropping factor. The queue length threshold is varied by using two fuzzy input parameters, channel condition and rate of flow of an application. The scheme has been extensively simulated to test the performance in terms of acceptance and dropping probability of real-time handoff and new calls

Human Rad52 binding renders ssDNA unfolded: image and contour length analyses by Atomic Force Microscopy

Atomic force microscopy imaging has been used to study the changes associated with human Rad52 (HsRad52) protein in solution, in dried state as well as following ssDNA (linear and circular) binding. In the dried state, the free protein exists predominantly as a characteristic panoply of novel trifoliate forms. However, in solution, the level of trifoliates diminishes significantly. Height analyses of either form reveal two categories: smaller (~ 3-5 nm) and larger ((~ 10-12 nm) particles, perhaps related to sub-heptameric and heptameric forms respectively. Interestingly, binding of the protein to linear ssDNA smoothly extends and unfolds the naked DNA. Contour length measurements performed on several individual circular ssDNA/nucleoprotein complexes reveal marked (about threefold) extension of naked ssDNA, following HsRad52 binding. We speculate that the alignment of HsRad52 on ssDNA into a smoothly extended and unfolded strand from that of highly compact morphology of naked ssDNA, may have bearing on the recombination function of HsRad52 protein

In vitro and in vivo anticancer studies of 2'-hydroxy chalcone derivatives exhibit apoptosis in colon cancer cells by HDAC inhibition and cell cycle arrest

Considering the therapeutic values of bioflavonoids in colon cancer treatment, six 2′-hydroxy chalcones (C1-C6) were synthesized, characterized and screened for in vitro cytotoxicity on human colon carcinoma (HCT116) and African green monkey kidney epithelial cells (Vero). Only C5 showed selective cytotoxicity against HCT116 cells. Other potent cytotoxic compounds were C1, C2 and C3. Further screening included enzyme inhibition studies on histone deacetylase (HDAC) enzyme where C1 showed lowest IC50 value (105.03 µM). Based on cytotoxicity data C1, C2 and C3 were selected for further in vitro mechanistic studies, namely apoptotic studies (Acridine or- ange/Ethidium bromide (AO/EB) and Annexin V), cell cycle analysis using propidium iodide (PI) stain and in vivo anticancer efficacy in 1,2-dimethyl hydrazine (DMH) induced colorectal carcinoma in Wistar rats. The com- pounds induced apoptosis in more than 30 % cells in AO/EB and Annexin V staining. They also showed cell cycle arrest in G2/M phase with PI staining. They showed a significant reduction in aberrant crypt foci formation and adenocarcinoma count along with a significant (p<0.05) reduction in TNF-α levels as compared to DMH control at 100 mg/kg dose. Thus, it can be concluded that the synthesized 2′-hydroxychalcones were effective against colon adenocarcinoma in in vitro and in vivo studies

Prevalence and component analysis of metabolic syndrome: An Indian atherosclerosis research study perspective

Asian Indians have a high predisposition to metabolic syndrome (MS) and coronary artery disease (CAD). The present study aimed to estimate MS prevalence in 531 Asian Indian families comprising of 2318 individuals. Anthropometrics and lipid profile were assessed. MS prevalence was estimated using standard Adult Treatment Panel III (ATP-III) and World Health Organisation (WHO) criteria and modified definitions which included lowered cut-offs for waist circumference (WC) (≥90 cm for men and ≥80 cm for women], body mass index (BMI) (≥23 kg/m2) and impaired fasting glucose (IFG) levels. ATP-III criteria identified a significantly higher proportion of people with MS (N = 933; 40.3%) compared with WHO (N = 708; 30.6%; p < 0.0001) while modified ATP-III showed maximum gain in percent prevalence among the revised criteria (17.3%; p = 0.0056). The IDF criteria identified similar proportion of subjects with MS (N = 809; 34.9%) as the revised WHO criteria (N = 792; 34.2%). The number of MS subjects was highest in the 50–59 years age group. MS was diagnosed a decade earlier in unaffected subjects compared with those with CAD/diabetes using the modified MS criteria. WC correlated significantly with BMI and waist–hip ratio (WHR) (p = 0.000). Among MS components, high density lipoprotein cholesterol and BMI contributed significantly in males (71.4% and 85.9%) and females (86.8% and 88.8%), respectively. The higher percentage contribution of WC among males and WHR among females indicates the influence of gynecoid/android pelvis on WHR measures. In conclusion, the revision of definition criteria for MS with lowered cut-offs for WC and BMI is critical for the accurate assessment of MS among Asian Indians

Genetic studies on the APOA1-C3-A5 gene cluster in Asian Indians with premature coronary artery disease

<p>Abstract</p> <p>Background</p> <p>The APOA1-C3-A5 gene cluster plays an important role in the regulation of lipids. Asian Indians have an increased tendency for abnormal lipid levels and high risk of Coronary Artery Disease (CAD). Therefore, the present study aimed to elucidate the relationship of four single nucleotide polymorphisms (SNPs) in the Apo11q cluster, namely the -75G>A, +83C>T SNPs in the APOA1 gene, the Sac1 SNP in the APOC3 gene and the S19W variant in the APOA5 gene to plasma lipids and CAD in 190 affected sibling pairs (ASPs) belonging to Asian Indian families with a strong CAD history.</p> <p>Methods & results</p> <p>Genotyping and lipid assays were carried out using standard protocols. Plasma lipids showed a strong heritability (h²48% – 70%; <it>P </it>< 0.0001). A subset of 77 ASPs with positive sign of Logarithm of Odds (LOD) score showed significant linkage to CAD trait by multi-point analysis (LOD score 7.42, <it>P </it>< 0.001) and to Sac1 (LOD score 4.49) and -75G>A (LOD score 2.77) SNPs by single-point analysis (<it>P </it>< 0.001). There was significant proportion of mean allele sharing (pi) for the Sac1 (pi 0.59), -75G>A (pi 0.56) and +83C>T (pi 0.52) (<it>P </it>< 0.001) SNPs, respectively. QTL analysis showed suggestive evidence of linkage of the Sac1 SNP to Total Cholesterol (TC), High Density Lipoprotein-cholesterol (HDL-C) and Apolipoprotein B (ApoB) with LOD scores of 1.42, 1.72 and 1.19, respectively (<it>P </it>< 0.01). The Sac1 and -75G>A SNPs along with hypertension showed maximized correlations with TC, TG and Apo B by association analysis.</p> <p>Conclusion</p> <p>The APOC3-Sac1 SNP is an important genetic variant that is associated with CAD through its interaction with plasma lipids and other standard risk factors among Asian Indians.</p

Carbon monoxide reverses established pulmonary hypertension

Pulmonary arterial hypertension (PAH) is an incurable disease characterized by a progressive increase in pulmonary vascular resistance leading to right heart failure. Carbon monoxide (CO) has emerged as a potently protective, homeostatic molecule that prevents the development of vascular disorders when administered prophylactically. The data presented in this paper demonstrate that CO can also act as a therapeutic (i.e., where exposure to CO is initiated after pathology is established). In three rodent models of PAH, a 1 hour/day exposure to CO reverses established PAH and right ventricular hypertrophy, restoring right ventricular and pulmonary arterial pressures, as well as the pulmonary vascular architecture, to near normal. The ability of CO to reverse PAH requires functional endothelial nitric oxide synthase (eNOS/NOS3) and NO generation, as indicated by the inability of CO to reverse chronic hypoxia-induced PAH in eNOS-deficient (nos3−/−) mice versus wild-type mice. The restorative function of CO was associated with a simultaneous increase in apoptosis and decrease in cellular proliferation of vascular smooth muscle cells, which was regulated in part by the endothelial cells in the hypertrophied vessels. In conclusion, these data demonstrate that CO reverses established PAH dependent on NO generation supporting the use of CO clinically to treat pulmonary hypertension

Aspergillus parasiticus crzA, Which Encodes Calcineurin Response Zinc-Finger Protein, Is Required for Aflatoxin Production under Calcium Stress

Two morphologically different Aspergillus parasiticus strains, one producing aflatoxins, abundant conidia but few sclerotia (BN9) and the other producing O-methyl-sterimatocystin (OMST), copious sclerotia but a low number of conidia (RH), were used to assess the role of crzA which encodes a putative calcium-signaling pathway regulatory protein. Under standard culture conditions, BN9ΔcrzA mutants conidiated normally but decreased slightly in radial growth, regardless of illumination conditions. RHΔcrzA mutants produced only conidia under light and showed decreased conidiation and delayed sclerotial formation in the dark. Regulation of conidiation of both A. parasiticus strains by light was independent of crzA. Increased concentrations of lithium, sodium, and potassium impaired conidiation and sclerotial formation of the RHΔcrzA mutants but they did not affect conidiation of the BN9ΔcrzA mutants. Vegetative growth and asexual development of both ΔcrzA mutants were hypersensitive to increased calcium concentrations. Calcium supplementation (10 mM) resulted in 3-fold and 2-fold decreases in the relative expression of the endoplasmic reticulum calcium ATPase 2 gene in the BN9 and RH parental strains, respectively, but changes in both ΔcrzA mutants were less significant. Compared to the parental strains, the ΔcrzA mutants barely produced aflatoxins or OMST after the calcium supplementation. The relative expression levels of aflatoxin biosynthesis genes, nor1, ver1, and omtA, in both ΔcrzA mutants were decreased significantly, but the decreases in the parental strains were at much lower extents. CrzA is required for growth and development and for aflatoxin biosynthesis under calcium stress conditions

Integrated Pest Management (IPM) for Reducing Pesticide Residues in Crops and Natural Resources

Investigation on the pesticide residues during 2006–2009 in various crops and natural resources (soil and water) in the study village (Kothapally, Telangana State (TS)) indicated the presence of a wide range of insecticidal residues. Pooled data of the 80 food crop and cotton samples, two rice grain samples (3 %) showed beta endosulfan residues, and two (3 %) soil samples showed alpha and beta endosulfan residues. In vegetables of the 75 tomato samples, 26 (35 %) were found contaminated with residues of which 4 % had residues above MRLs. Among the 80 brinjal samples, 46 (56 %) had residues, of these 4 % samples had residues above MRLs. Only 13 soil samples from vegetable fields were found contaminated. The frequency of contamination in brinjal fields was high and none of the pulses and cotton samples revealed any pesticide contamination. IPM fields showed substantial reduction sprays which in-turn reflected in lower residues. Initial studies on water analysis indicated the presence of residues in all water sources with higher in bore wells compared to open wells, however, by 2009 the water bodies reflected no residues above the detectable level