Manjita Srivastava

Role of Proinflammatory Cytokines (Interferon Gamma) and Anti-Inflammatory Cytokine (Interleukin-10) Gene Polymorphisms in Chronic Hepatitis B Infection: An Indian Scenario

Immune-mediated mechanisms have been found to play an important role in the progression of hepatitis B virus (HBV) infection. The outcomes of infection do not appear to be determined by viral strains. Instead, allelic variants in human genome are likely to affect the disease progression. Allelic variation of proinflammatory cytokines such as interferon gamma (IFN-γ) participates in the elimination of HBV, and interleukin-10 (IL-10) helps in inhibition of Th1 effector mechanisms for host defense. The aim of this study was to determine the influence of host genetic factors in chronic HBV infection and gene promoter polymorphism or single-nucleotide polymorphism analysis of IFN-γ+874 and IL-10 (-1082, -592, and -819) on disease progression and persistence. A total of 232 patients along with 76 healthy controls were included. Allele-specific primers for IFN-γ and restriction fragment length polymorphism for IL-10 were used. The study indicated that low IFN-γ expression probably impairs host immune response to HBV, rendering these subjects more prone to HBV infection. No significant differences were detected between the 2 groups in the distributions of IL-10 genotype at the -1082, -819, and -592 positions. Odds ratio indicated that heterozygosity of genotypes -819 CT and -592 AC was more strongly associated with liver chronicity. Significantly, AA homozygous genotype was dominant in chronic hepatitis B cases in IFN-γ+874 and IL-10 (-1082 and -592) and is associated with increased risk of persistent infection.

Predictors of survival in hepatitis B virus related decompensated cirrhosis on tenofovir therapy: an Indian perspective.

Decompensated cirrhosis has low survival rate compared to compensated state. Effective viral suppression due to antiviral therapy (tenofovir) has been shown to slow disease progression and may delay the burden of liver transplantation. We aimed to evaluate the usefulness of various prognostic indicators in predicting the 24-months survival in HBV related decompensated cirrhosis after tenofovir therapy and to evaluate the post-treatment outcome. Ninety-six HBV related decompensated patients on antiviral (tenofovir) therapy were prospectively studied for 24months survival and mortality. Cutoff levels for several prognostic indicators were generated by ROC. Prediction of overall probability of mortality was also calculated. The overall probability of survival observed at 12months was 0.947 whereas at 24months it was found to be 0.833. According to Cox proportional hazards model, the univariate analysis revealed cutoff of >7.4logcopies/ml for HBV DNA, >1.2mg/dl for serum creatinine, >3.7mg/dl for total bilirubin, ⩽0.75 for platelets count, >10 for CTP and >20 for MELD as predictors of poor survival. Multivariate analysis showed MELD score of >20 was the most robust predictor of mortality, with 58 times higher risk (HR: 58.73, p<0.001). Post-treatment response with tenofovir for 24months significantly improved the hepatic functions and reverses decompensation and showed incredible efficacy in improvement of hepatic functional status with reduced viremia in a great majority of decompensated cirrhosis subjects having high MELD and HBV DNA level.

Comparative evaluation of long-term monotherapies & combination therapies in patients with chronic hepatitis B: A pilot study

BACKGROUND & OBJECTIVES Reduction of viraemia in patients with chronic hepatitis B virus (HBV) infection using nucleoside/nucleotide analogues reduces fatal liver disease-related events, but development of resistance in virus presents serious clinical challenge. Therefore, comparative evaluation of prolonged antiviral monotherapy and combination therapies was prospectively studied to assess their influence on viral suppression, rapidity of response, development of drug resistance and surfacing mutants in chronic liver disease (CLD) patients. METHODS A total of 158 (62eAg-ve) chronic hepatitis B patients were prospectively studied for 24 months. Final analysis was performed on patients treated with lamivudine (LAM, n = 28), adefovirdipivoxil (ADV, n = 24), tenofovir disoproxil fumarate (TDF, n = 26), entecavir (ETV, n = 25), LAM + ADV (n = 28) and LAM + TDF (n = 27). Quantitative hepatitis B virus DNA was detected using real-time polymerase chain reaction. Multiple comparisons among drugs and genotypic mutations were analyzed. RESULTS Progressive biochemical and virological response were noted with all the regimens at 24 months except LAM and ADV which were associated with viral breakthrough (VBT) in 46.4 and 25 per cent, respectively. Mutations: rtM204V (39.3%), M204V+L180M (10.7%) while rtA181V (8.1%) and rtN236T (8.3%) were observed with LAM and ADV regimen, respectively. LAM + ADV combination therapy revealed VBT in seven per cent of the cases without mutations whereas TDF, ETV and LAM + TDF therapies neither showed VBT nor mutations. INTERPRETATION & CONCLUSIONS LAM was the least potent drug among all therapeutic options followed by ADV. TDF and ETV were genetically stable antivirals with a strong efficacy. Among newer combination therapies, LAM + TDF revealed more efficacy in virological remission and acted as a profound genetic barrier on long term. Hence, newer generation molecules (TDF, ETV) and effective combination therapy should be a certain choice.

Elastic scattering of electrons by N2, O2, and CO in the energy range 0.1–3 keV

Elastic differential cross sections for the scattering of electrons from N2, CO, and O2 are calculated at intermediate and high energies using the second order eikonal approximation and the multiple scattering approach due to Glauber in the independent atom model. The polarization potential describing the long range and nonlocal dynamic effects has been included. The second order eikonal approximation results show an improvement over those obtained in the first order eikonal approximation at scattering angles Θ≤30° and compare favorably with the available absolute experimental measurements. The interference of single and double scattering terms is investigated.

Inflammatory cytokine IL-10 polymorphism in patients of ulcerative colitis and irritable bowel syndrome

S 21 ANNUAL CONFERENCE—2013 M isella n eo u s Corresponding author: Jitendra Km Choudhary. E-mail: jitendra709@gmail.com INFLAMMATORY CYTOKINE IL-10 POLYMORPHISM IN PATIENTS OF ULCERATIVE COLITIS AND IRRITABLE BOWEL SYNDROME Manish Kumar Tripathi, Ashok Kumar Jain, Vinod Kumar Dixit, Pankaj Kaushik, Jitendra Kumar Choudhary, Manjita Srivastava, Neha Singh, Arttrika Ranjan, Neha Gupta, Sangey Chopel Lamtha, Smita Verma Department of Gastroenterology, Institute of Medical Sciences, BHU, Varanasi Background: Ulcerative colitis (U.C.) is a complex multifactorial trait involving both environmental and genetic factors. UC is characterized by activation of macrophages and T lymphocyte; pro-inflammatory cytokine, chemokines and adhesion molecule expression and an inability to adequately down-regulate immune activation. Aim: The aim of the present study is to examine Interleukin 10 gene polymorphism in patients with UC and IBS. Methods: Age and sex matched 56 patients of IBS and 36 patients of ulcerative colitis were enrolled in the study. Blood samples were obtained after informed consent for DNA isolation by phenol-chloroform method. PCR for IL 10 -1082, -819, -592 was done followed by restriction digestion by site specific enzyme Mnl1, RsaI and MaeIII respectively, the results was analyzed on 2% agarose gel. Results: The percentage distribution of genotypic frequencies of IL-10 -1082 homozygotes and heterozygotes are given in the table 1. Table 1 Genotypic frequencies of IL10 -1082, -819, -592 between IBS and UC patients Cytokines Genotype Frequency IL-10 (1082) AA AG GG IBS 32(57.1) 16(28.6) 8(14.3) Ulcerative Colitis 22(61.1) 8(22.2) 6(16.7) c2=0.479, p=0.787 IL-10 (819) TT TC CC IBS 13(23.2) 21(37.5) 22(39.3) Ulcerative Colitis 4(11.1) 20(55.6) 12(33.3) c2=3.550, p=0.169 IL-10 (592) AA AC CC IBS 36(64.3) 10(17.9) 10(17.9) Ulcerative Colitis 16(44.4) 12(33.3) 8(22.2) c2=3.934, p=0.140 S124 Conclusion: Genotypic frequencies of IL-10 between UC and IBS patients showed that there is no statistically significant difference in IL-10 -1082, -819, -592 cytokine genes. Genotype ATA/ATA correlate with low level of IL-10 production Hence the results of this study indicate low production of anti-inflammatory cytokines IL-10 in patients with UC and IBS. Corresponding author: V.K.Dixit. E-mail: manish.imsbhu@gmail.com

Total charge transfer cross-sections for protons colliding with hydrogen atom

Total charge transfer cross-sections for protons impinging on hydrogen has been calculated in Coulomb-projected Börn approximation. It is seen that the present calculation compares well with the available experimental data.

Electron impact optical excitation of helium-like ions in Coulomb-Glauber approximation

The Coulomb-Glauber approximation is applied to evaluate the electron-impact excitation integrated cross sections for 11S —n1P (n=2, 3) transitions in helium-like ions, C4+, N5+, O6+ and Ne8+. The results are presented in terms of scaled collision strengthn3Z2ki2σ and scaled integrated cross-sectionZ4σ. Our values when compared with other available theoretical results are found to be larger than the Coulomb-Born and distorted wave polarised orbital (DWPO) values.

Triple differential cross section for electron impact ionisation of the hydrogen atom

The triple differential cross section for electron impact ionisation of the ground state is calculated for atomic hydrogen in the Born, Coulomb-projected Born (CPB) and generalised Coulomb-projected Born (GCPB) approximations including exchange. The present CPB calculation is in agreement with the earlier calculation of Geltman and Hidalgo (1974). The authors have compared the present results with the experimental data of Weigold et al (1973) on the angular correlation of the scattered and ejected electrons. The CPB and GCPB calculations are in fairly good qualitative agreement with the shape of the experimental five-fold differential cross section (often called the triple differential cross section) for atomic hydrogen.

Charge-transfer cross sections for protons colliding with hydrogenic ions. I

Theoretical angular distributions and total charge-transfer cross sections have been studied for protons impinging on highly ionised (hydrogenic) systems He1+, Li2+, Be3+, B4+, C5+, N6+, O7+, Fe25+ in the Coulomb projected Born approximation of Geltman (1971). The angular distribution curves exhibit sharp dips in the forward direction for all the ionised systems. The present calculations of Glembocki and Halpern (1977). ZT7 sigma treated as a function of E/ZT2 for all the cases studied are found to follow an almost identical curve which lies lower than the OBK universal curve. The total cross sections converge to hydrogen results at high equivalent incident proton energy.