Ulcerative Colitis and Its Association with Salmonella Species.

Ulcerative colitis (UC) is characterized by presence of ulcer in colon and bloody diarrhea. The present study explores the possibility of association between Salmonella and ulcerative colitis. The present study comprised 59 cases of UC, 28 of colon cancer (CC), 127 of irritable bowel syndrome (IBS), and 190 of healthy control. The serological study was done by Widal and Indirect Haemagglutination Assay (IHA) for ViAb. Nested PCR was performed targeting fliC, staA, and stkG gene for Typhi and Paratyphi A, respectively. A total of 15.3% patients were positive for Salmonella "O" antigen among them 18.6% UC, 35.5% CC, 12.6% IBS, and 15.3% healthy control. A total of 36.9% patients were positive for "H" antigen including 39.0%, 57.1%, and 67.7% UC, CC, and IBS, respectively. About 1.73% show positive agglutination for AH antigen including 3.4%, 3.6%, and 1.6%, UC, CC, and IBS. A total of 10.89% were positive for ViAb. While 6.8% of UC, 10.7% of CC, 11.0% of IBS, and 12.1% of healthy subjects were positive for the antibody, the PCR positivity rates for Salmonella specific sequences were 79.7% in UC, 53.6% in CC, 66.1% in IBS, and 16.3% in healthy controls. The present study suggested that higher prevalence of Salmonella might play important role in etiopathogenesis of UC, IBS, and CC.

HBsAg Level as Predictor of Liver Fibrosis in HBeAg Positive Patients With Chronic Hepatitis B Virus Infection.

BACKGROUND AND AIMS: Preliminary data suggests lower serum hepatitis B surface antigen level is associated with more severe liver fibrosis in HBeAg positive patients. We evaluated the association of HBsAg level with biochemical, virological, and histological features in asymptomatic patients with chronic HBV infection. METHODS: HBsAg levels were measured at baseline in 481 asymptomatic, treatment naive patients with chronic HBV infection. Subjects were followed-up prospectively (median, 12; range, 8-36 months). Phases of HBV infection were defined after regular monitoring of HBV-DNA and transaminases. Liver histology was scored using the METAVIR system. RESULTS: HBeAg positive (n, 126) patients were significantly younger than HBeAg negative (n, 355), median age 26 vs 30 years; P < 0.01. HBV genotype could be determined in 350 patients, 240 (68.57%) had genotype D and 100 (28.57%) had genotype A. HBsAg level had modest correlation with serum HBV DNA(r = 0.6 vs 0.4 in eAg positive & negative respectively). HBeAg + ve patients with fibrosis score ≥ F2 showed significantly lower median serum HBsAg levels and serum HBV DNA levels compared with patients with F0-F1 score (median, range; 4.51, 2.99-6.10 vs 5.06, 4.13-5.89, P < 0.01) and (8.39, 3.85-10.60, P < 0.01) respectively. Significant inverse correlation of HBsAg level was found with liver fibrosis in eAg positive group (r = -0.76; P < 0.001). HBsAg level cut off value 4.7 log10 IU/ml predicted moderate to advance fibrosis (F ≥ 2) with 92% sensitivity, 85% specificity & 91% negative predictive value. CONCLUSION: Lower HBsAg level might reflect the status of advanced liver fibrosis in HBeAg positive chronic hepatitis B subjects.

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.

Assessment of the Model for End-stage Liver Disease (MELD) Score in Predicting Prognosis of Patients with Alcoholic Hepatitis.

BACKGROUND: Traditionally, Maddrey discriminant function (DF) score has been used for stratifying the prognosis of alcoholic hepatitis. Recently, the Model for end-stage liver disease (MELD) score has been applied to alcoholic hepatitis and some investigators consider MELD score as a better prognostic indicator. Another new prognostic approach, Lille model has been also suggested to accurately identify patients at high risk of death. Therefore, this prospective study was aimed to compare MELD, DF, Child-Turcotte-Pugh (CTP) scores and Lille model for predicting the short-term mortality in Indian patients with alcoholic hepatitis. METHODS: We calculated the DF, CTP, MELD and Lille scores in patients hospitalized with alcoholic hepatitis & evaluated if the scores predicted in-hospital mortality. RESULTS: A total of 104 patients were enrolled and thirty-two (30.7%) patients died during the hospitalization (2-30 days). Admission DF score (OR 1.1, P < 0.04), CTP (OR 2, P < 0.05) MELD score (OR 2.2, P < 0.005) and first week MELD score (OR 1.1, P < 0.05) were independently associated with in-hospital mortality. The area under the receiver-operating curve (AUROC) for the admission and day 7 MELD score was significantly higher than CTP score and was comparable to DF score and Lille model (AUC & 95% CI: 0.97 [0.95-1.0], 0.99 [0.99-1.0], 0.91 [0.83-0.91] and 0.92 [0.86-0.98] for MELD at admission & day 7, admission DF and Lille model, respectively). The MELD score >14 at admission and >12 at day 7 had high sensitivity and specificity in predicting short-term mortality (96%, 89% and 95%, 98% respectively). The cutoff of 0.45 for the Lille model was able to identify 79% of the observed deaths, whereas DF score ≥32 for DF were able to identify 85%. CONCLUSION: MELD score, as a predictive model for assessment of short-term mortality in alcoholic hepatitis is better than CTP and comparable to DF and Lille model.

Clinical Profile and Response to Treatment with Pegylated Interferon α 2b and Ribavirin in Chronic Hepatitis C-A Reappraisal from a Tertiary Care Center in Northern India.

AIM: To assess the clinical profile of 80 chronic hepatitis C patients in a tertiary health care center in Northern India and also to study the efficacy and tolerability of pegylated interferon (Peg-IFN) α 2b and ribavirin therapy in a cohort of chronic hepatitis C patients. METHODS: Thirty subjects with chronic hepatitis C (CH-C) with genotypes 2 and 3 received Peg-IFN α 2b 1.5 µg/kg subcutaneously weekly plus daily ribavirin 800 mg for 24 weeks .Subjects with genotype 1 infection received therapy for 48 weeks with ribavirin 1000 mg/day and Peg-IFN α 2b dose remained the same. The primary end point was the sustained viral response (SVR). Drug dosage was modified or temporarily discontinued if anemia or bone marrow suppression developed. RESULTS: The clinical profile of chronic hepatitis C infected patients showed decompensated cirrhosis in the more elderly patients. Genotype 3 was the commonest genotype and was seen in 21 (70%) patients. The mean baseline HCV RNA was high. SVR was achieved less commonly with genotype 1 than with genotype 2/3. Patients who became negative for HCV RNA at 4-weeks (rapid virological response or RVR) and 12 weeks (early virological response or EVR) of treatment showed significantly higher sustained virological response (SVR) rates. Similarly, patients who showed normalization of ALT level at 4-weeks and 12-weeks of treatment showed significant high rate of SVR. Overall treatment was well tolerated. CONCLUSION: In our region, CHC subjects have high viral load and genotype 3 being the most common. Treatment with Peg-IFN α 2b and ribavirin is effective and well tolerated. Genotype 1 was more resistant to the treatment. Patients who achieved RVR and EVR are more likely to achieve SVR. Although the numbers of patients in this study was small, considering the paucity of data of treatment from India, the data is relevant.

Hydatid Cyst of Liver Presented as Obstructive Jaundice in Pregnancy; Managed by PAIR.

Incidence of Hydatid disease in pregnancy ranges from 1in 20,000 to 1 in 30,000. The most common site of hydatid cysts is the liver. The diagnosis of liver hydatid cysts is not difficult but the management during pregnancy is problematic. Both medical and surgical treatments are available but there is no consensus and each case has to be individualized. We present a case of liver hydatid cyst presented with obstructive jaundice during pregnancy which was managed by Puncture of the cyst under USG guidance; Aspiration of the cystic fluid, Injection of hypertonic saline, and Re-aspiration of solution without drainage (PAIR) and albendazole therapy. Very few cases of liver hydatosis were reported previously which had been managed by PAIR.

Differential Larval Toxicity and Oviposition Altering Activity of Some Indigenous Plant Extracts against Dengue and Chikungunya Vector Aedes albopictus.

BACKGROUND: Mosquitoes are well known as vectors of several disease causing pathogens. The extensive use of synthetic insecticides in the mosquito control strategies resulted to the development of pesticide resistance and fostered environmental deterioration. Hence in recent years plants become alternative source of mosquito control agents. The present study assessed the larvicidal and oviposition altering activity of six different plants species-Alstonia scholaris, Callistemon viminalis, Hyptis suaveolens, Malvastrum coromandelianum, Prosopis juliflora, Vernonia cinerea against Aedes albopictus mosquito in laboratory. METHODS: Leaf extracts of all the six plants species in five different solvents of various polarities were used in the range of 20-400ppm for larval bioassay and 50,100 and 200ppm for cage bioassay (for the study of oviposition behavior) against Ae. albopictus. The larval mortality data were recorded after 24 h and subjected to Probit analysis to determine the lethal concentrations (LC50), while OAI (Oviposition activity index) was calculated for oviposition altering activity of the plant extracts. RESULTS: Vernonia cinerea extract in acetone and C. viminalis extract in isopropanol were highly effective against Aedes albopictus larvae with LC50 value 64.57, 71.34ppm respectively. Acetone extract of P. juliflora found to be strong oviposition-deterrent which inhibited >2 fold egg laying (OAI-0.466) at 100ppm. CONCLUSION: Vernonia cinerea and C. viminallis leaf extracts have the potential to be used as larvicide and P. juliflora as an oviposition-deterrent for the control of Ae. albopictus mosquito.

Cellular and antitumor activity of a new diethylene glycol benzoporphyrin derivative (lemuteporfin).

A newly synthesized diethylene glycol functionalized chlorin-type photosensitizer, lemuteporfin, was characterized for use in photodynamic therapy (PDT) in a panel of in vitro and in vivo test systems. The photosensitizer was highly potent, killing cells at low nanomolar concentrations upon exposure to activating light. The cellular uptake of lemuteporfin was rapid, with maximum levels reached within 20 min. Mitogen-activated lymphoid cells accumulated more of the lemuteporfin than their quiescent equivalents, supporting selectivity. Photosensitizer fluorescence in the skin increased rapidly within the first few minutes following intravenous administration to mice, then decreased over the next 24 h. Skin photosensitivity reactions indicated rapid clearance of the photosensitizer. Intravenous doses as low as 1.4 micromol/kg combined with exposure to 50 J/cm2 red light suppressed tumor growth in a mouse model. In conclusion, this new benzoporphyrin was found to be an effective photosensitizer, showing rapid uptake and clearance both in vitro and in vivo. This rapid photosensitization of tumors could be useful in therapies requiring a potent, rapidly accumulating photosensitizer, while minimizing the potential for skin photosensitivity reactions to sunlight following treatment.

Cloning and structural analysis of a cDNA clone encoding glycinin (Gly-1) seed storage protein of peanut

A cDNA clone (peanut Gly-1) encoding for glycinin protein was isolated from the immature seeds (from yellow-1 maturity pods) and characterized. The clone spanning a total of 1836 bp, predicted protein of 529 amino acid residues with a calculated mass of 60,447.61 Da. Peanut Gly-1 sequence comparison shows high level of sequence homology with other two peanut glycinin (arachin) genes [Ara h3 (95 percent) and Ara h4 (94 percent)] and glycinin (legumin) genes of other legumes such as soybean, broad bean, French bean and pea etc., both at nucleotide (67 to 69 percent) and amino acid (60 to 63 percent) levels. The N- and C-terminals of peanut Gly-1 are highly conserved with other glycinin genes; central region of the gene possess three variable regions, which also show conservation with other glycinin genes. Peanut glycinin-1 gene deciphers 11S type A seed storage protein. Mapping for conserved domains indicate that Peanut Gly-1 consists of bi-cupin domain. RNA gel blot studies demonstrate that the gene expressed during embryo development that is transcriptionally activated early in embryogenesis (white pod maturity) and is repressed late in seed maturation (orange pod maturity stage). Peanut Gly-1 does not express in other tissues like leaf, stem, root, flower, pegs or post germinating seedlings.

De novo breast cancer in patients with liver transplantation: University of Pittsburgh's experience and review of the literature.

De novo malignancies are one of the current problems in patients with organ transplantation. The incidence has been considered to be higher as a result of increases of oncogenic viruses in immunosuppressed organ recipients. Published reports have shown increased incidence of de novo tumors such as malignant lymphomas and cutaneous neoplasms but decreased incidence of breast cancer. A variety of factors affect de novo breast cancer development in organ recipients, including immunosuppression, viruses, and underlying disease. The aims of this review are to evaluate the incidence and management of patients with de novo breast cancer by giving the University of Pittsburgh's data, and to evaluate the incidence of de novo breast cancer in published reports in light of an age-adjusted rate. According to age-adjusted rates presented by the National Cancer Institute's Surveillance, Epidemiology and End Results data, we found increased incidence rate of de novo breast cancer in the previously published series. The University of Pittsburgh's incidence rate of de novo breast cancer was determined in a fashion similar to that for the Surveillance, Epidemiology and End Results data. Eighty-three percent of all patients were diagnosed at early stages, and it appeared to take longer for de novo breast cancer to develop in patients treated with tacrolimus than in patients treated with cyclosporine. In conclusion, surgical treatment of breast cancer in liver recipients is the same as treatment of breast cancer in patients without transplantation. However, the effects of chemotherapy, radiotherapy, and/or tamoxifen remain unclear in transplanted patients and need to be evaluated in larger studies.