Asian Health Care Foundation

Somajiguda, India

Asian Health Care Foundation

Somajiguda, India

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Mukherjee R.M.,Asian Health Care Foundation | Shravanti G.V.,Asian Institute of Gastroenterology | Jakkampudi A.,Asian Health Care Foundation | Kota R.,Asian Health Care Foundation | And 5 more authors.
Journal of Clinical and Experimental Hepatology | Year: 2013

Background: High mobility group box1 (HMGB1) and poly(ADP-ribose) polymerase1 (PARP1) proteins repair cellular DNA damage. Reduced expression of the corresponding genes can lead to an impaired DNA damage repair mechanism. Intracellular replication of hepatitis B virus (HBV) in such conditions can favor the integration of viral DNA into host genome leading to the development of hepatocellular carcinoma (HCC). Objective: This study was performed to assess the expression of HMGB1 and PARP1 mRNAs in conjunction with the estimation of HBV replication intermediate pregenomic RNA (PgRNA) in various phases of HBV infection. Materials: Eighty eight patients and 26 voluntary blood donors as controls were included in the study. Patients were grouped in to acute (AHB; n=15), inactive carriers (IC; n=36), cirrhosis (Cirr; n=25) and hepatocellular carcinoma (HCC; n=12). Serum HBV DNA was quantified by real time polymerase chain reaction (PCR) assay. Expression of HMGB1, PARP1 and PgRNA were evaluated using peripheral blood mononuclear cells (PBMCs) derived RNA by reverse transcription PCR (RT-PCR) and densitometry. Results: Significant reduction of HMGB1 and PARP1 gene expressions (P<0.05) were observed in patients than controls with more explicit decline of PARP1 (P=0.0002). Both genes were significantly downregulated (P<0.001) in ICs than controls. In ICs, HMGB1 was significantly lowered than cirrhosis (P=0.002) and HCC (P=0.0006) while PARP1 declined significantly (P=0.04) than HCC. Level of PgRNA was comparable in all the disease categories. Conclusion: In conclusion, our findings indicate impaired DNA damage repair mechanisms in HBV infected cells of ICs. This, along with low viral load but higher level of PgRNA in this group is suggestive of the diversion of HBV replication pathway that might facilitate viral DNA integration in to host genome. Intrusion of HBV PgRNA reverse transcription in early stage of infection might appear advantageous to thwart the development of HCC. © 2013 INASL.


Mitnala S.,Asian Health Care Foundation | Pondugala P.K.,Asian Health Care Foundation | Guduru V.R.,Asian Institute of Gastroenterology | Rabella P.,Asian Institute of Gastroenterology | And 5 more authors.
Pancreas | Year: 2010

Objectives: The present study was conducted to monitor the expression of pancreas and duodenal homeobox gene (PDX-1) for assessing β-cell function in islets from patients with chronic pancreatitis (CP). Methods: Islets isolated from the pancreata of 40 surgical patients categorized as control group, patients with mild CP, and patients with advanced CP were assessed for their yield, size, and glucose-stimulated insulin secretion. Expressions of genes coding for PDX-1, insulin, and glucagon were simultaneously monitored by reverse transcription polymerase chain reaction and confirmed by immunohistochemistry. Results: In comparison with the control group (2673 ± 592 islet equivalents [IEq]/g), islet yield did not differ much in the patients with mild CP (2344 ± 738 IEq/g) but was significantly reduced (P < 0.0001) in the patients with advanced CP (731 ± 167 IEq/g). Although the marginal decrease in islet size observed in the patients with mild CP was not significantly different from that observed in the control group, there was a 58% decrease observed in the patients with advanced CP that was also accompanied by a significant reduction in β-cell mass (P < 0.05). The expression of insulin and PDX-1 genes, but not of glucagon, was significantly reduced in the patients with advanced CP as confirmed by immunohistochemistry. Islets obtained from the patients with advanced CP retained 53% glucose-stimulated insulin secretion function in comparison with those of the control group. Conclusion: The results indicate that β-cell dysfunction during progression of CP correlates with the decrease in PDX-1 gene expression. Copyright © 2010 by Lippincott Williams & Wilkins.


Mukherjee R.M.,Asian Health Care Foundation | Bansode B.,Asian Health Care Foundation | Gangwal P.,Asian Health Care Foundation | Jakkampudi A.,Asian Health Care Foundation | And 4 more authors.
Journal of Clinical and Experimental Hepatology | Year: 2012

Background: The interferon regulatory factors (IRFs) are a family of transcription factors known to be involved in the modulation of cellular responses to interferons (IFNs) and viral infection. While IRF-1 acts as a positive regulator, IRF-2 is known to repress IFN-mediated gene expression. The increase in the IRF-1/IRF-2 ratio is considered as an important event in the transcriptional activation of IFN-α gene toward development of the cellular antiviral response. Objective: This study was performed to assess the expression of IRF mRNAs along with the expression level of IFN-α, its receptor (IFNAR-1), and the signal transduction factor (STAT-1) in treatment naive hepatitis C virus (HCV)-infected subjects. Materials: Thirty-five chronically infected (CHC) patients and 39 voluntary blood donors as controls were included in the study. Quantification of HCV-RNA (ribonucleic acid) and genotyping were done by real-time polymerase chain reaction (PCR) and hybridization assays, respectively, using patient's serum/plasma. In both controls and patients, the serum level of IFN-α and IFN-α was measured by flow cytometry. Target gene expressions were studied by retro-transcription of respective mRNAs extracted from peripheral blood mononuclear cells (PBMCs) followed by PCR amplification and densitometry. Minus-strand HCV-RNA as a marker of viral replication in PBMCs was detected by an inhouse PCR assay. Results: Both IRF-1 and IRF-2 genes were significantly enhanced in CHC than in control subjects (P < 0.001). A significant positive correlation (r2 = 0.386, P <0.01) was obtained between higher IRF-2 gene expression and increasing level of HCV-RNA. Chronically infected subjects (13%) harboring replicating HCV in PBMCs showed no significant differences in gene expressions than the subjects without HCV in PBMCs. Conclusion: Our findings indicate that HCV modulates host immunity by inducing IRF-2 gene to counteract IRF-1-mediated IFN-α gene expression. Since the IRF-2 gene is known to encode oncogenic protein, the role of IRF-2 in CHC patients developing hepatocellular carcinoma warrants further studies. © 2012 INASL.


PubMed | Asian Institute of Gastroenterology and Asian Health Care Foundation
Type: Journal Article | Journal: Journal of clinical and experimental hepatology | Year: 2015

The interferon regulatory factors (IRFs) are a family of transcription factors known to be involved in the modulation of cellular responses to interferons (IFNs) and viral infection. While IRF-1 acts as a positive regulator, IRF-2 is known to repress IFN-mediated gene expression. The increase in the IRF-1/IRF-2 ratio is considered as an important event in the transcriptional activation of IFN- gene toward development of the cellular antiviral response.This study was performed to assess the expression of IRF mRNAs along with the expression level of IFN-, its receptor (IFNAR-1), and the signal transduction factor (STAT-1) in treatment naive hepatitis C virus (HCV)-infected subjects.Thirty-five chronically infected (CHC) patients and 39 voluntary blood donors as controls were included in the study. Quantification of HCV-RNA (ribonucleic acid) and genotyping were done by real-time polymerase chain reaction (PCR) and hybridization assays, respectively, using patients serum/plasma. In both controls and patients, the serum level of IFN- and IFN- was measured by flow cytometry. Target gene expressions were studied by retro-transcription of respective mRNAs extracted from peripheral blood mononuclear cells (PBMCs) followed by PCR amplification and densitometry. Minus-strand HCV-RNA as a marker of viral replication in PBMCs was detected by an inhouse PCR assay.Both IRF-1 and IRF-2 genes were significantly enhanced in CHC than in control subjects (P < 0.001). A significant positive correlation (r (2) = 0.386, P <0.01) was obtained between higher IRF-2 gene expression and increasing level of HCV-RNA. Chronically infected subjects (13%) harboring replicating HCV in PBMCs showed no significant differences in gene expressions than the subjects without HCV in PBMCs.Our findings indicate that HCV modulates host immunity by inducing IRF-2 gene to counteract IRF-1-mediated IFN- gene expression. Since the IRF-2 gene is known to encode oncogenic protein, the role of IRF-2 in CHC patients developing hepatocellular carcinoma warrants further studies.


PubMed | Asian Institute of Gastroenterology and Asian Health Care Foundation
Type: | Journal: Hepatic medicine : evidence and research | Year: 2013

The chronicity of hepatitis B virus (HBV) infection is attributed to inappropriate functioning of cell-mediated immunity. Besides the importance of measuring serum HBV DNA and HBV surface antigen (HBsAg) as markers of viral replication and exposure, respectively, studies regarding their influence on immune cell status in chronic HBV infection are still scarce. Because such studies of chronic HBV patients have not been reported for India, we attempted to evaluate the relationship between serum concentrations of HBsAg, HBV DNA, and percentage of immune cells in peripheral blood of Indian subjects with chronic HBV infection.Thirty-one HbsAg-positive subjects were evaluated for serum HBe antigen (HBeAg), anti-HBe, and alanine transferase status by standard enzyme-linked immunosorbent assay (ELISA) and biochemical procedures. Serum HBV DNA level was determined by real-time TaqMan polymerase chain reaction assay. Serum HBsAg level was measured by a third-generation sandwich ELISA kit. Peripheral immune cell profiling was done by multifluorometric flow cytometry analysis, for which 21 healthy subjects were included as controls.The majority (93.5%) of the study subjects were HBeAg-negative and anti-HBeAg-positive. Mean viral load, HBsAg, and alanine transferase levels were 4.20 1.96 log copies/mL, 5.98 4.62 log IU/mL, and 74.5 110 IU/mL, respectively. In comparison with controls, total T cell and cytotoxic T cell populations were significantly (P < 0.05) reduced in HBV-infected subjects, while the status of B cells, natural killer cells, T helper cells, and ratio of T helper to cytotoxic cells remained unaltered.Suppression of the peripheral cytotoxic T cell population in chronic HBeAg-negative chronic HBV infection is influenced by increased viral load. Serum HBsAg concentration appeared independent of serum HBV DNA level and immune cell status. Nonelevation of natural killer cell and T helper cell numbers in subjects harboring lower to moderate HBV loads is further indicative of noninduction of innate as well as a coordinated adaptive immune response favoring chronicity of the disease.


Sathiaraj E.,Asian Health Care Foundation
Tropical gastroenterology : official journal of the Digestive Diseases Foundation | Year: 2010

Malnutrition is implicated as an etiological factor in tropical pancreatitis (TP). The aim of the present study was to elucidate whether malnutrition is the cause or the result of TP. Consecutive recently diagnosed patients with TP were evaluated for their nutritional status and dietary patterns before and after the onset of TP. The nutritional status of patients before the onset of TP was compared with that of healthy controls to demonstrate the role of malnutrition as an etiological factor for TP. Of 256 consecutive patients with chronic pancreatitis, 89 were diagnosed as TP patients with disease duration of less than 1 year (mean age 32.14 +/- 14 years; 60% males) and comprised the study group. The nutritional status before the onset of TP was comparable with that of controls (n = 101) with 15% of patients and 12% of the controls being malnourished (BMI < 18.5 kg/m2). However, after the onset of TP, 52% (n = 46) of patients lost weight and the percentage of malnourished patients increased from 15% to 38% (p = < 0.001) indicating that there was significant weight loss after the disease onset. When the causes of weight loss were evaluated, it was found that low calorie intake significantly contributed to weight loss (p = 0.001). Malnutrition is not an etiological factor of TP and weight loss occurred as a result of low calorie intake after the onset of TP.


PubMed | Asian Health Care Foundation
Type: Journal Article | Journal: Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology | Year: 2010

The role of Mycobacterium avium ss paratuberculosis (MAP) in the etiopathology of Crohns disease (CD) remains controversial, because of conflicting reports demonstrating the presence of MAP-specific insertion sequence from intestinal biopsy tissues of patients clinically diagnosed for the disease. The present study was carried out to investigate the presence of MAP DNA in the intestinal tissues of CD patients to ascertain the relevance of MAP in Indian patients with CD.Patients diagnosed as CD at our institute were recruited. Healthy individuals without inflammatory bowel disease served as controls. Mucosal biopsy specimens were collected from ileum and colon in duplicates and subjected to histopathological examination and polymerase chain reaction (PCR) amplification. Total DNA (81 CD patients, 85 healthy individuals) and total RNA (12 CD patients, 12 healthy individuals) isolated from tissue specimens was used for amplification of MAP-specific IS900 by nested PCR.MAP-specific IS900 DNA and RNA could not be detected by nested PCR in the intestinal tissues of any patient with CD.Our results do not support the etiological role of MAP in the pathogenesis of CD in Indian patients.


PubMed | Asian Health Care Foundation
Type: Journal Article | Journal: Tropical gastroenterology : official journal of the Digestive Diseases Foundation | Year: 2011

Malnutrition is implicated as an etiological factor in tropical pancreatitis (TP). The aim of the present study was to elucidate whether malnutrition is the cause or the result of TP.Consecutive recently diagnosed patients with TP were evaluated for their nutritional status and dietary patterns before and after the onset of TP. The nutritional status of patients before the onset of TP was compared with that of healthy controls to demonstrate the role of malnutrition as an etiological factor for TP.Of 256 consecutive patients with chronic pancreatitis, 89 were diagnosed as TP patients with disease duration of less than 1 year (mean age 32.14 +/- 14 years; 60% males) and comprised the study group. The nutritional status before the onset of TP was comparable with that of controls (n = 101) with 15% of patients and 12% of the controls being malnourished (BMI < 18.5 kg/m2). However, after the onset of TP, 52% (n = 46) of patients lost weight and the percentage of malnourished patients increased from 15% to 38% (p = < 0.001) indicating that there was significant weight loss after the disease onset. When the causes of weight loss were evaluated, it was found that low calorie intake significantly contributed to weight loss (p = 0.001).Malnutrition is not an etiological factor of TP and weight loss occurred as a result of low calorie intake after the onset of TP.

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