Satyavati Rana

Orocecal Transit Time and Small Intestinal Bacterial Overgrowth in Type 2 Diabetes Patients from North India

BACKGROUND Diarrhea, constipation, flatulence, and abdominal pain are common complaints in type 2 diabetes patients. Impaired intestinal motility is often followed by small intestinal bacterial overgrowth (SIBO). Therefore, this study was planned to determine the incidence of SIBO and its relation with orocecal transit time (OCTT) in type 2 diabetes patients. SUBJECTS AND METHODS SIBO and OCTT were measured by using noninvasive glucose and lactulose hydrogen breath tests, respectively. For this study, 84 patients with type 2 diabetes mellitus in the age range 30-65 years and 45 age-matched apparently healthy controls were enrolled. RESULTS The glucose hydrogen breath test was suggestive of SIBO in 15.5% of patients with type 2 diabetes mellitus but in one (2.2%) of controls. There was a significant increase (P<0.001) in OCTT in type 2 diabetes patients compared with controls. It was also observed that OCTT in type 2 diabetes patients with SIBO was significantly delayed (P<0.001) compared with type 2 diabetes patients without SIBO. CONCLUSION This study indicates that SIBO in diabetes patients may be due to delayed OCTT.

Is pancreatic exocrine insufficiency in celiac disease related to structural alterations in pancreatic parenchyma

Background Although exocrine pancreatic insufficiency (EPI) has been reported in a number of patients with celiac disease (CD), it is not clear if this is primarily a functional or a structural defect. We studied pancreatic structural abnormalities by endoscopic ultrasound (EUS) in adult CD patients with EPI. Methods Pancreatic exocrine function was prospectively assessed in 36 recently diagnosed CD patients (mean age: 29.8 years) by measuring fecal elastase. Pancreatic structural changes were assessed in CD patients with EPI by EUS and elastography. Exocrine functions were reassessed after 3 months of gluten-free diet. Results Of the 36 CD patients included, 30 (83%) had anemia, 21 (58%) diarrhea, and 7 (19%) hypothyroidism. Ten (28%) patients had EPI with mean elastase levels of 141.6 μg/g of stool, of whom only one had a history of recurrent acute pancreatitis while the rest 9 patients had no history of acute or chronic pancreatitis. Of these 10 patients, 8 (80%) had diarrhea, 8 (80%) anemia, and 2 (20%) hypothyroidism. EUS was done in 8 patients which showed: normal pancreas in 5 (50%), hyperechoic strands in 3 (30%), and hyperechoic foci without shadowing in 2 (20%) patients. None had lobularity or parenchymal calcification. All patients except the patient with recurrent pancreatitis had normal strain ratio. Follow-up fecal elastase was within normal range in 6 of 7 (86%) patients. Conclusion EPI, assessed by fecal elastase levels in adult CD patients, possibly does not relate to structural alterations in the pancreatic parenchyma and may be reversible by following a gluten-free diet.

A relationship between vitamin D, parathyroid hormone, calcium levels and lactose intolerance in type 2 diabetic patients and healthy subjects

BACKGROUND Type 2 diabetes mellitus is chronic metabolic disorder. Common gastrointestinal symptoms in type 2 diabetic patients are flatulence, constipation and/or diarrhea. Reason for these may be lactose intolerance leading to change in vitamin D, Calcium and parathyroid hormone which further regulate bone mineralization. AIM To measure lactose intolerance, vitamin D, calcium and parathyroid hormone in type 2 diabetic patients. MATERIAL AND METHODS 150 type 2 diabetic patients attending Endocrinology Clinic in PGI, Chandigarh and 150 age and sex matched healthy controls were enrolled. Lactose intolerance was measured using non-invasive lactose breath test. 25-hydroxyvitamin D (total) and Parathyroid hormone were measured in plasma using immunoassay. Serum calcium was measured using auto analyzer. T score was recorded from DXA scan for bone mineral density measurement. RESULTS Lactose intolerance was observed significantly higher (p<0.001) diabetic patients (59.3%) as compared to controls (42%). Levels of plasma 25-OH vitamin D (total), parathyroid hormone and serum calcium were significantly lower in patients as compared to controls. Furthermore, levels of plasma 25-OH vitamin D (total), parathyroid hormone and serum calcium were more decreased in lactose intolerant diabetic patients than lactose tolerant patients. Sixty seven percent (67%) of diabetic patients suffered from osteoporosis and 20% of controls. Eighty percent (80%) diabetic patients and 16% controls with osteoporosis suffered from lactose intolerance. CONCLUSION From this study we can conclude that measurement of lactose intolerance using non-invasive lactose breath test is suggested for type 2 diabetic patients along with timely measurement of 25-OH vitamin D (total), calcium and parathyroid hormone levels.

Wheatgrass and Antioxidant Levels in Carbon Tetrachloride-induced Hepatotoxicity in Rats

© 2011, INASL 43 Wheatgrass and Antioxidant Levels in Carbon Tetrachloride-induced Hepatotoxicity in Rats JK Kamboj*, SV Rana*, RP Ola*, DK Dhawan**, K Vahiphei*** Departments of Gastroenterology and ***Pathology, PGIMER, Chandigarh Background: Wheatgrass (Triticum aestivum), rich in various antioxidants, is known to treat a number of conditions including burns, common cold, anemia, cough, fever and eczema, etc. Aim: Therefore, this study was planned to determine the effect of wheatgrass on antioxidant levels and oxidative stress induced by CCl4 in hepatic tissue of rats. Materials and Methods: Eighteen Wistar rats with body weight of 120–150 gms were divided into 3 groups. Group 1—rats in this group were given normal saline injection subcutaneously twice a week for 4 weeks. Group 2—carbon tetrachloride was administered subcutaneously at a dose of 2 mL/Kg body weight twice a week for 4 weeks in this group. Group 3—wheatgrass was administered orally at 80 mg/100 g body weight in drinking water for 4 weeks along with CCl4 injection given subcutaneously twice a week at a dose of 2 mL/Kg body weight wheatgrass dose was started 2 weeks prior to first injection of CCl4. Reduced glutathione (GSH) was measured in liver tissue for antioxidant levels and lipid peroxidation (LPO) for oxidative stress. Results: GSH level was significantly decreased while LPO increased in hepatic tissue of group 2 (CCl4 treated rats) as compared to group 1 (controls). In group 3 (CCl4 + wheatgrass treated rats), GSH level was increased while LPO decreased as compare to group 2. Conclusion: This study shows that wheatgrass treatment decreased the oxidative stress and increased the antioxidant levels in CCl4 induced hepatotoxicity. Conflict of Interest: None Comparative Hepatoprotective Activity of Polygonum Bistorta Extract and Its Active Compound Against Carbon Tetrachloride-Induced Hepatotoxicity in Rats DK Mittal School of Studies in Zoology, Jiwaji University, Gwalior, India Aim: Many herbal preparations have been recommended in alternative system of medicine for the treatment of hepatic disorder. Druginduced hepatotoxicity is still a significant unresolved clinical problem as liver is the most common site of damage. Present findings is based on the protective effect of PB extract and TA against acute and sub chronic APAP and CCl4 intoxication. Methods: Male Sprague Dawley strain rats (150 ± 10 g body weight) were administered a single bolus dose of APAP (2 g/Kg, p.o.) and CCl4 (0.15 mL/Kg, i.p.). Plant extract (Polygonum bistorta) and its active principle (tannic acid) was given at the dose of 100 mg/Kg and 25 mg/Kg, respectively (p.o.) after 24 hours of toxicant administration. Results: The effect of PB, TA and silymarin on AST, ALT, SALP, Blood sugar, Protein, Albumin, Bilirubin, Urea, Creatinine were observed against APAP toxicity. Further, the effects of the PB and TA was confirmed on LPO, GSH, ATPase, SOD, GR, GPx, G6PDH, GST, AH, AND were estimated against CCl4 intoxication. Conclusions: TA produced significant hepatoprotective effect by decreasing the activities of above biochemical indices followed by PB extract. Histopathological and ultrastructural observations and in vitro study by MTT assay supported above findings. Conflict of Interest: None 03_JCEH-Abstract.indd 43 3/18/2011 11:13:05 AM

Effect of Different Doses of Wheatgrass in Prevention of Carbon Tetrachloride Induced Hepatotoxicity in Rats

© 2011, INASL 39 HEPATOTOXICITY Effect of Different Doses of Wheatgrass in Prevention of Carbon Tetrachloride Induced Hepatotoxicity in Rats JK Kamboj*, SV Rana*, DK Dhawan**, K Vahiphei*** Departments of *Gastroenterology and **Pathology, PGIMER, Chandigarh, ***Department of Biophysics, Punjab University, Chandigarh Introduction: Wheatgrass (Triticum aestivum), rich in chlorophyll and various antioxidants, is promoted to treat a number of conditions including common cold, cough, fever, eczema and burns, etc. Aim: To determine the protective effect of different doses of wheatgrass in hepatic tissue of Wistar rats damaged by CCl4. Material and Methods: Wheatgrass was administered orally at different doses of 20 mg, 40 mg, 60 mg and 80 mg/100 g by body weight in drinking water for 4 weeks along with CCl4 injection given subcutaneously at a dose of 2 mL/Kg body weight twice a week. Wheatgrass dose was started 2 weeks prior to first injection of CCl4. Carbon tetrachloride was also administered in control group for 4 weeks and one group was given only wheatgrass at a maximum dose of 80 mg/100 g by body weight/day to check any adverse effect of wheatgrass on liver. The effect to different treatments was studied on serum enzymes like alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in rats at different time intervals of 2 and 4 weeks and the rat liver was analyzed histologically at the end of study. Results: Serum ALP, AST, ALT activity was significantly increased when estimated at the intervals of 2 and 4 weeks as compared to baseline values in CCl4 group. Interestingly, supplementation of wheatgrass to rats helped in regulating the altered activities of ALP, AST and ALT in serum at 4 weeks. However, wheatgrass treatment to rats did not indicate any significant change in the activities of all abovementioned liver enzymes at the interval of 2 weeks. Histologically, there was necrosis, portal triaditis and lobular inflammation in CCl4 group. Maximum protection was observed biochemically and histologically with wheatgrass dose of 80 mg/100 g body weight Conclusion: Carbon tetrachloride caused liver toxicity and wheatgrass treatment prevented the increase in liver enzymes and histology depending on the dose of wheatgrass. Conflict of Interest: None Relation of NAT2, CYP2E1 and GST Gene Polymorphisms with Anti-tuberculosis Treatment Induced Hepatotoxicity in North Indian Patients SV Rana*, SK Sharma**, RP Ola*, SK Arora***, SK Sinha*, JK Kamboj*, K Singh* Department of Superspecialty of *Gastroenterology, **Biophysics and ***Immunopathology, PGIMER, Chandigarh Background: Antituberculosis treatment (ATT) induced hepatitis is attributed to isoniazid (INH). Isoniazid is metabolized by hepatic N-acetyltransferase-2 (NAT-2) and cytochrome P-450 2E1 (CYP2E1) to form hepatotoxins. Glutathione-S-transferase (GST) plays an important role in prevention of ATT-induced hepatotoxicity. Deficiency of GST activity because of homozygous null mutations at GSTM1 and GSTT1 loci may modulate susceptibility to ATT-induced hepatotoxicity. Aim: To evaluate whether polymorphisms of NAT-2, GST and CYP2E1 gene were associated with ATT-induced hepatotoxicity in North Indian patients. Methods: In this prospective study, 250 patients treated with ATT for tuberculosis were genotyped for polymorphisms of NAT-2, GST and CYP2E1. NAT-2, CYP2E1 and GST genotypes were determined by PCR and multiplex PCR with restriction fragment length polymorphism analysis (RFLP). Results: Two hundred fifty tuberculosis (TB) patients on ATT (153 males) were studied. Out of 250 patients, 32 (12.8%) developed hepatotoxicity. NAT-2 gene allele 4/4 was present in 18/32 (56.2%) of hepatotoxicity patients while in 76/218 (34.8%) in non-hepatotoxicity patients. Allele 4/6, 5/5, 6/6 and 7/7 were not present in hepatotoxicity patients while these were present in non-hepatotoxicity patients. In GST, out of 32 hepatotoxicity patients, 5 (15.6%) showed GSTM1, 9 out of 32 (28.0%) GSTT1 and 18 out of 32 (56.3%) GSTT1/ GSTM1/s-globulin. While 69 out of 218 (31.7%) showed GSTM1, 34 (15.6%) GSTT1, and 115 (52.7%) GSTT1/GSTM1/s-globulin in nonhepatotoxicity patients. For CYP2E1 c1/c1, c2/c2 and c1/c2 genotypes in INH-NH patients were 61.1%, 16.6% and 22.2% respectively while in INH-H patients 50.0%, 25.0% and 25.0% respectively. Conclusion: This study suggests that NAT-2 gene allele 4/4 was significantly higher in INH-induced hepatotoxicity as compared to nonhepatotoxicity group. There was no significant difference in CYP2E1 and GST genotypes between both the groups. Conflict of Interest: None 03_JCEH-Abstract.indd 39 3/18/2011 11:13:05 AM

Type 1 diabetes mellitus: Complex interplay of oxidative stress, cytokines, gastrointestinal motility and small intestinal bacterial overgrowth

Oxidative stress is risk factor in progression of diabetes. It can increase cytokine production via several different mechanisms. Inflammation can affect gut neural apparatus that may lead to dysmotility which may exaggerate occurrence of bacterial overgrowth in intestine. Thus, a study was planned to understand the complex interplay of oxidative stress, inflammatory cytokines, gut motility and small intestinal bacterial overgrowth in type 1 diabetes mellitus (T1DM) patients.

Prevalence of Gastrointestinal Cancers in India

Cancer is one of the leading causes of deaths worldwide. The absolute number of cancer deaths in India is projected to increase because of population growth, urbanization, industrialization, lifestyle changes and increasing life expectancy. The digestive tract is a major site of cancer in humans. There are great differences in incidence among the component sites from the esophagus to the anus. The most prevalent of these is colorectal cancer in the Western world and gastric cancer in the Eastern world. About 630,000 deaths occur due to colorectal cancer worldwide, accounting for 8 % of all cancer deaths. Gastric cancer accounts for approximately 800,000 deaths each year worldwide. In India, esophageal cancer is highest in northeastern region of India than other parts of the world for both males and females. Gastric cancer is also prominent problem in northeastern and southern states of the Indian subcontinent. Comparison of the data from the various urban population-based cancer registries in India indicates that gallbladder cancer is more common in northern India whereas rectal cancer among men is one among the ten leading sites of cancer in the southern India. Higher rates of liver cancer are seen in the male urban populations of western and northern India. However, the prevalence of pancreatic cancer is low in India and Squamous cell carcinoma of the anal canal is an underrecognized malignancy in India.

Combination of adenosine-deaminase and nucleic acid amplification assays for diagnosing tuberculous pleural effusion.

We read with interest the paper by Keng et al., who evaluated pleural adenosine-deaminase (ADA), ADA2, interferon-gamma (IFN-g), and interferon-gamma release assays (IGRA) by enzyme-linked immuno-spot (T-SPOT.TB) assay as diagnostic tools for tuberculous pleural effusion (TPE) and concluded that pleural ADA, ADA2, and IFN-g assays, but not T-SPOT.TB assay, have good diagnostic performances for TB pleurisy. The recent policy statement of the World Health Organization (WHO) has also concluded that serological tests provide inconsistent and imprecise estimates of sensitivity and specificity and should not be used for the diagnosis of pulmonary and extra-pulmonary TB. However, nucleic acid amplification tests (NAAT) have been endorsed by WHO and may play important role in rapid detection of TB. NAATs are now used for the direct detection of Mycobacterium tuberculosis complex in respiratory specimens, mainly in developed countries, because of their high sensitivity and specificity, especially in smear-positive respiratory specimens. In this context, we evaluated ADA, along with NAATs such as Loop-mediated isothermal amplification (LAMP) assay based on the amplification of IS6110 gene of M. tuberculosis complex (MTC) and IS6110 PCR, and conventional techniques (microscopy and culture) for the diagnosis of TPE in 106 patients with pleural effusion. The study was approved by the Institute Ethics Committee and written informed consent was obtained from all patients. The patients were categorized in following groups: Group A (n Z 31) included confirmed TPE patients which were smear or culture positive for M. tuberculosis from pleural fluid and/or with histology showing a caseating granuloma; Group B (n Z 61) included probable TPE patients with signs and symptoms of TB (cough, fever, chest pain, and pleural exudate) or histology showing a chronic inflammation without caseating granuloma, with response to treatment, or pleural effusion patients with a sputum culture positive for M. tuberculosis; and Group C (n Z 14) included pleural effusion patients with an

Lactose Intolerance in Liver Cirrhosis Patients

© 2011, INASL 20 population. Mean age of death being 47.25. Total years lived with disability 311. Considering disability weight of alcoholic cirrhosis as 0.33 and average life expectancy of male Keralites as 72 DALY calculated is 20.95. Conclusion: Alcoholic cirrhosis imparts a huge economic burden on family and society with loss of quality of life and early deaths. Conflict of Interest: None Lactose Intolerance in Liver Cirrhosis Patients SV Rana*, S Sharma*, RK Dhiman**, YK Chawla**, K Singh* Departments of *Gastroenterology and **Hepatology, PGIMER, Chandigarh Background: Malnutrition, characterized by protein and energy deficiency, is considered the most prevalent complication of liver disease. Studies of small bowel mucosa in cirrhosis report a diverse spectrum of histological abnormalities. These include increased mucosal edema, decreased villus to crypt ratio, villus atrophy and decreased total absorptive surface. This may result in decreased lactase activity causing lactose intolerance. Aim: Therefore, this study was planned to evaluate lactose intolerance in patients with liver cirrhosis. Materials and Methods: Lactose intolerance was estimated by using non-invasive lactose hydrogen breath test in 59 patients of liver cirrhosis and 63 ageand sex-matched apparently healthy controls. For lactose hydrogen breath test 25 g lactose dissolved in 250 mL water was given orally to the subjects after taking fasting breath H2 concentration. End expiratory breath was collected every 30 minutes up to 4 hours. H2 concentration was measured by using SC Microlyzer (Quintron, USA). Rise ≥ 20 ppm over baseline value in H2 concentration in two consecutive readings was considered as lactose intolerance. Results: In liver cirrhotic patient, 46 were males and 13 females, while in controls 49 males and 14 females. Out of 59 patients, 27 had viral cirrhosis and 32 had alcoholic cirrhosis. Mean ± SD of age in patients was 45.6 ± 16.4 years and in controls 47.8 ± 15.3 years. Out of 59 patients of liver cirrhosis, 41 (69.5%) were lactose intolerant while in controls 28 (44.4%) out of 63 subjects. The difference was statistically significant (p < 0.01). Lactose intolerance was present in 19 (70.4%) out of 27 viral cirrhosis patients while in 22 (68.75%) out of 32 alcoholic cirrhosis patients. Lactose intolerance was significantly higher in both the groups as compared to control group. Conclusion: This study indicates that lactose intolerance was significantly higher in cirrhotic patients. Conflict of Interest: None Impact of Diabetes Mellitus on the Clinical Outcome of Cirrhosis TM Ramachandran, AR Rajneesh, T Varghese Additional Professor, DM Trainee and Presenting Author, Professor, Department of Gastroenterology, Government Medical College, Calicut, Kerala Objectives: To assess the impact of diabetes mellitus on the natural history, complication rate, hospital admission rate and mortality of cirrhotic patients. Methods: Cirrhotic patients admitted at a tertiary care institution during the period of July 2009 to January 2011 with and without diabetes mellitus were analyzed in a prospective comparative study. The clinical characteristics, various complication rates and hospital admission rates in patients who died as well as survived were analyzed. Pregnant women, Stage IV and V chronic kidney disease, hepatoma and other secondary causes of diabetes were excluded from the study. Results: Of the 199 cirrhotic patients, 106 (53.3%) were diabetic and 93 (46.7%) were non-diabetic. Average age was 57.14 (diabetic) and 53.7 (non-diabetic) years. Mean CTP score was 10 in both groups. Average duration of cirrhosis was 19 months in both groups. Diabetics had a higher prevalence of cryptogenic etiology (p value 0.013) and family history of diabetes (p 0.001). Presentation as acute on chronic liver failure was more in non-diabetic group (p 0.035). Mean albumin value was higher in diabetics (2.72 vs. 2.5; p value 0.017). Number of prior hospital admissions (mean 2.93 vs. 2.17) and number of decompensation episodes (mean 2.96 vs. 2.16) were higher in the diabetic group (p value 0.023). Prevalence of gallstones were common in diabetics (26.41%) compared to non-diabetics (5.37%) (p value 0.001). Frequency of urinary tract infection was higher in the diabetic group (37.7%) vs. non-diabetics (5.3%) (p value 0.001). Frequency of spontaneous bacterial peritonitis was 19.8% (diabetic) and 23.63% (non-diabetics) (p value NS). Frequencies of other infections (pneumonia, tuberculosis, cellulitis, abscess) were also higher in diabetics than non-diabetics. Conclusion: Age, cryptogenic etiology, number of decompensation episodes, number of hospital admissions, serum albumin and gallstones were more in the diabetic group. Urinary tract infection was more common among diabetics whereas spontaneous bacterial peritonitis was present in both groups. Conflict of Interest: None 03_JCEH-Abstract.indd 20 3/18/2011 11:13:04 AM