Publications by authors named "Satyavati Rana"

19 Publications

  • Page 1 of 1

Nuclear receptor subfamily 5 group A member 2 (NR5A2): role in health and diseases.

Mol Biol Rep 2021 Oct 13. Epub 2021 Oct 13.

Department of Biochemistry, All India Institute of Medical Sciences (AIIMS) Rishikesh, Rishikesh, Uttarakhand, India.

Nuclear receptors are the regulatory molecules that mediate cellular signals as they interact with specific DNA sequences. NR5A2 is a member of NR5A subfamily having four members (Nr5a1-Nr5a4). NR5A2 shows involvement in diverse biological processes like reverse cholesterol transport, embryonic stem cell pluripotency, steroidogenesis, development and differentiation of embryo, and adult homeostasis. NR5A2 haploinsufficiency has been seen associated with chronic pancreatitis, pancreatic and gastrointestinal cancer. There is a close relationship between the progression of pancreatic cancer from chronic pancreatitis, NR5A2 serving a common link. NR5A2 activity is regulated by intracellular phospholipids, transcriptional coregulators and post-translational modifications. The specific ligand of NR5A2 is unknown hence called an orphan receptor, but specific phospholipids such as dilauroyl phosphatidylcholine and diundecanoyl phosphatidylcholine act as a ligand and they are established drug targets in various diseases. This review will focus on the NR5A2 structure, regulation of its activity, and role in biological processes and diseases. In future, need more emphasis on discovering small molecule agonists and antagonist, which act as a drug target for therapeutic applications.
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http://dx.doi.org/10.1007/s11033-021-06784-1DOI Listing
October 2021

COVID-19 and Gut Microbiota: A Potential Connection.

Indian J Clin Biochem 2021 Jan 21:1-12. Epub 2021 Jan 21.

Department of Biochemistry, AIIMS Rishikesh, Uttarakhand, 249203 India.

Currently, world is facing a global outbreak causing a pandemic threat known as COVID-19. This infectious disease is triggered by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Gut microbiota harbours multi species community with a strong impact on host immune homeostasis. However, our knowledge about this gut microbiota and its symbiotic relationship with immune activation in association with SARS-CoV-2 is limited. Unbalanced bacterial flora with too many opportunistic infections can shift immune system towards a cascade of inflammatory responses leading to multi organ damage. This review will highlight immune-regulation via various mechanisms in SARS-CoV-2 infection. Diet has an unbelievable influence on gut microbiome that allows a new state of homeostasis to be reached through timing, frequency and duration of intake. This review article focuses on gut, lung microbiota and immunomodulation with specific attention on immune activation by gut microbiota.
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http://dx.doi.org/10.1007/s12291-020-00948-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818076PMC
January 2021

Can serum resistin predict severity of acute pancreatitis?

Biomarkers 2021 Feb 8;26(1):31-37. Epub 2020 Dec 8.

Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Objective: Acute pancreatitis (AP) is a common disorder with high mortality in severe cases. Several markers have been studied to predict development of severe AP (SAP) including serum resistin with conflicting results. This study aimed at assessing the role of baseline serum resistin levels in predicting SAP.

Methods: This prospective study collected data from 130 AP patients from July 2017 to Nov 2018. Parameters measured included demographic profile, serum resistin at admission, severity scores, hospital stay, surgery, and mortality. Patients were divided into two groups, severe and non-severe AP. The two groups were compared for baseline characteristics, serum resistin levels, hospital stay, surgery and mortality.

Results: Among 130 patients, 53 patients had SAP. SAP patients had higher BMI, baseline CRP, APACHE II and CTSI scores (-value 0.045, <0.001, <0.001 and 0.001, respectively). Both groups had comparable serum resistin levels. Serum resistin levels were also not different for obese and non-obese patients (-value = 0.62). On multivariate analysis, BMI and high APACHE II score and CRP levels were found to independently predict SAP.

Conclusion: We found that serum resistin is not a useful marker for predicting the severity of AP and does not correlate with increasing body weight.
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http://dx.doi.org/10.1080/1354750X.2020.1841295DOI Listing
February 2021

High potency multistrain probiotic improves liver histology in non-alcoholic fatty liver disease (NAFLD): a randomised, double-blind, proof of concept study.

BMJ Open Gastroenterol 2019 7;6(1):e000315. Epub 2019 Aug 7.

Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Objective: Pharmacological treatment of non-alcoholic fatty liver disease (NAFLD) is still evolving. Probiotics could be a promising treatment option, but their effectiveness needs to be established. The present study aimed to evaluate the efficacy of a high potency multistrain probiotic in adult patients with NAFLD.

Methods: Thirty-nine liver biopsy-proven patients with NAFLD were randomised in a double-blind fashion to either lifestyle modifications plus an oral multistrain probiotic (675 billion bacteria daily, n=19) or identical placebo (n=20) for 1 year. Lifestyle modifications included regular exercise for all and control of overweight/obesity (with additional dietary restrictions), hypertension and hyperlipidaemia in those with these risk factors. Primary objective of the study was the histological improvement in NAFLD activity score (NAS) and its components and secondary objectives were improvement in alanine transaminase (ALT) and cytokine profile.

Results: Thirty (76.9%) out of 39 patients with NAFLD completed the study with 1 year of follow-up. A repeat liver biopsy at 1 year could be done in 10 patients (52.6%) in probiotic group and five patients (25%) in placebo group. In comparison to baseline, hepatocyte ballooning (p=0.036), lobular inflammation (p=0.003) and NAS score (p=0.007) improved significantly at 1 year in the probiotic group. When compared with placebo, the NAS score improved significantly in the probiotic group (p=0.004), along with improvements in hepatocyte ballooning (p=0.05) and hepatic fibrosis (p=0.018). A significant improvement in levels of ALT (p=0.046), leptin (p=0.006), tumour necrosis factor-α (p=0.016) and endotoxins (p=0.017) was observed in probiotic group in comparison to placebo at 1 year. No significant adverse events were reported in the study.

Conclusion: Patients with NAFLD managed with lifestyle modifications and multistrain probiotic showed significant improvement in liver histology, ALT and cytokines.

Trial Registration Number: The clinical trial is registered with CLINICAL TRIAL REGISTRYINDIA (CTRI); http://ctri.nic.in, No. CTRI/2008/091/000074.
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http://dx.doi.org/10.1136/bmjgast-2019-000315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6688701PMC
August 2019

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

Eur J Clin Invest 2018 Nov 19;48(11):e13021. Epub 2018 Sep 19.

Department of Super Specialty of Gastroenterology, Post Graduate Institute of Medical Education & Research, Chandigarh, India.

Background: 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.

Materials And Methods: Seventy-five T1DM patients and 75 healthy controls were enrolled. Small intestinal bacterial overgrowth (SIBO) and orocecal transit time (OCTT) were measured using noninvasive glucose and lactulose hydrogen breath tests, respectively. Plasma levels of interleukin-6 (IL-6), tissue necrosis factor-alfa (TNF-α) and interleukin-10 (IL-10) were measured in all subjects by ELISA. Oxidative stress and anti-oxidant parameters were measured by standard methods.

Results: Out of 75 T1DM patients, 36 were males with Mean ± SD age 22.3 ± 5.2 years, IL-6, TNF-α and IL-10 were significantly higher (P < 0.05) in T1DM patients as compared to controls. Lipid peroxidation (LPO) was significantly increased (P < 0.001), while reduced glutathione (GSH) significantly decreased (P < 0.01), whereas superoxide dismutase (SOD) and catalase significantly higher (P < 0.05) in T1DM patients as compared to controls. Positive correlation was observed between glycated haemoglobin (HbA1c) levels with LPO and negative correlation with GSH. Further, there was positive correlation between LPO and inflammatory cytokines (IL-6 & IL-10). OCTT was delayed and SIBO significantly higher in patients as compared to controls. On comparison of T1DM based on duration of disease, effect of all parameters was more pronounced in disease duration ≥5 years.

Conclusion: This study indicates that there is association between hyperglycaemia, oxidative stress (LPO), anti-oxidants (GSH, SOD and catalase), inflammatory cytokines, gut motility (OCTT), and small intestinal overgrowth in type 1 diabetes mellitus patients. This association is intensified as duration of disease increases.
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http://dx.doi.org/10.1111/eci.13021DOI Listing
November 2018

Gastrointestinal Dysmotility and Infections in Systemic Sclerosis- An Indian Scenario.

Curr Rheumatol Rev 2018 ;14(2):172-176

Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.

Introduction: Systemic Sclerosis is known to involve the gastrointestinal system and can lead to multitude of problems predominantly affecting the GI motility.

Methods: It was a prospective, observational, single centre study of fifty consecutive patients with SSc who presented to rheumatology clinic. Gut score was assessed using UCLA SCTC GIT 2.0 questionnaire. 35 patients underwent esophago- gastro duodenoscopy(UGIE), 31 underwent esophageal manometry, 37 underwent lactulose breath test to assess orocaecal transit time (OCTT) and glucose breath test for detecting small intestinal bacterial overgrowth (SIBO) and 36 underwent gastric emptying scintigraphy to measure gastric emptying time.

Results: GI involvement was seen in 98% of patients, with most common symptom being regurgitation (78%). Mean T score of the GUT score was 0.60±0.27. In UGIE, esophagitis was seen in 30, of which 3 had candidiasis and 1 had HSV esophagitis. Hiatus hernia was noted in 10 patients. Mean lower esophageal sphincter pressure was 16.1± 12.7 mmHg with hypotensive sphincture in twelve patients. Esophageal peristaltic abnormalities were observed in 28(90%) patients. Gastric emptying was delayed in10/36 patients. OCTT was prolonged in 23/ 37 patients whereas SIBO was noted in 7/37.

Conclusion: GI involvement is common in SSc with esophagus being most commonly affected. Motility abnormalities make them prone for super added infections especially infectious esophagitis and SIBO and should be investigated for early detection and treatment.
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http://dx.doi.org/10.2174/1573397113666170425145405DOI Listing
October 2018

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

Clin Chim Acta 2016 Nov 16;462:174-177. Epub 2016 Sep 16.

Department of Gastroenterology, Post Graduate Institute of Medical Research and Education, Chandigarh 160012, India. Electronic address:

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.
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http://dx.doi.org/10.1016/j.cca.2016.09.009DOI Listing
November 2016

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

Ann Gastroenterol 2016 Jul-Sep;29(3):363-6. Epub 2016 May 11.

Department of Gastroenterology (Surinder S. Rana, Arvind Dambalkar, Puneet Chhabra, Ravi Sharma, Vishal Sharma, Satyavati Rana, Deepak K. Bhasin), Chandigarh, India.

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.
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http://dx.doi.org/10.20524/aog.2016.0042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4923824PMC
July 2016

No preanalytical errors in laboratory testing: a beneficial aspect for patients.

Authors:
Satyavati V Rana

Indian J Clin Biochem 2012 Oct;27(4):319-21

Department of Super Specialty Gastroenterology, Post Graduate Institute of Medical Education & Research, Sector 12, Chandigarh, India.

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http://dx.doi.org/10.1007/s12291-012-0271-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3477456PMC
October 2012

Orocecal transit time and small intestinal bacterial overgrowth in type 2 diabetes patients from North India.

Diabetes Technol Ther 2011 Nov 19;13(11):1115-20. Epub 2011 Jul 19.

Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, 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.
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http://dx.doi.org/10.1089/dia.2011.0078DOI Listing
November 2011

Evaluation of CA 242 as a tumor marker in gallbladder cancer.

J Gastrointest Cancer 2012 Jun;43(2):267-71

Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.

Purpose: Gallbladder and pancreas share common embryological origin, and malignancies of these organs may share common tumor antigens. CA 242 is a tumor marker for pancreatic cancer, but has not been studied in gallbladder cancer (GBC). We measured serum CA 242 levels in patients with GBC and compared it with those in patients with gallstones (GS) and healthy volunteers.

Methods: We enrolled consecutive patients with GBC (cases), GS (disease controls), and healthy volunteers (healthy controls). Serum CA 242, CEA, and CA 19-9 levels were measured using ELISA. Receiver operator curve was plotted for all the three markers.

Results: We studied 117 patients with GBC, 58 with GS, and 10 healthy volunteers. Among patients with GBC, 81 (69%) also had GB calculi. Patients with GBC more often had elevated CA 242 levels (64%) compared to those with GS (17%; p < 0.001) and healthy controls (0%; p < 0.001). The median levels of CA 242 was higher in the GBC group (59 [199] U/ml) compared to the GS group (10 [13] U/ml; p < 0.001) and the control group (3 [14.5] U/ml; p < 0.001). The sensitivity, specificity, positive predictive value (PPV), and negative predictive values of CA 242 for diagnosis of GBC were 64%, 83%, 88%, and 53%, respectively. At a cutoff of 45 U/ml, the specificity and PPV increased to 100%. CA 242 had higher AOC (0.759) compared to CEA (0.528) and CA 19-9 (0.430).

Conclusions: CA 242 is a promising tumor marker for GBC and performs better than CEA and CA 19-9.
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http://dx.doi.org/10.1007/s12029-011-9288-7DOI Listing
June 2012

Role of small intestinal bacterial overgrowth and delayed gastrointestinal transit time in cirrhotic patients with minimal hepatic encephalopathy.

J Hepatol 2010 Nov 17;53(5):849-55. Epub 2010 Jul 17.

Department of Internal Medicine, Postgraduate Institute of Medical Education & Research, Chandigarh 160012, India.

Background & Aims: Minimal hepatic encephalopathy (MHE) is the mildest form in the spectrum of hepatic encephalopathy. This cross-sectional study was carried out to elucidate the role of bacterial overgrowth of the small intestine and delayed intestinal transit among patients with MHE.

Methods: Two-hundred-thirty patients with cirrhosis were screened; 102 patients (44.4%) who met the eligibility criteria were included in the study. MHE was diagnosed when the psychometric hepatic encephalopathy score was ≤-5. All patients underwent a glucose breath test for small intestinal bacterial overgrowth (SIBO) and lactulose breath test for oro-cecal transit time (OCTT).

Results: Fifty-seven (55.9%) patients with cirrhosis had MHE. Among these patients with MHE, 22 (38.6%) had SIBO, while 4 (8.9%) without MHE had SIBO (p = 0.001). The prevalence of SIBO was higher in patients with CTP classes B and C (69.2%) compared to those in CTP class A (30.8%); p = 0.054. OCTT was significantly prolonged in patients who had SIBO than in those who did not have SIBO (p<0.0001). Univariate analysis demonstrated that increased age, female gender, low educational status, low albumin, presence of SIBO, and prolonged OCTT were associated with the presence of MHE. Multivariate analysis demonstrated SIBO as the only factor associated with MHE.

Conclusions: Our study conclusively demonstrates high prevalence of SIBO in patients with cirrhosis with MHE. This study gives the rationale of treatment directed against SIBO and gut dysmotility, which may include non-absorbable antibiotics such as rifaximin, probiotics, and prokinetics.
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http://dx.doi.org/10.1016/j.jhep.2010.05.017DOI Listing
November 2010

Low folate transport across intestinal basolateral surface is associated with down-regulation of reduced folate carrier in in vivo model of folate malabsorption.

IUBMB Life 2009 Mar;61(3):236-43

Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

The process of folate transport regulation across biological membranes is of considerable interest because of its ultimate role in providing one-carbon moieties for key cellular metabolic reactions and exogenous requirement of the vitamin in mammals. Although, intestinal folate malabsorption is established phenomena in alcoholism; however, there is no knowledge regarding the mechanism of folate exit across intestinal basolateral membrane (BLM) to circulation during alcohol associated malabsorption. In the present study, male Wistar rats were fed 1 g/kg body weight/day ethanol (20% solution) orally for 3 months and regulatory characteristics of folate transport at BLM surface were evaluated. The folate transport was found to be carrier mediated, saturable, with pH optima at 7.0, besides exhibiting Na(+) independence. The chronic alcohol ingestion resulted in alteration of transport kinetics, shifting the process to K(+) dependent one besides affecting the status of S--S linkage of the transport system. Importantly, chronic ethanol ingestion reduced the folate exit across the BLM by decreasing the affinity of transporter (high K(m)) for substrate and by decreasing the number of transporter molecules (low V(max)) on the surface. The decreased basolateral transport activity was associated with down-regulation of the reduced folate carrier (RFC) which resulted in decreased RFC protein levels in BLM in rat model of alcoholism. The study suggests that during alcohol ingestion, RFC mediated deregulated folate transport across BLM also attributes to folate malabsorption.
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http://dx.doi.org/10.1002/iub.153DOI Listing
March 2009

Effect of different doses of carotenoids in isoniazid-rifampicin induced hepatotoxicity in rats.

Trop Gastroenterol 2008 Jul-Sep;29(3):153-9

Department of Gastroenterology & Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Aim: Isoniazid (INH) and Rifampicin (RIF) are hepatotoxic drugs. Oxidative stress has been reported as one of the mechanisms of INH+RIF induced hepatotoxicity.

Methods: Intragastric administration of INH and RIF (50 mg/kg body weight/day each) for 28 days in Wistar rats is hepatotoxic, indicated by raised transaminases and histology. Carotenoids have antioxidant properties. Therefore, different doses of carotenoids (2.5, 5, 10 and 20 mg/kg body weight/day) were administered to study the hepatoprotective effect against INH+RIF.

Results: The higher doses of carotenoids i.e.10 and 20 mg/kg body weight/day showed partial hepatoprotection indicated by return to normal of liver transaminase level and of liver histology in 33.3% of rats. There was no further protective effect seen by increasing the dose of carotenoids from 10 to 20 mg/kg body weight/day. Lower doses of carotenoids, i.e., 2.5 and 5 mg/kg body weight/day were not effective.

Conclusion: Thus, a minimum dose with maximum hepatoprotection (10 mg/kg b.wt/ day) was selected as the optimum dose in the present study. The hepatoprotective nature of carotenoids in INH+RIF treated rats may be attributed to their antioxidative property.
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February 2009

Lactose intolerance in prostate cancer patients: incidence and associated factors.

Scand J Gastroenterol 2008 Mar;43(3):270-6

Department of Urology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Objective: Osteoporosis is common in prostate cancer (CaP) patients both before and after institution of androgen deprivation therapy and is associated with significant morbidity. Lactose intolerance (LI) can affect bone mass but has not been studied in this group of patients. The objective of this study was to compare the incidence of LI in CaP patients with that in the general population and to identify factors affecting lactose intolerance in CaP patients.

Material And Methods: Fifty-five men with CaP planned for bilateral orchidectomy were enrolled in the study and their baseline characteristics including age, weight, height, body mass index (BMI), prostate-specific antigen, serum calcium profile, lactose tolerance status, physical activity, alcohol intake and smoking, bone mineral density and calcium intake were registered. The data on lactose tolerance in these patients were compared with those of 81 age-matched controls (data taken from the available database).

Results: The incidence of LI in CaP patients was significantly less than that in the control group (36.2% and 58.3%, respectively, p = 0.027). A significantly greater number of CaP patients in the lactose-tolerant group had a calcium intake of >1500 mg/day (p = 0.03) and that of milk >500 ml/day (p = 0.05) than those in the intolerant group. Age >70 years, BMI <25 kg/m2, height >163 cm, lower physical activity and co-abuse of alcohol and smoking significantly correlated with the presence of LI (p < or = 0.05). Patients with serum calcium <9 mg/dl had higher fasting breath H2 levels and a higher proportion had a BMI >25 kg/m2 and weight >65 kg.

Conclusions: The incidence of LI in CaP patients is less than that in the general population despite a higher incidence of osteoporosis, indicating a complex etiology of CaP-related osteoporosis. Certain physical characteristics and personal habits are important in determining lactose-tolerant status.
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http://dx.doi.org/10.1080/00365520701676831DOI Listing
March 2008

Down-regulation of reduced folate carrier may result in folate malabsorption across intestinal brush border membrane during experimental alcoholism.

FEBS J 2007 Dec 12;274(24):6317-28. Epub 2007 Nov 12.

Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Folate plays a critical role in maintaining normal metabolic, energy, differentiation and growth status of all mammalian cells. The intestinal folate uptake is tightly and diversely regulated, and disturbances in folate homeostasis are observed in alcoholism, attributable, in part, to intestinal malabsorption of folate. The aim of this study was to delineate the regulatory mechanisms of folate transport in intestinal absorptive epithelia in order to obtain insights into folate malabsorption in a rat model of alcoholism. The rats were fed 1 g.kg(-1) body weight of ethanol daily for 3 months. A reduced uptake of [(3)H]folic acid in intestinal brush border membrane was observed over the course of ethanol administration for 3 months. Folate transport exhibited saturable kinetics and the decreased intestinal brush border membrane folate transport in chronic alcoholism was associated with an increased K(m) value and a low V(max) value. Importantly, the lower intestinal [(3)H]folic acid uptake in ethanol-fed rats was observed in all cell fractions corresponding to villus tip, mid-villus and crypt base. RT-PCR analysis for reduced folate carrier, the major folate transporter, revealed that reduced folate carrier mRNA levels were decreased in jejunal tissue derived from ethanol-fed rats. Parallel changes were observed in reduced folate carrier protein levels in brush border membrane along the entire crypt-villus axis. In addition, immunohistochemical staining for reduced folate carrier protein showed that, in alcoholic conditions, deranged reduced folate carrier localization was observed along the entire crypt-villus axis, with a more prominent effect in differentiating crypt base stem cells. These changes in functional activity of the membrane transport system were not caused by a general loss of intestinal architecture, and hence can be attributed to the specific effect of ethanol ingestion on the folate transport system. The low folate uptake activity observed in ethanol-fed rats was found to be associated with decreased serum and red blood cell folate levels, which might explain the observed jejunal genomic hypomethylation. These findings offer possible mechanistic insights into folate malabsorption during alcoholism.
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http://dx.doi.org/10.1111/j.1742-4658.2007.06150.xDOI Listing
December 2007

Effects of malnutrition on the digestive enzymes of the large bowel of young rhesus monkeys.

Authors:
Satyavati Rana

Trop Gastroenterol 2003 Oct-Dec;24(4):189-92

Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India.

The aim of the present study was to investigate the effect of mild-to-moderate protein-energy malnutrition (PEM) and rehabilitation on the digestive enzymes of the large bowel in young rhesus monkeys. The presence of these enzymes has already been reported in the large bowel by many authors. The activities of the digestive enzymes, i.e. lactase, sucrase, maltase, trehalase, glucoamylase, leucine aminopeptidase, alkaline phosphatase and gamma-glutamyl transpeptidase, from different parts of the large bowel were determined in 6 controls, 6 PEM and 6 rehabilitated young rhesus monkeys. These monkeys had been used to study the effect of malnutrition on the small intestine and the results have already been published. There was a significant decrease in the sucrase in the ascending colon (p < 0.05); maltase in all the parts of the large bowel (p < 0.05); and glucoamylase activities (p < 0.05) in the caecum segment of the large bowel in the PEM group. The activity of other enzymes, i.e. lactase, trehalase, alkaline phosphatase, gamma-glutamyl transpeptidase and leucine aminopeptidase, was unaffected in the PEM group. The changes in the enzyme activities recovered on rehabilitation of 21 weeks. The result of this study suggest that even mild-to-moderate malnutrition affects the enzyme activity of the large bowel, which recovers on rehabilitation.
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June 2004

Effect of malnutrition on the digestive enzymes of the upper gastrointestinal tract of young rhesus monkeys.

Trop Gastroenterol 2003 Jan-Mar;24(1):22-4

Department of Gastroenterology (SSGE), Postgradaute Institute of Medical Education and Research, Chandigarh.

The present study was planned to observe the effect of protein-energy malnutrition on the gastric and duodenal mucosa. The activities of digestive enzymes (i.e. lactase, sucrase, maltase, trehalase, glucoamylase, leucine aminopeptidase, alkaline phosphatase and gamma-glutamyl transpeptidase) from the gastric (fundus, body and antrum) and duodenal mucosa [i.e. first (D1) and second (D2) part of the duodenum] were determined in 6 control, 6 protein-energy malnourished (PEM) and 6 rehabilitated young rhesus monkeys. There was a significant increase in the activity of the lactase enzyme in the antrum, and D1 and D2 portions of the duodenum of PEM monkeys, while the activity of all other enzymes was significantly increased in the D1 and D2 portions only. The increase in the activity of the above-mentioned enzymes became normal upon rehabilitation. There was no change in the enzyme activities of the gastric mucosa in mild-to-moderate PEM states. This study demonstrates that even mild-to-moderate malnutrition states affect the activity of enzymes in the gastric and duodenal mucosa. Enzyme activity recovers on rehabilitation.
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October 2003
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