Efficacy of Oral Psyllium in Pediatric Irritable Bowel Syndrome: A Double-Blind Randomized Control Trial.

OBJECTIVE: Pediatric irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder with variable response to various therapeutic agents. Psyllium has been proven to be effective in adults; however, there is no study in children. The objective of this study is to evaluate the efficacy of psyllium husk as compared to placebo in pediatric IBS patients. METHODS: In this double-blind randomized controlled trial, 43 children were assigned to psyllium arm (Group A) and 38 into placebo arm (Group B). Severity is assessed at baseline and after 4 weeks of treatment using IBS severity scoring scale (IBS-SSS) and classified into mild, moderate, and severe categories. Categorical data was compared with chi-square test and paired categorical variable was compared with McNemer test. RESULTS: Mean ages (±SD; in years) of Groups A and B were 9.87 (2.7) and 9.82 (3.17), respectively, with median duration of illness of 12 months. At baseline, type, severity, and parameters (IBS-SSS) of IBS were equally distributed in 2 groups. There was a significant reduction in median interquartile range (IQR) of total IBS-SSS in psyllium versus placebo [75 (42.5-140) vs 225 (185-270); P < 0.001] at 4 weeks. Similarly 43.9% in Group A versus 9.7% in Group B attained remission [IBS-SSS < 75 ( P < 0.0001)]. The mean difference in IBS-SSS between Group A and Group B was -122.85 with risk ratio of 0.64 (95% CI; 0.42-0.83; P = 0.001) and absolute risk reduction of 32% (NNT = 3). CONCLUSIONS: Psyllium husk is effective for the therapy of pediatric IBS when compared with placebo in short term.

Can serum resistin predict severity of acute pancreatitis?

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 (p-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 (p-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.

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

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.

COVID-19 and Gut Microbiota: A Potential Connection.

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.

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

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.

Neutrophil Gelatinase-associated Lipocalin Predicts Short-term Outcomes in Decompensated Cirrhosis With Acute Kidney Injury.

Background and aims: Acute kidney injury (AKI) increases mortality in cirrhosis. Early identification of the cause of AKI helps in planning appropriate management. We aimed to find whether neutrophil gelatinase-associated lipocalin (NGAL) can be used to differentiate between different types of AKI in cirrhosis and predict short-term outcomes in patients with decompensated cirrhosis and AKI. Method: This was a time-bound study in which consecutive hospitalized patients with cirrhosis and AKI were prospectively recruited and managed as per standard care. Acute on chronic liver failure (ACLF) was diagnosed as per the EASL-CLIF Acute-on-Chronic Liver Failure in Cirrhosis (CANONIC) criteria. Urine NGAL was measured by enzyme-linked immunosorbent assay (ELISA) by Epitope Diagnostics Inc. kit (San Diego, USA.) in all patients on admission, and patients were followed up until hospital discharge or death. Results: A total of 110 consecutive patients (median [range] age: 44 [28-81] years;87.3%were male; ACLF: 71.8%; acute decompensation 28.2%; Model for end-stage liver disease (MELD) 27 [13-46]; Child-Turcotte-Pugh (CTP) 11 [7-15]) with cirrhosis and AKI were recruited. Alcohol was the most common etiology of cirrhosis(64.5%)). Pre-renal azotemia (PRA) was the most common cause of AKI (n = 56). Urine NGAL was significantly elevated in acute tubular necrosis (ATN) (1747 [6-6141] ng/ml than in hepatorenal syndrome (HRS) (379 [33.5-2320] ng/ml; P < 0.0001) and PRA (167 ng/ml [3.34-660]; P < 0.0001). Sixty-four percent patients with ATN, 27.6% patients with HRS, and none with PRA required dialysis. A total of 79.31% patients with HRS and 76% with ATN died. Urine NGAL was significantly higher in patients who required hemodialysis than in those who did not (1733 [243-6141] ng/ml vs 235 [3.34-2320] ng/ml; P < 0.0001). Both urine NGAL (n = 110) and plasma NGAL (n = 90) were significantly higher in patients who died (urine NGAL: -475 [6-6141] ng/ml vs 247 [3.34-2320] ng/ml; P = 0.002;plasma NGAL-950 [94-4859] ng/ml vs 608 [18-3300)]g/ml; P < 0.001). On multivariate analysis, urine NGAL and INR could predict mortality. Conclusion: NGAL can differentiate between different types of AKI in cirrhosis and predict the need for hemodialysis and mortality in decompensated cirrhosis with AKI.

Secretory Phospholipase A2 (sPLA2) Isozymes as Potential Targets in Tobacco Condensate- induced Colon Damage.

AIMS: To find out the role of secretory phospholipase A2 (sPLA2) isozymes as potential targets in tobacco condensate-induced colon damage. BACKGROUND: The effects of cigarette smoke condensate (CSC) and the molecular mechanisms involved in the regulation of phospholipase A2 (PLA2) and its isozymes in colon cells, which are still unclear and emerging, are studied. OBJECTIVES: The study aimed to check the effect of CSC on cell viability and reactive oxygen species (ROS) and superoxide. Also, the effect of CSC on gene expression of different secretory phospholipase A2 (sPLA2) was evaluated. Moreover, the impact of inhibition of sPLA2 on various cell properties i.e. cell viability, cell proliferation, membrane damage and free radicals' generation is also studied. METHODS: CSC-induced changes were evaluated in cell viability by MTT assay, followed by the evaluation of membrane modulation by flow cytometry, free radical generation by fluorescent dyes, PLA2 isoforms gene expression patterns and their suppression by small interfering RNA (siRNA) studied in HCT-15 male and HT-29 female colon cells. RESULTS: Our results demonstrate that HCT-15 and HT-29 cells treated with CSC significantly reduced the cell viability by 50% within 48 h and significantly enhanced the total reactive oxygen species (ROS) by 2 to 10-fold, and mitochondrial ROS (mtROS) and superoxide radicals (SOR) by 2-fold each. Treatment with CSC significantly unregulated secretory phospholipase A2 (sPLA2) IID group and down-regulated IB and cytosolic phospholipase (cPLA2) IVA groups in HCT-15 cells without affecting them in HT-29 cells. Silencing the sPLA2 IID group results in an increase in cell viability and a decrease in ROS. Silencing the PLA2 IVA gene in the HCT-15 cells showed a reduced expression which had no impact on the CSC-induced cell proliferation, membrane damage and free radicals (ROS, mtROS, and SOR) generation. CONCLUSION: Therefore, identifying cell-specific sPLA2 isozymes seems to play a key role in controlling the ROSinduced damage by CSC and helps develop specific therapeutic strategies.

Efficacy of Pro-Kinetic Agents in Type 2 Diabetes Mellitus Patients With Gastroparesis Using Lactulose Hydrogen Breath Testing: A Randomized Trial.

Aim The aim of the study was to determine the efficacy of prokinetic agents in diabetic gastroparesis patients. Method This was a randomized open-label trial conducted on 50 patients with type 2 diabetes experiencing diabetic gastroparesis, which was diagnosed with the lactulose hydrogen breath test. After randomization, all 50 patients were divided into four arms (cinitapride, metoclopramide, levosulpiride, and domperidone) of different prokinetics and followed up for four weeks; after which, repeat gastroparesis cardinal symptom index score and orocecal transit time were recorded in order to assess the response to the treatment. Result There was no statistically significant difference among the four groups in terms of all the baseline characteristics except for gender (p=0.032). The follow-up gastroparesis cardinal symptom index was collected for 50 patients but repeat orocecal transit time could be performed only in 37 patients. In all four groups, there was a statistically significant (p<0.05) improvement in terms of orocecal transit time and gastroparesis cardinal symptom index scores. But there was no statistically significant difference in relative efficacy amongst these study groups. Conclusion Our study showed statistically significant improvement with four prokinetics drugs in terms of gastroparesis cardinal symptom index score and orocecal transit time, but there was no statistically significant benefit of one prokinetic drug over the other. Our study showed promising results with regard to prokinetic use in diabetic gastroparesis.

Assessment of Dyslipidemia, Lipid Ratios, and Atherogenic Indices as Cardiovascular Risk Factors in Prediabetic and Diabetic Subjects.

Background Uttarakhand is a small state in northern India that comprises mixed population with people dwelling in both hilly and plain areas. Globally, diabetes mellitus (DM) has already been considered to be a pandemic. Furthermore, cardiovascular diseases (CVD) significantly increase mortality and morbidity in patients suffering from DM. Additionally, dyslipidemia has been identified as an important marker in the development of atherosclerosis and ultimately CVD in patients of prediabetes and diabetes. Thus, the identification of subjects with dyslipidemia in prediabetes might be fruitful in lowering their progression to diabetes and ultimately in decreasing incidences of CVD. Hence, this study was undertaken to assess dyslipidemia via the calculation of atherogenic indices (AI) and lipid ratios in prediabetic and diabetic groups attending tertiary care hospital in Uttarakhand. Materials and Methods This study reviewed retrospective biochemical data of 500 study subjects from e-hospital software of the All India Institute of Medical Sciences, Rishikesh. All study subjects were divided into three groups: 122 controls, 137 prediabetics, and 241 diabetics based on the American Diabetes Association criteria. Study subjects were evaluated for glycated hemoglobin (HbA1c), lipid profile, and AI (total cholesterol [TC]/high-density lipoprotein cholesterol [HDLc], low-density lipoprotein cholesterol [LDLc]/HDLc, TC-HDLc/HDLc, triglycerides [TG]/HDLc). Results Results showed that TC, TG, LDLc, and AI were significantly higher, and HDLc was significantly decreased in prediabetic and diabetic groups compared with controls. Furthermore, HbA1c showed significant positive correlation with lipid profile and AI except atherogenic coefficient (TC-HDL/HDL). Conclusion In conclusion, the current study showed the presence of dyslipidemia in both prediabetic and diabetic groups underlining their importance for screening at the prediabetic stage. Hence, we also recommend screening of the prediabetic group for dyslipidemia to arrest the development of early cardiovascular complications.

Derivation of a Modified Friedewald's equation for LDL cholesterol estimation in Sub-Himalayan population: A comparative study.

Background: Despite the availability of alternative homogenous assays for LDL-C measurement, most of the laboratories still use Friedewald Equation (FE). However, various novel equations have shown better performance than FE specific to a particular population. Besides, no equation has been devised for use in Sub-Himalayan population. Methods: A cross-sectional laboratory data-based study was conducted by recruiting lipid profiles of 1851 samples to validate 10 different equations for calculating LDL and to devise a novel Modified Friedewald Equation (MFE) specific for Sub-Himalayan population. Results: The novel MFE is presented as: LDL-C = -2.421 + (0.752 × TC) - (0.047 × TG) - (0.350 × HDL). A significant difference was observed between direct LDL-C (118.84 ± 40.39 mg/dL) and all other equations except MFE (118.84 ± 37.96 mg/dl, P > 0.999) and Puavilai Equation (117.99 ± 49.05 mg/dL, P = 0.138). Additionally, MFE showed lowest mean percentage bias of 0.14% with 95% limits of agreement within ± 2SD on Bland-Altman analysis. On ROC analysis at cut-offs of clinical decision limits of 100 mg/dl, 130 mg/dl, 160 mg/dl, and 190 mg/dl, MFE outperformed all other equations with highest AUC (0.974, 0.978, 0.982, and 0.995) respectively with specificity >95% at higher levels. MFE also showed highest correlation (r = 0.954, P < 0.001) and least rMSE (13.8) with direct LDL although all the equations showed significant positive correlation with direct LDL (p < 0.001). Conclusion: MFE derived in this study showed a better diagnostic performance as compared to other 10 equations taking Direct LDL-C as gold standard for Sub-Himalayan Population and may be used as a substitute for FE in the study population.

Lower cyst fluid carcinoembryonic antigen cutoff is helpful in the differential diagnosis of mucinous versus non-mucinous pancreatic cysts.

BACKGROUND AND AIM: Pancreatic cystic lesions (PCLs) are being diagnosed with increased frequency and have varying neoplastic potential. We conducted this multimodal, prospective study to evaluate  the role of tumor cytology and molecular markers to differentiate PCL subtypes. METHODS: Consecutive undiagnosed patients with PCLs (n = 100, mean age: 50.37 years; 41% males) were prospectively studied. Cyst fluid carcinoembryonic antigen (CEA), CA19.9, CA125, CA72.4, and vascular endothelial growth factor-alpha (VEGF-α) levels were measured by quantitative enzyme-linked immunosorbent assay (ELISA) method. Mutational analysis of the KRAS gene (exon 2, Codon 12 and 13) and GNAS gene (Exon 8, Codon 201) were performed by Sanger's sequencing. RESULTS: The mean cyst size was 4.32 ± 2.4 cm. Fluid cytology revealed definitive diagnosis in 21 (22.3%) patients. All malignant PCLs could be identified on cytology whereas 10/14 (71%) non-malignant mucinous PCLs could also be identified on cytology based on mucin staining. Among the tested tumor markers, cyst fluid CEA had the best diagnostic performance for differentiation between mucinous and non-mucinous PCLs (AUC 0.933 [95% CI 0.86-0.91]). At a cyst fluid CEA cutoff level of 45.0 ng/mL, the sensitivity, specificity, positive predictive value, and negative predictive value for differentiation between mucinous and non-mucinous cysts were 88.5%, 96.8%, 92.0%, and 95.3%, respectively (p < 0.05). KRAS and GNAS mutation had no significant diagnostic benefit in comparison to fluid cytology and CEA levels. CONCLUSIONS: Fluid CEA at a lower cutoff of 45 ng/mL is the most accurate marker to differentiate between mucinous and non-mucinous PCL. The KRAS and GNAS mutational analysis does not improve upon the diagnostic performance of fluid cytology and tumor markers.

Serum ferritin as a predictive biomarker in COVID-19. A systematic review, meta-analysis and meta-regression analysis.

Ferritin is a known inflammatory biomarker in COVID-19. However, many factors and co-morbidities can confound the level of serum ferritin. This current metaanalysis evaluates serum ferritin level in different severity levels in COVID-19. Studies evaluating serum ferritin level in different clinical contexts (COVID-19 vs. control, mild to moderate vs. severe to critical, non-survivor vs. survivor, organ involvement, ICU and mechanical ventilation requirement) were included (total 9 literature databases searched). Metaanalysis and metaregression was carried out using metaphor "R" package. Compared to control (COVID-19 negative), higher ferritin levels were found among the COVID-19 patients [SMD -0.889 (95% C.I. -1.201, -0.577), I2 = 85%]. Severe to critical COVID-19 patients showed higher ferritin levels compared to mild to moderate COVID-19 patients [SMD 0.882 (0.738, 1.026), I2 = 85%]. In meta-regression, high heterogeneity was observed could be attributed to difference in "mean age", and "percentage of population with concomitant co-morbidities". Non-survivors had higher serum ferritin level compared to survivors [SMD 0.992 (0.672, 1.172), I2 = 92.33%]. In meta-regression, high heterogeneity observed could be attributed to difference in "mean age" and "percentage of male sex". Patients requiring ICU [SMD 0.674 (0.515 to 0.833), I2 = 80%] and mechanical ventilation [SMD 0.430 (0.258, 0.602), I2 = 32%] had higher serum ferritin levels compared to those who didn't. To conclude, serum ferritin level may serve as an important biomarker which can aid in COVID-19 management. However, presence of other co-morbid conditions/confounders warrants cautious interpretation.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.