Kim Vaiphei

Isoniazid- and rifampicin-induced oxidative hepatic injury - Protection by N-acetylcysteine

The role of N-acetylcysteine (NAC), a glutathione (GSH) precursor, was investigated in protection against isoniazid-(INH) and rifampicin-(RIF) induced oxidative hepatic injury in young Wistar rats. The hepatotoxic dose of INH and RIF was 50 mg kg-1 day-1 each and the hepatoprotective dose of NAC was 100 mg kgday-. All drugs were administered intraperitoneally (i.p.) in sterile water (4.0 ml kg-1 day-1) over a period of 3 weeks. Status of oxidative/antioxidative profiles was the mechanistic approach to assess the hepatotoxicity and/or hepatoprotection. The oxidative injury in INH-RIF co-exposed animals was closely associated with significant decline of GSH and related thiols, as well as with compromised antioxidant enzyme system. The oxidative stress was further supported by increased lipid peroxidation observed in these animals. The co-administration of NAC prevented the induction of oxidative stress in INH-RIF co-exposed animals. The amelioration of oxidative stress by NAC was faithfully reflected as normal morphology in these animals, except the presence of mild degree of portal triaditis in one animal co-exposed to INH-RIF and NAC. In contrast, the animals co-exposed to INH-RIF alone showed histological lesions which ranged from intralobular inflammation to patchy necrosis. These results suggest that INH-RIF-induced oxidative injury can be prevented by supporting the cellular antioxidant defense mechanism by NAC.

Study of Oxidative-Stress in Isoniazid-Rifampicin Induced Hepatic Injury in Young Rats

The role of oxidative-stress as a mechanism of hepatotoxicity caused by combination of isoniazid (INH) and Rifampicin (RMP) was investigated in young growing rats. A successful model of hepatotoxicity was produced by giving 50 mg/kg/day each of INH and RMP in two weeks. Liver showed type II hepatocellular changes (microvesicular fat deposition) with mild portal triaditis. The glutathione and related thiols were significantly decreased in both blood and liver tissues with combination of INH and RMP treatment. Superoxide dismutase, glutathione peroxidase, catalase and glutathione-S-transferases with CDNB and DCNB as substrates were decreased in the combination treated group. Glutathione reductase, glutathione-S-transferase with ethacrynic acid as substrate and lipid peroxidation exhibited a significant increase with treatment. The altered profile of antioxidant enzymes with increased lipid peroxidation indicated the enhanced oxidative-stress in combination of INH and RMP treatment. All the findings are faithfully reflected in the blood tissue except superoxide dismutase which showed significant enhancement in this tissue. INH and RMP hepatotoxicity is thus appeared to be mediated through oxidative-stress.

Primary sclerosing cholangitis : An experience from India

Primary sclerosing cholangitis (PSC) is considered to be rare in India. The aim of the present study was to investigate the incidence, clinical profile and outcome of PSC seen in a tertiary care centre. Over a period of 10 years (July, 1984‐June, 1994) 18 patients of PSC were diagnosed at cholangiography (14 patients by endoscopic retrograde cholangiopancreatography, two patients by percutaneous transhepatic cholangiography and two patients by both methods). The presence of secondary causes, such as choledocholithiasis, biliary tract surgery, congenital biliary tract anomalies, cholangiocarcinoma and pancreatic diseases, were excluded. These patients were evaluated retrospectively with respect to their clinical presentation, radiological findings, presence of associated idiopathic ulcerative colitis (IUC), treatment instituted and outcome. The mean (±s.d.) age at diagnosis of PSC was 39.0 (±16.1) years with a male: female ratio of 1.57:1. Nine (50%) patients had associated IUC. The diagnosis of IUC preceded that of PSC in all but one case. Fifteen (83.3%) patients had cholestatic jaundice at presentation, while three (16.7%) patients had asymptomatic rise of alkaline phosphatase. Three (16.7%) patients had recurrent cholangitis and five (27.8%) patients developed portal hypertension during the course of the disease. At cholangiography, intrahepatic radicles were involved in all and extrahepatic radicles in 12 (66.6%) cases. Patients were managed with steroids (n= 7), colchicine (n= 3), ursodeoxycholic acid (UDCA; n= 2) and methotrexate (n= 1), along with symptomatic measures. Mean duration of follow up available in 11 (61%) patients was 20.1 months (range: 1 month‐8 years). Four (36.4%) patients died. Steroids and colchicine did not have any effect while the one patient on UDCA and one on methotrexate showed improvement. In conclusion, in India PSC does not seem to be a rare entity. Its clinical profile and outcome are somewhat similar to those seen in Western countries.

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 [3H]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 Km value and a low Vmax value. Importantly, the lower intestinal [3H]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.

Epidemiology of Helicobacter pylori and peptic ulcer in India

There is a wide variation in the prevalence of peptic ulcer in India both before and since the use of endoscopy. We studied the prevalence of peptic ulcer disease in a community in northern India and its relationship with Helicobacter pylori infection.

Prevalence and clinical profile of celiac disease in type 1 diabetes mellitus in north India

Background and Aim:  There is scanty data on the occurrence of celiac disease in patients with type 1 diabetes mellitus in South Asia. Our aim was to study the prevalence and clinical profile of celiac disease in patients with type 1 diabetes mellitus in a tertiary care referral centre in north India.

Protein-energy malnutrition and oxidative injury in growing rats.

1 Weaning rats were fed ad libitum isocaloric diets containing 5% and 20% casein based proteins. 5% protein diet was protein deficient diet. Pair fed rats with the 5% protein group were maintained simulta neously on 20% protein diet but the amount restricted to the amount taken up by PEM group. 2 Glutathione, antioxidative enzymes, lipid peroxida tion and histopathological studies in liver and only glutathione and antioxidative enzymes in blood were carried out. 3 Rats fed the 5% protein diet developed a severe protein energy malnutrition (PEM) whereas those on pair-fed diet developed mild to moderate PEM. 4 Glutathione related thiols, superoxide dismutase, glutathione peroxidase, catalase and glutathione-S- transferase with (1 Chloro 2,4-dinitro benzene (CDNB) substrate) were decreased in liver with concomitant increase of lipid peroxidation in severe PEM. In blood glutathione, glutathione peroxidase and catalase were decreased while superoxide dismutase was increased in severe PEM group. 5 Mild to moderate PEM (pair-fed group) also resulted in similar changes in liver except glutathione peroxidase, lipid peroxidation in liver and superoxide dismutase in blood. 6 Hepatic injury was detectable only in the severe PEM group. 7 Oxidative-stress and hepatic injury occurred in severe PEM and to a lesser degree in mild to moderate PEM.

Diagnostic value of push-type enteroscopy: a report from India.

OBJECTIVE:We sought to assess the diagnostic value of push-type enteroscopy in relation to indications.METHODS:Ninety-nine consecutive patients (mean age, 42 ± 15 yr; 65 men) with suspected small bowel disorders underwent push enteroscopy. The indications were chronic diarrhea (n = 54), obscure gastrointestinal (GI) bleeding (n = 21), abdominal pain (n = 10), abnormal radiological studies of small bowel (n = 5), iron deficiency anemia (n = 5), and others (n = 4). Push enteroscopy was performed using the Olympus SIF-10 (160-cm) enteroscope.RESULTS:Endoscopic examination of the jejunum was successful in all the patients, except one with a distal duodenal stricture. The length of the jejunum examined ranged from 10 to 70 cm. The time taken to complete the procedure varied from 2 to 30 min. Lesions were found in nine (42.8%) patients with obscure GI bleeding; six (28.5%) had worms (Ascaris lumbricoides [n = 3], Ankylostoma duodenale [n = 3]) in the jejunum, producing multiple erosions and bleeding points. In the chronic diarrhea group, a diagnosis was made in 13 (24%) patients on enteroscopic visualization and jejunal histology: celiac disease (n = 6), tropical sprue (n = 3), Crohns disease (n = 1), secondary lymphangiectasia (n = 1), strongyloidiasis (n = 1), and nodular lymphoid hyperplasia with giardiasis (n = 1). In patients with abdominal pain, enteroscopy provided a diagnosis in one (10%) patient. No positive diagnosis could be made on enteroscopy in patients with iron deficiency anemia and abnormal radiological studies of small bowel.CONCLUSION:Push-type enteroscopy is a useful test in the evaluation of patients with obscure GI bleeding and chronic diarrhea. In developing countries, in patients with obscure GI bleeding, the presence of worms in the jejunum is an important finding on enteroscopy. Tropical sprue, giardiasis, and strongyloidiasis are distinct findings in patients with chronic diarrhea in the present series.

Melatonin treatment is beneficial in pancreatic repair process after experimental acute pancreatitis.

Current treatment options for acute pancreatitis are supportive and symptomatic. Due to lack of agents targeting the underlying pathophysiology a large amount of experimental work is going on to identify novel therapeutic agents. The present study was carried out to explore if melatonin can modulate the spontaneous regeneration process of the pancreas after experimentally induced acute pancreatitis. Rats were given two i.p. injections of l-arginine in a dose of 200mg/100g at an interval of 1h for induction of pancreatitis. After this rats were randomly divided into three groups i.e. saline, CCK-8 and melatonin. Drug treatment was started 2h after the last l-arginine injection and continued till the day of sacrifice. An additional only saline treated control group was included for comparison. Animals in each group were sacrificed at 24h, days 3, 14 and 28 after pancreatitis induction for determination of biochemical parameters (serum amylase, lipase and IL-10 and pancreatic amylase, total proteins and nucleic acid content) and histological examination. For rate of DNA synthesis and immunohistochemical studies animals were sacrificed at day 3 and day 7. Melatonin treatment was found to be beneficial in acute pancreatitis. Severity of acute pancreatitis was significantly reduced in melatonin group. Nucleic acid content, rate of DNA synthesis, pancreatic proteins and pancreatic amylase content were significantly improved. Histopathological examination showed significantly lower total scores in melatonin group. Results of melatonin group were comparable to that of positive control, CCK-8 group. Thus melatonin treatment was found to promote the spontaneous regeneration process of pancreatic tissue.

Fecal lactoferrin, myeloperoxidase and serum C-reactive are effective biomarkers in the assessment of disease activity and severity in patients with idiopathic ulcerative colitis.

Background and Aim:  Disease activity and severity of ulcerative colitis (UC) is assessed using colonoscopy, which is invasive, costly and has poor patient acceptability. The role of non‐invasive biomarkers of intestinal inflammation in the evaluation of patients with UC is not known. The aim of the study was to examine the role of serum C‐reactive protein (SCRP), fecal myeloperoxidase (FMPO) and fecal lactoferrin (FLF) in assessing disease severity, activity and response to therapy.