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Biomedical subjects

K Vaiphei

Publications and source records attributed to K Vaiphei.

At least 19 recordsLinked to original sources

Role of N-acetylcysteine in rifampicin-induced hepatic injury of young rats.

AIM: To study the role of N-acetylcysteine (NAC) as a protective agent in rifampicin (RMP)-induced oxidative hepatic injury of young rats. METHODS: Hepatic injury was produced by giving 50 mg/kg body weight/day of RMP for 3 wk. A dose of NAC (100 mg/kg body weight/day) was given in combination with RMP intraperitoneally. Analysis of lipid peroxidation, thiol levels, cytochrome P450, superoxide dismutase (SOD), catalase, glutathione peroxidase, reductase and transferase were estimated in liver along with the body weight, liver weight and histological observations. RESULTS: RMP exposure resulted in no change in body and liver weight while antioxidative enzymes were altered but the non protein thiol (GSH) status was well preserved. Cytochrome P450 system and peroxidation of lipids were induced by RMP exposure. Partial protection was observed with NAC against RMP-induced changes in liver, which was evidenced from the prevention of increase in lipid peroxidation and the reduction in SOD and catalase enzyme levels. CONCLUSION: NAC protects young rats against RMP-induced oxidative hepatic injury.

Acetylcysteine↗

P53, COX-2, iNOS protein expression changes and their relationship with anti-oxidant enzymes in surgically and multi-modality treated esophageal carcinoma patients.

Esophageal carcinoma has a high incidence in India but its etiology remains unknown. In the present study the correlation between apoptosis regulatory proteins and anti-oxidant enzymes in 40 esophageal carcinoma patients was examined. Patients in one group were operated by transhiatal esophagectomy and in the second group were administered cisplatin (30 mg/m2/day) and 5-fluorouracil (5-FU) (750 mg/m2/day) daily for three days followed by surgery after four weeks of neo-adjuvant therapy (NAT). Complete pathological response was achieved in 15% of patients. Results obtained by Western blot analysis showed over-expressed p53 and COX-2 protein levels in the tumor tissues as compared to the adjoining tissue and its paired normal mucosa in both groups of patients. Immunohistochemical studies showed heterogenous p53 staining pattern with sections showing both nuclear and cytoplasmic staining with 36.8% mild, 10.5% moderate and 52.6% intense p53 immunoreactivity. Both COX-2 and iNOS immunostaining revealed 25% negative and 75% mild to strongly positive immunoreactivity. Correlation studies demonstrated a positive relationship between p53 and COX-2 (P=0.030; r = +0.70) in surgically treated patients. The association of COX-2 and p53 with various anti-oxidant enzymes showed a significantly positive correlation between COX-2 expression and catalase activity and an inverse correlation between p53 expression and superoxide dismutase and catalase activity in the tumor tissue of patients given NAT. In addition, we observed a negative trend between p53 expression levels and GPx enzyme levels in both the adjoining and tumor tissue of patients having undergone surgery as main mode of treatment.

Adenocarcinoma↗

Utilization of antihepatocyte clone OCH1E5 (Hep Par 1) in histological evaluation of liver tumors.

Diagnosis of hepatocellular carcinoma (HCC) is not always easy on simple hematoxylin and eosin (H&E) stain. The diagnostic problems arise when tumor shows pseudoglandular, pleomorphic or clear cell differentiation. Various tumors markers have been described with varying sensitivity and specificity. Monoclonal antibody Hep Par 1 (OCH1E5) which is specific for hepatocytes offers great help in separation of these tumors. The aim of the present study was to determine utility of Hep Par 1 (OCH1E5) in differentiating HCC from metastatic tumors and cholangiocarcinoma. Total of 62 cases of liver tumors obtained from biopsies, resected or autopsy specimens were included in the study. Slides having representative sections were subjected to immunohistochemistry with monoclonal antibody Hep Par 1 (Dako Corp) using avidin biotin technique with primary antibody dilution of 1:40. Adjacent nontumorous hepatocytes were taken as positive control. Slides were examined by experienced pathologist without any information of clinical or H&E diagnosis. Cases were considered positive for Hep Par 1 if tumor cells showed cytoplasmic brown colored granules. The intensity and distribution (diffuse/ focal) of immunoreactivity was noted. Subsequently immunohistochemistry results were correlated with histology and clinical diagnosis. Hep Par 1 antibody was positive in 26 (42 %) and negative in 36 (58 %) liver tumors. On correlating with H&E sections, out of 26 positive cases, 25 (89.2%) were HCC and one was the case of metastasis of mucin secreting adenocarcinoma. From 36 tumors with negative staining 3 were cases of HCC, 27 metastatic adenocarcinomas and 6 cholangiocarcinomas. Only one case of liver metastasis of mucin secreting adenocarcinoma showed positivity. None of the cases of cholangiocarcinoma showed positivity for Hep Par 1. The three HCCs which did not take up staining for Hep Par 1 were 2 cases of moderately differentiated HCC having pseudoglandular pattern and a case of well differentiated HCC with trabecular arrangement. In 11(44%) cases staining was diffuse while in 14 (56%) it was focal but intense. Hep Par 1 is a useful marker in differentiating HCC from metastaic tumors and cholangiocarcinoma with sensitivity and specificity of 89 % and 97 % respectively and positive predictive value of 96 %. However one should be aware of limitations of immunohistochemistry.

Adult↗

Goblet cell status in idiopathic ulcerative colitis--implication in surveillance program.

Idiopathic ulcerative colitis (IUC) patients have higher incidence of dysplasia and malignancy. Close follow-up with biopsy at regular interval is mandatory. The study was done to correlate incidence of atypical epithelium, goblet cell hyperplasia (GCH) and disease duration (DD) with Ki67, AgNOR and p53 expression in IUC with disease for 5 or more years. Ki67 and AgNOR are good indicators of cellular proliferation and p53 tumour suppressor protein is a marker for neoplastic cell. Of 130 cases studied, 40 cases showed atypical epithelium and were selected for further study. DD in these 40 cases ranged from 60 to 228 months. All had GCH and showed histological features of chronicity. Low-grade dysplasia (LGD) was seen in 15 cases, indefinite for dysplasia (ID) in 8 and inflammatory atypia in 17 cases. Disease duration showed no influence in the type of atypical epithelium. A positive staining of lining epithelium by Ki67 and p53 was not restricted to dysplasia. LGD and ID showed stronger p53 nuclear staining. AgNOR appeared to be a more sensitive marker than Ki67. GCH showed a positive correlation with DD and AgNOR index. p53 expression correlated positively with goblet cell hyperplasia. Conclusion- goblet cell hyperplasia could indicate presence of epithelial cell dysplasia.

Adolescent↗

Intracellular cytokines in cells of necrotic tissue from patients with acute pancreatitis.

OBJECTIVE: To determine the alterations in intracellular cytokine responses in necrotic pancreatic tissue obtained on debridement from patients with acute pancreatitis. DESIGN: Laboratory study. SETTING: Teaching hospital, India. MATERIAL: Necrotic tissue obtained at necrosectomy from 34 patients with alcohol-induced or biliary pancreatitis (n = 17 in each) and at autopsy from 12 controls. INTERVENTIONS: Histopathological evaluation; measurement of intracellular content of the cytokines interleukin (IL)-2, IL-4, IL-10 and IFN-gamma in CD4+ and CD8+ T lymphocytes and IL-6 and IL-12 in CD14+ monocytes. MAIN OUTCOME MEASURES: Intracellular content of the measured cytokines. RESULTS: CD4+ and CD8+ T cells and CD14+ monocytes responded to in vitro stimulation of mitogens and synthesised cytokines to varying degrees in the three groups. The heterogeneous cytokine response pattern did not show a typical type 1/type 2 polarised model. CONCLUSIONS: This profile suggests that the cells retain the capacity to modulate their phenotype in response to local conditions at the effector site. These results could be taken into consideration when designing new and specific treatments for modifying the immune inflammatory response.

Acute Disease↗

Gastrointestinal stromal tumors the assessment of malignant potential.

GISTS are the largest category of non-epithelial neoplasms of stomach and small bowel. Numerous immunohistochemical, ultrastructural and flow cytometry studies have been carried out for evaluation of prognostic factors which could predict malignant behaviour of these neoplasms. Tumor size of 5 cm and mitosis of 2/10 hpf were suggested as two important parameters which could predict the chances of recurrence and clinically aggressive course. The aim of this study is to examine predictive value of these two important parameters in assigning the tumors as high, intermediate and low risk groups. Using these two parameters we categorized 30 cases of GIST over a period of 6 years (1990-95) into low, intermediate and high risk groups and examined other features of these cases. Based on these two parameters alone we found that 4 cases each in low and intermediate group could be assigned to a higher risk group clinically as there were presence of adjacent organ infiltration, lymphatic emboli, serosal nodules, lymph node metastasis and transmural infiltration. Hence, other features like hemorrhage, necrosis and anaplasia should also be included in risk assessment. Metaplastic tissues like bone, cartilage and adipose tissues were seen only in high-risk categories.

Adolescent↗

Protection against rotavirus diarrhoea in mice by trypsin inhibitor.

To investigate the role of soyabean trypsin inhibitor (TI) during rotavirus (RV) diarrhoea, changes in enzyme activities of six relevant mucosal enzymes (lactase, sucrase, maltase, trehalase, glucoamylase and alkaline phosphatase) were assayed following inoculation of suckling mice with EB rotavirus (serotype 3) along with the TI and compared with the age-matched healthy control mice. The animals were divided into three groups i.e. group 1 (controls), group 2 (RV inoculated) and group 3 (RV + TI inoculated and sacrificed under light anaesthesia on 0, 1, 3, 5, 7 and 10 day post inoculation (dpi). Then intestines were excised and divided into two parts (jejunum and ileum). They were separately homogenized in 0.9% cold normal saline and activities of mucosal enzyme were measured. Alkaline phosphatase and disaccharidases were found to be decreased significantly in RV inoculated animals in both the anatomical portions of small intestine of mice. These enzyme levels were restored with the administration of TI i.e. in group 3 and became comparable to the controls in both intestinal portions. These studies suggest that activity of intestinal enzymes which are important in digestive absorptive functions of small intestine were restored with the addition of TI whengiven to infant mice showing its protective efficacy during rotavirus infection.

Animals↗

Isolated gastric tuberculosis presenting as massive hematemesis: report of a case.

Tuberculous involvement of the stomach is rare. We report herein the unusual case of a 25-year-old man in whom a benign gastric ulcer was found along the lesser curvature after he presented with massive upper gastrointestinal bleeding. Histopathological examination helped to confirm a diagnosis of tuberculosis. The granulomas typical of tuberculosis were caseation with epithelioid and giant cells. The patient was successfully treated by a combination of appropriate surgical therapy and prompt institution of antituberculosis medication.

Adult↗

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), Crohn's 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.

Adult↗

Influence of soybean trypsin inhibitor on small bowel enzyme activities during rotavirus infection in malnourished infant mice.

Rotavirus (RV) is considered to be one of the major causes of acute episodic diarrhoea throughout the world. This study was undertaken to investigate the effect of soybean trypsin inhibitor (TI) on brush-border enzymes during rotavirus infection in protein energy malnourished (PEM) infant mice. Animals were divided into 4 groups, namely controls, PEM, PEM+RV and PEM+RV+TI (n = 36 each). Group 1 and 2 animals were orally inoculated with 50 microl of normal saline each. Group 3 animals were orally inoculated with 50 microl of 100 ID50 dose of RV stock each. Group 4 animals were similarly inoculated with 0.6 mg TI/g body weight along with 50 microl of RV stock each. Animals were examined daily for diarrhoea and their body weight was recorded on alternate days postinoculation (dpi). Animals were killed by cervical dislocation after being given light chloroform anesthesia on 0, 1, 3, 5, 7 and 10 dpi. Small intestines were excised and homogenized in normal saline. Proteins, gammaglutamyl transpeptidase, alkaline phosphatase and disaccharidases were estimated in jejunum and ileum. Body weight was significantly reduced in PEM animals and with RV infection. Histologically, focal areas of vacuolar degeneration of lining epithelium were seen in RV-infected animals. Disaccharidases and other enzyme activities were decreased significantly in the PEM group compared to healthy controls and further depressed with RV infection in malnourished animals as compared to non-infected PEM. The enzyme activities were restored in animals receiving TI along with RV compared to the group receiving RV without TI. With the administration of soybean TI, the activities of disaccharidases, alkaline phosphatase, gammaglutamyl transpeptidase and intestinal architecture were restored showing a protective effect in PEM during RV infection.

Animals↗

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 kg(-1) day(-1). 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.

Acetylcysteine↗