Medicine
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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty
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Item Effect of standardized decoction of Nigella sativa seed, Hemidesmus indicus root and smilax glabra rhizome on the expression of p53 and p21 genes in human hepatoma cells (HepG2) and mouse liver with chemically-induced hepatocarcinogenesis(University of Benin, 2012) Samarakoon, S.R.; Thabrew, I.; Galhena, P.B.; Tennekoon, K.H.PURPOSE: To evaluate in vitro (using human hepatoma HepG2 cells) and in vivo (using mouse liver with diethlynitrosamine (DEN)-induced hepatocarcinogenesis) effect of a standardized decoction on the expression of p53 (tumour suppressor) and p21 (cyclin kinase inhibitor) genes with the long-term goal of developing the formulation into a globally acceptable therapy for hepatocellular carcinoma (HCC). METHODS: The effect of the decoction on (a) mRNA and (b) protein expression of p53 and p21 genes in HepG2 cells and mouse livers with DEN-induced early hepatocarcinogenesis were evaluated by (a) reverse transcription PCR (RT-PCR) and (b) immunohistochemical and Western blot analysis, respectively. RESULTS: The results demonstrated that the decoction significantly (p < 0.001) enhanced the expression of p53 and p21 genes in a time-and dose-dependent manner in HepG2 cells. A dose of 75 μg/ml significantly increased p53 mRNA at 24 and 48 h and p21 mRNA at 12, 24, 48 h of incubation with the decoction (p < 0.01). Induction of hepatocarcinogenesis in mice significantly increased hepatic expression of both p53 and p21 compared to distilled water control (p < 0.001), while treatment with the decoction further enhanced expression of both genes in DEN-induced hepatocarcinogenesis (p < 0.01). CONCLUSION: Overall, the findings demonstrate that the decoction may mediate its reported antihepatocarcinogenic effect, at least in part, through the modulating activities of genes involved in tumour suppression and cell cycle arrest. All rights reserved. © Pharmacotherapy Group. All rights reserved.Item A comparative study of patients with pancreatic calcification in Sri Lanka(The College of Surgeons of Sri Lanka and SAARC Surgical Care Society, 2003) de Silva, M.; Selliah, S.; Thabrew, I.INTRODUCTION: Although alcohol abuse is a common cause of pancreatic calcification in the west, a non-alcoholic form called Tropical caicific Pancreatitis (TCP) is recognized in Asian countries.OBJECTIVE: To compare the clinical, biochemical, radiological and endoscopic profiles and success of endotherapy of TCP with Alcoholic Calcific Pancreatitis (ACP). METHODS:Biochemical assay. and ERCPs were performed on 50 patients with pancreatic calcification.There were 28 TCP and 22 ACP in the sample. Mean age of ACP (43.7y SD 8.9) was higher than TCP (37.7 SD 10 p<0/05). ACP was exclusively seen among males.Mean age of onset of pain was lower in the TCP. Nearly 80% of TCP had pain scores more or equal to 7 compared to 54.5% in ACP. Onset of diabetes mellitus in TCP occurred earlier than ACP (34y Vs 40y). Mean serum insulin and duodenal trypsin levels were higher in the TCP patients. On x-ray 85% of TCP had coarse calcium plaques and 71.4% of ACP had speckled plaques. ERCP was successful in nearly 70% of the total sample and 50% underwent stenting. Adequate pain relief was observed in 50% in TCP and 54% in ACP. CONCLUSION:Onset of pain and diabetes mellitus occurred at a younger age in TCP. Although more intraductal plaques were seen in TCP, no difference was observed in the response to endotherapy.Item Is cassava consumption related to tropical calcific pancreatitis in Sri Lanka(The College of Surgeons of Sri Lanka and SAARC Surgical Care Society, 2003) Siva, S.; de Silva, M.; Thabrew, I.INTRODUCTION: Presence of calcification in the pancreas confirms the diagnosis of Chronic Pancreatitis. In the developing countries, a non alcoholic form referred to as Tropical Calcific Pancreatitis (TCP) is been increasingly recognized. An association has been suggested to malnutrition and cassava consumption. OBJECTIVES: To assess the aetiological factors and BMI of TCP patients. METHODS: On 28 TCP patients a detailed questionnaire was administered to collect the aetiological factors. Height and weight measurements were taken. The results were compared with 50 healthy controls and 22 Alcoholic Calcific Pancreatitis (ACP). RESULTS: The mean age of TCP patients and ACP was 34. 7 (SD 10) yrs and 43.7 (SD 8.9) yrs respectively. The percentage with monthly income less than Rs: 5000.00 was high in ACP (70%) compared to TCP (60%) which was similar to control group (58%). TI1e proportion of severe malnutrition {BM! <20) was comparable in TCP and ACP (72%) and was significantly higher (p<0.05) than control group (35%). Regularity of consumption of cassava for last 5 years was significantly (p<0.05) higher in ACP (35%) compared to 19% in TCP, and 4% in the control group. There was no difference in the consumption of red, green chilli, pepper, tea and coffee in the 3 groups. CONCLUSION: The above data indicate higher consumption of manioc by ACP than TCP. A long term study will assist in establishing the association of cassava consumption and malnutrition in Chronic Calcific Pancreatitis.Item Biochemistry for clinical medicine(Greenwich Medical Media, 2001) Thabrew, I.; Ayling, R. M.; Wicks, C.No abstract availableItem In vitro anticancer effect of gedunin on human teratocarcinomal (NTERA-2) cancer stem-like cells(Hindawi, 2017) Tharmarajah, L.; Samarakoon, S.R.; Ediriweera, M.K.; Piyathilaka, P.; Thennakoon, K.H.; Senathilake, K.S.; Rajagopalan, U.; Galhena, P.B.; Thabrew, I.Gedunin is one of the major compounds found in the neem tree (Azadirachta indica). In the present study, antiproliferative potential of gedunin was evaluated in human embryonal carcinoma cells (NTERA-2, a cancer stem cell model) and peripheral blood mononuclear cells (PBMCs), using Sulforhodamine (SRB) and WST-1 assays, respectively. The effects of gedunin on expression of heat shock protein 90 (HSP90), its cochaperone Cdc37, and HSP client proteins (AKT, ErbB2, and HSF1) were evaluated by real-time PCR. Effects of gedunin on apoptosis were evaluated by (a) apoptosis associated morphological changes, (b) caspase 3/7 expression, (c) DNA fragmentation, (d) TUNEL assay, and (e) real-time PCR of apoptosis related genes (Bax, p53, and survivin). Gedunin showed a promising antiproliferative effect in NTERA-2 cells with IC50 values of 14.59, 8.49, and 6.55 μg/mL at 24, 48, and 72 h after incubations, respectively, while exerting a minimal effect on PBMCs. Expression of HSP90, its client proteins, and survivin was inhibited and Bax and p53 were upregulated by gedunin. Apoptosis related morphological changes, DNA fragmentation, and increased caspase 3/7 activities confirmed the proapoptotic effects of gedunin. Collectively, results indicate that gedunin may be a good drug lead for treatment of chemo and radiotherapy resistant cancer stem cells.Item Anti-hepatocarcinogenic and anti-oxidant effects of mangrove plant scyphiphora hydrophyllace(Medknow Publications and Media, 2017) Samarakoon, S.R.; Shanmuganathan, C.; Ediriweera, M.K.; Piyathilaka, P.; Tennekoon, K.H.; Thabrew, I.; Galhena, P.; de Silva, E.D.CONTEXT: Scyphiphora hydrophyllacea is a shrub mangrove plant of the family Rubiaceae and not yet been studied for anti-hepatocarcinogenic effects. OBJECTIVES: We investigated possible in vitro anti-hepatocarcinogenic and antioxidant properties of S. hydrophyllacea. MATERIALS AND METHODS: Dried leaves of S. hydrophyllacea were sequentially extracted into hexane, chloroform, ethyl acetate, and methanol and tested for cytotoxicity on HepG2 cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and sulforhodamine B assays, and for antioxidant activities by the free radical 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid (ABTS) assays. Total phenolic and flavonoid contents were estimated in all four extracts. The hexane and chloroform extracts were tested for pro-apoptotic properties in HepG2 cells, and bioactive components were identified by gas chromatography-mass spectrometry (GC-MS) analysis. RESULTS: The hexane and chloroform extracts showed dose-dependent and time-dependent cytotoxic effects. Morphological changes observed under fluorescence microscope related to apoptosis, and significant (P < 0.001) increases in caspase 3 and 9 levels were observed in hexane and chloroform extract-treated cells. Slight DNA fragmentation was observed only in response to the chloroform extract. mRNA expressions of p53 and Bax were significantly upregulated by low doses of hexane and chloroform extracts. Highest antioxidant activity was observed in the methanol extract. GC-MS profiles identified 24 and four major compounds in the hexane and chloroform extracts, respectively. These included some known anticancer compounds such as lupeol. CONCLUSION: Cytotoxicity, antioxidant effects, and apoptosis-related changes exerted by hexane and chloroform extracts of S. hydrophyllacea concluded that these two extracts are good source for isolation of possible anticarcinogenic compounds. SUMMARY: The hexane and chloroform extracts of Scyphiphora hydrophyllacea showed dose-dependent and time-dependent cytotoxic effects.Morphological changes related to apoptosis and significant (P < 0.001) increases in caspase 3 and 9 levels were observed in hexane and chloroform extract-treated cells.mRNA expressions of p53 and Bax were significantly upregulated by low doses of hexane and chloroform extracts.Highest antioxidant activity was observed in the methanol extract.GC-MS profiles identified 24 and four major compounds in the hexane and chloroform extracts, respectively. Abbreviation used: DPPH: 1,1-diphenyl-2-picryl-hydrazyl, ABTS: 2,2'-azinobis-3-ethylbenzthiazoline-6-sulfonic acid, GC-MS: gas chromatography-mass spectrometry, DNA: deoxyribonucleic acid, HCC: Hepatocellular carcinoma, GAE: gallic acid equivalents, SRB: sulforhodamine B, MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, AO/EB: acridine orange/ethidium bromide, GAPDH: Glyceraldehyde 3-phosphate dehydrogenase, IC50: half maximal inhibitory concentration; QE: quercetin equivalents, HE: hexane extract, CE: chloroform extract, EAE: ethyl acetate extract, ME: methanolic extract, TPC: total polyphenol content, TFC: total flavonoid content, ANOVA: Analysis of variance.Item Anti-hepatocarcinogenic Ayurvedic herbal remedy reduces the extent of diethylnitrosamine-induced oxidative stress in rats(Medknow Publications, 2009) Galhena, P.B.; Thabrew, I.; Mayuri, G.T.; Vasanthi, A.H.R.Previous studies have shown that a decoction prepared from a mixture of Nigella sativa seeds, Hemidesmus indicus roots and Smilax glabrarhizome, has the potential to protect against diethylnitrosamine (DEN) induced hepatocarcinogenic changes in rats. The present in-vivo investigation with Wistar rats was conducted to determine whether the treatment with above decoction (6 g / kg / day) for a period of 10 weeks can provide protection against DEN (200 mg / kg by a single i.p. injection) mediated changes in (a) lipid peroxidation, (b) glutathione (GSH) concentration, (c) activities of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx), and (d) activity of the phase II detoxification enzyme glutathione S-transferase (GST). DEN administration resulted in a significant (p<0.05) enhancement (+ 46.2%) of lipid peroxidation (as assessed by formation of thiobarbituric acid reactive substances, TBARS), accompanied by a decreased GSH concentration (- 21.7% in liver; - 5.9% in blood), and activities of SOD (- 34.3%), GPx (- 49.1%) and GST (- 19.38%). Administration of the decoction to DEN treated animals resulted in a significant (p<0.05) reduction in TBARS production, along with a restoration towards the normal levels, of the other biochemical parameters evaluated. The overall results obtained suggests that, protection against DEN - mediated changes in oxidative stress and enhancement of the activities of enzymes participating in carcinogen detoxification are possible mechanisms utilized by the decoction to mediate its anti-hepatocarcinogenic action.Item Modulation of apoptosis in human hepatocellular carcinoma (HepG2 cells) by a standardized herbal decoction of Nigella sativa seeds, Hemidesmus indicus roots and Smilax glabra rhizomes with anti- hepatocarcinogenic effects(BioMed Central, 2012) Samarakoon, S.R.; Thabrew, I.; Galhena, P.B.; Tennekoon, K.H.BACKGROUND A standardized poly-herbal decoction of Nigella sativa seeds, Hemidesmus indicus roots and Smilax glabra rhizomes used traditionally in Sri Lanka for cancer therapy has been demonstrated previously, to have anti-hepatocarcinogenic potential. Cytotoxicity, antioxidant activity, anti-inflammatory activity, and up regulation of p53 and p21 activities are considered to be some of the possible mechanisms through which the above decoction may mediate its anti-hepatocarcinogenic action. The main aim of the present study was to determine whether apoptosis is also a major mechanism by which the decoction mediates its anti-hepatocarcinogenic action. METHODS Evaluation of apoptosis in HepG2 cells was carried out by (a) microscopic observations of cell morphology, (b) DNA fragmentation analysis, (c) activities of caspase 3 and 9, as well as by (d) analysis of the expression of pro-apoptotic (Bax) and anti-apoptotic (Bcl-2) proteins associated with cell death. RESULTS The results demonstrated that in HepG2 cells, the decoction can induce (a) DNA fragmentation and (b) characteristic morphological changes associated with apoptosis (nuclear condensation, membrane blebbing, nuclear fragmentation and apoptotic bodies). The decoction could also, in a time and dose dependent manner, up regulate the expression of the pro-apoptotic gene Bax and down regulate expression of anti-apoptotic Bcl-2 gene (as evident from RT-PCR analysis, immunohistochemistry and western blotting). Further, the decoction significantly (p < .001) enhanced the activities of caspase-3 and caspase-9 in a time and dose dependent manner. CONCLUSIONS Overall findings provide confirmatory evidence to demonstrate that the decoction may mediate its reported anti-hepatocarcinogenic effect, at least in part, through modulation of apoptosis.Item Effect of standardized decoction of Nigella sativa seed, Hemidesmusindicus root and Smilax glabra rhizome on the expression of p53 and p21 genes in human hepatoma cells (HepG2) and mouse liver with chemically-induced hepatocarcinogenesis(Pharmacotherapy Group, University of Benin, Nigeria, 2012) Samarakoon, S.R.; Thabrew, I.; Galhena, P.B.; Tennekoon, K.H.Purpose: To evaluate in vitro (using human hepatoma HepG2 cells) and in vivo (using mouse liver with diethlynitrosamine (DEN)-induced hepatocarcinogenesis) effect of a standardized decoction on the expression of p53 (tumour suppressor) and p21 (cyclin kinase inhibitor) genes with the long-term goal of developing the formulation into a globally acceptable therapy for hepatocellular carcinoma (HCC). Methods: The effect of the decoction on (a) mRNA and (b) protein expression of p53 and p21 genes in HepG2 cells and mouse livers with DEN-induced early hepatocarcinogenesis were evaluated by (a) reverse transcription PCR (RT-PCR) and (b) immunohistochemical and Western blot analysis, respectively. Results: The results demonstrated that the decoction significantly (p < 0.001) enhanced the expression of p53 and p21 genes in a time- and dose-dependent manner in HepG2 cells. A dose of 75 µg/ml significantly increased p53 mRNA at 24 and 48 h and p21 mRNA at 12, 24, 48 h of incubation with the decoction (p < 0.01). Induction of hepatocarcinogenesis in mice significantly increased hepatic expression of both p53 and p21 compared to distilled water control (p < 0.001), while treatment with the decoction further enhanced expression of both genes in DEN-induced hepatocarcinogenesis (p < 0.01). Conclusion: Overall, the findings demonstrate that the decoction may mediate its reported antihepatocarcinogenic effect, at least in part, through the modulating activities of genes involved in tumour suppression and cell cycle arrest.Item Gender issues among medical students in sri lanka: a preliminary Study(Sri Lanka Medical Association, 2000) de Silva, N.R.; Thabrew, I.; Saparamadu, P.A.M.; Jayawardena, D.K.R.C.OBJECTIVE: Find out if gender issues affect the progress of medical students ill Sri Lanka, METHOD: Students of the Medical Faculty, Kelahrya University, were given a questionnaire that explored gender issues in relation to academic and extracurricular activities in the Faculty. Results of examinations conducted by the Faculty in 1997 and 1998, and data published by the University Grants Commission on final examinations conducted by four other medical faculties in 1996 and 1997 were also analysed for sex-related differences using the X test for dichotomous variables. RESULTS: The questionnaire was completed by 651/855 (76.1%) of registered students, including 341 females. Overall, most (43.6-73.0%) felt that their training was not affected by gender, but 14-42% (both male and female) answered positively; the percentage increased significantly with seniority (X2for linear trend-16.483, p=0.005). Females were significantly less likely to participate in extracurricular activities (220/341 vs. 239/310, X2=12.36, p<0.001). The proportion of females who obtained classes were higher than that of males in 12/15 examinations analysed, with statistically significant differences in four (two in Kelaniya and one each in Peradeniya and Ruhuna). Higher proportions of males were referred / failed in all eight examinations analysed; the differences were statistically significant in rwo. CONCLUSIONS: A significant minority of medical students of both sexes in the Kelaniya University feels that their gender is a disadvantage to them during training. Female students appear to do marginally better than males in undergraduate examinations.