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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty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 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 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.Item A Comparison of the cytotoxic potential of standardized aqueous and ethanolic extracts of a polyherbal mixture comprised of Nigella sativa (seeds), Hemidesmus indicus (roots) and Smilax glabra (rhizome)(Medknow Publications, 2010) Samarakoon, S.R.; Thabrew, I.; Galhena, P.B.; de Silva, D.; Tennekoon, K.H.BACKGROUND: A decoction (hot-water extract) comprised of Nigella sativa (seeds), Hemidesmus indicus (roots), and Smilax glabra (rhizome) has been reported to prevent chemically-induced hepatocarcinogenic changes in rats and to exert significant cytotoxic effects on human hepatoma (HepG2) cells. However, the decoction used in previous studies to determine cytotoxicity was not standardized. Further, during preparation of pharmaceuticals for clinical use, it is more convenient to use an ethanolic extract. Therefore this study was carried out to (a) develop standardizedaqueous and ethanolic extracts of the plant mixture (N. sativa, H. indicus, and S. glabra) used in the preparation of the original decoction, and (b) compare the cytotoxic effects of these two extracts by evaluating cytotoxicity to the human hepatoma (HepG2) cell line. METHODS: Aqueous and ethanolic extracts have been standardized by evaluating organoleptic characters, physicochemical properties, qualitative and quantitative analysis of chemical constituents, and analysis of High Performance Liquid Chromatography (HPLC) and Thin Layer Chromatography (TLC) profiles. Cytotoxic potentials of the above standardized extracts were compared by evaluating their effects on the survival and overall cell activity of HepG2 cells by use of the 3-(4, 5-dimethylthiazol-2yl) -2, 5 - biphenyl tetrazolium bromide (MTT) and Sulphorhodamine B (SRB) assays. RESULTS: Results from MTT and SRB assays demonstrated that both extracts exerted strong dose-dependent in vitro cytotoxicity to HepG2 cells. The standardized aqueous extract showed a marginally (though significantly, P<0.05) higher cyotoxic potential than the ethanolic extract. Thymoquinone, an already known cytotoxic compound isolated from N. sativa seeds was only observed in the standardized ethanolic extract. Thus, compounds other than thymoquinone appear to mediate the cytotoxicity of the standardized aqueous extract of this poly-herbal preparation. CONCLUSION: It may be concluded that results obtained in the present study could be used as a diagnostic tool for the correct identification of these aqueous or ethanolic extracts and would be useful for the preparation of a standardized pharmaceutical product that may be used in the future for clinical therapy of hepatocellular carcinoma.Item Descriptive study of chronic calcific pancreatitis in Sri Lanka(Sri Lanka Medical Association, 2005) de Silva, M.; Selliah, S.; Thabrew, I.OBJECTIVES: To describe the potential risk factors, clinical features, biochemical and radiological features, and management of chronic calcific pancreatitis. DESIGN: Cross-sectional descriptive study. SETTING: Tertiary care general hospital. PATIENTS: Fifty patients with pancreatic calcification referred to the Colombo South Teaching Hospital, and 50 age-matched controls from healthy relatives or friends of the patients. MEASUREMENT: Height and weight measurements, immunoreactive insulin levels and trypsin levels of duodenal aspirates were estimated. Plain abdominal xray and ultrasonography were performed. INTERVENTION: Endoscopic retrograde cholangiopancreaticography (ERCP) was attempted on all patients during which duodenal aspirates were collected. Success rates of ERCP and response to endotherapeutic procedures were recorded. RESULTS: Twenty two of the 50 chronic calcific pancreatitis (CP) patients were diagnosed to have chronic alcoholic calcific pancreatitis(CACP). Mean age of the CACP patients was significantly higher than that of the chronic calcific pancreatitis of the tropics (CCPT) patients. Severe malnutrition (BMI < 20), frequent consumption of Manihot esculenta (manioc, cassava) and a high consumption of chilli or pepper were identified as possible risk factors for both alcoholic and non-alcoholic CP. Onset of diabetes occurred at a much younger age in the CCPT group than in the CACP group. Mean serum insulin was significantly higher in the CCPT group than in the CACP group and duodenal trypsin level was significantly lower in the CCPT than in CACP group. CONCLUSIONS: Our results confirm the existence of both alcoholic (CACP) and non-alcoholic (CCPT) types of chronic calcific pancreatitis in Sri Lanka. A larger study is required to confirm the associated risk factors such as Manihot esculenta and foods with a high content of chilli or pepperItem Iron absorption from a traditio nal Sri Lankan weaning food and the enhancing effect of ascorbic acid in adult male volunteers(Sri Lanka Medical Association, 1996) Liyanage, C.; Goonaratna, C.; Thabrew, I.OBJECTIVE:To study absorption of iron from Centella gruel and the enhancing effect of ascorbic acid in young adult males.DESIGN: An in vivo absorption study. SETTING: Faculty of Medicine, Galle. METHODS: The percentage of iron absorbed from the Centella gruel was measured using a double isotope technique with 55Fe and 59Fe on 10 healthy male volunteers. OUTCOME MEASURE: Percentage of iron absorption from the gruel with and without ascorbic acid. RESULTS: The mean iron absorption from each meal of Centella gruel was 2.2% (SEM 0.8). This increased to 5% (SEM 1.6) by addition of 50 mg ascorbic acid. When ingested with ascorbic acid, the bioavailable nutrient density (BND) of the weaning food was increased from 0.23 to 0.53 mg iron/1,000 kcal. To satisfy the daily physiological requirements of iron in infants and toddlers, it was calculated that apart from ascorbic acid supplementation, the total iron content also needs to be increased from 2.05 mg to 4.0 mg/meal. CONCLUSION: Centella gruel cannot provide the amount of iron to meet the BND for iron required by infants and toddlers, unless supplemented with an enhancer of iron absorption such as ascorbic acid and its total iron content is increased.Item Does Aerua lanata have diuretic properties?(Dept. of Physiology, All-India Institute Of Medical Sciences, 1993) Goonaratna, C.; Thabrew, I.; Wijewardene, K.We have compared the diuretic activity of 200 ml of sucrose flavoured aqueous extract of the herb Aerua lanata with that of 200 ml sucrose flavoured weak infusion of tea leaves, and 200 ml of water, in 14 healthy volunteers under standardized conditions. Each volunteer acted as his or her own control in the three protocols, and chemical, physical and statistical analyses were performed "blind" by coding all urine and blood samples collected. A. lanata extract did not significantly increase urine flow, sodium excretion, potassium excretion, or urine and plasma osmolality as compared to an infusion of tea or plain water.