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Browsing by Author "Ratnatunga, N."

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    Hepatitis B virus markers in primary hepatocellular carcinoma
    (Faculty of Medicine, University of Peradeniya, Sri lanka, 1994) de Silva, H.J.; Ratnatunga, N.; Ramadasa, S.
    Based on serological studies, Sri Lanka has a relatively low Hepatitis B virus (HB V) [hepatitis B surface antigen (HBsAg)] carrier rate of 0.9% and a low prevalence of HBV (5-10%) among patients with primary hepatocellular carcinoma (PHC). To investigate this further we looked for HBV markers in PHC using more sensitive immunoliistochemical methods. Formalin fixed paraffin embedded tissue obtained from 18 PHCs were studied. Only 7 of the specimens contained non-tumour liver tis¬sue around the PHC, and evidence of cirrhosis was seen in 5 of them. Four micron thick sections of tissue were stained, with polyclonai antibod¬ies directed against HBsAg and hepatitis B core antigen (HBcAg) using a three stage immunoperoxidase technique (peroxidase-anti peroxidase). Positive control liver tissue was used in all experiments. HBsAg was detected in6(33.3%)of the 18 specimens (in the tumour tissue only in 3 speci¬mens, tumour tissue and surrounding cirrhotic liver tissue in 1. and surrounding cirrhotic liver tissue only and not in tumour tissue in 2 speci¬mens). The staining was cytoplasrnic. HBcAg was not detected in any of the tissue specimens tested. Nodatareg;irding serum alphafetoprotein levels were available from the patients medical records. From the preliminary results of this on going study, HBsAg markers appear to be more frequently associated with PHC than serological studies from Sri Lanka have indicated. HBV may, therefore, have arnore important aetiologi-cal role in PHC in this country than was previ¬ously believed.
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    An Investigation of the toxic effects of a herbal formulation with anti-carcinogenic properties
    (University of Colombo, 2005) Iddamaldeniya, S.; Wickremasinghe, S.M.D.N.; Thabrew, M.I.; Ratnatunga, N.; Tammitiyagodage, M.G.
    A decoction prepared from a mixture of Nigelld sativa seeds, Hemidesmus indicus root, and Smilax glabra rhizome used by some traditional medical practitioners in Sri Lanka is considered to be useful for the treatment of cancer patients. However, there is a lack of information about any adverse effects of this decoction. Experiments were carried out using Wistar rats and ICR mice as the experimental model, to evaluate any adverse effects mediated by the above decoction. Results of the investigations showed that administration of the decoction (at doses of 4g/kg body weight/day and 6g/kg body weight/day) to rats for three months had no adverse effects on the liver functions (as assessed by its effects on serum levels of alanine and aspartate aminotrans ferase and alkaline phosphatase) or haematological parameters (red blood cell count, white blood cell count, haemoglobin concentration, packed cell volume, mean corpuscular haemoglobin, mean corpuscular volume and mean corpuscular haemoglobin concentration). No significant pathological changes were observed in sections of the major body organs (liver, heart, lungs, stomach, duodenum and kidney) of animals treated with the decoction for three months. The investigations also demonstrated that the decoction did not have anti-ovulatory, an ti-implantation, spermicidal activity. An attempt to determine the LD50 concentration was unsuccessful. Even at a dose equivalent to 40 times (240g/kg/day) the normal therapeutic dose (6g/kg/day), no mortality or other toxic symptoms (loss of consciousness, salivation, muscle tremor, incoordination, hyperaesthesia, polyuria, anuria, polydipsea, defecation, piloerection, changes in locomotor activity, changes in posture, ataxia and loss of reflexes) were observed. Three month treatment with the decoction also did not produce any changes in average feed consumption, average body weight: liver weight ratios, or the general behaviour of the animals.
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    A Long-term investigation of the anti-hepatocarcinogenic potential of an indigenous medicine comprised of Nigella sativa, Hemidesmus indicus and Smilax glabra
    (BioMed Central, 2006) Iddamaldeniya, S.S.; Thabrew, M.I.; Wickramasinghe, S.M.D.N.; Ratnatunga, N.; Thammitiyagodage, M.G.
    BACKGROUND: A decoction comprised of Nigella sativa seeds, Hemidesmus indicus root bark and Smilax glabra rhizome is being recommended for cancer patients by a family of traditional medical practitioners of Sri Lanka. Previous investigations have demonstrated that a short term (10 weeks) treatment with the decoction can significantly inhibit diethylnitrosamine (DEN) mediated expression of Glutathione S-transferase P form (GST-P) in rat liver. The objective of the present investigation was to determine whether long term (16 months) treatment with the decoction would be successful in inhibiting in rat livers, not only DEN- mediated expression of GST-P, but also the carcinogen mediated development of overt tumours (OT) or histopathological changes leading to tumour development (HT). METHODS: Thirty-six male Wistar rats were divided into 3 groups of 12 each. Groups 1 and 2 were injected intraperitoneally (i.p) with DEN (200 mg/kg) while group 3 was injected normal saline (NS). Twenty-four hours later, decoction (DC; 6 g/kg body weight/day) was orally administered to group 1 rats, while groups 2 and 3 (DEN-control and normal control) were given distilled water (DW). Treatment with DC or DW continued for 16 months. At the end of the 9th month and 16th months (study 1 and study 2 respectively), six rats from each group were sacrificed, and livers observed for OT or HT, both visually and by subjecting liver sections to staining with Haemotoxylin and Eosin (H & E), Sweet's Silver stain (for reticulin fibers), Periodic Acid Schiff (PAS) staining (for glycogen), and immunohistochemical staining (for GST-P). RESULTS: At the end of 9 months (study 1) a hepatocellular adenoma (HA) developed in one of the rats in the DEN + DW treated group (group 2). At the end of 16 months (study 2), livers of all rats of group 2 developed OT and HT. Large areas of GST-P positive foci were also observed. No OT, HT or GST-P positive foci were detected in any of the other groups. CONCLUSION: Protection against DEN-mediated carcinogenic changes in rat liver can be achieved by long term treatment with the DC comprised of N. sativa seeds, S. glabra rhizome and H. indicus root bark.
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    Prevalence of hepatitis C virus markers in Sri Lankan patients with alcoholic cirrhosis
    (Blackwell Scientific Publications, 1994) de Silva, H.J.; Vitarana, T.; Ratnatunga, N.; Breschkin, A.; Withane, N.; Kularatne, W.N.S.
    A high prevalence of antibodies against hepatitis C virus (HCV) has been reported in patients with alcoholic cirrhosis. There are, however, doubts regarding the specificity of the first generation anti-HCV antibody assays used. We prospectively investigated HCV status in 47 Sri Lankan patients with alcoholic cirrhosis. A first generation assay (Ortho HCV enzyme-linked immunosorbent assay [ELISA]) and two second generation tests (Abbott HCV enzyme immunoassay and United Biomedical Incorporated HCV enzyme immunoassay) were used. Positive results were confirmed by the second generation recombinant immunoblot assay (RIBA 2). Of the 47 patients (46 males, mean age 41.7 years), 17 (36.2%) had previously had one or more blood or plasma transfusions. Seven (14.9%) of the samples were positive for anti-HCV antibodies using the Ortho-HCV ELISA, but only one (2.1%) sample was positive when tested with the second generation assays. The positive result was confirmed by RIBA 2. The prevalence of HCV in the patients was low despite many of them being exposed to blood or blood products. Hepatitis C virus, therefore, may not be an important pathogenic factor in alcoholic cirrhosis in Sri Lanka
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    Relationship between routine biochemical liver function tests and severity of liver damage in alcoholic patients
    (The Kandy Society of Medicine, 1993) de Silva, H.J.; Ratnatunga, N.; Wickremasinghe, A.R.; Kularatne, W.N.S.
    SUMMARY: The aim of this study was to investigate the relationship between routine biochemical liver function tests (LFT) that are perfoimed in Sri Lankan hospitals and the severity of liver damage (assessed histologically) in alcoholics. Results of routine LFT (serum bilirubin, SOFT, albumin and prothrombin time.) were correlated to histological changes in the liver in 50 (49 males and one female, mean age 46.6 years) out of 76 patients who were admitted to hospital with problems related to alcohol dependence. There was no mortality, and only minimal morbidity associated with the liver biopsy procedure. When 3 or more LFT were abnormal irreversible liver damage was always present histologically. When only 1 or 2 LFT were abnormal irreversible changes occurred in 42.9%. However, of 9 patients in whom all 4 LFT were normal, 7 (77.8%) had abnormal liver histology, including 4 (44.4%) with irreversible changes. Although there was a strong relationship between widespread abnormalities in routine LFT and irreversible liver damage, many patients with irreversible liver damage may have gone undetected if reliance was placed solely on these tests. Therefore, a liver biopsy is recommended for accurate assessment of the severity of liver damage in alcoholic patients.
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    Severe fatty change with hepatocellular necrosis following bite by a Russell's viper
    (Oxford University Press, 1992) de Silva, H.J.; Ratnatunga, N.; de Silva, U.; Kularatne, W.N.S.; Wijewickrema, R.
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    Traditional Remedy with possible antl-hepatocarclnogenlc potential
    (Sri Lanka Medical Association, 2004) Iddamaldeniya, S.S.; Thabrew, M.l.; Wickramasinghe, S.M.D.N.; Ratnatunga, N.; Thammitiyagodage, M.G.
    OBJECTIVES: To determine whether a decoction (DC) comprised of Nigella sativa seeds, Hemidesmus indicus root, and Srnilax glabra rhizome can protect against diethylnitrosamine (DEN) induced hepatocarcinogenesis (HC) as assessed by (i). Glutathione S-transferase P form (GST-P) expression in rat hepatocytes, and (ii). tumour development in rat livers. DESIGN, SETTING, AND METHODS: (i). Six groups of 10 rats each were used. Groups 1-4 were administered DEN (200mg/kg, i.p). Groups 1 and 2 received orally, DC at 4g/kg /day, and 6g/kg /day, respectively. Groups 3 and 4 received respectively, distilled water (DW), and garlic (20 g/kg /day). Groups 5 and 6 served as the Normal controls and DC controls, respectively. The number, area and staining intensity of GST-P + foci and the number of cells/cm2 of the + foci were recorded. (ii). Two groups of 6 rats each were injected with DEN (200mg/kg). Group 1 was fed with DC (6g/kg/day) for 16 months while group 2 received only DW. Livers were examined for overt tumours (OT) / tumour like lesions. Results; (i). The number and area of DEN- mediated GST-P positive foci, number of cells/cm of foci and staining intensity of the foci were significantly (P>0.001) reduced by the decoction and garlic in the order dose 2 = garlic >dose 1. (ii). OTs / tumour like lesions were observed in all DW fed rats but not in DC treated rats. CONCLUSION: The DC comprised of N. sativa, S. glabra and H. indicus has the potential to protect rat liver against DEN induced hepatocarcinogenesis.

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