University of Colombo e-Repository

UCER (University of Colombo Electronic Repository) is a collection of scientific research publications by researchers at the University of Colombo, Sri Lanka. This e-Repository serves to manage, preserve and make available the academic works of the faculty, postgraduate students, and research groups. The collection includes faculty publications, master's and doctoral theses abstracts. This repository is updated regularly, and new works are added to collections on a continuous basis

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Recent Submissions

A descriptive study of the genetic aetiology of rare and undiagnosed disorders in a cohort of Sri Lankan patients
(University of Colombo, 2021) Fernando, M.P.S.; Senevirathne, A.M.D.S.R.U.; Niman, K.V.H.; Pirannavan, R.; Anandagoda, G.G.; Hettiarachchi, D.; Wetthasinghe, K.T.; Sirisena, N.D.; Dissanayake, V.H.W.
Introduction: Today it is possible to detect the underlying genetic aetiology of rare and undiagnosed disorders using Whole Exome Sequencing (WES) without the need to sequence genes separately reducing the time from presentation to diagnosis. The objective of this study was to report the genetic aetiology of patients with rare undiagnosed disorders undergoing WES in the Human Genetics Unit, Colombo. Methods: A database of patients tested in our unit consisting of phenotype and genotype data was maintained prospectively from 13th November 2014 to 26th March 2021 and analysed retrospectively. Genotype data was generated by Illumina HiSeq platform. Results: 123 patients were sequenced. 75 (61%) were male. Age ranged from 14 days to 18 years. The genetic aetiology was confirmed in 58 (47.2%). 27 (22%) had novel variants. The systems affected, the total number and percentage of patients, the number and percentage of patients diagnosed and the total number with novel variants in each system respectively were: neurological, 66 (53.7%), 30 (45.5%), 17; musculoskeletal, 16 (13.0%%), 7 (43.8%), 2; multisystem, 16 (13.0%), 5 (31.3%), 2; eye, 7 (5.7%), 6 (85.7%), 3; metabolic, 7 (5.7%), 5 (71.4%), 2; blood and lymphoreticular, 4 (3.3%), 0 (0%), 0; cardiovascular, 3 (2.4%), 2 (66.7%), 0; skin, 2 (1.6%), 2 (100%), 1; gastrointestinal, 1 (0.8%), 1 (100%), 0 and renal, 1 (0.8%), 0 (0%) 0. In those with a definitive diagnosis, a pathogenic variant related to an autosomal dominant condition was found in 30 (51.7%); an autosomal recessive condition in 23 (39.7%); an x-linked dominant condition in 2 (3.4%) and an x-linked recessive condition in 3 (5.2%) Conclusion: The use of WES has made it possible to arrive at the genetic aetiology in nearly half of the patients with rare and undiagnosed disorders tested in our Unit. It has led to early diagnosis, accurate prognostication and appropriate treatment of these patients.
Isolation of a potential anti-cancer compound from Mangifera zeylanica leaves and investigation of its effects
(University of Colombo, 2023) Perera, A.A.D.N.; Samarakoon, S.R.; Ediriweera, M.K.; Tennekoon, K.H.
Lung cancer has been estimated to cause the highest number of cancer deaths in 2023. Of two subtypes of lung cancer, Non-Small Cell Lung Cancer (NSCLC) is the most frequently reported. Currently used treatment options for NSCLC are chemotherapy, radiotherapy and surgery. However, chemo- and radio- therapies result in severe side effects. Therefore, invention of new treatment strategies for NSCLC is timely needed. Investigations on plant derived compounds is becoming a promising approach for discovering potential anti-cancer drug leads. Mangifera zeylanica (family: Anacardiaceae) is a plant endemic to Sri Lanka and used for cancer treatment in traditional medicine. We have previously reported that the chloroform extract of M. zeylanica leaves is cytotoxic to non-small cell lung cancer cells (NCI-H292) with less cytotoxicity to normal lung fibroblasts. In the present study we isolated an active compound (B-II-c-a) from the chloroform extract using silica-gel column chromatography, size exclusion chromatography and reversed phase preparative high performance liquid hromatography. Cytotoxicity of B-II-c-a on NCI-H292 cells was evaluated using Sulforhodamin B (SRB) assay. The effects of B-II-c-a on cell migration and colony formation was investigated using wound healing assay and colony formation assay respectively. Assessment of potential apoptotic effects of B-II-c-a was carried out using Ethidium Bromide/Acridine Orange (AO/EB) staining. The compound B-II-c-a showed cytotoxic effects on NCI-H292 NSCLC cells and MRC-5 normal lung fibroblast cells following 24h exposure (IC50 of 3.22 μg/mL and 7.83 μg/mL respectively). Moreover B-II-c-a resulted in inhibition of colony formation and cell migration. AO/EB staining revealed that B-II-c-a induces apoptosis in NCI-2H92 cells. Structure determination of B-II-c-a is currently in progress. Keywords: SRB assay; Non-Small Cell Lung Cancer; anti-cancer This work was supported by the Ministry of Science, Technology and Research, Sri Lanka (Grant No: MSTR/TRD/AGR/3/02/08) and constitutes a part of the PhD studies of PAADN.
Design and implementation of a novel assay for a selected SERPINC1 Gene Variant in a cohort of portal vein thrombosis patients in the Sri Lankan population
(University of Colombo, 2021) Edirisinghe, E.M.D.T.; Noordeen, N.; Wetthasinghe, T.K.; Dissanayake, V.H.W.
Introduction: Portal vein thrombosis (PVT), is a thromboembolic disorder with a genetic etiology. In developing countries, PVT presents in 40% of portal hypertension cases. Anti-thrombin (AT) deficiency is a major risk factor for venous thromboembolic disorders. The SERPINC1 gene encodes AT-III, a protease inhibitor. A comprehensive literature review revealed that a variant of the SERPINC1 gene (rs2227589, g.5301G>A), is associated with an increased risk of thrombosis in South Asian populations. The objective of this study was to design and implement an assay for determining the presence of the SERPINC1 gene variant in a cohort of PVT patients. Methods: The study population comprised of 80 PVT diagnosed individuals, who were referred to the Human Genetics Unit, Faculty of Medicine, University of Colombo, for genetic screening. Their blood samples were acquisitioned following ethical clearance. DNA extraction was conducted by a silica membrane based nucleic acid purification technique. A novel tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) assay was designed and optimized to genotype the SERPINC1 gene variant. The optimization included a gradient PCR to detect the optimum melting temperature and also primer concentration series to detect the optimum primer concentrations. The optimized protocol was validated by Sanger sequencing. Results: The presence of two simultaneous peaks at the desired location in the Sanger chromatogram confirmed the PCR protocol. The allele frequency for the normal variant (G/G) and the heterozygous variant (G/A) was 62.4% and 31.2%, respectively. No homozygotes for the pathogenic variant were identified. The minor allele frequency for the g.5301G>A genotype was 0.01 (p=0.90) according to the Hardy Weinberg equilibrium. Conclusions: The designed T-ARMS-PCR assay can be implemented to genotype the SERPINC1 gene variant. Strong conclusions regarding the sensitivity and specificity cannot be drawn from a single study using a small sample size. Furthermore, no homozygotes for the pathogenic variant were detected in this study.
Effects of long-term meditation on telomere length, and plasma telomerase level: a case control study
(University of Colombo, 2021) Dasanayaka, N.N.; Sirisena, N.D.; Samaranayake, N.
Introduction: Meditation is being increasingly known as a practice of health promotion which enables the relationship between the human mind and body. A growing body of research suggested that long-term meditation practice has been popularized among multidisciplinary scientific communities due to its wide array of benefits including enhanced telomere maintainance. This study aims to compare the telomere length, and the levels of plasma telomerase enzyme between long-term meditators and controls. Method: In this case control study long-term meditators who practised meditation for more than 3 years were recruited from meditation centres in Sri Lanka and age, and gender matched controls (non-meditators) were recruited from the community using purposive sampling. Blood was collected into an Ethylenediaminetetraacetate (EDTA) tube using the venepuncture method. DNA was extracted from the buffy coat using a commercially available kit. Telomere length was measured via quantitative polymerase chain reaction using Absolute Human Telomere Length Quantification qPCR Assay Kit and plasma telomerase levels were measured using Human TE (Telomerase) Enzyme-linked Immunosorbent Assay (ELISA) Kit. Socio-demographic data were collected. Independent sample t-test was used to compare the mean relative telomere length, and plasma telomerase level between meditators and controls. Results: Twenty six of the 36 participants (72.2%) were male and the mean age ± standard deviation (SD) of the meditators and controls were 42.78 ± 9.8 and 42.83 ± 9.78 years, respectively. Average telomere length (meditators: mean ± SD=10.32 ±1.10 kb; controls: mean ± SD=6.82±0.65 kb; p=0.010) and telomerase level (meditators: mean ± SD=9.82 ±1.99 ng/mL; controls: mean ± SD=8.06±1.57 ng/mL; p=0.026) was significantly higher in meditators compared to controls. Conclusion: The findings of this study suggest that long-term meditation practice may have potentially beneficial effects on the telomere length and telomerase level and thus, delay cellular ageing.
The use of Caralluma fimbriata as an appetite suppressant and weight loss supplement: A systematic review and meta-analysis of clinical trials
(Springer Nature, 2021) Jayawardena, R.; Francis, T.V.; Abhayaratna, S.; Ranasinghe, P.
Introduction: Obesity prevalence has increased during the past few decades, causing a pandemic with an influx in other co-morbidities. Many factors influence weight gain in an obesogenic environment therefore strategies for treating obesity may vary from conventional dietary and physical activity interventions to pharmacotherapy. A shift in unconventional strategies as herbal products for treating obesity have been investigated and one such plant extract is Caralluma fimbriata (C. fimbriata), found as supplements in the form of capsules or powder sachets. The potential effects of C. fimbriata as an appetite suppressant and weight loss supplement was systematically reviewed by the studies included. Methods: A systematic review of clinical trials reporting the effects of C. fimbriata as appetite suppression and anti-obesity supplement was reported according to PRISMA guidelines. Data were obtained by searching three databases: PubMed®, Web of Science® and SciVerse Scopus® for studies published until 30th April 2020. Results: A total of 7 articles studying C. fimbriata satisfied the inclusion and exclusion criteria and belonged to various countries including Australia (3), Cuba (1), India (2) and Spain (1). Almost all studies recruited adults either overweight or obese with a BMI > 25kg/m2 (n=5). Parameters assessing obesity, biochemical and appetite factors were analysed via a meta-analysis. Compared to placebo group, C. fimbriata extract significantly reduced WC by 1.59 cm (95% CI, -3.07 to -0.10, p = 0.041) and WHR by 0.06 (95% CI, -0.12 to -0.01, p = 0.05) with no significant effects on BW, BMI and HC. Biochemical and appetite parameters outcome with C. fimbriata. had no significant changes. Side effects of the extract were reported by few studies, most common effects were constipation, diarrhoea, nausea and rashes. Conclusion: Appetite parameters showed no significant changes and metabolic parameters did not improve with C. fimbriata supplementation therefore it is unlikely to recommend C. fimbriata as a weight loss supplement and an appetite suppressant.