Browsing by Author "Weerasinghe, S."

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Clinically helpful rickettsial disease diagnostic IgG titers in relation to duration of illness in an endemic setting in Sri Lanka
(Biomed Central, 2012) Premaratna, R.; Weerasinghe, S.; Ranaweera, A.; Chandrasena, T.G.A.N.; Bandara, N.W.; Dasch, G.A.; de Silva, H.J.
BACKGROUND: Although an initial IFA-IgG titer greater or equal to 1/64 or 1/128 is considered positive in presumptive diagnosis, in clinical practice in an endemic setting for rickettsioses in Sri Lanka, some patients with IFA-IgG titer of 1/128 for either spotted fever group (SFG) or scrub typhus (ST) did not respond to treatment. FINDINGS: To determine a clinically helpful diagnostic algorithm, IFA-IgG results of serologically confirmed treatment responders were analyzed in relation to duration of illness at sampling. Of 146 suspected SFG, 3 responders of 25 patients had titers ≤1/128 with < 7 days of illness while all 9 with titers ≥1/256 responded (false negative with 1/256 cutoff was 12%, false positive was 0%). For illness > 7 days, the false negative and positive rates were 4.3% (3/59) and 11.3% (6/53). Of 115 suspected ST, false negative and positive rates with ≥1/256 cutoff at <7 days of illness were 14.2% (2/14) and 0% (0/8) respectively while > 7 days, false negative and positive rates were 2% (1/51) and 0% (0/42). CONCLUSIONS: For clinical decision making, duration of illness at sampling is important in interpreting serology results in an endemic setting. If sample is obtained ≤7 day of illness, an IgG titer of ≤1/128 requires a follow up sample in the diagnosis and > 7 days of illness, a single ≥1/256 titer is diagnostic for all ST and 90% of SFG.
A computational approach to identify suitable compounds from Sri Lankan flora envisaging remedial therapy for selected neurodegenerative diseases.
(International Research Symposium on Pure and Applied Sciences, 2017 Faculty of Science, University of Kelaniya, Sri Lanka., 2017) Thiruchittampalam, S.; Weerasinghe, S.
Gaining understanding of neurological disorders affecting a large number of people worldwide, contemplating lower quality of life of patients and their caregivers, would reduce the burden on the society. Neurodegenerative disorders, Alzheimer’s (AD), Parkinson’s (PD), prion and Huntington’s (HD) disorders are known to be caused by main common factors; oxidative stress, protein misfolding and aggregation triggered by metal accumulation. Since the metal ions have to be the prime consideration, chelation therapy is a plausible approach to restore metal balance. Therefore, apt metal binding ligands are categorized from an existing database of 200 chemical compounds identified from Sri Lankan flora, particularly for Fe3+, Cu2+, Zn2+ and Al3+ ions via a computational approach to be used as lead compounds for drug development. Screened compounds were evaluated regarding binding free energy with the aid of umbrella sampling molecular dynamics (MD) where 13 numbers of similar simulation system was restrained with harmonic potential along a reaction coordinate (z) assigned. Here, the reaction coordinate is the distance between the center of mass of the ligand and the metal ion. The MD simulations were performed using GROMACS 4.5.1 program on the LINUX operating system. The potential of mean force was computed using the weighted histogram analysis method (WHAM) from the independent trajectories of 13 windows. Upshots of the WHAM technique are given below in the figure. Overlap of neighbouring windows from the Figure ensures there are sufficient windows to cover the entire reaction coordinate space. The free energy change upon binding has been inferred from the inset of the Figure. Free energy calculations reveal number of compounds might possess the potential to alleviate the symptoms of AD (15 compounds) PD (13 compounds) and prion disease (6 compounds) which should be further analysed in an interdisciplinary way. Furthermore, it indicates no suitable compound for HD from the 200 compounds incorporated in this research. Moreover, this study upholds molecular dynamics simulation output viable within the expected time period.
The Health and nutritional status of school children in two rural communities in Sri Lanka
(Blackwell Scientific Publications, 2000) Fernando, S.D.; Paranavitane, S.R.; Rajakaruna, J.; Weerasinghe, S.; Silva, D.; Wickremasinghe, A.R.
There is growing evidence of considerable burden of morbidity and mortality due to infectious diseases and undernutrition in school children. This study describes the nutritional status and parasitic infections of school children in two areas of rural Sri Lanka. All children in four primary schools in the Moneragala district of Sri Lanka were included in the study. The height and weight of children were measured and anthropometric indices calculated. Stool and blood samples were examined for evidence of intestinal helminthiasis, malaria and anaemia. A greater proportion of boys than girls were underweight, wasted and stunted. Over 80 percent of the children were anaemic but did not apparently have iron deficiency anaemia according to their blood picture. The prevalence of parasitic infections such as hookworm and Plasmodium spp that may contribute to anaemia was low.
The Impact of Organizational Culture on Employee Engagement: with Special Reference to Library System of State Universities in Sri Lanka
(Department of Library and Information Science, University of Kelaniya, Sri Lanka, 2023) De Silva, M.T.C.N.S.; Weerasinghe, S.
Culture in organizations is considered as one amongst the most significant factors that results in the creation of a competitive advantage. An organizational culture which is highly effective also leads to the creation of superior levels of engagement and effectiveness amongst the employees which translates into high levels of productivity. Most of the past studies have concentrated on the link between organizational culture and employee engagement or have treated the concepts separately. Relatively very few studies have focused on the impact of organizational culture on employee engagement. There is a lack of empirical evidence that directly addresses this type of investigation, especially in Sri Lanka and particularly in the library field. Through this study, researchers intend to identify the salient dimension of organizational culture and assess the impact of organization culture on employee engagement with special reference to the Library system in Sri Lanka. This study is descriptive, correlation and conclusive in nature. To collect data, a sample of library academics attached to state universities in Sri Lanka (n=100) was selected by using the convenience sampling method. It was revealed that organizational culture had a strong and significant influence on employee engagement. The findings of this study contribute to the existing literature in the aspects of service quality and employee behavior. Also, the results can be used in developing strategies to enhance the level of service quality in libraries, particularly in the areas of training and development, creating new roles and responsibilities and maintaining an effective database system and information systems. These strategies will ultimately lead libraries to enhance the positive and motivated work environment, contributing to the stability and prosperity of higher education of Sri Lanka.
Influence of non-alcoholic fatty liver disease on the development of diabetes mellitus
(Wiley-Blackwell, 2013) Kasturiratne, A.; Weerasinghe, S.; Dassanayake, A.S.; Rajindrajith, S.; de Silva, A.P.; Kato, N.; Wickremasinghe, A.R.; de Silva, H.J.
BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is linked to metabolic syndrome, and is known to be associated with impaired fasting glycemia and diabetes mellitus. This prospective community-based study was conducted to determine the association between NAFLD and incidence of diabetes mellitus in an urban adult population in Sri Lanka. METHODS: Participants of the Ragama Health Study cohort were assessed for NAFLD using established ultrasound criteria in 2007. Those who were free of diabetes at baseline were followed up for 3 years. Incidence rates of diabetes mellitus were compared between subjects with and without NAFLD at baseline. RESULTS: Out of 2984 subjects, 926 had NAFLD and 676 had diabetes in 2007. Of the 2276 subjects who were free of diabetes in 2007, 1914 were re-assessed in 2010. After 3 years, 104 out of 528 subjects with NAFLD and 138 out of 1314 subjects without NAFLD had developed diabetes mellitus de novo. Incidence rates of diabetes were respectively 64.2 and 34 per 1000 person-years of follow up for those with and without NAFLD. NAFLD was an independent predictor of developing diabetes mellitus. Other independent predictors were impaired fasting glycemia and dyslipidemia. CONCLUSIONS: Subjects with ultrasonically diagnosed NAFLD have an increased risk of developing diabetes mellitus. Intervention for NAFLD through lifestyle modification may prevent progression of the current diabetes epidemic. © 2012 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.
Long-term survival of a patient with single atrium and single ventricular heart: a case report
(Sri Lanka Medical Association, 2018) Lohithalingam, P.; Lakmini, K.M.S.; Weerasinghe, S.; Pereira, T.; Premaratna, R.
Petchicine, a novel human DNMT enzyme inhibitor isolated from Sri Lankan medicinal plant: An in-silico approach
(Faculty of Science, University of Kelaniya, Sri Lanka, 2021) Dushanan, R.; Weerasinghe, S.; Dissanayake, D. P.; Senthilnithy, R.
The genetic information of humans has been regulating by various epigenetic mechanisms, which are stable and reversible. DNA methyltransferase (DNMT) is an enzyme that methylates the fifth carbon of the cytosine residue in DNA. Therefore, the methylated DNA interacts with the chromatins through the methyl-binding proteins, which leads to a cancer state. Many recent studies prove that inhibition of DNMT contributes to control cancer growth. Therefore, DNMT inhibitors have been considered as developed anticancer agents. The studies on the inhibition of the DNMT enzyme are an up-and-coming developing area for cancer therapy. Azacitidine is an approved DNMT inhibitor by the Food and Drug Administration. This work focuses on studying the impact of Azacitidine on the stability of the DNMT through computational techniques and, by performing the comparative study, suggest a new potent compound to inhibit the DNMT enzyme. These techniques can be used to investigate atomic-level descriptions of drug binding sites and how the DNMT inhibitors change the enzyme's active site. The crystal structure of the DNMT enzyme was downloaded from the Protein Data Bank, and the structure of Azacitidine was optimized by CBS-QB3 method using the G09W package. The non-toxic new compounds, Petchicine and Ouregidione, were obtained from the Sri Lanka flora database. The docking studies followed by molecular dynamics simulation were carried out to perform trajectory analysis. The results of RMSD, Rg, and hydrogen bond analysis are used to compare the behavior of the DNMT-Petchicine and DNMT-Ouregidione with the DNMT-Azacitidine complex in the aqueous environment. The results reveal that all the DNMT-inhibitor complexes attain a stable conformation during the simulation time. However, the results clearly show that the new compound Petchicine is more effective than the reference inhibitor Azacitidine; therefore, further investigations on Petchicine in future clinical trials would yield more promising results in the treatment of epigenetically caused cancer.
Protection against malaria in toque mokeys immunized with p.cynomolgi MSP1inv in alum
(Sri Lanka Association for the Advancement of Science, 2000) Amaratunga, C.; Nandasiri, K.; Weerasinghe, S.; Manamperi, A.; Holm, I.; Longacre, S.; Handunnetti, S.
Immunization of toque monkeys with baculovirus-expressed, His-tagged recombinant plasmodium cynomoigi ceylonensis (Pcc) C-terminal 19 kDa proteins of the major merozoite surface protein 1 (MSP1inv) with Freunds adjuvant, mediates long-term protection against homologous and heterologous p. cynomolgi blood-stage challenge infection. However, Freunds adjuvant is unsuitable for use in humans, which necessitates the testing of alternative adjuvants. Antigen-alum formulation and binding was optimized for the new preparation of matalloaffinity-purified MSP1inv antigen, under conditions acceptable for human trails, including 800ug aluminium per dose, in accordance with the permitted FDA maximum. This formulation was used in an immunization trial using the p. cynomolgi-toque monkeys system, which is analogous to the p.vivax-human system. Group 1 comprising 4 animals were immunized with alum+MSP1inv , and group 2 comprising 3 monkeys received alum alone. Four doses of immunization were given intramuscularly at 0,1,3 and 4 month intervals. After immunization, the anti-MSP1inv antibody titres of immunized animals reached 2.8x104 . all animals were given a homologous Pcc challenge infection one month after the last dose of immunization. One of the four immunized animals was completely protected while the other 3 animals showed low patent parasitaemia, resulting In an overall partially protective effect (p=0.02). immunization with alum did not result in sterile immunity, as seen with Freunds, where antibody titres range from 106 - 107 . Following treatment, the animals were given a second heterologous, blood-stage challenge infection of p.cynomolgi Gombak, (PcG) four months after the first challenge infection. Sequence analysis of PcG DNA reveald a single amino acid differing from that of Pcc. The substitution which occurs at the nt 207 position in the C-terminal 19-kDa sequence changes the amino acid glutamate into lysine. Statistically significant partial protection was observed in the immunized animals (p=0.04), despite having a lower titre of antibodies (3.3x103) at the time of re-challenge. Together with sequence data, this documents the ability of recombinant MSG1inv to protect against a heterologous infection.
Protection against malaria in toque monkeys immunized with P. cynomolgi MSPI-19 in alum
(The royal society of tropical medicine and hygiene, British society for parasitology, The American society of tropical medicine and hygiene, 2000) Amaratunga, C.; Nandasiri, K.; Weerasinghe, S.; Manamperi, A.; Longacre, S.; Holm, I.; Handunnetti, S.
In a pre-clinical trail of a vaccine against P.vivax malaria, toque monkeys were immunized with matalloaffinity-purified baculovirus-expressed. His-tagged recombinant Plasmodium cynomolgy ceylonensis (Pcc) C-terminal 19 kDa protiens of the major merozoite surface protein 1 (MSP1p19) with alum, under conditions acceptable for clinical trials. The P. cynomolgi-toque monkey system is highly analogous to P.vivax in humans. Eight animals were immunized with alum+MSP1p19 and 3 monkeys received alum alone. After four doses, the anti-MSP1p19 antibody titres of immunized animals reached 2.8x104. all animals were challenged with Pcc asexual blood stage parasites. The immunized animals showed significant, partial protection (p=0.0024). Four of these animals were given a second heterologous challenge infection of p.cynomolgi Gombak, (PcG) four months after the first challenge infection. Sequence analysis of PcG DNA revealed a single amino acid challenge differing from that of Pcc. The substitution which occurs at the nt 207 position in the C-terminal 19-kDa sequence changes the amino acid glutamate into lysine. Statistically significant protection was observed in the immunized animals (p=0.04), despite having a lower titre of antibodies at the time of re-challenge. This documents the ability of recombinant MSP1p19 with alum to protect against Pcc and PcG infections.
Sensitization patterns of allergens among asthmatics in Sri Lanka
(Lippincott Williams & Wilkins, 2007) Weerasinghe, A.; Weerasinghe, S.; Amarasena, M.; Medagoda, K.; Katelaris, C.H.
Introduction: The sensitization pattern among asthmatics in Sri Lanka is unknown. Objectives: To determine the sensitization pattern among asthmatics in Sri Lanka. Methodology: The study was carried out in forty physician-diagnosed asthmatic patients. Twenty two non-asthmatics were recruited as controls. Sensitization to 12 allergens was assessed by skin prick test using standardized allergen extracts. A skin wheal diameter, 3mm greater than the negative control was considered a positive reaction. Results: The mean age of asthmatics was 32.4 years (range 9Y59) and 57.5% were males. The mean age of controls was 32.2 years (range 14Y58) and 59.1% were males. The analysis of the data showed that 97.5% asthmatics had positive skin reaction to at least one allergen compared to 72.7% prevalence in the control group. The common allergens among asthmatics were Dermatophagoides pteronyssinus (77.5%), blomia (65.5%), cockroach (55%), storage mite (35%), latex (20%)), cat fur (17.5%), aspergillus (12.5%), grass pollen (12.5%), cow’s milk (12.5%) egg white (10%) cereals (7.5%) and dog hair (5.%). The pattern of sensitization among non-asthmatics was Dermatophagoides pteronyssinus (54.5%), cockroach (50%), blomia (36.4%), aspergillus (36.4%), grass pollen (27.3%), storage mite (22.7%), cow`s milk (18.2%), latex (13.6%), egg white (13.6%), cereals (13.6%), dog hair (9.1%) and cat fur (9.1%). Sixty two percent (n = 25) of the asthmatics had at least one other allergic manifestation while non-asthmatics with other allergic manifestation were 36.4% (n = 8). Other allergic manifestations in the asthmatic group were rhinitis alone 22 (55%), eczema alone 1(2.5%) and both rhinitis & eczema 2(5%) whereas in the non-asthmatic group it was rhinitis alone 7 (31%), eczema alone 0% and both rhinitis and eczema 1(4.5%). The pattern of sensitization for mites alone, cockroaches alone and mites and cockroaches in the asthmatic group with rhinitis (n = 24) was 23 (57%), 11(27%) and 11(27%) and in the non-asthmatic group with rhinitis (n = 7) was 3 (13%), 4 (18%) and 3 (13%) respectively. Conclusion: The results show that mites, and cockroaches are the most common sensitizing allergens in asthmatics and the commonest association of asthma was rhinitis in Sri Lanka.