Journal/Magazine Articles
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This collection contains original research articles, review articles and case reports published in local and international peer reviewed journals by the staff members of the Faculty of Medicine
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Item Proteome profiling of cutaneous leishmaniasis lesions due to dermotropic Leishmania donovani in Sri Lanka(BioMed Central, 2024) Manamperi, N.H.; Edirisinghe, N.M.; Wijesinghe, H.; Pathiraja, L.; Pathirana, N.; Wanasinghe, V.S.; De Silva, C.G.; Abeyewickreme, W.; Karunaweera, N.D.BACKGROUND Characterization of the host response in cutaneous leishmaniasis (CL) through proteome profiling has gained limited insights into leishmaniasis research compared to that of the parasite. The primary objective of this study was to comprehensively analyze the proteomic profile of the skin lesions tissues in patients with CL, by mass spectrometry, and subsequent validation of these findings through immunohistochemical methods.METHODS Eight lesion specimens from leishmaniasis-confirmed patients and eight control skin biopsies were processed for proteomic profiling by mass spectrometry. Formalin-fixed paraffin-embedded lesion specimens from thirty patients and six control skin specimens were used for Immunohistochemistry (IHC) staining. Statistical analyses were carried out using SPSS software. The chi-square test was used to assess the association between the degree of staining for each marker and the clinical and pathological features.RESULTS Sixty-seven proteins exhibited significant differential expression between tissues of CL lesions and healthy controls (p < 0.01), representing numerous enriched biological processes within the lesion tissue, as evident by both the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome databases. Among these, the integrated endoplasmic reticulum stress response (IERSR) emerges as a pathway characterized by the up-regulated proteins in CL tissues compared to healthy skin. Expression of endoplasmic reticulum (ER) stress sensors, inositol-requiring enzyme-1 (IRE1), protein kinase RNA-like ER kinase (PERK) and activating transcription factor 6 (ATF6) in lesion tissue was validated by immunohistochemistry.CONCLUSIONS In conclusion, proteomic profiling of skin lesions carried out as a discovery phase study revealed a multitude of probable immunological and pathological mechanisms operating in patients with CL in Sri Lanka, which needs to be further elaborated using more in-depth and targeted investigations. Further research exploring the intricate interplay between ER stress and CL pathophysiology may offer promising avenues for the development of novel diagnostic tools and therapeutic strategies in combating this disease.Item Unfolded protein response pathway in leishmaniasis: A review(Wiley, 2023) Edirisinghe, N.M.; Manamperi, N.H.; Wanasinghe, V.S.; Karunaweera, N.Alteration in the physiological state of the endoplasmic reticulum (ER) leads to the specific response known as unfolded protein response (UPR) or ER stress response. The UPR is driven by three sensor proteins, namely: Inositol-Requiring Enzyme 1, Protein Kinase RNA-like ER kinase and Activating Transcription Factor 6 to restore ER homeostasis. Pathogenic infection can initiate UPR activation; some pathogens can subvert the UPR to promote their survival and replication. Many intracellular pathogens, including Leishmania, can interact and hijack ER for their survival and replication, triggering ER stress and subsequently ER stress response. This review aims to provide a comprehensive overview of the ER stress response in infections with the Leishmania species.Item ELISA based evaluation of antibody response to Leishmania in a region endemic for cutaneous leishmaniasis(Oxford, 2022) Piyasiri, S.B.; Samaranayake, T.N.; Silva, H.; Manamperi, N.H.; Karunaweera, N.D.Aims: Leishmaniasis includes several clinical forms. While routine diagnosis of cutaneous leishmaniasis (CL) is by microscopy, an antibody response to CL has been reported in several recent studies. This study evaluated anti-leishmanial IgG antibody responses as a biomarker of active leishmaniasis and a measure of exposure to Leishmania. Methods and results: Sera from 50 untreated CL patients, 140 patients under treatment and 280 healthy individuals residing in endemic regions collected as part of an epidemiological survey, was analysed with an ELISA established in-house using receiver-operator-characteristic (ROC) curve at optimised cut-off value. The assay showed high performance as a diagnostic tool in identifying exposure in endemic individuals (sensitivity: 98%, specificity: 90.3%). All patients showed lower antibody levels over time since onset of lesion/s. Antibody levels were higher (p ˂ 0.01) and persisted for a longer period in untreated patients. In patients under treatment, the level of anti-IgG antibodies was negatively correlated with the total duration the patient had been on treatment. Conclusion: The anti-leishmanial IgG response in L. donovani induced CL is transient and is unlikely to confer protective immunity. Optimised serological assays may be useful in endemic settings for diagnosis and monitoring the treatment response in CL.Item Tissue impression smears as a supplementary diagnostic method for histopathology in cutaneous leishmaniasis in Sri Lanka(American Society of Tropical Medicine and Hygiene, 2018) Manamperi, N.H.; de Silva, M.V.C.; Pathirana, N.; Abeyewickreme, W.; Karunaweera, N.D.Cutaneous leishmaniasis (CL) is diagnosed mainly by light microscopy of smears made using lesion material. Histopathology is usually done in atypical presentations or when lesion smears are negative. Tissue impression smears (TIS) made from skin biopsy specimens were compared with histopathology for the diagnosis of CL. Out of the 111 patients included, 83 (74.8%) were positive by either methods. The TIS was positive in 70.3% whereas histopathology was positive in 56.8% of patients. Tissue impression smears can be used as a supplementary diagnostic test that gives sensitive and rapid results when tissue biopsies are used as the source of lesion material for diagnosis of CL.Item In situ immunopathological changes in cutaneous leishmaniasis due to Leishmania donovani(Oxford, Wiley, 2017) Manamperi, N.H.; Oghumu, S.; Pathirana, N.; de Silva, V.C.; Abeyewickreme, W.; Satoskar, A.R.; Karunaweera, N.D.INTRODUCTION: Cutaneous leishmaniasis in Sri Lanka is a newly established parasitic disease caused by the usually visceralizing Leishmania donovani. Skin lesions manifest as non-itchy, non-tender papules, nodules or ulcers. In situ cytokine expression provides clues for immunopathogenesis of this localized form of disease. METHODS: Skin biopsies from 58 patients were analyzed for histological appearance and in situ cytokine expression of T- helper 1 (Th1) and T- helper 2 (Th2) cytokines, namely interferon (IFN)-γ, interleukin (IL)-12A, tumor necrosis factor (TNF)-α, IL-4 and IL-10 by real-time RT- PCR. RESULTS: Significant up regulation of the Th1 cytokine IFN-γ and down regulation of the Th2 cytokine IL-4 was seen in patients compared to healthy controls. Significantly elevated tissue expression of IFN-γ and TNF-α was seen in lesions that presented later than 6 months from the time of onset, while IL-4 expression was more prominent in lesions that responded poorly to antimony therapy. CONCLUSION: A prominent Th1 response appears to support resolving of lesions, whereas a Th2 biased milieu tends to favor poor responsiveness to antimony and delayed lesion healing in L. donovani infections in Sri Lanka. This article is protected by copyright. All rights reserved.