Frequency of micronuclei among persons resident in the vicinity of a mineral sand processing factory in Pulmoddai, Sri Lanka.

Lanka Mineral Sands Ltd (LMS), a government-owned company, has been mining mineral sands including monazite which contains thorium (Th) at Pulmoddai, Sri Lanka since 1957. Th emits alpha particles on decay and gamma rays are emitted by the daughter products. The cytokinesis-blocked micronucleus (MN) assay is popular for large scale radiation exposure studies as it is an easy, fast and reliable method of biodosimetry. The objective of the study was to determine the frequency of micronuclei among persons residing in the vicinity of LMS. A cross-sectional study was conducted from November 2012 to September 2016 among persons 35-45 years of age to evaluate the frequency of micronuclei in peripheral blood lymphocytes. Fifty-three employees of LMS factory, 25 residents within 5 km from LMS, 25 residents 20-25 km from LMS and 29 residents from >50 km away from LMS were included in the study. The highest median frequency of micronuclei per 1000 binucleated (BN) cells was in the group residing within 5 km from LMS with a median (IQ range) of 0.67 (0.17-2.17). The median (IQ range) of MN frequency of employees of LMS, residents 20-25 km from LMS and residents >50 km from LMS were 0.66 (0.16-1.16), 0.33 (0.00-0.67) and 0.33 (0.33-0.67), respectively. There was no significant difference in the MN frequency between employees of LMS and the group residing within 5 km from LMS. Being a resident of Pulmoddai and being exposed to X-rays were significant predictors of MN frequency. Persons residing within 5 km from LMS had a higher risk of MN formation irrespective of being employed at LMS.

Efficacy and safety of deferoxamine, deferasirox and deferiprone triple iron chelator combination therapy for transfusion-dependent ß-thalassaemia with very high iron overload: a protocol for randomised controlled clinical trial.

INTRODUCTION: Despite the improvement in medical management, many patients with transfusion-dependent ß-thalassaemia die prematurely due to transfusion-related iron overload. As per the current guidelines, the optimal chelation of iron cannot be achieved in many patients, even with two iron chelators at their maximum therapeutic doses. Here, we evaluate the efficacy and safety of triple combination treatment with deferoxamine, deferasirox and deferiprone over dual combination of deferoxamine and deferasirox on iron chelation in patients with transfusion-dependent ß-thalassaemia with very high iron overload. METHODS AND ANALYSIS: This is a single-centre, open-label, randomised, controlled clinical trial conducted at the Adult and Adolescent Thalassaemia Centre of Colombo North Teaching Hospital, Ragama, Sri Lanka. Patients with haematologically and genetically confirmed transfusion-dependent ß-thalassaemia are enrolled and randomised into intervention or control groups. The intervention arm will receive a combination of oral deferasirox, oral deferiprone and subcutaneous deferoxamine for 6 months. The control arm will receive the combination of oral deferasirox and subcutaneous deferoxamine for 6 months. Reduction in iron overload, as measured by a reduction in the serum ferritin after completion of the treatment, will be the primary outcome measure. Reduction in liver and cardiac iron content as measured by T2* MRI and the side effect profile of trial medications are the secondary outcome measures. ETHICS AND DISSEMINATION: Ethical approval for the study has been obtained from the Ethics Committee of the Faculty of Medicine, University of Kelaniya (Ref. P/06/02/2023). The trial results will be disseminated in scientific publications in reputed journals. TRIAL REGISTRATION NUMBER: The trial is registered in the Sri Lanka Clinical Trials Registry (Ref: SLCTR/2023/010).

Persistent, Poorly Responsive Immune Thrombocytopenia Secondary to Asymptomatic COVID-19 Infection in a Child.

Immune thrombocytopenic purpura (ITP) secondary to asymptomatic COVID-19 infection, especially in children, is not reported. Furthermore, persistent, treatment-resistant ITP secondary to COVID-19 is not reported. We report a previously healthy 14-year-old Asian boy who developed secondary ITP following an asymptomatic COVID-19 infection and is having a relapsing and remitting cause with poor response to immunosuppressants even after 21 months following the diagnosis. This case emphasizes the importance of testing for COVID-19 in newly diagnosed ITP patients and the need for follow-up platelet counts in patients who recover from COVID-19 as it may follow into developing secondary ITP yet being asymptomatic until you present with a bleeding complication of ITP. The poor response to standard immunosuppression warrants more understanding of the pathophysiology of persistently low platelets following COVID-19 infection. Long-term sequelae of the disease highlight the importance of getting vaccinated for COVID-19 despite COVID-19 being no longer a global emergency.

Hemoglobin variants in patients with type 2 diabetes mellitus.

Measurement of HbA1c levels in diabetic patients is an established procedure for evaluating long-term control of diabetes. Despite its usefulness, conditions that effect hemoglobin concentration, such as hemoglobinopathies give rise to inappropriate HbA1c values. Since information about hemoglobinopathies in the diabetic population in Sri Lanka is limited, a prospective cross-sectional study was carried out among 2,695 diabetic subjects attending the diabetic clinic at Nawaloka Hospital, Sri Lanka. Hemoglobin type and HbA1c were measured by the HPLC method. The results reveal among 2,695 diabetic subjects, 53 (2%) had abnormal hemoglobin types (HbF and HbS). HbA1c concentrations in diabetic patients without Hb abnormalities show a higher correlation with fasting blood glucose than those with hemoglobin abnormalities. This study emphasizes that patients with inappropriate HbA1c values should be investigated for hemoglobinopathies.

BACKGROUND RADIATION LEVELS NEAR A MINERAL SAND MINING FACTORY IN SRI LANKA: CORRELATION OF RADIATION MEASUREMENTS WITH MICRONUCLEI FREQUENCY.

Lanka Mineral Sands Ltd (LMS) is a company operating in Pulmoddai, Sri Lanka, mining for rare earth minerals along with monazite which contains thorium that emits ionizing gamma and alpha radiation on decay. The objective of the study was to determine the background radiation levels and selected radionuclides and then to correlate these levels with the frequency of micronuclei (MN) among persons residing in the vicinity of LMS. A cross-sectional study was conducted among persons of both sexes between 35 and 45 years of age residing in the vicinity of LMS. Background radiation measurements were obtained by a survey metre, and gamma spectrometry was done on soil samples. Five millilitres of venous blood was drawn for cytokinesis-blocked MN assay. Background radiation levels measured by the survey metre; 232Th, 226Ra and 210Pb mass activities in soil were highest in the samples collected from the LMS. The background radiation measurements positively correlated with MN frequency although the magnitude of the correlation was small (r = 0.176, p = 0.04). This implies that chronic long-term exposure to low-dose radiation may result in genotoxicity. Prospective large-scale studies are recommended to evaluate the long-term effect of exposure to low-dose radiation at Pulmoddai.

The Porphyromonas gingivalis inhibitory effects, antioxidant effects and the safety of a Sri Lankan traditional betel quid - an in vitro study.

BACKGROUND: The Sri Lankan traditional betel quid (TBQ) which had been extensively used in the country before its colonization is claimed to have antiperiodontopathic effects in the Sri Lankan folklore. However, there is no reported scientific evidence to support the claimed antiperiodontopathic effects mediated by this TBQ. The present study was carried out to investigate the protective effect of the Sri Lankan TBQ in the pathogenesis of periodontitis. METHODS: We investigate the ethyl acetate extract of the Sri Lankan TBQ for its antibacterial effects against the keystone periodontopathic bacterium, P. gingivalis and also its antioxidant potential, which is important to protect the periodontium from oxidative stress. Further, its safety was analyzed using the cytokinesis block micronucleus assay on human peripheral blood lymphocytes (PBLs). RESULTS: Ethyl acetate extract of this TBQ inhibited the growth of P. gingivalis with a minimum bactericidal concentration (MBC) of 125 µg/ml. It was found to be a rich source of polyphenols and displayed considerable DPPH and ABTS radical scavenging activities and a strong ferric reducing antioxidant power. This extract could protect the cultured human gingival fibroblasts from H2O2 induced oxidative stress. In addition, this TBQ extract was not genotoxic to human PBLs even at a concentration of 2.5 mg/ml. Moreover, it exhibited protective effects against bleomycin induced genotoxicity in PBLs. CONCLUSION: Ethyl acetate extract of the Sri Lankan TBQ is a source of natural antibacterial compounds against P. gingivalis. It is also a source of natural antioxidants which can protect human gingival fibroblasts from H2O2 induced oxidative stress. These properties of the TBQ may have contributed to its claimed antiperiodontopathic effects. Besides, it was found to be relatively non-toxic to human cells. Thus this TBQ extract has a huge potential to be developed as a novel adjunctive therapeutic lead against periodontitis.

ATG vs thiotepa with busulfan and cyclophosphamide in matched-related bone marrow transplantation for thalassemia.

Matched-related bone marrow transplantation (BMT) may cure >80% of low-risk children with severe thalassemia (ST). Very long-term follow-up studies have shown how the standard busulfan-cyclophosphamide (BuCy) regimen may be associated with normalization of health-related quality of life, no second malignancies in the absence of chronic graft-versus-host disease, and fertility preservation in many patients. However, because BuCy may be associated with high rejection rates, some centers incorporate thiotepa (Tt) in busulfan- or treosulfan-based regimens, a combination that may increase the risk of permanent infertility. This study retrospectively compares matched-related BMT outcomes in 2 groups of low-risk ST patients conditioned with either Tt or anti-thymocyte globulin (ATG) in addition to BuCy. A total of 81 consecutive first BMTs were performed in 5 collaborating startup BMT centers in the Indian subcontinent between January 2009 and January 2016; 30 patients were transplanted after conditioning with Tt-BuCy between January 2009 and July 2013, whereas between August 2013 and January 2016, 51 patients received ATG-BuCy. All patients were <15 years and had no hepatomegaly (liver ≤2 cm from costal margin). Actuarial overall survival in the Tt-BuCy and ATG-BuCy groups was 87% and 94% and thalassemia-free survival was 80% and 85% at a median follow-up of 37 and 17 months, respectively, with no significant differences by log-rank statistics. Substituting Tt with ATG in the standard BuCy context seems safe and effective and may decrease transplant-related mortality. Higher fertility rates are expected for patients who received ATG-BuCy.

Suppression of erythropoiesis in malarial anemia is associated with hemozoin in vitro and in vivo.

Malarial anemia is a global public health problem and is characterized by a low reticulocyte response in the presence of life-threatening hemolysis. Although cytokines, in particular tumor necrosis factor-alpha (TNF-alpha), can suppress erythropoiesis, the grossly abnormal bone marrow morphology indicates that other factors may contribute to ineffective erythropoiesis. We hypothesized that the cytotoxic hemozoin (Hz) residues from digested hemoglobin (Hb) significantly contribute to abnormal erythropoiesis. Here, we show that not only isolated Hz, but also delipidated Hz, inhibits erythroid development in vitro in the absence of TNF-alpha. However, when added to cultures, TNF-alpha synergizes with Hz to inhibit erythropoiesis. Furthermore, we show that, in children with malarial anemia, the proportion of circulating monocytes containing Hz is associated with anemia (P < .001) and reticulocyte suppression (P = .009), and that this is independent of the level of circulating cytokines, including TNF-alpha. Plasma Hz is also associated with anemia (P < .001) and reticulocyte suppression (P = .02). Finally, histologic examination of the bone marrow of children who have died from malaria shows that pigmented erythroid and myeloid precursors are associated with the degree of abnormal erythroid development. Taken together, these observations provide compelling evidence for inhibition of erythropoiesis by Hz.