Therapeutic Potential of miRNAs for Type 2 Diabetes Mellitus: An Overview.

MicroRNA(miRNA)s have been identified as an emerging class for therapeutic interventions mainly due to their extracellularly stable presence in humans and animals and their potential for horizontal transmission and action. However, treating Type 2 diabetes mellitus using this technology has yet been in a nascent state. MiRNAs play a significant role in the pathogenesis of Type 2 diabetes mellitus establishing the potential for utilizing miRNA-based therapeutic interventions to treat the disease. Recently, the administration of miRNA mimics or antimiRs in-vivo has resulted in positive modulation of glucose and lipid metabolism. Further, several cell culture-based interventions have suggested beta cell regeneration potential in miRNAs. Nevertheless, few such miRNA-based therapeutic approaches have reached the clinical phase. Therefore, future research contributions would identify the possibility of miRNA therapeutics for tackling T2DM. This article briefly reported recent developments on miRNA-based therapeutics for treating Type 2 Diabetes mellitus, associated implications, gaps, and recommendations for future studies.

Seroprevalence and associated risk factors of human Brucella infection in selected provinces in Sri Lanka

Brucellosis is a systemic zoonotic bacterial infection. We studied the seroprevalence and risk factors for human Brucella infection in 1,294 healthy people from 4 provinces: Central, North-Western, North-Central and Western Provinces. Farmers in contact with farm-animals, veterinary staff, abattoir workers, and non-contact urban-dwellers were tested against B. abortus and B. melitensis antigens by SAT. Seroprevalence was 8.4% of the study population. Farm-animal owners and working full-time with livestock have a significantly higher risk of acquiring Brucella infection. Enhanced laboratory support and surveillance is necessary to control brucellosis in Sri Lanka. This is the first report on human Brucella infection.

Dermotropic Leishmania donovani in Sri Lanka: visceralizing potential in clinical and preclinical studies.

The visceralizing potential of apparently dermotropic Leishmania donovani in Sri Lanka (L. donovani-SL) was investigated through long-term follow-up of cutaneous leishmaniasis (CL) patients and in vivo and in vitro experimental infection models. CL patients (n = 250) treated effectively with intra-lesional antimony therapy were followed-up six monthly for 4 years. There was no clinical evidence of visceralization of infection (VL) during this period. Infection of BALB/c mice with L. donovani-SL (test) through intra-dermal route led to the development of cutaneous lesions at the site of inoculation with no signs of systemic dissemination, in contrast to the observations made in animals similarly infected with a visceralizing strain of L. donovani-1S (control). Cytokine (IL-10, IFN-γ) release patterns of splenocytes and lymph node cell cultures derived from mice primed with experimental infections (with either test or control parasites) revealed significantly high IFN-γ response associated with test mice with CL, while prominent IL-10 levels were observed in association with control mice with VL. Furthermore, diminished infection efficiency, intracellular growth and survival of L. donovani-SL parasites compared with L. donovani-1S were evident through in vitro macrophage infection experiments. These studies confirm, for the first time, the essential dermotropic nature of L. donovani-SL suggesting natural attenuation of virulence of local parasite strains.

Emergence of visceral leishmaniasis in Sri Lanka: a newly established health threat.

BACKGROUND: Sri Lanka is a new focus of human cutaneous leishmaniasis caused by a genetic variant of usually visceralizing parasite Leishmania donovani. Over 3000 cases have been reported to our institution alone, during the past two decades. Recent emergence of visceral leishmaniasis is of concern. METHODS: Patients suspected of having visceral leishmaniasis (n = 120) fulfilling at least two of six criteria (fever > 2 weeks, weight loss, tiredness affecting daily functions, splenomegaly, hepatomegaly and anemia) were studied using clinic-epidemiological, immunological and haematological parameters. Seven cases (four progressive, treated (group A) and 3 non- progressive, potentially asymptomatic and observed (group B) were identified. Clinical cases were treated with systemic sodium stibogluconate or amphotericin B and all were followed up at the leishmaniasis clinic of University of Colombo for 3 years with one case followed up for 9 years. RESULTS: All treated cases responded well to anti leishmanial treatment. Relapses were not noticed. Clinical features subsided in all non-progressive cases and did not develop suggestive clinical features or change of laboratory parameters. Visceral leishmaniasis cases have been originated from different districts within the country. Majority had a travel history to identified local foci of cutaneous leishmaniasis. CONCLUSION: Visceral leishmaniasis is recognized as an emerging health threat in Sri Lanka. At least a proportion of locally identified strains of L. donovani possess the ability to visceralize. Apparent anti leishmanial sensitivity is encouraging. Timely efforts in disease containment will be important in which accurate understanding of transmission characteristics, increased professional and community awareness, improved diagnostics and availability of appropriate treatment regimens.

Safety of subcutaneous adrenaline as prophylaxis against acute adverse reactions to anti-venom serum in snakebite.

OBJECTIVES: To study the safety of low dose subcutaneous adrenaline given as prophylaxis against acute adverse reactions to anti-venom serum (AVS) in patients bitten by snakes. METHODS: Patients admitted with snakebite envenoming who satisfied inclusion criteria were given 0.25 ml of 1:1000 adrenaline subcutaneously immediately before administration of AVS. They were observed for adverse effects, and pulse and blood pressure (BP) were monitored. RESULTS: 51 patients [35 males, mean age 34.8 years (SD 14)] were included in the study. Adverse reactions to AVS occurred in 15 (29.4%) patients. There was one death from suspected cerebral haemorrhage, and 3 (5.9%) patients developed small haematomas at the subcutaneous injection site. There were no significant changes in mean pulse or BP following administration of subcutaneous adrenaline. CONCLUSIONS: Low dose subcutaneous adrenaline did not cause significant changes in pulse rate or BP. Although the death was unlikely to be directly related to subcutaneous adrenaline, we suggest further studies on the safety of this prophylactic treatment before its routine use.