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.

Hump-nosed pit viper (Hypnale hypnale and Hypnale zara) envenoming in Deniyaya, Sri Lanka: Epidemiological and clinical features from a prospective observational study.

Hypnale hypnale, Hypnale zara and Hypnale nepa are the three species of Hump nosed pit vipers that are implicated in human bites in Sri Lanka. H. zara and H. nepa are two endemic species to the country. The objective of the study was to characterize epidemiology and clinical features after different Hump nosed pit viper species bites. A prospective observational study was conducted in Base Hospital Deniyaya from 2013 to 2015. Hump nosed pit viper as the offending snake was identified when the victims brought live or dead specimens. Species identification of dead specimen was done by a herpetologist. Clinical details were recorded during the hospital stay. 83 Hump nosed pit viper bite patients (19-81 years) were studied. Fifty two dead specimens were identified as 39 of H. zara and 13 of H. hypnale by the herpetologist. No H. nepa was identified. Thirty one live snakes were identified as Hump nosed pit vipers and released in to the wild. Envenoming was reported throughout the year. Eighty (96.4%) were daytime bites. Hands (43.4%), feet (55.4%) and arms (1.2%) were affected sites. Sixty two (74.7%) were bitten in tea plantations. All had pain over bite site. Overall, sixty nine (83.1%) had local swelling, seven (8.4%) extensive limb swelling, nineteen (22.9%) haemorrhagic blisters, and seven (8.4%) regional lymphadenopathy. Four (4.8%) patients had incoagulable blood by 20WBCT. H. zara bites had 28.2% haemorrhagic blisters, 7.7% extensive limb swelling and 2.6% coagulopathy. H. hypnale bites had 7.7% each extensive limb swelling and coagulopathy and 23.1% haemorrhagic blisters. None developed elevated serum creatinine. Neurotoxicity was not noted. Hump nosed pit viper bites caused substantial morbidity. Risk factors included day time outdoor activities and occupation. Pain, extensive limb swelling, bite site swelling, haemorrhagic blisters, regional lymphadenopathy and coagulopathy were prominent clinical features. Nephrotoxicity and neurotoxicity were notably absent. Clinical features varied depending on the species implicated.

Sri Lankan green pit viper (Trimeresurus trigonocephalus) bites in Deniyaya: A clinico-epidemiological study.

Green pit viper (Trimeresurus trigonocephalus) is endemic to Sri Lanka and bites are reported from tropical rain forest and plantation areas. As scant data exists on clinico-epidemiological features of Sri Lankan green pit viper bite, objective of this study was to address this knowledge gap. A prospective observational study was conducted in Base Hospital Deniyaya from October 2013 to September 2015. Green pit viper as the offending snake was identified when the victims brought live or dead specimens. When the specimen was not available, green pit viper was identified by the victim pointing to preserved specimens and photographs of green pit viper and different similar appearing snakes. Clinical details were recorded during the hospital stay. Twenty four green pit viper bite patients (17-68 years) were studied. All cases were daytime bites despite green pit viper being a nocturnally active snake. Sixteen patients (67%) were bitten while they were working in tea plantation. Hands (42%), feet, (33%), forearms (8%), legs (8%), thighs (4%) and shoulders (4%) were the sites of bites. Thirteen (54%) had extensive limb swelling. Nine (38%) had local swelling and two had no swelling. Three (12.5%) developed haemorrhagic blisters. Four (17%) had regional lymphadenopathy. Two (8%) developed non clotting blood by the TWBCT. Green pit viper bites caused substantial morbidity. Risk factors included day time outdoor activities in bordering villages of tropical rain forests and occupation. Pain, extensive limb swelling and bite site swelling were prominent clinical features. However haemorrhagic blisters, regional lymphadenopathy and coagulopathy were reported. Nephrotoxicity and neurotoxicity were notably absent.

Doxycycline Usage for Prevention of Leptospirosis among Farmers and Reasons for Failure to Use Chemoprophylaxis: A Descriptive Study from Southern Sri Lanka.

BACKGROUND: Leptospirosis causes substantial morbidity and mortality in Sri Lanka. Health authorities have implemented a chemoprophylaxis programme for prevention of disease for farmers who are at a high risk of leptospirosis. Only 39% of general population is aware of chemoprophylaxis. Awareness on chemoprophylaxis and its usage among the risk population and the reasons for non-usage was uncertain. Our aim was to assess the chemoprophylaxis usage for prevention of leptospirosis among farmers and reasons for failure to use such preventive strategy. METHODS: Cross-sectional descriptive study was conducted on farmers in community setting in Galle District. Multi-stage cluster sampling method was used. Out of the seventeen "Ministry of Health" (MOH) divisions within the Galle district, nine divisions were randomly selected and, subsequently, two subdivisions ("Public Health Midwife" divisions) were randomly selected from each MOH division. From each PHM division (total of 18), a cluster who does farming as the main source of income was selected. From these farmers, details on demographics, knowledge on leptospirosis and knowledge and practice on chemoprophylaxis usage were obtained through an interviewer administered open-ended questionnaire. From those who have not properly taken chemoprophylaxis, the reasons for non-usage were explored by semistructured interviews. RESULTS: We recruited 319 (77%-males) farmers to the study. Eighteen (5.6%) have already had leptospirosis. Majority (86.8%) of farmers were aware that doxycycline can be used to prevent the disease occurrence. Only 31% knew about correct recommendations of chemoprophylaxis usage adopted by the national guidelines. Only 28.5% (91) used doxycycline prophylaxis. Out of those, only 60 farmers (65.9%) continued the prophylaxis throughout the contact and followed national recommendations. Themes responsible for non-usage were elicited such as lack of awareness of chemoprophylaxis usage, false sense of security from the disease by perceived "immunity" due to prolong exposure or due to low prevalence of disease, lack of motivation, lack of availability of medication, and fear of side effects. CONCLUSIONS: Awareness of leptospirosis is better among farmers compared to the general population. Usage of chemoprophylaxis among farmers was highly inadequate. Individual and health system related hypotheses and myths exist for non-usage of chemoprophylaxis. Thus, an urgent concerted campaign aimed at increasing awareness within the target group through education and making medicines effectively distributed is essential for better prevention of the disease.

Genera of phytopathogenic fungi: GOPHY 1.

Genera of Phytopathogenic Fungi (GOPHY) is introduced as a new series of publications in order to provide a stable platform for the taxonomy of phytopathogenic fungi. This first paper focuses on 21 genera of phytopathogenic fungi: Bipolaris, Boeremia, Calonectria, Ceratocystis, Cladosporium, Colletotrichum, Coniella, Curvularia, Monilinia, Neofabraea, Neofusicoccum, Pilidium, Pleiochaeta, Plenodomus, Protostegia, Pseudopyricularia, Puccinia, Saccharata, Thyrostroma, Venturia and Wilsonomyces. For each genus, a morphological description and information about its pathology, distribution, hosts and disease symptoms are provided. In addition, this information is linked to primary and secondary DNA barcodes of the presently accepted species, and relevant literature. Moreover, several novelties are introduced, i.e. new genera, species and combinations, and neo-, lecto- and epitypes designated to provide a stable taxonomy. This first paper includes one new genus, 26 new species, ten new combinations, and four typifications of older names.

A study on paracetamol cardiotoxicity.

BACKGROUND: Sri Lanka has a high suicide rate, with more than 40 % of poisoning admissions due to overdose of drugs with Paracetamol being the commonest. Data regarding cardiotoxicity to paracetamol is very minimal though hepatotoxicity following poisoning is well studied. Paracetamol cardiotoxicity has rarely been clinically significant and may have well been overlooked. The possibility that paracetamol overdose might be directly cardiotoxic has been the subject of a few reports. Unexplained deaths and electrocardiographic changes associated with paracetamol poisoning have also been reported in which cardiac origin cannot be clearly ruled out. Although some studies state that paracetamol poisoning has no direct cardiotoxic effect, electrocardiographic changes due to metabolic derangement of hepatotoxicity have been shown in certain studies. Thus, we conducted this study to assess in detail the cardiotoxic effect of paracetamol poisoning. METHODS: This is a cross sectional descriptive study done on those with confirmed paracetamol poisoning. Serum paracetamol levels, Electrocardiogram, Echocardiogram, troponin I, and other basic investigations were done. RESULTS: Paracetamol ingestion is more common among teenagers and the young population in Sri Lanka. Although several cases of paracetamol poisoning induced cardiotoxicity has been described in the past, this study demonstrated no electrocardiographic, echocardiographic or cardiac biomarkers changes of myocardial toxicity. CONCLUSION: Though literature review support cardiotoxicity following paracetamol poisoning, our study does not provide enough evidence for this. Continuous cardiac monitoring, serial troponin and echocaediogram assessment would be voluble adjunct in its management. Further experiments and research in this subject would be useful with a larger number of samples to further evaluate this important problem.

Efficacy of low dose dexamethasone in severe thrombocytopenia caused by dengue fever: a placebo controlled study.

BACKGROUND: The use of corticosteroids in the management of thrombocytopenia in dengue fever remains untested. OBJECTIVES: To test whether intravenous low dose dexamethasone is efficacious in increasing platelet count in acute severe thrombocytopenia in dengue infection. METHODS: We undertook a placebo controlled study at the Teaching Hospital, Peradeniya, Sri Lanka in July 2004. Patients with thrombocytopenia (platelet count <50x10(9)/l) were allocated to the treatment and placebo groups using the sealed envelop method. The treatment group received an initial intravenous dose of 4 mg dexamethasone, followed by 2 mg doses every 8 h for 24 h, and the placebo group received normal saline. The primary outcome was the degree of mean platelet count rise. RESULTS: Each group comprised 100 patients and their baseline data and other variables (headaches, nausea, flush, temperature, pulse, blood pressure, haematocrit, white cell count and haemoglobin) were similar. The primary outcome--mean platelet count (x10(9)/l)--increased steadily in both groups from day 1 to 4 and showed no significant difference between the two groups (p>0.05): day 1, 35 vs 35 (p = 0.70); day 2, 47 vs 43 (p = 0.19); day 3, 64 vs 59 (p = 0.31); day 4, 72 vs 78 (p = 0.55). Analysis of variance (ANOVA) statistics showed a significant linear association of mean platelet counts by days in either group (p<0.001). Regression analysis identified the day of the illness and patient age as the independent predictors of platelet count change. CONCLUSION: At a low dose regimen, dexamethasone was not effective in achieving a higher rise of platelet count in dengue infection.

A copper(II)-selective chelator ameliorates left-ventricular hypertrophy in type 2 diabetic patients: a randomised placebo-controlled study.

AIMS/HYPOTHESIS: Cu(II)-selective chelation with trientine ameliorates cardiovascular and renal disease in a model of diabetes in rats. Here, we tested the hypothesis that Cu(II)-selective chelation might improve left ventricular hypertrophy (LVH) in type 2 diabetic patients. METHODS: We performed a 12 month randomised placebo-controlled study of the effects of treatment with the Cu(II)-selective chelator trientine (triethylenetetramine dihydrochloride, 600 mg given orally twice daily) on LVH in diabetic patients (n = 15/group at baseline) in an outpatient setting wherein participants, caregivers and those assessing outcomes were blinded to group assignment. Using MRI, we measured left ventricular variables at baseline, and at months 6 and 12. The change from baseline in left ventricular mass indexed to body surface area (LVM(bsa)) was the primary endpoint variable. RESULTS: Diabetic patients had LVH with preserved ejection fraction at baseline. Trientine treatment decreased LVM(bsa) by 5.0 +/- 7.2 g/m(2) (mean +/- SD) at month 6 (when 14 trientine-treated and 14 placebo-treated participants were analysed; p = 0.0056 compared with placebo) and by 10.6 +/- 7.6 g/m(2) at month 12 (when nine trientine-treated and 13 placebo-treated participants were analysed; p = 0.0088), whereas LVM(bsa) was unchanged by placebo treatment. In a multiple-regression model that explained ~75% of variation (R (2) = 0.748, p = 0.001), cumulative urinary Cu excretion over 12 months was positively associated with trientine-evoked decreases in LVM(bsa). CONCLUSIONS/INTERPRETATION: Cu(II)-selective chelation merits further exploration as a potential pharmacotherapy for diabetic heart disease. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN 12609000053224 FUNDING: The Endocore Research Trust; Lottery Health New Zealand; the Maurice and Phyllis Paykel Trust; the Foundation of Research, Science and Technology (New Zealand); the Health Research Council of New Zealand; the Ministry of Education (New Zealand) through the Maurice Wilkins Centre for Molecular Biodiscovery; and the Protemix Corporation.

Notification of random hyperglycaemia to general practitioners by an emergency medicine team: impact of a simple intervention plan.

AIM: To determine whether general practitioners (GPs) were being appropriately notified of patients' elevated random glucose levels by emergency medicine (EM) staff, and to investigate whether two simple interventions improved the notification rate. METHODS: Patients were included if their random venous plasma glucose (RVPG) at presentation to the Emergency Department (ED) was >or= 7.8 mmol/l and if they were discharged directly to their GP. Patients with known impaired glucose metabolism (IGM) were excluded. Patient discharge summaries were reviewed over a 5-month period before and a 5-week period after two simple interventions: first, a targeted educational session for EM staff and second, modifications to the automated message accompanying laboratory results. RESULTS: Before intervention, the GPs of 120 out of 178 patients received no notification of an elevated RVPG compared with 23 of 62 patients after intervention (P < 0.00001). Notification met a predefined standard in 25 of 178 patients before, and 34 of 62 patients after intervention (P < 0.01). CONCLUSIONS: EM staff education, together with an automated laboratory message, significantly improved the rate and quality of notification of elevated RVPG levels to GPs. These simple measures have the potential to hasten implementation of preventive and therapeutic measures in patients with IGM.

Severe hypomagnesaemia in long-term users of proton-pump inhibitors.

OBJECTIVE: To explore the mechanism underlying severe hypomagnesaemia in long-term users of proton-pump inhibitors (PPIs). PATIENTS: Two cases of severe hypomagnesaemia in adult long-term users of the PPI omeprazole, presenting with hypocalcaemic seizures. MEASUREMENTS: We studied renal magnesium handling during an incremental intravenous magnesium infusion, and assessed total body magnesium status by the 24-h retention of the parenteral load. We also observed the effects of oral magnesium supplements whilst continuing the PPI, and the effect of withdrawal of the PPI. RESULTS: Both patients were severely magnesium-depleted and had avid renal magnesium retention, implicating a failure of intestinal magnesium absorption. There was no evidence of generalized malabsorption. The hypomagnesaemia could be partially corrected by high dose oral magnesium supplementation, and resolved on withdrawal of PPIs. CONCLUSIONS: PPI use can inhibit active magnesium transport in the intestine, though it is not clear if this is an idiosyncratic effect. Long-term PPI users who are highly adherent to treatment can eventually deplete total body magnesium stores and present with severe complications of hypomagnesaemia.

Thyrotoxic, hypokalaemic periodic paralysis: Polynesians, an ethnic group at risk.

BACKGROUND: Thyrotoxic, hypokalaemic periodic paralysis (TPP) is a reversible cause of severe muscle weakness that occurs in a small minority of thyrotoxic patients. Most cases to date have been reported in Asian men. AIMS: To evaluate the ethnic distribution of patients with TPP. METHODS: Retrospective analysis of all patients presenting with thyrotoxicosis and hypokalaemia with paralysis to two New Zealand hospitals. RESULTS: Seventy-one per cent of the 21 patients with TPP were of Polynesian ethnicity (Maori and Pacific Islander), 24% Asian and 5% European. Based on population demographics, these figures suggest a 37-fold overrepresentation for Polynesians and 159-fold for Asians compared with New Zealand Europeans. CONCLUSION: Polynesian, in addition to Asian people, are two ethnic groups at particular risk of TPP, and this condition must be considered in the differential diagnosis for patients presenting to the emergency department with severe hypokalaemia and weakness.

Coconut fats.

In many areas of Sri Lanka the coconut tree and its products have for centuries been an integral part of life, and it has come to be called the "Tree of life". However, in the last few decades, the relationship between coconut fats and health has been the subject of much debate and misinformation. Coconut fats account for 80% of the fat intake among Sri Lankans. Around 92% of these fats are saturated fats. This has lead to the belief that coconut fats are 'bad for health', particularly in relation to ischaemic heart disease. Yet most of the saturated fats in coconut are medium chain fatty acids whose properties and metabolism are different to those of animal origin. Medium chain fatty acids do not undergo degradation and re-esterification processes and are directly used in the body to produce energy. They are not as 'bad for health' as saturated fats. There is the need to clarify issues relating to intake of coconut fats and health, more particularly for populations that still depend on coconut fats for much of their fat intake. This paper describes the metabolism of coconut fats and its potential benefits, and attempts to highlight its benefits to remove certain misconceptions regarding its use.

Evaluation of toxicity in tributaries of the Mersey estuary using the isopod Asellus aquaticus (L.).

Increasing numbers of industrial, agricultural and natural chemicals are present in sewage effluent and are known to elicit toxic effects in laboratory exposures, but little is known of their combined sub-lethal effect in the field. In this study, a combination of esterase activity and ventilation rate assays was performed to determine the neurological and physiological function of the freshwater crustacean Asellus aquaticus (L.) at sites above and below a sewage treatment works (STW). Cholinesterase and carboxylesterase activities were significantly inhibited (n=8, P<0.05) and ventilation rates increased (n=8, P=0.0001) in A. aquaticus at STW sites compared to those from reference sites, indicating a decrease in neurological and physiological function. The ecological relevance of these findings for the population dynamics of the organisms in the field is discussed.

Differential sensitivity of three marine invertebrates to copper assessed using multiple biomarkers.

Understanding how biomarkers relate to each other on exposure to particular contaminants in different species is key to their widespread application in environmental management. However, few studies have systematically used multiple biomarkers in more than a single species to determine the variability of sublethal effects of a particular contaminant. In this study, three marine invertebrates, the shore crab Carcinus maenas, the common limpet Patella vulgata and the blue mussel Mytilus edulis, were exposed over 7 days in the laboratory to environmentally realistic concentrations of the priority pollutant copper. A combination of molecular, cellular and physiological biomarkers was measured in each organism to detect the toxic effects of copper. Biomarkers included lysosomal stability (neutral red retention), neurotoxicity (acetylcholinesterase activity), metabolic impairment (total haemolymph protein), physiological status (heart rate) and induction of protective metallothionein proteins. P. vulgata was the most sensitive to copper with significant effects measured in all biomarkers at concentrations of 6.1 microg Cu l(-1). In C. maenas, cellular and neurotoxic endpoints were affected significantly only at 68.1 microg Cu l(-1). Exposure to copper also induced metallothionein production in crabs. Over a 7-day exposure period, M. edulis was the most tolerant species to copper with significant effects being observed at the cellular level only at 68.1 microg Cu l(-1) . In all three species, cellular and neurotoxic pathways were more sensitive to disruption than physiological processes (protein and heart rate). Results illustrate how a suite of biomarkers applied to different sentinel species can provide a 'diagnosis of stress', whereby, effects at the molecular level can be used to interpret the level of physiological impairment of the organism.

Effects of carbohydrate meals of varying consistency on gastric myoelectrical activity.

BACKGROUND: There is at present no agreement on the type of test meal to be used when performing EGG. To our knowledge the response of the stomach to high carbohydrate isocaloric meals of different consistencies has not been formally assessed. AIM: To study 1) the effects of high carbohydrate meals of varying consistency on EGG activity; and 2) the effects of increasing the calorie content of a meal without changing its consistency and composition on the postprandial EGG. SUBJECTS: Eighteen healthy volunteers, six males (age: 21-35 year, weight: 45-60 kg) and 12 females in the follicular phase of the menstrual cycle (age: 24-30 years, weight: 45-55 kg). METHODS: Following an overnight fast subjects were given three high carbohydrate, low fat, isocaloric meals (165-170 kcal) of different consistencies (solid, semisolid, liquid), on three separate days in a random order. The liquid and semisolid meals were equal in volume (200 ml) while the volume of the solid meal was smaller. One hour EGG recordings were done in the fasting and fed states in each subject. As a second step, ten of the above volunteers (taken randomly) were given the solid test meal on a separate day after increasing the calorie content of the meal to 350 kcal. RESULTS: The power of the EGG at the dominant frequency significantly increased after solid (175 kcal meal: fasting 49 +/- 12 dB vs. fed 57 +/- 13 dB; p < 0.05, 375 kcal meal: fasting 48.5 +/- 12.9 dB vs fed 58.1 +/- 11.7 dB) and semisolid (fasting 50 +/- 12 dB vs. fed 55 +/- 13; P < 0.05). The increase in power was not significantly different when fed with solids and semisolids. There was no statistically significant change in EGG power during the first 15 or 60 minutes after the liquid meal. Feeding showed no significant effect on the dominant frequency and the percentage of 2-4 cpm waves of the EGG with any of the three types of test meals. CONCLUSIONS: Solid and semisolid meals high in carbohydrate and low in fat are capable of inducing a significant increase in the EGG power in normal subjects. Isocaloric solid and semisolid meals have similar effects on gastric slow wave activity. EGG appears unaffected by the liquid meal. Therefore only an increase in the power of the EGG can be regarded as normal if a high carbohydrate solid or a semisolid meal is given as the test meal when performing an EGG.

Long-term complications in newly diagnosed Sri Lankan patients with type 2 diabetes mellitus.

We screened 597 newly-diagnosed diabetic patients (201 women) mean +/- SD age 42.3 +/- 6.2 years to determine the prevalence of diabetic complications; 22% presented because of symptoms of diabetes, 27% were diagnosed when hyperglycaemia was discovered at a health screening, and 36% were diagnosed while being treated for intercurrent illness. Neuropathy was present in 25.1%, nephropathy in 29%, retinopathy in 15%, coronary vascular disease in 21%, stroke in 5.6%, peripheral vascular disease in 4.8%, hypertension in 23%, obesity in 16%, central obesity in 21.3%, hypercholesterolaemia in 11%, hypertriglyceridaemia in 14%, and low high-density lipoprotein cholesterol in 12%. The prevalence of coronary vascular disease, hypertension, stroke, neuropathy and retinopathy at the time of diagnosis were higher in our patients than in Caucasian and Indo-Asian patients in the UK. Both a genetic predisposition to develop complications, and exposure to a longer duration of asymptomatic hyperglycaemia due to poor access to adequate health care, may contribute to the high frequency of complications at diagnosis. Since complications are already present at diagnosis, there is a case for implementing primary prevention programmes combined with screening for diabetes in high-risk groups.