Carbamates

Type 2 diabetes mellitus is characterised by abnormal beta-cell function (present at the time of diagnosis) that is often associated with insulin resistance. An important and consistent pathophysiological finding is the failure to produce adequate increments in insulin secretion in response to carbohydrate intake. Therefore, insulin secretagogue therapy, particularly when focused on prandial glucose regulation, is a logical approach to treatment because it addresses one of the most fundamental pathophysiological aspects of the disease. However, the traditional secretagogues-the sulphonylureas--have long been associated with the unwanted effect of hypoglycaemia. This is particularly likely to occur when drugs with lengthy plasma half-lives, prolonged drug-receptor interactions, active metabolites or a reliance on renal clearance are used. The problem is most prevalent in elderly patients, where sulphonylurea-induced hypoglycaemia may be related to failure to comply with strict mealti...

Since the development and release of sulfonylureas for the treatment of T2DM, additional oral glycemic control agents with different mechanisms of action have allowed for more flexibility in targeting drug to patient. Based on available evidence, metformin monotherapy is preferred for the vast majority of T2DM patients who are overweight or obese. Combination therapy has further improved glycemic control. However, limitations in use, including the challenges of side effects, to that of secondary oral agent failure will inevitably occur over time. These challenges leave ample room for the development of agents that address the pathophysiology not only of treating insulin resistance and decreasing insulin production but also of preventing or delaying the development of diabetes in populations at risk.

We investigated the effects of three different pesticides (carbendazim, dimethoate, and glyphosate) and their mixture on the growth and reproduction of the earthworm species, Eisenia fetida. The study was conducted following the suggestion of the International Workshop on Earthworm Ecotoxicology. The results showed that the pesticide treatment had a marked negative impact on the growth and reproduction of earthworms. Carbendazim and dimethoate were found to cause greater harm to the selected earthworm species than glyphosate.

A combination of bioenergetics and biochemical biomarkers in mussels was applied to assess possible pollution impacts in a protected semi-enclosed estuary (Amvrakikos Gulf, NW Greece) that receives pesticide discharges through riverine transport. Scope for growth, a physiological condition index representing the energy budget of the organism, was applied to detect general stress effects on the health status of mussels. The low energy budgets of mussels revealed stress conditions and provided early warning signals of possible consequences at higher levels of biological organization. Biochemical markers of exposure confirmed a risk of pesticide contamination. Decreased acetylcholinesterase activities indicated exposure to organophosphate and carbamate pesticides. Responses of the antioxidant enzyme glutathione peroxidase suggested the presence of contaminants capable of reactive oxygen species production that could be related to organochlorine pesticide contamination in the area. On the other hand, metallothionein levels implied low metal contamination.

Ethanolamine is a biogenic amine found naturally in the body as part of membrane lipids and as a metabolite of the cardioprotective substances, sphingosine-1-phosphate (S1P) and anandamide. In the brain, ethanolamine, formed from the breakdown of anandamide protects against ischaemic apoptosis. However, the effects of ethanolamine in the heart are unknown. Signal transducer and activator of transcription 3 (STAT-3) is a critical prosurvival factor in ischaemia/reperfusion (I/R) injury. Therefore, we investigated whether ethanolamine protects the heart via activation of STAT-3. Isolated hearts from wildtype or cardiomyocyte specific STAT-3 knockout (K/O) mice were pre-treated with ethanolamine (Etn) (0.3 mmol/L) before I/R insult. In vivo rat hearts were subjected to 30 min ischaemia/2 h reperfusion in the presence or absence of 5 mg/kg S1P and/or the FAAH inhibitor, URB597. Infarct size was measured at the end of each protocol by triphenyltetrazolium chloride staining. Pre-treatment with ethanolamine decreased infarct size in isolated mouse or rat hearts subjected to I/R but this infarct sparing effect was lost in cardiomyocyte specific STAT-3 deficient mice. Pre-treatment with ethanolamine increased nuclear phosphorylated STAT-3 [control 0.75 ± 0.08 vs. Etn 1.50 ± 0.09 arbitrary units; P < 0.05]. Our findings suggest a novel cardioprotective role for ethanolamine against I/R injury via activation of STAT-3.

Pesticides, due to their intensive use and their peculiar chemical features, can persist in the environment and enter the trophic chain, thus representing an environmental risk for the ecosystems and human health. Although there are several robust and reliable standard analytical techniques for their monitoring, the high frequency of contamination caused by pesticides requires methods for massive monitoring campaigns that are capable of rapidly detecting these compounds in many samples of different origin. Immunosensors represent a potential tool for simple, rapid, and sensitive monitoring of pesticides. Antibodies coupled to electrochemical or optical transducers have resulted in effective detection devices. In this review, the new trends in immunosensor development and the application of immunosensors for the detection of pesticides of environmental concern-such as glyphosate, organophosphates, and neonicotinoids-are described.