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    ABSTRACT: Most patients with type 2 diabetes mellitus (T2DM) are overweight or obese. Both T2DM and overweight/obesity are associated with increased patient risk of cardiovascular events and mortality. Despite being the recognized cornerstone of treatment, weight loss and maintenance of weight loss are difficult for patients with T2DM, particularly as treatments for T2DM may cause weight gain. Sodium glucose cotransporter 2 (SGLT2) inhibitors, a new class of drug for the treatment of patients with T2DM, reduce renal glucose reabsorption, resulting in urinary glucose excretion. Due to the caloric loss associated with decreased glucose in urine, treatment with SGLT2 agents offers the benefit of weight loss to patients, as well as reduction in hyperglycemia. Clinical trials of SGLT2 inhibitors in patients with T2DM, ranging in length from 4 to 90 weeks, have shown patient weight reductions from baseline of up to 4.7 kg. Such weight loss may have beneficial effects on adherence to medication, glycemic control, and cardiovascular risk in patients with T2DM.
    No preview · Article · Sep 2013 · Postgraduate Medicine
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    ABSTRACT: There is continuing belief that cardiac parasympathetic postganglionic fibres are sparse or absent from the ventricles. This review of the literature shows that the supposition is a myth. Early studies considered that fine silver stained fibres coursing amongst ventricle myocardial cells were likely cardiac parasympathetic postganglionic fibres. The conclusions were later supported by acetyl cholinesterase staining using a method that appeared not to be associated with noradrenaline nerve fibres. The conclusion is critically examined in the light of several recent histological studies using the acetyl cholinesterase method and also a more definitive technique (CHAT), that suggest a widespread location of parasympathetic ganglia and a relatively dense parasympathetic innervation of ventricular muscle in a range of mammals including man. The many studies demonstrating acetylcholine release in the ventricle on vagal nerve stimulation and a high density of acetylcholine M2 receptors is in accord with this as are tests of ventricular performance from many physiological studies. Selective control of cardiac functions by anatomically segregated parasympathetic ganglia is discussed. It is argued that the influence of vagal stimulation on ventricular myocardial action potential refractory period, duration, force and rhythm is evidence that vagal fibres have close apposition to myocardial fibres. This is supported by clear evidence of accentuated antagonism between sympathetic activity and vagal activity in the ventricle and also by direct effects of vagal activity independent of sympathetic. The idea of differential control of atrial and ventricle physiology by vagal C and vagal B preganglionic fibres is examined as well as differences in chemical phenotypes and their function. The latter is reflected in medullary and supramedullary control. The importance of this knowledge to understanding the normal physiology of cardiac autonomic control and significance to pathology is referred to.
    Full-text · Article · Jul 2013 · The Journal of Physiology
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    ABSTRACT: Significant advances have been made in the last 5 years that have finally allowed investigators to start targeting stromal cells such as fibroblasts in inflammatory disease. Rheumatoid arthritis is a prototype inflammatory disease, in which fibroblasts maintain the persistence of inflammation in the joint underpinned by a unique pathological phenotype driven by multiple epigenetic modifications. The step changes that are enabling the development of such therapies are an improved understanding of the mechanisms by which fibroblasts mediate persistence and the discovery of new markers that identify discrete functional subsets of fibroblast cells that have potential as disease-specific therapeutic targets.
    No preview · Article · Apr 2013 · Current Opinion in Pharmacology
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