Current Issue : July - September Volume : 2015 Issue Number : 3 Articles : 5 Articles
Diabetes is a worldwide epidemic that has led to a rise in diabetic kidney disease (DKD). Over the past two decades, there has\nbeen significant clarification of the various pathways implicated in the pathogenesis of DKD. Nonetheless, very little has changed\nin the way clinicians manage patients with this disorder. Indeed, treatment is primarily centered on controlling hyperglycemia and\nhypertension and inhibiting the renin-angiotensin system. The purpose of this review is to describe the current understanding of\nhow the hemodynamic, metabolic, inflammatory, and alternative pathways are all entangled in pathogenesis of DKD and detail the\nvarious therapeutic targets that may one day play a role in quelling this epidemic....
Type 2 diabetes mellitus (T2DM) has become one of the most prevalent noncommunicable diseases in the past years. It is\nundoubtedly associated with atherosclerosis and increased risk for cardiovascular diseases. Incretins, which are intestinal peptides\nsecreted during digestion, are able to increase insulin secretion and its impaired function and/or secretion is involved in the\npathophysiology of T2DM. Dipeptidyl peptidase 4 (DPP4) is an ubiquitous enzyme that regulates incretins and consequently is\nrelated to the pathophysiology of T2DM.DPP4 is mainly secreted by endothelial cells and acts as a regulatory protease for cytokines,\nchemokines, and neuropeptides involved in inflammation, immunity, and vascular function. In T2DM, the activity of DPP4 seems\nto be increased and there are a growing number of in vitro and in vivo studies suggesting that this enzyme could be a new link\nbetween T2DM and atherosclerosis. Gliptins are a new class of pharmaceutical agents that acts by inhibiting DPP4. Thus, it is\nexpected that gliptin represents a new pharmacological approach not only for reducing glycemic levels in T2DM, but also for the\nprevention and treatment of atherosclerotic cardiovascular disease in diabetic subjects. We aimed to review the evidences that\nreinforce the associations between DPP4, atherosclerosis, and T2DM....
Distal symmetric polyneuropathy (DSPN), the\nmost common form of diabetic neuropathy, has a complex\npathophysiology and can be a major source of physical and\npsychologic disability. Themanagement ofDSPN can be frustrating\nfor both patient and physician. This article provides a\ngeneral overview of typical patient pathways in DSPN, and\nhighlights variations in diagnosis, management, and referral\npatterns among different providers. DSPN is managed in several\nsettings by primary care physicians (PCPs), specialists,\nand nurse practitioners. The initial clinical management of\nthe patient is often dependent on the presenting complaint,\nthe referral pattern of the provider, level of comfort of the\nPCP in managing diabetic complications, and geographic access\nto specialists. The primary treatment of DSPN focuses\nmainly on glycemic control and adjustment of modifiable risk\nfactors, but other causes of neuropathy should also be investigated.\nSeveral pharmacologic agents are recommended by\ntreatment guidelines, and as DSPN typically exists with comorbid\nconditions, a multimodal therapeutic approach should\nbe considered. Barriers to effective management include failure\nto recognize DSPN, and misdiagnosis. Patient education\nalso remains important. Referral patterns vary widely according\nto geographic location, access to services, provider preferences,\nand comfort in managing complex aspects of the\ndisease. The variability in patient pathways affects patient\neducation, satisfaction, and outcomes. Standardized screening\ntools, a multidisciplinary team approach, and treatment algorithms\nfor diabetic neuropathy should improve future care. To\nimprove patient outcomes, DSPN needs to be diagnosed sooner\nand interventions made before significant nerve damage\noccurs....
Lipoxin A4 has been described as a major signal for the resolution of inflammation and is abnormally produced in the lungs of\npatients with cystic fibrosis (CF). In CF, the loss of chloride transport caused by the mutation in the cystic fibrosis transmembrane\nconductance regulator (CFTR) Cl? channel gene results in dehydration,mucus plugging, and reduction of the airway surface liquid\nlayer (ASL) height which favour chronic lung infection and neutrophil based inflammation leading to progressive lung destruction\nand early death of people with CF. This review highlights the unique ability of LXA4 to restore airway surface hydration, to\nstimulate airway epithelial repair, and to antagonise the proinflammatory programof the CF airway, circumventing someof the most\ndifficult aspects of CF pathophysiology. The report points out novel aspects of the cellular mechanism involved in the physiological\nresponse to LXA4, including release of ATP fromairway epithelial cell via pannexin channel and subsequent activation of and P2Y11\npurinoreceptor. Therefore, inadequate endogenous LXA4 biosynthesis reported in CF exacerbates the ion transport abnormality\nand defective mucociliary clearance, in addition to impairing the resolution of inflammation, thus amplifying the vicious circle of\nairway dehydration, chronic infection, and inflammation....
The traditionally recognized role of vitamin D consists in the regulation of bone metabolism and calcium-phosphorus homeostasis\nbut recently a lot of in vitro and in vivo studies recognized several ââ?¬Å?noncalcemicââ?¬Â effects of vitamin D metabolites. Accumulating\nevidence suggests that the metabolic pathways of this vitamin may play a key role in the developing of gynaecological/obstetric\ndiseases. VDR-mediated signalling pathways and vitamin D levels seem to (deeply) affect the risk of several gynaecological\ndiseases, such as polycystic ovary syndrome (PCOS), endometriosis, and ovarian and even breast cancer. On the other hand,\nsince also the maternal-fetal unit is under the influence of vitamin D, a breakdown in its homeostasis may underlie infertility,\npreeclampsia, and gestational diabetes mellitus (GDM). According to our literature review, the relationship between vitamin D and\ngynaecological/obstetric diseases must be replicated in future studies which could clarify the molecular machineries behind their\ndevelopment.We suggest that further investigation should take into account the different serum levels of this vitamin, the several\nactions which arise from the binding between it and its receptor (taking into account its possible polymorphism), and finally the\ninterplay between vitamin D metabolism and other hormonal and metabolic pathways...
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