Modulation of the Cellular Expression of Circulating Advanced Glycation End-Product Receptors in Type 2 Diabetic Nephropathy

Background. Advanced glycation end-products (AGEs) and their receptors are prominent contributors to diabetic kidney disease. Methods. Flow cytometry was used to measure the predictive capacity for kidney impairment of the AGE receptors RAGE, AGE-R1, and AGE-R3 on peripheral blood mononuclear cells (PBMCs) in experimental models of type 2 diabetes (T2DM) fed varied AGE containing diets and in obese type 2 diabetic and control human subjects. Results. Diets high in AGE content fed to diabetic mice decreased cell surface RAGE on PBMCs and in type 2 diabetic patients with renal impairment (RI). All diabetic mice had elevated Albumin excretion rates (AERs), and high AGE fed dbdb mice had declining Glomerular filtration rate (GFR). Cell surface AGE-R1 expression was also decreased by high AGE diets and with diabetes in dbdb mice and in humans with RI. PBMC expression of AGE R3 was decreased in diabetic dbdb mice or with a low AGE diet. Conclusions. The most predictive PBMC profile for renal disease associated with T2DM was an increase in the cell surface expression of AGE-R1, in the context of a decrease in membranous RAGE expression in humans, which warrants further investigation as a biomarker for progressive DN in larger patient cohorts

Glucose homeostasis can be differentially modulated by varying individual components of a western diet

Chronic overconsumption of a Western diet has been identified as a major risk factor for diabetes, yet precisely how each individual component contributes to defects in glucose homeostasis independent of consumption of other macronutrients remains unclear. Eight-week-old male Sprague Dawley rats were randomized to feeding with one of six semi-pure diets: control, processed (high advanced glycation end products/AGE), high protein, high dextrose (glucose polymer), high in saturated fat (plant origin), or high in saturated fat (animal origin). After chronic feeding for 24 weeks, body composition was determined by bioelectrical impedance spectroscopy and glucose homeostasis was assessed. When compared to the control and high AGE diets, excess consumption of the diet high in saturated fat (animal source) increased body weight and adiposity, and decreased insulin sensitivity, as defined by HOMA IR, impaired skeletal muscle insulin signaling and insulin hypersecretion in the context of increased circulating glucagon-like peptide (GLP-1). Compared to the control diet, chronic consumption of the high AGE, protein or dextrose diet increased fasting plasma glucose, decreased fasting plasma insulin and insulin secretion. These diets also reduced circulating GLP-1 concentrations. These data suggest that individual components of a western diet have differential effects in modulating glucose homeostasis and adiposity. These data provide clear evidence of a link between over-consumption of a western diet and the development of diabetes

Electrochemotherapy for the palliative management of cutaneous metastases: A systematic review and meta-analysis.

BACKGROUND: Electrochemotherapy combines electroporation in conjunction with chemotherapeutic agents and is used to treat tumours in many localisations, including cutaneous metastases. The symptoms associated with cutaneous malignant wounds can be distressing for patients and their management is a challenge in healthcare. AIM: The purpose of this systematic review was to investigate the effectiveness of electrochemotherapy in the context of palliative care. DESIGN: All aspects of the systematic review were followed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. DATA SOURCES: The following databases were searched for English-language reviews; Medline, Embase, CINAHL, British Nursing Index and the Cochrane Library. The search was conducted between the publication of Standard Operating Procedures in 2006 and the third week of October 2017. Studies involving oral cancers and studies with fewer than 10 patients were excluded. The selected studies were assessed for risk of bias and sub-group data were synthesised in a random-effects meta-analysis. RESULTS: From 425 studies, 29 studies were included involving 1503 patients, the pooled results were 46.6% for complete response and 82.2% for objective response according to the Response Evaluation Criteria in Solid Tumours. The meta-analysis indicated that small tumours were over twice as likely (2.25) to have a complete response than large. CONCLUSIONS: Electrochemotherapy is an effective, repeatable and minimally invasive intervention within the palliative population that can reduce symptom burden. This review is an update of previous systematic reviews by Mali et al. [1,2] and highlights the need for tailored treatment depending on each individual case