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Target to treat diabetes

Stela Vujosevic, Tommaso Torresin, Silvia Bini, Enrica Convento, Elisabetta Pilotto, Raffaele Parrozzani, Edoardo Midena
PURPOSE: To evaluate changes of specific retinal imaging biomarkers [intraretinal hyper-reflective retinal spots: HRS ; subfoveal neuroretinal detachment: SND; and increased foveal autofluorescence: IFAF after intravitreal steroid or anti-vascular endothelial growth factor treatment in diabetic macular oedema (DME)] as possible indicators of retinal inflammatory condition. METHODS: Retrospective analysis of images and clinical charts of 49 eyes (49 patients) with DME treated with intravitreal dexamethasone (dexamethasone, 23 eyes) or intravitreal ranibizumab (ranibizumab, 26 eyes)...
October 24, 2016: Acta Ophthalmologica
Julien Wils, Julie Favre, Jérémy Bellien
Diabetes induces a decrease in the number and function of different pro-angiogenic cells types generically designated as putative endothelial progenitor cells (EPC), which encompasses cells from myeloid origin that act in a paracrine fashion to promote angiogenesis and putative "true" EPC that contribute to endothelial replacement. This not only compromises neovasculogenesis in ischemic tissues but also impairs, at an early stage, the reendotheliziation process at sites of injury, contributing to the development of endothelial dysfunction and cardiovascular complications...
October 20, 2016: Pharmacology & Therapeutics
Vidya Narayanaswami, Linda P Dwoskin
Obesity is a global epidemic that contributes to a number of health complications including cardiovascular disease, type 2 diabetes, cancer and neuropsychiatric disorders. Pharmacotherapeutic strategies to treat obesity are urgently needed. Research over the past two decades has increased substantially our knowledge of central and peripheral mechanisms underlying homeostatic energy balance. Homeostatic mechanisms involve multiple components including neuronal circuits, some originating in hypothalamus and brain stem, as well as peripherally-derived satiety, hunger and adiposity signals that modulate neural activity and regulate eating behavior...
October 20, 2016: Pharmacology & Therapeutics
Fan-Shiu Tsai, Li-Wei Lin, Chi-Rei Wu
Lupeol belongs to pentacyclic lupane-type triterpenes and exhibits in edible vegetables, fruits and many plants. Many researches indicated that lupeol possesses many beneficial pharmacological activities including antioxidant, anti-inflammatory, anti-hyperglycemic, anti-dyslipidemic and anti-mutagenic effects. From various disease-targeted animal models, these reports indicated that lupeol has anti-diabetic, anti-asthma, anti-arthritic, cardioprotective, hepatoprotective, nephroprotective, neuroprotective and anticancer efficiency under various routes of administration such as topical, oral, subcutaneous, intraperitoneal and intravenous...
2016: Advances in Experimental Medicine and Biology
Alejandro R Chade, John E Hall
Obesity is largely responsible for the growing incidence and prevalence of diabetes, cardiovascular and renal diseases. Current strategies to prevent and treat obesity and its consequences have been insufficient to reverse the ongoing trends. Lifestyle modification or pharmacological therapies often produce modest weight loss which is not sustained and recurrence of obesity is frequently observed, leading to progression of target organ damage in many obese subjects. Therefore, research efforts have focused not only on the factors that regulate energy balance, but also on understanding mechanisms of target organ injury in obesity...
October 22, 2016: American Journal of Nephrology
Minjie Zhao, Michel Mozeika Arau Jo, Stéphanie Dal, Séverine Sigrist, Martine Bergaentzlé, David Ramanitrahasimbola, Charles Andrianjara, Eric Marchioni
This study describes a selective and effective pressurized liquid extraction (PLE) coupled with HPLC-DAD-ESI/MS method for the identification and quantification of three fructosazine analogues (FZAs), fructosazine, 2,6- and 2,5-deoxyfructosazine in Madeglucyl(®) (MG) which is an ammonia treated extract of Eugenia jambolana Lamarck seeds, and is the world's first anti-diabetic phytodrug. FZAs were extracted from MG by PLE using methanol as extraction solvent. The PLE extract was then analyzed directly by HPLC-DAD-ESI/MS without cleanup step...
October 13, 2016: Journal of Chromatography. A
XinWang Zhu, CongXiao Zhang, QiuLing Fan, XiaoDan Liu, Gang Yang, Yi Jiang, LiNing Wang
BACKGROUND Diabetic nephropathy (DN) is the most lethal diabetic microvascular complication; it is a major cause of renal failure, and an increasingly globally prominent healthcare problem. MATERIAL AND METHODS To identify susceptible microRNAs for the pathogenesis of DN and the targets of losartan treatment, microRNA arrays were employed to survey the glomerular microRNA expression profiles of KKAy mice treated with or without losartan. KKAy mice were assigned to either a losartan-treated group or a non-treatment group, with C57BL/6 mice used as a normal control...
October 22, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Helena Lenasi, Markos Klonizakis
Diabetes mellitus (DM) is associated with cardiovascular complications. Impairment of glycemic control induces noxious glycations, an increase in oxydative stress and dearangement of various metabolic pathways. DM leads to dysfunction of micro and macrovessels, connected to metabolic, endothelial and autonomic nervous system. Thus, assessing vascular reactivity might be one of the clinical tools to evaluate the impact of harmful effects of DM and potential benefit of treatment; skin and skeletal muscle microcirculation have usually been tested...
October 18, 2016: Clinical Hemorheology and Microcirculation
Finja Jockenhöfer, Katharina Herberger, Jörg Schaller, Katja Christina Hohaus, Maren Stoffels-Weindorf, Philipp Al Ghazal, Matthias Augustin, Joachim Dissemond
INTRODUCTION: Pyoderma gangrenosum (PG) is a rare neutrophilic, ulcerative skin disease of largely unknown pathophysiology. MATERIAL AND METHODS: In this study, potentially relevant cofactors and comorbidities in patients with PG from three dermatological wound care centers in Germany were evaluated. RESULTS: Of the 121 patients assessed, women (66.9 %) were more frequently affected than men. Patient age ranged from 18 to 96 years (mean 59...
October 2016: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
Chiranjit Ghosh, Santanu Mandal, Gourab D Banik, Abhijit Maity, Prabuddha Mukhopadhyay, Shibendu Ghosh, Manik Pradhan
The inability to envisage the acute onset and progression of type 1 diabetes (T1D) has been a major clinical stumbling block and an important area of biomedical research over the last few decades. Therefore there is a pressing need to develop a new and an effective strategy for early detection of T1D and to precisely distinguish T1D from type 2 diabetes (T2D). Here we describe the precise role of the enzymatic activity of carbonic anhydrase (CA) in erythrocytes in the pathogenesis of T1D and T2D. We show that CA activities are markedly altered during metabolism of T1D and T2D and this facilitates to the oxygen-18 ((18)O) isotopic fractionations of breath CO2...
October 21, 2016: Scientific Reports
Stepana Boukalova, Jan Stursa, Lukas Werner, Zuzana Ezrova, Jiri Cerny, Ayenachew Bezawork-Geleta, Alena Pecinova, Lanfeng Dong, Zdenek Drahota, Jiri Neuzil
Pancreatic cancer is one of the hardest-to-treat types of neoplastic diseases. Metformin, a widely prescribed drug against type 2 diabetes mellitus, is being trialed as an agent against pancreatic cancer, although its efficacy is low. With the idea of delivering metformin to its molecular target, the mitochondrial complex I (CI), we tagged the agent with the mitochondrial vector, triphenylphosphonium group. Mitochondrially targeted metformin (MitoMet) was found to kill a panel of pancreatic cancer cells 3-4 orders of magnitude more efficiently than found for the parental compound...
October 7, 2016: Molecular Cancer Therapeutics
Bhavana Sosale, Aravind Sosale, Arpandev Bhattacharyya
INTRODUCTION: Dapagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, is a promising drug approved for the treatment of type 2 diabetes mellitus (T2DM). However, its cost is an obstacle for use in developing countries like India. Thus, we aimed to analyse the impact on the cost of insulin therapy after adding dapagliflozin for patients using insulin in real-world clinical practice. METHODS: This retrospective chart review study included patients with uncontrolled T2DM previously on maximum doses of OADs and insulin therapy, initiated on dapagliflozin...
October 19, 2016: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Young Kwang Chae, Lauren Chiec, Nisha Mohindra, Ryan Gentzler, Jyoti Patel, Francis Giles
Immune checkpoint inhibitors such as pembrolizumab, ipilimumab, and nivolumab, now FDA-approved for use in treating several types of cancer, have been associated with immune-related adverse effects. Specifically, the antibodies targeting the programmed-cell death-1 immune checkpoint, pembrolizumab and nivolumab, have been rarely reported to induce the development of type 1 diabetes mellitus. Here we describe a case of a patient who developed antibody-positive type 1 diabetes mellitus following treatment with pembrolizumab in combination with systemic chemotherapy for metastatic adenocarcinoma of the lung...
October 19, 2016: Cancer Immunology, Immunotherapy: CII
Robyn T Rebbeck, Maram M Essawy, Florentin R Nitu, Benjamin D Grant, Gregory D Gillispie, David D Thomas, Donald M Bers, Razvan L Cornea
Using time-resolved fluorescence resonance energy transfer (FRET), we have developed and validated the first high-throughput screening (HTS) method to discover compounds that modulate an intracellular Ca(2+) channel, the ryanodine receptor (RyR), for therapeutic applications. Intracellular Ca(2+) regulation is critical for striated muscle function, and RyR is a central player. At resting [Ca(2+)], an increased propensity of channel opening due to RyR dysregulation is associated with severe cardiac and skeletal myopathies, diabetes, and neurological disorders...
October 19, 2016: Journal of Biomolecular Screening
Ajay Kumar, Edward Franek, Jonathan Wise, Marcus Niemeyer, Henriette Mersebach, Rafael Simó
PURPOSE: The efficacy and safety of insulin degludec/insulin aspart (IDegAsp) once daily (OD) compared with insulin glargine U100 (IGlar) OD over 52 weeks in insulin-naïve adults with type 2 diabetes mellitus (T2DM) was investigated. METHODS: In this open-label, parallel-group treat-to-target trial, participants were randomized (1:1) to receive IDegAsp OD (breakfast, n = 266) or IGlar OD (as per label, n = 264). Participants then entered a 26-week extension phase (IDegAsp OD, n = 192; IGlar OD, n = 221)...
2016: PloS One
Eda Cengiz, Peiyao Cheng, Katrina J Ruedy, Craig Kollman, William V Tamborlane, Georgeanna J Klingensmith, Robin L Gal, Janet Silverstein, Joyce Lee, Maria J Redondo, Roy W Beck
OBJECTIVE: Current data are limited on the course of type 1 diabetes (T1D) in children and adolescents through the first few years of diabetes. The Pediatric Diabetes Consortium T1D new onset (NeOn) Study was undertaken to prospectively assess natural history and clinical outcomes in children treated at 7 US diabetes centers from the time of diagnosis. This paper describes clinical outcomes in the T1D NeOn cohort during the first 3 years postdiagnosis. RESULTS: A total of 1048 participants (mean age 9...
October 19, 2016: Pediatric Diabetes
Michał Holecki, Gabriela Handzlik-Orlik, Agnieszka Almgren-Rachtan, Jan Duława, Jerzy Chudek
BACKGROUND: Statins are used to reduce a cardiovascular risk. However, the effectiveness of the therapy in many cases remains unsatisfactory. Therefore, the aim of this study was to evaluate the influence of obesity and diabetes on the achievement of therapeutic goal in lipid-lowering therapy in patients with a various cardiovascular risk in the daily clinical practice. METHODS: This study was conducted on the basis of questionnaires obtained from 7018 patients (41...
September 13, 2016: Pharmacological Reports: PR
Jongha Park
Cardiovascular (CV) risk assessment is not easy in chronic kidney disease (CKD) patients. Age, male sex, race, family history of CV disease, smoking status and diabetes should be considered as CV risk factors as the general population. It is also accepted that hypertension (HTN) is associated with the greater risk of CV complications in this population. However, there are some concerns in this issue.First, supporting evidence for specific blood pressure (BP) targets in CKD is scarce. Many observational studies reported a J-shaped association between BP level and CV mortality unlike a linear association in the general population...
September 2016: Journal of Hypertension
Ming Liu, Lihua Li, Jihong Chu, Guoliang Dai, Wenzheng Ju, Zhenxing Wang, Zhuyuan Fang
OBJECTIVE: Nicotinamide N-methyltransferase (NNMT) is a novel histone methylation modulator that regulates energy metabolism, and NNMT knockdown prevents diet-induced obesity in mice. However, whether NNMT plays a role in human obesity and type 2 diabetes mellitus (T2DM) remains to be elucidated. NNMT catalyzes methylation of nicotinamide to generate N-methylnicotinamide (me-NAM). We aimed to investigate the associations of serum me-NAM with obesity and T2DM in Chinese. DESIGN AND METHOD: The study subjects (n = 1160) were recruited from Dali, a city of Yunan province, in southwest China...
September 2016: Journal of Hypertension
Clive Rosendorff
Many guidelines for the management of hypertension have recommended that the goal of antihypertensive treatment in the elderly (usually specified as 80 years or above) should be less than 150/90 mmHg. SPRINT included subjects 50 years or above, and a substantial proportion of subjects 75 years and older. These are individuals at high risk for adverse cardiovascular events because of high prevalence of hypertension and atherosclerotic disease. The less stringent BP goals have been based on a percieved danger of lowering BP to levels that threaten vital organ pefusion (myocardium, brain, kidney)...
September 2016: Journal of Hypertension
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