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https://www.readbyqxmd.com/read/28218739/suppression-of-islet-homeostasis-protein-thwarts-diabetes-mellitus-progression
#1
Seh-Hoon Oh, Marda L Jorgensen, Clive H Wasserfall, Altin Gjymishka, Bryon E Petersen
During progression to type 1 diabetes, insulin-producing β-cells are lost through an autoimmune attack resulting in unrestrained glucagon expression and secretion, activation of glycogenolysis, and escalating hyperglycemia. We recently identified a protein, designated islet homeostasis protein (IHoP), which specifically co-localizes within glucagon-positive α-cells and is overexpressed in the islets of both post-onset non-obese diabetic (NOD) mice and type 1 diabetes patients. Here we report that in the αTC1...
February 20, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28202628/effects-of-upgrade-versus-de-novo-cardiac-resynchronization-therapy-on-clinical-response-and-long-term-survival-results-from-a-multicenter-study
#2
Mate Vamos, Julia W Erath, Zsolt Bari, Denes Vagany, Sven P Linzbach, Tatsiana Burmistrava, Carsten W Israel, Gabor Z Duray, Stefan H Hohnloser
BACKGROUND: Benefits of cardiac resynchronization therapy (CRT) on morbidity and mortality in selected patients are well known. Although the number of upgrade procedures from single- or dual-chamber devices to CRT is increasing, there are only sparse data on the outcomes of upgrade procedures compared with de novo CRT. This study aimed to evaluate clinical response and survival in patients receiving de novo versus upgrade CRT defibrillator therapy. METHODS AND RESULTS: Prospectively collected outcome data were compared in patients undergoing de novo or upgrade CRT defibrillator implantation at 3 implant centers in Germany and Hungary...
February 2017: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/28191533/inhibition-of-cyst-growth-in-pck-and-wpk-rat-models-of-polycystic-kidney-disease-with-low-doses-of-peroxisome-proliferator-activated-receptor-%C3%AE-agonists
#3
Stephanie M Flaig, Vincent H Gattone, Bonnie L Blazer-Yost
BACKGROUND AND OBJECTIVES: The studies were designed to test the efficacy of two peroxisome proliferator-activated receptor γ (PPARγ) agonists in two rodent models of polycystic kidney disease (PKD). MATERIALS AND METHODS: The PCK rat is a slowly progressing cystic model while the Wpk(-/-) rat is a rapidly progressing model. PCK rats were fed with a pharmacological (0.4 mg/kg body weight [BW]) and a sub-pharmacological (0.04 mg/kg BW) dose of rosiglitazone (week 4-28)...
September 1, 2016: Journal of Translational Internal Medicine
https://www.readbyqxmd.com/read/28168619/pure-endoscopic-management-of-epileptogenic-hypothalamic-hamartomas
#4
S Chibbaro, H Cebula, J Scholly, J Todeschi, I Ollivier, A Timofeev, M Ganau, P Di Emidio, M P Valenti, A M Staack, T Bast, B J Steinhoff, E Hirsch, P Kehrli, F Proust
Hypothalamic hamartomas (HH) are rare congenital malformations located in the region of the tuber cinereum and third ventricle. Their usual clinical presentation is characterized by gelastic/dacrystic seizures which often become pharmaco-resistant and progress to secondary focal/generalized intractable epilepsy causing mostly in children cognitive and behavioral problems (particularly in cases of progressive epileptic encephalopathy) and precocious puberty. Whereas gelastic seizures can be surgically controlled either by resection of the lesion or disconnection (tissue-destructive) procedures, aimed at functionally prevent the spreading of the epileptic burst; generalized seizures tend to respond better to HH excision rather than isolated neocortical resections, which generally fail to control them...
February 7, 2017: Neurosurgical Review
https://www.readbyqxmd.com/read/28138135/body-mass-index-as-a-predictor-of-healthy-and-disease-free-life-expectancy-between-ages-50-and-75-a-multicohort-study
#5
S Stenholm, J Head, V Aalto, M Kivimäki, I Kawachi, M Zins, M Goldberg, L G Platts, P Zaninotto, L L M Hanson, H Westerlund, J Vahtera
BACKGROUND: While many studies have shown associations between obesity and increased risk of morbidity and mortality, little comparable information is available on how body mass index (BMI) impacts health expectancy. We examined associations of BMI with healthy and chronic disease-free life expectancy in four European cohort studies. METHODS: Data were drawn from repeated waves of cohort studies in England, Finland, France and Sweden. BMI was categorized into four groups from normal weight (18...
January 31, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28121337/effects-of-sglt2-inhibitors-on-weight-loss-in-patients-with-type-2-diabetes-mellitus
#6
F A Ribola, F B Cançado, J H M Schoueri, V F De Toni, V H R Medeiros, D Feder
SGLT2 (sodium-glucose cotransporter type 2) inhibitors are a new class of drugs which reversibly block the glucose reabsorption that occurs in the kidneys. Since their mechanisms of action do not rely on insulin secretion, they constitute a complementary alternative to the classic treatment of type 2 diabetes mellitus. A glycemic level reduction in patients who used SGLT2 inhibitors due to the reversible block of their transporters could be observed. Associated with this, there was a reduction in body weight and blood pressure (BP) caused by osmotic diuresis...
January 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28110829/lipidomic-analysis-reveals-significant-lipogenesis-and-accumulation-of-lipotoxic-components-in-ob-ob-mouse-organs
#7
Jun Hayakawa, Miao Wang, Chunyan Wang, Rowland H Han, Zhen Y Jiang, Xianlin Han
To further understand the role of lipogenesis and lipotoxicity in the development of obesity and diabetes, lipidomes of various organs from ob/ob mice and their wild type controls were analyzed by shotgun lipidomics at 10, 12, and 16 weeks of age. We observed that the amounts of fatty acyl (FA) chains corresponding to those from de novo synthesis (e.g., 16:0, 16:1, and 18:1 FA) were substantially elevated in ob/ob mice, consistent with increased expression of genes and proteins involved in biosynthesis. Polyunsaturated fatty acid species were moderately increased in the examined tissues of ob/ob mice, since they can only be absorbed from diets or elongated from the ingested n-3 or n-6 FA...
January 11, 2017: Prostaglandins, Leukotrienes, and Essential Fatty Acids
https://www.readbyqxmd.com/read/28101643/polymorphisms-in-genes-encoding-mir-155-and-mir-146a-are-associated-with-protection-to-type-1-diabetes-mellitus
#8
Taís S Assmann, Guilherme C K Duarte, Letícia A Brondani, Pedro H O de Freitas, Égina M Martins, Luís H Canani, Daisy Crispim
AIMS: Type 1 diabetes mellitus (T1DM) is characterized by severe autoimmune destruction of pancreatic beta-cells. The triggering of autoimmunity against beta-cells is probably caused by a combination of environmental and genetic risk factors. Even though much is known about the genetic of T1DM, more information is needed to completely unravel this tangled disease. MicroRNAs (miRNAs) are a class of small noncoding RNAs molecules that negatively regulate gene expression by inducing target mRNA cleavage or by inhibiting protein translation...
January 19, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28100340/-outcome-comparison-of-different-therapy-procedures-in-surgical-high-risk-elderly-patients-with-severe-aortic-stenosis
#9
Y Q Ye, Y T Wang, Z Li, M Y Wang, H Y Xu, W J Zhang, Q R Liu, G N Niu, Y J Wu
Objective: To compare the outcome of surgical high-risk elderly patients with severe aortic stenosis(SAS) treated by different therapy procedures, including transcatheter aortic valve implantation(TAVI), surgical aortic valve replacement(SAVR), and drug therapy. Methods: We retrospectively analyzed the clinical data of 242 surgical high-risk elderly (age ≥65 years old) SAS patients hospitalized in Fuwai Hospital between September 2012 and June 2015. According to the treatment method, patients were divided into TAVI group (81 cases), SAVR group (59 cases) and drug therapy group (102 cases)...
January 25, 2017: Zhonghua Xin Xue Guan Bing za Zhi
https://www.readbyqxmd.com/read/28086882/differential-effects-of-glucagon-like-peptide-1-receptor-agonists-on-heart-rate
#10
REVIEW
Martin Lorenz, Francesca Lawson, David Owens, Denis Raccah, Christine Roy-Duval, Anne Lehmann, Riccardo Perfetti, Lawrence Blonde
While glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are known to increase heart rate (HR), it is insufficiently recognized that the extent varies greatly between the various agonists and is affected by the assessment methods employed. Here we review published data from 24-h time-averaged HR monitoring in healthy individuals and subjects with type 2 diabetes mellitus (T2DM) treated with either short-acting GLP-1 RAs, lixisenatide or exenatide, or long-acting GLP-1 RAs, exenatide LAR, liraglutide, albiglutide, or dulaglutide (N = 1112; active-treatment arms)...
January 13, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/27994747/discovery-and-optimization-of-a-novel-triazole-series-of-gpr142-agonists-for-the-treatment-of-type-2-diabetes
#11
Liangqin Guo, Dann L Parker, Yi Zang, Ramzi F Sweis, Weiguo Liu, Edward C Sherer, Nicole Buist, Jenna Terebetski, Terri Kelly, Randal Bugianesi, Birgit T Priest, Karen H Dingley, Xiaofang Li, Stan Mitelman, Gino Salituro, Maria E Trujillo, Michele Pachanski, Melissa Kirkland, Mary Ann Powles, George J Eiermann, Yue Feng, Jin Shang, Andrew D Howard, Feroze Ujjainwalla, Christopher J Sinz, John S Debenham, Scott D Edmondson, Ravi P Nargund, William K Hagmann, Derun Li
GPR142 has been identified as a potential glucose-stimulated insulin secretion (GSIS) target for the treatment of type 2 diabetes mellitus (T2DM). A class of triazole GPR142 agonists was discovered through a high throughput screen. The lead compound 4 suffered from poor metabolic stability and poor solubility. Lead optimization strategies to improve potency, efficacy, metabolic stability, and solubility are described. This optimization led to compound 20e, which showed significant reduction of glucose excursion in wild-type but not in GPR142 deficient mice in an oral glucose tolerance test (oGTT) study...
December 8, 2016: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27958378/large-scale-pharmacogenomic-study-of-sulfonylureas-and-the-qt-jt-and-qrs-intervals-charge-pharmacogenomics-working-group
#12
J S Floyd, C M Sitlani, C L Avery, R Noordam, X Li, A V Smith, S M Gogarten, J Li, L Broer, D S Evans, S Trompet, J A Brody, J D Stewart, J D Eicher, A A Seyerle, J Roach, L A Lange, H J Lin, J A Kors, T B Harris, R Li-Gao, N Sattar, S R Cummings, K L Wiggins, M D Napier, T Stürmer, J C Bis, K F Kerr, A G Uitterlinden, K D Taylor, D J Stott, R de Mutsert, L J Launer, E L Busch, R Méndez-Giráldez, N Sotoodehnia, E Z Soliman, Y Li, Q Duan, F R Rosendaal, P E Slagboom, K C Wilhelmsen, A P Reiner, Y-DI Chen, S R Heckbert, R C Kaplan, K M Rice, J W Jukema, A D Johnson, Y Liu, D O Mook-Kanamori, V Gudnason, J G Wilson, J I Rotter, C C Laurie, B M Psaty, E A Whitsel, L A Cupples, B H Stricker
Sulfonylureas, a commonly used class of medication used to treat type 2 diabetes, have been associated with an increased risk of cardiovascular disease. Their effects on QT interval duration and related electrocardiographic phenotypes are potential mechanisms for this adverse effect. In 11 ethnically diverse cohorts that included 71 857 European, African-American and Hispanic/Latino ancestry individuals with repeated measures of medication use and electrocardiogram (ECG) measurements, we conducted a pharmacogenomic genome-wide association study of sulfonylurea use and three ECG phenotypes: QT, JT and QRS intervals...
December 13, 2016: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/27957699/metabolic-surgery-in-the-treatment-algorithm-for-type-2-diabetes-a-joint-statement-by-international-diabetes-organizations
#13
Francesco Rubino, David M Nathan, Robert H Eckel, Philip R Schauer, K George M M Alberti, Paul Z Zimmet, Stefano Del Prato, Linong Ji, Shaukat M Sadikot, William H Herman, Stephanie A Amiel, Lee M Kaplan, Gaspar Taroncher-Oldenburg, David E Cummings
BACKGROUND: Despite growing evidence that bariatric/metabolic surgery powerfully improves type 2 diabetes (T2D), existing diabetes treatment algorithms do not include surgical options. AIM: The 2nd Diabetes Surgery Summit (DSS-II), an international consensus conference, was convened in collaboration with leading diabetes organizations to develop global guidelines to inform clinicians and policymakers about benefits and limitations of metabolic surgery for T2D. METHODS: A multidisciplinary group of 48 international clinicians/scholars (75% nonsurgeons), including representatives of leading diabetes organizations, participated in DSS-II...
January 2017: Obesity Surgery
https://www.readbyqxmd.com/read/27933516/costs-of-diabetes-medication-among-male-former-elite-athletes-in-later-life
#14
M K Laine, R Kujala, J G Eriksson, H Kautiainen, S Sarna, U M Kujala
AIMS: Regular physical activity plays a major role, in both prevention and treatment of type 2 diabetes. Less is known whether vigorous physical activity during young adulthood is associated with costs of diabetes medication in later life. The aim of this study is to evaluate this question. METHODS: The study population consisted of 1314 former elite-class athletes and 860 matched controls. The former athletes were divided into three groups based on their active career sport: endurance, mixed and power sports...
December 8, 2016: Acta Diabetologica
https://www.readbyqxmd.com/read/27926736/structure-of-cc-chemokine-receptor-2-with-orthosteric-and-allosteric-antagonists
#15
Yi Zheng, Ling Qin, Natalia V Ortiz Zacarías, Henk de Vries, Gye Won Han, Martin Gustavsson, Marta Dabros, Chunxia Zhao, Robert J Cherney, Percy Carter, Dean Stamos, Ruben Abagyan, Vadim Cherezov, Raymond C Stevens, Adriaan P IJzerman, Laura H Heitman, Andrew Tebben, Irina Kufareva, Tracy M Handel
CC chemokine receptor 2 (CCR2) is one of 19 members of the chemokine receptor subfamily of human class A G-protein-coupled receptors. CCR2 is expressed on monocytes, immature dendritic cells, and T-cell subpopulations, and mediates their migration towards endogenous CC chemokine ligands such as CCL2 (ref. 1). CCR2 and its ligands are implicated in numerous inflammatory and neurodegenerative diseases including atherosclerosis, multiple sclerosis, asthma, neuropathic pain, and diabetic nephropathy, as well as cancer...
December 15, 2016: Nature
https://www.readbyqxmd.com/read/27917297/an-intrinsic-agonist-mechanism-for-activation-of-glucagon-like-peptide-1-receptor-by-its-extracellular-domain
#16
Yanting Yin, X Edward Zhou, Li Hou, Li-Hua Zhao, Bo Liu, Gaihong Wang, Yi Jiang, Karsten Melcher, H Eric Xu
The glucagon-like peptide-1 receptor is a class B G protein coupled receptor (GPCR) that plays key roles in glucose metabolism and is a major therapeutic target for diabetes. The classic two-domain model for class B GPCR activation proposes that the apo-state receptor is auto-inhibited by its extracellular domain, which physically interacts with the transmembrane domain. The binding of the C-terminus of the peptide hormone to the extracellular domain allows the N-terminus of the hormone to insert into the transmembrane domain to induce receptor activation...
2016: Cell Discovery
https://www.readbyqxmd.com/read/27914923/alloantigen-gene-transfer-to-hepatocytes-promotes-tolerance-to-pancreatic-islet-graft-by-inducing-cd8-regulatory-t-cells
#17
Valentin Le Guen, Jean-Paul Judor, Françoise Boeffard, Vanessa Gauttier, Nicolas Ferry, Jean-Paul Soulillou, Sophie Brouard, Sophie Conchon
BACKGROUND & AIM: Induction of donor-specific immune tolerance is a good alternative to chronic life-long immunosuppression for transplant patients. Donor major histocompatibility complex (MHC) molecules represent the main targets of the allogeneic immune response of transplant recipients. Liver-targeted gene transfer with viral vectors induces tolerance toward the encoded antigen. The aim of this work was to determine whether alloantigen gene transfer to hepatocytes induces tolerance and promotes graft acceptance...
November 30, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27867889/liraglutide-effect-and-action-in-diabetes-in-lead-in-a-prospective-observational-study-assessing-safety-and-effectiveness-of-liraglutide-in-patients-with-type-2-diabetes-mellitus-treated-under-routine-clinical-practice-conditions-in-india
#18
Subhash Kumar Wangnoo, Surender Kumar, Arpandev Bhattacharyya, Sudhir Tripathi, Shahid Akhtar, Raman Shetty, Samit Ghosal
BACKGROUND: This 26-week, open-label observational study assessed the incidence and type of adverse events (AEs) associated with liraglutide use according to the standard clinical practice settings and the local label in India. MATERIALS AND METHODS: A total of 1416 adults with type 2 diabetes (T2D) treated with liraglutide in 125 sites across India were included in the study. Participants were newly diagnosed or already receiving antidiabetic medications. Safety and efficacy data were collected at baseline and at approximately weeks 13 and 26...
November 2016: Indian Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27866064/incretin-based-therapy-for-type-2-diabetes-a-real-class-effect
#19
Gianluigi Savarese, Lars H Lund, Giuseppe M C Rosano
No abstract text is available yet for this article.
January 15, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/27843569/conceptual-model-for-early-health-technology-assessment-of-current-and-novel-heart-valve-interventions
#20
Simone A Huygens, Maureen P M H Rutten-van Mölken, Jos A Bekkers, Ad J J C Bogers, Carlijn V C Bouten, Steven A J Chamuleau, Peter P T de Jaegere, Arie Pieter Kappetein, Jolanda Kluin, Nicolas M D A van Mieghem, Michel I M Versteegh, Maarten Witsenburg, Johanna J M Takkenberg
OBJECTIVE: The future promises many technological advances in the field of heart valve interventions, like tissue-engineered heart valves (TEHV). Prior to introduction in clinical practice, it is essential to perform early health technology assessment. We aim to develop a conceptual model (CM) that can be used to investigate the performance and costs requirements for TEHV to become cost-effective. METHODS: After scoping the decision problem, a workgroup developed the draft CM based on clinical guidelines...
2016: Open Heart
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