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https://www.readbyqxmd.com/read/29905825/targeting-the-incretin-glucagon-system-with-triagonists-to-treat-diabetes
#1
Megan E Capozzi, Richard D DiMarchi, Matthias H Tschöp, Brian Finan, Jonathan E Campbell
Glucagon-like peptide-1 (GLP-1) receptor agonists have been efficacious for the treatment of type 2 diabetes due to their ability to reduce weight and attenuate hyperglycemia. However, the activity of GLP-1R-directed strategies is sub-maximal, and the only potent, sustainable treatment for metabolic dysfunction is bariatric surgery, necessitating the development of novel therapeutics. GLP-1 is structurally related to glucagon and glucose-dependent insulinotropic peptide (GIP), allowing for the development of intermixed, unimolecular peptides with activity at each of their respective receptors...
June 13, 2018: Endocrine Reviews
https://www.readbyqxmd.com/read/29875876/prevalence-refractive-errors-among-medical-students-of-qassim-university-saudi-arabia-cross-sectional-descriptive-study
#2
Sultan H Al-Rashidi, Adel A Albahouth, Waleed A Althwini, Abdullah A Alsohibani, Abdulmejeed A Alnughaymishi, Abdulamlaik A Alsaeed, Fahad H Al-Rashidi, Salem Almatrafi
OBJECTIVE: To study the prevalence of various errors of refraction among the medical students studying at the college of medicine, Qassim University, Saudi Arabia. METHODS: This is a cross-sectional descriptive study conducted at Qassim University clinics over a period of two months. The study population comprised 162 male and female students from different academic years. The students were selected randomly so that around 35-40 students were taken from each academic class...
May 20, 2018: Open Access Macedonian Journal of Medical Sciences
https://www.readbyqxmd.com/read/29864167/classification-of-healthy-and-diseased-retina-using-sd-oct-imaging-and-random-forest-algorithm
#3
Md Akter Hussain, Alauddin Bhuiyan, Chi D Luu, R Theodore Smith, Robyn H Guymer, Hiroshi Ishikawa, Joel S Schuman, Kotagiri Ramamohanarao
In this paper, we propose a novel classification model for automatically identifying individuals with age-related macular degeneration (AMD) or Diabetic Macular Edema (DME) using retinal features from Spectral Domain Optical Coherence Tomography (SD-OCT) images. Our classification method uses retinal features such as the thickness of the retina and the thickness of the individual retinal layers, and the volume of the pathologies such as drusen and hyper-reflective intra-retinal spots. We extract automatically, ten clinically important retinal features by segmenting individual SD-OCT images for classification purposes...
2018: PloS One
https://www.readbyqxmd.com/read/29807519/pyrano-3-2-c-quinoline-derivatives-as-new-class-of-%C3%AE-glucosidase-inhibitors-to-treat-type-2-diabetes-synthesis-in-vitro-biological-evaluation-and-kinetic-study
#4
Zahra Heydari, Maryam Mohammadi-Khanaposhtani, Somaye Imanparast, Mohammad Ali Faramarzi, Mohammad Mahdavi, Parviz Rashidi Ranjbar, Bagher Larijani
BACKGROUND: Pyrano[3,2-c]quinoline derivatives 6a-n were synthesized via simple two-step reactions and evaluated for their in vitro α-glucosidase inhibitory activity. METHODS: Pyrano[3,2-c]quinoline derivatives 6a-n derivatives were prepared from a two-step reaction: cycloaddition reaction between 1-naphthyl amine 1 and malonic acid 2 to obtain benzo[h]quinoline-2(1H)-one 3 and reaction of 3 with aryl aldehydes 4 and Meldrum's acid 5. The anti- α-glucosidase activity and kinetic study of the synthesized compounds were evaluated using α-glucosidase from Saccharomyces cerevisiae and p-nitrophenyl-a-D-glucopyranoside as substrate...
May 27, 2018: Medicinal Chemistry
https://www.readbyqxmd.com/read/29802538/effects-of-the-sglt-2-inhibitor-empagliflozin-on-renal-tissue-oxygenation-in-non-diabetic-subjects-a-randomized-double-blind-placebo-controlled-study-protocol
#5
Marie-Eve Muller, Menno Pruijm, Olivier Bonny, Michel Burnier, Anne Zanchi
INTRODUCTION: Empagliflozin is an SGLT-2 inhibitor (SGLT-2i) which belongs to a new class of hypoglycemic drugs with the unique property of decreasing blood glucose independently from insulin, through an increase in glycosuria. In addition to decreasing cardiovascular morbidity and mortality, empagliflozin has nephroprotective properties in high cardiovascular risk patients with type 2 diabetes. Decreased hyperfiltration and shifting towards more favorable renal fuel energetics with improved renal oxygenation may explain some of these properties...
May 25, 2018: Advances in Therapy
https://www.readbyqxmd.com/read/29799667/subsequent-cardiovascular-events-among-patients-with-rheumatoid-arthritis-psoriatic-arthritis-or-psoriasis-patterns-of-disease-modifying-antirheumatic-drug-treatment
#6
Jeffrey A Sparks, Tamara Lesperance, Neil A Accortt, Daniel H Solomon
OBJECTIVES: To examine disease-modifying antirheumatic drug (DMARD) treatments and estimate risk of a subsequent cardiovascular (CV) event following an initial CV event in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or psoriasis (PsO). METHODS: We analyzed data from MarketScan® claims databases (1/1/2006-6/30/2015) for adults with RA, PsA, or PsO and initial/index CV event (acute myocardial infarction, stroke, or coronary revascularization) while receiving DMARDs (tumor necrosis factor inhibitor [TNFi] biologic DMARDs [bDMARDs], conventional synthetic DMARDs [csDMARDs], or non-TNFi bDMARDs)...
May 25, 2018: Arthritis Care & Research
https://www.readbyqxmd.com/read/29795760/design-synthesis-and-x-ray-of-selenides-as-new-class-of-agents-for-prevention-of-diabetic-cerebrovascular-pathology
#7
Andrea Angeli, Lorenzo di Cesare Mannelli, Elena Trallori, Thomas S Peat, Carla Ghelardini, Fabrizio Carta, Claudiu T Supuran
A series of novel selenides bearing benzenesulfonamide moieties was synthesized and investigated for their inhibition on six human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoforms such as the physiologically relevant hCA I, II, VA, VB, VII, and IX and the X-ray complex in adduct with hCA II for some of them investigated. These enzymes are involved in a variety of diseases including glaucoma, retinitis pigmentosa, epilepsy, arthritis, metabolic disorders, and cancer. The investigated compounds showed potent inhibitory action against hCA VA, VII, and IX, in the low nanomolar range, thus making them of interest for the development of isoform-selective inhibitors and as candidates for various biomedical applications...
May 10, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29754954/the-polycomb-dependent-epigenome-controls-%C3%AE-cell-dysfunction-dedifferentiation-and-diabetes
#8
Tess Tsai-Hsiu Lu, Steffen Heyne, Erez Dror, Eduard Casas, Laura Leonhardt, Thorina Boenke, Chih-Hsiang Yang, Sagar, Laura Arrigoni, Kevin Dalgaard, Raffaele Teperino, Lennart Enders, Madhan Selvaraj, Marius Ruf, Sunil J Raja, Huafeng Xie, Ulrike Boenisch, Stuart H Orkin, Francis C Lynn, Brad G Hoffman, Dominic Grün, Tanya Vavouri, Adelheid M Lempradl, J Andrew Pospisilik
To date, it remains largely unclear to what extent chromatin machinery contributes to the susceptibility and progression of complex diseases. Here, we combine deep epigenome mapping with single-cell transcriptomics to mine for evidence of chromatin dysregulation in type 2 diabetes. We find two chromatin-state signatures that track β cell dysfunction in mice and humans: ectopic activation of bivalent Polycomb-silenced domains and loss of expression at an epigenomically unique class of lineage-defining genes...
May 4, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29733433/statin-therapy-on-glycemic-control-in-type-2-diabetic-patients-a-network-meta-analysis
#9
J Y Cui, R R Zhou, S Han, T S Wang, L Q Wang, X H Xie
WHAT IS KNOWN AND OBJECTIVE: Statins are the cornerstone of primary and secondary prevention of cardiovascular diseases (CVDs) and are effective for the prevention of vascular events in diabetic patients. Diabetes mellitus is an important risk factor for CVDs .The majority of patients with diabetes mellitus benefits from statin therapy. According to the recent clinical guidelines of the American College of Cardiology and the American Heart Association, moderate-intensity or high-intensity statin therapy should be used as the primary prevention for individuals with diabetes mellitus, aged between 40 and 75 years and with low-density lipoprotein cholesterol (LDL-C) from 70 to 189 mg/dL...
May 7, 2018: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/29684922/saliva-versus-plasma-therapeutic-drug-monitoring-of-pregabalin-in-jordanian-patients
#10
Nasir Idkaidek, Salim Hamadi, Manal El-Assi, Ahmad Al-Shalalfeh, Ahmad Al-Ghazawi
The objective is using saliva instead of plasma for pregabalin therapeutic drug monitoring (TDM) since saliva reflects the free non-protein bound drug concentration, simple and noninvasive sampling, cheaper and does not require the expertise of drawing blood. Forty four patients participated in this study, two samples of saliva and another two of blood were taken from each patient; first sample of both saliva and blood is the trough sample and was taken just before the first dose of the day and second sample is the peak sample and was taken 1 h after taking the first dose of the day...
April 23, 2018: Drug Research
https://www.readbyqxmd.com/read/29660027/the-6-hydroxychromanol-derivative-sul-109-ameliorates-renal-injury-after-deep-hypothermia-and-rewarming-in-rats
#11
Pieter C Vogelaar, Maurits Roorda, Edwin L de Vrij, Martin C Houwertjes, Maaike Goris, Hjalmar Bouma, Adrianus C van der Graaf, Guido Krenning, Robert H Henning
Background: Mitochondrial dysfunction plays an important role in kidney damage in various pathologies, including acute and chronic kidney injury and diabetic nephropathy. In addition to the well-studied ischaemia/reperfusion (I/R) injury, hypothermia/rewarming (H/R) also inflicts acute kidney injury. Substituted 6-hydroxychromanols are a novel class of mitochondrial medicines that ameliorate mitochondrial oxidative stress and protect the mitochondrial network. To identify a novel 6-hydroxychromanol that protects mitochondrial structure and function in the kidney during H/R, we screened multiple compounds in vitro and subsequently assessed the efficacy of the 6-hydroxychromanol derivatives SUL-109 and SUL-121 in vivo to protect against kidney injury after H/R in rats...
April 11, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29655949/incidence-and-predictors-of-6-months-mortality-after-an-acute-heart-failure-event-in-rural-uganda-the-mbarara-heart-failure-registry-mahfer
#12
Fardous Charles Abeya, Boniface Amanee Elias Lumori, Suzan Joan Akello, Brian H Annex, Andrew J Buda, Samson Okello
OBJECTIVE: We sought to estimate the incidence and predictors of all-cause mortality 6 months after heart failure hospitalization in Uganda. METHODS: Mbarara Heart Failure Registry is a cohort of patients hospitalized with a clinical diagnosis of heart failure at Mbarara Regional Referral Hospital, Uganda. We measured serum electrolytes, cardiac markers, and echocardiograms. All participants were followed until death or end of 6 months. We used Fine and Gray models to estimate the incidence and predictors all-cause mortality...
August 1, 2018: International Journal of Cardiology
https://www.readbyqxmd.com/read/29599092/cardiorenal-syndrome-as-predictor-of-in-hospital-mortality-in-st-segment-elevation-myocardial-infarction
#13
Ailed Elena Rodríguez-Jiménez, Tessa Negrín-Valdés, Hugo Cruz-Inerarity, Pedro Javier Machural-de la Torre
INTRODUCTION: Cardiorenal syndrome includes numerous conditions affecting the heart and kidney, and is a strong predictor of cardiovascular mortality. METHOD: An analysis was performed on 157 consecutive patients admitted to the Coronary Care Unit of the Camilo Cienfuegos Hospital due to an ST-segment elevation myocardial infarction and heart failure, from January 2013 to December 2016. An analysis was made of the presence of cardiorenal syndrome and its relationship with epidemiological, clinical, and analytical variables, as well as complementary explorations...
March 26, 2018: Clínica e Investigación en Arteriosclerosis
https://www.readbyqxmd.com/read/29597053/associations-with-and-prognostic-and-discriminatory-role-of-n-terminal-pro-b-type-natriuretic-peptide-in-heart-failure-with-preserved-versus-mid-range-versus-reduced-ejection-fraction
#14
Gianluigi Savarese, Nicola Orsini, Camilla Hage, Ulf Dahlström, Ola Vedin, Giuseppe M C Rosano, Lars H Lund
BACKGROUND: The aim of this study was to characterize N-terminal pro-B-type natriuretic peptide (NT-proBNP) in terms of determinants of levels and of its prognostic and discriminatory role in heart failure with mid-range (HFmrEF) versus preserved (HFpEF) and reduced (HFrEF) ejection fraction. METHODS AND RESULTS: In 9847 outpatients with HFpEF (n = 1811; 18%), HFmrEF (n = 2122; 22%) and HFrEF (n = 5914; 60%) enrolled in the Swedish Heart Failure Registry, median NT-proBNP levels were 1428, 1540, and 2288 pg/mL, respectively...
March 27, 2018: Journal of Cardiac Failure
https://www.readbyqxmd.com/read/29580660/ckd-self-management-phenotypes-and-associations-with-clinical-outcomes
#15
Sarah J Schrauben, Jesse Y Hsu, Sylvia E Rosas, Bernard G Jaar, Xiaoming Zhang, Rajat Deo, Georges Saab, Jing Chen, Swati Lederer, Radhika Kanthety, L Lee Hamm, Ana C Ricardo, James P Lash, Harold I Feldman, Amanda H Anderson
BACKGROUND: To slow chronic kidney disease (CKD) progression and its complications, patients need to engage in self-management behaviors. The objective of this study was to classify CKD self-management behaviors into phenotypes and assess the association of these phenotypes with clinical outcomes. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Adults with mild to moderate CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study...
March 24, 2018: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/29572627/functional-impairment-and-risk-of-mortality-in-patients-on-chronic-hemodialysis-results-of-the-lazio-dialysis-registry
#16
Maurizio Bossola, Claudia Marino, Anteo Di Napoli, Nera Agabiti, Luigi Tazza, Marina Davoli
BACKGROUND: Functional impairment is associated with adverse outcomes in older people, as well as in patients on chronic hemodialysis. The aim of this study was to evaluate if functional impairment represents a risk factor for reduced survival in patients on chronic hemodialysis. METHODS: All incident chronic hemodialysis patients of Lazio, a large region of central Italy, registered in the Dialysis and Transplant Lazio Region Registry (DTLRR) in the period 2008-2013 were considered eligible...
March 23, 2018: Journal of Nephrology
https://www.readbyqxmd.com/read/29540798/application-of-a-genetic-risk-score-to-racially-diverse-type-1-diabetes-populations-demonstrates-the-need-for-diversity-in-risk-modeling
#17
Daniel J Perry, Clive H Wasserfall, Richard A Oram, MacKenzie D Williams, Amanda Posgai, Andrew B Muir, Michael J Haller, Desmond A Schatz, Mark A Wallet, Clayton E Mathews, Mark A Atkinson, Todd M Brusko
Prior studies identified HLA class-II and 57 additional loci as contributors to genetic susceptibility for type 1 diabetes (T1D). We hypothesized that race and/or ethnicity would be contextually important for evaluating genetic risk markers previously identified from Caucasian/European cohorts. We determined the capacity for a combined genetic risk score (GRS) to discriminate disease-risk subgroups in a racially and ethnically diverse cohort from the southeastern U.S. including 637 T1D patients, 46 at-risk relatives having two or more T1D-related autoantibodies (≥2AAb+ ), 790 first-degree relatives (≤1AAb+ ), 68 second-degree relatives (≤1 AAb+ ), and 405 controls...
March 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29534825/prevalent-and-incident-heart-failure-in-cardiovascular-outcome-trials-of-patients-with-type-2-diabetes
#18
REVIEW
Stephen J Greene, Muthiah Vaduganathan, Muhammad Shahzeb Khan, George L Bakris, Matthew R Weir, Jonathan H Seltzer, Naveed Sattar, Darren K McGuire, James L Januzzi, Norman Stockbridge, Javed Butler
Despite multiple examples of glucose-lowering therapies affecting heart failure (HF) risk, ascertainment of HF data in cardiovascular outcome trials of these medications has not been systematically characterized. In this review, large (n >1,000) published phase III and IV cardiovascular outcome trials evaluating glucose-lowering therapies through June 2017 were identified. Data were abstracted from publications, U.S. Food and Drug Administration advisory committee records, and U.S. Food and Drug Administration labeling documents...
March 27, 2018: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/29521244/synthesis-structural-characterization-and-docking-studies-of-sulfamoyl-phenyl-acid-esters-as-dpp-iv-inhibitors
#19
Reema Abdelkareem Abu Khalaf, Dima Sabbah, Eveen Al-Shalabi, Iyad Al-Sheikh, Ghadeer Albadawi, Ghassan Abu Sheikha
BACKGROUND: Diabetes mellitus is a major worldwide health concern that has several serious complications including retinopathy, neuropathy, nephropathy and macrovascular diseases. OBJECTIVE: Dipeptidyl peptidase-IV (DPP-IV) inhibitors, gliptins, are a new class of antidiabetic agents that potentiates the action of incretins in decreasing the blood glucose levels. METHODS: In the present study, synthesis and characterization of a series of ten N4-sulfonamido-acrylic and phthalamic acid methyl esters (3a-e and 5a-e) were achieved...
March 8, 2018: Current Computer-aided Drug Design
https://www.readbyqxmd.com/read/29521173/fixed-ratio-combination-therapy-for-type-2-diabetes-the-top-ten-things-you-should-know-about-insulin-and-glucagon-like-peptide-1-receptor-agonist-combinations
#20
Ian Blumer, Jeremy H Pettus, Tricia Santos Cavaiola
Many individuals with type 2 diabetes (T2D) will eventually require insulin therapy to help achieve and maintain adequate glycemic control. However, the use of insulin can be associated with adverse effects such as hypoglycemia and weight gain, and in some patients the addition of insulin to treatment regimens is often still insufficient to achieve target glycemic control. Combining basal insulin with a glucagon-like peptide-1 receptor agonist (GLP-1 RA) for the treatment of patients with T2D has been demonstrated to be effective and well tolerated, while mitigating many of the adverse events associated with giving either of these drug classes alone...
March 20, 2018: Postgraduate Medicine
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