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https://www.readbyqxmd.com/read/29035554/star-polymers-reduce-iapp-toxicity-via-accelerated-amyloid-aggregation
#1
Emily H Pilkington, May Lai, Xinwei Ge, William J Stanley, Bo Wang, Miaoyi Wang, Aleksandr Kakinen, Marc-Antoine Sani, Michael R Whittaker, Esteban N Gurzov, Feng Ding, John F Quinn, Thomas P Davis, Pu Chun Ke
Protein aggregation into amyloid fibrils is a ubiquitous phenomenon across the spectrum of neurodegenerative disorders and type 2 diabetes. A common strategy against amyloidogenesis is to minimize the populations of toxic oligomers and protofibrils by inhibiting protein aggregation with small molecules or nanoparticles. However, melanin synthesis in nature is realized by accelerated protein fibrillation to circumvent accumulation of toxic intermediates. Accordingly, we designed and demonstrated the use of star-shaped poly(2-hydroxyethyl acrylate) (PHEA) nanostructures for promoting the aggregation while ameliorating the toxicity of human islet amyloid polypeptide (IAPP), the peptide involved in glycemic control and the pathology of type 2 diabetes...
October 16, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/29032638/sodium-glucose-co-transporter-2-inhibitor-tofogliflozin-shows-better-improvements-of-blood-glucose-and-insulin-secretion-in-patients-with-high-insulin-levels-at-baseline
#2
Kazuyuki Tobe, Hideki Suganami, Kohei Kaku
INTRODUCTION: Sodium glucose co-transporter 2 (SGLT2) inhibitors are a new class of drugs for the treatment of type 2 diabetes mellitus that improve control of plasma glucose and body weight, giving great hope for the clinical utility of these agents. However, it is unclear for which patients that SGLT2 inhibitors will be useful. MATERIALS AND METHODS: We analyzed data from long-term tofogliflozin monotherapy in an open-label, randomized controlled trial in Japanese patients with type 2 diabetes mellitus...
October 15, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29031415/usefulness-of-the-crt-score-for-shared-decision-making-in-cardiac-resynchronization-therapy-in-patients-with-a-left-ventricular-ejection-fraction-of-%C3%A2-35
#3
Ulas Höke, Bart Mertens, Mand J H Khidir, Martin J Schalij, Jeroen J Bax, Victoria Delgado, Nina Ajmone Marsan
Individualized estimation of prognosis after cardiac resynchronization therapy (CRT) remains challenging. Our aim was to develop a multiparametric prognostic risk score (CRT-SCORE) that could be used for patient-specific clinical shared decision making about CRT implantation. The CRT-SCORE was derived from an ongoing CRT registry, including 1,053 consecutive patients (age 67 ± 10 years, 76% male). Using preimplantation variables, 100 multiple imputed datasets were generated for model calibration. Based on multivariate Cox regression models, cross-validated linear prognostic scores were calculated, as well as survival fractions at 1 and 5 years...
August 30, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/29021336/pooled-analysis-of-multiple-crossover-trials-to-optimize-individual-therapy-response-to-renin-angiotensin-aldosterone-system-intervention
#4
Sergei I Petrykiv, Gozewijn Dirk Laverman, Frederik Persson, Liffert Vogt, Peter Rossing, Martin H de Borst, Ronald T Gansevoort, Dick de Zeeuw, Hiddo J L Heerspink
BACKGROUND AND OBJECTIVES: In the treatment of CKD, individual patients show a wide variation in their response to many drugs, including renin-angiotensin-aldosterone system inhibitors (RAASi). To investigate whether therapy resistance to RAASi can be overcome by uptitrating the dose of drug, changing the mode of intervention (with drugs from similar or different classes), or lowering dietary sodium intake, we meta-analyzed individual responses to different modes of interventions. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Randomized crossover trials were analyzed to assess correlation of individual responses to RAASi and nonsteroidal anti-inflammatory drugs (NSAIDs; n=395 patients)...
October 11, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28983719/glucose-patterns-during-an-oral-glucose-tolerance-test-and-associations-with-future-diabetes-cardiovascular-disease-and-all-cause-mortality-rate
#5
Adam Hulman, Dorte Vistisen, Charlotte Glümer, Michael Bergman, Daniel R Witte, Kristine Færch
AIMS/HYPOTHESIS: In addition to blood glucose concentrations measured in the fasting state and 2 h after an OGTT, intermediate measures during an OGTT may provide additional information regarding a person's risk of future diabetes and cardiovascular disease (CVD). First, we aimed to characterise heterogeneity of glycaemic patterns based on three time points during an OGTT. Second, we compared the incidences of diabetes and CVD and all-cause mortality rates among those with different patterns...
October 6, 2017: Diabetologia
https://www.readbyqxmd.com/read/28932392/galectin-3-a-marker-of-cardiac-remodeling-is-inversely-related-to-serum-levels-of-marine-omega-3-fatty-acids-a-cross-sectional-study
#6
K Laake, I Seljeflot, E B Schmidt, P Myhre, A Tveit, J Norseth, H Arnesen, S Solheim
OBJECTIVE: Marine polyunsaturated n-3 fatty acids (n-3 PUFA) may have cardioprotective effects and beneficial influence on the fibrotic process. We evaluated the associations between serum marine n-3 PUFA and selected biomarkers of fibrosis and cardiac remodeling in elderly patients with acute myocardial infarction. SETTING: From the ongoing OMega-3 fatty acids in Elderly patients with Myocardial Infarction (OMEMI) trial, 299 patients were investigated. Soluble ST2 (sST2), Galectin-3 (Gal-3) and the serum content of major marine n-3 and n-6 PUFA were analyzed 2-8 weeks after the index acute myocardial infarction...
January 2017: JRSM Cardiovascular Disease
https://www.readbyqxmd.com/read/28903983/ivabradine-in-heart-failure-the-representativeness-of-shift-systolic-heart-failure-treatment-with-the-if-inhibitor-ivabradine-trial-in-a-broad-population-of-patients-with-chronic-heart-failure
#7
COMPARATIVE STUDY
Debraj Das, Gianluigi Savarese, Ulf Dahlström, Michael Fu, Jonathan Howlett, Justin A Ezekowitz, Lars H Lund
BACKGROUND: The sinus node inhibitor ivabradine was approved for patients with heart failure (HF) after the ivabradine and outcomes in chronic HF (SHIFT [Systolic Heart Failure Treatment With the IF Inhibitor Ivabradine Trial]) trial. Our objective was to characterize the proportion of patients with HF eligible for ivabradine and the representativeness of the SHIFT trial enrollees compared with those in the Swedish Heart Failure Registry. METHODS AND RESULTS: We examined 26 404 patients with clinical HF from the Swedish Heart Failure Registry and divided them into SHIFT type (left ventricular ejection fraction <40%, New York Heart Association class II-IV, sinus rhythm, and heart rate ≥70 beats per minute) and non-SHIFT type...
September 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/28894214/the-novel-compound-sul-121-preserves-endothelial-function-and-inhibits-progression-of-kidney-damage-in-type-2-diabetes-mellitus-in-mice
#8
S P H Lambooy, A Bidadkosh, D Nakladal, A van Buiten, R A T Girgis, A C van der Graaf, T J Wiedenmann, R A Koster, P Vogelaar, H Buikema, R H Henning, L E Deelman
Diabetic nephropathy is still a common complication of type 2 diabetes mellitus (T2DM) and improvement of endothelial dysfunction (ED) and inhibition of reactive oxygen species (ROS) are considered important targets for new therapies. Recently, we developed a new class of compounds (Sul compounds) which inhibit mitochondrial ROS production. Here, we tested the therapeutic effects of Sul-121 on ED and kidney damage in experimental T2DM. Diabetic db/db and lean mice were implanted with osmotic pumps delivering Sul-121 (2...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28884942/structural-properties-of-bioactive-peptides-with-%C3%AE-glucosidase-inhibitory-activity
#9
Mohammed Auwal Ibrahim, Megan J Bester, Albert W H Neitz, Anabella R M Gaspar
Bioactive peptides are emerging as promising class of drugs that could serve as α-glucosidase inhibitors for the treatment of type 2 diabetes. This article identifies structural and physicochemical requirements for the design of therapeutically-relevant α-glucosidase inhibitory peptides. So far, a total of 43 fully sequenced α-glucosidase inhibitory peptides have been reported and 13 of them had IC50 values several folds lower than acarbose. Analysis of the peptides indicates that the most potent peptides are tri- to hexapeptides with amino acids containing a hydroxyl or basic side chain at the N-terminal...
September 8, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28869934/typical-hemodialysis-in-india-a-case-report
#10
Georgi Abraham, Madhusudan Vijayan, Milly Mathew
We report here a typical case of a patient on hemodialysis (HD) for end-stage renal disease (ESRD) in India that highlights some of the management issues encountered in a country with an enormous burden of ESRD and major challenges of underdialysis and management of comorbidities. The patient, a 42-year-old multiparous woman with chronic kidney disease (CKD) stage V, type 2 diabetes mellitus, and hypertension is a homemaker from a middle-class family, living in a large city, with no family history of CKD. From May 2013 to December 2016, she has been receiving twice-weekly maintenance HD for 4 h (intermittent HD); access was via an internal jugular line initially and then via a left brachiocephalic arteriovenous fistula (AVF) from late June 2013...
2017: Blood Purification
https://www.readbyqxmd.com/read/28860225/is-cardiovascular-risk-reduction-therapy-effective-in-south-asian-chinese-and-other-patients-with-diabetes-a-population-based-cohort-study-from-canada
#11
Calvin H Ke, Steve Morgan, Kate Smolina, Danijela Gasevic, Hong Qian, Nadia A Khan
OBJECTIVES: Guidelines recommend ACE inhibitors (ACEi), angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs) and diuretics in all patients with diabetes mellitus. However, the effectiveness of these agents in South Asian and Chinese populations is unknown. We sought to determine whether ACEi, ARB, CCB and diuretics are associated with reduced mortality in South Asian, Chinese and other patients with diabetes. DESIGN: Population-based cohort study using administrative health databases...
August 31, 2017: BMJ Open
https://www.readbyqxmd.com/read/28840455/effects-of-laparoscopic-roux-en-y-gastric-bypass-on-chinese-type-2-diabetes-mellitus-patients-with-different-levels-of-obesity-outcomes-after-3%C3%A2-years-follow-up
#12
Xiao Du, Xiang-Hui Fu, Lei Shi, Jian-Kun Hu, Zong-Guang Zhou, Zhong Cheng
BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) has been proven to be effective on treating type 2 diabetes mellitus (T2DM) in severely obese patients, but whether LRYGB surgery should be performed in obese class I patients is controversial. MATERIALS AND METHODS: A retrospective study of 3-year bariatric and metabolic outcomes in different obese class T2DM patients who underwent LRYGB was conducted to compare the effectiveness of LRYGB in obese class I patients with that in obese class II/III patients in a Chinese T2DM population...
August 24, 2017: Obesity Surgery
https://www.readbyqxmd.com/read/28834219/human-leucocyte-antigens-class-ii-allele-and-haplotype-association-with-type-1-diabetes-in-madeira-island-portugal
#13
H Spínola, A Lemos, A R Couto, B Parreira, M Soares, I Dutra, J Bruges-Armas, A Brehm, S Abreu
This study confirms for Madeira Island (Portugal) population the Type 1 Diabetes (T1D) susceptible and protective Human leucocyte antigens (HLA) markers previously reported in other populations and adds some local specificities. Among the strongest T1D HLA associations, stands out, as susceptible, the alleles DRB1*04:05 (OR = 7.3), DQB1*03:02 (OR = 6.1) and DQA1*03:03 (OR = 4.5), as well as the haplotypes DRB1*04:05-DQA1*03:03-DQB1*03:02 (OR = 100.9) and DRB1*04:04-DQA1*03:01-DQB1*03:02 (OR = 22.1), and DQB1*06:02 (OR = 0...
August 20, 2017: International Journal of Immunogenetics
https://www.readbyqxmd.com/read/28830709/early-carotid-endarterectomy-performed-2-to-5-days-after-the-onset-of-neurologic-symptoms-leads-to-comparable-results-to-carotid-endarterectomy-performed-at-later-time-points
#14
Efthymios D Avgerinos, Alik Farber, Adham N Abou Ali, Denis Rybin, Gheorghe Doros, Mohammad H Eslami
BACKGROUND: Timing of carotid endarterectomy (CEA) after onset of neurologic symptoms remains controversial. We assessed the association of CEA timing with postoperative outcomes. METHODS: The Vascular Study Group of New England (VSGNE) database (2003-2014) was queried to identify CEA performed for symptomatic carotid stenosis during the same hospitalization. Cases were divided into four groups based on the time from onset of neurologic symptoms to CEA: group I, <2 days; group II, 2 to 5 days; group III, ≥6 days; and group IV, same-day CEA...
August 19, 2017: Journal of Vascular Surgery
https://www.readbyqxmd.com/read/28826523/clinical-applications-of-radiolabeled-peptides-for-pet
#15
REVIEW
Isaac M Jackson, Peter J H Scott, Stephen Thompson
Radiolabeled peptides are a valuable class of radiotracer that occupies the space between small molecules and large biologics, and are able to exploit the advantages of both classes of compound. To date, radiolabeled peptides have mainly been utilized in oncology, where the same peptide can often be exploited for diagnostic imaging and targeted radiotherapy by simply varying the radionuclide. In this review, we introduce the main strategies used for synthesis of radiolabeled peptides, and highlight the state of the art for clinical imaging (and therapy) in oncology using the main classes of radiolabeled peptides that have been translated to date...
September 2017: Seminars in Nuclear Medicine
https://www.readbyqxmd.com/read/28822994/glucagon-like-peptide-1-receptor-agonist-stimulates-mitochondrial-bioenergetics-in-human-adipocytes
#16
Joanna Góralska, Agnieszka Śliwa, Anna Gruca, Urszula Raźny, Monika Chojnacka, Anna Polus, Bogdan Solnica, Małgorzata Malczewska-Malec
Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are relatively new pharmacological agents used to normalize glucose level in type 2 diabetes. Recently, GLP-1RAs have been approved for the treatment of obesity to reduce body weight in non-diabetic patients. The extra-pancre-atic effects of GLP-1RAs, as well as their molecular mechanism of action, are still poorly understood. Thus this study was aimed to verify the hypothesis that the mechanism of action of the GLP-1RAs involves mitochondria and that GLP-1RAs administration can improve mitochondrial functions...
2017: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/28821636/twenty-four-hour-rhythmicity-of-circulating-metabolites-effect-of-body-mass-and-type-2-diabetes
#17
Cheryl M Isherwood, Daan R Van der Veen, Jonathan D Johnston, Debra J Skene
Metabolic profiling of individuals with type 2 diabetes mellitus (T2DM) has previously been limited to single-time-point samples, ignoring time-of-day variation. Here, we tested our hypothesis that body mass and T2DM affect daily rhythmicity and concentrations of circulating metabolites across a 24-h day in 3 age-matched, male groups-lean, overweight/obese (OW/OB), and OW/OB with T2DM-in controlled laboratory conditions, which were not confounded by large meals. By using targeted liquid chromatography/mass spectrometry metabolomics, we quantified 130 plasma metabolites every 2 h over 24 h, and we show that average metabolite concentrations were significantly altered by increased body mass (90 of 130) and T2DM (56 of 130)...
August 18, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28746788/a-randomized-placebo-controlled-trial-of-prophylactic-dexamethasone-for-transcatheter-arterial-chemoembolization
#18
Sadahisa Ogasawara, Tetsuhiro Chiba, Yoshihiko Ooka, Naoya Kanogawa, Tenyu Motoyama, Eiichiro Suzuki, Akinobu Tawada, Kazue Nagai, Tomoo Nakagawa, Takeshi Sugawara, Hideki Hanaoka, Fumihiko Kanai, Osamu Yokosuka
This randomized, double-blind, placebo-controlled trial evaluated dexamethasone efficacy in preventing fever, anorexia, and nausea/vomiting, the most frequent adverse events of transcatheter arterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). Child-Pugh class A/B patients with HCC and no macrovascular invasion/extrahepatic metastases were randomly assigned to either a dexamethasone (day 1, intravenous dexamethasone [20 mg] and granisetron [3 mg] before TACE; days 2 and 3, intravenous dexamethasone [8 mg]) or a control regimen (day 1, intravenous placebo [saline] and granisetron [3 mg]; days 2 and 3, intravenous placebo)...
July 26, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28738846/long-non-coding-rnas-as-novel-players-in-%C3%AE-cell-function-and-type-1-diabetes
#19
REVIEW
Aashiq H Mirza, Simranjeet Kaur, Flemming Pociot
BACKGROUND: Long non-coding RNAs (lncRNAs) are a sub-class within non-coding RNA repertoire that have emerged as crucial regulators of the gene expression in various pathophysiological conditions. lncRNAs display remarkable versatility and wield their functions through interactions with RNA, DNA, or proteins. Accumulating body of evidence based on multitude studies has highlighted the role of lncRNAs in many autoimmune and inflammatory diseases, including type 1 diabetes (T1D). This review highlights emerging roles of lncRNAs in immune and islet β cell function as well as some of the challenges and opportunities in understanding the pathogenesis of T1D and its complications...
July 24, 2017: Human Genomics
https://www.readbyqxmd.com/read/28733878/role-of-tgf-%C3%AE-in-self-peptide-regulation-of-autoimmunity
#20
REVIEW
Bhagirath Singh, Michael D Krawetz, Rachel M De Lima, Rinee Mukherjee, Pratibha Chaturvedi, Edwin Lee-Chan, Edward H Leiter, Kelly L Summers
Transforming growth factor (TGF)-β has been implicated in regulation of the immune system, including autoimmunity. We have found that TGF-β is readily produced by T cells following immunization with self-peptide epitopes that downregulate autoimmune responses in type 1 diabetes (T1D) prone nonobese diabetic (NOD) mice. These include multiple peptide epitopes derived from the islet β-cell antigens GAD65 (GAD65 p202-221, GAD65 p217-236), GAD67 (GAD67 p210-229, GAD67 p225-244), IGRP (IGRP p123-145, IGRP p195-214) and insulin B-chain (Ins...
July 21, 2017: Archivum Immunologiae et Therapiae Experimentalis
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