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https://www.readbyqxmd.com/read/28717973/design-and-development-of-repaglinide-microemulsion-gel-for-transdermal-delivery
#1
Ujwala A Shinde, Sheela H Modani, Kavita H Singh
Microemulsion formulation of repaglinide, a BCS class II hypoglycemic agent with limited oral bioavailability, was developed considering its solubility in various oils, surfactants, and cosurfactants. The pseudo-ternary phase diagrams for microemulsion regions were constructed by water titration method at K m 1:1 and characterized for optical birefringence, percentage transmittance, pH, refractive index, globule size, zeta potential, viscosity, drug content, and thermodynamic stability. To enhance the drug permeation and residence time, the optimized microemulsions having mean globule size of 36...
July 17, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/28700790/association-of-changes-in-medication-use-and-adherence-with-accountable-care-organization-exposure-in-patients-with-cardiovascular-disease-or-diabetes
#2
J Michael McWilliams, Mehdi Najafzadeh, William H Shrank, Jennifer M Polinski
Importance: Many of the quality measures used to assess accountable care organization (ACO) performance in the Medicare Shared Savings Program (MSSP) focus on disease control and medication use among patients with cardiovascular disease and diabetes. To date, the association between participation in the MSSP by provider organizations and medication use or adherence among their patients with cardiovascular disease or diabetes has not been described. Objective: To assess the association between exposure to the MSSP and changes in the use of and adherence to common antihypertensive, lipid-lowering, and hypoglycemic medications...
July 12, 2017: JAMA Cardiology
https://www.readbyqxmd.com/read/28699089/cardiovascular-safety-of-antidiabetic-drugs-in-the-hospital-setting
#3
REVIEW
Stacey A Seggelke, Mark C Lindsay, Ingrid Hazlett, Rebecca Sanagorski, Robert H Eckel, Cecilia C Low Wang
PURPOSE OF REVIEW: Patients with diabetes and/or stress hyperglycemia requires good glycemic control in the hospital setting, often requiring the use of glucose-lowering therapy. Standard-of-care dictates that non-insulin therapy be discontinued, with insulin therapy initiated using a basal-bolus approach. However, insulin is associated with a high risk for hypoglycemia and medical errors. Alternatives to insulin are needed in the inpatient setting, but the cardiovascular (CV) safety of non-insulin therapy is a concern...
August 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28698040/role-of-class-ii-p-fimbriae-and-cytokine-response-in-the-pathogenesis-of-escherichia-coli-kidney-infection-in-diabetic-mice
#4
Chin-Chung Tseng, Ming-Cheng Wang, Wei-Hung Lin, I-Chuang Liao, Wen-Chung Chen, Ching-Hao Teng, Jing-Jou Yan, An-Bang Wu, Jiunn-Jong Wu
BACKGROUND: The role of class II P fimbriae (P fimbriae II) in diabetic kidney infections is uncertain, although some genetic and epidemiological studies suggest a lower prevalence of P fimbriae II genes in Escherichia coli strains isolated from diabetic patients with complicated kidney infections. METHODS: We inoculated a P fimbriae II deficient E. coli (DH5αT) or an isogenic P fimbriae II expressing transformant (DH5αTP) into the bladders of diabetic and non-diabetic BALB/C mice, and sacrificed them after 3 days...
June 29, 2017: Journal of Microbiology, Immunology, and Infection, Wei Mian Yu Gan Ran za Zhi
https://www.readbyqxmd.com/read/28685973/efficacy-and-tolerability-of-the-new-autoinjected-suspension-of-exenatide-once-weekly-versus-exenatide-twice-daily-in-patients-with-type-2-diabetes
#5
Carol H Wysham, Julio Rosenstock, Marion L Vetter, Fang Dong, Peter Öhman, Nayyar Iqbal
AIMS: To simplify administration of aqueous exenatide once weekly, which requires reconstitution, the exenatide microspheres have been reformulated in a ready-to-use autoinjector with a Miglyol® diluent (exenatide QWS-AI). This study compared the efficacy and safety of exenatide QWS-AI with the first-in-class glucagon-like peptide-1 receptor agonist exenatide twice daily (BID). MATERIALS AND METHODS: This randomized, open-label, controlled study in patients with type 2 diabetes on diet and exercise or stable oral glucose-lowering medication randomized patients 3:2 to either exenatide QWS-AI (2 mg) or exenatide BID (10 μg) for 28 weeks...
July 7, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28683654/efficacy-and-safety-of-multitarget-therapy-with-cyclophosphamide-and-tacrolimus-for-lupus-nephritis-a-prospective-single-arm-single-centre-open-label-pilot-study-in-japan
#6
R Sakai, T Kurasawa, E Nishi, T Kondo, Y Okada, A Shibata, K Nishimura, K Chino, A Okuyama, H Takei, H Nagasawa, K Amano
Background Pulsed cyclophosphamide or mycophenolate mofetil for lupus nephritis has limited efficacy. We previously reported a case of mixed-class IV + V lupus nephritis successfully treated with cyclophosphamide and tacrolimus. This study assessed the efficacy and safety of multitarget therapy with cyclophosphamide and tacrolimus for the treatment of lupus nephritis. Methods In a prospective, single-arm, open label pilot study, we recruited 15 patients aged 18-64 years with active lupus nephritis who met the American College of Rheumatology criteria for a diagnosis of systemic lupus erythematosus (1997)...
January 1, 2017: Lupus
https://www.readbyqxmd.com/read/28645260/within-class-differences-in-cancer-risk-for-sulfonylurea-treatments-in-patients-with-type-2-diabetes-zodiac-55-a-study-protocol
#7
Dennis Schrijnders, Geertruida H de Bock, Sebastiaan T Houweling, Kornelis J J van Hateren, Klaas H Groenier, Jeffrey A Johnson, Henk J G Bilo, Nanne Kleefstra, Gijs W D Landman
BACKGROUND: Patients with type 2 diabetes (T2D) are at increased risk for developing cancer. As approximately 8% of the world's population is living with T2D, even a slight increase in cancer risk could result in an enormous impact on the number of persons developing cancer. In addition, several glucose lowering drug classes for treating patients with T2D have been associated with a difference in risk of cancer overall, and especially for obesity related cancers. In what way and to what degree cancer risk is modified by the use of different sulfonylureas (SU) is unclear...
June 23, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28614667/n-glycosylation-of-asparagine-130-in-the-extracellular-domain-of-the-human-calcitonin-receptor-significantly-increases-peptide-hormone-affinity
#8
Sang-Min Lee, Jason M Booe, Joseph J Gingell, Virginie Sjoelund, Debbie L Hay, Augen A Pioszak
The calcitonin receptor (CTR) is a class B G protein-coupled receptor that is activated by the peptide hormones calcitonin and amylin. Calcitonin regulates bone remodeling through CTR, whereas amylin regulates blood glucose and food intake by activating CTR in complex with receptor activity-modifying proteins (RAMPs). These receptors are targeted clinically for the treatment of osteoporosis and diabetes. Here, we define the role of CTR N-glycosylation in hormone binding using purified calcitonin and amylin receptor extracellular domain (ECD) glycoforms and fluorescence polarization/anisotropy and isothermal titration calorimetry peptide-binding assays...
July 5, 2017: Biochemistry
https://www.readbyqxmd.com/read/28605194/discovery-of-two-bacterial-nitric-oxide-responsive-proteins-and-their-roles-in-bacterial-biofilm-regulation
#9
Sajjad Hossain, Lisa-Marie Nisbett, Elizabeth M Boon
Bacterial biofilms form when bacteria adhere to a surface and produce an exopolysaccharide matrix ( Costerton Science 1999 , 284 , 1318 ; Davies Science 1998 , 280 , 295 ; Flemming Nat. Rev. Microbiol. 2010 , 8 , 623 ). Because biofilms are resistant to antibiotics, they are problematic in many aspects of human health and welfare, causing, for instance, persistent fouling of medical implants such as catheters and artificial joints ( Brunetto Chimia 2008 , 62 , 249 ). They are responsible for chronic infections in the lungs of cystic fibrosis patients and in open wounds, such as those associated with burns and diabetes...
June 12, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28584626/mmp2-and-mmp9-associate-with-crescentic-glomerulonephritis
#10
Tessa M Phillips, Mitali Fadia, Tom N Lea-Henry, Jonathan Smiles, Giles D Walters, Simon H Jiang
Background: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by multiple organ involvement. Lupus nephritis (LN) is a common manifestation with a wide variety of histological appearances. Matrix metalloproteinases (MMP) 2 and 9 are gelatinases capable of degrading glomerular basement membrane type IV collagen, which have been associated with LN. We examine the expression of MMP2 and MMP9 in different classes of LN. Methods: MMP2 and MMP9 expression was detected by immunohistochemistry in sections from renal biopsy specimens with class III, class IV and class V LN (total n = 31), crescentic immunoglobulin A nephropathy (n = 6), pauci-immune glomerulonephritis (n = 7), minimal change disease (n = 2), mesangiocapillary glomerulonephritis (n = 7), diabetic nephropathy (n = 12) and histologically normal controls (n = 8)...
April 2017: Clinical Kidney Journal
https://www.readbyqxmd.com/read/28584109/dapagliflozin-suppresses-glucagon-signaling-in-rodent-models-of-diabetes
#11
May-Yun Wang, Xinxin Yu, Young Lee, Sara Kay McCorkle, Shiuhwei Chen, Jianping Li, Zhao V Wang, Jaime A Davidson, Philipp E Scherer, William L Holland, Roger H Unger, Michael G Roth
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of antidiabetic drug used for the treatment of diabetes. These drugs are thought to lower blood glucose by blocking reabsorption of glucose by SGLT2 in the proximal convoluted tubules of the kidney. To investigate the effect of inhibiting SGLT2 on pancreatic hormones, we treated perfused pancreata from rats with chemically induced diabetes with dapagliflozin and measured the response of glucagon secretion by alpha cells in response to elevated glucose...
June 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28573460/brain-glp-1-igf-1-signaling-and-autophagy-mediate-exendin-4-protection-against-apoptosis-in-type-2-diabetic-rats
#12
Emanuel Candeias, Inês Sebastião, Susana Cardoso, Cristina Carvalho, Maria Sancha Santos, Catarina Resende Oliveira, Paula I Moreira, Ana I Duarte
Type 2 diabetes (T2D) is a modern socioeconomic burden, mostly due to its long-term complications affecting nearly all tissues. One of them is the brain, whose dysfunctional intracellular quality control mechanisms (namely autophagy) may upregulate apoptosis, leading to cognitive dysfunction and Alzheimer disease (AD). Since impaired brain insulin signaling may constitute the crosslink between T2D and AD, its restoration may be potentially therapeutic herein. Accordingly, the insulinotropic anti-T2D drugs from glucagon-like peptide-1 (GLP-1) mimetics, namely, exendin-4 (Ex-4), could be a promising therapy...
June 2, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28562585/crystal-structure-of-the-glp-1-receptor-bound-to-a-peptide-agonist
#13
Ali Jazayeri, Mathieu Rappas, Alastair J H Brown, James Kean, James C Errey, Nathan J Robertson, Cédric Fiez-Vandal, Stephen P Andrews, Miles Congreve, Andrea Bortolato, Jonathan S Mason, Asma H Baig, Iryna Teobald, Andrew S Doré, Malcolm Weir, Robert M Cooke, Fiona H Marshall
Glucagon-like peptide 1 (GLP-1) regulates glucose homeostasis through the control of insulin release from the pancreas. GLP-1 peptide agonists are efficacious drugs for the treatment of diabetes. To gain insight into the molecular mechanism of action of GLP-1 peptides, here we report the crystal structure of the full-length GLP-1 receptor bound to a truncated peptide agonist. The peptide agonist retains an α-helical conformation as it sits deep within the receptor-binding pocket. The arrangement of the transmembrane helices reveals hallmarks of an active conformation similar to that observed in class A receptors...
June 8, 2017: Nature
https://www.readbyqxmd.com/read/28545784/pro-and-antiarrhythmic-actions-of-sulfonylureas-mechanistic-and-clinical-evidence
#14
REVIEW
Charles E Leonard, Sean Hennessy, Xu Han, David S Siscovick, James H Flory, Rajat Deo
Sulfonylureas are the most commonly used second-line drug class for treating type 2 diabetes mellitus (T2DM). While the cardiovascular safety of sulfonylureas has been examined in several trials and nonrandomized studies, little is known of their specific effects on sudden cardiac arrest (SCA) and related serious arrhythmic outcomes. This knowledge gap is striking, because persons with DM are at increased risk of SCA. In this review, we explore the influence of sulfonylureas on the risk of serious arrhythmias, with specific foci on ischemic preconditioning, cardiac excitability, and serious hypoglycemia as putative mechanisms...
May 22, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/28544369/american-association-of-clinical-endocrinologists-2017
#15
EDITORIAL
Abigail E Dove, Payal H Marathe, Helen X Gao, Kelly L Close
The 26th annual scientific and clinical sessions of the American Association of Clinical Endocrinologists (AACE) gathered in Austin, TX, USA from May 3-7, 2017. The meeting included little in the way of new data, but was rich in commentary from leaders in the diabetes field, particularly with regard to sodium/glucose cotransporter 2 (SGLT-2) inhibitors and glucagon-like peptide 1 (GLP-1) agonists. In a deep-dive session on the renal effects of SGLT-2 inhibitors, both Dr Ralph DeFronzo and DrMatthew Weir were extremely positive about the renal benefit of these agents and expressed strong confidence that the benefits extend to all members of the class...
May 23, 2017: Journal of Diabetes
https://www.readbyqxmd.com/read/28515269/effect-of-omega-3-supplementation-on-neuropathy-in-type-1-diabetes-a-12-month-pilot-trial
#16
Evan J H Lewis, Bruce A Perkins, Leif E Lovblom, Richard P Bazinet, Thomas M S Wolever, Vera Bril
OBJECTIVE: To test the hypothesis that 12 months of seal oil omega-3 polyunsaturated fatty acids (ω-3 PUFA) supplementation will stop the known progression of diabetic sensorimotor polyneuropathy (DSP) in type 1 diabetes mellitus (T1DM). METHODS: Individuals with T1DM and evidence of DSP as determined by a Toronto Clinical Neuropathy Score ≥1 were recruited to participate in a single-arm, open-label trial of seal oil ω-3 PUFA supplementation (10 mL·d(-1); 750 mg eicosapentaenoic acid, 560 mg docosapentaenoic acid, and 1,020 mg docosahexaenoic acid) for 1 year...
June 13, 2017: Neurology
https://www.readbyqxmd.com/read/28485264/effects-of-nwt-03-an-egg-protein-hydrolysate-on-blood-pressure-in-normotensive-high-normotensive-and-mild-hypertensive-men-and-women-a-dose-finding-study
#17
Jogchum Plat, Nadine Severins, Steve Morrison, Ronald P Mensink
Angiotensin-converting enzyme (ACE) inhibitors are important agents in blood pressure (BP) management. It was recently shown that the egg-protein hydrolysate NWT-03 inhibited ACE in Zucker diabetic fatty rats. We therefore designed a dose-finding study to assess the effects of 1, 2 and 5 g NWT-03 on daytime, 36-h, and night-time systolic and diastolic BP (SBP and DBP) in ninety-two generally healthy subjects with normal BP (n 29), high-normal BP (n 34) or mild hypertension (n 29). The study had a cross-over design with six treatment arms (1 g NWT-03 or placebo in period 1 and placebo or 1 g NWT-03 in period 2, 2 g NTW-03 or placebo in period 1 and placebo or 2 g NWT-03 in period 2, or 5 g NTW-03 or placebo in period 1 and placebo or 5 g NTW-03 in period 2)...
May 9, 2017: British Journal of Nutrition
https://www.readbyqxmd.com/read/28474736/effect-of-out-of-pocket-cost-on-medication-initiation-adherence-and-persistence-among-patients-with-type-2-diabetes-the-diabetes-study-of-northern-california-distance
#18
Andrew J Karter, Melissa M Parker, Matthew D Solomon, Courtney R Lyles, Alyce S Adams, Howard H Moffet, Mary E Reed
OBJECTIVE: To estimate the effect of out-of-pocket (OOP) cost on nonadherence to classes of cardiometabolic medications among patients with diabetes. DATA SOURCES/SETTING: Electronic health records from a large, health care delivery system for 223,730 patients with diabetes prescribed 842,899 new cardiometabolic medications during 2006-2012. STUDY DESIGN: Observational, new prescription cohort study of the effect of OOP cost on medication initiation and adherence...
May 5, 2017: Health Services Research
https://www.readbyqxmd.com/read/28461573/genetic-and-small-molecule-disruption-of-the-aid-rad51-axis-similarly-protects-nonobese-diabetic-mice-from-type-1-diabetes-through-expansion-of-regulatory-b-lymphocytes
#19
Jeremy J Ratiu, Jeremy J Racine, Muneer G Hasham, Qiming Wang, Jane A Branca, Harold D Chapman, Jing Zhu, Nina Donghia, Vivek Philip, William H Schott, Clive Wasserfall, Mark A Atkinson, Kevin D Mills, Caroline M Leeth, David V Serreze
B lymphocytes play a key role in type 1 diabetes (T1D) development by serving as a subset of APCs preferentially supporting the expansion of autoreactive pathogenic T cells. As a result of their pathogenic importance, B lymphocyte-targeted therapies have received considerable interest as potential T1D interventions. Unfortunately, the B lymphocyte-directed T1D interventions tested to date failed to halt β cell demise. IgG autoantibodies marking humans at future risk for T1D indicate that B lymphocytes producing them have undergone the affinity-maturation processes of class switch recombination and, possibly, somatic hypermutation...
June 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28452063/risk-factors-of-adverse-health-outcomes-after-hospital-discharge-modifiable-by-clinical-pharmacist-interventions-a-review-with-a-systematic-approach
#20
REVIEW
B Morath, T Mayer, A F J Send, T Hoppe-Tichy, W E Haefeli, H M Seidling
AIM: This review assessed the evidence on risk factors for the occurrence of adverse health outcomes after discharge (i.e. unplanned readmission or adverse drug event after discharge) that are potentially modifiable by clinical pharmacist interventions. The findings were compared with patient characteristics reported in guidelines that supposedly indicate a high risk of drug-related problems. METHODS: First, guidelines and risk assessment tools were searched for patient characteristics indicating a high risk of drug-related problems...
April 27, 2017: British Journal of Clinical Pharmacology
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