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Ghazaleh Arabzadeh, Azar Shahpiri
Acetohydroxyacid synthase (AHAS) is the first enzyme in the biosynthesis pathway of the branched chain amino acids (valine, lleucine and isoleucine). AHAS is the common target site of five herbicide chemical groups: sulfonylurea, imidazolinone, triazolopyrimidine, pyrimidinyl-thiobenzoates, and sulfonyl-aminocarbonyl-triazolinone. The gene encoding catalytic subunit of rice AHAS (cOsAHAS) without part of the chloroplast transit sequence was cloned into the bacterial expression vector pET41a and heterologously expressed in Escherichia coli as carboxy-terminal extensions of glutathione-S-transferase (GST)...
November 14, 2018: Protein and Peptide Letters
Birthe Gade-Rasmussen, Sten Madsbad, Maria Saur Svane, Christoffer Martinussen, Torben Hansen
In this case report a 40-year-old insulin-treated male patient presented with a KCNJ11 R201H mutation, which can cause neonatal diabetes. After initiation of treatment with high doses of the sulfonylurea glibencamide in combination with the glucagon-like peptide 1 receptor agonist liraglutide, insulin treatment of the patient could be terminated. The first nine months after termination of insulin treatment the glycated haemoglobin concentration was 48-54 mmol/mol (i.e. 6.5-7.1%).
November 12, 2018: Ugeskrift for Laeger
Nathaniel J Hart, Craig Weber, Klearchos K Papas, Sean W Limesand, Josef Vagner, Ronald M Lynch
Linking two pharmacophores that bind different cell surface receptors into a single molecule can enhance cell-targeting specificity to cells that express the complementary receptor pair. In this report, we developed and tested a synthetic multivalent ligand consisting of glucagon-like peptide-1 (GLP-1) linked to glibenclamide (Glb) for signaling efficacy in β-cells. Expression of receptors for these ligands, as a combination, are relatively specific to the β-cell in the pancreas. The multivalent GLP-1/Glb increased both intracellular cAMP and Ca2+ , although Ca2+ responses were significantly depressed compared to the monomeric Glb...
November 7, 2018: American Journal of Physiology. Cell Physiology
Timothy M E Davis, David G Bruce, Judith Finn, Bradley H Curtis, Helen Barraclough, Wendy A Davis
AIMS: Since recent changes in therapies and management may have influenced the risk of severe hypoglycaemia complicating type 2 diabetes, we determined its incidence and predictors in community-based patients studied between 2008 and 2013 and compared them with those in a cohort with type 2 diabetes from the same geographical area assessed a decade earlier. METHODS: We studied 1,551 participants (mean age 65.7 years, 51.9% males) with type 2 diabetes from the longitudinal observational Fremantle Diabetes Study Phase II (FDS2)...
October 28, 2018: Diabetes, Obesity & Metabolism
Lavanya Cherukuri, Michael S Smith, John A Tayek
Introduction: Cost of generic medications has risen more in the past few years than any other time in history. While medical insurance covers much of these costs, health care professionals can better provide medications that have the longest duration of action when compared to placebo - treated controls. This will save health care costs and improve prescribing accuracy. Methods: Papers in PubMed were identified with keywords placebo. The study must be at least 2 years in length to evaluate the change in A1c over time...
September 2018: Endocrinology, diabetes and metabolism journal
Bao Yang, Xiwei Zheng, David S Hage
Ultrafast affinity extraction was evaluated and used with microcolumns containing human serum albumin (HSA) to measure the global affinity constants and dissociation rate constants for several second- and third-generation sulfonylurea drugs with solution-phase normal HSA or glycated HSA. Glibenclamide, glimepiride and glipizide were used as model drugs for this work. Both single- and two-column systems were considered for the analysis of global affinities for the model drugs. These methods were optimized with respect to the flow rates, column sizes and sample residence times that were employed with each drug for ultrafast affinity extraction...
October 17, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Michael S Bohnen, Lijiang Ma, Na Zhu, Hongjian Qi, Conor McClenaghan, Claudia Gonzaga-Jauregui, Frederick E Dewey, John D Overton, Jeffrey G Reid, Alan R Shuldiner, Aris Baras, Kevin J Sampson, Marta Bleda, Charaka Hadinnapola, Matthias Haimel, Harm J Bogaard, Colin Church, Gerry Coghlan, Paul A Corris, Mélanie Eyries, J Simon R Gibbs, Barbara Girerd, Arjan C Houweling, Marc Humbert, Christophe Guignabert, David G Kiely, Allan Lawrie, Rob V MacKenzie Ross, Jennifer M Martin, David Montani, Andrew J Peacock, Joanna Pepke-Zaba, Florent Soubrier, Jay Suntharalingam, Mark Toshner, Carmen M Treacy, Richard C Trembath, Anton Vonk Noordegraaf, John Wharton, Martin R Wilkins, Stephen J Wort, Katherine Yates, Stefan Gräf, Nicholas W Morrell, Usha Krishnan, Erika B Rosenzweig, Yufeng Shen, Colin G Nichols, Robert S Kass, Wendy K Chung
BACKGROUND: In pulmonary arterial hypertension (PAH), pathological changes in pulmonary arterioles progressively raise pulmonary artery pressure and increase pulmonary vascular resistance, leading to right heart failure and high mortality rates. Recently, the first potassium channelopathy in PAH, because of mutations in KCNK3, was identified as a genetic cause and pharmacological target. METHODS: Exome sequencing was performed to identify novel genes in a cohort of 99 pediatric and 134 adult-onset group I PAH patients...
October 2018: Circulation. Genomic and precision medicine
Sanjay Kalra, Deepak Khandelwal
This editorial discusses the concept of flexibility in diabetes care. Flexibility of an oral antidiabetic drug (OAD) is defined as its ability to be used efficaciously and safely, in flexible, convenient doses and frequencies, at flexible timings of administration. This flexibility also includes OAD usage alone or in combination with a wide spectrum of drugs, in a wide spectrum of patients, irrespective of their age, gender, health status, or dietary patterns, with flexible dose titration, glucose monitoring and healthcare contact schedules...
September 2018: European Endocrinology
Sanjay Kalra, Deepak Khandelwal, Sarita Bajaj, Ashok Kumar Das
The kidney is important in the context of diabetes not only because it is involved in normal glucose homeostasis, but also because it is one of the most important end organs to be involved in diabetes complications. Glomeruli are the meeting point of both microvascular, or renal; and macrovascular, or cardiovascular, health in diabetes. Sulfonylureas are effective glucose-lowering drugs. While a sulfonylurea-based glucose-lowering strategy is nephro-safe and nephro-protective, this aspect of sulfonylurea pharmaco-biology has not been highlighted earlier...
September 2018: European Endocrinology
W R Powell, C L Christiansen, D R Miller
AIM: To examine the risks of all-cause mortality and cardiovascular events associated with adding vs switching to second-line therapies in a comparative safety study of people with Type 2 diabetes mellitus. METHODS: We conducted a retrospective cohort study using an as-treated analysis of people served by the Veterans Health Administration who were on metformin and subsequently augmented this treatment or switched to other oral glucose-lowering treatments between 1998 and 2012...
October 21, 2018: Diabetic Medicine: a Journal of the British Diabetic Association
Jens Bohlken, Louis Jacob, Karel Kostev
BACKGROUND: There is a conflicting literature on the association between the use of antihyperglycemic drugs and dementia risk. OBJECTIVE: The goal of this case-control study was to analyze the association between the use of antihyperglycemic drugs and dementia risk in patients followed in general practices in Germany. METHODS: This study included patients with type 2 diabetes mellitus who had received a first dementia diagnosis in 972 general practices in Germany between January 2013 and December 2017 (index date)...
2018: Journal of Alzheimer's Disease: JAD
John-Michael Gamble, Jennifer R Donnan, Eugene Chibrikov, Laurie K Twells, William K Midodzi, Sumit R Majumdar
Although the glucose lowering effect of dipeptidyl peptidase-4 (DPP4) inhibitors is well established, several potential serious acute safety concerns have been raised including acute kidney injury, respiratory tract infections, and acute pancreatitis. Using the UK-based Clinical Practice Research Datalink (CPRD), we identified initiators (365-day washout period) of DPP4 inhibitors and relevant comparators including initiators of sulfonylureas, metformin, thiazolidinediones, and insulin between January 2007 and January 2016 to quantify the association between DPP4 inhibitors and three acute health events - acute kidney injury, respiratory tract infections, and acute pancreatitis...
October 11, 2018: Scientific Reports
O Montvida, J B Green, J Atherton, S K Paul
AIMS: In people with metformin-treated diabetes, to evaluate the risk of acute pancreatitis, pancreatic cancer and other diseases of the pancreas post second-line anti-hyperglycaemic agent initiation. METHODS: People with Type 2 diabetes diagnosed after 2004 who received metformin plus a dipeptidyl peptidase-4 inhibitor (DPP-4i, n = 50 095), glucagon-like peptide-1 receptor agonist (GLP-1RA, n = 12 654), sulfonylurea (n = 110 747), thiazolidinedione (n = 17 597) or insulin (n = 34 805) for at least 3 months were identified in the US Centricity Electronic Medical Records...
October 10, 2018: Diabetic Medicine: a Journal of the British Diabetic Association
Brian Gibson, Virve Vidgren, Gopal Peddinti, Kristoffer Krogerus
Diacetyl contributes to the flavor profile of many fermented products. Its typical buttery flavor is considered as an off flavor in lager-style beers, and its removal has a major impact on time and energy expenditure in breweries. Here, we investigated the possibility of lowering beer diacetyl levels through evolutionary engineering of lager yeast for altered synthesis of α-acetolactate, the precursor of diacetyl. Cells were exposed repeatedly to a sub-lethal level of chlorsulfuron, which inhibits the acetohydroxy acid synthase responsible for α-acetolactate production...
October 10, 2018: Journal of Industrial Microbiology & Biotechnology
B P Gupta, I Sharma, N Kohli, S Sharma, A Rathi, A K Sharma
In view of the overall health impact of NIDDM, inventers understand the necessity of improving glycemic control in adults with type 2 diabetes. BGR-34 provides an effective treatment option for adults with type 2 diabetes who have been inadequately controlled on lifestyle with or without other oral hypoglycemic agents (OHGAs) such as metformin, sulfonylurea, or a glitazones. BGR-34 is an appropriate option to consider for addition to a managed care drug formulary. Treatment with BGR-34 produced clinically relevant and statistically significant reductions in all three key measures of glucose control studied -FPG, PPBG and HbA1c- when compared with placebo...
October 2018: Journal of Traditional and Complementary Medicine
Ramsankar Basak, John P Bentley, David J McCaffrey, Donna West-Strum, Sarahmona M Przybyla, Benjamin F Banahan
BACKGROUND: Adherence to multiple medications (i.e., separate dosage forms) intended for a disease can be measured by different single estimators, termed as composite estimators of intra-disease multiple medication adherence: 80% days covered (a) by at least one medication ("at least one"); (b) by both medications ("both"); (c) by each medication measured separately ("all"); and (d) computing an average of the individual medication adherence estimates ("average")...
October 2, 2018: Research in Social & Administrative Pharmacy: RSAP
John-Michael Gamble, Eugene Chibrikov, William K Midodzi, Laurie K Twells, Sumit R Majumdar
OBJECTIVES: To compare population-based incidence rates of new-onset depression or self-harm in patients initiating incretin-based therapies with that of sulfonylureas (SU) and other glucose-lowering agents. DESIGN: Population-based cohort study. SETTING: Patients attending primary care practices registered with the UK-based Clinical Practice Research Datalink (CPRD). PARTICIPANTS: Using the UK-based CPRD, we identified two incretin-based therapies cohorts: (1) dipeptidyl peptidase-4 inhibitor (DPP-4i)-cohort, consisting of new users of DPP-4i and SU and (2) glucagon-like peptide-1 receptor agonists (GLP-1RA)-cohort, consisting of new users of GLP-1RA and SU, between January 2007 and January 2016...
October 8, 2018: BMJ Open
Sadaf Moeez, SyedaKiran Riaz, Nosheen Masood, Naghmana Kanwal, Mohammad Ali Arif, Rauf Niazi, Sumbul Khalid
OBJECTIVES: Type 2 diabetes is a complex genetic disorder, and a large number of genetic polymorphisms may be involved in its pathogenesis. Pharmacologically, type 2 diabetes can be treated with 9 different approved classes of drugs, but metformin is suggested as the first line of therapy, followed by sulfonylureas. METHODS: This was a case-control study consisting of 300 metformin responders and 300 metformin nonresponders in patients with type 2 diabetes and 300 healthy Pakistani subjects...
July 17, 2018: Canadian Journal of Diabetes
Alexander Sidelmann Christensen, Heidi Storgaard, Sofie Hædersdal, Torben Hansen, Filip Krag Knop, Tina Vilsbøll
INTRODUCTION: Hepatocyte nuclear factor 1α (HNF1A)-diabetes is the most common monogenetic subtype of diabetes. Strict glycaemic control is crucial for a good prognosis for patients with HNF1A-diabetes. Sulfonylurea (SU) is used as a first-line therapy in HNF1A-diabetes. However, SU therapy may be problematic as it confers a high risk of hypoglycaemia. We hypothesise that low dose of SU in combination with a dipeptidyl peptidase 4 inhibitor provides a safer and more efficacious treatment in patients with HNF1A-diabetes compared with SU as monotherapy...
October 3, 2018: BMJ Open
Jong Seo Yoon, Kyu Jung Park, Young Bae Sohn, Hae Sang Lee, Jin Soon Hwang
Permanent neonatal diabetes mellitus is most commonly caused by mutations in the ATP-sensitive potassium channel (KATP) subunits. Prompt initiation of sulfonylurea treatment can improve glycemic control in children with KCNJ11 mutation. In this report, we present a case of permanent neonatal diabetes caused by a mutation in the KCNJ11 gene that was successfully treated via early switching of insulin to sulfonylurea treatment. A 53-day-old female infant presented with diabetic ketoacidosis. Insulin was administered for the ketoacidosis and blood glucose regulation...
September 2018: Annals of Pediatric Endocrinology & Metabolism
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