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https://www.readbyqxmd.com/read/28423178/head-to-head-comparison-of-structurally-unrelated-dpp4-inhibitors-in-the-setting-of-renal-ischemia-reperfusion-injury
#1
Christoph Reichetzeder, Karoline von Websky, Oleg Tsuprykov, Azadeh Mohagheghi Samarin, Luise Gabriele Falke, Sulistyo Emantoko Dwi Putra, Ahmed Abdallah Hasan, Viktoriia Antonenko, Caterina Curato, Jörg Rippman, Thomas Klein, Berthold Hocher
BACKGROUND AND PURPOSE: Results regarding protective effects of DPP4 inhibitors in renal ischemia-reperfusion-injury (IRI) are conflicting. The current study performed a head-to-head comparison of structurally unrelated DPP4 inhibitors in the setting of renal IRI. EXPERIMENTAL APPROACH: IRI was induced in uninephrectomized male rats by renal artery clamping for 30 minutes. The sham group was uninephrectomized but not subjected to IRI. DPP4 inhibitors or vehicle were given p...
April 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28418203/effectiveness-of-vildagliptin-as-add-on-to-metformin-monotherapy-among-uncontrolled-type-2-diabetes-mellitus-patients-in-a-real-world-setting
#2
Cheli Melzer Cohen, Carla Davis, Varda Shalev, Gabriel Chodick
BACKGROUND: Vildagliptin is a dipeptidyl peptidase-4 inhibitor (DPP4-i) commonly used as a dual oral agent with metformin, thiazolidinediones, or sulfonylurea for type 2 diabetes mellitus (T2DM). The efficacy of dual therapy with vildagliptin and metformin has been established in randomized clinical trials but little evidence exists from observational studies. The aims of the present study were to evaluate the effectiveness of vildagliptin as an add-on therapy to metformin in reducing HbA1c as well as its influences on body weight and blood lipids in a real-life setting...
April 18, 2017: Journal of Diabetes
https://www.readbyqxmd.com/read/28417296/dpp4-inhibitors-and-cardiovascular-outcomes-safety-on-heart-failure
#3
REVIEW
Chang Xia, Aditya Goud, Jason D'Souza, CHanukya Dahagam, Xiaoquan Rao, Sanjay Rajagopalan, Jixin Zhong
Diabetes is an important risk factor for cardiovascular disease. However, clinical data suggests intensive glycemic control significantly increase rather than decrease cardiovascular mortality, which is largely due to the fact that a majority of oral anti-diabetic drugs have adverse cardiovascular effect. There are several large-scale clinical trials evaluating the cardiovascular safety of DPP4 inhibitors, a novel class of oral anti-diabetic medications, which have been recently completed. They were proven to be safe with regard to cardiovascular outcomes...
April 18, 2017: Heart Failure Reviews
https://www.readbyqxmd.com/read/28393419/synthesis-and-evaluation-of-novel-1-2-4-triazolo-5-1-c-1-2-4-triazines-and-pyrazolo-5-1-c-1-2-4-triazines-as-potential-antidiabetic-agents
#4
Vladimir L Rusinov, Irina M Sapozhnikova, Anastasiya M Bliznik, Oleg N Chupakhin, Valery N Charushin, Alexander A Spasov, Pavel M Vassiliev, Valentina A Kuznetsova, Andrey I Rashchenko, Denis A Babkov
Inhibition of the dipeptidyl peptidase-4 (DPP4) enzyme activity and prevention of advanced glycation end (AGE) products formation represents a reliable approach to achieve control over hyperglycemia and the associated pathogenesis of diabetic vascular complications. In the frames of this research study, several triazolo- and pyrazolotriazines were synthesized and evaluated as inhibitors of AGE products formation, DPP4, glycogen phosphorylase and α-glucosidase activities, as well as AGE cross-link breakers...
April 10, 2017: Archiv der Pharmazie
https://www.readbyqxmd.com/read/28377531/further-evidence-for-bats-as-the-evolutionary-source-of-middle-east-respiratory-syndrome-coronavirus
#5
S J Anthony, K Gilardi, V D Menachery, T Goldstein, B Ssebide, R Mbabazi, I Navarrete-Macias, E Liang, H Wells, A Hicks, A Petrosov, D K Byarugaba, K Debbink, K H Dinnon, T Scobey, S H Randell, B L Yount, M Cranfield, C K Johnson, R S Baric, W I Lipkin, J A K Mazet
The evolutionary origins of Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) are unknown. Current evidence suggests that insectivorous bats are likely to be the original source, as several 2c CoVs have been described from various species in the family Vespertilionidae Here, we describe a MERS-like CoV identified from a Pipistrellus cf. hesperidus bat sampled in Uganda (strain PREDICT/PDF-2180), further supporting the hypothesis that bats are the evolutionary source of MERS-CoV. Phylogenetic analysis showed that PREDICT/PDF-2180 is closely related to MERS-CoV across much of its genome, consistent with a common ancestry; however, the spike protein was highly divergent (46% amino acid identity), suggesting that the two viruses may have different receptor binding properties...
April 4, 2017: MBio
https://www.readbyqxmd.com/read/28376584/a-novel-multi-epitope-vaccine-based-on-dipeptidyl-peptidase-4-prevents-streptozotocin-induced-diabetes-by-producing-anti-dpp4-antibody-and-immunomodulatory-effect-in-c57bl-6j-mice
#6
Zhixin Li, Jinzhi Fang, Rui Jiao, Xiaomin Wei, Yanjie Ma, Xiaoran Liu, Peng Cheng, Taiming Li
Type 1 diabetes is a chronic organ-specific autoimmune disease in which selective destruction of insulin-producing β-cells leads to impaired glucose metabolism and its attendant complications. A series of Dipeptidyl peptidase 4 (DPP4) inhibitors have been developed and granted approval in the treatment of type 2 diabetes mellitus by inhibiting the enzymatic degradation of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). An increasing number of studies have shown the potential benefits of DPP4 inhibitors for type 1 diabetes...
March 31, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28373475/cancer-stem-cell-gene-variants-in-cd44-predict-outcome-in-stage-ii-and-stage-iii-colon-cancer-patients
#7
Michael Stotz, Sereina A Herzog, Martin Pichler, Maria Smolle, Jakob Riedl, Christopher Rossmann, Angelika Bezan, Herbert Stöger, Wilfried Renner, Andrea Berghold, Armin Gerger
BACKGROUND/AIM: Growing evidence suggests that human cancers are stem cell diseases and recent data support the existence of cancer stem cells (CSCs) in a variety of malignancies, including colon cancer. These CSCs were shown to be capable of initiating tumor development and progression. Several studies have suggested CD133, CD26 and CD44 as markers of tumor-initiating cells of colon cancer. The purpose of the present study was to assess the impact of single-nucleotide polymorphisms (SNPs) in stem cell-related genes on clinical outcome in a large cohort of colon cancer patients with clinical stage II and III...
April 2017: Anticancer Research
https://www.readbyqxmd.com/read/28372289/dpp4-regulates-the-inflammatory-response-in-a-rat-model-of-febrile-seizures
#8
Qi Sun, Yusong Zhang, Jie Huang, Fang Yu, Jian Xu, Biwen Peng, Wanhong Liu, Song Han, Jun Yin, Xiaohua He
Febrile seizures (FS) are the most common seizure disorders in children aged 6 months to 5 years. Children suffering from complex FS have a high risk of developing subsequent temporal lobe epilepsy (TLE). Neuroinflammation is involved in the pathogenesis of FS although the mechanism remains unknown. Our previous study using the Whole Rat Genome Oligo Microarray determined that Dipeptidyl peptidase IV (DPP4) is potentially a related gene in FS rats. In this study, we demonstrated that DPP4 expression was significantly increased at both the protein and mRNA levels after hyperthermia induction...
2017: Bio-medical Materials and Engineering
https://www.readbyqxmd.com/read/28370279/sensitive-and-specific-lc-esi-ms-ms-method-for-determination-of-zydpla1-a-novel-long-acting-dpp4-inhibitor-in-rat-plasma-an-application-for-toxicokinetics-study-in-rats
#9
Poonam Giri, Nirmal Patel, Bharat Patel, Harilal Patel, Rajesh Bahekar, Nuggehally R Srinivas, Pankaj R Patel, Ranjit Desai
A rapid and highly specific assay was developed and validated for estimation ofZYDPLA1 in rat plasma using liquid chromatography coupled to tandem mass spectrometry with positive electrospray ionization. Method validation comprised of parameters such as: specificity, matrix effect, precision, accuracy, recovery, stability etc. The assay procedure involved a simple protein precipitation of ZYDPLA1 and alprazolam (internal standard, IS) from rat plasma using acetonitrile. Chromatographic separation was achieved with a gradient mobile phase comprising of (A) 0...
March 31, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28358038/candidate-genes-for-inherited-autism-susceptibility-in-the-lebanese-population
#10
Silva Kourtian, Jihane Soueid, Nadine J Makhoul, Dikran Richard Guisso, Maria Chahrour, Rose-Mary N Boustany
Autism spectrum disorder (ASD) is characterized by ritualistic-repetitive behaviors and impaired verbal/non-verbal communication. Many ASD susceptibility genes implicated in neuronal pathways/brain development have been identified. The Lebanese population is ideal for uncovering recessive genes because of shared ancestry and a high rate of consanguineous marriages. Aims here are to analyze for published ASD genes and uncover novel inherited ASD susceptibility genes specific to the Lebanese. We recruited 36 ASD families (ASD: 37, unaffected parents: 36, unaffected siblings: 33) and 100 unaffected Lebanese controls...
March 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28348219/mouse-adapted-mers-coronavirus-causes-lethal-lung-disease-in-human-dpp4-knockin-mice
#11
Kun Li, Christine L Wohlford-Lenane, Rudragouda Channappanavar, Jung-Eun Park, James T Earnest, Thomas B Bair, Amber M Bates, Kim A Brogden, Heather A Flaherty, Tom Gallagher, David K Meyerholz, Stanley Perlman, Paul B McCray
The Middle East respiratory syndrome (MERS) emerged in Saudi Arabia in 2012, caused by a zoonotically transmitted coronavirus (CoV). Over 1,900 cases have been reported to date, with ∼36% fatality rate. Lack of autopsies from MERS cases has hindered understanding of MERS-CoV pathogenesis. A small animal model that develops progressive pulmonary manifestations when infected with MERS-CoV would advance the field. As mice are restricted to infection at the level of DPP4, the MERS-CoV receptor, we generated mice with humanized exons 10-12 of the mouse Dpp4 locus...
April 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28344320/dpp4-truncated-gm-csf-il-3-manifest-distinct-receptor-binding-regulatory-functions-compared-to-their-full-length-forms
#12
H A O'Leary, M Capitano, S Cooper, C Mantel, H S Boswell, R Kapur, B Ramdas, R Chan, L Deng, C-K Qu, H E Broxmeyer
Dipeptidylpeptidase 4 (DPP4/CD26) enzymatically cleaves select penultimate amino acids of proteins, including colony stimulating factors (CSFs), and has been implicated in cellular regulation. To better understand the role of DPP4 regulation of hematopoiesis, we analyzed the activity of DPP4 on the surface of immature blood cells and then comparatively assessed the interactions and functional effects of full-length (FL) and DPP4 truncated factors [(T)-GM-CSF and- IL-3] on both in vitro and in vivo models of normal and leukemic cells...
March 27, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28334048/hepatoprotective-effect-of-sitagliptin-against-methotrexate-induced-liver-toxicity
#13
Hany M Abo-Haded, Mohamed A Elkablawy, Zeyad Al-Johani, Osama Al-Ahmadi, Dina S El-Agamy
Sitagliptin is selective dipeptidyl peptidase-4 inhibitor (DPP4-I), used clinically as a new oral anti-diabetic agent. This study explored the underlying mechanisms of the hepatoprotective role of sitagliptin pretreatment against methotrexate (MTX) induced hepatotoxicity in mice. Forty mice were divided into four groups (10 mice each); control, MTX, and two sitagliptin groups (pretreated with sitagliptin 10 and 20 mg/kg/day, respectively) for five consecutive days prior to MTX injection. Results showed that MTX induced marked hepatic injury in the form of cloudy swelling, hydropic degeneration, apoptosis and focal necrosis in all hepatic zones...
2017: PloS One
https://www.readbyqxmd.com/read/28288852/altered-circulating-concentrations-of-active-glucagon-like-peptide-glp-1-and-dipeptidyl-peptidase-4-dpp4-in-obese-subjects-and-their-association-with-insulin-resistance
#14
Radwan H Ahmed, Hasniza Zaman Huri, Sekaran Muniandy, Zaid Al-Hamodi, Boshra Al-Absi, Abdulsamad Alsalahi, Muhammad Fm Razif
OBJECTIVES: Soluble DPP4 (sDPP4) is a novel adipokine that degrades glucagon-like peptide (GLP-1). We evaluated the fasting serum levels of active GLP-1 and sDPP4 in obese, overweight and normal weight subjects to assess the association between sDPP4 levels, active GLP-1 levels and insulin resistance in obese subjects. METHODS: The study involved 235 Malaysian subjects who were randomly selected (66 normal weight subjects, 97 overweight, 59 obese subjects, and 13 subjects who were underweight)...
March 11, 2017: Clinical Biochemistry
https://www.readbyqxmd.com/read/28285800/perspectives-on-cardiovascular-effects-of-incretin-based-drugs-from-bedside-to-bench-return-trip
#15
Michaela Luconi, Giulia Cantini, Antonio Ceriello, Edoardo Mannucci
Recently, cardiovascular outcome trials with glucose-lowering drugs used in type 2 diabetes mellitus, namely glucagon-like peptide-1 receptor agonists (GLP-1RA), liraglutide and semaglutide, showed a reduction in cardiovascular events, which had not been observed in trials with other incretin-based drugs, such as lixisenatide or with dipeptidyl peptidase-4 inhibitors (DPP4i). Mechanisms underlying the observed cardiovascular differences between DPP4i and GLP1-RA, and across individual GLP1-RA are poorly understood...
March 2, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28250448/valvular-disease-dpp4-inhibitors-to-prevent-aortic-valve-calcification
#16
Irene Fernández-Ruiz
No abstract text is available yet for this article.
April 2017: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/28242256/gastric-bypass-in-the-pig-increases-gip-levels-and-decreases-active-glp-1-levels
#17
Andreas Lindqvist, Mikael Ekelund, Stefan Pierzynowski, Leif Groop, Jan Hedenbro, Nils Wierup
Gastric bypass surgery results in remission of type 2 diabetes in the majority of patients. The incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) have been implicated in the observed remission. Most knowledge so far has been generated in obese subjects. To isolate the surgical effects of gastric bypass on metabolism and hormone responses from the confounding influence of obesity, T2D, or food intake, we performed gastric bypass in lean pigs, using sham-operated and pair-fed pigs as controls...
February 24, 2017: Peptides
https://www.readbyqxmd.com/read/28239939/combining-the-g-protein-coupled-receptor-40-agonist-fasiglifam-with-sitagliptin-improves-glycaemic-control-in-patients-with-type-2-diabetes-with-or-without-metformin-a-randomized-12-week-trial
#18
Xuejun V Peng, John F Marcinak, Marsha G Raanan, Charlie Cao
AIMS: To evaluate the efficacy and safety of fasiglifam, an orally active G-protein-coupled receptor 40 agonist, in combination with the dipeptidyl peptidase-4 inhibitor sitagliptin, in patients with type 2 diabetes inadequately controlled with diet/exercise (± metformin). MATERIALS AND METHODS: In this randomized, double-blind, phase II study, 368 patients received once-daily placebo, sitagliptin 100 mg, fasiglifam 25 or 50 mg, or the combination of sitagliptin 100 mg plus fasiglifam 25 or 50 mg...
February 27, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28238223/glucose-lowering-agents-for-treating-pre-existing-and-new-onset-diabetes-in-kidney-transplant-recipients
#19
REVIEW
Clement Lo, Min Jun, Sunil V Badve, Helen Pilmore, Sarah L White, Carmel Hawley, Alan Cass, Vlado Perkovic, Sophia Zoungas
BACKGROUND: Kidney transplantation is the preferred form of kidney replacement therapy for patients with end-stage kidney disease (ESKD) and is often complicated by worsening or new-onset diabetes. Management of hyperglycaemia is important to reduce post-transplant and diabetes-related complications. The safety and efficacy of glucose-lowering agents after kidney transplantation is largely unknown. OBJECTIVES: To evaluate the efficacy and safety of pharmacological interventions for lowering glucose levels in patients who have undergone kidney transplantation and have diabetes...
February 27, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28222401/combination-of-sitagliptin-and-silymarin-ameliorates-liver-fibrosis-induced-by-carbon-tetrachloride-in-rats
#20
Samia Salem Sokar, Magda El-Sayed El-Sayad, Mai El-Sayed Ghoneim, Abdelhadi Mohamed Shebl
Liver fibrosis is a common pathological condition that occurs in most conditions associated with chronic liver injury. Silymarin is a herbal product widely used for its hepatoprotective effect. Sitagliptin, a dipeptidyl peptidase-4 inhibitor (DPP4-I), is clinically used as an oral antidiabetic agent. This study was designed to investigate the effects of Sitagliptin, Silymarin, and their combination on established liver fibrosis in carbon tetrachloride (CCl4) rat model. Male albino rats received intraperitoneal injections of CCl4 three times a week for 7 weeks, as well as daily oral treatments of Sitagliptin (100mg/kg) or Silymarin (100mg/kg) or their combination during the 7 weeks of intoxication...
February 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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