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René Rodriguez-Gutierrez, Victor M Montori
No abstract text is available yet for this article.
March 20, 2018: Annals of Internal Medicine
Chi Zhang, Huaigao Liu, Shangwu Chen, Yongkang Luo
Dipeptidyl peptidase-IV (DPP-IV) is a serine exo-peptidase that can inactivate incretins by removing N-terminal dipeptides. Currently, inhibiting the DPP-IV activity is a common treatment for type 2 diabetes (T2D). The goal of this study is to investigate whether IADHFL, a novel DPP-IV inhibitory peptide identified from bighead carp (Hypophthalmichthys nobilis), has the potential to modulate T2D. IADHFL remained stable after simulated gastrointestinal digestion and significantly decreased the activity and expression of both soluble and membrane-bound DPP-IV after 24 h and 48 h of treatment...
March 19, 2018: Food & Function
Keiichi Torimoto, Yosuke Okada, Yoshiya Tanaka
Vascular endothelial function is important for maintaining the homeostasis of the living body. Especially, nitric oxide (NO) produced in vascular endothelial cells regulates blood vessel tone and has an antiatherosclerotic effect. Type 2 diabetes is a typical disease that causes impaired vascular endothelial function, resulting in various vascular complications and damage to organs. Cardiovascular disease associated with type 2 diabetes is a chronic inflammatory disease that starts with endothelial dysfunction (ED), and vascular ED is important as an initial change in arteriosclerotic lesions...
2018: Journal of UOEH
Gian Paolo Fadini, Mayur Sarangdhar, Angelo Avogaro
INTRODUCTION: In the SAVOR-TIMI trial, the risk of heart failure (HF) was increased by 27% in T2D patients randomized to the dipeptidyl peptidase-4 inhibitor (DPP4i) saxagliptin. Other studies have provided inconsistent results regarding this association. Herein, we performed a pharmacovigilance analysis of the rate of HF associated with DPP4is, focusing on stimulated reporting and moderation by drug-drug interactions. METHODS: We mined the FDA adverse event (AE) reporting system (FAERS) from 2004q1 to 2017q3, including a total of 9906,642 AE reports...
March 16, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Gustavo F Paz, Jeronimo M N Rugani, Andreza P Marcelino, Célia M F Gontijo
The aim of this study was to evaluate the relationship between naturally occurring Leishmania spp. infections in dogs (Canis familiaris) and the practical implications of the use of serological and molecular methods to confirm diagnoses. The study population consisted of 96 domestic dogs in southeastern Brazil. Serum samples were tested for the presence of anti-Leishmania immunoglobulin G (IgG) antibodies using four commercial canine visceral leishmaniasis kits. Dogs confirmed positive by immunofluorescence antibody test (IFAT) were culled and samples from mesenteric lymph nodes, spleen border, bone marrow and ear skin were taken and submitted to DNA extraction...
March 12, 2018: Acta Tropica
Kazuaki Negishi
We are now entering the very exciting era of treatment and management of diabetes mellitus (DM) with the emergence of new therapeutic agents, including sodium-glucose cotransporter 2 inhibitors (SGLT2i) and dipeptidyl peptidase-4 inhibitor (DPP-4i). From a cardiology and echocardiography perspective, the existence of diabetic cardiomyopathy has been proven through over four decades of discussion. DM is highly prevalent in patients with heart failure (HF). Independent associations are found after adjusting for hypertension (HTN) and coronary artery disease (CAD)...
February 2018: Cardiovascular Diagnosis and Therapy
Julio Rosenstock, Vlado Perkovic, John H Alexander, Mark E Cooper, Nikolaus Marx, Michael J Pencina, Robert D Toto, Christoph Wanner, Bernard Zinman, David Baanstra, Egon Pfarr, Michaela Mattheus, Uli C Broedl, Hans-Juergen Woerle, Jyothis T George, Maximilian von Eynatten, Darren K McGuire
BACKGROUND: Cardiovascular (CV) outcome trials in type 2 diabetes (T2D) have underrepresented patients with chronic kidney disease (CKD), leading to uncertainty regarding their kidney efficacy and safety. The CARMELINA® trial aims to evaluate the effects of linagliptin, a DPP-4 inhibitor, on both CV and kidney outcomes in a study population enriched for cardio-renal risk. METHODS: CARMELINA® is a randomized, double-blind, placebo-controlled clinical trial conducted in 27 countries in T2D patients at high risk of CV and/or kidney events...
March 14, 2018: Cardiovascular Diabetology
Tiffany L Gary-Webb, Elizabeth A Walker, Lindsey Realmuto, Alexandra Kamler, Jennifer Lukin, William Tyson, Olveen Carrasquillo, Linda Weiss
The Diabetes Prevention Program (DPP) landmark randomized trial demonstrated that participants with prediabetes could reduce their risk for type 2 diabetes by 58% if they achieved 5%-7% weight loss through healthy eating and increasing physical activity. The National DPP (NDPP) is a group intervention based on the DPP and has been widely disseminated by the Centers for Disease Control and Prevention (CDC) and many healthcare institutions. While data show that the program is effective in diverse populations, enrollment among men from low-income and minority communities is low...
March 1, 2018: American Journal of Men's Health
Juan Jose Fraire-Zamora, Johannes Jaeger, Jérôme Solon
Evolution of morphogenesis is generally associated with changes in genetic regulation. Here, we report evidence indicating that dorsal closure, a conserved morphogenetic process in dipterans, evolved as the consequence of rearrangements in epithelial organization rather than signaling regulation. In Drosophila melanogaster , dorsal closure consists of a two-tissue system where the contraction of extraembryonic amnioserosa and a JNK/Dpp-dependent epidermal actomyosin cable result in microtubule-dependent seaming of the epidermis...
March 14, 2018: ELife
Olga Montvida, Jonathan Shaw, Lawrence Blonde, Sanjoy K Paul
AIMS: To inform patients and their carers about the probability of reducing HbA1c to clinically desirable levels and sustainability of such control over 2 years with major second-line anti-diabetic therapies under individual risk scenario, with and without third-line intensification. MATERIALS AND METHODS: From US Centricity Electronic Medical Records, 163,081 patients with type 2 diabetes aged 18-80 years, who initiated metformin; intensified with DPP-4 inhibitor (DPP-4i), GLP-1 receptor agonist (GLP-1RA), sulfonylurea, insulin, or thiazolidinedione; and continued second-line ≥ 6 month, were selected...
March 14, 2018: Diabetes, Obesity & Metabolism
Rajesh B Patil, Euzebio G Barbosa, Jaiprakash N Sangshetti, Vishal P Zambre, Sanjay D Sawant
Dipeptidyl peptidase-IV (DPP-IV) inhibitors are promising antidiabetic agents. Currently, several DPP-IV inhibitors have been approved for therapeutic use in diabetes mellitus. Receptor-dependent 4D-QSAR is comparatively a new approach which uses molecular dynamics simulations to generate conformational ensemble profiles of compounds representing a dynamic state of compounds at a target's binding site. This work describes a receptor-dependent 4D-QSAR study on triazolopiperazine derivatives. QSARINS multiple linear regression method was adopted to generate 4D-QSAR models...
March 13, 2018: Molecular Diversity
Emeline Riboldi, Flavio Carvalho, Pedro Roosevelt Torres Romão, Regina Bones Barcellos, Graziele Lima Bello, Raquel Rocha Ramos, Rosemari Terezinha de Oliveira, João Pessoa Araújo Júnior, Maria Lucia Rossetti, Eliane Dallegrave
In Brazil, visceral leishmaniasis (VL) is expanding and becoming urbanized, especially in non-endemic areas such as the State of Rio Grande do Sul. Considering that infected dogs are the main reservoir for zoonotic VL, this study evaluated the prevalence of canine visceral leishmaniasis (CVL) in the metropolitan area of Porto Alegre, a new area of expansion of VL in Brazil. Serum and plasma from 405 asymptomatic dogs from the municipalities of Canoas (n=107), São Leopoldo (n=216), and Novo Hamburgo (n=82) were tested for CVL using immunochromatographic (DPP® ) and ELISA EIE® assays (2 assays officially adopted by the Brazilian government for the diagnosis of CVL) and real-time PCR to confirm the results...
February 2018: Korean Journal of Parasitology
Milton Packer
Although dipeptidyl peptidase (DPP)-4 inhibitors have been reported to have a neutral effect on thromboembolic vaso-occlusive events in large-scale trials, they act to potentiate several endogenous peptides that can exert deleterious cardiovascular effects. Experimentally, DPP-4 inhibitors may augment the ability of glucagon-like peptide-1 to stimulate cyclic adenosine monophosphate in cardiomyocytes, and potentiation of the effects of stromal cell-derived factor-1 by DPP-4 inhibitors may aggravate cardiac fibrosis...
March 1, 2018: JACC. Heart Failure
Miriam Moreno-Montoro, Paula Jauregi, Miguel Navarro-Alarcón, Manuel Olalla-Herrera, Rafael Giménez-Martínez, Lourdes Amigo, Beatriz Miralles
In this study, ultrafiltered goat milks fermented with the classical starter bacteria Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus salivarus subsp. thermophilus or with the classical starter plus the Lactobacillus plantarum C4 probiotic strain were analyzed using ultra-high performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) and/or high performance liquid chromatography-ion trap (HPLC-IT-MS/MS). Partial overlapping of the identified sequences with regard to fermentation culture was observed...
March 10, 2018: Analytical and Bioanalytical Chemistry
Bárbara Socas-Rodríguez, Javier González-Sálamo, Antonio V Herrera-Herrera, Álvaro Santana-Mayor, Javier Hernández-Borges
In this work, a new method has been developed for the determination of 14 phthalic acid esters (i.e., benzylbutyl phthalate (BBP), bis-2-n-butoxyethyl phthalate (DBEP), dibutyl phthalate (DBP), dicyclohexyl phthalate (DCHP), bis-2-ethoxyethyl phthalate (DEEP), diethyl phthalate (DEP), diisodecyl phthalate (DIDP), diisononyl phthalate (DINP), bis-isopentyl phthalate (DIPP), bis (2-methoxyethyl) phthalate (DMEP), dimethyl phthalate (DMP), di-n-octyl phthalate (DNOP), bis-n-pentyl phthalate (DNPP), dipropyl phthalate (DPP)) and one adipate (bis (2-ethylhexyl) adipate (DEHA)) in different baby foods...
March 9, 2018: Analytical and Bioanalytical Chemistry
Hale M Tasyurek, Yunus E Eksi, Ahter D Sanlioglu, Hasan A Altunbas, Mustafa K Balci, Thomas S Griffith, Salih Sanlioglu
Type 2 diabetes mellitus (T2DM) is characterised by insulin resistance, glucose intolerance and beta cell loss leading to hyperglycemia. Vasoactive intestinal peptide (VIP) has been regarded as a novel therapeutic agent for the treatment of T2DM because of its insulinotropic and anti-inflammatory properties. Despite these beneficial properties, VIP is extremely sensitive to peptidases (DPP-4) requiring constant infusion or multiple injections to observe any therapeutic benefit. Thus, we constructed an HIV-based lentiviral vector encoding human VIP (LentiVIP) to test the therapeutic efficacy of VIP peptide in a diet-induced obesity (DIO) animal model of T2DM...
March 9, 2018: Gene Therapy
Jung Gi Lee, Jae Ha Ryu, Seon-Myung Kim, Moon-Young Park, San-Ho Kim, Young G Shin, Jong-Woo Sohn, Ha Hyung Kim, Zee-Yong Park, Jae Young Seong, Jae Il Kim
Exendin-4, a 39 amino acid peptide isolated from the saliva of the Gila monster, plays an important role in regulating glucose homeostasis, and is used clinically for the treatment of type 2 diabetes. Exendin-4 shares 53% sequence identity with the incretin hormone glucagon-like peptide 1 (GLP-1) but, unlike GLP-1, is highly resistant to proteolytic enzymes such as dipeptidyl peptidase IV (DPP-IV) and neutral endopeptidase 24.11 (NEP 24.11). Herein, we focused on the structure and function of the C-terminal Trp-cage of exendin-4, and suggest that it may be structurally required for resistance to proteolysis by NEP 24...
March 6, 2018: Biochemical Pharmacology
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
Jitjiroj Ittichaicharoen, Arintaya Phrommintikul, Nipon Chattipakorn, Siriporn Chattipakorn
OBJECTIVES: The present study is to investigate the salivary gland function of metabolic syndrome (MetS) patients, as indicated by salivary flow rate, amylase activity, and salivary oxidative stress, by measuring MDA level. MATERIALS AND METHODS: One hundred and eighty-one MetS patients from Maharaj Nakorn Chiang Mai Hospital were enrolled onto this study. The metabolic parameters of each patient were collected and evaluated. Unstimulated saliva was also collected for 5 min...
March 8, 2018: Clinical Oral Investigations
A H Heald, A A Fryer, S G Anderson, M Livingston, M Lunt, M Davies, Gyc Moreno, R Gadsby, R J Young, M Stedman
AIMS: Despite increasing spend on new Type 2 diabetes mellitus (T2DM) therapies, the proportion of people with T2DM achieving target glycaemia outcomes is declining. Our aim was to determine, using published General Practice level data, how differences in T2DM prescribing patterns relate to glycaemic target achievement levels. METHODS: Multiple linear regression modelling was used to link practice characteristics and defined daily dose (DDD) of class of medication in 2015/16 and changes to 2014/15 in medication to proportions achieving target glycaemic control (TGC; glycated haemoglobin A1c (HbA1c) ≤7...
March 8, 2018: Diabetes, Obesity & Metabolism
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