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https://www.readbyqxmd.com/read/28230778/caffeic-acid-expands-anti-tumor-effect-of-metformin-in-human-metastatic-cervical-carcinoma-htb-34-cells-implications-of-ampk-activation-and-impairment-of-fatty-acids-de-novo-biosynthesis
#1
Malgorzata Tyszka-Czochara, Pawel Konieczny, Marcin Majka
The efficacy of cancer treatments is often limited and associated with substantial toxicity. Appropriate combination of drug targeting specific mechanisms may regulate metabolism of tumor cells to reduce cancer cell growth and to improve survival. Therefore, we investigated the effects of anti-diabetic drug Metformin (Met) and a natural compound caffeic acid (trans-3,4-dihydroxycinnamic acid, CA) alone and in combination to treat an aggressive metastatic human cervical HTB-34 (ATCC CRL-1550) cancer cell line...
February 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28230579/hospital-outpatient-visits-associated-with-medication-related-problems-in-thailand-a-multicenter-prospective-observational-study
#2
Supinya Dechanont, Arom Jedsadayanmata, Bodin Butthum, Chuenjid Kongkaew
OBJECTIVES: The aims of the study were to investigate the prevalence of hospital visits associated with medication-related problems (MRPs, i.e., adverse drug events [ADEs], adverse drug reactions [ADRs], nonadherence [NA] to medication, and medication error) and to identify the medications involved in hospital visits associated with MRPs in outpatient departments (OPDs). METHODS: A prospective observational study was carried out in OPD of 11 hospitals in the lower northern region of Thailand...
February 22, 2017: Journal of Patient Safety
https://www.readbyqxmd.com/read/28230206/mirna-21-mediates-the-antiangiogenic-activity-of-metformin-through-targeting-pten-and-smad7-expression-and-pi3k-akt-pathway
#3
Mao Luo, Xiaoyong Tan, Lin Mu, Yulin Luo, Rong Li, Xin Deng, Ni Chen, Meiping Ren, Yongjie Li, Liqun Wang, Jianbo Wu, Qin Wan
Metformin, an anti-diabetic drug commonly used for type 2 diabetes therapy, is associated with anti-angiogenic effects in conditions beyond diabetes. miR-21 has been reported to be involved in the process of angiogenesis. However, the precise regulatory mechanisms by which the metformin-induced endothelial suppression and its effects on miR-21-dependent pathways are still unclear. Bioinformatic analysis and identification of miR-21 and its targets and their effects on metformin-induced antiangiogenic activity were assessed using luciferase assays, quantitative real-time PCR, western blots, scratch assays, CCK-8 assays and tubule formation assays...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28228317/short-term-therapy-with-combination-dipeptidyl-peptidase-4-inhibitor-saxagliptin-metformin-extended-release-xr-is-superior-to-saxagliptin-or-metformin-xr-monotherapy-in-prediabetic-women-with-polycystic-ovary-syndrome-a-single-blind-randomized-pilot-study
#4
Karen E Elkind-Hirsch, Martha S Paterson, Ericka L Seidemann, Hanh C Gutowski
OBJECTIVE: To evaluate efficacy with the dipeptidyl peptidase-4 inhibitor saxagliptin (SAXA), metformin extended release (MET), and combination (SAXA-MET) in patients with polycystic ovary syndrome (PCOS) and impaired glucose regulation. DESIGN: Prospective, randomized, single-blind drug study. SETTING: Outpatient clinic. PATIENT(S): Patients (n = 38) with PCOS (aged 18-42 years) and prediabetic hyperglycemia determined by a 75-gram oral glucose tolerance test...
January 2017: Fertility and Sterility
https://www.readbyqxmd.com/read/28223391/evaluation-of-para-aminosalicylic-acid-pas-as-a-substrate-of-multiple-solute-carrier-slc-uptake-transporters-and-possible-drug-interactions-with-nsaids-in-vitro
#5
Md Masud Parvez, Ho Jung Shin, Jin Ah Jung, Jae-Gook Shin
para-Aminosalicylic acid (PAS) is a second-line anti-tuberculosis drug used to treat multidrug-resistant and extensively drug-resistant tuberculosis for more than 60 years. Renal secretion and glomerular filtration are the major pathways for elimination of PAS. We comprehensively studied PAS transport by using cell lines that overexpressed various transporters, and found that PAS acts as a novel substrate of organic anionic polypeptide (OATP1B1), organic cationic transporters (OCT1 and OCT2), and organic anion transporters (OAT1 and OAT3) but not a substrate of any ATP-binding cassette (ABC) transporters...
February 21, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28223003/treatment-of-metformin-intoxication-complicated-by-lactic-acidosis-and-acute-kidney-injury-the-role-of-prolonged-intermittent-hemodialysis
#6
Giuseppe Regolisti, Riccardo Antoniotti, Filippo Fani, Paolo Greco, Enrico Fiaccadori
Metformin intoxication with lactic acidosis, a potentially lethal condition, may develop in diabetic patients when the drug dose is inappropriate and/or its clearance is reduced. Diagnosis and therapy may be delayed due to nonspecific symptoms at presentation, with severe anion gap metabolic acidosis and elevated serum creatinine values being the most prominent laboratory findings. Confirmation requires measurement of serum metformin by high-performance liquid chromatography-tandem mass spectrometry, but this technique is available only at specialized institutions and cannot be relied on as a guide to immediate treatment...
February 17, 2017: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/28222147/the-desert-gerbil-psammomys-obesus-as-a-model-for-metformin-sensitive-nutritional-type-2-diabetes-to-protect-hepatocellular-metabolic-damage-impact-of-mitochondrial-redox-state
#7
Inès Gouaref, Dominique Detaille, Nicolas Wiernsperger, Naim Akhtar Khan, Xavier Leverve, Elhadj-Ahmed Koceir
INTRODUCTION: While metformin (MET) is the most widely prescribed antidiabetic drug worldwide, its beneficial effects in Psammomys obesus (P. obesus), a rodent model that mimics most of the metabolic features of human diabetes, have not been explored thoroughly. Here, we sought to investigate whether MET might improve insulin sensitivity, glucose homeostasis, lipid profile as well as cellular redox and energy balance in P. obesus maintained on a high energy diet (HED). MATERIALS AND METHODS: P...
2017: PloS One
https://www.readbyqxmd.com/read/28217526/the-rule-of-two-thirds-in-diabetes-epidemiology
#8
Sanjay Kalra, Banshi Saboo, Rakesh Sahay, Deepak Khandelwal, Vipin Talwar, A G Unnikrishnan
This communication hypothesises a rule of two thirds which seems to operate in Indian diabetes epidemiology. Two thirds of all persons with dysglycemia are prediabetic; two thirds of all persons with diabetes are diagnosed to have the condtion; and two thirds are diagnosed before the age of 50 years. Two thirds of people with diabetes have concomitant hypetension or dyslipidemia; two thirds do not get their HbA1c assessed; and two thirds of those who do, do not achiev target values. Yet, two thirds of people with diabetes report satisfactory psychosocial health and quality of life, and adherence to dietary therapy and medication...
January 2017: Indian Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28212524/role-of-nrf2-and-protective-effects-of-metformin-against-tobacco-smoke-induced-cerebrovascular-toxicity
#9
Shikha Prasad, Ravi K Sajja, Mohammad Abul Kaisar, Jee Hyun Park, Heidi Villalba, Taylor Liles, Thomas Abbruscato, Luca Cucullo
Cigarette smoking (CS) is associated with vascular endothelial dysfunction in a causative way primarily related to the TS content of reactive oxygen species (ROS), nicotine, and inflammation. TS promotes glucose intolerance and increases the risk of developing type-2 diabetes mellitus (2DM) with which it shares other pathogenic traits including the high risk of cerebrovascular and neurological disorders like stroke via ROS generation, inflammation, and blood-brain barrier (BBB) impairment. Herein we provide evidence of the role played by nuclear factor erythroid 2-related factor (Nrf2) in CS-induced cerebrobvascular/BBB impairments and how these cerebrovascular harmful effects can be circumvented by the use of metformin (MF; a widely prescribed, firstline anti-diabetic drug) treatment...
February 12, 2017: Redox Biology
https://www.readbyqxmd.com/read/28211632/amp-activated-protein-kinase-activator-a-769662-increases-intracellular-calcium-and-atp-release-from-astrocytes-in-an-ampk-independent-manner
#10
Julia M Vlachaki Walker, Josephine L Robb, Ana M Cruz, Amrinder Malhi, Paul G Weightman Potter, Michael L J Ashford, Rory J McCrimmon, Kate L J Ellacott, Craig Beall
AIM: Astrocytes are the main sources of extracellular ATP (eATP) within the brain, which functions as a gliotransmitter, capable of modulating neuronal and astrocytic activity. These cells play an important role in regulating energy homeostasis partly via astrocyte-derived ATP. Given the role of AMPK in regulating intracellular ATP levels, we hypothesised that AMPK may alter ATP release from astrocytes. METHODS: Measurements of ATP release were made from human U373 astrocytoma cells, primary mouse hypothalamic (HTAS) and cortical astrocytes (CRTAS) and wild type and AMPK α1/α2 null mouse embryonic fibroblasts (MEFs)...
February 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28211604/delays-in-treatment-intensification-with-oral-antidiabetic-drugs-and-risk-of-microvascular-and-macrovascular-events-in-patients-with-poor-glycemic-control-an-individual-patient-simulation-study
#11
Henry J Folse, Jayanti Mukherjee, John J Sheehan, Alexandra J Ward, Ryan L Pelkey, Tuan A Dinh, Lei Qin, Jennifer Kim
AIMS: Despite guideline recommendations, many patients with type 2 diabetes on oral antidiabetic drugs (OADs) whose HbA1c results remain above target do not experience timely treatment intensification. This study uses the Archimedes Model® to estimate the consequences of delays in OAD treatment intensification on glycemic control and long-term outcomes at 5 and 20 years. MATERIALS AND METHODS: Using real world data, we modeled a cohort of hypothetical patients with HbA1c ≥8%, on metformin, with no history of insulin use...
February 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28208942/comparing-the-effects-of-agnugol-and-metformin-on-oligomenorrhea-in-patients-with-polycystic-ovary-syndrome-a-randomized-clinical-trial
#12
Arezoo Shayan, Seyedeh Zahra Masoumi, Fatemeh Shobeiri, Shahin Tohidi, Arash Khalili
INTRODUCTION: Polycystic Ovarian Syndrome (PCOS) is the most common endocrinopathy and cause of oligomenorrhea in women. AIM: The present study was conducted with the aim to compare the effect of Agnugol and Metformin drugs on oligomenorrhea in patients with PCOS. MATERIALS AND METHODS: This study was a clinical trial on 120 women with PCOS and had oligomenorrhea, referring to a gynaecology clinic Fatemieh, Hamadan city, Iran, 2015. Women were randomly divided into 2 groups using permutation blocks (getting the medications Agnugol and Metformin) and were treated with drugs Agnugol and Metformin for 3 months...
December 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28208838/the-effect-of-metformin-and-gant61-combinations-on-the-radiosensitivity-of-prostate-cancer-cells
#13
Annelies Gonnissen, Sofie Isebaert, Chad M McKee, Ruth J Muschel, Karin Haustermans
The anti-diabetes drug metformin has been shown to have anti-neoplastic effects in several tumor models through its effects on energy metabolism and protein synthesis. Recent studies show that metformin also targets Hedgehog (Hh) signaling, a developmental pathway re-activated in several tumor types, including prostate cancer (PCa). Furthermore, we and others have shown that Hh signaling is an important target for radiosensitization. Here, we evaluated the combination of metformin and the Hh inhibitor GANT61 (GLI-ANTagonist 61) with or without ionizing radiation in three PCa cell lines (PC3, DU145, 22Rv1)...
February 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28208582/nutrients-in-energy-and-one-carbon-metabolism-learning-from-metformin-users
#14
REVIEW
Fedra Luciano-Mateo, Anna Hernández-Aguilera, Noemi Cabre, Jordi Camps, Salvador Fernández-Arroyo, Jose Lopez-Miranda, Javier A Menendez, Jorge Joven
Metabolic vulnerability is associated with age-related diseases and concomitant co-morbidities, which include obesity, diabetes, atherosclerosis and cancer. Most of the health problems we face today come from excessive intake of nutrients and drugs mimicking dietary effects and dietary restriction are the most successful manipulations targeting age-related pathways. Phenotypic heterogeneity and individual response to metabolic stressors are closely related food intake. Understanding the complexity of the relationship between dietary provision and metabolic consequences in the long term might provide clinical strategies to improve healthspan...
February 10, 2017: Nutrients
https://www.readbyqxmd.com/read/28207836/tmg-123-a-novel-glucokinase-activator-exerts-durable-effects-on-hyperglycemia-without-increasing-triglyceride-in-diabetic-animal-models
#15
Yoshinori Tsumura, Yu Tsushima, Azusa Tamura, Makiko Hasebe, Masanobu Kanou, Hirotsugu Kato, Tsunefumi Kobayashi
Glucokinase (GK) plays a critical role for maintaining glucose homeostasis with regulating glucose uptake in liver and insulin secretion in pancreas. GK activators have been reported to decrease blood glucose levels in patients with type 2 diabetes mellitus. However, clinical development of GK activators has failed due to the loss of glucose-lowering effects and increased plasma triglyceride levels after chronic treatment. Here, we generated a novel GK activator, TMG-123, examined its in vitro and in vivo pharmacological characteristics, and evaluated its risks of aforementioned clinical issues...
2017: PloS One
https://www.readbyqxmd.com/read/28206714/opposite-effects-of-a-glucokinase-activator-and-metformin-on-glucose-regulated-gene-expression-in-hepatocytes
#16
Ziad H Al-Oanzi, Sophia Fountana, Tabassum Moonira, Susan J Tudhope, John L Petrie, Ahmed Alshawi, Gillian Patman, Catherine Arden, Helen L Reeves, Loranne Agius
AIM: Small molecule activators of glucokinase (GKAs) have been extensively explored as potential anti-hyperglycaemic drugs for type 2 diabetes (T2D). Several GKAs were remarkably effective at lowering blood glucose during early therapy but then lost their glycaemic efficacy chronically during clinical trials. We used rat hepatocytes to test the hypothesis that GKAs raise hepatocyte glucose 6-phosphate, (G6P, the glucokinase product) and down-stream metabolites with consequent repression of the liver glucokinase gene (Gck)...
February 16, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28202017/association-between-metformin-use-and-below-the-knee-arterial-calcification-score-in-type-2-diabetic-patients
#17
Aurélien Mary, Agnes Hartemann, Sophie Liabeuf, Carole Elodie Aubert, Salim Kemel, Joe Elie Salem, Philippe Cluzel, Aurélie Lenglet, Ziad A Massy, Jean-Daniel Lalau, Romuald Mentaverri, Olivier Bourron, Saïd Kamel
BACKGROUND: Vascular calcification (VC) is common in type 2 diabetes, and is associated with cardiovascular complications. Recent preclinical data suggest that metformin inhibits VC both in vitro and in animal models. However, metformin's effects in patients with diabetic VC have not previously been characterized. The present study investigated the association between metformin use and lower-limb arterial calcification in patients with type 2 diabetes and high cardiovascular risk. METHODS: The DIACART cross-sectional cohort study included 198 patients with type 2 diabetes but without severe chronic kidney disease...
February 15, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28193239/buformin-inhibits-the-stemness-of-erbb-2-overexpressing-breast-cancer-cells-and-premalignant-mammary-tissues-of-mmtv-erbb-2-transgenic-mice
#18
Amanda B Parris, Qingxia Zhao, Erin W Howard, Ming Zhao, Zhikun Ma, Xiaohe Yang
BACKGROUND: Metformin, an FDA-approved drug for the treatment of Type II diabetes, has emerged as a promising anti-cancer agent. Other biguanide analogs, including buformin and phenformin, are suggested to have similar properties. Although buformin was shown to reduce mammary tumor burden in carcinogen models, the anti-cancer effects of buformin on different breast cancer subtypes and the underlying mechanisms remain unclear. Therefore, we aimed to investigate the effects of buformin on erbB-2-overexpressing breast cancer with in vitro and in vivo models...
February 13, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28192606/metformin-alleviates-aging-cellular-phenotypes-in-hutchinson-gilford-progeria-syndrome-dermal-fibroblasts
#19
Seul-Ki Park, Ok Sarah Shin
Metformin is a popular antidiabetic biguanide, which has been considered as a candidate drug for cancer treatment and aging prevention. Hutchinson-Gilford progeria syndrome (HGPS) is a devastating disease characterized by premature aging and severe age-associated complications leading to death. The effects of metformin on HGPS dermal fibroblasts remain largely undefined. In this study, we investigated whether metformin could exert a beneficial effect on nuclear abnormalities and delay senescence in fibroblasts derived from HGPS patients...
February 13, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28190613/therapeutics-for-equine-endocrine-disorders
#20
REVIEW
Andy E Durham
Equine endocrine disease is commonly encountered by equine practitioners. Pituitary pars intermedia dysfunction (PPID) and equine metabolic syndrome (EMS) predominate. The most logical therapeutic approach in PPID uses dopamine agonists; pergolide mesylate is the most common. Bromocryptine and cabergoline are alternative drugs with similar actions. Drugs from other classes have a poor evidence basis, although cyproheptadine and trilostane might be considered. EMS requires management changes as the primary approach; reasonable justification for use of drugs such as levothyroxine and metformin may apply...
February 9, 2017: Veterinary Clinics of North America. Equine Practice
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