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https://www.readbyqxmd.com/read/28729113/activation-of-rage-stat3-pathway-by-methylglyoxal-contributes-to-spinal-central-sensitization-and-persistent-pain-induced-by-bortezomib
#1
Jia-You Wei, Cui-Cui Liu, Han-Dong Ouyang, Chao Ma, Man-Xiu Xie, Meng Liu, Wan-Long Lei, Huan-Huan Ding, Shao-Ling Wu, Wen-Jun Xin
Bortezomib is a first-line chemotherapeutic drug widely used for multiple myeloma and other nonsolid malignancies. Although bortezomib-induced persistent pain is easily diagnosed in clinic, the pathogenic mechanism remains unclear. Here, we studied this issue with use of a rat model of systemic intraperitoneal administration of bortezomib for consecutive 5days. Consisted with our previous study, we found that bortezomib treatment markedly induced mechanical allodynia in rats. Furthermore, we first found that bortezomib treatment significantly induced the upregulation of methylglyoxal in spinal dorsal horn of rats...
July 17, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28728159/oxamate-enhances-the-anti-inflammatory-and-insulin-sensitizing-effects-of-metformin-in-diabetic-mice
#2
Mu-Chao Wu, Wei-Ran Ye, Yi-Jia Zheng, Shan-Shan Zhang
Metformin (MET) is the first-line drug for treating type 2 diabetes mellitus (T2DM). However, MET increases blood lactate levels in patients with T2DM. Lactate possesses proinflammatory properties and causes insulin resistance (IR). Oxamate (OXA), a lactate dehydrogenase inhibitor, can decrease tissue lactate production and blood lactate levels. This study was conducted to examine the effects of the combination of OXA and MET on inflammation, and IR in diabetic db/db mice. Supplementation of OXA to MET led to lowered tissue lactate production and serum lactate levels compared to MET alone, accompanied with further decreased tissue and blood levels of pro-inflammatory cytokines, along with better insulin sensitivity, beta-cell mass, and glycemic control in diabetic db/db mice...
July 21, 2017: Pharmacology
https://www.readbyqxmd.com/read/28725599/effects-of-metformin-on-endothelial-health-and-erectile-dysfunction
#3
REVIEW
Jay Pravin Patel, Eric Hweegeun Lee, Carlos Ignacio Mena, Charles N Walker
Erectile dysfunction (ED) affects approximately 18 million American men. ED may be attributed to several etiologies, including arteriogenic, psychogenic, neurogenic, hormonal, drug-induced, and systemic disease or aging related factors. Specific to arteriogenic ED, three major mechanisms have been identified: (I) endothelium-dependent vasodilatory impairment; (II) sympathetic nerve activity elevation; (III) atherosclerotic luminal narrowing. Additionally, these insults have been linked to the insulin resistant state, which in turn is comorbid with obesity, dyslipidemia, diabetes, and hypertension...
June 2017: Translational Andrology and Urology
https://www.readbyqxmd.com/read/28725321/effect-of-switching-from-an-anti-diabetic-loose-dose-combination-to-a-fixed-dose-combination-regimen-at-equivalent-dosage-for-6-months-on-glycemic-control-in-japanese-patients-with-type-2-diabetes-a-pilot-study
#4
Kazutaka Aoki, Mieko Nagakura, Masataka Taguri, Hiroshi Kamiyama, Makoto Masumura, Tadashi Furuie, Masanao Oka, Kazunari Kamiko, Shigeru Nakajima, Noriko Akema, Yasuo Terauchi
BACKGROUND: Patients with type 2 diabetes mellitus often take multiple anti-diabetic drugs for a long period. Fixed dose combination (FDC) therapy is expected to improve drug adherence for patients with diabetes. The effect of switching from a loose dose combination (LDC) regimen to an FDC regimen at equivalent dosage on glycemic control has not been evaluated fully. Therefore, we investigated the effect of switching from LDC to FDC at equivalent dosage for 6 months on glycemic control in Japanese patients with type 2 diabetes...
August 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28725138/comparative-assessment-of-saliva-and-plasma-for-drug-bioavailability-and-bioequivalence-studies-in-humans
#5
Nasir M Idkaidek
Aims: To study the pharmacokinetics of selected drugs in plasma and saliva matrixes in healthy human volunteers, and to suggest using non-invasive saliva sampling instead of plasma as a surrogate in bioavailability and bioequivalence (BA/BE) studies. Methods: Four different pilot BA/BE studies were done in 12-18 healthy humans. Saliva and plasma samples were collected for 3-5 half life values of metformin, tolterodine, rosuvastatin, and paracetamol after oral dosing. Saliva and plasma samples were assayed using LC-MSMS, and then pharmacokinetic parameters were calculated by non-compartmental analysis using Kinetica program...
July 2017: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
https://www.readbyqxmd.com/read/28723808/continuous-use-of-metformin-can-improve-survival-in-type-2-diabetic-patients-with-ovarian-cancer-a-retrospective-study
#6
Shan-Bing Wang, Kai-Jian Lei, Jia-Pei Liu, Yu-Ming Jia
Evidence indicates that type 2 diabetes may stimulate the initiation and progression of several types of cancer. Metformin, a drug most commonly used to treat type 2 diabetes, may inhibit cancer cell growth and reduce the risk of cancer. However, evidence of the antitumor effects of metformin on ovarian cancer is still limited.In this study, we retrospectively examined the effects of metformin on ovarian cancer patients with diabetes at our institution.We identified 568 consecutive patients who were newly diagnosed with ovarian cancer and treated between January 2011 and March 2014...
July 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28723636/redox-dependent-modulation-of-metformin-contributes-to-enhanced-sensitivity-of-esophageal-squamous-cell-carcinoma-to-cisplatin
#7
Pin Dong Li, Zhao Liu, Tian Tian Cheng, Wen Guang Luo, Jing Yao, Jing Chen, Zhen Wei Zou, Li Li Chen, Charlie Ma, Xiao Fang Dai
Glutathione is the major intracellular anti-oxidant against reactive oxygen species and serves as a detoxification essential. The anti-diabetic drug metformin has been showed to exert anti-tumor activity via modulation of redox homeostasis. In this study, we provided evidence that metformin inhibits proliferation and induces apoptosis of esophageal squamous cancer cells. Importantly, we found that metformin acts as pro-oxidant via depletion of intracellular glutathione. Co-treatment with metformin reversed the elevated intracellular glutathione induced by cisplatin and therefore enhanced the sensitivity to cisplatin in vitro and in vivo...
July 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28722177/metformin-induced-alterations-in-nucleotide-metabolism-cause-5-fluorouracil-resistance-but-gemcitabine-susceptibility-in-oesophageal-squamous-cell-carcinoma
#8
Charissa Mynhardt, Leonard Howard Damelin, Rupal Jivan, Jade Peres, Sharon Prince, Robin Bruce Veale, Demetra Mavri-Damelin
5-Fluorouracil (5-FU) is a chemotherapeutic agent used to treat a variety of gastric cancers including oesophageal squamous cell carcinoma (OSCC), for which the 5-year mortality rate exceeds 85%. Our study investigated the effects of metformin, an antidiabetic drug with established anti-cancer activity, in combination with 5-FU as a novel chemotherapy strategy, using the OSCC cell lines, WHCO1 and WHCO5. Our results indicate that metformin treatment induces significant resistance to 5-FU in WHCO1 and WHCO5 cells, by more than 5-fold and 6-fold respectively, as assessed by MTT assay...
July 19, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28721138/the-effect-of-orlistat-versus-metformin-on-body-composition-and-insulin-resistance-in-obese-premenopausal-women-3-month-randomized-prospective-open-label-study
#9
Magdalena Kujawska-Łuczak, Katarzyna Musialik, Monika Szulińska, Ewelina Swora-Cwynar, Angelina Kargulewicz, Małgorzata Grzymisławska, Danuta Pupek-Musialik, Paweł Bogdański
INTRODUCTION: Our aim was to evaluate the effects of metformin and orlistat on body composition and glucose-insulin homeostasis in obese premenopausal women. MATERIAL AND METHODS: Seventy-three obese premenopausal Caucasian women aged 32.4 ±8.3 years were treated with either metformin (1000 mg/day; n = 37) or orlistat (360 mg/day; n = 36). Anthropometric parameters were measured using dual-energy X-ray absorptiometry. Glucose tolerance, using the oral glucose tolerance test; insulin resistance, using the homeostasis model assessment (HOMA-IR); and insulin sensitivity, using the Matsuda insulin sensitivity index (ISI Matsuda), were assessed at the commencement of the study and after 3 months...
June 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/28719837/prescription-trends-and-the-selection-of-initial-oral-antidiabetic-agents-for-patients-with-newly-diagnosed-type-2-diabetes-a-nationwide-study
#10
C-H Liu, S-T Chen, C-H Chang, L-M Chuang, M-S Lai
OBJECTIVES: The aim of this study was to examine the characteristics of patients, physicians, and medical facilities, and their association with prescriptions that do not include metformin as the initial oral antidiabetic agent. STUDY DESIGN: Observational, cross-sectional study. METHODS: Patients with incident type 2 diabetes between January 1, 2006, and December 31, 2010, were identified from the Taiwan National Insurance Research Database...
July 15, 2017: Public Health
https://www.readbyqxmd.com/read/28719077/metformin-synergistic-pemetrexed-suppresses-non-small-cell-lung-cancer-cell-proliferation-and-invasion-in-vitro
#11
Yan Zhang, Xiuli Feng, Tao Li, Erpan Yi, Yu Li
The aim of this study was to investigate whether metformin in combination with pemetrexed has an effect on the treatment of non-small-cell lung cancer (NSCLC) models and to explore the related molecular mechanism. The half maximal inhibitory concentration (IC50) and combination index (CI) of metformin and pemetrexed were detected by the CCK8 assay to assess the antiproliferative and therapeutic effects of the two-drug combination. Flow cytometry (FCM) and invasion assays were used to estimate the variation in apoptosis rate and invasion ability of the differently treated NSCLC cell lines...
July 18, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28714741/the-efficacy-and-safety-of-adding-either-vildagliptin-or-glimepiride-to-ongoing-metformin-therapy-in-patients-with-type-2-diabetes-mellitus
#12
Gyuri Kim, Sewon Oh, Sang-Man Jin, Kyu Yeon Hur, Jae Hyeon Kim, Moon-Kyu Lee
OBJECTIVE: To compare the effects of either vildagliptin or glimepiride on glycemic variability, oxidative stress, and endothelial parameters in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin alone. METHODS: In this randomized, open-label, parallel study, 34 patients with T2DM being treated with metformin having an HbA1c of 7.0-10.0% were allocated into either the vildagliptin or glimepiride group. A mixed-meal tolerance test and 72-hour continuous glucose monitoring were conducted, and urinary 8-iso-prostaglandinF2α (PGF2α) and endothelial-dependent flow-mediated dilatation (FMD) were evaluated at baseline and after 12 weeks of treatment...
July 17, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28709912/excipient-mediated-alteration-in-drug-bioavailability-in-the-rat-model-depends-on-the-sex-of-the-animal
#13
Yang Mai, Francisco Afonso-Pereira, Sudaxshina Murdan, Abdul Basit
The pharmaceutical excipient, polyethylene glycol 400 (PEG 400), unexpectedly alters the bioavailability of the BCS class III drug ranitidine in a sex-dependent manner. As ranitidine is a substrate for the efflux transporter P-glycoprotein (P-gp), we hypothesized that the sex-related influence could be due to interactions between PEG 400 and P-gp. In this study, we tested this hypothesis by: i) measuring the influence of PEG 400 on the oral bioavailability of another P-gp substrate (ampicillin) and of a non-P-gp substrate(metformin); and ii) measuring the effect of PEG 400 on drug bioavailability in the presence of a P-gp inhibitor (cyclosporine A) in male and female rats...
July 11, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28709719/metformin-effects-on-the-heart-and-the-cardiovascular-system-a%C3%A2-review-of-experimental-and-clinical-data
#14
REVIEW
L Nesti, A Natali
BACKGROUND: Metformin, the eldest and most widely used glucose lowering drug, is likely to be effective also on cardiac and vascular disease prevention. Nonetheless, uncertainty still exists with regard to its effects on the cardiovascular system as a whole and specifically on the myocardium, both at the organ and cellular levels. METHODS: We reviewed the available data on the cardiac and vascular effects of metformin, encompassing both in vitro, either tissue or isolated organ, and in vivo studies in experimental animals and humans, as well as the evidence generated by major clinical trials...
May 10, 2017: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/28708480/optimizing-diabetes-treatment-in-the-presence-of-obesity
#15
REVIEW
Mary Angelynne Esquivel, M Cecilia Lansang
Evidence of a neurophysiologic mechanism that involves hormones from adipocytes, pancreatic islet cells, and the gastrointestinal tract implicated in both obesity and diabetes has led to a search for drugs that not only either target obesity and diabetes or reduce hemoglobin A1c, but also have weight loss as a potential side effect. The authors review medications approved for the treatment of type 2 diabetes mellitus (including pramlintide, also approved for type 1 diabetes) that also have weight loss as a side effect...
July 2017: Cleveland Clinic Journal of Medicine
https://www.readbyqxmd.com/read/28705620/application-of-continuous-twin-screw-granulation-for-the-metformin-hydrochloride-extended-release-formulation
#16
Su-Hyeon Kim, Kyu-Min Hwang, Cheol-Hee Cho, Thi-Tram Nguyen, Su Hyun Seok, Kyu-Mok Hwang, Ju-Young Kim, Chun-Woong Park, Yun-Seok Rhee, Eun-Seok Park
This study focuses on evaluating the potential of transferring from a batch process to continuous process for manufacturing of the extended release formulation. Metformin hydrochloride (HCl) was used in the model formulation which was intended to contain the high amount of hydrophilic drug. The effects of barrel temperature, binder type, powder feed rate, and screw speed on granule properties (size and strength) and torque value in twin screw granulation were investigated. Due to the high content of hydrophilic model drug, the granules prepared at a higher temperature with HPMC binding solution had the narrower size distribution and greater strength than the granules prepared with distilled water as a binding solution...
July 10, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28704854/switching-from-premixed-insulin-to-basal-insulin-analogue-for-type-2-diabetes-and-role-of-dipeptidyl-peptidase-4-inhibitors
#17
Fernando Gómez-Peralta, Cristina Abreu, Gustavo Mora-Navarro, Pilar López-Morandeira, Esteban Pérez-Gutierrez, Blanca Cordero-García, Miguel Brito-Sanfiel
Introduction This study aimed to confirm the usefulness of basal insulin analogue plus oral antidiabetic drugs (OADs) for type 2 diabetes (T2D) patients inadequately controlled with premixed insulin with/without OADs and assess the role of dipeptidyl peptidase-4 (DPP-4) inhibitors within this regimen in clinical practice. Methods Spanish retrospective observational study that included 186 T2D patients with glycosylated hemoglobin (HbA1c) >7% (53 mmol/mol) despite premixed insulin with/without OADs who had been switched to basal insulin analogue plus OADs...
July 13, 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28702329/metformin-causes-a-futile-intestinal-hepatic-cycle-which-increases-energy-expenditure-and-slows-down-development-of-a-type-2-diabetes-like-state
#18
Philipp Schommers, Anna Thurau, Insa Bultmann-Mellin, Maria Guschlbauer, Andreas R Klatt, Jan Rozman, Martin Klingenspor, Martin Hrabe de Angelis, Jens Alber, Dirk Gründemann, Anja Sterner-Kock, Rudolf J Wiesner
OBJECTIVE: Metformin, the first line drug for treatment of type 2 diabetes, suppresses hepatic gluconeogenesis and reduces body weight in patients, the latter by an unknown mechanism. METHODS: Mice on a high fat diet were continuously fed metformin in a therapeutically relevant dose, mimicking a retarded formulation. RESULTS: Feeding metformin in pharmacologically relevant doses to mice on a high fat diet normalized HbA1c levels and ameliorated glucose tolerance, as expected, but also considerably slowed down weight gain...
July 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28701284/cost-effectiveness-analysis-of-different-dipeptidyl-peptidase-4-inhibitor-drugs-for-treatment-of-type-2-diabetes-mellitus
#19
M S Cazarim, Estael Luzia Coelho da Cruz-Cazarim, A O Baldoni, Thais Bueno Enes Dos Santos, Paula Gonçalves de Souza, Ingrid de Almeida Silva, Roberta Niriam Reis Rodrigues, Alda Cristina Franco Correa Maia, Leonardo Régis Leira Pereira, Cristina Sanches
INTRODUCTION: Type 2 diabetes mellitus (T2DM) has burdened health systems in the world to the value of 500 billion dollars/year. Dipeptidyl peptidase 4 inhibitors (DPP-4 Inhibitors) have been strongly associated with spending on the treatment of T2DM by the courts in Brazil. The aim of this study was to estimate the most cost-effective DPP-4 Inhibitor for T2DM treatment. A pharmacoeconomic study of cost-effectiveness was performed in a medium-sized municipality in Minas Gerais state, Brazil...
July 3, 2017: Diabetes & Metabolic Syndrome
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
#20
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
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