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https://www.readbyqxmd.com/read/29774523/acute-and-subacute-antidiabetic-studies-of-enp-9-a-new-1-5-diarylpyrazole-derivative
#1
Eduardo Hernández-Vázquez, Sandra Young-Peralta, Litzia Cerón-Romero, Sara García-Jiménez, Samuel Estrada-Soto
OBJECTIVES: To explore the antihyperglycaemic and antidiabetic effects and to determine the acute toxicity of 5-(4-chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide (ENP-9). METHODS: The antihyperglycaemic effect of ENP-9 (50 mg/kg) was determined by oral glucose tolerance test (OGTT). Also, the acute (16, 50 and 160 mg/kg) and subacute (50 mg/kg/day for 10 days) antidiabetic effects of ENP-9 were determined. After subacute treatment, blood samples were analysed to determine glucose and lipid profiles...
May 17, 2018: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/29774466/rs2227982-and-rs2227981-in-pdcd1-gene-are-functional-snps-associated-with-t1d-risk-in-east-asian
#2
Yong Gu, Lei Xiao, Wei Gu, Shu Chen, Yingjie Feng, Jian Wang, Zhixiao Wang, Yun Cai, Heng Chen, Xinyu Xu, Yun Shi, Mei Zhang, Kuanfeng Xu, Tao Yang
AIMS: To investigate whether PDCD1 gene polymorphisms are functional, and their associations with T1D risk and related clinical characteristics. METHODS: A total of 3060 Chinese Han individuals (1019 T1D patients and 2041 healthy controls) were genotyped for 4 tag single nucleotide polymorphisms (SNPs) within the PDCD1 region (rs2227982, rs7421861, rs10204525, and rs6710479) and another most studied synonymous SNP, rs2227981. In addition, 251 healthy individuals underwent an oral glucose tolerance test (OGTT); measures of insulin release and sensitivity were estimated from insulinogenic, BIGTT, Matsuda...
May 17, 2018: Acta Diabetologica
https://www.readbyqxmd.com/read/29773934/iglarlixi-a-new-once-daily-fixed-ratio-combination-of-basal-insulin-glargine-and-lixisenatide-for-the-management-of-type-2-diabetes
#3
Debbie Hinnen, Jodi Strong
Background: Patients with type 2 diabetes require treatment intensification to maintain glycemic control. Clinician reluctance, patient injection fears, hypoglycemia, weight gain, or other objections may lead to clinical inertia, whereby therapy is not intensified and patients live with uncontrolled hyperglycemia and increased risk for complications. Initiation of injectable therapy with a glucagon-like peptide (GLP)-1 receptor agonist and/or basal insulin is a recommended option for patients with type 2 diabetes inadequately controlled on one or more oral agents...
May 2018: Diabetes Spectrum: a Publication of the American Diabetes Association
https://www.readbyqxmd.com/read/29773885/metabolic-perturbations-of-post-load-hyperglycemia-vs-fasting-hyperglycemia
#4
Jing-Yi Lu, Jia-Hui Peng, Xiao-Jing Ma, Yi-Nan Zhang, Wei Zhu, Xing-Xing He, Ling-Wen Ying, Yu-Qian Bao, Jian Zhou, Wei-Ping Jia
There is evidence that post-load/post-meal hyperglycemia is a stronger risk factor for cardiovascular disease than fasting hyperglycemia. The underlying mechanism remains to be elucidated. The current study aimed to compare the metabolic profiles of post-load hyperglycemia and fasting hyperglycemia. All subjects received an oral glucose tolerance test (OGTT) and were stratified into fasting hyperglycemia (FH) or post-load hyperglycemia (PH). Forty-six (FH, n = 23; PH, n = 23) and 40 patients (FH, n = 20; PH, n = 20) were recruited as the exploratory and the validation set, respectively, and underwent metabolic profiling...
May 17, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29773207/poor-sleep-during-early-pregnancy-increases-subsequent-risk-of-gestational-diabetes-mellitus
#5
Chunrong Zhong, Renjuan Chen, Xuezhen Zhou, Shangzhi Xu, Qian Li, Wenli Cui, Weiye Wang, Xiating Li, Jiangyue Wu, Chaoqun Liu, Mei Xiao, Guoqiang Sun, Xuefeng Yang, Liping Hao, Nianhong Yang
OBJECTIVES: To examine the relationship between poor sleep quality during pregnancy and the risk of gestational diabetes mellitus (GDM). METHODS: A total of 4066 singleton pregnant women from the Tongji Maternal and Child Health Cohort (TMCHC) without overt diabetes before pregnancy were analyzed. Sleep quality and duration during early pregnancy were self-reported by enrolled women at their first antenatal care visit before 16 weeks of gestation. Gestational diabetes mellitus (GDM) was assessed with a 75-g, 2-h oral glucose tolerance test at 24-28 weeks of gestation...
June 2018: Sleep Medicine
https://www.readbyqxmd.com/read/29773001/combined-administration-of-monosodium-glutamate-and-high-sucrose-diet-accelerates-the-induction-of-type-2-diabetes-vascular-dysfunction-and-memory-impairment-in-rats
#6
Kaja Saikrishna, Ringu Kumari, Kantamaneni Chaitanya, Subhankar Biswas, Pawan G Nayak, Jayesh Mudgal, Anoop Kishore, Krishnadas Nandakumar
In this study, we aimed to develop an experimental animal model for type 2 diabetes mellitus (T2DM) using a combination of monosodium glutamate (MSG) and high sucrose diet (HSD). Young male Wistar rats (20-30 g) were injected with MSG (2 or 4 mg/g, i.p. for 4 days). These rats were also fed an HSD, while the control group was fed a starch diet (SFD) for 150 days. Parameters assessed periodically were body weight, feed intake, blood glucose level, and oral glucose tolerance test (OGTT), lipid profile, liver and kidney function tests, skeletal muscle glucose uptake, cognitive function tests, and microvascular changes using isolated rat aorta...
2018: Journal of Environmental Pathology, Toxicology and Oncology
https://www.readbyqxmd.com/read/29771255/return-of-the-tetracyclines-omadacycline-a-novel-aminomethylcycline-antimicrobial
#7
J C Cho, L M Childs-Kean, M T Zmarlicka, M P Crotty
Omadacycline is a novel aminomethylcycline antimicrobial agent that is available in both oral and intravenous formulations. The distinguishing structural characteristics of omadacycline from other tetracyclines allow for its continued antimicrobial activity in the presence of traditional tetracycline resistance mechanisms (efflux pumps and ribosomal protection proteins). Omadacycline has been found to have potent activity against antibiotic-resistant pathogens including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, extended spectrum beta-lactamase-producing Escherichia coli and multidrug-resistant Streptococcus pneumoniae...
March 2018: Drugs of Today
https://www.readbyqxmd.com/read/29769449/fatty-acid-receptor-modulator-pbi-4050-inhibits-kidney-fibrosis-and-improves-glycemic-control
#8
Yan Li, Sungjin Chung, Zhilian Li, Jessica M Overstreet, Lyne Gagnon, Brigitte Grouix, Martin Leduc, Pierre Laurin, Ming-Zhi Zhang, Raymond C Harris
Extensive kidney fibrosis occurs in several types of chronic kidney diseases. PBI-4050, a potentially novel first-in-class orally active low-molecular weight compound, has antifibrotic and antiinflammatory properties. We examined whether PBI-4050 affected the progression of diabetic nephropathy (DN) in a mouse model of accelerated type 2 diabetes and in a model of selective tubulointerstitial fibrosis. eNOS-/- db/db mice were treated with PBI-4050 from 8-20 weeks of age (early treatment) or from 16-24 weeks of age (late treatment)...
May 17, 2018: JCI Insight
https://www.readbyqxmd.com/read/29769258/anti-tumor-efficacy-of-a-novel-clk-inhibitor-via-targeting-rna-splicing-and-myc-dependent-vulnerability
#9
Kenichi Iwai, Masahiro Yaguchi, Kazuho Nishimura, Yukiko Yamamoto, Toshiya Tamura, Daisuke Nakata, Ryo Dairiki, Yoichi Kawakita, Ryo Mizojiri, Yoshiteru Ito, Moriteru Asano, Hironobu Maezaki, Yusuke Nakayama, Misato Kaishima, Kozo Hayashi, Mika Teratani, Shuichi Miyakawa, Misa Iwatani, Maki Miyamoto, Michael G Klein, Wes Lane, Gyorgy Snell, Richard Tjhen, Xingyue He, Sai Pulukuri, Toshiyuki Nomura
The modulation of pre-mRNA splicing is proposed as an attractive anti-neoplastic strategy, especially for the cancers that exhibit aberrant pre-mRNA splicing. Here, we discovered that T-025 functions as an orally available and potent inhibitor of Cdc2-like kinases (CLKs), evolutionally conserved kinases that facilitate exon recognition in the splicing machinery. Treatment with T-025 reduced CLK-dependent phosphorylation, resulting in the induction of skipped exons, cell death, and growth suppression in vitro and in vivo Further, through growth inhibitory characterization, we identified high CLK2 expression or MYC amplification as a sensitive-associated biomarker of T-025...
May 16, 2018: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29769013/antidiabetic-effect-of-spearmint-in-streptozotocin-induced-diabetic-rats
#10
Omar Farid, A El Haidani, Mohamed Eddouks
In this work the effect of Mentha spicata (L.) (M. spicata) aerial part aqueous extract (A.P.A.E) at a dose of 20 mg/kg body weight on blood glucose levels has been demonstrated in normal and streptozotocin (STZ) diabetic rats. Additionally, a preliminary phytochemical screening for various bioactive constituents was realized and a dosage of polyphenols and flavonoid has been done. Moreover, the histopathological changes in liver and pancreas have been evaluated both in normal and STZ diabetic rats. The effect of M...
May 16, 2018: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/29768336/primary-diffuse-large-b-cell-lymphoma-in-the-maxilla-a-case-report
#11
Haixiao Zou, Haili Yang, Yuan Zou, Lang Lei, Li Song
RATIONALE: Lymphomas are the second most common non-epithelial malignant tumors in the oral and maxillofacial region. Non-Hodgkin's lymphoma (NHL) develops at extranodal sites, and cases involving the maxilla account for less than 1% of all NHLs. We describe a case of diffuse large B-cell lymphoma (DLBCL) in the maxilla, and highlight the clinical signs, symptoms, differential diagnosis, and appropriate treatment of DLBCL in the oral cavity and maxillofacial region. PATIENT CONCERNS: A 67-year-old woman was admitted to our surgical department with pain and swelling in her right upper posterior teeth for about six months...
May 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29768280/phase-i-ii-trial-of-chemotherapy-with-docetaxel-cisplatin-and-s-1-for-unresectable-advanced-squamous-cell-carcinoma-of-the-esophagus
#12
Toshiyasu Ojima, Masaki Nakamura, Mikihito Nakamori, Masahiro Katsuda, Keiji Hayata, Shimpei Maruoka, Toshio Shimokawa, Hiroki Yamaue
Our previous trial with a docetaxel, cisplatin, and 5-fluorouracil (DCF) regimen showed high response rates in metastatic squamous cell carcinoma of the esophagus (SCCE). The observed increased toxicity of the DCF regimen, however, was clinically harmful. S-1, an oral anticancer drug, has been approved as a combination therapy for SCCE, and alternate-day regimen with S-1 has shown lower levels of toxicity. This prospective single-center phase I/II trial examines the efficacy and toxicity of a combination of docetaxel, cisplatin, and an alternate-day regimen of S-1 (modified DCS) for patients with metastatic SCCE...
May 16, 2018: Oncology
https://www.readbyqxmd.com/read/29766652/mucosal-microflora-in-head-and-neck-cancer-patients
#13
A Almståhl, C Finizia, A Carlén, B Fagerberg-Mohlin, T Alstad
OBJECTIVE: To analyse the tongue and buccal microflora prospectively in head and neck cancer patients treated with radiation therapy (RT). METHODS: In 33 dentate patients, microbial samples from the tongue and buccal mucosa were collected pretreatment, during treatment, and 6 months, 1 year and 2 years post-treatment. Microorganisms associated with oral health and oral disorders were analysed using cultivation technique. Oral mucositis was scored at the appointment during treatment...
May 15, 2018: International Journal of Dental Hygiene
https://www.readbyqxmd.com/read/29766636/empagliflozin-as-add-on-to-linagliptin-in-a-fixed-dose-combination-in-japanese-patients-with-type-2-diabetes-glycemic-efficacy-and-safety-profile-in-a-52-week-randomized-placebo-controlled-trial
#14
Ryuzo Kawamori, Masakazu Haneda, Keiko Suzaki, Gang Cheng, Kosuke Shiki, Yuki Miyamoto, Fernando Solimando, Christopher Lee, Jisoo Lee, Jyothis George
AIMS: This double-blind, randomized, placebo-controlled trial evaluated the efficacy and safety of empagliflozin (Empa) 10 or 25 mg as add-on to linagliptin (Lina) 5 mg (fixed-dose combination, Empa/Lina 10/5 or 25/5) in insufficiently controlled Japanese type 2 diabetes patients. METHODS: The trial (40 sites; May 2015-March 2017) screened 433 adults (≥20 years) who were treatment-naive or on one oral antidiabetic drug for ≥12 weeks (discontinued at enrolment)...
May 15, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29766601/functional-high-intensity-exercise-training-ameliorates-insulin-resistance-and-cardiometabolic-risk-factors-in-type-2-diabetes
#15
Ciarán E Fealy, Stephan Nieuwoudt, Julie A Foucher, Amanda R Scelsi, Steve K Malin, Mangesh Pagadala, Lauren A Cruz, Miranda Li, Michael Rocco, Bartolome Burguera, John P Kirwan
AIM: Functional high intensity training (F-HIT) is a novel fitness paradigm that integrates simultaneous aerobic and resistance training in sets of constantly varied movements, based on real-world situational exercises, performed at high intensity in workouts that range from ∼8-20 min/session. We hypothesized that F-HIT would be an effective exercise mode for reducing insulin resistance in type 2 diabetes (T2D). METHODS: We recruited 13 overweight/obese adults (5 males, 8 females; 53 ± 7 years; BMI 34...
May 15, 2018: Experimental Physiology
https://www.readbyqxmd.com/read/29766563/the-effects-of-gestational-diabetes-mellitus-on-fetal-growth-and-neonatal-birth-measures-in-an-african-cohort
#16
S Macaulay, R J Munthali, D B Dunger, S A Norris
AIM: Fetal exposure to gestational diabetes mellitus (GDM) is said to alter fetal growth and increase the risk of macrosomia. However, little research on GDM exists in African populations. This study aimed to assess longitudinal fetal growth and neonatal birth measures among Black African babies exposed to GDM. METHODS: Pregnant women (Soweto, South Africa) enrolled into a cohort study were followed up with repeated fetal ultrasounds. At 24-28 weeks' gestation a 2-h 75 g oral glucose tolerance test was performed and GDM was diagnosed using the World Health Organization's 2013 criteria...
May 15, 2018: Diabetic Medicine: a Journal of the British Diabetic Association
https://www.readbyqxmd.com/read/29766337/a-phase-i-trial-to-determine-safety-and-pharmacokinetics-of-aslan002-an-oral-met-superfamily-kinase-inhibitor-in-patients-with-advanced-or-metastatic-solid-cancers
#17
Aflah Roohullah, Adam Cooper, Anna J Lomax, Jennifer Aung, Alan Barge, Lilian Chow, Mark McHale, Jayesh Desai, James R Whittle, Ben Tran, Paul de Souza, Lisa G Horvath
Background The MET tyrosine kinase and its ligand, hepatocyte growth factor (HGF) also known as scatter factor, are associated with tumourigenesis and metastasis by promotion of scattering, proliferation, angiogenesis, motility and invasion. ASLAN-002 is a potent inhibitor of MET as well as related kinases. A phase I dose escalation study was conducted to determine the safety and pharmacokinetics of ASLAN-002 in patients with advanced cancer. Methods Patients with advanced or metastatic solid tumours, who had progressed on standard therapy or for whom standard therapy was not known, were administered ASLAN-002 orally...
May 16, 2018: Investigational New Drugs
https://www.readbyqxmd.com/read/29765987/insulin-secretion-and-risk-for-future-diabetes-in-subjects-with-a-nonpositive-insulinogenic-index
#18
Daisuke Aono, Rie Oka, Mitsuhiro Kometani, Yoshimichi Takeda, Shigehiro Karashima, Kenichi Yoshimura, Yoshiyu Takeda, Takashi Yoneda
Aim: To characterize subjects with a nonpositive insulinogenic index and longitudinally observe changes in their glucose tolerance. Subjects and Methods: A historical cohort study was conducted using data from the medical checkups of public school workers. Indices of insulin secretion and insulin sensitivity derived from oral glucose tolerance test (OGTT) and the incidences of diabetes and impaired glucose tolerance (IGT) were compared among subgroups of subjects with different insulinogenic index (change in insulin/change in glucose over the first 30 min on the OGTT)...
2018: Journal of Diabetes Research
https://www.readbyqxmd.com/read/29765613/basic-lifestyle-advice-to-individuals-at-high-risk-of-type-2-diabetes-a-2-year-population-based-diabetes-prevention-study-the-de-plan-intervention-in-the-hunt-study-norway
#19
Anne Jølle, Bjørn Olav Åsvold, Jostein Holmen, Sven Magnus Carlsen, Jaakko Tuomilehto, Johan Håkon Bjørngaard, Kristian Midthjell
Objective: Among individuals at high risk for diabetes identified through a population survey, we performed an intervention study with basic lifestyle advice aiming to prevent diabetes. Research design and methods: Among 50 806 participants in the HUNT3 Survey (2006-2008), 5297 individuals with Finnish Diabetes Risc Score (FINDRISC ≥15 were invited to an oral glucose tolerance test (OGTT) and an education session with lifestyle advice, and 2634 (49.7%) attended...
2018: BMJ Open Diabetes Research & Care
https://www.readbyqxmd.com/read/29765386/design-of-a-type-1-diabetes-vaccine-candidate-using-edible-plants-expressing-a-major-autoantigen
#20
Edoardo Bertini, Matilde Merlin, Elisa Gecchele, Andrea Puggia, Annalisa Brozzetti, Mauro Commisso, Alberto Falorni, Vittorio Bini, Victor Klymyuk, Mario Pezzotti, Linda Avesani
Type-1 diabetes (T1D) is a metabolic disease involving the autoimmune destruction of insulin-producing pancreatic beta cells. It is often diagnosed by the detection of autoantibodies, typically those recognizing insulin itself or the 65-kDa isoform of glutamic acid decarboxylase (GAD65). Oral insulin can be used to induce systemic immunological tolerance and thus prevent or delay the onset of T1D, suggesting that combination treatments with other autoantigens such as GAD65 could be even more successful. GAD65 has induced oral tolerance and prevented T1D in preclinical studies but it is difficult to produce in sufficient quantities for clinical testing...
2018: Frontiers in Plant Science
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