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https://www.readbyqxmd.com/read/28515940/nivolumab-induced-autoimmune-diabetes-mellitus-presenting-as-diabetic-ketoacidosis-in-a-patient-with-metastatic-lung-cancer
#1
James Luke Godwin, Shuchie Jaggi, Imali Sirisena, Pankaj Sharda, Ajay D Rao, Ranee Mehra, Colleen Veloski
BACKGROUND: Advances in cancer immunotherapy have generated encouraging results in multiple malignancies refractory to standard chemotherapies. As the use of immune checkpoint inhibitors (ICI) proliferates, the incidence of autoimmune side effects associated with these agents, termed immune related adverse events (irAE), is expected to increase. The frequency of significant irAE in ICI treated patients is about 10-20% and early recognition is critical to prevent serious morbidity and even mortality...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28511130/design-synthesis-and-biological-evaluation-of-uncharged-catechol-derivatives-as-selective-inhibitors-of-ptp1b
#2
Xiang-Qian Li, Qi Xu, Jiao Luo, Li-Jun Wang, Bo Jiang, Ren-Shuai Zhang, Da-Yong Shi
Protein tyrosine phosphatases 1B (PTP1B) is a promising and validated therapeutic target to effectively treat T2DM and obesity. However, the development of charged PTP1B inhibitors was restricted due to their low cell permeability and poor bioavailability. Based on active natural products, two series of uncharged catechol derivatives were identified as PTP1B inhibitors by targeting a secondary aryl phosphate-binding site as well as the catalytic site. The most potent inhibitor 22 showed an IC50 of 0.487 μM against PTP1B and strong selectivity (27-fold) over TCPTP...
May 3, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28508346/testosterone-insulin-like-effects-an-in-vitro-study-on-the-short-term-metabolic-effects-of-testosterone-in-human-skeletal-muscle-cells
#3
C Antinozzi, F Marampon, C Corinaldesi, E Vicini, P Sgrò, G B Vannelli, A Lenzi, C Crescioli, L Di Luigi
PURPOSE: Testosterone by promoting different metabolic pathways contributes to short-term homeostasis of skeletal muscle, the largest insulin-sensitive tissue and the primary site for insulin-stimulated glucose utilization. Despite evidences indicate a close relationship between testosterone and glucose metabolism, the molecular mechanisms responsible for a possible testosterone-mediated insulin-like effects on skeletal muscle are still unknown. METHODS: Here we used undifferentiated proliferating or differentiated human fetal skeletal muscle cells (Hfsmc) to investigate the short-term effects of testosterone on the insulin-mediated biomolecular metabolic machinery...
May 15, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/28507773/rapid-onset-clozapine-induced-loss-of-glycaemic-control-case-report
#4
Alejandro Porras-Segovia, Amir Krivoy, Mark Horowitz, George Thomas, Mark Bolstridge, Dragos Ion, Sukhwinder S Shergill
Clozapine has proved to be an effective antipsychotic for the treatment of refractory schizophrenia - characterised by the persistence of symptoms despite optimal treatment trials with at least two different antipsychotics at adequate dose and duration - but its use is hampered by adverse effects. The development of clozapine-induced diabetes is commonly considered to arise as part of a metabolic syndrome, associated with weight gain, and thus evolves slowly. We present the case of an individual with refractory schizophrenia and metformin-controlled diabetes who developed rapid-onset insulin-dependent hyperglycaemia immediately after starting clozapine...
May 2017: BJPsych Open
https://www.readbyqxmd.com/read/28497248/-aseptic-loosening-of-total-ankle-replacement-one-stage-revision-ankle-arthroplasty
#5
G Pagenstert, M D Wimmer, M Jacxsens, C L Saltzman, A Barg
OBJECTIVE: To revise one or both loosened prosthesis components, to achieve postoperative pain relief, and preserve ankle range of motion. INDICATIONS: Aseptic loosening of the tibial and/or talar ankle prosthesis components without substantial bone defect of the tibial or talar bone stock. CONTRAINDICATIONS: General surgical or anesthesiological risks, infections, critical soft tissue conditions, nonmanageable hindfoot instability, neurovascular impairment of the lower extremity, neuroarthropathy (e...
May 11, 2017: Operative Orthopädie und Traumatologie
https://www.readbyqxmd.com/read/28480657/urinary-glucose-screening-for-early-detection-of-asymptomatic-type-2-diabetes-in-jeonbuk-province-korean-schoolchildren
#6
Min Sun Kim, Dae Yeol Lee
This study aimed to investigate the prevalence of glucosuria and the characteristics of diabetes in schoolchildren as detected by a school urine glucose screening program implemented from 2010 to 2013 in the Jeonbuk province area of Korea. A total of 110 children without known diabetes were analyzed. They were checked with an oral glucose tolerance test (OGTT) with other laboratory tests and their clinical data were collected. A total of 707,238 schoolchildren from a school population of 1,064,999 were screened for glucosuria...
June 2017: Journal of Korean Medical Science
https://www.readbyqxmd.com/read/28478824/the-role-of-aquaporins-in-polycystic-ovary-syndrome-a-way-towards-a-novel-drug-target-in-pcos
#7
Agata Wawrzkiewicz-Jałowiecka, Karolina Kowalczyk, Dagmara Pluta, Łukasz Blukacz, Paweł Madej
Aquaporins (AQPs) are transmembrane proteins, able to transport water (and in some cases also small solutes, e. g. glycerol) through the cell membrane. There are twelve types of aquaporins (AQP1-AQP12) expressed in mammalian reproductive systems. According to literature, many diseases of the reproductive organs are correlated with changes of AQPs expression and their malfunction. That is the case in the polycystic ovary syndrome (PCOS), where dysfunctions of AQPs 7-9 and alterations in its levels occur. In this work, we postulate how AQPs are involved in PCOS-related disorders, in order to emphasize their potential therapeutic meaning as a drug target...
May 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28474889/promotion-of-glucose-uptake-in-c2c12-myotubes-by-cereal-flavone-tricin-and-its-underlying-molecular-mechanism
#8
Sohyun Kim, Gwang-Woong Go, Jee-Young Imm
The effect of tricin, a methylated flavone widely distributed in cereals, on glucose uptake and the underlying molecular mechanism was investigated using C2C12 myotubes. Tricin significantly increased glucose uptake in C2C12 myotubes, regardless of the absence (1.4-fold at 20 μM) or presence (1.6-fold at 20 μM) of insulin. The GLUT4 expression on the plasma membrane was increased 1.6-fold after tricin treatment (20 μM) in the absence of insulin. Tricin treatment significantly activated the insulin-dependent cell signaling pathway, including the activation of insulin receptor substrate-1 (IRS1), phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and AKT substrate of 160 kDa (AS160)...
May 5, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28470093/genetic-and-epigenetic-mechanisms-underlying-arsenic-associated-diabetes-mellitus-a-perspective-of-the-current-evidence
#9
Elizabeth M Martin, Miroslav Stýblo, Rebecca C Fry
Chronic exposure to arsenic has been associated with the development of diabetes mellitus (DM), a disease characterized by hyperglycemia resulting from dysregulation of glucose homeostasis. This review summarizes four major mechanisms by which arsenic induces diabetes, namely inhibition of insulin-dependent glucose uptake, pancreatic β-cell damage, pancreatic β-cell dysfunction and stimulation of liver gluconeogenesis that are supported by both in vivo and in vitro studies. Additionally, the role of polymorphic variants associated with arsenic toxicity and disease susceptibility, as well as epigenetic modifications associated with arsenic exposure, are considered in the context of arsenic-associated DM...
May 4, 2017: Epigenomics
https://www.readbyqxmd.com/read/28463061/exercise-protects-against-insulin-dependent-diabetes-induced-osteoarthritis-in-rats-a-scanning-electron-microscopy-study
#10
Fahaid Al-Hashem, Abbas O El Karib, Ismaeel Bin-Jaliah, Mohammad Dallak, Hussein F Sakr, Refaat A Eid, Mohamed Samir A Zaki, Mariam Al-Shamsi, Mohamed A Haidara, Bahjat Al-Ani
We tested the hypothesis that swim exercise can protect the articular cartilage from damages induced secondary to insulin-dependent diabetes mellitus in rats using the scanning electron microscopy and to monitor the blood levels of oxidative and antioxidative stress biomarkers that are known to be modulated in osteoarthritis (OA). A profound damage to the cartilage was observed in the diabetic rats. Our findings also show that swim exercise protects the knee joints from damage induced by diabetes as well as significantly inhibiting OA-induced upregulation of thiobarbituric acid reactive substances (TBARS) and tumor necrosis factor alpha (TNF-α) and augmented superoxide dismutase (SOD) inhibition by OA...
May 2, 2017: Ultrastructural Pathology
https://www.readbyqxmd.com/read/28462703/divergent-roles-of-irs-insulin-receptor-substrate-1-and-2-in-liver-and-skeletal-muscle
#11
Sabine Eckstein, Cora Weigert, Rainer Lehmann
IRS1 and IRS2 are the most important representatives of the IRS protein family and critical nodes in insulin/IGF1-signalling. Although they are quite similar in their structural and functional features they show tissue-specific differences. In this review we outline the functions of IRS1 and IRS2 in skeletal muscle and liver with regard to their importance for metabolism, growth and differentiation. Mechanisms contributing to IRS1 and IRS2 dysregulation in disease states as well as consequences thereof are discussed...
April 26, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28462458/crossreactivity-of-an-antiserum-directed-to-the-gram-negative-bacterium-neisseria-gonorrhoeae-with-the-snare-complex-protein-snap23-correlates-to-impaired-exocytosis-in-sh-sy5y-cells
#12
A Almamy, C Schwerk, H Schroten, H Ishikawa, A R Asif, B Reuss
Early maternal infections with Neisseria gonorrhoeae (NG) correlate to an increased lifetime schizophrenia risk for the offspring, which might be due to an immune-mediated mechanism. Here, we investigated the interactions of polyclonal antisera to NG (α-NG) with a first trimester prenatal brain multiprotein array, revealing among others the SNARE-complex protein Snap23 as a target antigen for α-NG. This interaction was confirmed by Western blot analysis with a recombinant Snap23 protein, whereas the closely related Snap25 failed to interact with α-NG...
May 1, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28459862/mechanism-of-insulin-resistance-in-a-rat-model-of-kidney-disease-and-the-risk-of-developing-type-2-diabetes
#13
François Dion, Christopher Dumayne, Nathalie Henley, Stéphanie Beauchemin, Edward B Arias, François A Leblond, Sylvie Lesage, Stéphane Lefrançois, Gregory D Cartee, Vincent Pichette
Chronic kidney disease is associated with homeostatic imbalances such as insulin resistance. However, the underlying mechanisms leading to these imbalances and whether they promote the development of type 2 diabetes is unknown. The effect of chronic kidney disease on insulin resistance was studied on two different rat strains. First, in a 5/6th nephrectomised Sprague-Dawley rat model of chronic kidney disease, we observed a correlation between the severity of chronic kidney disease and hyperglycemia as evaluated by serum fructosamine levels (p<0...
2017: PloS One
https://www.readbyqxmd.com/read/28452737/immunological-distress-in-experimental-cranial-trauma-combined-with-insulin-dependent-diabetes-experimental-study
#14
M Korda, V Meretskyi, I Meretska
This article describes the immunological events and investigates important mediators of the inflammatory immune response after experimental cranial trauma combined with type I diabetes. It was shown that the rats with induced diabetes and traumatic brain injury suffered more profound damage to the immune system that was not restored back to the basal level within 14 days. Proinflammatory cytokine concentrations increased, while anti-inflammatory cytokine concentrations decreased by day 14, increasing risk for systemic inflammatory response syndrome and multi-organ failure...
February 2017: Georgian Medical News
https://www.readbyqxmd.com/read/28449358/incident-rate-and-risk-factors-for-tuberculosis-among-patients-with-type-2-diabetes-retrospective-cohort-study-in-shanghai-china
#15
Hanbi Qiu, Yan Shi, Yanyun Li, Xin Shen, Rui Li, Qundi Yang, Qichao Pan, Fei Yan
OBJECTIVE: To examine the incident rate of tuberculosis (TB) and its associates among adults with type 2 diabetes in Shanghai, China. METHODS: We conducted a retrospective cohort study among 170,399 type 2 diabetes patients aged ≥18 years who were registered in Shanghai Community-Based Diabetes Management System between 2004 and 2009. Their TB status was tracked until December 31, 2014. Cox regression was performed to identify the risk factors for TB RESULTS: We documented 785 new TBcases during 654,977 person-years of follow-up...
April 27, 2017: Tropical Medicine & International Health: TM & IH
https://www.readbyqxmd.com/read/28444660/effects-of-cycling-and-exergaming-on-neurotrophic-factors-in-elderly-type-2-diabetic-men-a-preliminary-investigation
#16
Christian Brinkmann, Leonie Schäfer, Magd Masoud, Joachim Latsch, Daniel Lay, Wilhelm Bloch, Klara Brixius
Patients with type 2 diabetes mellitus (T2DM) are at increased risk of developing neurodegenerative diseases. There is growing evidence that repeated exercise-induced transient increases in neurotrophic factors can augment neurogenesis and neuroplasticity. This pilot study compares the effects of 30-min submaximal cycling with those of exergaming (combining exercise and video gaming) at the same duration and same rating of perceived exertion (BORG RPE: 14-15) on serum neurotrophic factors in 8 elderly non-insulin-dependent T2DM patients (71±4 years) (2×2 crossover design)...
April 25, 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28438417/comparing-hospital-outcomes-between-open-and-closed-tibia-fractures-treated-with-intramedullary-fixation
#17
Evan J Smith, Xiangyu Kuang, Rajeev Pandarinath
INTRODUCTION: Tibial shaft fractures comprise a large portion of operatively treated long bone fractures, and present with the highest rate of open injuries. Intramedullary fixation has become the standard of care for both open and closed injuries. The rates of short term complications and hospital length of stay for open and closed fractures treated with intramedullary fixation is not fully known. Previous series on tibia fractures were performed at high volume centers, and data were not generalizable, further they did not report on length of stay and the impact of preoperative variables on infections, complications and reoperation...
March 30, 2017: Injury
https://www.readbyqxmd.com/read/28432734/monogenic-diabetes-syndromes-locus-specific-databases-for-alstr%C3%A3-m-wolfram-and-thiamine-responsive-megaloblastic-anaemia
#18
Dewi Astuti, Ataf Sabir, Piers Fulton, Malgorzata Zatyka, Denise Williams, Carol Hardy, Gabriella Milan, Francesca Favaretto, Patrick Yu-Wai-Man, Julia Rohayem, Miguel López de Heredia, Tamara Hershey, Lisbeth Tranebjaerg, Jian-Hua Chen, Annabel Chaussenot, Virginia Nunes, Bess Marshall, Susan McAfferty, Vallo Tillmann, Pietro Maffei, Veronique Paquis-Flucklinger, Tarekign Geberhiwot, Wojciech Mlynarski, Kay Parkinson, Virginie Picard, Gema Esteban Bueno, Renuka Dias, Amy Arnold, Caitlin Richens, Richard Paisey, Fumi Urano, Robert Semple, Richard Sinnott, Timothy G Barrett
We developed a variant database for diabetes syndrome genes, using the Leiden Open Variation Database platform, containing observed phenotypes matched to the genetic variations. We populated it with 628 published disease associated variants (December 2016) for: WFS1 (n = 309), CISD2 (n = 3), ALMS1 (n = 268), and SLC19A2 (n = 48) for Wolfram type 1, Wolfram type 2, Alström and Thiamine-responsive megaloblastic anaemia syndromes respectively; and included 23 previously unpublished novel germline variants in WFS1 and 17 variants in ALMS1...
April 21, 2017: Human Mutation
https://www.readbyqxmd.com/read/28424732/evidence-for-loss-in-identity-de-differentiation-and-trans-differentiation-of-islet-%C3%AE-cells-in-type-2-diabetes
#19
REVIEW
Chad S Hunter, Roland W Stein
The two main types of diabetes mellitus have distinct etiologies, yet a similar outcome: loss of islet β-cell function that is solely responsible for the secretion of the insulin hormone to reduce elevated plasma glucose toward euglycemic levels. Type 1 diabetes (T1D) has traditionally been characterized by autoimmune-mediated β-cell death leading to insulin-dependence, whereas type 2 diabetes (T2D) has hallmarks of peripheral insulin resistance, β-cell dysfunction, and cell death. However, a growing body of evidence suggests that, especially during T2D, key components of β-cell failure involves: (1) loss of cell identity, specifically proteins associated with mature cell function (e...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28418115/aggravation-of-diabetes-and-incompletely-deficient-insulin-secretion-in-a-case-with-type-1-diabetes-resistant-hla-drb1-15-02-treated-with-nivolumab
#20
Kimio Matsumura, Kaoru Nagasawa, Yoichi Oshima, Shouta Kikuno, Kyohei Hayashi, Akihiro Nishimura, Minoru Okubo, Hironori Uruga, Kazuma Kishi, Tetsuro Kobayashi, Yasumichi Mori
Anti-programmed cell death-1 (PD-1) antibody therapy induces various adverse effects especially in endocrine systems. Several cases of acute onset insulin-dependent diabetes after anti-PD-1 antibody therapy have been reported. Many of these cases have a susceptible HLA genotype for type 1 diabetes possibly suggesting that human leukocyte antigen (HLA) might be involved in the onset of diabetes with anti PD-1 therapy. We describe an atypical case of hyperglycemia after anti PD-1 antibody administration. A 68-year-old Japanese man with pancreatic diabetes and steroid diabetes was administered nivolumab three times for chemoresistant adenocarcinoma of the lung...
April 18, 2017: Journal of Diabetes Investigation
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