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Fumarate diabetes

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https://www.readbyqxmd.com/read/29707388/risk-factors-and-co-morbidities-associated-with-changes-in-renal-function-among-antiretroviral-treatment-na%C3%A3-ve-adults-in-south-africa-a-chart-review
#1
Shirelle Assaram, Tivani P Mashamba-Thompson, Nombulelo P Magula
Introduction: Our systematic scoping review has demonstrated a research gap in antiretroviral treatment (ART) nephrotoxicity as well as in the long-term outcomes of renal function for patients on ART in South Africa. Bearing in mind the high prevalence of human immunodeficiency virus (HIV) in South Africa, this is of great concern. Objectives: To determine the risk factors and co-morbidities associated with changes in renal function in HIV-infected adults in South Africa...
2018: Southern African Journal of HIV Medicine
https://www.readbyqxmd.com/read/29702139/renal-health-after-long-term-exposure-to-tenofovir-disoproxil-fumarate-tdf-in-hiv-hbv-positive-adults-in-ghana
#2
G Villa, R O Phillips, C Smith, A J Stockdale, A Beloukas, L T Appiah, D Chadwick, A Ruggiero, F S Sarfo, F Post, A M Geretti
OBJECTIVES: The study assessed markers of renal health in HIV/HBV co-infected patients receiving TDF-containing antiretroviral therapy in Ghana. METHODS: Urinary protein-to-creatinine ratio (uPCR) and albumin-to-protein ratio (uAPR) were measured cross-sectionally after a median of four years of TDF. At this time, alongside extensive laboratory testing, patients underwent evaluation of liver stiffness and blood pressure. The estimated glomerular filtration rate (eGFR) was measured longitudinally before and during TDF therapy...
April 24, 2018: Journal of Infection
https://www.readbyqxmd.com/read/29696665/using-the-chronic-kidney-disease-guidelines-to-evaluate-the-renal-safety-of-tenofovir-disoproxil-fumarate-in-hepatitis-b-patients
#3
H J Tsai, Y W Chuang, S W Lee, C Y Wu, H Z Yeh, T Y Lee
BACKGROUND: Renal dysfunction remains an issue in tenofovir disoproxil fumarate (TDF) for chronic hepatitis B (CHB) patients. AIM: To evaluate renal safety of TDF according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. METHODS: We retrospectively recruited CHB patients who received either TDF or entecavir (ETV) monotherapy from January 2008 to August 2015. After excluding confounding conditions, 253 patients who received TDF were randomly matched 1:2 with 506 patients who received ETV through the propensity scores, which consisted of age, gender, cirrhosis, chronic kidney disease (CKD) and estimated glomerular filtration rate (eGFR)...
April 25, 2018: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29626092/identification-of-a-metabolic-disposal-route-for-the-oncometabolite-s-2-succino-cysteine-in-bacillus-subtilis
#4
Thomas D Niehaus, Jacob Folz, Donald R McCarty, Arthur J L Cooper, David Moraga Amador, Oliver Fiehn, Andrew D Hanson
Cellular thiols such as cysteine spontaneously and readily react with the respiratory intermediate fumarate, resulting in the formation of stable S -(2-succino)-adducts. Fumarate-mediated succination of thiols increases in certain tumors and in response to glucotoxicity associated with diabetes. Therefore, S -(2-succino)-adducts such as S -(2-succino)cysteine (2SC) are considered oncometabolites and biomarkers for human disease. No disposal routes for S -(2-succino) compounds have been reported prior to this study...
April 6, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29614759/high-glucose-induced-cardiomyocyte-death-may-be-linked-to-unbalanced-branched-chain-amino-acids-and-energy-metabolism
#5
Xi Zhang, Qiuting Lin, Jiuxia Chen, Tingting Wei, Chen Li, Liangcai Zhao, Hongchang Gao, Hong Zheng
High glucose-induced cardiomyocyte death is a common symptom in advanced-stage diabetic patients, while its metabolic mechanism is still poorly understood. The aim of this study was to explore metabolic changes in high glucose-induced cardiomyocytes and the heart of streptozotocin-induced diabetic rats by ¹H-NMR-based metabolomics. We found that high glucose can promote cardiomyocyte death both in vitro and in vivo studies. Metabolomic results show that several metabolites exhibited inconsistent variations in vitro and in vivo...
April 1, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29602394/the-warburg-effect-in-diabetic-kidney-disease
#6
REVIEW
Guanshi Zhang, Manjula Darshi, Kumar Sharma
Diabetic kidney disease (DKD) is the leading cause of morbidity and mortality in diabetic patients. Defining risk factors for DKD using a reductionist approach has proven challenging. Integrative omics-based systems biology tools have shed new insights in our understanding of DKD and have provided several key breakthroughs for identifying novel predictive and diagnostic biomarkers. In this review, we highlight the role of the Warburg effect in DKD and potential regulating factors such as sphingomyelin, fumarate, and pyruvate kinase muscle isozyme M2 in shifting glucose flux from complete oxidation in mitochondria to the glycolytic pathway and its principal branches...
March 2018: Seminars in Nephrology
https://www.readbyqxmd.com/read/29568552/prevalence-and-factors-associated-with-renal-dysfunction-in-patients-on-tenofovir-disoproxil-fumarate-based-antiretroviral-regimens-for-hiv-infection-in-southern-india
#7
EDITORIAL
Nagalingeswaran Kumarasamy, Sruthi Sundaram, Selvamuthu Poongulali, Chandrasekaran Ezhilarasi, Ambrose Pradeep, Devaraj Chitra
Objectives: Tenofovir disoproxil fumarate (TDF) is a nucleotide reverse transcriptase inhibitor commonly used in the treatment of HIV infection. This retrospective study aims to establish the prevalence of abnormal renal function among patients with HIV receiving TDF, and to investigate the risks for TDF-related renal dysfunction in this population. Methods: Patients at the YRGCARE Medical Centre, Voluntary Health Services, receiving TDF-containing antiretroviral (ART) regimens between January 2002 and March 2017, were assessed for renal dysfunction using creatinine level and eGFR (DAIDS/NIH) during continuum of care...
January 1, 2018: Journal of Virus Eradication
https://www.readbyqxmd.com/read/29561293/long-term-kidney-function-proteinuria-and-associated-risks-among-hiv-infected-and-uninfected-men
#8
Frank Palella, Xiuhong Li, Samir K Gupta, Michelle M Estrella, John P Phair, Joseph B Margolick, Roger Detels, Lawrence Kingsley, Lisa P Jacobson
BACKGROUND: Factors affecting kidney function and proteinuria among HIV+ and HIV- persons need better characterization. METHODS: We evaluated estimated glomerular filtration rate (eGFR, mL/min per 1.73 m) changes, proteinuria prevalence (a urine protein-to-creatinine ratio [UPCr] of ≥0.2 at two consecutive visits) and associated factors among HIV+ and HIV- men. RESULTS: There were 917 HIV+ men receiving HAART, 159 HIV+ men not receiving HAART, and 1305 HIV- men seen from 10/2003 to 9/2014...
March 20, 2018: AIDS
https://www.readbyqxmd.com/read/29455073/dimethyl-fumarate-in-a-patient-with-multiple-sclerosis-and-type-1-diabetes-mellitus-the-importance-of-ketonuria
#9
Ewa Krzystanek, Przemyslawa Jarosz-Chobot
BACKGROUND: Dimethyl fumarate (DMF) is approved for use in patients with relapsing-remitting multiple sclerosis (MS). Its mechanism of action is still not well understood, but besides the immunological pathways in MS, it may also affect the metabolism of normally functioning internal organs, tissues and cells. CASE PRESENTATION: We report on the case of 29-year-old woman with satisfactorily-controlled type 1 diabetes (T1D), who was diagnosed as having MS. After administration of DMF she experienced intense, adverse gastro-intestinal reactions together with ketonuria up to 160 mg/dL...
April 2018: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29447051/targeting-crosstalk-between-nuclear-factor-erythroid-derived-2-like-2-and-nuclear-factor-kappa-beta-pathway-by-nrf2-activator-dimethyl-fumarate-in-epileptogenesis
#10
Neha Singh, Sheekha Vijayanti, Lekha Saha
Purpose/Aim: Epilepsy is a complex, chronic neurological disorder characterized by increased and abnormal synchronization of neuronal electrical activity, which is manifested as seizures. It is associated with many comorbid conditions such as depression, anxiety, sleep disorder, psychiatric disorder etc., which consequently causes higher mortality rate. The understanding of its cellular and molecular mechanism is partial, because of which it remains an ongoing health problem, despite the increasing availability of newer antiepileptic drugs...
February 25, 2018: International Journal of Neuroscience
https://www.readbyqxmd.com/read/29443737/effect-of-tenofovir-on-renal-function-in-patients-with-chronic-hepatitis-b
#11
Woo Jin Jung, Jae Young Jang, Won Young Park, Soung Won Jeong, Hee Jeong Lee, Sang Joon Park, Sae Hwan Lee, Sang Gyune Kim, Sang-Woo Cha, Young Seok Kim, Young Deok Cho, Hong Soo Kim, Boo Sung Kim, Suyeon Park, Baigal Baymbajav
Tenofovir disoproxil fumarate (TDF) is widely used to treat patients with hepatitis B virus (HBV) infection. We investigated the effect of TDF on renal insufficiency in patients with chronic hepatitis B (CHB).A consecutive cohort analysis was applied to CHB patients taking prescribed TDF from January 2012 to May 2016 at Soonchunhyang University Seoul Hospital. Alterations over time in corrected calcium, phosphate, creatinine, and estimated glomerular filtration rate (eGFR) were analyzed using the generalized estimating equation method...
February 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29408448/protection-by-dimethyl-fumarate-against-diabetic-cardiomyopathy-in-type-1-diabetic-mice-likely-via-activation-of-nuclear-factor-erythroid-2-related-factor-2
#12
Xinyue Hu, Mohanraj Rajesh, Jian Zhang, Shanshan Zhou, Shudong Wang, Jian Sun, Yi Tan, Yang Zheng, Lu Cai
Oxidative stress and inflammation play key roles in the development of diabetic cardiomyopathy (DCM). Dimethyl fumarate (DMF), an FDA approved medicine for relapsing multiple sclerosis, has manifested its antioxidant and anti-inflammatory function mostly in the central nervous system. In this study, we investigated whether DMF could attenuate the development of DCM. Type 1 diabetes mouse model was established using multiple low-dose streptozotocin, and the diabetic mice were treated with DMF (10 mg/kg body weight) for 3 months...
May 1, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29070571/lithium-induces-aerobic-glycolysis-and-glutaminolysis-in-collecting-duct-principal-cells
#13
Mohammad Alsady, Theun de Groot, Marleen L A Kortenoeven, Claudia Carmone, Kim Neijman, Melissa Bekkenkamp-Grovenstein, Udo Engelke, Ron Wevers, Ruben Baumgarten, Ron Korstanje, Peter M T Deen
Lithium, given to bipolar disorder patients, causes nephrogenic diabetes insipidus (Li-NDI), a urinary-concentrating defect. Li-NDI occurs due to downregulation of principal cell AQP2 expression, which coincides with principal cell proliferation. The metabolic effect of lithium on principal cells, however, is unknown and investigated here. In earlier studies, we showed that the carbonic anhydrase (CA) inhibitor acetazolamide attenuated Li-induced downregulation in mouse-collecting duct (mpkCCD) cells. Of the eight CAs present in mpkCCD cells, siRNA and drug treatments showed that downregulation of CA9 and to some extent CA12 attenuated Li-induced AQP2 downregulation...
February 1, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29028660/cumulative-exposure-of-tdf-is-associated-with-kidney-tubulopathy-whether-it-is-currently-used-or-discontinued
#14
Takeshi Nishijima, Yoshikazu Mutoh, Yohei Kawasaki, Kiyomi Tomonari, Yoshimi Kikuchi, Hiroyuki Gatanaga, Shinichi Oka
OBJECTIVE: Tenofovir disoproxil fumarate (TDF) increases the risk of kidney tubular dysfunction (KTD). This study was conducted to elucidate whether KTD persists after discontinuation of TDF. DESIGN: A prospective cross-sectional study which enrolled 941 HIV-1-infected patients. METHODS: KTD was predefined as the presence of at least two abnormalities among the five tubular markers (fractional excretion of phosphate, fractional excretion of uric acid, β2 microglobulinuria, N-acetyl-β-D-glucosaminidase, nondiabetic glycosuria)...
January 14, 2018: AIDS
https://www.readbyqxmd.com/read/28954230/fumarate-hydratase-deletion-in-pancreatic-%C3%AE-cells-leads-to-progressive-diabetes
#15
Julie Adam, Reshma Ramracheya, Margarita V Chibalina, Nicola Ternette, Alexander Hamilton, Andrei I Tarasov, Quan Zhang, Eduardo Rebelato, Nils J G Rorsman, Rafael Martín-Del-Río, Amy Lewis, Gizem Özkan, Hyun Woong Do, Peter Spégel, Kaori Saitoh, Keiko Kato, Kaori Igarashi, Benedikt M Kessler, Christopher W Pugh, Jorge Tamarit-Rodriguez, Hindrik Mulder, Anne Clark, Norma Frizzell, Tomoyoshi Soga, Frances M Ashcroft, Andrew Silver, Patrick J Pollard, Patrik Rorsman
We explored the role of the Krebs cycle enzyme fumarate hydratase (FH) in glucose-stimulated insulin secretion (GSIS). Mice lacking Fh1 in pancreatic β cells (Fh1βKO mice) appear normal for 6-8 weeks but then develop progressive glucose intolerance and diabetes. Glucose tolerance is rescued by expression of mitochondrial or cytosolic FH but not by deletion of Hif1α or Nrf2. Progressive hyperglycemia in Fh1βKO mice led to dysregulated metabolism in β cells, a decrease in glucose-induced ATP production, electrical activity, cytoplasmic [Ca(2+)]i elevation, and GSIS...
September 26, 2017: Cell Reports
https://www.readbyqxmd.com/read/28770596/high-rates-of-viral-suppression-in-adults-and-children-with-high-cd4-counts-using-a-streamlined-art-delivery-model-in-the-search-trial-in-rural-uganda-and-kenya
#16
RANDOMIZED CONTROLLED TRIAL
Dalsone Kwarisiima, Moses R Kamya, Asiphas Owaraganise, Florence Mwangwa, Dathan M Byonanebye, James Ayieko, Albert Plenty, Doug Black, Tamara D Clark, Bridget Nzarubara, Katherine Snyman, Lillian Brown, Elizabeth Bukusi, Craig R Cohen, Elvin H Geng, Edwin D Charlebois, Theodore D Ruel, Maya L Petersen, Diane Havlir, Vivek Jain
INTRODUCTION: The 2015 WHO recommendation of antiretroviral therapy (ART) for all HIV-positive persons calls for treatment initiation in millions of persons newly eligible with high CD4+ counts. Efficient and effective care models are urgently needed for this population. We evaluated clinical outcomes of asymptomatic HIV-positive adults and children starting ART with high CD4+ counts using a novel streamlined care model in rural Uganda and Kenya. METHODS: In the 16 intervention communities of the HIV test-and-treat Sustainable East Africa Research for Community Health Study (NCT01864603), all HIV-positive individuals irrespective of CD4 were offered ART (efavirenz [EFV]/tenofovir disoproxil fumarate + emtricitabine (FTC) or lamivudine (3TC)...
July 21, 2017: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/28764611/incidence-of-renal-fanconi-syndrome-in-patients-taking-antiretroviral-therapy-including-tenofovir-disoproxil-fumarate
#17
Nicholas A Medland, Eric Pf Chow, Rowan G Walker, Marcus Chen, Tim Rh Read, Christopher K Fairley
The objective of this study was to determine the incidence and predictors of Fanconi Syndrome (FS) in a cohort of patients taking tenofovir disoproxil fumarate (TDF). Clinical records and laboratory investigations from patients receiving TDF between 2002 and 2016 were extracted. FS was defined as normoglycaemic glycosuria and proteinuria and at least one other marker of renal dysfunction. Regression analysis was performed with time to development of FS and the following covariates: ritonavir co-administration, age, gender, co-morbidities (hypertension, hyperlipidaemia, diabetes, viral hepatitis), CD4 cell count nadir and baseline eGFR...
March 2018: International Journal of STD & AIDS
https://www.readbyqxmd.com/read/28707319/tenofovir-disoproxil-fumarate-significantly-decreases-serum-lipoprotein-levels-compared-with-entecavir-nucleos-t-ide-analogue-therapy-in-chronic-hepatitis-b-carriers
#18
COMPARATIVE STUDY
A A Shaheen, M AlMattooq, S Yazdanfar, K W Burak, M G Swain, S E Congly, M A Borman, S S Lee, R P Myers, C S Coffin
BACKGROUND: Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are first-line treatments for chronic hepatitis B (CHB). Studies suggest lipid lowering effect of TDF in human immunodeficiency virus positive (HIV+) individuals, but the effect on lipids and cardiovascular disease (CVD) risk in CHB is unknown. AIM: To compare TDF vs ETV effects on lipid levels in CHB. METHODS: In this retrospective cohort study, data on serum lipids and CVD risk factors at baseline and ~1 year on TDF or ETV were collected from CHB carriers...
September 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28465407/role-of-nrf2-signaling-in-the-regulation-of-vascular-bk-channel-%C3%AE-1-subunit-expression-and-bk-channel-function-in-high-fat-diet-induced-diabetic-mice
#19
Tong Lu, Xiaojing Sun, Yong Li, Qiang Chai, Xiao-Li Wang, Hon-Chi Lee
The large conductance Ca2+ -activated K+ (BK) channel β1-subunit (BK-β1) is a key modulator of BK channel electrophysiology and the downregulation of BK-β1 protein expression in vascular smooth muscle cells (SMCs) underlies diabetic vascular dysfunction. In this study, we hypothesized that the nuclear factor erythroid-2-related factor 2 (Nrf2) signaling pathway plays a significant role in the regulation of coronary BK channel function and vasodilation in high-fat diet (HFD)-induced obese/diabetic mice. We found that the protein expressions of BK-β1 and Nrf2 were markedly downregulated, whereas those of the nuclear factor-κB (NF-κB) and the muscle ring finger protein 1 (MuRF1 [a ubiquitin E3 ligase for BK-β1]) were significantly upregulated in HFD mouse arteries...
October 2017: Diabetes
https://www.readbyqxmd.com/read/28429615/regulation-of-vascular-large-conductance-calcium-activated-potassium-channels-by-nrf2-signalling
#20
Yong Li, Xiao-Li Wang, Xiaojing Sun, Qiang Chai, Jingchao Li, Benjamin Thompson, Win-Kuang Shen, Tong Lu, Hon-Chi Lee
BK channels are major ionic determinants of vasodilation. BK channel function is impaired in diabetic vessels due to accelerated proteolysis of its beta-1 (BK-β1) subunits in response to increased oxidative stress. The nuclear factor E2-related factor-2 (Nrf2) signalling pathway has emerged as a master regulator of cellular redox status, and we hypothesized that it plays a central role in regulating BK channel function in diabetic vessels. We found that Nrf2 expression was markedly reduced in db/db diabetic mouse aortas, and this was associated with significant downregulation of BK-β1...
July 2017: Diabetes & Vascular Disease Research
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