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Fumarate diabetes

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...
February 7, 2018: Multiple Sclerosis and related Disorders
Neha Singh, Sheekha Vijayanti, Lekha Saha
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 15, 2018: International Journal of Neuroscience
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)
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...
February 2, 2018: Toxicology Letters
Mohammad Alsady, Theun de Groot, Marleen Louise Adriënne 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 is 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. Earlier, we have shown 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...
October 25, 2017: American Journal of Physiology. Renal Physiology
Takeshi Nishijima, Yoshikazu Mutoh, Yohei Kawasaki, Kiyomi Tomonari, Yoshimi Kikuchi, Hiroyuki Gatanaga, Shinichi Oka
OBJECTIVE: 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, non-diabetic glycosuria)...
October 12, 2017: AIDS
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
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
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...
January 1, 2017: International Journal of STD & AIDS
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
Tong Lu, Xiaojing Sun, Yong Li, Qiang Chai, Xiao-Li Wang, Hon-Chi Lee
The large conductance Ca(2+)-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...
October 2017: Diabetes
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
Latt S Mansor, Maria da Luz Sousa Fialho, Georgina Yea, Will A Coumans, James A West, Matthew Kerr, Carolyn A Carr, Joost J F P Luiken, Jan F C Glatz, Rhys D Evans, Julian L Griffin, Damian J Tyler, Kieran Clarke, Lisa C Heather
Aims: The type 2 diabetic heart oxidizes more fat and less glucose, which can impair metabolic flexibility and function. Increased sarcolemmal fatty acid translocase (FAT/CD36) imports more fatty acid into the diabetic myocardium, feeding increased fatty acid oxidation and elevated lipid deposition. Unlike other metabolic modulators that target mitochondrial fatty acid oxidation, we proposed that pharmacologically inhibiting fatty acid uptake, as the primary step in the pathway, would provide an alternative mechanism to rebalance metabolism and prevent lipid accumulation following hypoxic stress...
June 1, 2017: Cardiovascular Research
Allison M Manuel, Michael D Walla, Adam Faccenda, Stephanie L Martin, Ross M Tanis, Gerardo G Piroli, Julie Adam, Boris Kantor, Bulent Mutus, Danyelle M Townsend, Norma Frizzell
AIMS: Protein succination by fumarate increases in the adipose tissue of diabetic mice and in adipocytes matured in high glucose as a result of glucotoxicity-driven mitochondrial stress. The endoplasmic reticulum (ER) oxidoreductase protein disulfide isomerase (PDI) is succinated in adipocytes that are matured in high glucose, and in this study we investigated whether succination would alter PDI oxidoreductase activity, directly linking mitochondrial stress and ER stress. RESULTS: Protein succination and the ER stress marker C/EBP homologous protein (CHOP) were diminished after pharmaceutical targeting of mitochondrial stress with the chemical uncoupler niclosamide in adipocytes matured in high-glucose concentrations...
December 1, 2017: Antioxidants & Redox Signaling
Melanie Peckruhn, Jörg Tittelbach, Peter Elsner
Necrobiosis lipoidica (NL) is a rare granulomatous disease of hitherto unclear etiology frequently seen in patients with diabetes. Characterized by its potential for ulcerations, it often presents a serious burden for those affected. There are currently neither German nor European guidelines for the treatment of NL. At the same time, standard treatment with topical or intralesional corticosteroids does not always show satisfactory results. We therefore set out to evaluate whether the various treatment regimens published since 2000 have actually expanded the therapeutic armamentarium in a relevant manner...
February 2017: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
Kerry M Sheets, Mohamed G Atta, Derek M Fine, Katie Zook, Allison M Mcfall, Michelle M Estrella, George J Schwartz, Gregory M Lucas
BACKGROUND: Proximal tubular dysfunction (PTD) is common in HIV-positive persons and has been associated with tenofovir disoproxil fumarate (TDF). However, few studies have assessed the natural history PTD in HIV-positive and -negative individuals, or the association of PTD with the subsequent trajectory of directly measured glomerular filtration rate (mGFR). METHODS: We followed 192 HIV-positive and 100 HIV-negative, nondiabetic participants for 3 years. We measured 3 PTD markers (normoglycemic glycosuria, fractional excretion of phosphorus, and tubular proteinuria) and mGFR (by iohexol disappearance from serum) annually...
May 1, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Hyo Jun Ahn, Myeong Jun Song, Jeong Won Jang, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon
BACKGROUND & AIMS: We evaluated the efficacy and safety of Tenofovir disoproxil fumarate (TDF)-based therapy in naïve and treatment-experienced chronic hepatitis B (CHB) patients for 96 weeks in Korean real life practice. METHODS: A total of 209 CHB patients with a prescription for TDF at the Seoul and Daejeon St. Mary's hospitals were enrolled from December 2012 to October 2014. We compared the virological responses and evaluated the renal safety of treatment-naive and treatment-experienced patients...
2017: PloS One
Antonio Anax F de Oliveira, Tiago F de Oliveira, Larissa L Bobadilla, Camila C M Garcia, Carolina Maria Berra, Nadja C de Souza-Pinto, Marisa H G Medeiros, Paolo Di Mascio, Roberto Zatz, Ana Paula de M Loureiro
The occurrence of biochemical alterations that last for a long period of time in diabetic individuals even after adequate handling of glycemia is an intriguing phenomenon named metabolic memory. In this study, we show that a kidney pathway is gradually altered during the course of diabetes and remains persistently changed after late glycemic control in streptozotocin-induced diabetic rats. This pathway comprises an early decline of uric acid clearance and pAMPK expression followed by fumarate accumulation, increased TGF-β expression, reduced PGC-1α expression, and downregulation of methylation and hydroxymethylation of mitochondrial DNA...
January 12, 2017: Scientific Reports
Luiz Roberto Ramos, Noemia Urruth Leão Tavares, Andréa Dâmaso Bertoldi, Mareni Rocha Farias, Maria Auxiliadora Oliveira, Vera Lucia Luiza, Tatiane da Silva Dal Pizzol, Paulo Sérgio Dourado Arrais, Sotero Serrate Mengue
OBJECTIVE: To analyze variations in the prevalence of chronic use of medicines by older adults in Brazil according to its possible association with the most prevalent chronic diseases and demographic and health factors, and to identify risk factors for polypharmacy. METHODS: A study based on data from the National Survey on Access, Use and Promotion of Rational Use of Medicines (PNAUM), a cross-sectional, population-based survey with probability sampling in Brazilian urban areas...
December 2016: Revista de Saúde Pública
S Gibiino, A Trappoli, B Balzarro, A R Atti, D De Ronchi
A 71-year-old man developed coma with severe respiratory failure, hypotension, and tachycardia induced by the intentional ingestion of quetiapine fumarate extended release (XR) 20 g. At the time, he had been treated for bipolar depression with venlafaxine 75 mg/day, lamotrigine 100 mg/day, pregabalin 75 mg/day, and quetiapine XR 400 mg/day for approximately 1 year. Comorbidities were hypertension treated with metoprolol, diabetes mellitus type 2 treated with metformin, and benign prostatic hyperplasia treated with silodosin...
December 2015: Drug Safety—Case Reports
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