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Fumarate diabetes

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
Hao Yang, Jiang W Wu, Shu P Wang, Ilenia Severi, Loris Sartini, Norma Frizzell, Saverio Cinti, Gongshe Yang, Grant A Mitchell
Obesity and type 2 diabetes are associated with impaired mitochondrial function in adipose tissue. To study the effects of primary deficiency of mitochondrial energy metabolism in fat, we generated mice with adipose-specific deficiency of fumarate hydratase (FH), an integral Krebs cycle enzyme (AFHKO mice). AFHKO mice have severe ultrastructural abnormalities of mitochondria, ATP depletion in white adipose tissue (WAT) and brown adipose tissue, low WAT mass with small adipocytes, and impaired thermogenesis with large unilocular brown adipocytes...
November 2016: Diabetes
Bouchra Lify, G Dabo, O Nascimento, S Iraqui, S Elkhayat, M Zamd, G Medkouri, M Benghanem, B Ramdani, M M Sodqi, L Marih, A Chakib, K El FilaliMarhoum
Tenofovir disoproxil fumarate (TDF) is a nucleotide reverse transcriptase inhibitor discovered in the USA in 2001. It is currently the treatment of choice for patients co-infected with human immunodeficiency virus (HIV) and hepatitis B virus. Its antiretroviral efficacy and good tolerance are responsible for the higher frequency of prescriptions compared with other nucleoside analogs. However, it can induce acute renal toxicity causing impairment of the proximal tubular function of the kidney. This is highly dependent on factors such as associated co-prescription didanosine or a protease inhibitor "boosted" with ritonavir, preexisting renal insufficiency, low body weight, or presence of associated diabetes...
July 2016: Saudi Journal of Kidney Diseases and Transplantation
Amit C Achhra, Melinda Nugent, Amanda Mocroft, Lene Ryom, Christina M Wyatt
Chronic kidney disease (CKD) has emerged as an important health concern in HIV-positive individuals. Preventing long-term kidney toxicity from an antiretroviral therapy is therefore critical. Selected antiretroviral agents, especially tenofovir disoproxil fumarate (TDF) and some ritonavir-boosted protease inhibitors (PI/rs), have been associated with increased risk of CKD. However, the CKD risk attributable to these agents is overall small, especially in those with low baseline risk of CKD and normal renal function...
June 2016: Current HIV/AIDS Reports
Karl Swedberg, Jeffrey S Borer, Bertram Pitt, Stuart Pocock, Jean Rouleau
No abstract text is available yet for this article.
April 21, 2016: New England Journal of Medicine
John J V McMurray, Henry Krum, William T Abraham, Kenneth Dickstein, Lars V Køber, Akshay S Desai, Scott D Solomon, Nicola Greenlaw, M Atif Ali, Yanntong Chiang, Qing Shao, Georgia Tarnesby, Barry M Massie
BACKGROUND: Among patients with chronic heart failure, angiotensin-converting-enzyme (ACE) inhibitors reduce mortality and hospitalization, but the role of a renin inhibitor in such patients is unknown. We compared the ACE inhibitor enalapril with the renin inhibitor aliskiren (to test superiority or at least noninferiority) and with the combination of the two treatments (to test superiority) in patients with heart failure and a reduced ejection fraction. METHODS: After a single-blind run-in period, we assigned patients, in a double-blind fashion, to one of three groups: 2336 patients were assigned to receive enalapril at a dose of 5 or 10 mg twice daily, 2340 to receive aliskiren at a dose of 300 mg once daily, and 2340 to receive both treatments (combination therapy)...
April 21, 2016: New England Journal of Medicine
Mei Huang, Sabina Paglialunga, Julia M-K Wong, Monica Hoang, Renjitha Pillai, Jamie W Joseph
Type 2 diabetes is associated with impaired nutrient-regulated anaplerosis and insulin secretion in pancreatic β-cells. One key anaplerotic substrate that may be involved in regulating insulin release is α-ketoglutarate (αKG). Since prolyl hydroxylase domain proteins (PHDs) can metabolize cytosolic αKG, we sought to explore the role of this enzyme in the regulation of β-cell function. The oxygen-sensing PHDs regulate the stability of hypoxia-inducible factor 1α (HIF1α) as well as other proline-containing proteins by catalyzing the hydroxylation of proline residues...
March 2016: Physiological Reports
Paul Devakar Yesudian, Joyce Leman, Periasamy Balasubramaniam, Andy W Macfarlane, Firas Al-Niaimi, Christopher E M Griffiths, Arthur David Burden, Richard B Warren
BACKGROUND: Oral methotrexate (MTX) has been a first line systemic agent in the treatment of chronic plaque psoriasis (CPP) for more than 50 years. Parenteral MTX, administered as a subcutaneous (SC) injection has gained favour in recent years. The effectiveness of SC MTX has been proven in rheumatological conditions but there has been no assessment of its role in CPP. METHODS: We retrospectively reviewed case notes of 85 patients prescribed SC MTX for psoriasis in three dermatology centres in the UK (Betsi Cadwaladr University Health Board, Western Infirmary, Glasgow, and Salford Royal NHS Foundation Trust)...
March 2016: Journal of Drugs in Dermatology: JDD
Jasmine R Marcelin, Melody L Berg, Eugene M Tan, Hatem Amer, Nathan W Cummins, Stacey A Rizza
BACKGROUND: Risk factors for and optimal surveillance of renal dysfunction in patients on tenofovir disoproxil fumarate (TDF) remain unclear. We investigated whether a urine protein-osmolality (P/O) ratio would be associated with renal dysfunction in HIV-infected persons on TDF. METHODS: This retrospective, single-center study investigated the relationship between parameters of renal function (estimated glomerular filtration rate (eGFR) and P/O-ratio) and risk factors for development of kidney dysfunction...
2016: PloS One
Xiaoting Luo, Jinzi Wu, Siqun Jing, Liang-Jun Yan
Diabetes and its complications are caused by chronic glucotoxicity driven by persistent hyperglycemia. In this article, we review the mechanisms of diabetic glucotoxicity by focusing mainly on hyperglycemic stress and carbon stress. Mechanisms of hyperglycemic stress include reductive stress or pseudohypoxic stress caused by redox imbalance between NADH and NAD(+) driven by activation of both the polyol pathway and poly ADP ribose polymerase; the hexosamine pathway; the advanced glycation end products pathway; the protein kinase C activation pathway; and the enediol formation pathway...
January 2016: Aging and Disease
Hsin-Ming Wang, Chao-Hung Hung, Chuan-Mo Lee, Sheng-Nan Lu, Jing-Houng Wang, Yi-Hao Yen, Kwong-Ming Kee, Kuo-Chin Chang, Po-Lin Tseng, Tsung-Hui Hu, Chien-Hung Chen
BACKGROUND AND AIMS: This study compared the efficacy and safety of tenofovir disoproxil fumarate (TDF) up to 3 years of innucleos(t)ide analog (NA)-naïve and NA-experienced chronic hepatitis B (CHB) patients. METHODS: Tenofovir disoproxil fumarate-treated NA-naïve and NA-experienced CHB patients were retrospectively analyzed. RESULTS: After 3 years of TDF therapy, 97.7%, 71%, and 45.5% NA-naïve patients achieved a virological response, alanine aminotransferase normalization, and hepatitis B e antigen seroconversion, respectively...
July 2016: Journal of Gastroenterology and Hepatology
José L Casado, Sara Bañón, Carmen Santiuste, Jorge Serna, Paula Guzman, Maite Tenorio, Fernando Liaño, José M del Rey
OBJECTIVES: Patients receiving tenofovir, disoproxil, fumarate (TDF) had an increased prevalence of proximal renal tubular dysfunction (PRTD), but contributing factors and its clinical significance remain controversial. DESIGN AND METHODS: Cross-sectional evaluation of different urinary parameters (proteinuria, albuminuria, phosphaturia, uricosuria, glycosuria) in 200 HIV-infected patients receiving TDF, 26 following TDF discontinuation, and 22 never treated with TDF, included in a prospective cohort study...
January 2016: AIDS
Andrea Calcagno, Jessica Cusato, Letizia Marinaro, Marco Simiele, Manuela Lucchiari, Chiara Alcantarini, Maria C Tettoni, Laura Trentini, Giulio Mengozzi, Antonio D'Avolio, Giovanni Di Perri, Stefano Bonora
OBJECTIVE: To assess if tenofovir (TFV) clearance is associated with urinary retinal-binding protein (RBP) in HIV-positive patients with normal estimated filtration rate. DESIGN: A cross-sectional diagnostic study. METHODS: HIV-positive patients with estimated creatinine clearance above 60 ml/min, on tenofovir disoproxil fumarate (TDF)-containing combination since at least 6 months, taking TDF at night, and without significant comorbidities (diabetes, untreated hypertension, known renal malformations, recurrent nephrolithiasis) and nephrotoxic drugs were included...
March 27, 2016: AIDS
Gianluca Miglio, Alessandro Damiano Sabatino, Eleonora Veglia, Maria Teresa Giraudo, Marco Beccuti, Francesca Cordero
The adduction of fumaric acid to the sulfhydryl group of certain cysteine (Cys) residues in proteins via a Michael-like reaction leads to the formation of S-(2-succino)cysteine (2SC) sites. Although its role remains to be fully understood, this post-translational Cys modification (protein succination) has been implicated in the pathogenesis of diabetes/obesity and fumarate hydratase-related diseases. In this study, theoretical approaches to address sequence- and 3D-structure-based features possibly underlying the specificity of protein succination have been applied to perform the first analysis of the available data on the succinate proteome...
February 2016: Biochimica et Biophysica Acta
Sanjiv M Baxi, Rebecca Scherzer, Ruth M Greenblatt, Howard Minkoff, Anjali Sharma, Mardge Cohen, Mary A Young, Alison G Abraham, Michael G Shlipak
OBJECTIVE: Tenofovir disoproxil fumarate is a commonly used antiretroviral drug, but risk factors for tenofovir (TFV)-associated kidney disease are not fully understood. We used intensive pharmacokinetic studies in a cohort of HIV-infected women on TFV-based therapy to study the relationship between TFV exposure and subsequent kidney function. DESIGN: This is a nested study within the Women's Interagency HIV Study, a multicenter, prospective cohort of HIV-infected women...
February 20, 2016: AIDS
Yu-Shan Huang, Chieh-Kai Chan, Mao-Song Tsai, Kuan-Yeh Lee, Shu-Wen Lin, Sui-Yuan Chang, Chien-Ching Hung, Shan-Chwen Chang
BACKGROUND/PURPOSE: Tenofovir disoproxil fumarate (TDF) is associated with kidney tubular dysfunction, for which the risk may vary among patients of different ethnicities. Data are limited, however, on the association between renal function changes and TDF exposure in human immunodeficiency virus (HIV)-infected Taiwanese patients. METHODS: Medical records of HIV-infected Taiwanese patients seeking HIV care at a university hospital from 2011 to 2014 were reviewed...
September 9, 2015: Journal of Microbiology, Immunology, and Infection, Wei Mian Yu Gan Ran za Zhi
F Butsch, B Weidenthaler-Barth, E von Stebut
Granuloma annulare is a benign, chronic inflammatory skin disease. Its pathogenesis is still unclear, but reports on infections as a trigger can be found. In addition, some authors reported an association with other systemic disease, e.g., cancer, trauma, and diabetes mellitus; however, these have not been verified. The clinical picture of granuloma annulare ranges from the localized form predominantly at the extremities to disseminated, subcutaneous, or perforating forms. Diagnosis is based on the typical clinical presentation which may be confirmed by a biopsy...
November 2015: Der Hautarzt; Zeitschrift Für Dermatologie, Venerologie, und Verwandte Gebiete
Daniel A Enquobahrie, Marie Denis, Mahlet G Tadesse, Bizu Gelaye, Habtom W Ressom, Michelle A Williams
CONTEXT: Significant gaps remain in the understanding of genetic and environmental risk factors, as well as related mechanisms that contribute to gestational diabetes mellitus (GDM). OBJECTIVES: This study aimed to investigate early pregnancy maternal serum metabolites and subsequent risk of GDM. DESIGN: Information on participant characteristics and GDM diagnosis was collected using in-person interviews and medical record abstraction, respectively...
November 2015: Journal of Clinical Endocrinology and Metabolism
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