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T Herta, U Beuers
BACKGROUND: Immune-mediated cholangiopathies comprise primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and IgG4-associated cholangitis (IAC). A common feature is the progressive destruction of bile ducts leading to cholestasis with fibrosis and cirrhosis of the liver over time. The diseases are mostly identified during routine laboratory testing. Clinical signs and symptoms such as pruritus, fatigue or jaundice are infrequent in the early stage. DIAGNOSIS: The diagnostic work-up involves the patient's history, physical examination, serological tests, abdominal ultrasonography, magnetic resonance cholangiopancreatography (MRCP) and, where necessary, liver biopsy and genetic testing...
March 15, 2019: Der Radiologe
Hye-Ri Kang, Lauren Waskowicz, Andrea M Seifts, Dustin J Landau, Sarah P Young, Dwight D Koeberl
Glycogen storage disease type Ia (GSD Ia) is a rare inherited disease caused by mutations in the glucose-6-phosphatase (G6Pase) catalytic subunit gene ( G6PC ). Absence of G6Pase causes life-threatening hypoglycemia and long-term complications because of the accumulations of metabolic intermediates. Bezafibrate, a pan-peroxisome proliferator-activated receptor (PPAR) agonist, was administered in the context of genome editing with a zinc-finger nuclease-containing vector (AAV-ZFN) and a G6Pase donor vector (AAV-RoG6P)...
June 14, 2019: Molecular Therapy. Methods & Clinical Development
Nevton Teixeira da Rosa-Junior, Belisa Parmeggiani, Mateus Struecker da Rosa, Nícolas Manzke Glänzel, Leonardo de Moura Alvorcem, Moacir Wajner, Guilhian Leipnitz
3-Methylglutaric acid (MGA) is an organic acid that accumulates in 3-methylglutaconic (MGTA) and 3-hydroxy-3-methylglutaric (HMGA) acidurias. Patients affected by these disorders present with neurological dysfunction that usually appears in the first years of life. In order to elucidate the pathomechanisms underlying the brain injury in these disorders, we evaluated the effects of MGA administration on redox homeostasis, mitochondrial respiratory chain activity, and biogenesis in the cerebral cortex of developing rats...
March 9, 2019: Neurotoxicity Research
Ana M Gorito, Ana R Ribeiro, Carlos Rocha Gomes, C Marisa R Almeida, Adrián M T Silva
The presence of organic micropollutants (MPs) in the aquatic environment is strongly related to their difficult elimination by conventional water and wastewater treatment processes. Therefore, alternative treatment technologies are required to overcome this problem. In this domain, constructed wetlands (CWs) have gained increasing attention in the last years, mainly due to the low-cost, simple operation/maintenance and environmental friendliness of these systems. However, studies on the application of CWs to remove MPs from freshwater aquaculture effluents are still scarce...
December 10, 2018: Science of the Total Environment
Akira Honda, Atsushi Tanaka, Tetsuji Kaneko, Atsumasa Komori, Masanori Abe, Mie Inao, Tadashi Namisaki, Naoaki Hashimoto, Kazuhito Kawata, Atsushi Takahashi, Masashi Ninomiya, Jong-Hon Kang, Mie Arakawa, Satoshi Yamagiwa, Satoru Joshita, Takeji Umemura, Ken Sato, Akira Kaneko, Kentaro Kikuchi, Jun Itakura, Takako Nomura, Keisuke Kakisaka, Hideki Fujii, Norifumi Kawada, Yasuhiro Takikawa, Tsutomu Masaki, Hiromasa Ohira, Satoshi Mochida, Hitoshi Yoshiji, Satoshi Iimuro, Yasushi Matsuzaki, Hajime Takikawa
In Japan, bezafibrate (BF) is a second-line agent for primary biliary cholangitis (PBC) that is refractory to ursodeoxycholic acid (UDCA) treatment. From a retrospective cohort (n=873) from the Japan PBC Study Group, we enrolled 118 patients who had received UDCA monotherapy for ≥1 year followed by combination therapy with UDCA+BF for ≥1 year. GLOBE and UK-PBC scores after UDCA monotherapy (that is, immediately before UDCA+BF combination therapy) were compared with those after 1 year of UDCA+BF combination therapy...
February 8, 2019: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Daniel S Pratt
The recently published BEZURSO trial (Corpechot C, Chazouilleres A, Rousseau A, et al. A placebo-controlled trial of bezafibrate in primary biliary cholangitis. NEJM 2018;378:2171-2181.) studied the role of bezafibrate, a peroxisome proliferator-activated receptor α (PPARα) agonist, in patients with primary biliary cholangitis (PBC) who failed to achieve a biochemical response with ursodeoxycholic acid (UDCA).1 The BEZURSO trial, a phase 3, double blind, placebo-controlled trial, randomized patients to receive 24 months of either bezafibrate, 400 mg a day, or placebo...
January 23, 2019: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Miri Lutski, Galit Weinstein, Uri Goldbourt, David Tanne
BACKGROUND: Lipid levels are associated with an increased risk of cardiovascular disease. OBJECTIVE: We investigated the association between plasma lipids, apolipoproteins levels, apolipoprotein B/low-density lipoprotein cholesterol (Apo-B/LDL-C), and Apo-B/Apo-A ratios and rate of cognitive decline two decades later in men with coronary heart disease (CHD). METHODS: A subset of 337 men (mean age at baseline 56.6±6.4 years) who previously participated in the Bezafibrate Infarction Prevention (BIP) trial (1990-1997) underwent cognitive evaluations 15±3 years (T1) and 19...
January 14, 2019: Journal of Alzheimer's Disease: JAD
Vanessa Kraege, Oriane Aebischer, Yaniv Chocron, Cédric Bongard, Virginie Moulin, Alexandra Schneider, Grégoire Humair, Émilie Solimando, Henri Lu, Olivier Lamy
2018 has continued to bring important progress in all areas of internal medicine, impacting our daily practice. From bezafibrate in primary biliary cholangitis to the new Clostridioides difficile guidelines, passing by use of procalcitonine, cristalloids, copeptin and how to administer furosemide, internal medicine journals are full of novelties. Every year, the chief residents of the CHUV internal medicine ward meet up to share their readings : here is their selection of 12 articles, chosen, summarized and commented for you...
January 9, 2019: Revue Médicale Suisse
F Javier Rivas, Rafael R Solís, Fernando J Beltrán, Olga Gimeno
This study investigates the efficacy of the system O3 /sunlight radiation compared to dark ozonation when treating pharmaceuticals compounds of different reactivity, namely bezafibrate, cotinine, and iopamidol. Results show the beneficial effects of simulated sunlight radiation (300-800 nm) when treating ozone recalcitrant compounds such as cotinine and iopamidol. The system O3 /sunlight radiation increased mineralization extent in all cases if compared to dark ozonation. Transformation products identified in individual runs suggest that amine oxidation and further alkyl chain attack is the main route of bezafibrate ozonation...
December 21, 2018: Water Research
Takashi Yamaguchi, Kohji Shirai, Daiji Nagayama, Shoko Nakamura, Rena Oka, Sho Tanaka, Yasuhiro Watanabe, Haruki Imamura, Yuta Sato, Hidetoshi Kawana, Masahiro Ohira, Atsuhito Saiki, Naomi Shimizu, Ichiro Tatsuno
AIM: Cardio-ankle vascular index (CAVI) reflects arterial stiffness and has been established as a useful surrogate marker of atherosclerosis. Contrary to the abundant data indicating slower progression of atherosclerosis with statins, studies on fibrates remain scarce. The aim of this study was thus to clarify the effect of bezafibrate on CAVI as well as on oxidative stress. METHODS: A randomized, open-label, controlled study was performed. 66 hypertriglyceridemic patients with type 2 diabetes were assigned to two groups: bezafibrate (400 mg/day) group and eicosapentaenoic acid (EPA 1...
December 22, 2018: Journal of Atherosclerosis and Thrombosis
Patrícia Duarte, C Marisa R Almeida, Joana P Fernandes, Daniela Morais, Marta Lino, Carlos R Gomes, Maria F Carvalho, Ana P Mucha
The present work aimed to explore the potential of autochthonous microorganisms from an urban estuary and from activated sludge of an associated wastewater treatment plant (WWTP), for biodegradation of an antidepressant drug, paroxetine, and on a cholesterol-lowering agent, bezafibrate. These compounds were chosen as representatives of extensively used pharmaceuticals. Autochthonous microorganisms from the indicated sources were exposed to the target pharmaceuticals (1 mg/L) in co-metabolism with sodium acetate (500 mg/L) along a two-weeks period, for a total of 7 two-weeks periods (here referred as cycles)...
November 20, 2018: Science of the Total Environment
Masahiko Gosho
Rhabdomyolysis is one of the most concerning complications of antidyslipidemic drugs. Most patients with dyslipidemia take multiple medications. Our objective was to explore which two-drug combinations lead to a higher risk of rhabdomyolysis. We analyzed data from the Japanese Adverse Drug Event Report (JADER) database between April 2004 and September 2017. The primary outcome was the report of rhabdomyolysis. We assessed the risk of rhabdomyolysis for the two-drug concomitant use of antidyslipidemic drugs (statin, fibrate, and ezetimibe) with antihypertensive and antidiabetic medications...
December 21, 2018: Fundamental & Clinical Pharmacology
Xu Han, Kentaro Nonaka, Hiroki Kato, Haruyoshi Yamaza, Hiroshi Sato, Takashi Kifune, Yuta Hirofuji, Keiji Masuda
Leigh syndrome is a highly heterogeneous condition caused by pathological mutations in either nuclear or mitochondrial DNA regions encoding molecules involved in mitochondrial oxidative phosphorylation, in which many organs including the brain can be affected. Among these organs, a high incidence of poor bone health has been recognized in primary mitochondrial diseases including Leigh syndrome. However, the direct association between mitochondrial dysfunction and poor bone health has not been fully elucidated...
March 2019: Biochemistry and Biophysics Reports
Maiara Destro Inácio, Alex Rafacho, Nathália Aparecida de Paula Camaforte, Poliana Teixeira, Priscilla Maria Ponce Vareda, Natália Moretti Violato, José Roberto Bosqueiro
Objective: Fibrates are used as lipid-lowering drugs and are well tolerated as cotreatments when glucose metabolism disturbances are also present. Synthetic glucocorticoids (GCs) are diabetogenic drugs that cause dyslipidemia, dysglycemia, glucose intolerance, and insulin resistance when in excess. Thus, we aimed to describe the potential of bezafibrate in preventing or attenuating the adverse effects of GCs on glucose and lipid homeostasis. Methods: Male Wistar rats were treated with high-dose bezafibrate (300 mg/kg, body mass (b...
2018: International Journal of Endocrinology
Miaozhen Pan, Shiming Jiao, Peter S Reinach, Jiaofeng Yan, Yanan Yang, Qihang Li, Nethrajeith Srinivasalu, Jia Qu, Xiangtian Zhou
Purpose: To determine if drug-induced peroxisome proliferator-activated receptor α (PPARα) signal pathway modulation affects refractive development and myopia in guinea pigs. Methods: Pigmented guinea pigs were randomly divided into normal vision (unoccluded) and form deprivation myopia (FDM) groups. Each group received daily peribulbar injections of either a vehicle or (1) PPARα agonist, GW7647, clofibrate, or bezafibrate or (2) PPARα antagonist, GW6471, for 4 weeks...
December 3, 2018: Investigative Ophthalmology & Visual Science
Angela T S Wyse, Mateus Grings, Moacir Wajner, Guilhian Leipnitz
Sulfite oxidase (SO) deficiency is an autosomal recessive inherited neurometabolic disease caused by deficient activity of SO. It is biochemically characterized by tissue accumulation and high urinary excretion of sulfite, thiosulfate, and S-sulfocysteine. Severe neurological symptoms, including neonatal seizures, encephalopathy, and psychomotor retardation, are commonly observed in the affected patients, but the pathogenesis of the neurologic dysfunction is still poorly understood. In this minireview, we will briefly summarize the knowledge obtained from in vivo and in vitro findings from animal studies indicating that oxidative stress and mitochondrial dysfunction are involved in the pathophysiology of the brain damage in this disease...
December 5, 2018: Neurotoxicity Research
Kwangu M Kanama, Adegbenro P Daso, Lizzy Mpenyana-Monyatsi, Marthie A A Coetzee
The presence of 17 pharmaceutical and personal care products (PPCPs) belonging to various therapeutic categories was investigated in two hospital wastewater treatment plants (WWTPs) in North West Province, South Africa. The compounds were extracted from wastewater samples by solid-phase extraction and analysed by liquid chromatography-tandem mass spectrometry. The results showed that ofloxacin, chloramphenicol, and bezafibrate were generally below the limit of quantification (LOQ) in the analysed samples. Acetaminophen and ibuprofen were the dominant pharmaceuticals in the influent streams with corresponding concentrations ranging from 21 to 119 μ g/L and 0...
2018: Journal of Toxicology
Li-Fang Feng, Xiao-Hong Chen, Dong-Xiao Li, Xi-Yuan Li, Jin-Qing Song, Ying Jin, Yan-Ling Yang
A boy aged 6 years and 3 months developed upper respiratory tract infection and pyrexia 2 months ago and was given oral administration of nimesulide by his parents according to directions. Half an hour later, the boy experienced convulsions and cardiopulmonary arrest, and emergency examination found hypoketotic hypoglycemia, metabolic acidosis, significant increases in serum aminotransferases and creatine kinase, and renal damage. Recovery of consciousness and vital signs was achieved after cardiopulmonary resuscitation, but severe mental and movement regression was observed...
November 2018: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
Kenji Yamada, Takeshi Taketani
Mitochondrial fatty acid oxidation disorders (FAODs) are caused by defects in β-oxidation enzymes, including very long-chain acyl-CoA dehydrogenase (VLCAD), trifunctional protein (TFP), carnitine palmitoyltransferase-2 (CPT2), carnitine-acylcarnitine translocase (CACT) and others. During prolonged fasting, infection, or exercise, patients with FAODs present with hypoglycemia, rhabdomyolysis, cardiomyopathy, liver dysfunction, and occasionally sudden death. This article describes the diagnosis, newborn screening, and treatment of long-chain FAODs with a focus on VLCAD deficiency...
November 6, 2018: Journal of Human Genetics
Zaza Khuchua, Aleksandr I Glukhov, Arnold W Strauss, Sabzali Javadov
Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that bind to DNA and regulate transcription of genes involved in lipid and glucose metabolism. A growing number of studies provide strong evidence that PPARs are the promising pharmacological targets for therapeutic intervention in various diseases including cardiovascular disorders caused by compromised energy metabolism. PPAR agonists have been widely used for decades as lipid-lowering and anti-inflammatory drugs. Existing studies are mainly focused on the anti-atherosclerotic effects of PPAR agonists; however, their role in the maintenance of cellular bioenergetics remains unclear...
November 4, 2018: International Journal of Molecular Sciences
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