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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
G Klose, S Nitschmann
No abstract text is available yet for this article.
December 2018: Der Internist
Jacob Korula
No abstract text is available yet for this article.
October 16, 2018: Annals of Internal Medicine
Justyna Augustyniak, Jacek Lenart, Paweł Gaj, Monika Kolanowska, Krystian Jazdzewski, Piotr Pawel Stepien, Leonora Buzanska
Bezafibrate (BZ) regulates mitochondrial biogenesis by activation of PPAR's receptors and enhancing the level of PGC-1α coactivator. In this report, we investigated the effect of BZ on the expression of genes (1) that are linked to different pathways involved in mitochondrial biogenesis, e.g., regulated by PPAR's receptors or PGC-1α coactivator, and (2) involved in neuronal or astroglial fate, during neural differentiation of hiPSC. The tested cell populations included hiPSC-derived neural stem cells (NSC), early neural progenitors (eNP), and neural progenitors (NP)...
October 13, 2018: Molecular Neurobiology
Leire Mijangos, Haizea Ziarrusta, Oihana Ros, Leire Kortazar, Luis Angel Fernández, Maitane Olivares, Olatz Zuloaga, Ailette Prieto, Nestor Etxebarria
In this study, the spatial and temporal-distribution of 41-multiclass organic compounds were assessed in three estuaries of the Basque Country, from winter 2016 to winter 2017 by grab (active) sampling methods and an extra campaign combining both, grab and passive sampling methods. Wastewater treatment plant (WWTP) effluents were also evaluated to assess their impact on the estuaries. Moreover, the physicochemical features (phosphate and nitrate concentrations, pH, etc.) of each site were measured and included in the statistical analysis...
September 29, 2018: Water Research
Yen-Ping Lin, Ying-Lin Lee, Chien-Ya Hung, Chuan-Fa Chang, Yi Chen
Helium, a minor component of natural gas and radioactive minerals, is most commonly used as a carrier in gas chromatography-mass spectrometry (GC-MS). Its scarcity leads to limited availability and higher costs. In this experiment, hydrogen from a safe source of a hydrogen generator was tested as a substitutive carrier gas for the detection of adulterant in traditional Chinese medicine (TCM) and food supplements by GC-MS analysis. We found that the limits of detection (LODs) of using hydrogen were from 10 to 1000 μg/g...
2018: PloS One
Bernardo Duarte, Diogo Prata, Ana Rita Matos, Maria Teresa Cabrita, Isabel Caçador, João Carlos Marques, Henrique N Cabral, Patrick Reis-Santos, Vanessa F Fonseca
Pharmaceutical residues impose a new and emerging threat to the marine environment and its biota. In most countries, ecotoxicity tests are not required for all pharmaceutical residues classes and, even when mandatory, these tests are not performed using marine primary producers such as diatoms. These microalgae are among the most abundant class of primary producers in the marine realm and key players in the marine trophic web. Blood-lipid-lowering agents such as bezafibrate and its derivatives are among the most prescribed drugs and most frequently found human pharmaceuticals in aquatic environments...
February 10, 2019: Science of the Total Environment
Laura B Ferguson, Lingling Zhang, Shi Wang, Courtney Bridges, R Adron Harris, Igor Ponomarev
Peroxisome proliferator activated receptors (PPARs) are nuclear hormone receptors that act as transcription factors in response to endogenous lipid messengers. The fibrates and thiazolidinediones are synthetic PPAR agonists used clinically to treat dyslipidemia and Type 2 Diabetes Mellitus, respectively, but also improve symptoms of several other diseases. Transposable elements (TEs), repetitive sequences in mammalian genomes, are implicated in many of the same conditions for which PPAR agonists are therapeutic, including neurodegeneration, schizophrenia, and drug addiction...
2018: Frontiers in Molecular Neuroscience
Banzragchgarav Orkhon, Kyoko Kobayashi, Batkhuu Javzan, Kenroh Sasaki
Continuous estrogen stimulation in the uterus has been known to cause excess proliferation of the functional layer of endometrium, resulting in endometrial hyperplasia and leading to infertility. Estrogens can modulate other nuclear receptor signaling pathways, such as peroxisome proliferator‑activated receptors (PPARs). Astragalus root (AsR) has exhibited strong PPARα agonistic activity. Female Imprinting Control Region mice were fed a powder diet that included 5% AsR hot water extract or 0.1% bezafibrate as a positive control for 56 days to investigate AsR effects on the reproductive tract, ovary and uterus...
December 2018: Molecular Medicine Reports
Suhair H Jasim, Ghassan M Abu Sheikha, Haneen M Abuzaid, Tariq M Al-Qirim, Ghassan F Shattat, Dima A Sabbah, Samah A Ala, Mustafa S Aboumair, Kamal A Sweidan, Majdi M Bkhaitan
A new series of imidazole-5-carboxamide derivatives were prepared and tested for their anti-hyperlipidemic activity in Triton-WR-1339-induced hyperlipidemic Wistar rats. The purpose of this research was to improve benzophenone carboxamides water solubility maintaining at the same time the antihyperlipidemic activity. Compounds 4, 6, 10, and 11 were synthesized through a coupling reaction between imidazoles-5-carbonyl chloride and amino benzophenones. The tested animals (n=48) were divided into six groups: the first group (hyperlipidemic control group; HCG) received an intraperitoneal injection (i...
2018: Chemical & Pharmaceutical Bulletin
Lauren R Waskowicz, Jin Zhou, Dustin J Landau, Elizabeth D Brooks, Andrea Lim, Zollie A Yavarow, Tsubasa Kudo, Haoyue Zhang, Yajun Wu, Stuart Grant, Sarah P Young, Bay Boon Huat, Paul M Yen, Dwight D Koeberl
Glucose-6-phosphatase α (G6Pase) deficiency, also known as von Gierke's Disease or GSD Ia, is characterized by decreased ability of the liver to convert glucose-6-phosphate (G6P) to glucose leading to glycogen accumulation and hepatosteatosis. Long-term complications of GSD Ia include hepatic adenomas and carcinomas, in association with the suppression of autophagy in the liver. The G6pc-/- mouse and canine models for GSD Ia were treated with the pan-peroxisomal proliferator-activated receptor (PPAR) agonist, bezafibrate, to determine the drug's effect on liver metabolism and function...
September 25, 2018: Human Molecular Genetics
Andreas E Kremer, Aline Le Cleac'h, Sara Lemoinne, Katharina Wolf, Luc De Chaisemartin, Sylvie Chollet-Martin, Lydie Humbert, Dominique Rainteau, Raoul Poupon, Alexandra Rousseau, Olivier Chazouillères, Christophe Corpechot
No abstract text is available yet for this article.
September 18, 2018: Gut
Sho Tanaka, Takahiro Ueno, Akiko Tsunemi, Yoshihiro Nakamura, Hiroki Kobayashi, Yoshinari Hatanaka, Akira Haketa, Noboru Fukuda, Masayoshi Soma, Masanori Abe
A 40-year-old Japanese man presented with child-onset hypertriglyceridemia recently complicated by diabetes mellitus. The patient's diabetes mellitus was maintained, but he had persistent insulin resistance. The patient also had persistent severe hypertriglyceridemia (1,224-4,104 mg/dL), despite the administration of bezafibrate and ezetimibe. Type V dyslipidemia was revealed by agarose gel electrophoresis and the refrigerator test, and a significantly reduced post-heparin lipoprotein lipase mass of 26 ng/mL was confirmed...
September 12, 2018: Internal Medicine
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