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Metabolic side effects

Tristan Pascart, Frédéric Lioté
This review article summarizes the relevant English literature on gout from 2010 through April 2017. It emphasizes that the current epidemiology of gout indicates a rising prevalence worldwide, not only in Western countries but also in Southeast Asia, in close relationship with the obesity and metabolic syndrome epidemics. New pathogenic mechanisms of chronic hyperuricaemia focus on the gut (microbiota, ABCG2 expression) after the kidney. Cardiovascular and renal comorbidities are the key points to consider in terms of management...
March 13, 2018: Rheumatology
Carolina Ribeiro, Rosa Quinta, Ana Raposo, Ana Valentim, José Albuquerque, Manuela Grazina
Objective: Prospective observational study to analyze CYP2D6 pharmacogenetics in 55 Portuguese adult parturients undergoing elective cesarean section and to investigate the association between CYP2D6 alleles and pain score. Methods: DNA was extracted from peripheral blood by standard methods. Genetic analysis included allelic discrimination (CYP2D6*1, *2, *3, *4, *5, *6, *10, *17, and *41) and copy number determination with TaqMan probes by real-time polymerase chain reaction (PCR)...
March 12, 2018: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
Lu Xie, Wei Guo, Yi Yang, Tao Ji, Jie Xu
5,10-Methylenetrahydrofolate reductase (MTHFR), a key enzyme for folate metabolism, catalyses the irreversible conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, which is located at the end of the short arm (1p36.3). Two common non-synonymous variants, the C677T (Ala222Val) and A1298C (Glu429Ala), were mainly described with decreased enzymatic activity and an alteration of intracellular folate distribution. Osteosarcomas are currently treated with high dose of methotrexate (MTX). The decreased enzyme activity of MTHFR theoretically could increase the drug action of MTX and at the same time increase toxic and side effect...
February 20, 2018: Oncotarget
M G Carta, A Preti, H S Akiskal
Human population is increasing in immense cities with millions of inhabitants, in which life is expected to run 24 hours a day for seven days a week (24/7). Noise and light pollution are the most reported consequences, with a profound impact on sleep patterns and circadian biorhythms. Disruption of sleep and biorhythms has severe consequences on many metabolic pathways. Suppression of melatonin incretion at night and the subsequent effect on DNA methylation may increase the risk of prostate and breast cancer...
2018: Clinical Practice and Epidemiology in Mental Health: CP & EMH
Jie Zhu, Hao Chen, Zhixiu Song, Xudong Wang, Zhenshuang Sun
Objective: This article aims to assess the effects of ginger (Zingiber officinale Roscoe) on type 2 diabetes mellitus (T2DM) and/or components of the metabolic syndrome (MetS). Methods: Electronic literature was searched in PubMed, Embase, the Cochrane Library, Chinese Biomedical Database, China National Knowledge Infrastructure, and Wanfang Database from inception of the database to May 19, 2017, and supplemented by browsing reference lists of potentially eligible articles...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
Antonio A F De Salles, Daniel A N Barbosa, Fernando Fernandes, Julio Abucham, Debora M Nazato, Juliana D Oliveira, Abrão Cury, Alexandre Biasi, Ronaldo Rossi, Camila Lasagno, Priscila T Bueno, Renato H N Santos, Lucas P Damiani, Alessandra A Gorgulho
BACKGROUND: Human morbid obesity is increasing worldwide in an alarming way. The hypothalamus is known to mediate its mechanisms. Deep brain stimulation (DBS) of the ventromedial hypothalamus (VMH) may be an alternative to treat patients refractory to standard medical and surgical therapies. OBJECTIVE: To assess the safety, identify possible side effects, and to optimize stimulation parameters of continuous VMH-DBS. Additionally, this study aims to determine if continuous VMH-DBS will lead to weight loss by causing changes in body composition, basal metabolism, or food intake control...
March 12, 2018: Neurosurgery
Asuka Kikuchi, Fairuz Binti Mohammadi Nasir, Akie Inami, Attayeb Mohsen, Shoichi Watanuki, Masayasu Miyake, Kazuko Takeda, Daigo Koike, Takayasu Ito, Junpei Sasakawa, Rin Matsuda, Kotaro Hiraoka, Marcus Maurer, Kazuhiko Yanai, Hiroshi Watabe, Manabu Tashiro
OBJECTIVE: Antihistamines often have sedative side effects. This was the first study to measure regional cerebral glucose (energy) consumption and hemodynamic responses in young adults during cognitive tests after antihistamine administration. METHODS: In this double-blind, placebo-controlled, three-way crossover study, 18 healthy young Japanese men received single doses of levocetirizine 5 mg and diphenhydramine 50 mg at intervals of at least six days. Subjective feeling, task performances, and brain activity were evaluated during three cognitive tests (word fluency, two-back, and Stroop)...
March 13, 2018: Human Psychopharmacology
Z Hashemizadeh, S A Malek-Hosseini, P Badiee
Background: Patients with hepatic diseases are treated with numerous drugs metabolized by cytochrome P450. Objective: To evaluate the frequencies of CYP2C19 variant alleles (*2, *3, and *17), genotypes, and phenotypes, and the relationship between the frequency of these alleles and the underlying hepatic diseases among patients with advanced liver diseases who were candidates for liver transplantation. Methods: The Study was conducted on 120 patients suffering from various hepatic disorders, candidates for liver transplantation, and 52 healthy volunteers...
2018: International Journal of Organ Transplantation Medicine
Yoshiyuki Henning, Nella Mladěnková, Hynek Burda, Karol Szafranski, Sabine Begall
Mammals usually possess a majority of medium-wavelength sensitive (M-) and a minority of short-wavelength sensitive (S-) opsins in the retina, enabling dichromatic vision. Unexpectedly, subterranean rodents from the genus Fukomys exhibit an S-opsin majority, which is exceptional among mammals, albeit with no apparent adaptive value. Because thyroid hormones (THs) are pivotal for M-opsin expression and metabolic rate regulation, we have, for the first time, manipulated TH levels in the Ansell's mole-rat (Fukomys anselli) using osmotic pumps...
March 12, 2018: Scientific Reports
Faaiza Shahid, Zeba Farooqui, Farah Khan
Cisplatin (cis-diamminedichloroplatinum [II], CP) is most widely prescribed in chemotherapy and efficaciously treats diverse human cancers, with remission rates >90% in testicular cancers. However, clinical use of CP is associated with numerous untoward side effects, in particular, at the gastrointestinal level that reduces the therapeutic efficacy of CP and often results in withdrawal of its clinical usage in long term cancer chemotherapy. Substantial strides have been made to identify effective protective strategies against CP-induced nephrotoxicity, hepatotoxicity and ototoxicity...
March 9, 2018: European Journal of Pharmacology
Thomas Vorherr, Ian Lewis, Joerg Berghausen, Sandrine Desrayaud, Michael Schaefer
Recently, a variety of studies concerned with the permeability and oral bioavailability of cyclic peptides have been reported. In particular, strategies aiming at modifying peptides to maintain or to enhance solubility while enabling permeability constitute a significant challenge, but are of high interest to ensure a smooth drug discovery process. Current methodologies include N -methylation, matching of hydrogen bonding acceptors and donors across the macrocycle, and additional masking of polarity. In this study, we investigate further the pivotal effects of shielding on permeability and studied the metabolism of the corresponding peptides in more detail by comparing peptide concentrations in the portal versus the jugular vein in rats...
2018: International Journal of Peptide Research and Therapeutics
Jun Li, Hui-Chen Hsu, John D Mountz, John G Allen
Fucosylation is a biological process broadly observed in vertebrates, invertebrates, plants, bacteria, and fungi. Fucose moieties on cell-surface glycans are increasingly recognized as critical to many cell-cell interaction and signaling processes. One of the characteristic roles of fucose is its regulation of selectin-dependent leukocyte adhesion that has been well studied over the last two decades. Recent studies of fucose in immune cell development and function regulation have significantly expanded the contemporary understanding of fucosylation...
February 24, 2018: Cell Chemical Biology
Eric P Hoffman, Valerie Riddle, Maxime A Siegler, Daniel Dickerson, Miroslav Backonja, William G Kramer, Kanneboyina Nagaraju, Heather Gordish-Dressman, Jesse M Damsker, John M McCall
BACKGROUND: Glucocorticoid drugs are highly effective anti-inflammatory agents, but chronic use is associated with extensive pharmacodynamic safety concerns that have a considerable negative impact on patient quality of life. PURPOSE: Vamorolone (VBP15) is a first-in-class steroidal multi-functional drug that shows potent inhibition of pro-inflammatory NFkB pathways via high-affinity binding to the glucocorticoid receptor, high affinity antagonism for the mineralocorticoid receptor, and membrane stabilization properties...
March 7, 2018: Steroids
E Yu Bezsudnova, K M Boyko, V O Popov
Branched-chain amino acid aminotransferases (BCATs) catalyze reversible stereoselective transamination of branched-chain amino acids (BCAAs) L-leucine, L-isoleucine, and L-valine. BCATs are the key enzymes of BCAA metabolism in all organisms. The catalysis proceeds through the ping-pong mechanism with the assistance of the cofactor pyridoxal 5'-phosphate (PLP). BCATs differ from other (S)-selective transaminases (TAs) in 3D-structure and organization of the PLP-binding domain. Unlike other (S)-selective TAs, BCATs belong to the PLP fold type IV and are characterized by the proton transfer on the re-face of PLP, in contrast to the si-specificity of proton transfer in fold type I (S)-selective TAs...
December 2017: Biochemistry. Biokhimii︠a︡
Takayuki Amano, Tatsuki Fukami, Takuo Ogiso, Daisuke Hirose, Jeffrey P Jones, Tsuyoshi Taniguchi, Miki Nakajima
Dantrolene is used for malignant hyperthermia during anesthesia, and it sometimes causes severe liver injury as a side effect. Dantrolene is metabolized to acetylaminodantrolene, which is formed via the reduction of dantrolene to aminodantrolene and subsequent acetylation. Formation of hydroxylamine during the metabolic process may be associated with liver injury. We identified the enzymes responsible for dantrolene metabolism in humans to elucidate the mechanism of liver injury. Dantrolene reductase activity was not detected in human liver microsomes, but it was detected in cytosol...
March 6, 2018: Biochemical Pharmacology
Katarzyna Klysik, Aneta Pietraszek, Anna Karewicz, Maria Nowakowska
BACKGROUND: Herpes simplex (HSV) viruses are widely spread, highly contagious human pathogens. The statistics indicate that 50-90% of adults worldwide are seropositive for these viruses, mainly HSV-1 and HSV-2. The primary infection results in the appearance of watery blisters (cold sores) on the skin, lips, tongue, buccal mucosa or genitals. The ocular infection is the major cause of corneal blindness in the Western World. Once the HSV virus enters human body it cannot be completely eradicated because HSV viruses are able to change into their latent form which can survive the treatment...
March 8, 2018: Current Medicinal Chemistry
Oleg B Shevelev, Alisa A Seryapina, Evgenii L Zavjalov, Lyudmila A Gerlinskaya, Tatiana N Goryachkovskaya, Nikolay M Slynko, Leonid V Kuibida, Sergey E Peltek, Arcady L Markel, Mikhail P Moshkin
BACKGROUND: As the standard clinically used hypotensive medicines have many undesirable side effects, there is a need for new therapeutic agents, especially ones of a natural origin. PURPOSE: One possible candidate is extract from the mushroom Reishi (Ganoderma lucidum), which is used in the treatment and prevention of many chronic diseases. STUDY DESIGN AND METHODS: To study the effectiveness of Reishi, which grows in the Altai Mountains, as an antihypertensive agent, we intragastrically administered Reishi water extract to adult male hypertensive ISIAH (inherited stress-induced arterial hypertension) rats...
March 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Hoe-Yune Jung, Bobae Kim, Yosep Ji, Hye-Guk Ryu, Soyoung Park, Seung Hee Choi, In-Kyu Lee, Munki Kim, You Jeong Lee, Woojin Song, Young Hee Lee, Hyung Jin Choi, Chang-Kee Hyun, Wilhelm H Holzapfel, Kyong-Tai Kim
Although peroxisome proliferator-activated receptors (PPARs)α/γ dual agonists can be beneficial for treatment of dyslipidemia in patients with type 2 diabetes, their use is limited owing to various side effects, including body weight gain, edema, and heart failure. Here, we demonstrate that amodiaquine, an antimalarial agent, has potential as a PPARα/γ dual agonist with low risk of adverse effects. Amodiaquine selectively activated the transcriptional activities of PPARα/γ, and enhanced both fatty acid oxidation and glucose uptake without altering insulin secretion in vitro...
March 8, 2018: Diabetes, Obesity & Metabolism
Hana You, Louise-Laure Mariani, Graziella Mangone, Delphine Le Febvre de Nailly, Fanny Charbonnier-Beaupel, Jean-Christophe Corvol
There is currently no cure for Parkinson's disease. The symptomatic therapeutic strategy essentially relies on dopamine replacement whose efficacy was demonstrated more than 50 years ago following the introduction of the dopamine precursor, levodopa. The spectacular antiparkinsonian effect of levodopa is, however, balanced by major limitations including the occurrence of motor complications related to its particular pharmacokinetic and pharmacodynamic properties. Other therapeutic strategies have thus been developed to overcome these problems such as the use of dopamine receptor agonists, dopamine metabolism inhibitors and non-dopaminergic drugs...
March 7, 2018: Cell and Tissue Research
Roberto Bini, Osvaldo Chiara, Stefania Cimbanassi, Giorgio Olivero, Antonella Trombetta, Paolo Cotogni
Background: Hemorrhagic shock (HS) is a major threat to patients with trauma and spontaneous bleeding. The aim of the study was to investigate early effects of vasopressin on metabolic and hemodynamic parameters and endothelium permeability by measuring capillary leakage compared to those of other resuscitation strategies in a HS model. Methods: Forty-five Sprague-Dawley rats were randomized into five groups: S group ( n  = 5), sham-operated rats without shock or resuscitation; HS group ( n  = 10), HS and no resuscitation; RL group ( n  = 10), HS and resuscitation with Ringer's lactate (RL); RLB group ( n  = 10), HS and resuscitation with two-third shed blood plus RL; and vasopressin group ( n  = 10), HS and resuscitation with RL, followed by continuous infusion of 0...
2018: World Journal of Emergency Surgery: WJES
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