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Drug metabolism

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https://www.readbyqxmd.com/read/28441724/multiple-udp-glucuronosyltransferase-and-sulfotransferase-enzymes-are-responsible-for-the-metabolism-of-verproside-in-human-liver-preparations
#1
Ju-Hyun Kim, Deok-Kyu Hwang, Ju-Yeon Moon, Yongnam Lee, Ji Seok Yoo, Dae Hee Shin, Hye Suk Lee
Verproside, an active iridoid glycoside component of Veronica species, such as Pseudolysimachion rotundum var. subintegrum and Veronica anagallis-aquatica, possesses anti-asthma, anti-inflammatory, anti-nociceptive, antioxidant, and cytostatic activities. Verproside is metabolized into nine metabolites in human hepatocytes: verproside glucuronides (M1, M2) via glucuronidation, verproside sulfate (M3) via sulfation, picroside II (M4) and isovanilloylcatalpol (M5) via O-methylation, M4 glucuronide (M6) and M4 sulfate (M8) via further glucuronidation and sulfation of M4, and M5 glucuronide (M7) and M5 sulfate (M9) via further glucuronidation and sulfation of M5...
April 22, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28441491/a-naturally-occurring-isoform-specific-probe-for-highly-selective-and-sensitive-detection-of-human-cytochrome-p450-3a5
#2
Jing-Jing Wu, Yun-Feng Cao, Liang Feng, Yu-Qi He, James Y Hong, Tong-Yi Dou, Ping Wang, Da-Cheng Hao, Guang-Bo Ge, Ling Yang
Cytochrome P450 (CYP) 3A5 characterized with polymorphic and extensive expression in multiple tissues is the most important P450 enzyme among the minor CYP3A isoforms. However, a selective and sensitive probe for CYP3A5 remains unavailable. In this study, we identified and characterized a naturally-occurring lignan 12 (Schisantherin E) as an isoform-specific probe for selective detection of CYP3A5 activity in complex biological samples. With thorough characterization including LC-MS and NMR, we found that 12 can be metabolized by CYP3A5 to generate a major metabolite 2-O-demethylated 12...
April 25, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28441462/transcriptomic-profiling-of-a-chicken-lung-epithelial-cell-line-clec213-reveals-a-mitochondrial-respiratory-chain-activity-boost-during-influenza-virus-infection
#3
Léa Meyer, Olivier Leymarie, Christophe Chevalier, Evelyne Esnault, Marco Moroldo, Bruno Da Costa, Sonia Georgeault, Philippe Roingeard, Bernard Delmas, Pascale Quéré, Ronan Le Goffic
Avian Influenza virus (AIV) is a major concern for the global poultry industry. Since 2012, several countries have reported AIV outbreaks among domestic poultry. These outbreaks had tremendous impact on poultry production and socio-economic repercussion on farmers. In addition, the constant emergence of highly pathogenic AIV also poses a significant risk to human health. In this study, we used a chicken lung epithelial cell line (CLEC213) to gain a better understanding of the molecular consequences of low pathogenic AIV infection in their natural host...
2017: PloS One
https://www.readbyqxmd.com/read/28440988/-how-safe-is-the-recombinant-human-growth-hormone
#4
Raúl Calzada-León
In this paper, several aspects related to the safety of the use of biosynthetic human growth hormone are reviewed. For example, its classification as a biosynthetic drug, the phases that need to be performed in Mexico to verify its safety (obtaining, purification, preclinical studies, clinical trials, and finally observational clinical studies), as well as the evidence that exists in relation to the association of intracranial hypertension, muscular events, scoliosis, slipped capital femoral epiphysis, obstructive sleep apnea, pancreatitis, alterations in cortisol, thyroid hormones alterations, cardiovascular disease, metabolic risk, mortality and cancer, adverse events not related to its use, and finally dosing and safety...
May 2017: Revista Médica del Instituto Mexicano del Seguro Social
https://www.readbyqxmd.com/read/28440827/molecular-dynamics-investigations-of-membrane-bound-cyp2c19-polymorphisms-reveal-distinct-mechanisms-for-peripheral-variants-by-long-range-effects-on-the-enzymatic-activity
#5
Ying-Lu Cui, Rong-Ling Wu
Increasing sophistication in methods used to account for human polymorphisms in susceptibility to drug metabolism has been one of the success stories in the prevention of adverse drug reactions. Genetic polymorphisms in drug-metabolizing enzymes can affect enzyme activity and cause differences in treatment response or drug toxicity. CYP2C19 is one of the most highly polymorphic CYP enzymes and acts on 10-15% of drugs in current clinical use. Despite the number of experimental analyses carried out for this system, the detailed structural basis for altered catalytic properties of polymorphic CYP2C19 variants remains unexplained at the atomic level...
April 25, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28440782/systematization-of-clinical-trials-related-to-treatment-of-metabolic-syndrome-1980-2015
#6
Santiago Cardona Velásquez, Laura Guzmán Vivares, Jaiberth Antonio Cardona-Arias
INTRODUCTION: Despite the clinical, epidemiological, and economic significance of metabolic syndrome, the profile of clinical trials on this disease is unknown. OBJECTIVE: To characterize the clinical trials related to treatment of metabolic syndrome during the 1980-2015 period. METHODS: Systematic review of the literature using an ex ante search protocol which followed the phases of the guide Preferred Reporting Items for Systematic Reviews and Meta-Analyses in four multidisciplinary databases with seven search strategies...
February 2017: Endocrinol Diabetes Nutr
https://www.readbyqxmd.com/read/28440768/clinical-and-metabolic-profile-of-patients-with-latent-autoimmune-diabetes-in-adults-in-specialized-care-in-madrid
#7
Alfonso Arranz Martín, Edurne Lecumberri Pascual, Miguel Ángel Brito Sanfiel, Víctor Andía Melero, Lia Nattero Chavez, Iván Sánchez López, Gloria Cánovas Molina, Francisco Arrieta Blanco, Noemí González Perez Del Villar
OBJECTIVE: To report the clinical characteristics of patients with latent autoimmune diabetes in adults (LADA), and to ascertain their metabolic control and associated chronic complications. METHODS: Patients with DM attending specialized medical care in Madrid who met the following criteria: age at diagnosis of DM >30years, initial insulin independence for at least 6months and positive GAD antibodies were enrolled. Clinical profiles, data on LADA diagnosis, associated autoimmunity, C-peptide levels, therapeutic regimen, metabolic control, and presence of chronic complications were analyzed...
January 2017: Endocrinol Diabetes Nutr
https://www.readbyqxmd.com/read/28440761/recommendations-on-the-effect-of-antidiabetic-drugs-in-bone
#8
Pedro Rozas-Moreno, Rebeca Reyes-García, Esteban Jódar-Gimeno, Mariela Varsavsky, Inés Luque-Fernández, María Cortés-Berdonces, Manuel Muñoz-Torres
OBJECTIVE: To provide recommendations on the effect of antidiabetic drugs on bone fragility to help select the most adequate antidiabetic treatment, especially in diabetic patients with high risk of fracture. PARTICIPANTS: Members of the Bone Metabolism Working Group of the Spanish Society of Endocrinology. METHODS: The GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) was used to establish both the strength of recommendations and the quality of evidence...
March 2017: Endocrinol Diabetes Nutr
https://www.readbyqxmd.com/read/28440570/mass-spectrometric-characterization-of-the-selective-androgen-receptor-modulator-sarm-yk-11-for-doping-control-purposes
#9
Mario Thevis, Thomas Piper, Josef Dib, Andreas Lagojda, Dirk Kuehne, Lars Packschies, Hans Geyer, Wilhelm Schaenzer
RATIONALE: Selective androgen receptor modulators (SARMs) represent an emerging class of therapeutics targeting inter alia conditions referred to as cachexia and sarcopenia. Due to their anabolic properties, the use of SARMs is prohibited in sports as regulated by the World Anti-Doping Agency (WADA), and doping control laboratories test for these anabolic agents in blood and urine. In order to accomplish and maintain comprehensive test methods, the characterization of new drug candidates is critical for efficient sports drug testing...
April 25, 2017: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/28440519/-prevention-diagnosis-and-treatment-of-perioperative-complications-of-bariatric-and-metabolic-surgery
#10
Haifu Wu, Ming Zhong, Di Zhou, Chenye Shi, Heng Jiao, Wei Wu, Xinxia Chang, Jing Cang, Hua Bian
Surgical operation in treating obesity and type 2 diabetes is popularizing rapidly in China. Correct prevention and recognition of perioperation-related operative complications is the premise of ensuring surgical safety. Familiar complications of the operation include deep venous thrombosis, pulmonary artery embolism, anastomotic bleeding, anastomotic fistula and marginal ulcer. The prevention of deep venous thrombosis is better than treatment. The concrete measures contain physical prophylaxis (graduated compression stocking and intermittent pneumatic compression leg sleeves) and drug prophylaxis (unfractionated heparin and low molecular heparin), and the treatment is mainly thrombolysis or operative thrombectomy...
April 25, 2017: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/28440517/-efficacy-and-future-of-endoscopic-bariatric-surgery-in-the-treatment-of-obesity-and-metabolic-diseases
#11
Shangjia Huang, Junchang Zhang, Zhiyong Dong, Cunchuan Wang
The emerging endoscopic technologies are proved to be effective treatments for obesity in selected patients and to offer the potential advantages of reduced invasiveness, reversibility and repeatability. From the view of operation principle, endoscopic technologies can be classified as restrictive procedure, malabsorption procedure and endoscopic revision of gastric bypass. Restrictive procedures include intragastric balloon, aspiration therapy, endoscopic sleeve gastroplasty (ESG) and transoral gastroplasty...
April 25, 2017: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/28440493/the-extracellular-signal-regulated-kinase-1-2-pathway-in-neurological-diseases-a-potential-therapeutic-target-review
#12
Jing Sun, Guangxian Nan
Signaling pathways are critical modulators of a variety of physiological and pathological processes, and the abnormal activation of some signaling pathways can contribute to disease progression in various conditions. As a result, signaling pathways have emerged as an important tool through which the occurrence and development of diseases can be studied, which may then lead to the development of novel drugs. Accumulating evidence supports a key role for extracellular signal-regulated kinase 1/2 (ERK1/2) signaling in the embryonic development of the central nervous system (CNS) and in the regulation of adult brain function...
April 21, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28440407/effects-of-cytochrome-p450-family-3-subfamily-a-member%C3%A2-5-gene-polymorphisms-on-daunorubicin-metabolism-and-adverse-reactions-in-patients-with-acute-leukemia
#13
Zhen Huang, Juxiang Wang, Jiangchao Qian, Yuan Li, Zhisheng Xu, Min Chen, Hongfei Tong
The present study aimed to investigate the association between the genetic polymorphism of cytochrome P450 family 3 subfamily A member 5 (CYP3A5) and the activity of CYP3A and plasma concentrations of daunorubicin (DNR) in patients with acute leukemia. A total of 36 children with newly diagnosed acute lymphoblastic leukemia were enrolled in the study. Polymerase chain reaction (PCR)‑restriction fragment length polymorphism and PCR product sequencing were used to detect the genotype of CYP3A5*3. PCR was then used to express the mRNA expression of CYP3A5...
April 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28440341/quantitative-profiling-of-the-ugt-transcriptome-in-human-drug-metabolizing-tissues
#14
A Tourancheau, M Rouleau, S Guauque-Olarte, L Villeneuve, I Gilbert, A Droit, C Guillemette
Alternative splicing as a mean to control gene expression and diversify function is suspected to considerably influence drug response and clearance. We report the quantitative expression profiles of the human UGT genes including alternatively spliced variants not previously annotated established by deep RNA-sequencing in tissues of pharmacological importance. We reveal a comprehensive quantification of the alternative UGT transcriptome that differ across tissues and among individuals. Alternative transcripts that comprise novel in-frame sequences associated or not with truncations of the 5'- and/or 3'- termini, significantly contribute to the total expression levels of each UGT1 and UGT2 gene averaging 21% in normal tissues, with expression of UGT2 variants surpassing those of UGT1...
April 25, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28440204/apixaban-metabolism-pharmacologic-properties-and-drug-interaction
#15
Peter Kubisz, Lucia Stanciakova, Miroslava Dobrotova, Matej Samos, Marian Mokan, Jan Stasko
BACKGROUND: Apixaban is an oral, potent, highly selective, reversible and direct inhibitor of activated coagulation factor X, that is the end point of the intrinsic and extrinsic coagulation pathway. Additionally, apixaban has the capacity to indirectly inhibit thrombin-induced platelet aggregation. This new oral anticoagulant represents an immediate-release form of peroral drug with quick dissolution, linear pharmacokinetics, good bioavailability and rapid onset and offset of action...
April 24, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28440197/hyperprolactinemia-induced-by-antipsychotics-from-diagnosis-to-treatment-approach
#16
Walter Milano, Chiara Colletti, Anna Capasso
Schizophrenia is one of the most severe psychiatric diseases with a significant impact on the psychosocial functioning of the patients. People with schizophrenia are at risk to die prematurely because of their illness with their poor lifestyle contributing to the excess morbidity and higher mortality rate. In particular, lifestyle (e.g. poor diet, low rates of physical activity and increased likelihood to smoke cigarettes) predisposes them to poor physical health and comorbid medical diseases. In addition, the treatment of schizophrenia usually involves the long-term administration of antipsychotic drugs and some of these medications are implicated in the increased risk of metabolic and cardiovascular effects...
April 23, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/28440185/a-therapeutic-potential-of-animal-%C3%AE-hairpin-antimicrobial-peptides
#17
Tatiana V Ovchinnikova, Pavel V Panteleev, Sergey V Balandin, Vadim T Ivanov
Endogenous antimicrobial peptides (AMPs) are evolutionary ancient molecular factors of innate immunity that play the key role in host defense. Because of the low resistance rate, AMPs have caught extensive attention as possible alternatives to conventional antibiotics. Over the last years, it has become evident that biological functions of AMPs are beyond direct killing of microbial cells. This review focuses on a relatively small family of animal host defense peptides with the β-hairpin structure stabilized by disulfide bridges...
April 24, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28439316/epigenetic-assays-for-chemical-biology-and-drug-discovery
#18
REVIEW
Sheraz Gul
The implication of epigenetic abnormalities in many diseases and the approval of a number of compounds that modulate specific epigenetic targets in a therapeutically relevant manner in cancer specifically confirms that some of these targets are druggable by small molecules. Furthermore, a number of compounds are currently in clinical trials for other diseases including cardiovascular, neurological and metabolic disorders. Despite these advances, the approved treatments for cancer only extend progression-free survival for a relatively short time and being associated with significant side effects...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28438933/pyrazinoic-acid-inhibits-a-bifunctional-enzyme-in-mycobacterium-tuberculosis
#19
Moses Njire, Na Wang, Bangxing Wang, Yaoju Tan, Xingshan Cai, Yanwen Liu, Julius Mugweru, Jintao Guo, H M Adnan Hameed, Shouyong Tan, Jianxiong Liu, Wing Wai Yew, Eric Nuermberger, Gyanu Lamichhane, Jinsong Liu, Tianyu Zhang
Pyrazinamide (PZA), an indispensable component of modern tuberculosis treatment, acts as a key sterilizing drug. While the mechanism of activation of this prodrug by Mycobacterium tuberculosis into pyrazinoic acid (POA) has been extensively studied, not all molecular determinants that confer resistance to this mysterious drug have been identified. Here, we report a new PZA resistance determinant: Asp67Asn substitution in Rv2783 confers M. tuberculosis resistance to PZA. Expression of the mutant but not the wild-type allele in M...
April 24, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28438758/diabetes-mellitus-and-acquired-haemophilia-new-association
#20
Carlos Tavares Bello, Yuliya Vasylenko, José Esteves, Carlos Augusto Vasconcelos
Diabetes mellitus encompasses a group of highly prevalent carbohydrate metabolic disorders with an increasing incidence. Some subtypes are thought to be associated with other immune-mediated diseases. Acquired haemophilia on the other hand is a quite rare autoimmune disease that is thought to be secondary to the emergence of inhibiting anticoagulation factor VIII antibodies (inhibitors) in patients with previously normal haemostatic function. More recently, numerous different diseases have been associated with acquired haemophilia namely immune-mediated diseases, drugs and solid and haematologic neoplasms...
April 24, 2017: BMJ Case Reports
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