Read by QxMD icon Read


Hung-Pin Lin, Yu-Hsueh Wu, Julia Yu-Fong Chang, Yi-Ping Wang, Hsin-Ming Chen, Andy Sun
BACKGROUND/PURPOSE: Gastric parietal cell antibody (GPCA), thyroglobulin antibody (TGA), and thyroid microsomal antibody (TMA) were rarely examined in Behcet's disease (BD) patients. This study mainly assessed the frequencies of serum GPCA, TGA, and TMA positivities in 63 BD patients. METHODS: The frequencies of serum GPCA, TGA, and TMA positivities in 63 BD patients, 19 major-typed recurrent aphthous stomatitis (RAS)/BD (major RAS/BD) patients, 44 minor-typed RAS/BD (minor RAS/BD) patients, 520 RAS patients, and 126 healthy control subjects were calculated and compared...
March 14, 2018: Journal of the Formosan Medical Association, Taiwan Yi Zhi
Hwei-Ming Peng, Chase Barlow, Richard J Auchus
Unlike most of the drug-metabolizing cytochrome P450s, microsomal P450 17A1 and mitochondrial P450 11B2 catalyze sequential multi-step reactions in steroid biosynthesis. The membrane phospholipid composition might be one parameter that modulates the efficiency and processivity of specific pathways. Here we systematically examined the effects of physiologically relevant phospholipids on the catalysis of purified P450 17A1, P450 11B2, and P450 11B1 in reconstituted assay systems. Both dioleoylphosphatidylcholine (DOPC, 18:1) and dilauroylphosphatidylcholine (DLPC, 12:0) were found to be very efficient in reconstituting 17-hydroxylase and 17,20-lyase reactions of P450 17A1...
March 13, 2018: Journal of Steroid Biochemistry and Molecular Biology
Kazushi Yamamoto, Yui Iwagaki, Kouichi Watanabe, Tomonori Nochi, Hisashi Aso, Tsuyoshi Tsuduki
OBJECTIVES: We examined a moderate-fat (MF) diet that is enriched with fish oil (FO) and assessed whether lipid absorption was inhibited in senescence-accelerated prone mice (SAM-P8). METHODS: All mice (N = 70) were fed a normal diet that contained 4 g soybean oil/100 g of diet for 6 mo and then divided the mice into four groups (n = 10 or 20/group). Mice in the baseline group were euthanized at 6 mo old, those in the control group continued on a normal diet until 15 mo of age, those in the MF diet group switched to an MF diet (8 g soybean oil/100 g of diet) until 15 mo of age, and those in the MF + FO group switched to an MF diet that was enriched with FO (6...
December 2, 2017: Nutrition
Jared T Hammill, Deepak Bhasin, Daniel C Scott, Jaeki Min, Yizhe Chen, Yan Lu, Lei Yang, Ho Shin Kim, Michele C Connelly, Courtney Hammill, Gloria Holbrook, Cynthia Jeffries, Bhuvanesh Singh, Brenda A Schulman, R Kiplin Guy
We previously reported the discovery, validation, and structure-activity relationships of a series of piperidinyl ureas that potently inhibit the DCN1-UBE2M interaction. We demonstrated that compound 7 inhibits both the DCN1-UBE2M protein-protein interaction and DCN1-mediated cullin neddylation in biochemical assays and reduces levels of steady-state cullin neddylation in a squamous carcinoma cell line harboring DCN1 amplification. Although compound 7 exhibits good solubility and permeability, it is rapidly metabolized in microsomal models (CLint = 170 mL/min/kg)...
March 16, 2018: Journal of Medicinal Chemistry
Wenge Chen, Yunlong Cheng, Jianzhong Chen, Jiahang Chen, Kai Jiang, Yuyang Zhou, Lee Jia
Mifepristone (RU486) is developed originally as a contraceptive used by hundreds of millions of women world-wide, and also reported as a safe and long-term psychotic depressant, or as a cancer chemotherapeutic agent used by both sexes. In our preliminary study aimed at developing mifepristone as a cancer metastatic chemopreventive, we coincidentally observed that blood mifepristone concentrations in female rats seem to be higher than those in male ones post administration. To substantiate if the pharmacokinetic differences between sexes exist, we established a fast UPLC-MS/MS method to determine mifepristone concentrations in plasma, and analyzed blood concentrations of mifepristone over time in rats and dogs of both sexes...
March 8, 2018: Journal of Pharmaceutical and Biomedical Analysis
So-Young Kim, Drew R Jones, Ji-Yeon Kang, Chul-Ho Yun, Grover P Miller
Coumadin (R/S-warfarin) metabolism plays a critical role in patient response to anticoagulant therapy. Several cytochrome P450s oxidize warfarin into R/S-6-, 7-, 8-, 10, and 4'-hydroxywarfarin that can undergo subsequent glucuronidation by UDP-glucuronosyltransferases (UGTs); however, current studies on recombinant UGTs cannot be adequately extrapolated to microsomal glucuronidation capacities for the liver. Herein, we estimated the capacity of the average human liver to glucuronidate hydroxywarfarin and identified UGTs responsible for those metabolic reactions through inhibitor phenotyping...
March 15, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Fadzilah Adibah Abd Majid, Nur Syukriah Ab Rahman, Effendy Abd Wahid, Ain Nabihah Zainudin, Siti Nurazwa Zainol, Hassan Fahmi Ismail, Tet Soon Wong, K Vijaya Bhargava, Nirbhay Kumar Tiwari, Sanjeev Giri
Drug interaction of SynacinnTM polyherbal with known diabetic drugs is unknown. SynacinnTM contains standardized extracts of five herbal against gallic acid, curcumin, rosmarinic acid, catechin and andrographolide. SynacinnTM and its five standard markers were analysed for its possible interaction with CYP450 enzymes assay. This study was conducted using liquid chromatography-tandem mass spectroscopy (LC-MS/MS) using probe substrates using human liver microsomes against CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4(Midazolam) and CYP3A4 (Testosteron)...
March 13, 2018: Drug Metabolism Letters
Moayad Saad, Sebastiaan Bijttebier, An Matheeussen, Evy Verbueken, Casper Pype, Christophe Casteleyn, Chris Van Ginneken, Louis Maes, Paul Cos, Steven Van Cruchten
This article represents data regarding a study published in Toxicology in vitro entitled " in vitro CYP-mediated drug metabolism in the zebrafish (embryo) using human reference compounds" (Saad et al., 2017) [1]. Data were acquired with ultra-performance liquid chromatography - accurate mass mass spectrometry (UPLC-amMS). A full spectrum scan was conducted for the testosterone (TST) metabolites from the microsomal stability assay in zebrafish and humans. The microsomal proteins were extracted from adult zebrafish male (MLM) and female (FLM) livers, whole body homogenates of 96 h post fertilization larvae (EM) and a pool of human liver microsomes from 50 donors (HLM)...
February 2018: Data in Brief
Francisco Lopez-Tapia, Christine Brotherton-Pleiss, Peibin Yue, Heide Murakami, Ana Carolina Costa Araujo, Bruna Reis Dos Santos, Erin Ichinotsubo, Anna Rabkin, Raj Shah, Megan Lantz, Suzie Chen, Marcus A Tius, James Turkson
The molecular determinants for the activities of the reported benzoic acid (SH4-54), salicylic acid (BP-1-102), and benzohydroxamic acid (SH5-07)-based STAT3 inhibitors were investigated to design optimized analogues. All three leads are based on an N -methylglycinamide scaffold, with its two amine groups condensed with three different functionalities. The three functionalities and the CH2 group of the glycinamide scaffold were separately modified. The replacement of the pentafluorobenzene or cyclohexylbenzene, or replacing the benzene ring of the aromatic carboxylic or hydroxamic acid motif with heterocyclic components (containing nitrogen and oxygen elements) all decreased potency...
March 8, 2018: ACS Medicinal Chemistry Letters
Laura Hedges, Susan Brown, Audrey Vardy, Edward Doyle, Miyoung Yoon, Thomas G Osimitz, Brian G Lake
1. The metabolism of deltamethrin (DLM), cis-permethrin (CPM) and trans-permethrin (TPM) was studied in liver microsomes, liver cytosol and plasma from male Sprague-Dawley rats aged 15, 21 and 90 days and from adult humans. 2. DLM and CPM were metabolised by rat hepatic microsomal cytochrome P450 (CYP) enzymes and to a lesser extent by microsomal and cytosolic carboxylesterase (CES) enzymes, whereas TPM was metabolised to a greater extent by CES enzymes. 3. In human liver, DLM and TPM were mainly metabolised by CES enzymes, whereas CPM was metabolised by CYP and CES enzymes...
March 14, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Ines Greco, Bernard D Hummel, Jaspreet Vasir, Jeffrey L Watts, Jason Koch, Johannes E Hansen, Hanne Mørck Nielsen, Peter Damborg, Paul R Hansen
Antimicrobial peptides (AMPs) hold promise as the next generation of antimicrobial agents, but often suffer from rapid degradation in vivo. Modifying AMPs with non-proteinogenic residues such as peptoids (oligomers of N -alkylglycines) provides the potential to improve stability. We have identified two novel peptoid-based compounds, B1 and D2 , which are effective against the canine skin pathogen Staphylococcus pseudintermedius , the main cause of antibiotic use in companion animals. We report on their potential to treat infections topically by characterizing their release from formulation and in vitro ADME properties...
March 10, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Espérance Moine, Nathalie Moiré, Isabelle Dimier-Poisson, Kévin Brunet, William Couet, Cyril Colas, Nathalie Van Langendonck, Cécile Enguehard-Gueiffier, Alain Gueiffier, Bruno Héraut, Caroline Denevault-Sabourin, Françoise Debierre-Grockiego
The current therapeutic arsenal for toxoplasmosis is restricted to drugs non-specific to the parasite which cause important side effects. Development of more efficient and specific anti-Toxoplasma compounds is urgently needed. Imidazo[1,2-b]pyridazines designed to inhibit the calcium-dependent protein kinase 1 of Toxoplasma gondii (TgCDPK1) and effective against tachyzoite growth in vitro at submicromolar ranges were modified into hydrochloride salts to be administered in vivo in a mouse model of acute toxoplasmosis...
March 7, 2018: International Journal for Parasitology
Weijie Hou, Yan Ren, Zhenhua Zhang, Huan Sun, Yongfen Ma, Bo Yan
A series of novel quinazoline derivatives bearing various C-6 benzamide substituents were synthesized and evaluated as EGFR inhibitors, and most showed significant inhibitory potency against EGFR kinase. In particular, compound 6g possessed potent inhibitory activity against EGFR wild-type (IC50  = 5 nM), and strong antiproliferative activity against HCC827 and Ba/F3 (L858R) cell lines. Kinase profiling against a panel of 365 kinases showed that 6g was highly selective for EGFR. Furthermore, 6g showed desirable properties in assays of liver microsome metabolic stability and cytochromes P450 inhibition and preliminary pharmacokinetic study...
February 16, 2018: Bioorganic & Medicinal Chemistry
Kristina Beijer, Maria Jönsson, Siraz Shaik, Daphné Behrens, Björn Brunström, Ingvar Brandt
Antifungal azoles are widely used in medicine, agriculture, and material protection and several antifungal azoles have been found in environmental samples. Although these compounds were designed to inhibit fungal enzymes such as lanosterol-14-demethylase (cytochrome P450 (CYP) 51), it is well established that the inhibitory actions of azoles are not specific for fungal CYP isozymes. We refined a gill filament assay to determine the inhibition of CYP1, measured as reduced 7-ethoxyresorufin-O-deethylase (EROD) activity, in rainbow trout (Oncorhynchus mykiss) gill tissue ex vivo...
February 21, 2018: Aquatic Toxicology
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
Dinakaran Murugesan, Peter C Ray, Tracy Bayliss, Gareth A Prosser, Justin R Harrison, Kirsteen Green, Candice Soares de Melo, Tzu-Shean Feng, Leslie J Street, Kelly Chibale, Digby F Warner, Valerie Mizrahi, Ola Epemolu, Paul Scullion, Lucy Ellis, Jennifer Riley, Yoko Shishikura, Liam Ferguson, Maria Osuna-Cabello, Kevin D Read, Simon R Green, Dirk A Lamprecht, Peter M Finin, Adrie J C Steyn, Thomas R Ioerger, Jim Sacchettini, Kyu Y Rhee, Kriti Arora, Clifton E Barry Iii, Paul G Wyatt, Helena Ingrid M Boshoff
Mycobacterium tuberculosis (MTb) possesses two non-proton pumping type II NADH dehydrogenase (NDH-2) enzymes which are predicted to be jointly essential for respiratory metabolism.. Furthermore, the structure of a closely related bacterial NDH-2 has been reported recently, allowing for the structure-based design of small-molecule inhibitors. Herein, we disclose MTb whole-cell structure-activity relationships (SAR) for a series of 2-mercapto-quinazolinones which target the ndh encoded NDH-2 with nanomolar potencies...
March 9, 2018: ACS Infectious Diseases
Shimpei Watanabe, Unnikrishnan Kuzhiumparambil, Shanlin Fu
The number of new psychoactive substances keeps on rising despite the controlling efforts by law enforcement. Although metabolism of the newly emerging drugs is continuously studied to keep up with the new additions, the exact structures of the metabolites are often not identified due to the insufficient sample quantities for techniques such as nuclear magnetic resonance (NMR) spectroscopy. The aim of the study was to characterise several metabolites of the synthetic cannabinoid (1-pentyl-1H-indol-3-yl) (2,2,3,3-tetramethylcyclopropyl) methanone (UR-144) by NMR spectroscopy after the incubation with the fungus Cunninghamella elegans...
March 8, 2018: AAPS Journal
Zhaowei Zhang, Tianzi Fang, Hongyun Zhou, Jie Yuan, Qingwang Liu
Evodiamine is an indoloquinazoline alkaloid isolated from the fruit of Evodia rutaecarpa , which has a wide range of pharmacological effects like anti-tumor and anti-inflammatory effects. This study was intended to investigate the metabolic characteristics of evodiamine in human liver microsomes and hepatocytes by ultra-high performance liquid chromatography coupled with a Q Exactive mass spectrometer. A total of 12 phase I metabolites were detected in human liver microsomes; whereas in human hepatocytes 19 metabolites, including seven phase II metabolites were detected...
2018: Frontiers in Pharmacology
Nagarajan Muthukaman, Sanjay Deshmukh, Macchindra Tambe, Dnyandeo Pisal, Shital Tondlekar, Mahamadhanif Shaikh, Neelam Sarode, Vidya G Kattige, Pooja Sawant, Monali Pisat, Vikas Karande, Srinivasa Honnegowda, Abhay Kulkarni, Dayanidhi Behera, Satyawan B Jadhav, Ramchandra R Sangana, Girish S Gudi, Neelima Khairatkar-Joshi, Laxmikant A Gharat
In an effort to identify CYP and hERG clean mPGES-1 inhibitors from the dihydrofuran-fused tricyclic benzo[d]imidazole series lead 7, an extensive structure-activity relationship (SAR) studies were performed. Optimization of A, D and E-rings in 7 afforded many potent compounds with human whole blood potency in the range of 160-950 nM. Selected inhibitors 21d, 21j, 21m, 21n, 21p and 22b provided selectivity against COX-enzymes and mPGES-1 isoforms (mPGES-2 and cPGES) along with sufficient selectivity against prostanoid synthases...
February 28, 2018: Bioorganic & Medicinal Chemistry Letters
Hiroyuki Niwa, Katsumi Iizuka, Takehiro Kato, Wudelehu Wu, Hiromi Tsuchida, Ken Takao, Yukio Horikawa, Jun Takeda
The regulation of hepatic very-low-density lipoprotein (VLDL) secretion plays an important role in the pathogenesis of dyslipidemia and fatty liver diseases. VLDL is controlled by hepatic microsomal triglyceride transfer protein (MTTP). Mttp is regulated by carbohydrate response element binding protein (ChREBP) and small heterodimer partner (SHP). However, it is unclear whether both coordinately regulate Mttp expression and VLDL secretion. Here, adenoviral overexpression of ChREBP and SHP in rat primary hepatocytes induced and suppressed Mttp mRNA, respectively...
March 7, 2018: Nutrients
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"