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https://www.readbyqxmd.com/read/29148835/2017-white-paper-on-recent-issues-in-bioanalysis-aren-t-bmv-guidance-guidelines-scientific-part-1-lcms-small-molecules-peptides-and-small-molecule-biomarkers
#1
Jan Welink, Eric Yang, Nicola Hughes, Brian Rago, Eric Woolf, Jens Sydor, Laura Coppola, Brad Ackermann, Wenkui Li, Stephen C Alley, Mark Arnold, Isabella Berger, Chad Briscoe, Michael Buonarati, Mark Bustard, Mark Cancilla, Seongeun Julia Cho, Jeff Duggan, Daniela Fraier, Fabio Garofolo, Rachel Green, Sam Haidar, Lucinda Hittle, Akiko Ishii-Watabe, Rafiq Islam, Rand Jenkins, Barry Jones, John Kadavil, Sean Kassim, Olga Kavetska, Olivier Le Blaye, Anita Lee, Hanlan Liu, John Mehl, Gustavo Mendes Lima Santos, Adrien Musuku, Ragu Ramanathan, Yoshiro Saito, Natasha Savoie, Scott Summerfield, Sekhar Surapaneni, Matthew Szapacs, Nilufer Tampal, Tom Verhaeghe, Stephen Vinter, Emma Whale
The 2017 11th Workshop on Recent Issues in Bioanalysis (11th WRIB) took place in Los Angeles/Universal City, California from 3 April 2017 to 7 April 2017 with participation of close to 750 professionals from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations and regulatory agencies worldwide. WRIB was once again a 5-day, weeklong event - A Full Immersion Week of Bioanalysis, Biomarkers and Immunogenicity. As usual, it was specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest including both small and large molecule analysis involving LCMS, hybrid LBA/LCMS and ligand-binding assay (LBA) approaches...
November 17, 2017: Bioanalysis
https://www.readbyqxmd.com/read/29145415/plant-organ-cultures-as-masked-mycotoxin-biofactories-deciphering-the-fate-of-zearalenone-in-micropropagated-durum-wheat-roots-and-leaves
#2
Laura Righetti, Enrico Rolli, Gianni Galaverna, Michele Suman, Renato Bruni, Chiara Dall'Asta
"Masked mycotoxins" senso strictu are conjugates of mycotoxins resulting from metabolic pathways activated by the interplay between pathogenic fungi and infected plants. Zearalenone, an estrogenic mycotoxin produced by Fusarium spp, was the first masked mycotoxin ever described in the literature, but its biotransformation has been studied to a lesser extent if compared to other compounds such as deoxynivalenol. We presented herein the first application of organ and tissue culture techniques to study the metabolic fate of zearalenone in durum wheat, using an untargeted HR-LCMS approach...
2017: PloS One
https://www.readbyqxmd.com/read/29144822/testosterone-levels-achieved-by-medically-treated-transgender-women-in-a-united-states-endocrinology-clinic-cohort
#3
Jennifer J Liang, Divya Jolly, Kelly J Chan, Joshua D Safer
OBJECTIVE: Most transgender women depend on medical treatment alone to lower testosterone levels in order to align physical appearance with gender identity. The medical regimen in the United States typically includes spironolactone and estrogens. The purpose of this cross-sectional study was to assess the testosterone suppression achieved among transgender women treated with spironolactone and estrogens. METHODS: Testosterone and estradiol levels were extracted from the electronic medical records of 98 anonymized transgender women treated with oral spironolactone and oral estrogen therapy at the Endocrinology Clinic at Boston Medical Center...
November 16, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/29120380/in-vitro-phase-i-metabolism-of-crv431-a-novel-oral-drug-candidate-for-chronic-hepatitis-b
#4
Daniel J Trepanier, Daren R Ure, Robert T Foster
The cytochrome P450-mediated Phase I in vitro metabolism of CRV431 was studied using selective chemical inhibition and recombinant human enzymes. Additionally, the metabolic profile of CRV431 in human, rat, and monkey liver microsomes was investigated. Liver microsomes were incubated for 0-80 min with CRV431, and the metabolite profile was assessed by electrospray ionization liquid chromatography mass spectrometry (ESI-LCMS). CRV431 was extensively metabolized through oxidation to produce various hydroxylated and demethylated species...
November 9, 2017: Pharmaceutics
https://www.readbyqxmd.com/read/29107617/assessment-of-preclinical-pharmacokinetics-and-acute-toxicity-of-pioglitazone-and-telmisartan-combination
#5
Pinaki Sengupta, Bappaditya Chatterjee, Tapan Kumar Pal
The prevalence of hypertension is very common amongst the diabetic patients and is reported as the major cause of mortality in diabetes. Pioglitazone reported to have an ability to alter the blood cholesterol level and cardioprotective efficiency along with its antidiabetic activity. Telmisartan, through activation of PPAR-γ receptor exerts insulin sensitizing property in addition to its primary cardioprotective efficiency. Theoretically, a combination of pioglitazone and telmisartan may be beneficial to effectively control the high blood glucose level and management of coexisting cardiovascular complication in diabetes...
October 28, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/29051099/hyperglycemia-induced-reactive-species-trigger-structural-changes-in-human-serum-albumin-of-type-1-diabetic-subjects
#6
Zarina Arif, Km Neelofar, Mir Yasir Arfat, Asif Zaman, Akhlas Tarannum, Iffat Parveen, Shafeeque Ahmad, Md Adnan Khan, Asim Badar, Shireen Naaz Islam
Chronic oxidative stress fuels pathogenesis of a large set of diseases. Oxidative stress is the cause and consequence of numerous diseases including type 1 diabetes mellitus (T1DM), in which there is selective destruction of insulin producing pancreatic β-cells. Studies have documented that hyperglycemia produces profound stress. In vivo production of numerous reactive oxygen, nitrogen, chlorine species and lipid/sugar oxidation products are result of persistent hyperglycemia. Post-translational modifications by reactive species may create new antigenic epitopes and play a role in the development of autoimmune response...
October 16, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29035051/integrating-carbamylation-and-ultraviolet-photodissociation-mass-spectrometry-for-middle-down-proteomics
#7
James D Sanders, Sylvester M Greer, Jennifer S Brodbelt
The most popular bottom-up proteomics workflow uses trypsin to enzymatically cleave proteins C-terminal to lysine and arginine residues prior to LCMS/MS analysis of the resulting peptides. The high frequency of these residues generates short peptides, some of which are too small or uninformative for optimal analysis and which potentially contribute to gaps in sequence coverage of proteins. Analysis of larger peptides, termed "middle-down", has the potential to span greater sections of protein sequences if the larger peptides are adequately characterized based on their fragmentation patterns...
November 7, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29034541/characteristic-components-profiling-and-identification-of-different-uncaria-species-based-on-high-performance-liquid-chromatography-photodiode-array-detector-tandem-ion-trap-and-time-of-flight-mass-spectrometer-coupled-with-rdna-its-sequence
#8
Bingqiang Zhao, Yanjun Huang, Qiulan Chen, Qizhao Chen, Hui Miao, Shuang Zhu, Changqing Zeng
The Uncaria is a multi-source herb and its species identification has become a bottleneck in quality control. To study the identification method of different Uncaria species herbs through HPLC-MS coupled with rDNA Internal Transcribed Spacer (rDNA ITS) sequence, both plant morphological traits and molecular identification were used to determine the species of every collected Uncaria herbs. The genetic analysis of different Uncaria species was performed by using their rDNA ITS sequence as a molecular marker...
October 16, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28978931/isotope-coded-protein-label-based-quantitative-proteomic-analysis-reveals-significant-up-regulation-of-apolipoprotein-a1-and-ovotransferrin-in-the-myopic-chick-vitreous
#9
Feng-Juan Yu, Thomas Chuen Lam, Long-Qian Liu, Rachel Ka-Man Chun, Jimmy Ka-Wai Cheung, King-Kit Li, Chi-Ho To
This study used isotope-coded protein label (ICPL) quantitative proteomics and bioinformatics analysis to examine changes in vitreous protein content and associated pathways during lens-induced eye growth. First, the vitreous protein profile of normal 7-day old chicks was characterized by nano-liquid chromatography electrospray ionization tandem mass spectrometry. A total of 341 unique proteins were identified. Next, myopia and hyperopia were induced in the same chick by attaching -10D lenses to the right eye and +10D lenses to the left eye, for 3 and 7 days...
October 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28974368/correlation-of-pharmacokinetics-and-brain-penetration-data-of-adult-zebrafish-with-higher-mammals-including-humans
#10
Pushkar Kulkarni, Raghavender Medishetti, Nagaraju Nune, Swapna Yellanki, Vijaykumar Sripuram, Pallavi Rao, Dharmarajan Sriram, Uday Saxena, Srinivas Oruganti, Perumal Yogeeswari
INTRODUCTION: Adult zebrafish pharmacology is evolving rapidly for creating efficacy and safety models for drug discovery. However, there is very limited research in understanding pharmacokinetics (PK) in adult zebrafish. Methods for understanding PK will help in conducting pharmacokinetic - pharmacodynamic (PK-PD) correlations and improving the quality and applicability of data obtained using zebrafish. METHODS: We conducted adult zebrafish PK and brain penetration studies on two known compounds (irinotecan and lorcaserin) with distinct PK and brain penetration properties using validated LCMS/MS method...
September 30, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28935667/upregulation-of-human-endogenous-retrovirus-k-is-linked-to-immunity-and-inflammation-in-pulmonary-arterial-hypertension
#11
Toshie Saito, Kazuya Miyagawa, Shih-Yu Chen, Rasa Tamosiuniene, Lingli Wang, Orr Sharpe, Erik Samayoa, Daisuke Harada, Jan-Renier A J Moonen, Aiqin Cao, Pin-I Chen, Jan K Hennigs, Mingxia Gu, Caiyun G Li, Ryan D Leib, Dan Li, Christopher M Adams, Patricia A Del Rosario, Matthew Bill, Francois Haddad, Jose G Montoya, William H Robinson, Wendy J Fantl, Garry P Nolan, Roham T Zamanian, Mark R Nicolls, Charles Y Chiu, Maria E Ariza, Marlene Rabinovitch
BACKGROUND: Immune dysregulation has been linked to occlusive vascular remodeling in pulmonary arterial hypertension (PAH) that is hereditary, idiopathic, or associated with other conditions. Circulating autoantibodies, lung perivascular lymphoid tissue, and elevated cytokines have been related to PAH pathogenesis but without a clear understanding of how these abnormalities are initiated, perpetuated, and connected in the progression of disease. We therefore set out to identify specific target antigens in PAH lung immune complexes as a starting point toward resolving these issues to better inform future application of immunomodulatory therapies...
November 14, 2017: Circulation
https://www.readbyqxmd.com/read/28918200/profiling-the-short-linear-non-disulfide-bond-containing-peptidome-from-the-venom-of-the-scorpion-tityus-obscurus
#12
Nathalia Baptista Dias, Bibiana Monson de Souza, Fernando Kamimura Cocchi, Hipócrates M Chalkidis, Valquíria Abrão Coronado Dorce, Mario Sergio Palma
Many scorpion accidents occur in the Brazilian Amazonian region and are frequently caused by Tityus obscurus. Approximately 5% of the crude venom of this species is composed of short linear, non-disulfide-bridged peptides, which have not been intensively investigated. As a consequence, only a few of these peptides have been structurally and functionally characterized to date. In the present paper, the peptide fraction of the venom was subjected to peptide profiling using an LCMS-IT-TOF/MS and MS(n) system. The analysis detected 320 non-disulfide bond-containing peptides (NDBPs), of which twenty-seven had their sequences assigned; among them, thirteen peptides were characterized, constituting novel toxins in T...
January 6, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/28895884/interaction-of-recombinant-gallus-gallus-sept5-and-brain-proteins-of-h5n1-avian-influenza-virus-infected-chickens
#13
Jasmine Elanie Khairat, Vinod Balasubramaniam, Iekhsan Othman, Abdul Rahman Omar, Sharifah Syed Hassan
Septin forms a conserved family of cytoskeletal guanosine triphosphate (GTP) binding proteins that have diverse roles in protein scaffolding, vesicle trafficking, and cytokinesis. The involvement of septins in infectious viral disease pathogenesis has been demonstrated by the upregulation of SEPT5 protein and its mRNA in brain tissues of H5N1-infected chickens, thus, providing evidence for the potential importance of this protein in the pathogenesis of neurovirulence caused by the avian influenza virus. In this study, cloning, expression, and purification of Gallus gallus SEPT5 protein was performed in Escherichia coli...
September 12, 2017: Proteomes
https://www.readbyqxmd.com/read/28877224/transformation-products-elucidation-of-forchlorfenuron-in-postharvest-kiwifruit-by-time-of-flight-mass-spectrometry
#14
Zhiwei Zhang, Zhenhong Gao, Yuan Wang, Yahong Yuan, Jing Dong, Tianli Yue
Forchlorfenuron (1-(2-chloro-4-pyridyl)-3-phenylurea, FCF) is a plant growth regulator, being extensively used for increasing kiwifruit size. The toxicological properties of its may persist in their transformation products (TPs) or even higher toxicity than FCF. TPs elucidation of FCF in postharvest kiwifruit (Actinidia chinensis, Chinese gooseberry) by the liquid chromatography ionization hybrid ion trap and time-of-flight mass spectrometry (LC-ESI-IT-TOF/MS) in positive mode was the objective of the present study...
2017: PloS One
https://www.readbyqxmd.com/read/28874834/immunology-lcms-and-the-liver-additional-surveillance
#15
Katrina Ray
No abstract text is available yet for this article.
November 2017: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28851636/sle-autoantibodies-are-well-recognized-by-peroxynitrite-modified-hsa-its-implications-in-the-pathogenesis-of-sle
#16
Zarina Arif, Km Neelofar, Akhlas Tarannum, Mir Yasir Arfat, Shafeeque Ahmad, Asif Zaman, Mohd Adnan Khan, Asim Badar, Shireen Naaz Islam, Mohammad Arif Iqubal
Systemic lupus erythematosus (SLE) is an autoimmune disorder where the role of inflammatory processes in the etiopathogenesis is well documented. Despite extensive research, the trigger for initiation of the disease has not been identified. Peroxynitrite, a strong nitrating/oxidizing agent has been reported in SLE and other autoimmune diseases. In this study, human serum albumin (HSA) was exposed to peroxynitrite for 30min at 37°C. The structure of HSA was grossly perturbed when examined by various physico-chemical techniques...
August 26, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28846849/cyclic-hexapeptide-dimers-antatollamides-a-and-b-from-the-ascidian-didemnum-molle-a-tryptophan-derived-auxiliary-for-l-and-d-amino-acid-assignments
#17
Mariam N Salib, Tadeusz F Molinski
Two dimerized cyclic hexapeptides, antatollamides A (1) and B (2), were isolated from the colonial ascidian Didemnum molle collected in Pohnpei. The amino acid compositions and sequences were determined by interpretation of MS and 1D and 2D NMR data. Raney Ni reduction of antatollamide A cleaved the dimer to the corresponding monomeric cyclic hexapeptide with replacement of Cys by Ala. The amino acid configuration of 1 was established, after total hydrolysis, by derivatization with a new chiral reagent, (5-fluoro-2,4-dinitrophenyl)-N(α)-l-tryptophanamide (FDTA), prepared from l-Trp, followed by LCMS analysis; all amino acids were found to be l-configured except for d-Ala...
September 18, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28815210/lpxk-is-essential-for-growth-of-acinetobacter-baumannii-atcc-19606-relationship-to-toxic-accumulation-of-lipid-a-pathway-intermediates
#18
Jun-Rong Wei, Daryl L Richie, Mina Mostafavi, Louis E Metzger, Christopher M Rath, William S Sawyer, Kenneth T Takeoka, Charles R Dean
Acinetobacter baumannii ATCC 19606 can grow without lipid A, the major component of lipooligosaccharide. However, we previously reported that depletion of LpxH (the fourth enzyme in the lipid A biosynthetic pathway) prevented growth of this strain due to toxic accumulation of lipid A pathway intermediates. Here, we explored whether a similar phenomenon occurred with depletion of LpxK, a kinase that phosphorylates disaccharide 1-monophosphate (DSMP) at the 4' position to yield lipid IVA. An A. baumannii ATCC 19606 derivative with LpxK expression under the control of an isopropyl β-d-1-thiogalactopyranoside (IPTG)-regulated expression system failed to grow without induction, indicating that LpxK is essential for growth...
July 2017: MSphere
https://www.readbyqxmd.com/read/28814950/morinda-citrifolia-l-leaf-extract-prevent-weight-gain-in-sprague-dawley-rats-fed-a-high-fat-diet
#19
Najla Gooda Sahib Jambocus, Amin Ismail, Alfi Khatib, Fawzi Mahomoodally, Nazamid Saari, Muhammad Waseem Mumtaz, Azizah Abdul Hamid
Background: Morinda citrifolia L. is widely used as a folk medicinal food plant to manage a panoply of diseases, though no concrete reports on its potential anti-obesity activity. This study aimed to evaluate the potential of M. citrifolia leaf extracts (MLE60) in the prevention of weight gain in vivo and establish its phytochemical profile. Design: Male Sprague-Dawley rats were divided into groups based on a normal diet (ND) or high fat diet (HFD), with or without MLE60 supplementation (150 and 350 mg/kg body weight) and assessed for any reduction in weight gain...
2017: Food & Nutrition Research
https://www.readbyqxmd.com/read/28813662/a-liver-capsular-network-of-monocyte-derived-macrophages-restricts-hepatic-dissemination-of-intraperitoneal-bacteria-by-neutrophil-recruitment
#20
Frederic Sierro, Maximilien Evrard, Simone Rizzetto, Michelle Melino, Andrew J Mitchell, Manuela Florido, Lynette Beattie, Shaun B Walters, Szun Szun Tay, Bo Lu, Lauren E Holz, Ben Roediger, Yik Chun Wong, Alessandra Warren, William Ritchie, Claire McGuffog, Wolfgang Weninger, David G Le Couteur, Florent Ginhoux, Warwick J Britton, William R Heath, Bernadette M Saunders, Geoffrey W McCaughan, Fabio Luciani, Kelli P A MacDonald, Lai Guan Ng, David G Bowen, Patrick Bertolino
The liver is positioned at the interface between two routes traversed by pathogens in disseminating infection. Whereas blood-borne pathogens are efficiently cleared in hepatic sinusoids by Kupffer cells (KCs), it is unknown how the liver prevents dissemination of peritoneal pathogens accessing its outer membrane. We report here that the hepatic capsule harbors a contiguous cellular network of liver-resident macrophages phenotypically distinct from KCs. These liver capsular macrophages (LCMs) were replenished in the steady state from blood monocytes, unlike KCs that are embryonically derived and self-renewing...
August 15, 2017: Immunity
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