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https://www.readbyqxmd.com/read/28639229/pharmacokinetics-of-mhaa4549a-an-anti-influenza-a-monoclonal-antibody-in-healthy-subjects-challenged-with-influenza%C3%A2-a-virus-in-a-phase-iia-randomized-trial
#1
Rong Deng, Ai Ping Lee, Mauricio Maia, Jeremy J Lim, Tracy Burgess, Priscilla Horn, Michael A Derby, Elizabeth Newton, Jorge A Tavel, William D Hanley
BACKGROUND AND OBJECTIVES: MHAA4549A, a human anti-influenza immunoglobulin (Ig) G1 monoclonal antibody, is being developed to treat patients hospitalized for influenza A infection. This study examined the pharmacokinetics (PKs) of MHAA4549A in a phase IIa, randomized, double-blind, dose-ranging trial in healthy volunteers challenged with influenza A virus. METHODS: Serum PK data were collected from 60 subjects in three single-dose groups (400, 1200, or 3600 mg) who received MHAA4549A intravenously 24-36 h after inoculation with the influenza A virus...
June 21, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28633821/enhanced-production-of-hypocrellin-a-by-ultrasound-stimulation-in-submerged-cultures-of-shiraia-bambusicola
#2
Chun Xiao Sun, Yan Jun Ma, Jian Wen Wang
Hypocrellin A (HA), a naturally occurring fungal perylenequinone, is widely used in clinic to treat skin diseases and developed as a photodynamic therapy (PDT) agent against cancers. In this study, a low intensity ultrasound (US, 0.28W/cm(2) at 40kHz) was conducted thrice of repeated US exposure (5-min) with an interval of 12h to stimulate HA production of Shiraia bambusicola after 72h of the initial submerged cultures. US not only increased the content of HA by 177.2% in mycelia, but stimulated the release of HA into the medium with the highest total production of HA (247...
September 2017: Ultrasonics Sonochemistry
https://www.readbyqxmd.com/read/28632895/genome-mining-reveals-high-incidence-of-putative-lipopeptide-biosynthesis-nrps-pks-clusters-containing-fatty-acyl-amp-ligase-genes-in-biofilm-forming-cyanobacteria
#3
Tomáš Galica, Pavel Hrouzek, Jan Mareš
Cyanobacterial lipopeptides exhibit antimicrobial and antifungal bioactivities with potential for use in pharmaceutical research. However, due to their haemolytic activity and cytotoxic effects against human cells, they may pose a health issue if produced in substantial amounts in the environment. In bacteria, lipopeptides can be synthesized via several well-evidenced mechanisms. In one of them, fatty acyl-AMP ligase (FAAL) initiates the biosynthesis by activation of a fatty acyl residue. We have performed a bioinformatic survey of the cyanobacterial genomic information available in the public databases for the presence of FAAL-containing non-ribosomal peptide synthetase/polyketide synthetase (NRPS/PKS) biosynthetic clusters, as a genetic basis for lipopeptide biosynthesis...
June 20, 2017: Journal of Phycology
https://www.readbyqxmd.com/read/28631514/pharmacokinetics-and-dosing-requirements-of-digoxin-in-pregnant-women-treated-for-fetal-supraventricular-tachycardia
#4
Ana Martin-Suarez, Jose German Sanchez-Hernandez, Fabiola Medina-Barajas, Jonas Samuel Perez Blanco, Jose M Lanao, Luisa Garcia-Cuenllas Alvarez, M Victoria Calvo
BACKGROUND: The objective of this study was to characterize the pharmacokinetics (PK) of digoxin in pregnant women and its potential implications for drug dosing. METHODS: Serum digoxin concentrations (SDCs) obtained in pregnant women treated for fetal supraventricular tachycardia (SVT) was retrospectively collected. PK analysis was comparatively performed using a two-stage approach (PKS™) and a Population PK approach (NONMEM™). As clinical outcome the fetal heart rate was recorded...
June 20, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28625782/complex-sexual-deception-in-an-orchid-is-achieved-by-co-opting-two-independent-biosynthetic-pathways-for-pollinator-attraction
#5
Haiyang Xu, Björn Bohman, Darren C J Wong, Claudia Rodriguez-Delgado, Adrian Scaffidi, Gavin R Flematti, Ryan D Phillips, Eran Pichersky, Rod Peakall
Sexually deceptive orchids lure their specific male pollinators using volatile semiochemicals that mimic female sex pheromones. To date, the semiochemicals known to be involved consist of blends of chemically and biosynthetically related compounds. In contrast, we report that (S)-β-citronellol and 2-hydroxy-6-methylacetophenone, two biosynthetically distinct compounds, are the active semiochemicals in Caladenia plicata, which is pollinated by male Zeleboria sp. thynnine wasps. They are also sex pheromone components of the female Zeleboria...
June 12, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28623508/clinical-pharmacokinetic-characteristics-of-cebranopadol-a-novel-first-in-class-analgesic
#6
Elke Kleideiter, Chiara Piana, Shaonan Wang, Robert Nemeth, Michael Gautrois
BACKGROUND AND OBJECTIVES: Cebranopadol is a novel first-in-class analgesic acting as a nociceptin/orphanin FQ peptide and opioid peptide receptor agonist with central analgesic activity. It is currently in clinical development for the treatment of chronic pain conditions. This trial focuses on the clinical pharmacokinetic (PK) properties of cebranopadol after oral single- and multiple-dose administration. METHODS: The basic PK properties of cebranopadol were assessed by means of noncompartmental methods in six phase I clinical trials in healthy subjects and patients...
June 16, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28620891/population-pharmacokinetic-modeling-of-olaratumab-an-anti-pdgfr%C3%AE-human-monoclonal-antibody-in-patients-with-advanced-and-or-metastatic-cancer
#7
Gary Mo, John R Baldwin, Debra Luffer-Atlas, Robert L Ilaria, Ilaria Conti, Michael Heathman, Damien M Cronier
BACKGROUND AND OBJECTIVES: Olaratumab is a recombinant human monoclonal antibody that binds to platelet-derived growth factor receptor-α (PDGFRα). In a randomized phase II study, olaratumab plus doxorubicin met its predefined primary endpoint for progression-free survival and achieved a highly significant improvement in overall survival versus doxorubicin alone in patients with advanced or metastatic soft tissue sarcoma (STS). In this study, we characterize the pharmacokinetics (PKs) of olaratumab in a cancer patient population...
June 15, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28620184/transcriptomic-analysis-of-the-regulation-of-lipid-fraction-migration-and-fatty-acid-biosynthesis-in-schizochytrium-sp
#8
Lujing Ren, Xuechao Hu, Xiaoyan Zhao, Shenglan Chen, Yi Wu, Dan Li, Yadong Yu, Lingjun Geng, Xiaojun Ji, He Huang
Schizochytrium sp. is the main source of docosahexaenoic acid-rich oil, which is widely used in food additive and pharmaceutical industry. In this study, using RNA-seq, comparative transcriptomic analyses were performed at four stages of DHA fermentation by Schizochytrium sp to get potential genes related to cell transition from cell growth to lipid accumulation and then to lipid turnover. 1406, 385, 1384 differently expressed genes were identified by comparisons in pairs of S2 vs S1, S3 vs S2 and S4 vs S3...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28618182/mechanism-and-regulation-of-sorbicillin-biosynthesis-by-penicillium-chrysogenum
#9
Fernando Guzmán-Chávez, Oleksandr Salo, Yvonne Nygård, Peter P Lankhorst, Roel A L Bovenberg, Arnold J M Driessen
Penicillium chrysogenum is a filamentous fungus that is used to produce β-lactams at an industrial scale. At an early stage of classical strain improvement, the ability to produce the yellow-coloured sorbicillinoids was lost through mutation. Sorbicillinoids are highly bioactive of great pharmaceutical interest. By repair of a critical mutation in one of the two polyketide synthases in an industrial P. chrysogenum strain, sorbicillinoid production was restored at high levels. Using this strain, the sorbicillin biosynthesis pathway was elucidated through gene deletion, overexpression and metabolite profiling...
June 15, 2017: Microbial Biotechnology
https://www.readbyqxmd.com/read/28616082/prevalence-of-pks-positive-escherichia-coli-in-japanese-patients-with-or-without-colorectal-cancer
#10
Takayuki Shimpoh, Yoshihiro Hirata, Sozaburo Ihara, Nobumi Suzuki, Hiroto Kinoshita, Yoku Hayakawa, Yumiko Ota, Akiko Narita, Shuntaro Yoshida, Atsuo Yamada, Kazuhiko Koike
BACKGROUND: Recent studies show that some Escherichia coli strains possessing a gene cluster named the pks island might have a causative role in the development of human colorectal cancer (CRC). In several reports from Europe, they are found more prevalently in colon tissue specimens derived from CRC patients compared to those from controls. In this study we sought to clarify the difference in pks prevalence between CRC patients and non-CRC controls in the Japanese population, by using non-invasive sample collection technique during colonoscopy...
2017: Gut Pathogens
https://www.readbyqxmd.com/read/28604695/a-scalable-platform-to-identify-fungal-secondary-metabolites-and-their-gene-clusters
#11
Kenneth D Clevenger, Jin Woo Bok, Rosa Ye, Galen P Miley, Maria H Verdan, Thomas Velk, Cynthia Chen, KaHoua Yang, Matthew T Robey, Peng Gao, Matthew Lamprecht, Paul M Thomas, Md Nurul Islam, Jonathan M Palmer, Chengcang C Wu, Nancy P Keller, Neil L Kelleher
The genomes of filamentous fungi contain up to 90 biosynthetic gene clusters (BGCs) encoding diverse secondary metabolites-an enormous reservoir of untapped chemical potential. However, the recalcitrant genetics, cryptic expression, and unculturability of these fungi prevent scientists from systematically exploiting these gene clusters and harvesting their products. As heterologous expression of fungal BGCs is largely limited to the expression of single or partial clusters, we established a scalable process for the expression of large numbers of full-length gene clusters, called FAC-MS...
June 12, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28588808/pallister-killian-syndrome-in-a-two-year-old-boy
#12
Leigh Stone, Ramya Tripuraneni, Michelle Bain, Claudia Hernandez
Pallister-Killian syndrome (PKS) is a rare, sporadic, multisystem developmental disorder characterized by craniofacial dysmorphic features. We report a case of a two-year-old boy with PKS to highlight the cutaneous findings and emphasize the importance of diagnostic skin biopsies in patients with cutaneous pigmentation changes and distinctive facial features.
June 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/28577129/effects-of-mild-to-severe-hepatic-impairment-on-the-pharmacokinetics-of-sonidegib-a-multicenter-open-label-parallel-group-study
#13
Yves Horsmans, Jocelyn Zhou, Mateva Liudmila, George Golor, Oren Shibolet, Michelle Quinlan, Corinne Emotte, Hildegard Boss, Henry Castro, Dalila Sellami, Richard A Preston
BACKGROUND AND OBJECTIVE: Sonidegib is a potent, selective and orally bioavailable inhibitor of the Hedgehog signaling pathway, primarily metabolized by the liver. In order to make dose recommendations for patients with hepatic impairment, we have assessed here the pharmacokinetics (PKs) and safety of sonidegib in subjects with varying degrees of hepatic function. METHODS: The primary objective of this phase I, multicenter, open-label study was to evaluate the PKs of a single oral 800 mg dose of sonidegib in subjects with impaired hepatic function compared with healthy subjects...
June 2, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28575792/optimization-of-hydrogen-and-syngas-production-from-pks-gasification-by-using-coal-bottom-ash
#14
Muhammad Shahbaz, Suzana Yusup, Abrar Inayat, David Onoja Patrick, Angga Pratama, Muhamamd Ammar
Catalytic steam gasification of palm kernel shell is investigated to optimize operating parameters for hydrogen and syngas production using TGA-MS setup. RSM is used for experimental design and evaluating the effect of temperature, particle size, CaO/biomass ratio, and coal bottom ash wt% on hydrogen and syngas. Hydrogen production appears highly sensitive to all factors, especially temperature and coal bottom ash wt%. In case of syngas, the order of parametric influence is: CaO/biomass>coal bottom ash wt%>temperature>particle size...
May 24, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28561946/new-paradigm-for-translational-modeling-to-predict-long-term-tuberculosis-treatment-response
#15
I H Bartelink, N Zhang, R J Keizer, N Strydom, P J Converse, K E Dooley, E L Nuermberger, R M Savic
Disappointing results of recent tuberculosis chemotherapy trials suggest that knowledge gained from preclinical investigations was not utilized to maximal effect. A mouse-to-human translational pharmacokinetics (PKs) - pharmacodynamics (PDs) model built on a rich mouse database may improve clinical trial outcome predictions. The model included Mycobacterium tuberculosis growth function in mice, adaptive immune response effect on bacterial growth, relationships among moxifloxacin, rifapentine, and rifampin concentrations accelerating bacterial death, clinical PK data, species-specific protein binding, drug-drug interactions, and patient-specific pathology...
May 31, 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/28547376/nonribosomal-peptides-and-polyketides-of-burkholderia-new-compounds-potentially-implicated-in-biocontrol-and-pharmaceuticals
#16
Qassim Esmaeel, Maude Pupin, Philippe Jacques, Valérie Leclère
Bacteria belonging to the genus Burkholderia live in various ecological niches and present a significant role in the environments through the excretion of a wide variety of secondary metabolites including modular nonribosomal peptides (NRPs) and polyketides (PKs). These metabolites represent a widely distributed biomedically and biocontrol important class of natural products including antibiotics, siderophores, and anticancers as well as biopesticides that are considered as a novel source that can be used to defend ecological niche from competitors and to promote plant growth...
May 25, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28546487/draft-genome-sequence-of-saccharomonospora-sp-strain-lrs4-154-a-moderately-halophilic-actinobacterium-with-the-biotechnologically-relevant-polyketide-synthase-and-nonribosomal-peptide-synthetase-systems
#17
Scarlett Alonso-Carmona, Blanca Vera-Gargallo, Rafael R de la Haba, Antonio Ventosa, Horacio Sandoval-Trujillo, Ninfa Ramírez-Durán
The draft genome sequence of Saccharomonospora sp. strain LRS4.154, a moderately halophilic actinobacterium, has been determined. The genome has 4,860,108 bp, a G+C content of 71.0%, and 4,525 open reading frames (ORFs). The clusters of PKS and NRPS genes, responsible for the biosynthesis of a large number of biomolecules, were identified in the genome.
May 25, 2017: Genome Announcements
https://www.readbyqxmd.com/read/28540166/inhibition-of-protein-kinases-by-anticancer-dna-intercalator-4-butylaminopyrimido-4-5-4-5-thieno-2-3-b-quinoline
#18
HeggoduG Rohit Kumar, Chethan S Kumar, Hulihalli N Kiran Kumar, Gopal M Advi Rao
Targeting protein kinases (PKs) has been a promising strategy in treating cancer, as PKs are key regulators of cell survival and proliferation. Here in this study, we studied the ability of pyrimido[4',5':4,5]thieno(2,3-b)quinolines (PTQ) to inhibit different PKs by performing computational docking and in vitro screening. Docking studies revealed that 4-butylaminopyrimido[4',5':4,5]thieno(2,3-b)quinoline (BPTQ) has a higher order of interaction with the kinase receptors than other PTQ derivatives. In vitro screening confirms that BPTQ inhibits VEGFR1 and CHK2, with the IC50 values of 0...
May 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/28535042/dudawalamides-a-d-antiparasitic-cyclic-depsipeptides-from-the-marine-cyanobacterium-moorea-producens
#19
Jehad Almaliti, Karla L Malloy, Evgenia Glukhov, Carmenza Spadafora, Marcelino Gutiérrez, William H Gerwick
A family of 2,2-dimethyl-3-hydroxy-7-octynoic acid (Dhoya)-containing cyclic depsipeptides, named dudawalamides A-D (1-4), was isolated from a Papua New Guinean field collection of the cyanobacterium Moorea producens using bioassay-guided and spectroscopic approaches. The planar structures of dudawalamides A-D were determined by a combination of 1D and 2D NMR experiments and MS analysis, whereas the absolute configurations were determined by X-ray crystallography, modified Marfey's analysis, chiral-phase GCMS, and chiral-phase HPLC...
May 23, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28529817/coordinated-and-iterative-enzyme-catalysis-in-fungal-polyketide-biosynthesis
#20
Leibniz Hang, Nicholas Liu, Yi Tang
Fungal polyketides are natural products with great chemical diversity that exhibit a wide range of biological activity. This chemical diversity stems from specialized enzymes encoded in the biosynthetic gene cluster responsible for the natural product biosynthesis. Fungal polyketide synthases (PKS) are the megasynthases that produce the carbon scaffolds for the molecules. Subsequent downstream tailoring enzymes such as oxygenases will then further modify the organic framework. In fungi, many of these enzymes have been found to work iteratively-catalyzing multiple reactions on different sites of the substrate...
September 2, 2016: ACS Catalysis
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