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https://www.readbyqxmd.com/read/28411181/monoclonal-antibodies-to-the-reactive-centre-loop-rcl-of-human-corticosteroid-binding-globulin-cbg-can-protect-against-proteolytic-cleavage
#1
John G Lewis, Peter A Elder
Corticosteroid-binding globulin (CBG) binds most of the cortisol in circulation and is a non-functional member of the family of serine protease inhibitors (serpins) with an exposed elastase sensitive reactive centre loop (RCL). The RCL can be cleaved by human neutrophil elastase, released from activated neutrophils, and can also be cleaved at nearby site(s) by elastase released by Pseudomonas aeruginosa, and at two further sites, also within the RCL, by bovine chymotrypsin. Cleavage of the RCL results in a conformational change accompanied by a marked decrease in affinity for cortisol and hence its release at the site of proteolysis...
April 12, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28406896/inferring-modulators-of-genetic-interactions-with-epistatic-nested-effects-models
#2
Martin Pirkl, Madeline Diekmann, Marlies van der Wees, Niko Beerenwinkel, Holger Fröhlich, Florian Markowetz
Maps of genetic interactions can dissect functional redundancies in cellular networks. Gene expression profiles as high-dimensional molecular readouts of combinatorial perturbations provide a detailed view of genetic interactions, but can be hard to interpret if different gene sets respond in different ways (called mixed epistasis). Here we test the hypothesis that mixed epistasis between a gene pair can be explained by the action of a third gene that modulates the interaction. We have extended the framework of Nested Effects Models (NEMs), a type of graphical model specifically tailored to analyze high-dimensional gene perturbation data, to incorporate logical functions that describe interactions between regulators on downstream genes and proteins...
April 13, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28401824/-biosimilar-registered-despite-the-netherlands-opposing-vote-greater-uncertainty-about-authorised-drugs-in-the-netherlands
#3
A G Vulto
On 1 April 2016 the Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion on a new biological medicine, Flixabi®, a biosimilar to infliximab (Remicade®); however, in the appendix of the European Public Assessment Report (EPAR) it appeared that an important minority (14 of 33 votes) opposed this decision, among them the Netherlands representative. In an original article, the Dutch Medicines Board (CBG-MEB) explained the reason for this decision, but still allowed the drug on the market...
2017: Nederlands Tijdschrift Voor Geneeskunde
https://www.readbyqxmd.com/read/28383656/premosa-extracting-2d-surfaces-from-3d-microscopy-mosaics
#4
Corinna Blasse, Stephan Saalfeld, Raphaël Etournay, Andreas Sagner, Suzanne Eaton, Eugene W Myers
Motivation: A significant focus of biological research is to understand the development, organization and function of tissues. A particularly productive area of study is on single layer epithelial tissues in which the adherence junctions of cells form a 2D manifold that is fluorescently labeled. Given the size of the tissue, a microscope must collect a mosaic of overlapping 3D stacks encompassing the stained surface. Downstream interpretation is greatly simplified by preprocessing such a dataset as follows: (a) extracting and mapping the stained manifold in each stack into a single 2D projection plane, (b) correcting uneven illumination artifacts, (c) stitching the mosaic planes into a single, large 2D image, and (d) adjusting the contrast...
April 5, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28348416/cannabinoid-cb2-receptors-are-involved-in-the-protection-of-raw264-7-macrophages-against-the-oxidative-stress-an-in-vitro-study
#5
Sabrina Giacoppo, Agnese Gugliandolo, Oriana Trubiani, Federica Pollastro, Gianpaolo Grassi, Placido Bramanti, Emanuela Mazzon
Research in the last decades has widely investigated the anti-oxidant properties of natural products as a therapeutic approach for the prevention and the treatment of oxidative-stress related disorders. In this context, several studies were aimed to evaluate the therapeutic potential of phytocannabinoids, the bioactive compounds of Cannabis sativa. Here, we examined the anti-oxidant ability of Cannabigerol (CBG), a non-psychotropic cannabinoid, still little known, into counteracting the hydrogen peroxide (H2O2)-induced oxidative stress in murine RAW264...
January 23, 2017: European Journal of Histochemistry: EJH
https://www.readbyqxmd.com/read/28343385/development-of-a-rapid-lc-ms-ms-method-for-the-quantification-of-cannabidiol-cannabidivarin-%C3%AE-9-tetrahydrocannabivarin-and-cannabigerol-in-mouse-peripheral-tissues
#6
Fabiana Piscitelli, Ester Pagano, Anna Lauritano, Angelo A Izzo, Vincenzo Di Marzo
Cannabis has been known as a medicine for several thousand years across many cultures and its beneficial effects are mostly due to the presence of cannabinoids, unique natural products, whose pharmacology is going to gain increasing interest in the scientific community. The discovery of the main psychoactive constituent of Cannabis sativa L., Δ(9)-tetrahydrocannabinol (Δ(9)-THC), led to the identification of at least 100 additional phytocannabinoids, including cannabidiol (CBD), cannabidivarin (CBDV), Δ(9)-tetrahydrocannabivarin (Δ(9)-THCV), and cannabigerol (CBG)...
April 3, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28290007/impact-of-urban-neighborhood-disadvantage-on-late-stage-breast-cancer-diagnosis-in-virginia
#7
Pam Baker DeGuzman, Wendy F Cohn, Fabian Camacho, Brandy L Edwards, Vanessa N Sturz, Anneke T Schroen
Research suggests that residents of inner-city urban neighborhoods have higher rates of late stage cancer diagnosis. Identifying urban neighborhoods with high rates of both concentrated disadvantage and late stage cancer diagnosis may assist health care providers to target screening interventions to reduce disparities. The purposes of this study were to (1) create an index to evaluate concentrated disadvantage (CD) using non-racial measures of poverty, (2) determine the impact of neighborhood CD on late stage breast cancer diagnosis in US cities, and (3) to understand the role of obesity on this relationship...
March 13, 2017: Journal of Urban Health: Bulletin of the New York Academy of Medicine
https://www.readbyqxmd.com/read/28166688/pyrexia-s-effect-on-the-cbg-cortisol-thermocouple-rather-than-cbg-cleavage-elevates-the-acute-free-cortisol-response-to-tnf-%C3%AE-in-humans
#8
Marni Anne Nenke, Signe Tellerup Nielsen, Louise Lang Lehrskov, John Goodwyn Lewis, Wayne Rankin, Kirsten Møller, David James Torpy
Corticosteroid-binding globulin (CBG) cleavage promotes local cortisol delivery in inflammation. Enzymatic cleavage of high-affinity CBG to low-affinity CBG (haCBG to laCBG) occurs at inflammatory sites and is now measurable in vivo; however, the time kinetics of haCBG depletion following an inflammatory stimulus is unknown. Hence our aim was to determine the immediate effect of the key pro-inflammatory cytokine TNF-α on CBG levels and cleavage. We performed a crossover study of 12 healthy males receiving a TNF-α versus saline infusion, measuring total CBG, haCBG, laCBG and free and total cortisol hourly for 6 h...
February 28, 2017: Stress: the International Journal on the Biology of Stress
https://www.readbyqxmd.com/read/28125508/a-cannabigerol-rich-cannabis-sativa-extract-devoid-of-increment-9-tetrahydrocannabinol-elicits-hyperphagia-in-rats
#9
Daniel I Brierley, James Samuels, Marnie Duncan, Benjamin J Whalley, Claire M Williams
Nonpsychoactive phytocannabinoids (pCBs) from Cannabis sativa may represent novel therapeutic options for cachexia because of their pleiotropic pharmacological activities, including appetite stimulation. We have recently shown that purified cannabigerol (CBG) is a novel appetite stimulant in rats. As standardized extracts from Cannabis chemotypes dominant in one pCB [botanical drug substances (BDSs)] often show greater efficacy and/or potency than purified pCBs, we investigated the effects of a CBG-rich BDS, devoid of psychoactive [INCREMENT]-tetrahydrocannabinol, on feeding behaviour...
January 25, 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/28120229/phytochemistry-of-cannabis-sativa-l
#10
Mahmoud A ElSohly, Mohamed M Radwan, Waseem Gul, Suman Chandra, Ahmed Galal
Cannabis (Cannabis sativa, or hemp) and its constituents-in particular the cannabinoids-have been the focus of extensive chemical and biological research for almost half a century since the discovery of the chemical structure of its major active constituent, Δ(9)-tetrahydrocannabinol (Δ(9)-THC). The plant's behavioral and psychotropic effects are attributed to its content of this class of compounds, the cannabinoids, primarily Δ(9)-THC, which is produced mainly in the leaves and flower buds of the plant...
2017: Progress in the Chemistry of Organic Natural Products
https://www.readbyqxmd.com/read/28117322/quality-control-of-traditional-cannabis-tinctures-pattern-markers-and-stability
#11
Wieland Peschel
Traditional tinctures of Cannabis sativa L. became obsolete before elucidation of the main cannabinoids and routine quality testing for medicines. In view of increasing medicinal use of cannabinoids and associated safety concerns, tinctures from a Δ9-tetrahydrocannabinol (THC)-type chemovar were studied. High-performance liquid chromatography with diode-array detection (HPLC/DAD) was used to determine THC, Δ9-tetrahydrocannabinolic acid A (THCA), cannabinol (CBN), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabigerol (CBG), cannabigerolic acid (CBGA), cannflavin A/B, and total phenolics...
April 18, 2016: Scientia Pharmaceutica
https://www.readbyqxmd.com/read/28108446/chaincleaner-improves-genome-alignment-specificity-and-sensitivity
#12
Hernando G Suarez, Bjoern E Langer, Pradnya Ladde, Michael Hiller
MOTIVATION: Accurate alignments between entire genomes are crucial for comparative genomics. However, computing sensitive and accurate genome alignments is a challenging problem, complicated by genomic rearrangements. RESULTS: Here we present a fast approach, called chainCleaner, that improves the specificity in genome alignments by accurately detecting and removing local alignments that obscure the evolutionary history of genomic rearrangements. Systematic tests on alignments between the human and other vertebrate genomes show that chainCleaner (i) improves the alignment of numerous orthologous genes, (ii) exposes alignments between exons of orthologous genes that were masked before by alignments to pseudogenes, and (iii) recovers hundreds of kilobases in local alignments that otherwise would fall below a minimum score threshold...
January 19, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28098040/-hypocortisolism-associated-with-nephrotic-syndrome
#13
R H Westerdijk, B H R Wolffenbuttel, I P Kema, R S M E Wouters
BACKGROUND: With nephrotic syndrome, cortisol levels may be falsely lowered by loss of cortisol-binding globulin (CBG) in the urine. An incorrect diagnosis of adrenal insufficiency could therefore be made. CASE DESCRIPTION: We describe the case of a 52-year-old female with nephrotic syndrome that did not sufficiently respond to medication. Treatment management was complicated by symptomatic hypotension, which was thought to be caused by adrenal insufficiency. The cortisol levels in the blood were low and a clinical cause could not be identified...
2017: Nederlands Tijdschrift Voor Geneeskunde
https://www.readbyqxmd.com/read/28068807/measuring-cortisol-in-serum-urine-and-saliva-are-our-assays-good-enough
#14
Nadia El-Farhan, D Aled Rees, Carol Evans
Cortisol is a steroid hormone produced in response to stress. It is essential for maintaining health and wellbeing and leads to significant morbidity when deficient or present in excess. It is lipophilic and is transported bound to cortisol-binding globulin (CBG) and albumin; a small fraction (∼10%) of total serum cortisol is unbound and biologically active. Serum cortisol assays measure total cortisol and their results can be misleading in patients with altered serum protein concentrations. Automated immunoassays are used to measure cortisol but lack specificity and show significant inter-assay differences...
May 2017: Annals of Clinical Biochemistry
https://www.readbyqxmd.com/read/28063472/the-effect-of-free-and-carrier-bound-cortisol-on-equine-neutrophil-function
#15
Melanie A Fratto, Kelsey A Hart, Natalie A Norton, Michelle H Barton, Steeve Giguère, David J Hurley
Cortisol is a key anti-inflammatory hormone that increases in bacterial sepsis and circulates predominantly bound to cortisol binding globulin (CBG). Only unbound cortisol was believed to be biologically active, but recent evidence suggests that CBG-bound cortisol also regulates inflammation. The objective of this study was to evaluate the effects of free and CBG-bound cortisol on equine neutrophil function ex vivo. We hypothesized that CBG would enhance cortisol-mediated suppression of neutrophil pro-inflammatory responses...
January 2017: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/28063163/immediate-versus-modified-release-hydrocortisone-in-mitotane-treated-patients-with-adrenocortical-cancer
#16
Marianne Weigel, Stefanie Hahner, Mark Sherlock, Amar Agha, Lucy Ann Behan, Paul M Stewart, Wiebke Arlt, Daniela Beier, Kathrin Frey, Kathrin Zopf, Marcus Quinkler
OBJECTIVE: Mitotane induces hepatic CYP3A4 activity, resulting in accelerated cortisol inactivation, and also increases cortisol binding globulin (CBG). Therefore, higher hydrocortisone doses are required in patients with adrenocortical cancer (ACC) on mitotane treatment. Modified release hydrocortisone has not been used in mitotane-treated ACC patients yet. AIM: Case series to compare serum cortisol, calculated free serum cortisol and ACTH levels in ACC patients on mitotane treatment with immediate and modified release hydrocortisone...
April 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/28027946/how-serpins-transport-hormones-and-regulate-their-release
#17
REVIEW
Robin W Carrell, Randy J Read
The adaptation of the serpin framework and its mechanism to perform diverse functions is epitomised in the hormone carriers of the blood. Thyroxine and the corticosteroids are transported bound in a 1:1 ratio on almost identical sites in the two homologous binding-globulins, TBG and CBG. Recent structural findings show an equilibrated, rather than on-and-off, release of the hormones from the carriers, reflecting small reversible movements of the hinge region of the reactive loop that modify the conformational flexibility of the underlying hormone-binding site...
February 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28024808/total-and-free-cortisol-responses-and-their-relation-to-outcomes-after-cardiopulmonary-bypass-in-infants
#18
Eric L Wald, Carl L Backer, Joseph A Dearani, Zhuo Li, William C Oliver, Sheri S Crow
BACKGROUND: Hypothalamic-pituitary-adrenal (HPA) axis dysfunction may be partially responsible for the hemodynamic instability experienced by infants after cardiopulmonary bypass (CPB). We report the full spectrum of the HPA response surrounding CPB for infant congenital cardiac surgery. METHODS: We enrolled 84 infants who received 1 mg/kg of dexamethasone before initiation of CPB. Total cortisol (TC), free cortisol (FC), adrenocorticotropic hormone (ACTH), and corticosteroid-binding globulin (CBG) were measured at 3 time points: immediately before CPB (TP1), on intensive care unit arrival (TP2), and at 24 hours after surgery (TP3)...
May 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28007663/dynamic-interactions-between-corticosterone-corticosteroid-binding-globulin-and-testosterone-in-response-to-capture-stress-in-male-breeding-eurasian-tree-sparrows
#19
Yaqing Li, Yanfeng Sun, Jesse S Krause, Mo Li, Xuelu Liu, Weiwei Zhu, Yao Yao, Yuefeng Wu, Dongming Li
In birds, corticosterone (CORT), testosterone (T), and corticosteroid binding globulin (CBG) are involved in modulating the trade-off between reproduction and survival. In response to acute stress, increased total plasma CORT is a ubiquitous phenomenon while T levels can decrease, or remain unchanged. Since CORT and T bind competitively with CBG in birds, the underlying regulatory mechanisms and consequences of their dynamic interactions remain largely unknown. Here, we studied the dynamic changes of total CORT, T, and CBG, and estimated free and bound CORT and T in response to capture stress in male Eurasian tree sparrows (Passer montanus) across the nest building, egg-laying, and nestling stages...
March 2017: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/27973029/stroke-treatment-cost-analysis-for-consideration-on-health-cost-determination-using-ina-cbg-s-indonesia-case-based-groups-in-indonesia-national-health-insurance-programme-2014
#20
I Hadning, F Fathurrohmah
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
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