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https://www.readbyqxmd.com/read/29161255/neurogenic-mediators-contribute-to-local-edema-induced-by-micrurus-lemniscatus-venom
#1
Luciana Lyra Casais-E-Silva, Catarina Teixeira
BACKGROUND/AIMS: Micrurus is one of the four snake genera of medical importance in Brazil. Coral snakes have a broad geographic distribution from the southern United States to Argentina. Micrurine envenomation is characterized by neurotoxic symptoms leading to dyspnea and death. Moreover, various local manifestations, including edema formation, have been described in patients bitten by different species of Micrurus. Thus, we investigated the ability of Micrurus lemniscatus venom (MLV) to induce local edema...
November 21, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29158025/oligomycins-a-and-e-major-bioactive-secondary-metabolites-produced-by-streptomyces-sp-strain-hg29-isolated-from-a-saharan-soil
#2
N Khebizi, H Boudjella, C Bijani, N Bouras, H-P Klenk, F Pont, F Mathieu, N Sabaou
An actinobacterial strain, HG29, with potent activity against pathogenic, toxigenic and phytopathogenic fungi was isolated from a Saharan soil sample of Algeria. On the basis of morphological and chemotaxonomic characteristics, the strain was classified in the genus Streptomyces. Analysis of the 16S rRNA gene sequence showed a similarity level of 99.3% with Streptomyces gancidicus NBRC 15412(T). The comparison of its cultural and physiological characteristics with this species revealed significant differences...
November 17, 2017: Journal de Mycologie Médicale
https://www.readbyqxmd.com/read/29130344/neurokinin-1-receptor-antagonists-in-the-prevention-of-chemotherapy-induced-nausea-and-vomiting-focus-on-fosaprepitant
#3
Bernardo L Rapoport, Karin Jordan, Cindy Weinstein
Chemotherapy-induced nausea and vomiting (CINV) remains a challenge in cancer care. Improved understanding of CINV pathophysiology has triggered the development of new antiemetic therapeutic options, such as selective neurokinin-1 (NK1) receptor antagonists (RAs), which effectively prevent CINV when added to a standard antiemetic regimen (serotonin-3 RA and dexamethasone). Aprepitant and its water-soluble prodrug, fosaprepitant dimeglumine, are the most widely used NK1 RAs, with extensive clinical use worldwide...
November 13, 2017: Future Oncology
https://www.readbyqxmd.com/read/29107510/substance-p-attenuates-hypoxia-reoxygenation-induced-apoptosis-via-the-akt-signalling-pathway-and-the-nk1-receptor-in-h9c2cells
#4
Ying Xu, Qin Gu, Jian Tang, Yajun Qian, Xiao Tan, Zhuxi Yu, Chen Qu
BACKGROUND: Myocardial ischaemia/reperfusion (I/R) injury is a major cause of morbidity and mortality associated with coronary heart disease. During I/R injury, cardiomyocytes undergo cell death including apoptosis and necrosis with increased frequency, and this leads to compensatory cardiac hypertrophy, dysfunction, ventricular remodelling, and ultimately, heart failure. Accumulating evidence indicates that substance P is cardio-protective following I/R primarily due to its potent coronary vasodilator actions...
October 12, 2017: Heart, Lung & Circulation
https://www.readbyqxmd.com/read/29092012/a-randomized-phase-3-study-evaluating-the-efficacy-of-single-dose-nepa-a-fixed-antiemetic-combination-of-netupitant-and-palonosetron-versus-an-aprepitant-regimen-for-prevention-of-chemotherapy-induced-nausea-and-vomiting-cinv-in-patients-receiving-highly-emetogenic
#5
L Zhang, S Lu, J Feng, A Dechaphunkul, J Chang, D Wang, S Chessari, C Lanzarotti, K Jordan, M Aapro
Background: Co-administration of multiple antiemetics that inhibit several molecular pathways involved in emesis is required to optimize CINV control in patients receiving highly emetogenic chemotherapy (HEC). NEPA, a fixed combination of a highly selective NK1 receptor antagonist (RA), netupitant (300 mg), and the pharmacologically distinct 5-HT3RA, palonosetron (PALO 0.50 mg), has shown superior CINV prevention compared to PALO in cisplatin and anthracycline/cyclophosphamide-based settings...
October 28, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29091759/cd5-nk1-1-%C3%AE-%C3%AE-t-cells-that-develop-in-a-bcl11b-independent-manner-participate-in-early-protection-against-infection
#6
Shinya Hatano, Tesshin Murakami, Naoto Noguchi, Hisakata Yamada, Yasunobu Yoshikai
We recently found that a unique subset of innate-like γδ T cells develops from the DN2a stage of the fetal thymus independently of the zinc-finger transcription factor B cell leukemia/lymphoma 11b (Bcl11b). Herein, we characterize these Bcl11b-independent γδ T cells in the periphery as CD5(-)NK1.1(+) and Granzyme B(+), and we show that they are capable of producing interferon (IFN)-γ upon T cell receptor stimulation without Ca(2+) influx. In wild-type mice, these cells were sparse in lymphoid tissues but abundant in non-lymphoid tissues, such as the liver...
October 31, 2017: Cell Reports
https://www.readbyqxmd.com/read/29075004/from-receptor-binding-kinetics-to-signal-transduction-a-missing-link-in-predicting-in-vivo-drug-action
#7
Indira Nederpelt, Maria Kuzikov, Wilbert E A de Witte, Patrick Schnider, Bruno Tuijt, Sheraz Gul, Adriaan P IJzerman, Elizabeth C M de Lange, Laura H Heitman
An important question in drug discovery is how to overcome the significant challenge of high drug attrition rates due to lack of efficacy and safety. A missing link in the understanding of determinants for drug efficacy is the relation between drug-target binding kinetics and signal transduction, particularly in the physiological context of (multiple) endogenous ligands. We hypothesized that the kinetic binding parameters of both drug and endogenous ligand play a crucial role in determining cellular responses, using the NK1 receptor as a model system...
October 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29062837/endothelinergic-contractile-hyperreactivity-in-rat-contralateral-carotid-to-balloon-injury-integrated-role-for-etb-receptors-and-superoxide-anion
#8
Larissa Pernomian, Lilian R Gimenes, Mayara S Gomes, Bruno N do Vale, Cristina R B Cardoso, Ana M de Oliveira, Josimar D Moreira
Temporal consequences of neurocompensation to balloon injury on endothelinergic functionality in rat contralateral carotid were evaluated. Rats underwent balloon injury in left carotid and were treated with CP-96345 (NK1 antagonist). Concentration-response curves for endothelin-1 were obtained in contralateral (right) carotid at 2, 8, 16, 30, or 45 days after surgery in the absence or presence of BQ-123 (ETA antagonist), BQ-788 (ETB antagonist), or Tempol (superoxide-dismutase mimic). Endothelin-1-induced calcium mobilization was evaluated in functional assays carried out with BQ-123, BQ-788, or Tempol...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29055101/substance-p-and-dopamine-interact-to-modulate-the-distribution-of-delta-opioid-receptors-on-cholinergic-interneurons-in-the-striatum
#9
Emily Heath, Billy Chieng, Macdonald J Christie, Bernard W Balleine
It recently been demonstrated that predictive learning induces a persistent accumulation of delta-opioid receptors (DOPr's) at the somatic membrane of cholinergic interneurons (CINs) in the nucleus accumbens shell (Nac-S). This accumulation is required for predictive learning to influence subsequent choice between goal-directed actions. The current experiments investigated the local neurochemical events responsible for this translocation. We found that (1) local administration of substance P into multiple striatal sub-territories induced DOPr translocation and (2) that this effect was mediated by the NK1 receptor, likely through its expression on CINs...
October 20, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29042196/dcir3-and-dcir4-are-co-expressed-on-inflammatory-and-patrolling-monocytes
#10
Yu Hsu, Ryo Okada, Takashi Nishimura, Norihito Kawasaki, Kazuo Yamamoto, Naoki Matsumoto
Dendritic cell inhibitory receptor 3 (DCIR3) is a member of dendritic immuno-receptor family, of which protein expression has been unknown. We established a specific monoclonal antibody against mouse DCIR3 and investigated the expression of DCIR3 on immune cells of various immune organs. We found that DCIR3 was expressed on monocytes, but not on eosinophils and neutrophils. We also found the existence of a dichotomy in the levels of the expression of DCIR3 on monocytes in bone marrow, blood and spleen. Further investigation of the expression of several cell surface markers on DCIR3(High) cells and DCIR3(Low) cells revealed that DCIR3(High) cells were Ly-6C(-) CD43(High) CD11c(+) CD80(+) NK1...
October 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29038541/nk-cells-are-negatively-regulated-by-scd83-in-experimental-autoimmune-uveitis
#11
Wei Lin, Xuejing Man, Peng Li, Nannan Song, Yingying Yue, Bingqing Li, Yuanbin Li, Yufei Sun, Qiang Fu
Natural killer (NK) cells represent a subset of lymphocytes that contribute to innate immunity and have been reported to play a role in autoimmune uveitis. However, the mechanisms regulating NK cellular function in this condition remain unclear. Herein, we investigated the status of NK cells in experimental autoimmune uveitis (EAU). We found that the number of CD83(+)CD3(-)NK1.1(+) cells was increased in the inflamed eyes and spleens of the EAU mouse model. At the recovery stage of EAU, serum concentrations of soluble CD83 (sCD83) were increased...
October 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29030486/single-cell-rna-sequencing-reveals-developmental-heterogeneity-among-early-lymphoid-progenitors
#12
Llucia Alberti-Servera, Lilly von Muenchow, Panagiotis Tsapogas, Giuseppina Capoferri, Katja Eschbach, Christian Beisel, Rhodri Ceredig, Robert Ivanek, Antonius Rolink
Single-cell RNA sequencing is a powerful technology for assessing heterogeneity within defined cell populations. Here, we describe the heterogeneity of a B220(+)CD117(int)CD19(-)NK1.1(-) uncommitted hematopoietic progenitor having combined lymphoid and myeloid potential. Phenotypic and functional assays revealed four subpopulations within the progenitor with distinct lineage developmental potentials. Among them, the Ly6D(+)SiglecH(-)CD11c(-) fraction was lymphoid-restricted exhibiting strong B-cell potential, whereas the Ly6D(-)SiglecH(-)CD11c(-) fraction showed mixed lympho-myeloid potential...
October 13, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28978206/overview-of-chemotherapy-induced-nausea-and-vomiting-and-evidence-based-therapies
#13
Nelly Adel
Among patients with cancer, chemotherapy-induced nausea and vomiting (CINV) is a common adverse effect that not only impacts quality of life, but also treatment outcomes. It is important to address these issues from both prevention and treatment standpoints so that patients remain adherent to their regimens. With CINV being classified into 5 different types, the primary medication options for prevention and treatment include 5-HT3 receptor antagonists, NK1 receptor antagonists, and corticosteroids. Other medications used, but to a lesser extent, include dopamine antagonists, benzodiazepines, cannabinoids, and olanzapine...
September 2017: American Journal of Managed Care
https://www.readbyqxmd.com/read/28969417/development-of-a-ligand-targeted-therapeutic-agent-for-neurokinin-1-receptor-expressing-cancers
#14
Ananda Kumar Kanduluru, Philip S Low
The neurokinin-1 receptor (NK1R) plays a significant role in the progression and metastasis of several neuroendocrine tumors. Due to its upregulation in these cancers, NK1R constitutes an attractive receptor for development of ligand-targeted imaging and therapeutic agents. In this report, we present the design and synthesis of an NK1R targeting ligand conjugated to the chemotherapeutic agent, tubulysin B hydrazide (TubBH), via a self-immolative linker. We then explore the ability of this low molecular weight tubulysin conjugate to kill NK1R overexpressing cancer cells both in vitro and in vivo without killing receptor negative healthy cells...
November 6, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28943322/contribution-of-intercellular-adhesion-molecule-1-icam-1-to-control-mycobacterium-avium-infection
#15
Rafaella R de Paula, Fábio V Marinho, Julia S Fahel, Sergio C Oliveira
Mycobacterium avium is a facultative intracellular opportunistic pathogen especially relevant in cases of people living with AIDS. The aim of this study was to evaluate the role of intercellular adhesion molecule 1 (ICAM-1) in the inflammatory response against M. avium infection. Mice deficient for ICAM-1 (ICAM KO) and infected with M. avium presented increased bacterial load in the spleen, liver and lungs compared to C57BL/6. Moreover, ICAM deficient mice presented reduced granuloma area in liver at 30 days post-infection with reduced numbers of lymphocytes and granulocytes...
September 22, 2017: Microbes and Infection
https://www.readbyqxmd.com/read/28929404/rolapitant-a-review-in-chemotherapy-induced-nausea-and-vomiting
#16
Young-A Heo, Emma D Deeks
Oral rolapitant (Varubi™; Varuby(®)), a long-acting neurokinin-1 (NK1) receptor antagonist (RA), is indicated in the USA and EU as part of an antiemetic regimen to prevent delayed chemotherapy-induced nausea and vomiting (CINV) in adults receiving highly or moderately emetogenic chemotherapy (HEC or MEC). In randomized, phase III trials, a single oral dose of rolapitant 180 mg was effective in preventing delayed CINV compared with placebo, when each was used in combination with a 5-HT3 RA plus dexamethasone, in adults receiving their first course of HEC or MEC...
October 2017: Drugs
https://www.readbyqxmd.com/read/28861627/is-the-addition-of-a-neurokinin-1-receptor-antagonist-beneficial-in-moderately-emetogenic-chemotherapy-a-systematic-review-and-meta-analysis
#17
Karin Jordan, Luisa Blättermann, Axel Hinke, Carsten Müller-Tidow, Franziska Jahn
PURPOSE: This systematic review evaluates the efficacy of neurokinin-1 receptor antagonists (NK1RAs) for the prevention of chemotherapy-induced nausea and vomiting (CINV) in moderately emetogenic chemotherapy (MEC) excluding anthracycline-cyclophosphamide-based regimens. METHODS: A systematic review of MEDLINE (via PubMed and OVID) and Central databases, plus major oncology conferences, identified randomized trials evaluating NK1RAs in combination with a 5-HT3 RA plus a glucocorticoid for management of CINV...
August 31, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28837064/hepatocyte-growth-factor-mediates-enhanced-wound-healing-responses-and-resistance-to-transforming-growth-factor-%C3%AE-%C3%A2-driven-myofibroblast-differentiation-in-oral-mucosal-fibroblasts
#18
Jordanna Dally, Jabur S Khan, Alex Voisey, Chrisandrea Charalambous, Hannah L John, Emma L Woods, Robert Steadman, Ryan Moseley, Adam C Midgley
Oral mucosal wounds are characterized by rapid healing with minimal scarring, partly attributable to the "enhanced" wound healing properties of oral mucosal fibroblasts (OMFs). Hepatocyte growth factor (HGF) is a pleiotropic growth factor, with potential key roles in accelerating healing and preventing fibrosis. HGF can exist as full-length or truncated (HGF-NK), NK1 and NK2 isoforms. As OMFs display elevated HGF expression compared to dermal fibroblasts (DFs), this study investigated the extent to which HGF mediates the preferential cellular functions of OMFs, and the influence of pro-fibrotic, transforming growth factor-β₁ (TGF-β₁) on these responses...
August 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28830530/prenatal-tobacco-smoke-exposure-predisposes-offspring-mice-to-exacerbated-allergic-airway-inflammation-associated-with-altered-innate-effector-function
#19
Maria Ferrini, Sophia Carvalho, Yoon Hee Cho, Britten Postma, Lucas Miranda Marques, Kent Pinkerton, Kevan Roberts, Zeina Jaffar
BACKGROUND: Epidemiological studies suggest that prenatal and early life environmental exposures have adverse effects on pulmonary function and are important contributors in the development of childhood asthma and allergic disease. The mechanism by which environmental tobacco smoke (ETS) exposure in utero promotes the development of allergic asthma remains unclear. In this study, we investigated the immunological consequences of prenatal exposure to ETS in order to understand events responsible for the development or exacerbation of allergic asthma...
August 22, 2017: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/28827556/characterization-and-structural-determination-of-a-new-anti-met-function-blocking-antibody-with-binding-epitope-distinct-from-the-ligand-binding-domain
#20
Danielle M DiCara, Dimitri Y Chirgadze, Anthony R Pope, Aneesh Karatt-Vellatt, Anja Winter, Peter Slavny, Joop van den Heuvel, Kothai Parthiban, Jane Holland, Len C Packman, Georgia Mavria, Jens Hoffmann, Walter Birchmeier, Ermanno Gherardi, John McCafferty
The growth and motility factor Hepatocyte Growth Factor/Scatter Factor (HGF/SF) and its receptor, the product of the MET proto-oncogene, promote invasion and metastasis of tumor cells and have been considered potential targets for cancer therapy. We generated a new Met-blocking antibody which binds outside the ligand-binding site, and determined the crystal structure of the Fab in complex with its target, which identifies the binding site as the Met Ig1 domain. The antibody, 107_A07, inhibited HGF/SF-induced cell migration and proliferation in vitro and inhibited growth of tumor xenografts in vivo...
August 21, 2017: Scientific Reports
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