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https://www.readbyqxmd.com/read/28929404/rolapitant-a-review-in-chemotherapy-induced-nausea-and-vomiting
#1
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...
September 20, 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
#2
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
#3
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
#4
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
#5
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
https://www.readbyqxmd.com/read/28817088/the-role-of-neurogenic-inflammation-in-blood-brain-barrier-disruption-and-development-of-cerebral-oedema-following-acute-central-nervous-system-cns-injury
#6
REVIEW
Annabel J Sorby-Adams, Amanda M Marcoionni, Eden R Dempsey, Joshua A Woenig, Renée J Turner
Acute central nervous system (CNS) injury, encompassing traumatic brain injury (TBI) and stroke, accounts for a significant burden of morbidity and mortality worldwide, largely attributable to the development of cerebral oedema and elevated intracranial pressure (ICP). Despite this, clinical treatments are limited and new therapies are urgently required to improve patient outcomes and survival. Originally characterised in peripheral tissues, such as the skin and lungs as a neurally-elicited inflammatory process that contributes to increased microvascular permeability and tissue swelling, neurogenic inflammation has now been described in acute injury to the brain where it may play a key role in the secondary injury cascades that evolve following both TBI and stroke...
August 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28814387/effects-of-nk1-receptors-on-gastric-motor-functions-and-satiation-in-healthy-humans-results-from-a-controlled-trial-with-the-nk1-antagonist-aprepitant
#7
Deepti Jacob, Irene A Busciglio, Duane D Burton, Houssam Halawi, Ibironke Oduyebo, Deborah Rhoten, Michael Ryks, W Scott Harmsen, Michael Camilleri
Aprepitant, an NK1 receptor antagonist, is approved for the treatment of chemotherapy-induced or postoperative emesis by blocking NK1 receptors in the brain stem vomiting center. Effects of NK1 receptors on gastric functions and postprandial symptoms in humans are unclear; a single, crossover study did not show a significant effect of aprepitant on gastrointestinal transit. Our aim was to compare, in a randomized, double-blind, placebo-controlled, parallel-group study (12 healthy volunteers per group), effects of aprepitant vs...
August 16, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28814338/anti-nausea-effects-and-pharmacokinetics-of-ondansetron-maropitant-and-metoclopramide-in-a-low-dose-cisplatin-model-of-nausea-and-vomiting-in-the-dog-a-blinded-crossover-study
#8
Hannah Kenward, Jonathan Elliott, Terry Lee, Ludovic Pelligand
BACKGROUND: Nausea is a subjective sensation which is difficult to measure in non-verbal species. The aims of this study were to determine the efficacy of three classes of antiemetic drugs in a novel low dose cisplatin model of nausea and vomiting and measure change in potential nausea biomarkers arginine vasopressin (AVP) and cortisol. A four period cross-over blinded study was conducted in eight healthy beagle dogs of both genders. Dogs were administered 18 mg/m(2) cisplatin intravenously, followed 45 min later by a 15 min infusion of either placebo (saline) or antiemetic treatment with ondansetron (0...
August 16, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28808842/colonic-motor-dysfunctions-in-a-mouse-model-of-high-fat-diet-induced-obesity-an-involvement-of-a2b-adenosine-receptors
#9
Luca Antonioli, Carolina Pellegrini, Matteo Fornai, Erika Tirotta, Daniela Gentile, Laura Benvenuti, Maria Cecilia Giron, Valentina Caputi, Ilaria Marsilio, Genny Orso, Nunzia Bernardini, Cristina Segnani, Chiara Ippolito, Balázs Csóka, Zoltán H Németh, György Haskó, Carmelo Scarpignato, Corrado Blandizzi, Rocchina Colucci
Adenosine A2B receptors (A2BR) regulate several enteric functions. However, their implication in the pathophysiology of intestinal dysmotility associated with high-fat diet (HFD)-induced obesity has not been elucidated. We investigated the expression of A2BR in mouse colon and their role in the mechanisms underlying the development of enteric dysmotility associated with obesity. Wild-type C57BL/6J mice were fed with HFD (60% kcal from fat) or normocaloric diet (NCD; 18% kcal from fat) for 8 weeks. Colonic A2BR localization was examined by immunofluorescence...
August 14, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28783481/fosaprepitant-for-the-management-of-refractory-pain-in-a-patient-with-cancer-related-dermatomyositis
#10
Jennifer D Dulin, Patrick J Coyne, Nicole M Bohm, Mary Adler
OBJECTIVE: Optimal pain management often requires multiple pharmacological interventions with the goal of disrupting the pain-signaling pathway and targeting the underlying pathophysiology. Off label use of nonpain medications may have a role in treating refractory pain syndromes. BACKGROUND: We report a case of a 60-year-old female with refractory nociceptive and neuropathic pain. Conventional therapies were either ineffective or fraught with side effects. Given the underlying inflammatory nature of her pain syndrome, and the role of substance P (SP) in pain transmission and modulation, we decided to use fosaprepitant, an SP and neurokinin-1 (NK1) receptor antagonist...
August 7, 2017: Journal of Palliative Medicine
https://www.readbyqxmd.com/read/28760930/down-modulation-of-effector-functions-in-nk-cells-upon-t-gondii-infection
#11
Afifa M Sultana, Ann Du, Berit Carow, Catrine M Angbjär, Jessica M Weidner, Sachie Kanatani, Jonas M Fuks, Tamara De Koning, Jaime James, Imogen O Mansfield, Tessa M Campbell, Lifeng Liu, Nadir Kadri, Henrik Lambert, Antonio Barragan, Benedict J Chambers
The obligate intracellular parasite Toxoplasma gondii (T. gondii) can actively infect any nucleated cell type including cells from the immune system. Rapid transfer of T. gondii from infected dendritic cells to effector natural killer (NK) cells may contribute to the parasite's sequestration and shielding from immune recognition shortly after infection. However, subversion of NK cell functions, such as cytotoxicity or production of pro-inflammatory cytokines such as IFNγ, upon parasite infection might also be beneficial to the parasite...
July 31, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28753469/nk1-receptor-antagonists-for-depression-why-a-validated-concept-was-abandoned
#12
REVIEW
Nadia M J Rupniak, Mark S Kramer
BACKGROUND: NK1 receptor antagonists were abandoned despite antidepressant efficacy in five randomized clinical trials. The loss of confidence may be attributed to the failure of a Phase III clinical program with the NK1 receptor antagonist aprepitant in Major Depression. This review examines how PET receptor occupancy was used to select doses for aprepitant and that these may not have achieved adequate exposure. METHODS: PubMed, Google Scholar, and FDA databases were searched for articles concerning NK1 receptor antagonists, human PET receptor occupancy and clinical trials in Major Depression...
July 20, 2017: Journal of Affective Disorders
https://www.readbyqxmd.com/read/28747426/intestinal-epithelial-cell-endoplasmic-reticulum-stress-promotes-mult1-up-regulation-and-nkg2d-mediated-inflammation
#13
Shuhei Hosomi, Joep Grootjans, Markus Tschurtschenthaler, Niklas Krupka, Juan D Matute, Magdalena B Flak, Eduardo Martinez-Naves, Manuel Gomez Del Moral, Jonathan N Glickman, Mizuki Ohira, Lewis L Lanier, Arthur Kaser, Richard Blumberg
Endoplasmic reticulum (ER) stress is commonly observed in intestinal epithelial cells (IECs) and can, if excessive, cause spontaneous intestinal inflammation as shown by mice with IEC-specific deletion of X-box-binding protein 1 (Xbp1), an unfolded protein response-related transcription factor. In this study, Xbp1 deletion in the epithelium (Xbp1(ΔIEC) ) is shown to cause increased expression of natural killer group 2 member D (NKG2D) ligand (NKG2DL) mouse UL16-binding protein (ULBP)-like transcript 1 and its human orthologue cytomegalovirus ULBP via ER stress-related transcription factor C/EBP homology protein...
July 26, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28745324/a-committed-postselection-precursor-to-natural-tcr%C3%AE-%C3%AE-intraepithelial-lymphocytes
#14
Christoph S N Klose, Jonas F Hummel, Lena Faller, Yannick d'Hargues, Karolina Ebert, Yakup Tanriver
The intestine is a major immune organ with several specialized lymphoid structures and immune cells. Among these are thymus-derived natural intraepithelial lymphocytes (IELs) that lack expression of the classical co-receptors CD4 or CD8αβ (double negative (DN)). Natural IELs are both αβ(+) and γδ(+) T cells that play important roles in the maintenance of the epithelial barrier at steady state and during inflammation. The transcription factor T-bet is essential for the peripheral development of natural IELs, but its role during thymic development has remained less clear...
July 26, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28744630/effects-of-chronic-tobacco-smoking-on-the-distribution-of-tachykinin-receptors-in-rat-pial-arteries
#15
N V Zakharchuk, V M Chertok, V A Nevzorova, E Yu Gonchar
Pial arteries of different diameter were studied in intact rats and after 6-month modeling of chronic tobacco smoking in rats. Expression of tachykinin NK1 receptors in pial arteries was studied by biomicroscopy and immunohistochemical methods. Chronic tobacco smoking induced considerable reorganizations of the arterial bed. The intensity of changes depended on the diameter of vessels. In small pial vessels that directly participate in the blood supply to the brain, pronounced vasodilatation and enhanced expression of NK1 receptors in the endothelium mediating the effects of substance P were observed; the number of these vessels also increased...
July 25, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28710964/design-synthesis-and-biological-studies-of-a-library-of-nk1-receptor-ligands-based-on-a-5-arylthiosubstituted-2-amino-4-6-diaryl-3-cyano-4h-pyran-core-switch-from-antagonist-to-agonist-effect-by-chemical-modification
#16
Rocío Recio, Empar Vengut-Climent, Bernard Mouillac, Hélène Orcel, Miguel López-Lázaro, José Manuel Calderón-Montaño, Eleuterio Álvarez, Noureddine Khiar, Inmaculada Fernández
A library of 5-arylthiosubstituted 2-amino-4,6-diaryl-3-cyano-4H-pyrans has been synthesized as a new family of non-peptide NK1 receptor ligands by a one-pot cascade process. Their biological effects via interaction with the NK1 receptor were experimentally determined as percentage of inhibition (for antagonists) and percentage of activation (for agonists), compared to the substance P (SP) effect, in IPone assay. A set of these amino compounds was found to inhibit the action of SP, and therefore can be considered as a new family of SP-antagonists...
June 28, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28701994/the-role-of-substance-p-in-secondary-pathophysiology-after-traumatic-brain-injury
#17
REVIEW
Robert Vink, Levon Gabrielian, Emma Thornton
It has recently been shown that substance P (SP) plays a major role in the secondary injury process following traumatic brain injury (TBI), particularly with respect to neuroinflammation, increased blood-brain barrier (BBB) permeability, and edema formation. Edema formation is associated with the development of increased intracranial pressure (ICP) that has been widely associated with increased mortality and morbidity after neurotrauma. However, a pharmacological intervention to specifically reduce ICP is yet to be developed, with current interventions limited to osmotic therapy rather than addressing the cause of increased ICP...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28699350/analgesic-properties-of-opioid-nk1-multitarget-ligands-with-distinct-in-vitro-profiles-in-naive-and-chronic-constriction-injury-mice
#18
Joanna Starnowska, Roberto Costante, Karel Guillemyn, Katarzyna Popiolek-Barczyk, Nga N Chung, Carole Lemieux, Attila Keresztes, Joost Van Duppen, Adriano Mollica, John Streicher, Jozef Vanden Broeck, Peter W Schiller, Dirk Tourwé, Joanna Mika, Steven Ballet, Barbara Przewlocka
The lower efficacy of opioids in neuropathic pain may be due to the increased activity of pronociceptive systems such as substance P. We present evidence to support this hypothesis in this work from the spinal cord in a neuropathic pain model in mice. Biochemical analysis confirmed the elevated mRNA and protein level of pronociceptive substance P, the major endogenous ligand of the neurokinin-1 (NK1) receptor, in the lumbar spinal cord of chronic constriction injury (CCI)-mice. To improve opioid efficacy in neuropathic pain, novel compounds containing opioid agonist and neurokinin 1 (NK1) receptor antagonist pharmacophores were designed...
July 26, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28698251/trpa1-mechanoreceptors-mediate-the-il-6-response-to-a-single-pd-dwell-in-the-rat
#19
Daniel Nilsson, Eva Jennische, Nicola Cavallini, Magnus Braide
BACKGROUND: The development of modern, biocompatible peritoneal dialysis (PD) fluids has not entirely eliminated the local pro-inflammatory effects of PD fluid administration. The present study was performed in order to establish the importance of known signaling pathways connected to mechano-, osmo- and chemo-sensors of the transient receptor potential (TRP) family for the acute inflammatory response to PD. METHODS: Rats were exposed to a single 4-hour dwell of lactate-buffered, 2...
July 11, 2017: Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis
https://www.readbyqxmd.com/read/28669862/spontaneous-and-bite-evoked-muscle-pain-are-mediated-by-a-common-nociceptive-pathway-with-differential-contribution-by-trpv1
#20
Sheng Wang, Jongseuk Lim, John Joseph, Sen Wang, Feng Wei, Jin Y Ro, Man-Kyo Chung
Spontaneous pain and function-associated pain are prevalent symptoms of multiple acute and chronic muscle pathologies. We established mouse models for evaluating spontaneous pain and bite-evoked pain from masseter muscle, and determined the roles of transient receptor potential cation channel subfamily V member 1 (TRPV1) and the contribution of TRPV1- or neurokinin 1 (NK1)-dependent nociceptive pathways. Masseter muscle inflammation increased Mouse Grimace Scale scores and face-wiping behavior, which were attenuated by pharmacological or genetic inhibition of TRPV1...
June 29, 2017: Journal of Pain: Official Journal of the American Pain Society
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