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Priming agents

Pini Koplovitch, Marshall Devor
Ectopic impulse discharge (ectopia) generated in the soma of afferent neurons in dorsal root ganglia (DRGs) following nerve injury is thought to be a major contributor to neuropathic pain. The DRG is thus a prime interventional target. The process of electrogenesis (impulse generation) in the DRG is far more sensitive to systemically administered Na channel blockers than the process of impulse propagation along sensory axons. It should therefore be possible to selectively suppress DRG ectopia with local application of membrane stabilizing agents without blocking normal impulse traffic...
March 12, 2018: Pain
Regla M Medina-Gali, María Del Mar Ortega-Villaizán, Luis Mercado, Beatriz Novoa, Julio Coll, Luis Perez
The antiviral effects of beta-glucan, an immunostimulatory agent were studied in zebrafish both in vitro and in vivo. Here we show that zebrafish ZF4 cells as well as whole fish primed with yeast β-glucan zymosan exhibited increased cytokine expression and elevated response to spring viremia of carp virus (SVCV) infection. In vitro, previous treatment of β-glucan enhanced ZF4 cell viability against SVCV infection which is associated to the activation of interferon signaling pathway and inflammatory cytokines gene expression...
March 7, 2018: Developmental and Comparative Immunology
Letizia Romeo, Renato Iori, Patrick Rollin, Placido Bramanti, Emanuela Mazzon
The use of plant-derived products as antimicrobial agents has been investigated in depth. Isothiocyanates (ITCs) are bioactive products resulting from enzymatic hydrolysis of glucosinolates (GLs), the most abundant secondary metabolites in the botanical order Brassicales. Although the antimicrobial activity of ITCs against foodborne and plant pathogens has been well documented, little is known about their antimicrobial properties against human pathogens. This review collects studies that focus on this topic...
March 9, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Jpm Tribst, L C Anami, M Özcan, M A Bottino, R M Melo, Gsfa Saavedra
This study tested whether a self-etching surface agent and the conventional hydrofluoric acid (HF) would provide the same bonding capacity between resin cement and feldspathic (Fd) and lithium disilicate (Ld) ceramics. Ceramic blocks were cut with a low-speed diamond saw with water cooling (Isomet 1000, Buehler, Lake Bluff, IL, USA) into 20 blocks of 5 × 7 × 4 mm, which were ground flat in a polishing machine (EcoMet/AutoMet 250, Buehler) under water cooling. The blocks were randomly divided into eight groups (n=5), according to ceramic type (Ld or Fd), surface conditioning (HF + Monobond Plus or Etch and Prime), and aging by thermocycling (TC or absence-baseline)...
March 7, 2018: Operative Dentistry
Anja Mottok, Christian Steidl
Hodgkin lymphoma is considered a prime example of treatment success with cure rates exceeding 80% using modern combined modality therapies. However, especially in adolescents and young adults, treatment-related toxicity and long-term morbidity still represent persistent challenges. Moreover, outcomes in patients with relapsed or refractory disease remain unfavorable in the era of high-dose chemotherapy and stem cell transplantation. Hence, there is a high demand for novel and innovative alternative treatment approaches...
March 2, 2018: Blood
Seyed Mostafa Mousavinasab, Mohammad Atai, Mehrdad Barekatain, Parisa Fattahi, Amir Fattahi, Vahid Rakhshan
Background: The aim of this study was to assess for the first time the effects of different amounts of ethanol solvent on the microtensile bond strength of composite bonded to dentin using a polyhedral oligomeric silsesquioxane (POSS)-incorporated adhesive. Materials and Methods: This experimental study was performed on 120 specimens divided into six groups (in accordance with the ISO TR11405 standard requiring at least 15 specimens per group). Occlusal dentin of thirty human molar teeth was exposed by removing its enamel...
January 2018: Dental Research Journal
Divya Singh, Himanshi Tanwar, Sudeshna Das, Lilly Ganju, Shashi Bala Singh
OBJECTIVE: Kaempferol, a natural flavonol present in various traditional medicinal plants, is known to possess potent anti-inflammatory properties. This study was designed to study the adjuvant effect of kaempferol administration along with ovalbumin antigen (K + O) in balb/c mice. METHODS: Mice were immunized with kaempferol (100 and 50 mg/kg body weight) without or with ovalbumin (20 µg/mouse). After priming, booster was administered on day 21. Antigen specific IgG titers and its subtypes, on day 28, were estimated by indirect ELISA...
February 28, 2018: Immunopharmacology and Immunotoxicology
Joanna C Evans, Valerie Mizrahi
Claiming close to two million lives each year, tuberculosis is now the leading cause of death from an infectious disease. The rise in number of Mycobacterium tuberculosis (Mtb) strains resistant to existing TB drugs has underscored the urgent need to develop new antimycobacterials with novel mechanisms of action. To meet this need, a drug pipeline has been established that is populated with new and repurposed drugs. Recent advances in identifying molecules with inhibitory activity against Mtb under conditions modelled on those encountered during infection, and in elucidating their mechanisms of action, have primed the pipeline with promising drug/target couples, hit compounds and new targets...
February 23, 2018: Current Opinion in Microbiology
Martina Sundqvist, Karin Christenson, André Holdfeldt, Michael Gabl, Jonas Mårtensson, Lena Björkman, Regis Dieckmann, Claes Dahlgren, Huamei Forsman
GPR84 is a recently de-orphanized member of the G-protein coupled receptor (GPCR) family recognizing medium chain fatty acids, and has been suggested to play important roles in inflammation. Due to the lack of potent and selective GPR84 ligands, the basic knowledge related to GPR84 functions is very limited. In this study, we have characterized the GPR84 activation profile and regulation mechanism in human phagocytes, using two recently developed small molecules that specifically target GPR84 agonistically (ZQ16) and antagonistically (GLPG1205), respectively...
February 22, 2018: Biochimica et Biophysica Acta
Chih-Jung Yao, Shuang-En Chuang, Ya-Yu Yang, Gi-Ming Lai
OBJECTIVE: To investigate the potential neuroprotective effect of human urine extract cell differentiation agent 2 (CDA-2) by the model of serum deprivation-induced apoptosis of PC12 cells and study the underlying molecular mechanisms. METHODS: Apoptosis of PC12 cells was induced by serum deprivation. CDA-2 at doses of 0.5-4 mg/mL was used to treat the serum-deprived PC12 cells. The cellular viability was measured by sulforhodamine B binding assay and the cell apoptosis was determined by flow cytometer...
February 17, 2018: Chinese Journal of Integrative Medicine
Khushboo Agrawal, Viswanath Das, Pankhuri Vyas, Marián Hajdúch
DNA methylation plays a pivotal role in the etiology of cancer by mediating epigenetic silencing of cancer-related genes. Since the relationship between aberrant DNA methylation and cancer has been understood, there has been an explosion of research at developing anti-cancer therapies that work by inhibiting DNA methylation. From the discovery of first DNA hypomethylating drugs in the 1980s to recently discovered second generation pro-drugs, exceedingly large number of studies have been published that describe the DNA hypomethylation-based anti-neoplastic action of these drugs in various stages of the pre-clinical investigation and advanced stages of clinical development...
February 15, 2018: Pharmacology & Therapeutics
Shizuka Takaku, Hideji Yako, Naoko Niimi, Tomoyo Akamine, Daiji Kawanami, Kazunori Utsunomiya, Kazunori Sango
Co-culture models of neurons and Schwann cells have been utilized for the study of myelination and demyelination in the peripheral nervous system; in most of the previous studies, however, these cells were obtained by primary culture with embryonic or neonatal animals. A spontaneously immortalized Schwann cell line IFRS1 from long-term cultures of adult Fischer rat peripheral nerves has been shown to retain fundamental ability to myelinate neurites in co-cultures with adult rat dorsal root ganglion neurons and nerve growth factor-primed PC12 cells...
February 12, 2018: Histochemistry and Cell Biology
Yuji Masuta, Takuya Yamamoto, Yayoi Natsume-Kitatani, Tomohiro Kanuma, Eiko Moriishi, Kouji Kobiyama, Kenji Mizuguchi, Yasuhiro Yasutomi, Ken J Ishii
The priming, boosting, and restoration of memory cytotoxic CD8+ T lymphocytes by vaccination or immunotherapy in vivo is an area of active research. Particularly, nucleic acid-based compounds have attracted attention due to their ability to elicit strong Ag-specific CTL responses as a vaccine adjuvant. Nucleic acid-based compounds have been shown to act as anticancer monotherapeutic agents even without coadministration of cancer Ag(s); however, so far they have lacked efficacy in clinical trials. We recently developed a second-generation TLR9 agonist, a humanized CpG DNA (K3) complexed with schizophyllan (SPG), K3-SPG, a nonagonistic Dectin-1 ligand...
February 5, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Dioneia Araldi, Eugen V Khomula, Luiz F Ferrari, Jon D Levine
Systemic fentanyl induces hyperalgesic priming, long-lasting neuroplasticity in nociceptor function characterized by prolongation of inflammatory mediator hyperalgesia. To evaluate priming at both nociceptor terminals, we studied, in male Sprague--Dawley rats, the effect of local administration of agents that reverse Type I (protein translation) or Type II (combination of Src and mitogen-activated protein kinase [MAPK]) priming. While at the central terminal, priming induced by systemic, intradermal or intrathecal fentanyl was reversed by the combination of Src and MAPK inhibitors, at the peripheral terminal it was reversed by the protein translation inhibitor...
February 5, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Ivana Halova, Elin Rönnberg, Lubica Draberova, Harissios Vliagoftis, Gunnar P Nilsson, Petr Draber
Mast cells play a key role in allergy and other inflammatory diseases involving engagement of multivalent antigen with IgE bound to high-affinity IgE receptors (FcεRIs). Aggregation of FcεRIs on mast cells initiates a cascade of signaling events that eventually lead to degranulation, secretion of leukotrienes and prostaglandins, and cytokine and chemokine production contributing to the inflammatory response. Exposure to pro-inflammatory cytokines, chemokines, bacterial and viral products, as well as some other biological products and drugs, induces mast cell transition from the basal state into a primed one, which leads to enhanced response to IgE-antigen complexes...
March 2018: Immunological Reviews
Matthias Gromeier, Smita K Nair
Mechanisms to elicit antiviral immunity, a natural host response to viral pathogen challenge, are of eminent relevance to cancer immunotherapy. "Oncolytic" viruses, naturally existing or genetically engineered viral agents with cell type-specific propagation in malignant cells, were ostensibly conceived for their tumor cytotoxic properties. Yet, their true therapeutic value may rest in their ability to provoke antiviral signals that engage antitumor immune responses within the immunosuppressive tumor microenvironment...
January 29, 2018: Annual Review of Medicine
Carlos Eduardo Sampaio Guedes, Beatriz Rocha Simões Dias, Antonio Luis de Oliveira Almeida Petersen, Kercia Pinheiro Cruz, Niara de Jesus Almeida, Daniela Rodrigues Andrade, Juliana Perrone Bezerra de Menezes, Valéria de Matos Borges, Patricia Sampaio Tavares Veras
BACKGROUND: Leishmaniasis, one of the most neglected diseases, is a serious public health problem in many countries, including Brazil. Currently available treatments require long-term use and have serious side effects, necessitating the development of new therapeutic interventions. Because translocator protein (TSPO) levels are reduced in Leishmania amazonensis-infected cells and because this protein participates in apoptosis and immunomodulation, TSPO represents a potential target for Leishmania chemotherapy...
February 5, 2018: Memórias do Instituto Oswaldo Cruz
Charles C Wykoff, W Lloyd Clark, Jared S Nielsen, Joel V Brill, Laurence S Greene, Cherilyn L Heggen
BACKGROUND: The introduction of anti-vascular endothelial growth factor (anti-VEGF) drugs to ophthalmology has revolutionized the treatment of neovascular age-related macular degeneration (nAMD). Despite this significant progress, gaps and challenges persist in the diagnosis of nAMD, initiation of treatment, and management of frequent intravitreal injections. Thus, nAMD remains a leading cause of blindness in the United States. OBJECTIVE: To present current knowledge, evidence, and expert perspectives on anti-VEGF therapies in nAMD to support managed care professionals and providers in decision making and collaborative strategies to overcome barriers to optimize anti-VEGF treatment outcomes among nAMD patients...
February 2018: Journal of Managed Care & Specialty Pharmacy
H M H Spronk, T Padro, J E Siland, J H Prochaska, J Winters, A C van der Wal, J J Posthuma, G Lowe, E d'Alessandro, P Wenzel, D M Coenen, P H Reitsma, W Ruf, R H van Gorp, R R Koenen, T Vajen, N A Alshaikh, A S Wolberg, F L Macrae, N Asquith, J Heemskerk, A Heinzmann, M Moorlag, N Mackman, P van der Meijden, J C M Meijers, M Heestermans, T Renné, S Dólleman, W Chayouâ, R A S Ariëns, C C Baaten, M Nagy, A Kuliopulos, J J Posma, P Harrison, M J Vries, H J G M Crijns, E A M P Dudink, H R Buller, Y M C Henskens, A Själander, S Zwaveling, O Erküner, J W Eikelboom, A Gulpen, F E C M Peeters, J Douxfils, R H Olie, T Baglin, A Leader, U Schotten, B Scaf, H M M van Beusekom, L O Mosnier, L van der Vorm, P Declerck, M Visser, D W J Dippel, V J Strijbis, K Pertiwi, A J Ten Cate-Hoek, H Ten Cate
Atherothrombosis is a leading cause of cardiovascular mortality and long-term morbidity. Platelets and coagulation proteases, interacting with circulating cells and in different vascular beds, modify several complex pathologies including atherosclerosis. In the second Maastricht Consensus Conference on Thrombosis, this theme was addressed by diverse scientists from bench to bedside. All presentations were discussed with audience members and the results of these discussions were incorporated in the final document that presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following five topics: 1...
February 2018: Thrombosis and Haemostasis
Lingjie Meng, Xunan Jing, Zhe Zhi, Daquan Wang, Jing Liu, Yongping Shao
Liver cancer is currently among the most challenging cancers to diagnose and treat. It is of prime importance to minimize the side effects on healthy tissues and reduce drug resistance for precise diagnoses and effective treatment of liver cancer. Herein, we report a facile, but high-yield approach to fabricate a multifunctional nanomaterial through the loading of chitosan and metformin on Mn-doped Fe3O4@MoS2 nanoflowers. Mn-doped Fe3O4 cores are used as simultaneous T1/T2 magnetic resonance imaging (MRI) agents for sensitive and accurate cancer diagnosis, while MoS2 nanosheets are used as effective near-infrared photothermal conversion agents for potential photothermal therapy...
January 27, 2018: Bioconjugate Chemistry
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