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Immunomodulatory drugs

Heidi Barth, Morgane Solis, Wallys Kack-Kack, Eric Soulier, Aurélie Velay, Samira Fafi-Kremer
Developments of genome amplification techniques have rapidly expanded the family of human polyomaviruses (PyV). Following infection early in life, PyV persist in their hosts and are generally of no clinical consequence. High-level replication of PyV can occur in patients under immunosuppressive or immunomodulatory therapy and causes severe clinical entities, such as progressive multifocal leukoencephalopathy, polyomavirus-associated nephropathy or Merkel cell carcinoma. The characterization of known and newly-discovered human PyV, their relationship to human health, and the mechanisms underlying pathogenesis remain to be elucidated...
October 22, 2016: Viruses
Angelika Drynda, Bożena Obmińska-Mrukowicz, Ewa Zaczyńska, Michał Zimecki, Iwona Kochanowska, Stanisław Ryng, Marcin Mączyński
Isoxazoles are an important class of compounds of potential therapeutic value. The aim of this study was to determine immunotropic effects of 5-amino-3-methyl-4-isoxazolecarboxylic acid hydrazide derivatives on spontaneous and mitogen-induced lymphocyte proliferation in young and old mice, cytokine production by peritoneal cells as well as possible mechanism of action in a model of Jurkat cells. Three month and thirteen month old BALB/c mice were used as donors of the cells from a thymus, a spleen, mesenteric lymph nodes and a peritoneal cavity...
October 25, 2016: Chemical Biology & Drug Design
Mohammad Islamuddin, Garima Chouhan, Muzamil Yaqub Want, Hani A Ozbak, Hassan A Hemeg, Farhat Afrin
BACKGROUND: The therapy of visceral leishmaniasis (VL) is limited by resistance, toxicity and decreased bioavailability of the existing drugs coupled with dramatic increase in HIV-co-infection, non-availability of vaccines and down regulation of cell-mediated immunity (CMI). Thus, we envisaged combating the problem with plant-derived antileishmanial drug that could concomitantly mitigate the immune suppression of the infected hosts. Several plant-derived compounds have been found to exert leishmanicidal activity via immunomodulation...
October 2016: PLoS Neglected Tropical Diseases
Lulu Jiang, Charles C T Hindmarch, Mark Rogers, Colin Campbell, Christy Waterfall, Jane Coghill, Peter W Mathieson, Gavin I Welsh
Glucocorticoids are steroids that reduce inflammation and are used as immunosuppressive drugs for many diseases. They are also the mainstay for the treatment of minimal change nephropathy (MCN), which is characterised by an absence of inflammation. Their mechanisms of action remain elusive. Evidence suggests that immunomodulatory drugs can directly act on glomerular epithelial cells or 'podocytes', the cell type which is the main target of injury in MCN. To understand the nature of glucocorticoid effects on non-immune cell functions, we generated RNA sequencing data from human podocyte cell lines and identified the genes that are significantly regulated in dexamethasone-treated podocytes compared to vehicle-treated cells...
October 24, 2016: Scientific Reports
Prithviraj Bose, Srdan Verstovsek
INTRODUCTION: Primary myelofibrosis (PMF) is the least common but the most aggressive of the classic Philadelphia chromosome-negative myeloproliferative neoplasms. Survival is much shorter in PMF than in polycythemia vera (PV) or essential thrombocythemia (ET). Post-PV/ET myelofibrosis (MF) is clinically indistinguishable from PMF and approached similarly. AREAS COVERED: Current pharmacologic therapy of MF revolves around the Janus kinase 1/2 (JAK1/2) inhibitor ruxolitinib, which dramatically improves constitutional symptoms and splenomegaly in the majority of patients, and improves overall survival (OS)...
October 22, 2016: Expert Opinion on Pharmacotherapy
Namrita Lall, Vivek Kumar, Debra Meyer, Nomasomi Gasa, Chris Hamilton, Motlalepula Matsabisa, Carel Oosthuizen
ETHNOPHARMACOLOGICAL RELEVANCE: The Natal gwarri or Natal ebony (Euclea natalensis A.DC.) is a deciduous tree found widespread throughout southern Africa, especially in Kwazulu-Natal and the southern cost. It has been widely used by indigenous communities such as the Zulus, Tsongas and Vendas for symptoms related to tuberculosis (TB). The decoctions made from the plant parts are administered for chest diseases to treat complications such as chest pains, bronchitis, pleurisy and asthma...
October 20, 2016: Journal of Ethnopharmacology
Seyyed Shamsadin Athari, Zahra Pourpak, Gert Folkerts, Johan Garssen, Mostafa Moin, Ian M Adcock, Masoud Movassaghi, Mehdi Shafiee Ardestani, Seyed Mohammad Moazzeni, Esmaeil Mortaz
Asthma is a chronic respiratory disease characterized by airway inflammation, bronchoconstriction, airway hyperresponsiveness and recurring attacks of impaired breathing. Vasoactive intestinal peptide (VIP) has been proposed as a novel anti-asthma drug due to its effects on airway smooth muscle relaxation, bronchodilation and vasodilation along with its immunomodulatory and anti-inflammatory properties. In the current study, we investigated the therapeutic effects of VIP when conjugated with α-alumina nanoparticle (α-AN) to prevent enzymatic degradation of VIP in the respiratory tract...
October 19, 2016: European Journal of Pharmacology
Ting Hu, Qilin Huang, Kahing Wong, Hong Yang
Four polysaccharide fractions, LRP-1, LRP-2, LRP-3 and LRP-4 were extracted stepwise from Lignosus rhinocerotis sclerotia with distilled water at 25, 95, 120°C and 1.0M NaOH solution at 4°C. Their structure, molecular size and chain conformation were clarified using SEC-MALLS-RI, GC, FT-IR and UV-VIS. Furthermore, their immunomodulatory activities were evaluated by the model of cyclophosphamide (Cy)-induced immunosuppression. The LRP-1 and LRP-2 were polysaccharide-protein complexes (46-68% β-D-glucan and 27-48% protein), while LRP-3 and LRP-4 were absolutely composed of β-D-glucose...
October 18, 2016: International Journal of Biological Macromolecules
Izabela Jatczak-Pawlik, Michal Gorzkiewicz, Maciej Studzian, Dietmar Appelhans, Brigitte Voit, Lukasz Pulaski, Barbara Klajnert-Maculewicz
PURPOSE: Fourth-generation poly(propylene imine) dendrimers fully surface-modified by maltose (dense shell, PPI-m DS) were shown to be biocompatible in cellular models, which is important for their application in drug delivery. We decided to verify also their inherent bioactivity, including immunomodulatory activity, for potential clinical applications. We tested their effects on the THP-1 monocytic cell line model of innate immunity effectors. METHODS: To estimate the cytotoxicity of dendrimers the reasazurin assay was performed...
October 20, 2016: Pharmaceutical Research
Sheikh Mohammad Fazle Akbar, Mamun Al-Mahtab, Md Sakilur Islam Khan, Ruksana Raihan, Ananta Shrestha
Although several antiviral drugs are now available for treatment of patients with chronic hepatitis B (CHB), sustained off-treatment clinical responses and containment of CHB-related complications are not achieved in majority of CHB patients by antiviral therapy. In addition, use of these drugs is endowed with substantial long term risk of viral resistance and drug toxicity. The infinite treatment regimens of antiviral drugs for CHB patients are also costly and usually unbearable by most patients of developing and resource-constrained countries...
September 2016: Annals of Translational Medicine
Jlenia Brunetti, Giulia Roscia, Ilaria Lampronti, Roberto Gambari, Leila Quercini, Chiara Falciani, Luisa Bracci, Alessandro Pini
The synthetic antimicrobial peptide SET-M33 has strong activity against bacterial infections due to Gram-negative bacteria. It is currently in preclinical development as a new drug to treat lung infections caused by Gram-negative bacteria. Here we report its strong anti-inflammatory activity in terms of reduced expression of a number of cytokines, enzymes and signal transduction factors involved in inflammation triggered by lipopolysaccharides (LPS) from P. aeruginosa, K. pneumoniae and E. coli. Sixteen cytokines and other major agents involved in inflammation were analyzed in macrophages and bronchial cells after stimulation with LPS and incubation with SET-M33...
October 7, 2016: Journal of Biological Chemistry
Crystal S Y Cheung, Nima Noordeh, Chloe C Gottlieb
BACKGROUND: The objectives of this study are to assess Canadian ophthalmologists' awareness of established uveitis treatment guidelines and clinical management of uveitis and to assess the frequency of government applications for immunomodulatory therapy (IMT) and identify primary prescribers. A 25-item questionnaire was sent to 759 practicing Canadian ophthalmologists. Six questions assessed demographics including the year of residency completion, training by uveitis specialists during residency, and fellowship training...
December 2016: Journal of Ophthalmic Inflammation and Infection
Héloïse M Delagrèverie, Constance Delaugerre, Sharon R Lewin, Steven G Deeks, Jonathan Z Li
In chronic human immunodeficiency virus (HIV)-1 infection, long-lived latently infected cells are the major barrier to virus eradication and functional cure. Several therapeutic strategies to perturb, eliminate, and/or control this reservoir are now being pursued in the clinic. These strategies include latency reversal agents (LRAs) designed to reactivate HIV-1 ribonucleic acid transcription and virus production and a variety of immune-modifying drugs designed to reverse latency, block homeostatic proliferation, and replenish the viral reservoir, eliminate virus-producing cells, and/or control HIV replication after cessation of antiretroviral therapy...
October 2016: Open Forum Infectious Diseases
Nathan B Roberts, Aniket S Wadajkar, Jeffrey A Winkles, Eduardo Davila, Anthony J Kim, Graeme F Woodworth
Glioblastoma (GBM) is a fatal brain cancer for which new treatment options are sorely needed. Platinum-based drugs have been investigated extensively for GBM treatment but few have shown significant efficacy without major central nervous system (CNS) and systemic toxicities. The relative success of platinum drugs for treatment of non-CNS cancers indicates great therapeutic potential when effectively delivered to the tumor region(s). New insights into the broad anticancer effects of platinum drugs, particularly immunomodulatory effects, and innovative delivery strategies that can maximize these multi-modal effects and minimize toxicities may promote the re-purposing of this chemotherapeutic drug class for GBM treatment...
2016: Oncoimmunology
Feng Zhou, Ying Zhang, Jing Chen, Xuemei Hu, Yancheng Xu
Liraglutide, an effective drug for the treatment of diabetes, has been proven to demonstrate anti-inflammatory and immunomodulatory effects. Hence, this study explored the effects and mechanism of action of liraglutide on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Male BALB/c mice were pre-conditioned with liraglutide or saline prior to intraperitoneal LPS or saline administration. Histopathological examination of lung, the wet/dry (W/D)weight ratio, protein content, inflammatory cell numbers and pro-inflammatory cytokine levels in broncho-alveolar lavage fluid (BAL fluid) were conducted...
October 15, 2016: European Journal of Pharmacology
Mallaiah Devanabanda, Shaik Abdul Latheef, Ramanadham Madduri
Understanding the effects of nanoparticles (NP) on immune cell functions is essential in designing safe and effective NP-based in vivo drug delivery systems. The immunomodulatory potential of gold nanoparticles (GNP) and silver nanoparticles (SNP) was investigated in vitro using murine splenic and human peripheral blood lymphocytes (PBL) in terms of effects on viability and mitogen-induced proliferation. Hydrodynamic size and number of NP were characterized using NP tracking analysis (NTA); modal diameters of GNP and SNP were 28 (±1...
October 18, 2016: Journal of Immunotoxicology
Muhammad Husnain, Sandra Kurtin, Nikki Barkett, Irbaz Bin Riaz, Amit Agarwal
Patients with relapsed and refractory multiple myeloma have poor prognosis. A recent analysis of patients with relapsed and refractory multiple myeloma who were refractory to both proteasome inhibitors and immunomodulatory drugs showed the median overall survival of 9 months only. Daratumumab is the first-in-class human monoclonal antibody against CD38 cells which was studied in phase I/II trials for treatment of these patients with relapsed refractory multiple myeloma. It showed an overall response rate of 36% and a median overall survival (OS) of 17 months in these patients...
2016: Case Reports in Oncological Medicine
Jesús F San-Miguel, Vania T M Hungria, Sung-Soo Yoon, Meral Beksac, Meletios A Dimopoulos, Ashraf Elghandour, Wieslaw W Jedrzejczak, Andreas Günther, Thanyaphong N Nakorn, Noppadol Siritanaratkul, Robert L Schlossman, Jian Hou, Philippe Moreau, Sagar Lonial, Jae H Lee, Hermann Einsele, Monika Sopala, Bourras-Rezki Bengoudifa, Florence Binlich, Paul G Richardson
BACKGROUND: Panobinostat plus bortezomib and dexamethasone significantly increased median progression-free survival compared with placebo plus bortezomib and dexamethasone in the phase 3 PANORAMA 1 trial. Here, we present the final overall survival analysis for this trial. METHODS: PANORAMA 1 is a randomised, placebo-controlled, double-blind, phase 3 trial of patients with relapsed or relapsed and refractory multiple myeloma with one to three previous treatments...
October 14, 2016: Lancet Haematology
Zhen Qu, Chunping Jiang, Junhua Wu, Yitao Ding
Hepatocellular carcinoma (HCC) remains a disease with a high mortality rate, and the treatment for HCC remains limited. It is necessary to develop efficient and low toxicity drugs for the clinical treatment of HCC. Lenalidomide is a novel analogue of thalidomide and has anti‑inflammatory, immunomodulatory and anti‑angiogenic effects. The current study investigated the inhibitory effect against HCC cells of lenalidomide and thalidomide. The MTT assay was used to determine the cytotoxicity of lenalidomide and thalidomide, and morphological changes were observed by fluorescence microscopy...
October 5, 2016: Molecular Medicine Reports
Arshad Khan, Robert L Hunter, Chinnaswamy Jagannath
Mesenchymal stem cells (MSCs) are non-hematopoietic cells that occur in almost all human tissues and can be cultured and expanded to large numbers in vitro. They secrete growth factors, cytokines, and chemokines and express Toll-like receptors on their surface, although multiple cell biological mechanisms remain unclear. MSCs are multi-potent and can differentiate into many cell types including adipocytes, neuronal cells and osteoclasts. Despite gaps in cell biology, because of their immunomodulatory and regenerative capacity, several hundred clinical trials have used MSCs for therapy of cancer, autoimmune diseases and control of inflammation during organ transplantation...
September 28, 2016: Tuberculosis
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