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immune modulatory drugs

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
Georgia M Walton, James A Stockley, Diane Griffiths, Charandeep S Sadhra, Thomas Purvis, Elizabeth Sapey
Drug classes used in the treatment of Chronic Obstructive Pulmonary Disease (COPD) have not changed for many years, and none to date have shown disease-modifying activity. Statins are used to help reduce cardiovascular risk, which is high in many patients with COPD. Their use has been associated with improvements in some respiratory manifestations of disease and reduction in all-cause mortality, with greatest reductions seen in patients with the highest inflammatory burden. The mechanism for these effects is poorly understood...
October 11, 2016: Journal of Clinical Medicine
Thomas Lombard, Virginie Neirinckx, Bernard Rogister, Yves Gilon, Sabine Wislet
In recent years, medication-related osteonecrosis of the jaw (MRONJ) became an arising disease due to the important antiresorptive drug prescriptions to treat oncologic and osteoporotic patients, as well as the use of new antiangiogenic drugs such as VEGF antagonist. So far, MRONJ physiopathogenesis still remains unclear. Aiming to better understand MRONJ physiopathology, the first objective of this review would be to highlight major molecular mechanisms that are known to be involved in bone formation and remodeling...
2016: Stem Cells International
Amber M Smith
Secondary bacterial infections (SBIs) exacerbate influenza-associated disease and mortality. Antimicrobial agents can reduce the severity of SBIs, but many have limited efficacy or cause adverse effects. Thus, new treatment strategies are needed. Kinetic models describing the infection process can help determine optimal therapeutic targets, the time scale on which a drug will be most effective, and how infection dynamics will change under therapy. To understand how different therapies perturb the dynamics of influenza infection and bacterial coinfection and to quantify the benefit of increasing a drug's efficacy or targeting a different infection process, I analyzed data from mice treated with an antiviral, an antibiotic, or an immune modulatory agent with kinetic models...
September 27, 2016: Journal of Pharmacokinetics and Pharmacodynamics
Antonio Gambardella, Angelo Labate, Pierangelo Cifelli, Gabriele Ruffolo, Laura Mumoli, Eleonora Aronica, Eleonora Palma
Mesial temporal lobe epilepsy (MTLE) is frequently associated with hippocampal sclerosis (Hs), possibly caused by a primary brain injury that occurs a long time before the appearance of neurological symptoms. MTLE-Hs is, however, a heterogeneous condition that evolves with time, involving both environmental and genetic components. Recent experimental studies emphasize that drugs or drug combinations that target modulation and circuitry reorganization of the epileptogenic networks favorably modify the complex molecular and cellular alterations underlying MTLE...
September 19, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Xiaoli Han, Dan Su, Xiaoyan Xian, Mingyang Zhou, Xianzhe Li, Jian Huang, Jinhui Wang, Huiyuan Gao
ETHNOPHARMACOLOGICAL RELEVANCE: Saussurea involucrate (Kar. et Kir.) Sch. -Bip is an endangered species of the Compositae family, and this species has long been used for the treatment of rheumatoid arthritis, dysmenorrhea, stomachache, and altitude sickness in Uighur folk and Chinese medicine. AIM OF THE STUDY: This study aimed to investigate the different therapeutic efficacy of alcohol infusion (SEI) and water decoction (SWD) of S. involucrata in treating rheumatoid arthritis using complete Freund's adjuvant (CFA)-induced arthritis (AA) in a rat model...
September 8, 2016: Journal of Ethnopharmacology
Akiko Furukawa, Steven A Wisel, Qizhi Tang
Immunosuppression strategies that selectively inhibit effector T cells while preserving and even enhancing CD4FOXP3 regulatory T cells (Treg) permit immune self-regulation and may allow minimization of immunosuppression and associated toxicities. Many immunosuppressive drugs were developed before the identity and function of Treg were appreciated. A good understanding of the interactions between Treg and immunosuppressive agents will be valuable to the effective design of more tolerable immunosuppression regimens...
August 3, 2016: Transplantation
Hyo Won Jung, Kyung-Ho Kim, Yong-Ki Park
OBJECTIVE: To investigated whether the dried root of Phellodendron amurense Ruprecht (Phellodendri cortex; PC) extract improves arthritic symptoms through anti-inflammatory and immune-modulatory effects in collagen-induced arthritis in mice. METHODS: Rheumatoid arthritis (RA) was induced in male DBA/1 mice by immunization with type II collagen (ColII). CIA mice were divided into 5 groups (n=10 per a group) with normal, CIA control, PC extract (50 mg/kg and 100 mg/kg)-treated, and meloxicam (50 mg/kg)-treated as the reference drug...
July 26, 2016: Chinese Journal of Integrative Medicine
Richard W Scott, Gregory N Tew
New infection treatments are urgently needed to combat the rising threat of multi-drug resistant bacteria. Despite early clinical set-backs attention has re-focused on host defense proteins (HDPs), as potential sources for new and effective antimicrobial treatments. HDPs appear to act at multiple targets and their repertoire includes disruptive membrane and intracellular activities against numerous types of pathogens as well as immune modulatory functions in the host. Importantly, these novel activities are associated with a low potential for emergence of resistance and little cross-resistance with other antimicrobial agents...
July 13, 2016: Current Topics in Medicinal Chemistry
Alexandra Schifferli, Thomas Kühne
In 2008, new drugs that mimic the effects of thrombopoietin became available for the treatment of primary immune thrombocytopenia, eg, romiplostim and eltrombopag. These drugs activate the thrombopoietin receptor, stimulate the production of megakaryocytes, and increase the production of platelets. Important clinical observation has been gained, such as unexpected long-term remission after stopping thrombopoietin receptor agonists. The pathophysiology of this unforeseen cure is currently the subject of discussion and is investigated in clinical trials and laboratory research projects...
April 2016: Seminars in Hematology
Ruchika Khanna, Nisha Dua, Anand Kumar, Ruchit Khanna, Pyare Mohan Lal Khanna
Herbal medication still happens to be the backbone of the major world's population essentially because of the assumption that these drugs are free of any side effects and easily available. LongoVital (LV) is a herbal preparation with documented immune-modulatory and immune-stimulatory effects in man. Various studies conducted to date, have shown LV to have prolonged and beneficial impact in the treatment of orofacial diseases, when administered in recommended daily doses. With its combined antimicrobial and immunostimulatory effects, LV can be regarded as an emerging therapeutic modality in the treatment of orofacial diseases...
April 2016: Journal of Clinical and Diagnostic Research: JCDR
Jeremías Corradi, Cecilia Bouzat
The nicotinic acetylcholine receptor (nAChR) belongs to a superfamily of pentameric ligand-gated ion channels involved in many physiologic and pathologic processes. Among nAChRs, receptors comprising the α7 subunit are unique because of their high Ca(2+) permeability and fast desensitization. nAChR agonists elicit a transient ion flux response that is further sustained by the release of calcium from intracellular sources. Owing to the dual ionotropic/metabotropic nature of α7 receptors, signaling pathways are activated...
September 2016: Molecular Pharmacology
Franco Giubilei
Inflammation is a common response of an individual against either exogenous or endogenous damage. The role of inflammation and of inflammatory cells recently emerged also in the pathogenesis of neurodegenerative disorders. Experimental evidences show how neurotransmitters, besides their role in the synapses, play a modulatory role during immune response. Drugs used for treatment of dementia symptoms are able to increase neurotransmitters levels, and likely to have a modulatory role during immune response. Aim of this review is to discuss the most recent advances on inflammation role during neurodegeneration and also to individuate the potential anti-inflammatory role played by drugs currently used for Alzheimer's disease treatment...
2016: CNS & Neurological Disorders Drug Targets
X Chen, N Haddish-Berhane, P Moore, T Clark, Y Yang, H Li, D Xuan, H A Barton, A M Betts, F Barletta
A bispecific immunomodulatory biotherapeutic molecule (P-cadherin LP-DART) based on the Dual Affinity Re-Targeting (DART) scaffold has been developed as a potential antitumor treatment showing efficacy in preclinical testing. A minimal anticipated biological effect level (MABEL) approach was applied to project the first-in-human (FIH) dose, because of its immune agonistic properties following target engagement. The pharmacological activity of P-cadherin LP-DART is driven by binding to both P-cadherin on the tumor cells and CD3 on T cells...
September 2016: Clinical Pharmacology and Therapeutics
V Leuci, F Maione, R Rotolo, E Giraudo, F Sassi, G Migliardi, M Todorovic, L Gammaitoni, G Mesiano, L Giraudo, P Luraghi, F Leone, F Bussolino, G Grignani, M Aglietta, L Trusolino, A Bertotti, D Sangiolo
BACKGROUND: Angiogenesis inhibition is a promising approach for treating metastatic colorectal cancer (mCRC). Recent evidences support the seemingly counterintuitive ability of certain antiangiogenic drugs to promote normalization of residual tumor vessels with important clinical implications. Lenalidomide is an oral drug with immune-modulatory and anti-angiogenic activity against selected hematologic malignancies but as yet little is known regarding its effectiveness for solid tumors...
2016: Journal of Translational Medicine
Dana M Evans, Jennifer M Thorn, Katherine Arch-Douglas, Justin B Sperry, Bruce Thompson, Heather L Davis, Michael J McCluskie
The United States Food and Drug Administration recently removed the requirement for a General Safety Test (GST) for biologics in the Code of Federal Regulations (21 CFR 610.11). The GST, as well as abnormal toxicity (European Pharmacopeia) and innocuity tests (World Health Organization), were designed to test for extraneous toxic contaminants on each product lot intended for human use. Tests require one-week observations for general health and weight following injection of specified volumes of product batches into guinea pigs and mice...
May 2016: Biologicals: Journal of the International Association of Biological Standardization
Cesarina Giallongo, Daniele Tibullo, Nunziatina L Parrinello, Piera La Cava, Michelino Di Rosa, Vincenzo Bramanti, Cosimo Di Raimondo, Concetta Conticello, Annalisa Chiarenza, Giuseppe A Palumbo, Roberto Avola, Alessandra Romano, Francesco Di Raimondo
Granulocytic-Myeloid-derived suppressor cells (G-MDSC) are increased in Multiple Myeloma (MM) patients but the mechanisms of G-MDSC generation are still unknown. There are many evidences of the role of mesenchymal stem cells (MSC) in promoting MM cell growth, survival and drug-resistance. We here used a specific experimental model in vitro to evaluate the ability of MSC to induce G-MDSC. We found that although MSC derived from healthy donors (HD), MGUS and MM were able to generate the same amount of MDSC, only MM-MSC-educated G-MDSC exhibited suppressive ability...
March 7, 2016: Oncotarget
Georg Petzold, Eric S Fischer, Nicolas H Thomä
Thalidomide and its derivatives, lenalidomide and pomalidomide, are immune modulatory drugs (IMiDs) used in the treatment of haematologic malignancies. IMiDs bind CRBN, the substrate receptor of the CUL4-RBX1-DDB1-CRBN (also known as CRL4(CRBN)) E3 ubiquitin ligase, and inhibit ubiquitination of endogenous CRL4(CRBN) substrates. Unexpectedly, IMiDs also repurpose the ligase to target new proteins for degradation. Lenalidomide induces degradation of the lymphoid transcription factors Ikaros and Aiolos (also known as IKZF1 and IKZF3), and casein kinase 1α (CK1α), which contributes to its clinical efficacy in the treatment of multiple myeloma and 5q-deletion associated myelodysplastic syndrome (del(5q) MDS), respectively...
April 7, 2016: Nature
Sandeep T Koshy, David J Mooney
Cancer immunotherapy is becoming a standard approach to treat many cancers. However, shortcomings of current methods limit therapeutic benefit in many patients. Rationally designed biomaterial strategies to deliver immune modulatory drugs can potentially show improved safety profiles, while providing multifunctional and spatiotemporally controlled signals to immune cells to improve their anti-cancer activity. This brief review describes biomaterials-based strategies that enhance immune cell function at various tissue sites to improve anti-cancer immunity...
August 2016: Current Opinion in Biotechnology
Jesús F Bermejo-Martin, David Andaluz-Ojeda, Raquel Almansa, Francisco Gandía, Jose Ignacio Gómez-Herreras, Esther Gomez-Sanchez, María Heredia-Rodríguez, Jose Maria Eiros, David J Kelvin, Eduardo Tamayo
OBJECTIVES: Immunological dysregulation is now recognised as a major pathogenic event in sepsis. Stimulation of immune response and immuno-modulation are emerging approaches for the treatment of this disease. Defining the underlying immunological alterations in sepsis is important for the design of future therapies with immuno-modulatory drugs. METHODS: Clinical studies evaluating the immunological response in adult patients with Sepsis and published in PubMed were reviewed to identify features of immunological dysfunction...
May 2016: Journal of Infection
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