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OPEN ACCESS PLUS
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Contents
10(5): Pp. 327 - 338
M. E. Christopher and J. P. Wong
[Open Access Plus] |
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Respiratory RNA viruses are constantly evolving, thus requiring development of additional prophylactic and therapeutic strategies. Harnessing the innate immune system to non-specifically respond to viral infection has the advantage of being able to circumvent viral mutations that render the virus resistant to a particular therapeutic agent. Viruses are recognized by various cellular receptors, including Toll-like receptor (TLR) 3 which recognizes doublestranded (ds)RNA produced during the viral replication cycle. TLR3 agonists include synthetic dsRNA such as poly (IC), poly (ICLC) and poly (AU). These agents have been evaluated and found to be effective against a number of viral agents. One major limitation has been the toxicity associated with administration of these drugs. Significant time and effort have been spent to develop alternatives/modifications that will minimize these adverse effects. This review will focus on the TLR3 agonist, poly (IC)/(ICLC) with respect to its use in treatment/prevention of respiratory viral infections.
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10(4): Pp. 315 - 322
Giovanni Mantovani
[Open Access Plus] |
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Cachexia is a complex metabolic syndrome associated with many chronic or end-stage diseases, especially cancer, and is characterized by loss of muscle with or without loss of fat mass. The management of cancer-related anorexia/cachexia syndrome (CACS) is a complex challenge that should address the different causes underlying this clinical event with an integrated or multimodal treatment approach targeting the different factors involved in its pathophysiology. Among the treatments proposed in the literature for CACS, some proved to be ineffective, namely, cyproheptadine, hydrazine, metoclopramide, and pentoxifylline. Among effective treatments, progestagens are currently considered the best available treatment option for cancer-related cachexia, and they are the only drugs approved in Europe. Drugs with a strong rationale that have failed or have not shown univocal results in clinical trials so far include eicosapentaenoic acid, cannabinoids, bortezomib, and anti-TNF-α MoAb. Several emerging drugs have shown promising results but are still under clinical investigation (thalidomide, selective cyclooxygenase-2 (COX-2) inhibitors, ghrelin mimetics, insulin, oxandrolone, and olanzapine). However, to date, despite several years of co-ordinated efforts in basic and clinical research, practice guidelines for the prevention and treatment of cancer-related muscle wasting are lacking, mainly because of the multifactorial pathogenesis of the syndrome. From all the data presented, one can speculate that one single therapy may not be completely successful in the treatment of cachexia. A more effective approach might be a combination therapy targeting the different mechanisms contributing to CACS.
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10(3): Pp. 215 - 229
Xiao Wu, Oreoluwa O. Adedoyin and Heidi M. Mansour
[Open Access Plus] |
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Most respiratory infections, diseases and allergic reactions have varying degrees of inflammation. Inflammation is a natural immunodefensive response to the presence of allergens or foreign particles that come into contact or affect the cells and tissues within the respiratory tract. The three main types of therapeutic drug classes available for anti-inflammatory and anti-allergy effects are corticosteroids, antihistamines and decongestants. Corticosteroid drugs for pulmonary inhalation and/or nasal delivery include beclomethasone dipropionate, budesonide, ciclesonide, fluticasone furoate, fluticasone propionate, mometasone furoate, and triamcinolone acetonide. Antihistamine drugs for nasal delivery include azelastine and olopatadine. Two common decongestants available are oxymetazoline and phenylephrine. Another therapeutic class, the anticholinergic agents, such as ipratropium bromide and tiotropium bromide, are used in pulmonary delivery in the treatment of inflammatory diseases such as asthma and chronic obstructive pulmonary disease. The mast cell stabilizer therapeutic class, cromolyn sodium, can be used to prevent and relieve nasal allergic symptoms. Additionally cromolyn sodium was the first dry powder inhaler product for pulmonary drug delivery several decades ago and currently is on the market as a pressurized metered dose inhaler for pulmonary inhalation delivery. Based on the devices used in pulmonary drug delivery, this route can be subdivided into three categories; namely nebulizers, pressurized metered dose inhalers, and dry powder inhalers. Nasal delivery of anti-inflammatory and antiallergy drugs is most commonly available commercially in an aqueous spray form. This article comprehensively reviews and discusses different kinds of drugs used for anti-inflammatory and anti-allergic effects via the pulmonary and nasal delivery route, as well as their mechanisms of action, marketed products, disease state indications while highlighting drug delivery and therapeutic aspects.
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8(2): Pp. 184 - 191
Katherine Conant, Arun Venkatesan and Avindra Nath
[Open Access Plus] |
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The use of methamphetamine is steadily increasing worldwide. Its use is associated with high-risk sexual behavior and subsequent infection with HIV. Methamphetamine has profound effects on the brain both as an acute intoxicant and following chronic exposure. The combined effects of HIV and methamphetamine appear to result in widespread neuronal and white matter injury. These changes are most prominent in the basal ganglia and frontal lobe, and are not restricted to dopaminergic neurons. Additionally, methamphetamine and HIV proteins disrupt the blood brain barrier, cause glial cell activation and impair the function of neural progenitor cells. Methamphetamine also results in increased HIV replication via activation of chemokine receptors involved in HIV entry. Common pathways in several of these effects seem to involve induction of oxidative stress. Characterization of these subcellular pathways and identification of common targets is essential for development of therapeutic strategies for HIV-infected methamphetamine abusers.
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10(2): Pp. 92 - 120
Yuan Ming Di, Zhi-Wei Zhou, Chun Guang Li and Shu-Feng Zhou
[Open Access Plus] |
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Rheumatoid arthritis (RA) is a chronic systematic autoimmune disease which affects about 1% of the population world wide. This article aimed to identify current therapeutic targets for RA based on data from the literature and drug target related databases. Identified targets were further analysed using a powerful bioinformatics tool, PANTHER (Protein ANalysis THrough Evolutionary Relationships). Additionally, we explored future possible therapeutic targets for RA and discussed the possibility of discovering novel drugs with improved efficacy and reduced toxicity for RA treatment. Data on current clinical drugs for RA treatment were extracted from the US Food and Drugs Administration (FDA) website. Candidate targets of RA were extracted from three online databases: Drugbank, Therapeutic Target Database (TTD) and Potential Drug Target Database (PDTD). A total of 95 clinical protein targets for RA have been identified and were analysed using the PANTHER Classification System. According to the PANTHER analysis, most commonly involved pathways in current RA targeting includes inflammation mediated by chemokine and cytokine signalling pathways, angiogenesis, p53 pathway, de novo purine biosynthesis, T-cell activation, apoptosis signalling pathway and vascular endothelial growth factor (VEGF) receptor signalling pathway. Accordingly, current clinical agents for the treatment of RA mainly include corticosteroids, non-steriodal anti-inflammatory drugs (NSAIDs) and disease-modifying antirheumatic drugs (DMARDs). In addition, a number of investigational targets for RA have been identified and many novel drugs for RA therapy are under investigation. Current approaches to handle RA aim to ameliorate inflammation, to relieve pain, and most importantly to protect the cartilage, joints and bones from further damage by blocking proinflammatory molecules and inhibit the production of matrix-degrading factors. New drugs for RA with improved efficacy and safety should be developed.
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