Showing papers in "Recent Patents on Inflammation & Allergy Drug Discovery in 2009"
TL;DR: The antioxidant defense systems, free radicals production and their role in cancer and age related diseases and also some of the recent patent relevant to the field are reviewed.
Abstract: Chronic inflammation is a pathological condition characterized by continued active inflammation response and tissue destruction. Many of the immune cells including macrophages, neutrophils and eosinophils are involved directly or by production of inflammatory cytokine production in pathology of chronic inflammation. From literatures, it is appear that there is a general concept that chronic inflammation can be a major cause of cancers and express aging processes. Moreover, many studies suggest that chronic inflammation could have serious role in wide variety of age-related diseases including diabetes, cardiovascular and autoimmune diseases. Inflammatory process induces oxidative stress and reduces cellular antioxidant capacity. Overproduced free radicals react with cell membrane fatty acids and proteins impairing their function permanently. In addition, free radicals can lead to mutation and DNA damage that can be a predisposing factor for cancer and age-related disorders. This article reviews the antioxidant defense systems, free radicals production and their role in cancer and age related diseases and also some of the recent patent relevant to the field. Study of the role of free radicals in human diseases can help the investigators to consider the antioxidants as proper agents in preventive medicine, especially for cancer and aging processes.
730 citations
TL;DR: Evidence has been presented that while the aberrant NF-kappaB activation in either keratinocytes or lymphocytes could not reproduce Psoriasis-like histology, such activation in both reproduced all of the aforementioned "hallmarks" of psoriasis pathology.
Abstract: Psoriasis is a common, chronic and relapsing autoimmune skin disease. Clinical characteristics of this disease are sharply-demarcated erythematous plaques covered with silver scales. Histologically, it is characterized by increased epidermal thickness, elongated papillae, and a moderate inflammatory infiltrate composed of lymphocytes, macrophages and neutrophils. The histological hallmark of psoriasis is Munro's microabscess, which is an accumulation of polymorphonuclear leukocytes in the keratinous layer. The mechanism of this disease is still an enigma, but genetic susceptibility, abnormal function of keratinocytes, or immunological disturbance, especially in T cells, are postulated. Over the past decades, there have been arguments about "keratinocyte-dependent" pathology as opposed to "immunocyte-dependent" pathology. Thus far, there have been some rodent models for psoriasis. Among them, the recent article from Rebholz et al. is quite intriguing because they explain the crosstalk between keratinocytes and lymphocytes: now evidence has been presented that while the aberrant NF-kappaB activation in either keratinocytes or lymphocytes could not reproduce psoriasis-like histology, such activation in both reproduced all of the aforementioned "hallmarks" of psoriasis pathology. Therefore, NF-kappaB may well act as a link between the T cell-mediated and keratinocyte-mediated arguments concerning the pathogenesis of psoriasis. This article also discusses some recent patent related to the field.
103 citations
TL;DR: The most known molecular events in corneal NV are reviewed and also some of the recent patents relevant to the field are reviewed to help the investigators to design therapeutic options for controlling this debilitating condition.
Abstract: Corneal neovascularization (NV) is a significant complication of numerous infectious and non-infectious ocular surface disorders. Presence of newly formed blood vessels in the cornea can compromise clarity and therefore vision. Various growth factors and proteinases seem to be involved in the corneal NV. During corneal injury, angiogenic factors are released from corneal epithelial and stromal cells as well as infiltrating immune cells like macrophages. In fact, the balance between angiogenic and anti-angiogenic factors is shifted towards angiogenic molecules in the corneal NV. Numerous investigations support this idea that vascular endothelial growth factor (VEGF) plays a pivotal role in corneal NV by inducing endothelial cells proliferation, migration, and tubulogenesis. There is a growing body of evidence that corneal NV can be reduced by using anti-VEGF agents. This article reviews the most known molecular events in corneal NV and also some of the recent patents relevant to the field. Understanding the role of growth factors, proteinases and inflammatory cytokines in corneal NV can help the investigators to design therapeutic options for controlling this debilitating condition.
68 citations
TL;DR: Several novel therapeutic adjuncts for the management of critically ill patients with sepsis are reviewed, largely focus on those therapies that directly target the host inflammatory response, specifically those that result in activation of the transcription factor, nuclear factor (NF)-kappaB.
Abstract: Sepsis is currently the 10th leading cause of death overall and accounts for significant healthcare expenditures in the developed world. There are now more deaths attributable to sepsis than coronary artery disease, stroke, or cancer, and it is widely believed that the incidence of sepsis and sepsis-related mortality will continue to rise. Based on these sobering statistics, there is great interest in identifying novel treatments for managing critically ill children and adults with sepsis. Unfortunately, to date, there have been very few successful therapeutic agents employed in the clinical setting. Despite these disappointing results, new therapeutic agents continue to be identified, and there is reason for optimism and hope for the future. Herein, we will briefly review several novel therapeutic adjuncts for the management of critically ill patients with sepsis. We will largely focus on those therapies that directly target the host inflammatory response, specifically those that result in activation of the transcription factor, nuclear factor (NF)-κB. We will also reference some of the patents recently filed that pertain to the host innate immune response and sepsis.
56 citations
TL;DR: Probiotics are usually defined as live microbial food ingredients beneficial to health which comprise of normal commensally bacteria as a part of the healthy human gut micro flora.
Abstract: Probiotics are usually defined as live microbial food ingredients beneficial to health which comprise of normal commensally bacteria as a part of the healthy human gut micro flora. The gut microflora is an important component of the gut defense barrier and have been shown to induce and maintain oral tolerance in experimental animal models. Functional foods, including probiotic bacteria, are an attractive medium for maintaining the steady nutritional state of the host with defective gut barrier functions. The gut-associated lymphoid tissue (GALT) embraces a crucial component of the total immunological capacity of the host in recognizing and selectively handling alien antigens for the initiation of immune responses. Normalization of increased intestinal permeability and altered gut micro ecology can ensure improvement of the function of the gut barrier. Probiotics do modify the composition of the gut microflora and, as a consequence, they have been shown to influence both intestinal and body functions. This review also discussed some patent related to the field.
54 citations
TL;DR: This review examines HIF-1 signaling with a special focus on the gastrointestinal tract and the patents pertaining to the modulation of Hif- 1 signaling are summarized and their relevance to the treatment of inflammatory bowel disease is discussed.
Abstract: In response to hypoxia, adaptive hypoxia-inducible factor-1 (HIF-1) signaling events are activated to increase oxygen transport, anaerobic energy production and protective pathways to minimize ischemic tissue damage. Although the activation and subsequent induction of gene transcription by HIF-1 is normally associated with hypoxia, it is now established that HIF-1 signaling can be triggered under inflammatory conditions. HIF-1 has been implicated in a number of inflammatory diseases including rheumatoid arthritis, allergic asthma, psoriasis and inflammatory bowel disease (IBD). In the gastrointestinal tract, HIF-1-regulated gene products, such as vascular endothelial growth factor, intestinal trefoil factor and CD73, have been shown to provide protection in animal models of intestinal inflammation. Given the importance of HIF-1 signaling in the aforementioned diseases, there exists considerable interest in the development of methods to modulate HIF-1 expression as well as down-stream signaling events. This review examines HIF-1 signaling with a special focus on the gastrointestinal tract. The patents pertaining to the modulation of HIF-1 signaling are summarized, and their relevance to the treatment of inflammatory bowel disease is discussed.
46 citations
TL;DR: There continues to be a constant need to discover more effective ways to treat seasonal and perennial allergic conjunctivitis.
Abstract: Seasonal and perennial allergic conjunctivitis are IgE-mediated, hypersensitivity ophthalmic conditions characterized by ocular pruritus, epiphora, and hyperemia. Proper diagnosis is usually made clinically based on history and physical examination. Diagnostic procedures are rarely necessary. Non-pharmacological measures, such as environmental modification and proper eye care, should be considered for all patients with allergic conjunctivitis. Pharmacological interventions may also be required. Milder cases can be treated with short-term topical ophthalmic therapy such as a decongestant/antihistamine combination, a mast cell stabilizer, or a multi-action agent. Moderate to severe cases may require longer usage of the above agents or the addition of an oral antihistamine. Refractory cases may necessitate the use of topical ophthalmic corticosteroids and/or immunotherapy. Despite all the available therapeutic agents, there continues to be a constant need to discover more effective ways to treat seasonal and perennial allergic conjunctivitis. This review article also discusses recent patents related to the field.
39 citations
TL;DR: Bovine intestinal alkaline phosphatase can be administered safely in an attempt to reduce the inflammatory response in coronary artery bypass grafting patients with a low to intermediate EuroSCORE, and the anti-inflammatory effects might be more pronounced in patients developing more fulminant postoperative inflammatory responses.
Abstract: Laboratory and clinical data have implicated endotoxin as an important factor in the inflammatory response to cardiopulmonary bypass. Alkaline phosphatase prevents endotoxin-induced systemic inflammation in animals and humans. We assessed the effects of the administration of bovine intestinal alkaline phosphatase on surgical complications in patients undergoing coronary artery bypass grafting. In a double blind, randomized, placebo-controlled study, a total of 63 patients undergoing coronary artery bypass grafting were enrolled. Bovine intestinal alkaline phosphatase or placebo was administered as an intravenous bolus followed by continuous infusion for 36 hours. The primary endpoint was reduction of post-surgical inflammation. No significant safety concerns were identified. The overall inflammatory response to coronary artery bypass grafting with cardiopulmonary bypass was low in both placebo and bovine intestinal alkaline phosphatase patient group. Five patients in the placebo group displayed a significant TNFalpha response followed by an increase in plasma levels of IL-6 and IL-8. Such a TNFalpha response was not observed in the bovine intestinal alkaline phosphatase group, suggesting anti-inflammatory activity of bovine intestinal alkaline phosphatase. Other variables related to systemic inflammation showed no statistically significant differences. Bovine intestinal alkaline phosphatase can be administered safely in an attempt to reduce the inflammatory response in coronary artery bypass grafting patients with a low to intermediate EuroSCORE. The anti-inflammatory effects might be more pronounced in patients developing more fulminant postoperative inflammatory responses. This will be investigated in a further trial with inclusion of patients undergoing complicated cardiac surgery, demanding extended cardiopulmonary bypass and aortic cross clamp time. In this review article some recent patents related to the field are also discussed.
35 citations
TL;DR: The recent understandings of the pathophysiology of sepsis are summarized, recent patents on diagnosis, treatment and prophylaxis for sepsi are introduced, and recent patents for biological response modifiers are introduced.
Abstract: Despite advances in the development of powerful antibiotics and intensive care unit, sepsis is still life threatening and the mortality rate remains unchanged for the past three decades. Recent prospective trials with biological response modifiers have shown a modest clinical benefit. The pathological basis of sepsis is initially an excessive inflammatory response against invading pathogens, leading to systemic inflammatory response syndrome (SIRS). Evidence reveals that a variety of inflammatory mediators orchestrate the intense inflammation through complicated cellular interactions. More recent data indicate that most septic patients survive this stage and then subjected to an immunoparalysis phase, termed compensatory anti-inflammatory response syndrome (CARS), which is more fatal than the initial phase. Sepsis is a complicated clinical syndrome with multiple physiologic and immunologic abnormalities. In this review, we summarize the recent understandings of the pathophysiology of sepsis, and introduce recent patents on diagnosis, treatment and prophylaxis for sepsis.
29 citations
TL;DR: This review includes most recent developments and patents on usage of monoclonal antibodies for the treatment of allergic disorders, which can provide access to development of more specific therapies in order to control the disease progression.
Abstract: Allergic disorders, as asthma, allergic rhinitis/rhinoconjunctivitis, atopic dermatitis, food allergies and anaphylaxis have an increasing burden in the general population and a growing body of evidence has shown that an increased interest has aroused to seek for more effective treatment strategies. Conventional pharmacotherapy by antihistamines, anti-leukotrienes, corticosteroids and bronchodilators can routinely control most of the cases, in addition to allergen avoidance which saves the date. Furthermore, allergen specific immunotherapy stands as the only curative method to treat the underlying cause of allergic immune response by induction of immune tolerance. However, response to pharmacotherapies can show diversity depending on the genotype and phenotype of the allergic disorders, which are known to be under the influence of multifactorial triggers. Thus, understanding the mechanisms of development of allergic disorders, in addition to selective description of the phenotypes can provide access to development of more specific therapies in order to control the disease progression. Monoclonal antibodies can be the major actors in this targeting process. Concerns about the safety, efficacy and long-term tolerability of these molecules always stand as a question for them, in order to gain indications for the treatment of allergic disorders. This review includes most recent developments and patents on usage of monoclonal antibodies for the treatment of allergic disorders.
15 citations
TL;DR: The most commonly used drugs, including mesalazine, azathioprine, 6-mercaptopurine, cyclosporine, and more recently anti-tumor necrosis factor monoclonal antibody, are chosen to suppress the immune system in intestinal mucosa to induce and maintain clinical remission.
Abstract: Ulcerative colitis (UC) is a chronic, relapsing and debilitating idiopathic inflammation of the gastrointestinal tract. Dysregulation of the mucosal immune response toward commensal bacterial flora together with genetic and environmental factors plays an important role in the pathogenesis. Refractory UC refers to disease that does not respond to or responds poorly to the many drugs used to treat the disease. The aim of medical treatment is to induce and maintain clinical remission. The most commonly used drugs, including mesalazine, azathioprine, 6-mercaptopurine, cyclosporine, and more recently anti-tumor necrosis factor (TNF) monoclonal antibody (e.g., infliximab), are chosen to suppress the immune system in intestinal mucosa. Additionally, colectomy may be required if medical treatments are unsuccessful or if complications develop. Some of the recent patent related to the field also discuss in this review article.
TL;DR: The article outlines recent patents related to probiotics therapy to reduce radiation induced mocositis and encouraging results have been obtained in clinical trials, the potential of oral probiotics to manage gastrointestinal symptoms needs further research.
Abstract: Although pelvic radiotherapy, either alone or combined with chemotherapy, has proved to be successful in the treatment of patients with rectal, gynecological and urologic cancer, it is not devoid of side effects. Among patients receiving pelvic radiotherapy more than 70% develop acute inflammatory changes causing gastrointestinal symptoms during treatment. The most frequently reported symptom related to radiation-induced intestinal mucositis is diarrhoea. Among nutritional interventions used to manage radiation-induced diarrhoea, probiotics has gained popularity. This term describes organisms and substances that improve microbial balance in the intestines. Although encouraging results have been obtained in clinical trials, the potential of oral probiotics to manage gastrointestinal symptoms needs further research. The article also outlines recent patents related to probiotics therapy to reduce radiation induced mocositis.
TL;DR: This article reviews some patents related to the treatment of contact dermatitis and other inflammatory skin diseases and suggests that mechanisms responsible for cross-reactivity may occur at T lymphocyte level during antigen presentation.
Abstract: Contact allergy to topical corticosteroids (TCs) is an emerging problem, whose diagnosis can be complex owing to the peculiar characteristics of steroid allergens and the possible inadequacy of current diagnostic methods, including concentration and vehicle used in patch testing. The occurrence of cross-reactions among different TCs is not rare, but prediction of these is not sufficiently reliable. Moreover, the distinction between true cross-reactivity and concomitant sensitization may be difficult. The original classification proposed by Coopman et al. has been distinguished corticosteroids into four groups according to their molecular structure. These authors hypothesized that allergic contact reactions were more frequent with corticosteroids belonging to the same group. However, the clinical practice has evidenced that cross reactivity exists also among corticosteroids belonging to different groups. The potential to cross-react among corticosteroids is thought to be related not only to the structural homology but also to the stereoisomerism and metabolism of these drugs. Recent evidence suggests that mechanisms responsible for cross-reactivity may occur at T lymphocyte level during antigen presentation. Further investigations are needed to gain a more complete understanding of this important topic. This article also reviews some patents related to the treatment of contact dermatitis and other inflammatory skin diseases.
TL;DR: There are placebo-controlled trials indicating good efficacy and safety of SLIT in patients allergic to latex and to foods and in children with atopic dermatitis, that indicate SLIT as a real treatment option in such clinical entities.
Abstract: Specific immunotherapy is the only treatment targeting the causes, and not only the symptoms, of allergic diseases. Sublingual immunotherapy (SLIT) was introduced and developed to solve the problem of the adverse reactions, uncommon but possibly severe and rarely fatal, to the traditional subcutaneous immunotherapy (SCIT). The evidence of SLIT efficacy concerns rhinitis and asthma caused by sensitization to pollens and to house dust mites, but there are increasing data suggesting that SLIT could be applied in forms of allergy hardly feasible for SCIT because of its poor safety (this is true for food allergy and latex allergy) or could be considered for new applications, such as atopic dermatitis or bakers asthma. In particular, there are placebo-controlled trials indicating good efficacy and safety of SLIT in patients allergic to latex and to foods and in children with atopic dermatitis, that indicate SLIT as a real treatment option in such clinical entities. This article also discusses some patent related to the field.
TL;DR: Antioxid, anti-inflammatory, hypo-lipidemic,Anti-proliferative properties of BHUx have been studied on several experimental models based on chemical tests, cell culture, in vitro models, and in vivo experiments with normal and transgenic animals to prove its safety margin in therapeutic doses.
Abstract: Since hyperlipidemia, inflammation and obesity are closely related to atherosclerosis, therefore management of these factors together would be beneficial for overall treatment approach for atherosclerosis. Although, Indian system of medicine, especially Ayurveda has several medicinal plants with proven beneficial claims towards these pathological conditions, but most of them lack enough experimental data. BHUx is a novel polyherbal formulation, consisting of 5 medicinal plants namely Termenalia arjuna, Strychnox nux vomica, Boswellia serrata, Commiphora mukul, and Semecarpus anacardium, which have history of clinical use as single or in other combinations, but these plant fractions were never tried collectively in this ratio as in BHUx, which has been found to be effective on all the etiological factors, together. In this paper, antioxidant, anti-inflammatory, hypo-lipidemic, anti-proliferative properties of BHUx have been studied on several experimental models based on chemical tests, cell culture, in vitro models, and in vivo experiments with normal and transgenic animals. A separate pre-clinical toxicity study has also been carried out to prove its safety margin in therapeutic doses. Further, clinical trail of BHUx is under way, before it comes to market for public use as functional food to maintain healthy heart. This article also review some patent related to the field.
TL;DR: Performance of each drug delivery device depends on a variety of factors including the device type, particle size and distribution, the product formulation and patient-related factors, and drug delivery can differ even when the same drug is delivered via an HFA pMDI, a CFC pMDi, a DPI or a nebulizer.
Abstract: It is well established that airway inflammatory processes are pivotal as the pathological features of asthma. Prominent infiltration of eosinophils and Th2 lymphocytes is a hallmark of the allergic inflammation, and inhaled corticosteroids markedly suppress such inflammatory changes, resulting in clinical beneficial effects. Aerosol delivery of anti-asthma drugs such as corticosteroids is ideal from the standpoint of maximizing local effects in the lung as well as minimizing systemic side effects compared with oral therapy. The 1987 Montreal protocol banned chlorofluorocarbon (CFC) propellant in pressurized metered-dose inhalers (pMDIs), which has been replaced with hydrofluoroalkane (HFA) propellant. The aerodynamic diameters of HFA are much smaller than those of CFC, suggesting a greater distribution in peripheral airways. New types of dry powder inhalers (DPIs) and nebulizers, that do not use propellants, also have been introduced. Performance of each drug delivery device depends on a variety of factors including the device type, particle size and distribution, the product formulation and patient-related factors. Therefore, drug delivery can differ even when the same drug is delivered via an HFA pMDI, a CFC pMDI, a DPI or a nebulizer. New and advanced devices can be helpful to maximize the advantages of these modes of drug delivery, and patents of novel invention of inhalation devices are described.
TL;DR: There is evidence supporting that the use of statins may be associated with a decreased hospital mortality caused by the above disorders and investigations also suggest that these agents are infrequently associated with adverse events and are generally safe and well tolerated.
Abstract: Statins, beyond their lipid lowering properties, have pleiotropic properties that may modulate the inflammatory cascade and potentially could be useful in the management of inflammatory conditions such as bacteremia and sepsis. In this article, we aimed to review significant patents and available evidence regarding the anti-inflammatory characteristics of these agents and their role in the clinical outcome of inflammatory conditions. Several studies have demonstrated beneficial effects of prior use of statins in the development and the progression of bacteremia, sepsis and pneumonia and there is evidence supporting that the use of statins may be associated with a decreased hospital mortality caused by the above disorders. These investigations also suggest that these agents are infrequently associated with adverse events and are generally safe and well tolerated. However, it should be underlined that these data come mainly from observational retrospective investigations and randomized prospective studies are warranted to confirm these encouraging results.
TL;DR: The efficacious aspects of chimeric CTLA-4 in phase I, II and III clinical trials for rheumatoid arthritis, psoriasis, multiple sclerosis are concisely described.
Abstract: Co-stimulatory molecules are antigen-independent generators of secondary signals which aid in maintaining the homeostasis of the immune system. CTLA-4 is one among extensively studied co-stimulatory molecules which down-regulate immune response. The attributes of immunosuppressive qualities and capacity to induce tolerance have made its recognition as a potential immuno-therapeutic agent for autoimmune mediated inflammatory disorders. In 2007, European Medical Drug Agency (EMEA) has approved administration of CTLA-4Ig (commercial name: Orencia; generic name: Abatacept), as a mean for co-stimulation blockade, for treating patients with rheumatoid arthritis. This review is focused on working mechanism of CTLA-4 from its recognition (bench) to its usage as a potential therapeutic agent (bedside) for several inflammatory diseases. The efficacious aspects of chimeric CTLA-4 in phase I, II and III clinical trials for rheumatoid arthritis, psoriasis, multiple sclerosis are concisely described. This article highlights recent patents and the future usage of co-stimulatory molecules as a therapeutic agent providing a promising immuno-modulatory approach in regulating inflammation.
TL;DR: Patents related to CTLA-4 function as well as possible clinical applications are discussed in this paper.
Abstract: Cytotoxic lymphocyte-associated molecule-4 (CTLA-4, CD152) is a member of the CD28 receptor family. Blocking CD28 interaction with its ligands through the use of CTLA-4Ig might contribute to better control of dysregulated immune response processes. The ligands binding to CTLA-4 are the B7 family members, B7-1 (CD80) and B7-2 (CD86). CTLA-4Ig is now a Food and Drug Administration-approved drug for use treating patients with Rheumatoid arthritis (RA) but its use is explored also in other autoimmune diseases, transplantation as well as allergic diseases. Patents related to CTLA-4 function as well as possible clinical applications are discussed in this paper.
TL;DR: Patents are described that address a potential pharmacological use of promoting or targeting IL-17, which might prove useful in a variety of diseases including asthma, chronic obstructive pulmonary disease, Crohn's disease, cystic fibrosis, multiple sclerosis, psoriatic disease and rheumatoid arthritis.
Abstract: Recently, a third subset of Th17 cells has been described. This T helper subset induces the release of chemokines and growth factors and causes neutrophil accumulation in several mammalian organs. Pharmacological intervention blocking Th17 generation as well as IL-17 signaling might prove useful in a variety of diseases including asthma, chronic obstructive pulmonary disease, Crohn's disease, cystic fibrosis, multiple sclerosis, psoriatic disease and rheumatoid arthritis. Here, we describe the patents that address a potential pharmacological use of promoting or targeting IL-17.
TL;DR: The current patents on leptin in different clinic applications are reviewed and several leptin-based approaches to modulate the metabolic and endocrine status, to reduce inflammation, and to improve immune responses are reviewed.
Abstract: Leptin is an adipocyte-derived hormone with pleiotropic effects on energy homeostasis, endocrine and reproductive functions, and immune responses. The multiple actions of leptin have led to the design and development of several leptin-based approaches to modulate the metabolic and endocrine status, to reduce inflammation, and to improve immune responses. Here, we review the current patents on leptin in different clinic applications.
TL;DR: This review is a brief summary of relevant scientific basis as well as clinical research on the role of dehydroepian drosterone in immune haemostasis and inflammatory diseases, including asthma, atopic diseases, chronic urticaria, pointing also to the significance ofhydroepiandrosterone therapy and the related US patents (1999-2005).
Abstract: Dehydroepiandrosterone (DHEA) and its sulfate derivative (DHEA-S) are weak androgens produced in the adrenals and serve as primary precursors in biosynthesis of both, androgens and estrogens. These hormones are proposed to perform immunoenhancing activities and may play a crucial role in regulating cytokine production by Th1/Th2 cells; however, their role in immune-mediated diseases is controversial. The primary physiological role of DHEA-(S) and its mechanism is unclear. This review is a brief summary of relevant scientific basis as well as clinical research on the role of dehydroepian drosterone in immune haemostasis and inflammatory diseases, including asthma, atopic diseases, chronic urticaria, pointing also to the significance of dehydroepiandrosterone therapy and the related US patents (1999-2005).
TL;DR: The rapid progress in understanding the immunology of infectious diseases and genetics of asthma is providing a better understanding of the pathogenesis of bronchial asthma, and that will help to define patient populations who are most likely to benefit from various treatments, and lead to development of new treatments.
Abstract: Chlamydophila pneumoniae is an intracellular pathogen and a major cause of pneumonia that can cause chronic, persistent, and often asymptomatic, infections in target cells such as monocytes, macrophages, endothelial cells, fibroblasts, and smooth muscle cells. Chlamydial infections play roles in new-onset wheezing, exacerbation of prevalent asthma, and long-term decrements in lung function. However, accurate standardized laboratory tests to diagnose infection with C. pneumoniae have not been established. Human and animal studies have clarified the molecular mechanisms of resistance to C. pneumoniae and have shown the importance of innate and mucosal immune responses to the microorganisms. A large number of genetic studies have intensively examined the associations between asthma and polymorphisms in the genes located at the interface between innate immune sensing and regulation. The rapid progress in understanding the immunology of infectious diseases and genetics of asthma is providing a better understanding of the pathogenesis of bronchial asthma, and that will help to define patient populations who are most likely to benefit from various treatments, and lead to development of new treatments. The review article also discussed some patent related to the field.
TL;DR: The blockage of the expression of CD86 could be a potential therapeutical target to reduce the magnitude or the progression of the allergic reaction.
Abstract: CD86 is a well-known costimulatory molecule in its interaction with CD28 and/or CTLA present on T cells, and is essential for full activation of naive T-cell and subsequent differentiation. Usually the B7 molecules are expressed mainly on APCs and B cells and in specific conditions on other activated cells. These costimulatory molecules are involved in the development of allergic inflammation and airways hyperreactivity (AHR) in allergen-challenged mice. Activated T cells, CD4+CD25+, express CD86 in the first 60 minutes after the specific inhalatory exposure. These T cells can be relevant in IgE mediated allergic reaction possibly by an autocrine costimulation via CD28/CTLA activation pathway. The blockage of the expression of CD86 could be a potential therapeutical target to reduce the magnitude or the progression of the allergic reaction. The review article also discussed relevant patents.
TL;DR: This review discusses articles, recent patents and patent applications that explore the selective depletion of pathological cells by targeting chemokine receptors withChemokine ligands, monoclonal antibodies and different bispecific constructs as a therapeutic strategy for allergic, autoimmune and inflammatory diseases.
Abstract: Targeting cell surface antigens or receptors with lytic monoclonal antibodies and specific ligand-directed fusion proteins in order to eliminate cancer cells has been in development for at least forty years. More recently, leukocyte populations known to drive a host of allergic, autoimmune and inflammatory diseases have been targeted. For fusion protein constructs, a number of different classes of cellular toxins have been fused to a variety of ligands such as monoclonal antibodies, growth factors and cytokines. Although there has been great clinical success using these biologics, there are some limitations. The target antigens are often expressed on normal cells leading to side effects. More recently, several groups have explored the use of chemokine receptor ligands and antibodies to target leukocytes and cancer cells. There are a number of inducible chemokine receptors that are only up-regulated in inflammation and their expression is relatively restricted to pathological cells. This confers another degree of specificity on biologics that are composed of chemokine receptor targeting agents. This review discusses articles, recent patents and patent applications that explore the selective depletion of pathological cells by targeting chemokine receptors with chemokine ligands, monoclonal antibodies and different bispecific constructs as a therapeutic strategy for allergic, autoimmune and inflammatory diseases.
TL;DR: It seems likely that a therapy with anti-TNF-alpha should be limited to a small subgroup of patients with a specific phenotype manifested by an increased TNF axis, which underlined a significant polymorphism in asthma phenotypes.
Abstract: Asthma is the most common pulmonary disease in children worldwide. As its prevalence significantly increases from 30% to 50% every 10 years it seems that finding the exact form of treatment is crucial to achieve a long-term-benefit effect. Sometimes it appears hard, especially in case of difficult and severe asthma when a standard therapy is not sufficient. The success of omalizumab inspired further studies which turned the spotlight on other pro-inflammatory cytokines such as TNF-alpha. After the success of anti-TNF-alpha therapy in many other inflammatory diseases such as for instance Crohn's Disease and Rheumatoid Arthritis, there appeared several trials discussing the usage of anti-TNF agents in asthma. The first wave of enthusiasm over positive results in treating asthma patients was blunted by other researches which challenged the benefit of anti-TNF-alpha in asthma. What is more, they warned about serious problems and adverse events related to that kind of treatment. These results hindered further investigation, especially in case of children's population, because of the ambiguity as far as the risks and benefits of the treatment were concerned. Nevertheless, the research on anti-TNF-alpha and asthma underlined a significant polymorphism in asthma phenotypes. It seems likely that a therapy with anti-TNF-alpha should be limited to a small subgroup of patients with a specific phenotype manifested by an increased TNF axis. The purpose of this review article is to discuss some recent patents in anti-TNF-alpha therapy.
TL;DR: The aim of the present work was to compile a bibliographic review of the diverse potentially anti-inflammatory drugs along with some recent patents in an effort to systematize the current knowledge on this topic.
Abstract: The concern for management of intraocular inflammation has led to a continuing search for newer and more effective drugs. Though entry of antimetabolites, cytotoxic agents for the treatment of intraocular inflammation came as a great boon, latest research has been going on to improve the treatment modalities. Drugs like biologicals show effective anti inflammatory action in uveitis patients. The aim of the present work was to compile a bibliographic review of the diverse potentially anti-inflammatory drugs along with some recent patents in an effort to systematize the current knowledge on this topic. Also the present work intends to show the mechanism of action of different anti-inflammatory drugs which will be a good benefit in the treatment of uveitis.