Inflammation & Allergy-Drug Targets (v.10, #1)

Editorial by Kurt S. Zaenker (1-1).
Scientific publishing is, in some way a virtual market for the best ideas, the proof of principle and concepts, influenced not only by the scientific content, which should be transported within the scientific community, but also by many other factors, like allocation of money for research, like the impetus to publish novel and non-main stream conform ideas, and to gain power in science, either personally or institutionally. It is our job as a scientist and as Editor-in-Chief to raise awarness about the consequences of scientific, political and public interference in science in an accessibly way - and this issue is the fertile ground of the progress of a scientific journal. The ongoing effort to increase awareness of novel scientific findings worldwide and the scientific issues amongst scientists and non-scientists alike is essential to restore independent science to each and every one that follows. Due to the persistent and energetic engagement of all scientists, interested in the special publication organ: and#x201C;Inflammation and Allergy - Drug Targetsand#x201D;, and due to the excellent editing work of the staff of Bentham Publishing House, I like to thank all of you doing this great job in the past. However, as Editor-in-Chief, I carry responsibility for the development of the journal in the near future. All of you know that scientific publishing is within a revolutionary stage. Both, in terms of quality and quantity, published data and approved patents in life science reflect the strength of science and biotechnology of a country. In a global world, the global leaders are on a transition and the and#x201C;Eastand#x201D; is now showing up a tough competition to and#x201C;Westand#x201D; in terms of presenting pausible and novel data, in competing for publication space in highly ranked journals and in obtaining funds from global players of the pharmaceutical industry.Of course, within this highly competitive processes of i) asking new questions, of ii) validating the raised questions and of iii) painting a picture of reality, which might be materialized, either economic- and or ethic-wise, under political or personally focused career pressure, scientists might pursue scientific research and presenting data with among other goals of attaining first knowledge - just by fabricate data. In the past, a substantial number of editors of prestigious journals are notified by reports that, e.g. university committees of research integrity have investigated allegations of falsified or fabricated published data. Scientific misconduct is a violation, and, for such a growing and now widely accepted journal within its scientific community, like and#x201C;Inflammation and Allergy - Drug Targetsand#x201D;, this would be a deadly process; above all, as it is the goal and wish of the Editors, to attract manuscripts from those authors, who have submitted their papers to highly ranked journals, however rejected, but, not because of a mediocre scientific content, but of the limited space available within the journal. and#x201C;Inflammation and Allergy - Drug Targetsand#x201D; wants also become a journal for those authors working in countries which improve the standards of scientific publishing by the help of the peers of the Editorial Board; it is the academic task of the peers of this journal to promote a manuscript scientifically to a higher grade; it is not acceptable that a manuscript will be declined for publication because of cultural reasons or scientific paradigms not compatible with Western views - at the very end, there is only one truth in nature. As Editor-in Chief, I like to thank all authors, peers and the member of the Editorial Board that they have a keen eye on the Swedish Definition of scientific misconduct: and#x201C;Intentional distortion of the research process by fabrication of data, text, hypothesis, or methods from another researcher's manuscript form or publication; or distortion of the research process in other waysand#x201D;. It is with pleasure that Armen Yuri Gasparyan, MD, PhD, Associate Professor of Medicine, Dudley Group of Hospitals, UK, will join in 2011 the journal as Deputy Editor. His broad experience as a Member of the World Association of Medical Editors and as a Member of the European Association of Science Editors will further substantiate the journal's maxim: (1) Rapid decision about the fate of a submitted manuscript, (2) generally within 21 days, (3) timely publishing and (4) to get the best expertise in basic, translational and personalized medicine for the benefit of the authors submitting their manuscripts to IA-DT. I like to end in reminding all members of the Editorial Board, that IA-DT is a highly recognized journal in the specialized field of inflammation, allergy, drug targeting and development. We approved the membership in IA-DT by asking the Editorial Members to show up with their manuscripts, whenever appropriate, and to respect and honor the results of their colleagues by citation of relevant articles. For 2011, as Editor-in-Chief, I like to thank and to extend the best wishes to all supporters of IA-DT; and that IA-DT might keep on going for the success of publishing data, which might help individuals - soon or later - for a better and peaceful life and to increase the awarness of the public sector about the mandatory importance of life science - now, and in the future.

Xolair in Asthma Therapy: An Overview by Monica Di Domenico, Angelica Bisogno, Mario Polverino, Concetta De Rosa, Vilma Ricci, Anna Capasso (2-12).
Asthma is a chronic lung inflammatory disease affecting from 5 to 10and#x25; of the population. It generally appears with periods of crisis alternating with free periods, but inflammation is always present. Allergic asthma manifests with paroxysmal crisis of bronchospasm, hissing-like respiratory noises, dyspnea, and respiratory distress syndrome. Different studies have shown an increase of IgE serum levels in subjects suffering from allergic asthma. Xolair is a monoclonal antibody that binds the C3 domain of IgEs, inducing a conformational change of the immunoglobulin, a concealment of FcRI and FcRII receptors binding sites, thus precluding binding by IgEs and therefore stopping the release of inflammation mediators. Xolair is indicated as add-on therapy to improve asthma control in adult and adolescent patients (12 years of age and above) suffering from severe persistent allergic asthma. The aim of this review is 1) to explore the safety and tolerability of Xolair in asthma therapy and 2) to examine recent important developments focusing on treatment strategies of asthma with Xolair.

Tissue factor (TF) is an initiator of the extrinsic blood coagulation, which is often susceptible to upregulation by tissue injury, advanced glycation end-product, or diverse inflammation. TF hypercoagulability is accompanied by elevated generation of clotting factors (e.g., FVIIa, FXa, and thrombin) and fibrin production, all of which are proinflammatory. In this laboratory, our in vitro experimental results show that polycationic anticoagulants (compound 48/80, ruthenium red, polybrene, protamine, Buforin I, and cationic polyamino acids) intervene TF hypercoagulability at posttranslational level. Polycations preferentially suppress TF-dependent FVII activation with diminished FVIIa formation shown on Western blotting, resulting in non- or un-competitive inhibition on FVIIa amidolytic activity. In contrast, polycations have no effect on FVIIa catalysis, FXa activity, or thrombin activity per se. Polycations could present a new class of anticoagulants with such unique upstream downegulation of blood coagulation. In view of coagulation-dependent inflammation and the new paradigm of blood coagulation-inflammation-thrombosis circuit, the polycations as a new class of anticoagulants could effectively contribute to antiinflammation, antithrombosis, and cardioprotection. Further development of effective anticoagulants is of biopharmaceutical significance in broadly easing disease conditions.

Systemic Sclerosis (SSc) is a multisystem connective tissue disease of unknown etiology that is characterized by inflammation, vascular dysfunction and fibrosis of the skin and visceral organs. SSc is clinically diverse both in terms of the burden of skin and organ involvement and the rate of progression of the disease. Recent studies indicate that the endothelin system, especially ET-1 and the ETA and ETB receptors may play a key role in the pathogenesis of SSc. A new class of drugs, endothelin receptor antagonists has been introduced for treatment of patients with pulmonary arterial hypertension (PAH). Bosentan, a dual endothelin receptor antagonist as well as Sitaxsentan and Ambrisentan, selective blockers of the ETA receptor have proven effective in SSc-PAH. This effect may be mediated through both a vasodilatory and antifibrotic effect, thus making these agents attractive as potential disease modifying agents for SSc.

Correlation Between Circulating Adhesion Molecules and Resistin Levels in Hypertensive Type-2 Diabetic Patients by Jose Juan Lozano-Nuevo, Teresa Estrada-Garcia, Hilda Vargas-Robles, Bruno A. Escalante-Acosta, Alberto F. Rubio-Guerra (27-31).
Background: Endothelial dysfunction, a common feature among hypertensive and type-2 diabetic patients, has been associated with inflammation and increased concentrations of serum soluble adhesion molecules and resistin, a monocyte-macrophage- and adipocyte-derived cytokine. The Aim of this Study: To determine if there is a correlation between the serum concentrations of ICAM-1, VCAM-1, Eselectin and resistin in hypertensive type-2 diabetic patients. Methods: Thirty hypertensive type-2 diabetic patients were enrolled in the study. Serum ICAM-1, VCAM-1, E-selectin and resistin concentrations were determined by ELISA and correlated with the Spearman correlation coefficient. Results: The patients' serum resistin concentrations significantly correlated with VCAM-1 (r = 0.31, p = 0.05) concentrations but not with ICAM-1 (r = 0.29, p = > 0.05) and E-selectin (r = 0.10, p = 0.24) concentrations. Conclusion: VCAM-1 and resistin may participate in the pathophysiology of vascular damage in hypertensive type-2 diabetic patients. Serum resistin concentrations may be a marker of endothelial dysfunction.

Anti-Inflammatory Activity and Clinical Efficacy of a 3-Month Levocetirizine Therapy in Mite-Allergic Children by Francesco Marcucci, Laura Giovanna Sensi, Piera Abate, Giusiana Allocca, Eleonora Ugolini, Giuseppe Di Cara, Cristoforo Incorvaia (32-38).
The non-sedating third generation antihistamine levocetirizine has ample evidence of efficacy in allergic rhinitis. In vitro studies suggested that levocetirizine has anti-inflammatory properties not simply related to the antihistamine activity but also to regulation of eosinophils. We performed a double-blind placebo-controlled study in 40 children allergic to house dust mites with persistent rhinitis with the primary aim to evaluate the anti-inflammatory efficacy of levocetirizine measuring eosinophil-related parameters and exhaled nitric oxide (eNO). After one month of treatment, a significant improvement in nasal symptom-medication scores was observed in actively but not in placebotreated patients. After 3 months of treatment, a significant effect was detected on eosinophilic cationic protein (ECP) in nasal mucosa and on nasal eNO in active treated patients. This suggests that during treatment of mite-allergic children with levocetirizine the early improvement in nasal symptoms is due to the antihistamine activity, while more time is needed to achieve an effect on allergic inflammation.

Up-Regulation of Gr1+CD11b+ Population in Spleen of Dextran Sulfate Sodium Administered Mice Works to Repair Colitis by Rong Zhang, Sachiko Ito, Naomi Nishio, Zhao Cheng, Haruhiko Suzuki, Ken-ichi Isobe (39-46).
Dextran sulfate sodium (DSS) is commonly used in rodent IBD models to chemically induce acute intestinal inflammation. The acute course of colitis includes colon tissue damages and recovery from wounded tissues. As skin wound repair was delayed by splenectomy, we asked whether splenectomy would induce the delay of colonic wound healing. In splenectomized mice, body weight recovery, disease score and colon length were delayed. Surprisingly we found a great increase of Gr1+CD11b+ cells in spleen and bone marrow of DSS-administered mice. Anti-Gr-1 antibody treatment worsened the DSS- administered colitis. These results indicate that Gr1+CD11b+ cells induced by DSS worked to repair colon wound healing and repair colitis.

Cytokine Therapies in Crohn's Disease: Where are We Now and where should We Go? by Flavio Caprioli, Francesco Pallone, Giovanni Monteleone (47-53).
In the gut of patients with Crohn's disease (CD), one of the major forms of inflammatory bowel diseases in humans, distinct subsets of T helper (Th) cells produce large amounts of cytokines, which are supposed to orchestrate the immuno-inflammatory process leading to the tissue damage. Indeed, cytokine blockers, including the three licensed anti- TNF-and#945; and the neutralizing IL-12/p40 antibodies, have already been tested with success in CD. More than one third of patients do not respond to these treatments and response can wane with time. Moreover, blockade of such cytokines has been reported to associate with development of severe side effects and/or new immune-mediated pathologies. These findings and our better understanding of cytokine-associated effector pathways of tissue destruction suggest the necessity of novel cytokine-based therapies in CD.

As elements of the antioxidant system, cofactors of enzymes, components of transcription factors, and epigenetic modulators, micronutrients, such as vitamins and trace elements, influence various metabolic processes that are directly associated with immune functions. Specifically, the vitamins C and D have been shown to have significance immune function. Therefore, the objective of this review is to elucidate interactions between micronutrients and the immune system. In the initial section of this review, we present a general overview of interactions between the immune system and micronutrients, with a focus on the immunobiologically relevant functions of vitamin C. Immune competent cells accumulate vitamin C against a concentration gradient, with a close relationship between vitamin C supply and immune cell activity, especially phagocytosis activity and T-cell function. Accordingly, one of the consequences of vitamin C deficiency is impaired resistance to various pathogens, while an enhanced supply increases antibody activity and infection resistance.

As explained in the first part of the article, vitamins and trace elements influence various metabolic functions that are directly related to immune function. In this context, secosteroid vitamin D has met with growing interest. The discussion has focused on whether and, if so, to what extent, vitamin D might contribute to the prevention and possibly the treatment of infections and autoimmune diseases. We know, for instance, that immune cells are capable of synthesizing calcitriol from its precursor calcidiol, whereby the former enhances the synthesis of antibacterial peptides by macrophages while simultaneously inhibiting the (auto)immune response mediated by T helper cells (Th1). Numerous observational studies support the hypothesis that a vitamin D deficit increases the risk of autoimmune diseases such as type 1 diabetes mellitus, multiple sclerosis, psoriasis and rheumatoid arthritis; however, there are few reliable interventional studies to date. In general, immune status represents a sensitive indicator of micronutrient supply. Conversely, the activity of the immune system has an effect on the status of and requirements for nutrients.