Inflammation & Allergy-Drug Targets (Discontinued) - Volume 9, Issue 1, 2010

The Journal of Inflammation & Allergy - Drug Targets has entered its 9th volume in 2010. The aim of a scientific journal is to exchange ideas, experiences and to supply an optimal amount of information on new findings and developments in a particular field - in this case in inflammation & allergy and, moreover, how molecular pathways and key molecules can be specifically targeted by interventions to prevent, to restore and/or to modulate physiological and pathophysiological functions in health and disease. The rapid and continuous upsurge of interesting and fascinating ideas and solid data in the subject of inflammation and allergy necessitate the publication of a prestigious journal to furnish the updated materials to the students, researchers, clinicians and politicians engaged in public health worldwide. The scientific success of volume 8 in 2009 was only made possible, because of the authors' solicitated articles, the rapid decisions about the fate of the manuscripts and, after peer-review and acceptance, the short time of production and release, either electronically or as hard cover. To produce a journal of this international calibre means to handle and administer an intellectual network, starting with the expectations of the authors, creating constructive criticisms by the peers and putting the articles into a scientific context to better understand inflammation & allergy on a molecular and clinical basis by the readers. Therefore, as Editor-in-Chief, I like to thank them all, who have made this journal as a well recognized sounding board to keep on ears and eyes to the rest of the scientific world in this field of life sciences. Many Utopias of a scientific paradise on earth have been evaporated over time, also heralded in scientific meetings and publications. There is no good or bad journal, we can not blame a journal for good or bad contents as long the as Editors strictly follow the guidelines of the “Council of Science Editors”, because we want to keep the scientific freedom to learn from hundreds or thousands of scientific stories the final lession of truth between faith and reason. As this journal's circulation is truly international, there is a continuous tendency to update this journal for all needs, for the authors as well for the readers. It is the joint task of all of us, Editors and members of the editorial advisory board to ensure a conscise and condensed presentation of the ideas, results, and critical comments. It is to emphasise, that we shall have to change the journal gradually in accordance with expertise and progress in inflammation & allergy. We welcome scientists from all over the world who understand that there is an urgent demand to administer science at the cutting edge of knowledge and, above all, that life science has to be changed by curious ideas, which do not always fit the so called mainstream. A prestigeous journal, like “Inflammation & Allergy - Drug Target” contributes not only to solid science in the particular field but has also to take responsibility for the political impact within the scientific community. Measurement of scientific impact has been and is still a big debated issue. Therefore, we are very proud to publish in the first issue of volume 9, besides high impact science, solid thoughts on impact factors and editing medical journals, written by Yuri Gasparyan (United Kingdom), who is truly expert because of his many duties as member of distinguished associations of medical editors. Maybe, we open hereby a forum for Editors, Editorial Advisory Board Members and Readers how to deal with this issue, beause to reach and hold a career is closely related to the publication policy of the individual researcher.

Publishing original papers, reviews, editorials, letters-to-the-editor, and other types of scientific articles is a crucial stage of the research process impacting author and journal profiles and research institutions ranking. A high quality publication is a means of science communication and collaboration of scientists in their field of expertise [1]. Scholarly publications facilitate comprehensive discussion of scientific achievements and prospects of future research studies, including those with international collaboration. Importantly, articles published in biomedical journals can substantially change existing medical research and education practices and suggest better quality diagnostic, preventive and curative methods. Successful publications attracting attention of other researchers, stimulating new ideas, and becoming highly-cited boost authors' research profile, strengthen positions of institutions supporting scientific productivity, and increase chances to get funding for future research studies. Currently, in most countries, academic promotion of an individual, faculty recruitment, and distribution of financial sources for research are all subjected to the evaluation of a researcher/institution profile in worldrenown indexing systems and catalogues, such as PubMed, Scopus, Index Copernicus, Institute for Scientific Information (ISI). Over the past decades, indexes have proliferated to quantify impact of scientific productivity. Most notably, citation indexing and analysis proposed in 1950th by Eugene Garfield [2] have evolved into the expanded system of tracking citations and journal ranking through ISI [3]. Introduction of the Hirsch (h) index in 2005 [4] facilitated evaluation of an individual's research output and his/her scientific impact based on a number of highly-cited publications indexed on Scopus, ISI, or Google Scholar. The hindex is defined as h number of papers out of all publications of the author with at least h citations each. It was initially devised by J.E. Hirsch to distinguish physicists with a small number of high quality papers attracting more citations from those with a large number of papers without significant impact on the field. Simplicity of this index made it essential indicator of career advancement in other fields of science, as well as institution and journal ranking by Scopus and other leading abstracting/indexing databases. Meanwhile, several important limitations of the h-index became apparent, one being its inability to objectively measure scientific impact of young scientists and those with a small number of publications, particularly in the field of biomedicine [5]. It also became clear that comparisons between different levels of the h-index are appropriate only within certain fields of science (e.g., cardiovascular medicine, rheumatology, general medicine, etc.). Measurement of scientific impact practised over the past decades has become an objective link between standards of education and research output in academic institutions worldwide. Notably, citation analysis of scientific publications indexed on Scopus over a 5-year period has been incorporated into the system of annual ranking of academic institutions by prestigious The Times Higher Education QS World University Rankings [6]. Today, world universities competing for leading 600 places are those with the highest number of highly-cited papers (reflected in the so called citations per faculty score), which indirectly make these universities famous all over the world (this brings points for the so called academic peer-review) and attractive for international academic and research collaboration (international factors used for a university ranking include proportion of international faculty). In 2009, Universities of Harvard, Cambridge and Yale were among 3 top academic institutions with the highest scores.

The development of colorectal cancer in ulcerative colitis is a function of disease duration, with the risk approaching 14% at 25 years. Colitic cancer has become an issue in the last decades, as the availability of effective immune suppressors has reduced resort to curative colectomies. Scrutiny of the available drug options for ulcerative colitis has generated solid evidence of a chemopreventive role of mesalamines. Recent studies on the thiopurines azathioprine and mercaptopurine have unraveled the ability of these drugs to reduce inflammation and influence adaptive immunity by enhancing apoptosis. This evidence, speaking in favor of a chemopreventive role of thiopurines, has not been supported until recently by clinical studies. By contrast, endoscopic and clinical data in our hands have continued to suggest such a role: of a cohort of ulcerative colitis patients treated with azathioprine for 17 years, those on active treatment had no mucosal inflammation on endoscopy and overall none in this cohort developed cancer. This retrospective data have now been validated by cutting-edge information from a prospective nationwide study from an independent group which found a significant chemopreventive effect of azathioprine in those with extended longstanding colitis. Combination of our single-center experience with the data from this large study strongly indicates that the immune modulatory properties of thiopurines can translate into clinically meaningful anti-cancer activity in colitis. These results are likely to influence the medical choices of inflammatory bowel disease caregivers in the decades to come.

Primary Sjogren's syndrome (pSS) is a common autoimmune disease which can lead to considerable complications and diminished quality of life. Recent insights into disease mechanisms and the advent of biological agents have provided new options for the treatment of pSS. In particular, B cell targeted intervention has shown promising results. In this review, we focus on emerging treatment strategies and therapeutic targets beyond B cells. Interference with proinflammatory cytokines and mechanisms that link innate and adaptive immunity offers new options in the treatment of pSS. Approaches directed against interleukin (IL)-1β, Toll-like receptors and the inflammasome are emerging. Targeting IL-12, IL-18, the IL-23/IL-17 system, macrophage migration inhibitory factor and chemokines might be considered. The inhibition of apoptosis of glandular cells, the promotion of cell regeneration and organ-specific stem cell transplantation are potential strategies directed at preserving and restoring functional exocrine tissue. The recognition of patients who benefit most from a particular strategy might help to design more efficient therapeutic approaches. Since efficacy of many agents depends on the presence of residual functional glandular tissue, future studies should focus on patients with recent onset of pSS.

Acute pancreatitis (AP) and sepsis are inflammatory disorder varying in magnitude of response to infection or inflammatory stimuli. The specific role of various causative factors in AP, septic shock, current pharmacological treatments, animal models, role of infiltrating cells and novel molecules that play an important role in the disease progression to sepsis are explored. AP is an inflammatory disease of the pancreas. Over the years accumulating evidence suggests numerous molecules as key regulators of the inflammatory signaling cascade such as selectins, chemokine signaling and expression of intergrins on leukocytes facilitate adhesion to vessel wall. Inhibition of any of these molecules has proven to be effective in animal models of AP. Recently, the biochemical role of hydrogen sulfide (H2S) and substance P in caerulein induced AP and in cecal ligation and puncture induced sepsis and their role in the pathogenesis of the disease have highlighted the importance of novel molecules as therapeutic targets in addition to the known proinflammatory molecules, cytokines and chemoattractant chemokines and their receptors upregulated in AP and sepsis. This review aims to give an overview of the multifaceted complex interactions in a prearranged fashion and their functional role in the inflammatory process that afflict AP and sepsis. The interlinking molecules in AP and sepsis emphasize the similarities in the inflammatory response and the importance of pharmacological agents that reduce or inhibit the progression to chronic stage.

Blood coagulation could be recognized as intrinsic inflammation. The coagulant mediators (FVIIa, FXa, thrombin (FIIa), FXIIa) and fibrin(ogen) activate cellular signaling, eliciting the production of cytokines, chemokines, growth factors, and other proinflammatory mediators. Hypercoagulability with elevated coagulant mediators would certainly trigger hyper-inflammatory state not to mention about the direct hypercoagulable actions on thrombosis, and platelet and complement activations, all of which contribute to inflammatory events. Furthermore, anticoagulant's antiinflammatory effects readily reinforce the proposal that blood coagulation results in inflammation. The observations on protease activated receptor (PAR) activation and PAR antagonists modulating inflammation are also in line with the concept of coagulation-dependent inflammation.

Rheumatoid arthritis (RA) is one of the most common chronic inflammatory disorders associated with enhanced cardiovascular morbidity and mortality. Established high prevalence of classical cardiovascular risk factors may only partly explain cardiovascular phenomenon in this disease. Emerging risk factors, markers of inflammation and prothrombotic state such as platelet size are believed to reflect activity of RA. We aimed to study mean platelet volume (MPV) in a cohort of patients with RA and to clarify possible effects of classical cardiovascular and RA-associated risk factors on MPV. Demographic, clinical and a wide range of laboratory parameters, including MPV and platelet count, were obtained for 400 RA patients. Platelet size and count were also assessed in 360 non-RA controls from the local population. We found significantly increased MPV in RA patients compared with controls (P=0.001). The difference retained significant after adjustment for age and sex. High values of MPV (Reg 10.7 femtoliter [fL]) were more frequent in RA patients than in controls (21% vs 9.2%; P<0.0001). In RA patients, blood pressure greater than 140/90 mmHg was associated with high levels of MPV (Odds Ratio [OR] 2.2, 95% Confidence Interval [CI] 1.3-3.7; P=0.003). It is possible that MPV as a surrogate marker of platelet function reflects enhanced vascular risk. To further explore the role of MPV as a marker for cardiovascular risk in RA, prospective studies are warranted.

Functional disability in rheumatoid arthritis (RA) reflects the cumulative effects of the disease over time and is an important outcome measure. Various factors are responsible for functional disability, such as pain, swollen joints, joint tenderness and damage, deformities but also fatigue and depression. The most commonly used instrument for evaluating functional disability in RA is the health assessment questionnaire (HAQ), a self reported questionnaire. Numerous longitudinal studies have attempted to identify predictors of disability in RA and their results show that the most common variables associated with future disability are baseline HAQ or its variation during the first year of follow-up, female sex and old age. The HAQ score is a valuable indicator of disability in RA and has been shown to be predictive of loss of employment and mortality in RA. It may therefore be regarded as a relevant outcome variable in clinical trials and for the management of patients with RA in clinical practice.

In response to infection or injury, a ubiquitous nucleosomal protein, HMGB1 is secreted actively by innate immune cells, and/or released passively by injured/damaged cells. Subsequently, extracellular HMGB1 alerts, recruits, and activates various innate immune cells to sustain a rigorous inflammatory response. A growing number of HMGB1 inhibitors ranging from neutralizing antibodies, endogenous hormones, to medicinal herb-derived small molecules (such as nicotine, glycyrrhizin, tanshinones, and EGCG) are proven protective against lethal infection and ischemic injury. Here we review emerging evidence that support extracellular HMGB1 as a proinflammatory alarmin(g) danger signal, and discuss a wide array of HMGB1 inhibitors as potential therapeutic agents for sepsis and ischemic injury.