Inflammation & Allergy-Drug Targets (Discontinued) - Volume 11, Issue 1, 2012

As Editor-in-Chief, I got a note in August 2011 that a suspected highly overlapping of word to word repetition was found in a Lancet article (Lancet, 2004 Sep 11-17, 364(9438), 985-996) and an article published in Curr. Drug Targets Inflam. Allergy, 2005 Dec, 4(6), 675-683. The source was: “Emerging targets of COPD therapy” by Barnes PJ, National Heart and Lung Institute, Imperial College, London, UK. At that time, I was not responsible for the journal, but now, I am responsible for an adequate reaction to this note. Plagiarism can be separated into two parts: plagiarism of ideas and plagiarism of words (verbatim) [1]. Plagiarism in any form is a scientific misconduct, even fraud, and can be hazardous to any career. It is apparently that many leading academics and administrators are extremely reluctant to take actions against plagiarist colleagues - especially against well-known and recognized senior academics, who support the phrase “publish” or “perish” for their own success, for the success of (in-) dependent individuals and research institutions. Moreover, as long as it is believed that scientific money follows those articles published in highly ranked and indexed journals, mainstream-wise and not unconventional ideas, plagiarizers might speculate that laziness is the most likely cause and excuse of plagiarism for authors, and especially for those who are not native English speakers and lack to generate an original text. The significance of plagiarism can vary widely, depends on its extent and context in which it occurs. One sentence or paragraph would not usually be cause for concern, whereas sections and paragraphs copied almost verbatim would be considered a gross violation of academic norms. Any retraction of a paper should follow the COPE guidelines and, above all, the author(s) should be given a chance to respond to the comments. I tried to establish this contact, but failed. Dr. Peter Barnes is in respect to his publication oeuvre with more than 1300 publications listed in PubMed- NCBI an outstanding research person and clinician. Because of the academic privation experienced, the publishing house Bentham Science and I decided to retract the paper by Peter Barnes from Inflammation & Allergy - Drug Targets. We are fully aware that this act will not tackle Dr. Barnes's ranking within the clinician stardom and this misconduct is not heralded far and wide in the academic world. But it is a sign and attempt to reduce authors´ temptation taking and using as one's own thoughs, writings, or inventions of another or, to increase personally the number of publications by essentially duplicating a previously published paper. We know that money and politics are also behind this plague of plagiarism. As long as the academics receive bonuses and promotions based on how much they publish and not based on what is the predictable impact of the publication e.g. for the society, for the human being, for the patient or for the natural environment, in general, for the increasing quality of life at this planet earth, episodes of committed plagiarism will have their ups and downs in science. As an Editor-in-Chief, I am committed to fight against scientific fraud. This journal is especially widely open to invite and accept articles from those scientific communities of the world, where growing science becomes a hallmark for the future, for freedom, social and financial prosperity and we should therefore encourage the best and brightest students, researchers and clinicians from these countries not to start the “publishing career” by plagiarism, but to rely on the ethical education, scientific self-confidence, knowledge and scientific curiosity. The purpose of any publication is to show the own thinking and not to create a patchwork of borrowed ideas. However, it is the individual's intellectual performance to give proper references to all the readings and ideas encountering during the process of chain studying and eventually solving a problem or answering a scientific question. Electronic informations are easily available, but that does not mean that they are “free”. For example, the numbers of websites that have the endorsements of universities are steadily increasing and part/all of the content for a certain theme can easily be downloaded to be used for “copy” and “paste”. Resist the temptation to use this material without giving those people the credit who actually deserve it. Many software programs for detection of plagiarism are now developed to counter-attacking this misconduct [2]. Plagiarism is a complex, socially, financially and culturally constructed loaded concept which causes a lot of individual and society oriented problems - it is a crime against the academic community within one unified and scientific world. It is an important and mandatory task of universities, editors of scientific journals and administrators/academic staff to educate as a preventive approach the young academics to take away the anxiety of plagiarism from them by encouraging recognition of and engagement with cultural diversity in scientific writing, but in parallel, to obey ethos and values of academic honesty and integrity. Any deviation from this philosophy constitutes academic misconduct and should incur appropriate sanctions.

Objectives: Diarrhea the second leading cause of death in childhood is caused by a variety of organisms. Rehydration reduces the risk of death but it is not effective in shortening duration of disease. Recently, probiotics have been recommended for prevention or treatment of gastrointestinal disorders including diarrhea. Considering existing documents from different aspects, it seems that results are somehow controversial or non-conclusive. Thus, we aimed to meta-analyze clinical trials to show actual benefit of probiotics in treatment of diarrhea. Methodology: The literature search provided 1228 articles while only 19 articles focusing on the analyses performed on children were eligible to be included in the meta-analysis with a total of 3867 patients enrolled in the study. Studies in adults’ diarrhea, HIV patients, diarrhea induced by Clostridium difficile, radiation and chemotherapy were also systematically reviewed. Results: The meta-analysis showed that probiotics decrease the duration of diarrhea and fever significantly in children while their effects on the duration of hospitalization, vomiting and number of stools per day were not significant. The results of systematic review on adults' diarrhea, amoebiasis, clostridium difficile-associated diarrhea, diarrhea in HIV positive patients, radiation-induced diarrhea, and chemotherapy-induced diarrhea did not support efficacy of probiotics in acute diarrhea. Conclusion: Probiotics may reduce duration of diarrhea and fever in children but their exact efficacy in treatment of diarrhea is not obvious yet.

Hypersensitivity pneumonitis (HP) is characterized by a lymphocytic alveolitis, classically delineated by an increase of CD8+ lymphocytes, with an inversion of the CD4+/CD8+ ratio. The aim of this study is both to describe the yield and cell bronchoalveolar lavage (BAL) profile and to revisit the assumption of low BAL CD4/CD8 ratio in the diagnosis of HP. A multicentric study was conducted on 139 patients who fulfilled the standardized diagnostic criteria of HP, mainly affected by farmer's lung. Mean total cell count in BAL fluid was 594 ± 401.103 cells /ml. Prominent absolute lymphocytic alveolitis, moderate neutrophilia, and mild eosinophilia and mastocytosis were found. Mean CD4/CD8 ratio was 3.8 ± 6.1 (median 2.1). Thirty four percent of the patients showed lymphocytic CD8 alveolitis (ratio<1). The CD4/CD8 ratio was not different between forms, etiologies of HP, and time elapsed since last antigen exposure, but was higher in women (p=0.02). BAL in HP shows high total cell and lymphocyte counts, moderate neutrophilia, and mild eosinophilia and mastocytosis. An absence of low CD4/CD8 ratio should not at all exclude diagnosis.

Atopic dermatitis is an allergic inflammatory skin disease that is characterized by late eczematous skin lesions which result from non-IgE-mediated immune responses. It is well known that food allergy is an important cause of atopic dermatitis. Moreover, with recent advances in the diagnosis and treatment of food allergy, it becomes possible to elucidate the role of IgE- and non-IgE-mediated food allergies. Interprerations for blood eosinophil counts and total serum IgE levels are updated based on the immunopathogenesis of AD relating with these IgE- and non-IgE-mediated food allergies. The clinical significances of skin prick test and allergen-specific IgE are re-evaluated according to the out-to in and in-to out sensitization. Atopic march is reconsturcted by the sequential sensitization of foods and aeroallergens. In this review, the revized immunopathogenesis and relevant interpretations of food allergy in atopic dermatitis are described for the evaluation of precise clinical status of AD.

Matrix metalloproteinase-9 (MMP-9) has been implicated in both inflammation and fibrosis. It has been reported that cigarette smoke induced MMP-9 expression and that lycopene may act as an anti-inflammatory agent and may counteract several signal pathways affected by cigarette smoke exposure. However, at the moment, it is unknown if lycopene may inhibit cigarette smoke-induced MMP-9 expression. Presently, we examined the inhibitory mechanism of lycopene on MMP-9 induction in cultured human macrophages (THP-1 cells), in isolated rat alveolar macrophages (AMs) and in cultured RAT-1 fibroblasts, all cellular sources of MMP-9, exposed to cigarette smoke extract (CSE). CSE induced a marked increase in MMP-9 expression in cultured as well as in isolated cells. A 8 h-lycopene pre-treatment (0.5-2 μM) reduced CSE-mediated MMP-9 induction in a dose- and time-dependent manner. Lycopene attenuated CSE-mediated activation of Ras, enhancing the levels of this protein in the cytosolic fraction. Moreover, lycopene inhibited CSE-induced ERK1/2 and NF-κB activation in a dose-dependent manner. Lycopene-mediated inhibition of MMP-9 was reversed by mevalonate and associated with a reduced expression of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. Taken together, these results suggest that lycopene may inhibit CSE-mediated MMP-9 induction, primarily by blocking prenylation of Ras in a signaling pathway, in which MEK1/2-ERK1/2 and NF-κB are involved.

Peyronie's disease (PD) is a connective tissue disorder characterized by a fibrous plaque involving the tunica albuginea of the penis. The inelastic fibrous plaque leads to a penile curvature. Several Authors have suggested an immunological genesis of this disease, others have linked PD with Dupuytren's contracture. Signs of this disease are curvature, penile pain, penile deformity, difficulty with coitus, shortening, hinging, narrowing and erectile dysfunction. The natural history of PD and the clinical course can develop from spontaneous resolution of symptoms to progressive penile deformity and impotence. Surgical treatment is indicated when patients fail the conservative medical treatment and however, only in case of disease stabilization with a condition of impossibility of penetration. The medical treatment is indicated in the development stage of PD for at least one year after diagnosis and whenever in case of penile pain. Current non-surgical therapy includes vitamin-E, verapamil, para-aminobenzoate, propoleum, colchicine, carnitine, tamoxifen, interferons, collagenase, hyaluronidase, cortisone, pentoxifylline, superoxide dismutase, iontophoresis, radiation, extracorporeal shock wave therapy (ESWT) and the penile extender. The etiology of this fibrotic disease is not widely known, although in recent years pathophysiological knowledge has evolved and new studies propose the penile trauma as cause of the disease. The penile trauma results in a delamination of the tunica albuginea with a consequent small hematoma, then the process evolves as an inflammation with accumulation of inflammatory cells and production of reactive oxygen species (ROS). In the course of the inflammation, Peyronie's disease occurs due to the activation of nuclear factor kappa-B, that induces the production of inducible nitric oxide synthase (iNOS), with an increase of nitric oxide, leading to increased production of peroxynitrite anion. All these processes result in the proliferation of fibroblasts and myo-fibroblasts and excessive production of collagen between the layers of the tunica albuginea (penile plaque). Referring to the current knowledge of inflammatory and oxidative mechanisms of PD, a possible therapeutic strategy is then analyzed.

Cyclopentenone prostaglandins play a modulatory role in inflammation, in part through their ability to covalently modify key proinflammatory proteins. Using mesangial cells as a cellular model of inflammation we have observed that 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) exerts a biphasic effect on cell activation by cytokines, with nanomolar concentrations eliciting an amplification of nitric oxide (NO) production and iNOS and COX-2 levels, and concentrations of 5 μM and higher inhibiting proinflammatory gene expression. An analog of 15d-PGJ2 lacking the cyclopentenone structure (9,10-dihydro-15d-PGJ2) showed reduced ability to elicit both types of effects, suggesting that the electrophilic nature of 15d-PGJ2 is important for its biphasic action. Interestingly, the switch from stimulatory to inhibitory actions occurred within a narrow concentration range and correlated with the ability of 15d-PGJ2 to induce heme oxygenase 1 and γ-GCSm expression. These events are highly dependent on the triggering of the antioxidant response, which is considered as a sensor of thiol group modification. Indeed, the levels of the master regulator of the antioxidant response Nrf2 increased upon treatment with concentrations of 15d-PGJ2 above 5 μM, an effect that could not be mimicked by 9,10-dihydro-15d-PGJ2. Thus, an interplay of redox and electrophilic signalling mechanisms can be envisaged by which 15d-PGJ2, as several other redox mediators, could contribute both to the onset and to the resolution of inflammation in a context or concentration-dependent manner.

Iron sucrose originator (ISORIG) has been used to treat iron deficiency and iron deficiency anemia for decades. Iron sucrose similars (ISSs) have recently entered the market. In this non-clinical study of non-anemic rats, five doses (40 mg iron/kg body weight) of six ISSs marketed in Asian countries, ISORIG or saline solution (control) were administered intravenously over four weeks to compare their toxicologic effects. Vasodilatory effects, impaired renal function and hepatic damage were only observed in the ISS groups. Significantly elevated serum iron and transferrin saturation levels were observed in the ISS groups suggesting a higher release of iron resulting in higher amounts of non-transferrin bound (free) iron compared to ISORIG. This might explain the elevated oxidative stress and increased levels of inflammatory markers and antioxidant enzymes in the liver, heart and kidneys of ISS-treated animals. Physico-chemical analyses showed that the molecular structure of most of the ISSs differed greatly from that of the ISORIG. These differences may be responsible for the organ damage and oxidative stress observed in the ISS groups. Significant differences were also found between different lots of a single ISS product. In contrast, polarographic analyses of three different ISORIG lots were identical, indicating that the molecular structure and thus the manufacturing process for ISORIG is highly consistent. Data from this study suggest that ISSs and ISORIG differ significantly. Therefore, before widespread use of these products it would be prudent to evaluate additional non-clinical and/or clinical data proving the safety, therapeutic equivalence and interchangeability of ISSs with ISORIG.