Inflammation & Allergy-Drug Targets (v.11, #1)

As Editor-in-Chief, I got a note in August 2011 that a suspected highly overlapping of word to word repetition was found in aLancet 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 formis a scientific misconduct, even fraud, and can be hazardous to any career. It is apparently that many leading academics andadministrators are extremely reluctant to take actions against plagiarist colleagues – especially against well-known andrecognized 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 articlespublished in highly ranked and indexed journals, mainstream-wise and not unconventional ideas, plagiarizers might speculatethat laziness is the most likely cause and excuse of plagiarism for authors, and especially for those who are not native Englishspeakers 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 paragraphwould not usually be cause for concern, whereas sections and paragraphs copied almost verbatim would be considered a grossviolation 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 respondto the comments. I tried to establish this contact, but failed. Dr. Peter Barnes is in respect to his publication oeuvre with morethan 1300 publications listed in PubMed- NCBI an outstanding research person and clinician. Because of the academicprivation experienced, the publishing house Bentham Science and I decided to retract the paper by Peter Barnes fromInflammation & 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 notheralded far and wide in the academic world. But it is a sign and attempt to reduce authors´ temptation taking and using asone’s own thoughs, writings, or inventions of another or, to increase personally the number of publications by essentiallyduplicating a previously published paper.We know that money and politics are also behind this plague of plagiarism. As long as the academics receive bonuses andpromotions based on how much they publish and not based on what is the predictable impact of the publication e.g. for thesociety, for the human being, for the patient or for the natural environment, in general, for the increasing quality of life at thisplanet 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 andaccept articles from those scientific communities of the world, where growing science becomes a hallmark for the future, forfreedom, social and financial prosperity and we should therefore encourage the best and brightest students, researchers andclinicians from these countries not to start the “publishing career” by plagiarism, but to rely on the ethical education, scientificself-confidence, knowledge and scientific curiosity. The purpose of any publication is to show the own thinking and not tocreate a patchwork of borrowed ideas. However, it is the individual´s intellectual performance to give proper references to allthe readings and ideas encountering during the process of chain studying and eventually solving a problem or answering ascientific question.Electronic informations are easily available, but that does not mean that they are “free”. For example, the numbers of websitesthat have the endorsements of universities are steadily increasing and part/all of the content for a certain theme can easily bedownloaded 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 thismisconduct [2].Plagiarism is a complex, socially, financially and culturally constructed loaded concept which causes a lot of individual andsociety oriented problems – it is a crime against the academic community within one unified and scientific world. It is animportant and mandatory task of universities, editors of scientific journals and administrators/academic staff to educate as apreventive approach the young academics to take away the anxiety of plagiarism from them by encouraging recognition of andengagement with cultural diversity in scientific writing, but in parallel, to obey ethos and values of academic honesty andintegrity. Any deviation from this philosophy constitutes academic misconduct and should incur appropriate sanctions.

A Meta-Analysis and Systematic Review on the Effect of Probiotics in Acute Diarrhea by Pooneh Salari, Shekoufeh Nikfar, Mohammad Abdollahi (3-14).
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 havebeen recommended for prevention or treatment of gastrointestinal disorders including diarrhea. Considering existingdocuments from different aspects, it seems that results are somehow controversial or non-conclusive. Thus, we aimed tometa-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 onchildren were eligible to be included in the meta-analysis with a total of 3867 patients enrolled in the study. Studies inadults’ diarrhea, HIV patients, diarrhea induced by Clostridium difficile, radiation and chemotherapy were alsosystematically reviewed.Results: The meta-analysis showed that probiotics decrease the duration of diarrhea and fever significantly in childrenwhile their effects on the duration of hospitalization, vomiting and number of stools per day were not significant. Theresults of systematic review on adults’ diarrhea, amoebiasis, clostridium difficile-associated diarrhea, diarrhea in HIVpositive patients, radiation-induced diarrhea, and chemotherapy-induced diarrhea did not support efficacy of probiotics inacute diarrhea.Conclusion: Probiotics may reduce duration of diarrhea and fever in children but their exact efficacy in treatment ofdiarrhea is not obvious yet.

Bronchoalveolar Lavage in Hypersensitivity Pneumonitis: A Series of 139 Patients by Denis M. Caillaud, Jean M. Vergnon, Anne Madroszyk, Boris M. Melloni, Marlene Murris, Jean C. Dalphin (15-19).
Hypersensitivity pneumonitis (HP) is characterized by a lymphocytic alveolitis, classically delineated by anincrease of CD8+ lymphocytes, with an inversion of the CD4+/CD8+ ratio. The aim of this study is both to describe theyield and cell bronchoalveolar lavage (BAL) profile and to revisit the assumption of low BAL CD4/CD8 ratio in thediagnosis of HP.A multicentric study was conducted on 139 patients who fulfilled the standardized diagnostic criteria of HP, mainlyaffected by farmer’s lung.Mean total cell count in BAL fluid was 594 ± 401.103 cells /ml. Prominent absolute lymphocytic alveolitis, moderateneutrophilia, and mild eosinophilia and mastocytosis were found. Mean CD4/CD8 ratio was 3.8 ± 6.1 (median 2.1). Thirtyfour percent of the patients showed lymphocytic CD8 alveolitis (ratio<1). The CD4/CD8 ratio was not different betweenforms, 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 lesionswhich result from non-IgE-mediated immune responses. It is well known that food allergy is an important cause of atopicdermatitis. Moreover, with recent advances in the diagnosis and treatment of food allergy, it becomes possible to elucidatethe role of IgE- and non-IgE-mediated food allergies. Interprerations for blood eosinophil counts and total serum IgElevels 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-toout 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 theevaluation of precise clinical status of AD.

Modulation of MMP-9 Pathway by Lycopene in Macrophages and Fibroblasts Exposed to Cigarette Smoke by Paola Palozza, Rossella E. Simone, Assunta Catalano, Flavia Saraceni, Leonardo Celleno, Maria Cristina Mele, Giovanni Monego, Achille Cittadini (36-47).
Matrix metalloproteinase-9 (MMP-9) has been implicated in both inflammation and fibrosis. It has beenreported that cigarette smoke induced MMP-9 expression and that lycopene may act as an anti-inflammatory agent andmay counteract several signal pathways affected by cigarette smoke exposure. However, at the moment, it is unknown iflycopene may inhibit cigarette smoke-induced MMP-9 expression. Presently, we examined the inhibitory mechanism oflycopene 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 induceda 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-mediatedactivation of Ras, enhancing the levels of this protein in the cytosolic fraction. Moreover, lycopene inhibited CSE-inducedERK1/2 and NF-κB activation in a dose-dependent manner. Lycopene-mediated inhibition of MMP-9 was reversed bymevalonate 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 blockingprenylation of Ras in a signaling pathway, in which MEK1/2-ERK1/2 and NF-..B are involved.

Peyronie’s disease (PD) is a connective tissue disorder characterized by a fibrous plaque involving the tunicaalbuginea of the penis. The inelastic fibrous plaque leads to a penile curvature. Several Authors have suggested animmunological genesis of this disease, others have linked PD with Dupuytren's contracture. Signs of this disease arecurvature, penile pain, penile deformity, difficulty with coitus, shortening, hinging, narrowing and erectile dysfunction. Thenatural history of PD and the clinical course can develop from spontaneous resolution of symptoms to progressive peniledeformity 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 thedevelopment stage of PD for at least one year after diagnosis and whenever in case of penile pain. Current non-surgicaltherapy includes vitamin-E, verapamil, para-aminobenzoate, propoleum, colchicine, carnitine, tamoxifen, interferons,collagenase, hyaluronidase, cortisone, pentoxifylline, superoxide dismutase, iontophoresis, radiation, extracorporeal shockwave therapy (ESWT) and the penile extender. The etiology of this fibrotic disease is not widely known, although in recentyears pathophysiological knowledge has evolved and new studies propose the penile trauma as cause of the disease. Thepenile trauma results in a delamination of the tunica albuginea with a consequent small hematoma, then the process evolvesas an inflammation with accumulation of inflammatory cells and production of reactive oxygen species (ROS). In the courseof the inflammation, Peyronie’s disease occurs due to the activation of nuclear factor kappa-B, that induces the production ofinducible nitric oxide synthase (iNOS), with an increase of nitric oxide, leading to increased production of peroxynitriteanion. All these processes result in the proliferation of fibroblasts and myo-fibroblasts and excessive production of collagenbetween the layers of the tunica albuginea (penile plaque). Referring to the current knowledge of inflammatory and oxidativemechanisms of PD, a possible therapeutic strategy is then analyzed.

15-Deoxy-.. 12,14-Prostaglandin J2 Exerts Pro- and Anti-Inflammatory Effects in Mesangial Cells in a Concentration-Dependent Manner by Alma E. Martinez, Francisco J. Sanchez-Gomez, Beatriz Diez-Dacal, Clara L. Oeste, Dolores Perez-Sala (58-65).
Cyclopentenone prostaglandins play a modulatory role in inflammation, in part through their ability tocovalently modify key proinflammatory proteins. Using mesangial cells as a cellular model of inflammation we haveobserved that 15-deoxy-..12,14-prostaglandin J2 (15d-PGJ2) exerts a biphasic effect on cell activation by cytokines, withnanomolar concentrations eliciting an amplification of nitric oxide (NO) production and iNOS and COX-2 levels, andconcentrations of 5 µM and higher inhibiting proinflammatory gene expression. An analog of 15d-PGJ2 lacking thecyclopentenone structure (9,10-dihydro-15d-PGJ2) showed reduced ability to elicit both types of effects, suggesting thatthe electrophilic nature of 15d-PGJ2 is important for its biphasic action. Interestingly, the switch from stimulatory toinhibitory actions occurred within a narrow concentration range and correlated with the ability of 15d-PGJ2 to induceheme oxygenase 1 and ..-GCSm expression. These events are highly dependent on the triggering of the antioxidantresponse, which is considered as a sensor of thiol group modification. Indeed, the levels of the master regulator of theantioxidant response Nrf2 increased upon treatment with concentrations of 15d-PGJ2 above 5 µM, an effect that could notbe mimicked by 9,10-dihydro-15d-PGJ2. Thus, an interplay of redox and electrophilic signalling mechanisms can beenvisaged by which 15d-PGJ2, as several other redox mediators, could contribute both to the onset and to the resolution ofinflammation 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 (40mg iron/kg body weight) of six ISSs marketed in Asian countries, ISORIG or saline solution (control) were administeredintravenously over four weeks to compare their toxicologic effects. Vasodilatory effects, impaired renal function andhepatic damage were only observed in the ISS groups. Significantly elevated serum iron and transferrin saturation levelswere 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 inflammatorymarkers and antioxidant enzymes in the liver, heart and kidneys of ISS-treated animals. Physico-chemical analysesshowed that the molecular structure of most of the ISSs differed greatly from that of the ISORIG. These differences may beresponsible for the organ damage and oxidative stress observed in the ISS groups. Significant differences were also foundbetween different lots of a single ISS product. In contrast, polarographic analyses of three different ISORIG lots wereidentical, indicating that the molecular structure and thus the manufacturing process for ISORIG is highly consistent. Datafrom this study suggest that ISSs and ISORIG differ significantly. Therefore, before widespread use of these products itwould be prudent to evaluate additional non-clinical and/or clinical data proving the safety, therapeutic equivalence andinterchangeability of ISSs with ISORIG.