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INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY

0394-6320 (2013)Copyright © by BIOLIFE, s.a.s.

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INTEREST RELEVANT TO THIS ARTICLE.

EDITORIAL

Vol. 26, no. 2, 283-290 (2013)

Vaccines have eradicated or controlled many infectious diseases, saving each year millions of lives and quality of life of many other millions of people. In spite of the success of vaccines over the last two centuries, parents (and also some health care workers) gloss over the devastating consequences of diseases, which are now avoided thanks to vaccines, and direct their attention to possible negative effects of immunization. Three immunological objections are raised: vaccines cause antigenic overload, natural immunity is safer and better than vaccine-induced immunity, and vaccines induce autoimmunity. The last point is examined in this review. Theoretically, vaccines could trigger autoimmunity by means of cytokine production, anti-idiotypic network, expression of human histocompatibility leukocyte antigens, modification of surface antigens and induction of novel antigens, molecular mimicry, bystander activation, epitope spreading, and polyclonal activation of B cells. There is strong evidence that none of these mechanisms is really effective in causing autoimmune diseases. Vaccines are not a source of autoimmune diseases. By contrast, absolute evidence exists that infectious agents can trigger autoimmune mechanisms and that they do cause autoimmune diseases.

VACCINES AND AUTOIMMUNITY

M. DE MARTINO, E. CHIAPPINI and L. GALLI

Department of Health Sciences, University of Florence, Anna Meyer Children’s University Hospital, Florence, Italy

Received December 31, 2012 – Accepted March 14, 2013






Vol. 26, no. 2, 291-298 (2013)

Treatment options for prostate cancer consist of radical prostatectomy, hormonal therapy and radiation therapy. Hormonal and radiation therapy have well-known, often profound, effects on the histological appearance of benign and malignant prostate tissue. Novel therapies including focal ablative treatments, chemotherapies and targeted molecular therapies are beginning to emerge and pathologists will play a central role in documenting the effects of these treatments at the tissue level. As such, knowledge of treatment-related changes and access to clinical information are essential to ensure accurate interpretation and reporting of post-treatment prostate specimens by pathologists.

TREATMENT EFFECTS IN PROSTATE CANCER FOLLOWING TRADITIONAL AND EMERGING THERAPIES

R. MAZZUCCHELLI1, M. SCARPELLI1, A. LOPEZ-BELTRAN2, L. CHENG3, R. DI PRIMIO4

and R. MONTIRONI1

1Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Ancona, Italy; 2Department of Pathology and Surgery, University of

Cordoba, Cordoba, Spain; 3Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA; 4Department of Clinical and Molecular Sciences,

Polytechnic University of the Marche Region, School of Medicine, Ancona, Italy

Received February 17, 2013 – Accepted March 7, 2013

The first two authors contributed equally to this work

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Vol. 26, no. 2, 299-304 (2013)

Anxiety disorders (ADs) are the most common type of psychiatric disorders. Pharmacologic options studied for treating ADs may include benzodiazepines, tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRIs), noradrenergic and specific serotonergic antidepressants (NaSSA) and serotonin and noradrenaline reuptake inhibitors (SNRIs). Agomelatine, a new melatonergic antidepressant, has been shown effective in various types of mood disorders. Moreover, some evidence points towards a possible efficacy of such a drug in the treatment of ADs. Therefore, the aim of this review was to elucidate current (facts and views) data on the role of agomelatine in the treatment of ADs. The trials evaluating agomelatine in the treatment of generalized anxiety disorder are few but, overall, encouraging in regards to its efficacy. However, further randomized, placebo-controlled studies on larger samples use are needed. Apart from some interesting case reports, no large studies are, to date, present in literature regarding agomelatine in the treatment of other ADs, such as panic disorder, social anxiety disorder, obsessive-compulsive disorder and post-traumatic stress disorder. Therefore, the clinical efficacy and the relative good tolerability of agomelatine in generalized anxiety (GAD) warrants further investigation in ADs.

IS THERE A ROLE FOR AGOMELATINE IN THE TREATMENT OF ANXIETY DISORDERS? A REVIEW OF PUBLISHED DATA

D. DE BERARDIS1,2, C.M. CONTI2, S. MARINI1,2, F. FERRI1, F. IASEVOLI3, A. VALCHERA4, M. FORNARO5, M. CAVUTO6, V. SRINIVASAN7, G. PERNA8,9,10, A. CARANO11,

M. PIERSANTI12, G. MARTINOTTI2 and M. DI GIANNANTONIO2

1Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, Hospital “G. Mazzini”, ASL 4 Teramo, Italy; 2Department of Neurosciences and Imaging, University “G.

D’Annunzio”, Chieti, Italy; 3Laboratory of Molecular Psychiatry and Psychopharmacotherapeutics, Section of Psychiatry, Department of Neuroscience, University School of Medicine “Federico II”, Naples, Italy; 4Hermanas Hospitalarias, FoRiPsi, Villa S. Giuseppe Hospital, Ascoli Piceno, Italy;

5Department of “Scienze della Formazione”, University of Catania, Italy; 6IASM, L’Aquila, Italy, 7Sri Sathya Sai Medical Educational and Research Foundation, International Medical Sciences Research Study Center, Prasanthi Nilayam, Tamilnadu, India; 8Hermanas Hospitalarias, FoRiPsi, Department of Clinical Neurosciences, Villa San Benedetto Menni, Albese con Cassano, Como, Italy; 9Department

of Psychiatry and Behavioral Sciences, Leonard Miller School of Medicine, University of Miami, USA; 10Department of Psychiatry and Neuropsychology, University of Maastricht, The Netherlands;

11Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, Hospital “C.G. Mazzoni” Ascoli Piceno, Italy; 12Pharmacy Hospital, ASL 4, Teramo, Italy

Received November 1, 2012 – Accepted March 25, 2013






Vol. 26, no. 2, 305-313 (2013)

The hypothesis of a relationship between sarcoidosis and malignancy was firstly formulated in 1972 by Brincker. He documented an association of sarcoid reactions or sarcoidosis with 19 lymphomas and associated malignancies. Based on various epidemiological studies, for more than 20 years sarcoidosis has been considered as a condition at increased risk for cancer, particularly lymphoproliferative disorders. The existence of a sarcoidosis-lymphoma syndrome was therefore proposed, highlighting, as a potential mechanism, the uncontrolled lymphocyte proliferation and mitotic activity. A reduced ability to eliminate an antigen and chronic inflammation have been suggested as triggering events. Leading to a reduced tumor immune surveillance, a diminished myeloid dendritic cells (mDC) function, despite up-regulated co-stimulatory and maturation markers, was also raised as potential mechanism. However, some subsequent studies have questioned the presence of a close association between the two entities and have explained those previously published as the result of selection bias and misclassification. Recently, a Swedish population-based cohort study documented a significant overall excess incidence of cancer among sarcoidosis patients, especially those with multiple hospitalizations or admission in older age, emphasizing again a potential neoplastic risk. Therefore, currently, whether these patients have an increased risk of developing malignant lesions is still debated. Larger and unbiased studies are needed before drawing definite conclusions.

IMMUNOPATHOGENESIS OF SARCOIDOSIS AND RISK OF MALIGNANCY:A LOST TRUTH?

C. TANA1, M.A. GIAMBERARDINO1, M. DI GIOACCHINO2, A. MEZZETTI1

and C. SCHIAVONE1

1Department of Medicine and Science of Aging, “G. D’Annunzio” University, Chieti, Italy;2Unit of Immunotoxicology and Allergy, Ce.S.I., “G. D’Annunzio” University Foundation, Chieti, Italy

Received December 20, 2012 – Accepted April 19, 2013

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EDITORIAL

Vol. 26, no. 2, 315-326 (2013)

Fever of unknown origin (FUO) in adults is conventionally defined by the occurrence of body temperatures above 38.3°C (101°F) for a period of 3 weeks without any identified etiology after a period of 1-week hospitalization. The issue of FUO in pediatrics is rather hazy and still represents a challenging diagnostic dilemma. Most of the available data are limited to nationwide cohorts of patients of any age. The major difficulty in establishing a diagnosis is that the characteristic features rendering specific disorders clinically recognizable are absent or subtle, hence only a painstaking questioning on family background may elicit the correct investigative path. No diagnostic algorithms are actually available and clinicians must rely on a very careful step-by-step evaluation of the single patient. The need for invasive diagnostic techniques should be closely taken into consideration when laboratory tests or simple imaging procedures fail to discern the origin of FUO. Fevers with no reasonable explanation and no localizing signs often conceal different common diseases in children, which tend to display an unusual or atypical pattern. The principal causes behind FUO in pediatric age remain infections, followed by collagen vascular diseases and neoplastic disorders, although most children with malignancies present other systemic signs or suggestive laboratory abnormalities. The possibility of autoinflammatory syndromes, drug fever, and factitious fever should also be taken into account.

A ROADMAP FOR FEVER OF UNKNOWN ORIGIN IN CHILDREN

D. RIGANTE1 and S. ESPOSITO2

1Institute of Pediatrics, Università Cattolica Sacro Cuore, Rome, Italy; 2Pediatric Clinic 1, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione

IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

Received February 17, 2013 – Accepted April 17, 2013






Vol. 26, no. 2, 327-335 (2013)

Vascular endothelial growth factor (VEGF) is one of the most important inducers of angiogenesis, therefore blocking angiogenesis has led to great promise in the treatment of various cancers and inflammatory diseases. VEGF, expressed in response to soluble mediators such as cytokines and growth factors, is important in the physiological development of blood vessels as well as development of vessels in tumors. In cancer patients VEGF levels are increased, and the expression of VEGF is associated with poor prognosis in diseases. VEGF is a mediator of angiogenesis and inflammation which are closely integrated processes in a number of physiological and pathological conditions including obesity, psoriasis, autoimmune diseases and tumor. Mast cells can be activated by anti-IgE to release potent mediators of inflammation and can also respond to bacterial or viral antigens, cytokines, growth factors and hormones, leading to differential release of distinct mediators without degranulation. Substance P strongly induces VEGF in mast cells, and IL-33 contributes to the stimulation and release of VEGF in human mast cells in a dose-dependent manner and acts synergistically in combination with Substance P. Here we report a strong link between VEGF and mast cells and we depict their role in inflammation and immunity.

VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF),MAST CELLS AND INFLAMMATION

Y.B. SHAIK-DASTHAGIRISAHEB1, G. VARVARA2, G. MURMURA2, A. SAGGINI3,G. POTALIVO4, A. CARAFFA4, P. ANTINOLFI4, S. TETÈ2, D. TRIPODI2, F. CONTI5,

E. CIANCHETTI6, E. TONIATO7, M. ROSATI5, P. CONTI7, L. SPERANZA8,A. PANTALONE9, R. SAGGINI10, T.C. THEOHARIDES11 and F. PANDOLFI12

1Department of Medicine, Boston University School of Medicine, Boston, MA, USA; 2Dental School, University of Chieti-Pescara, Italy; 3Department of Dermatology, University of Rome Tor Vergata, Rome, Italy; 4Orthopeadics Division, University of Perugia, Italy; 5Gynecology Clinic,

Pescara Hospital, Pescara, Italy; 6Surgery Division, Ortona Hospital, Ortona, Italy; 7Immunology Division, Medical School, University of Chieti-Pescara, Italy; 8Department of Human Movement Science, University of Chieti-Pescara, Chieti, Italy; 9Orthopedic Division, University of Chieti-Pescara, Italy; 10Department of Neuroscience and Imaging, University of Chieti-Pescara, Italy;

11Department of Pharmacology and Experimental Therapeutics, Biochemistry and Internal Medicine Tufts University School of Medicine, Tufts-New England Medical Center, Boston, MA, USA; 12Department of Internal Medicine, Catholic University of the Sacred Heart, Rome, Italy

Received March 21, 2013 – Accepted June 10, 2013

PROOF






Vol. 26, no. 2, 337-347 (2013)

Insulin-like growth factor 1 (IGF-1) and its receptor (insulin-like growth factor 1 receptor, IGF1R) can regulate the extracellular matrix synthesis and play a crucial role in maintaining the normal functions of the intervertebral disc (IVD). The objective of this study was to investigate whether there would be accelerated IVD degeneration (IVDD) in IGF1R+/- mice. Three IGF1R+/- male mice and three wild-type male mice were sacrificed respectively at 6, 12, and 18 weeks after birth. Six lumbar disc samples were harvested from each mouse, with a total of 54 disc samples taken from each genotype. Histomorphological analysis for the IVD was performed to assess the degenerative extent according to the classification system proposed by Boos et al. Quantitative real-time PCR and semi-quantitative histologic scoring (HScore) for immunohistochemical staining were used to evaluate the expression level of type-II collagen, aggrecan and matrix metallopeptidase 13 (MMP-13). Histomorphological analysis for the discs revealed significantly less amounts of proteoglycan and type-II collagen, and significantly higher total degenerative score in IGF1R+/- mice than in wild-type mice. Real-time PCR showed that the mRNA expressions of type-II collagen and aggrecan in the discs were significantly lower, while MMP-13 was significantly higher in IGF1R+/- mice than in wild-type mice. The results of HScore analysis were similar to those obtained from the quantitative real-time PCR. Taken together, our study indicates that reduced expression of IGF1R would lead to accelerated degeneration of IVD. IGF1R+/- mice could be regarded as a good animal model to study IVD degeneration (IVDD), and studies on the IVD of IGF1R+/- mice could provide further insight into the pathogenesis of IVDD.

REDUCED EXPRESSION OF INSULIN-LIKE GROWTH FACTOR 1 RECEPTOR LEADS TO ACCELERATED INTERVERTEBRAL DISC DEGENERATION IN MICE

B. LI, X-F. ZHENG, B-B. NI, Y-H. YANG, S-D. JIANG, H. LU and L-S. JIANG

Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong UniversitySchool of Medicine, Shanghai, China

Received January 27, 2013 – Accepted March 27, 2013






Vol. 26, no. 2, 349-359 (2013)

More and more studies have demonstrated the anti-inflammatory effects of heparin. However, in the aspect of allergic airway inflammation, data about its daily use in animal model is scarce. To evaluate the efficacy of 22-day intranasal heparin administration in mite-induced airway allergic inflammation in BALB/c mice, the murine model of house dust-mite allergen-induced asthma was used to assess the effect of heparin (h) and low molecular weight heparin (l mwh) administered intra-nasally (IN) throughout the full study period (22 days). Effects were monitored by histopathology, cell counts in broncho-alveolar lavage fluid (BALF), local cytokine production, serum, specific antibody levels, and airway resistance measurements. Compared to the positive control group, both hIN and lmwhIN groups had lower peri-bronchiolar/alveolar inflammatory pathology score and lower goblet cell scores (p<0.01); lower eosinophil and neutrophil counts in BALF (p<0.0001); and lower cytokine levels including IL-17A/F, IL-5, IL-13, IL-8 and eotaxin in lung tissue (p <0.001). Serum Der p-specific IgE level was also lower in heparin-treated groups (p<0.004). The two heparin-treated groups also revealed lower value of Penh after Mch stimulation. In conclusion, heparin and lmw heparin decrease serum Der p-specific IgE level and possess anti-inflammatory effects on mite-induced airway allergic inflammation model in BALB/c mice.

HEPARIN PROTECTS BALB/c MICE FROM MITE-INDUCED AIRWAY ALLERGIC INFLAMMATION

L.S. FU1,3,4, J.J. TSAI2, Y.J. CHEN1, H.K. LIN1, M.C. TSAI1 and M.D.T. CHANG5,6

1Pediatric Department, 2Medical Research Department, Taichung Veterans General Hospital, Taichung, Taiwan; 3Department of Pediatrics, National Yang-Ming Medical University,Taipei;

4Institute of Technology, National Chi-Nan University, Nan-To, Taiwan, 5Institute of Molecular and Cellular Biology, and 6Department of Medical Science, National Tsing Hua University, Hsinchu,

Taiwan, Republic of China

Received October 5, 2012 – Accepted March 26, 2013

PROOF






Vol. 26, no. 2, 361-370 (2013)

Matrix metalloproteinase 11 (MMP11 or stromelysin-3) has recently been reported to play a crucial role in the development and progression of multiple malignancies. The aim of this study was to investigate the function of MMP11 expression in human gastric adenocarcinoma (GAC). Using immunohistochemistry assay, we studied the expression level of MMP11 in GAC and adjacent non-cancerous tissues (ANCT). The association between MMP11 expression and tumor size and pathological grade, as well as metastatic potential was analyzed. Through small hairpin RNA (shRNA)-mediated MMP11 knockdown in SGC-7901 GAC cells, we observed the changes of the biological behaviors of GAC cells. Our results indicated that the rate of positive expression of MMP11 was higher in GAC tissues than in ANCT (55.0% vs 30.0%, P=0.025). MMP11 expression had no association with the factors of age or gender of the GAC patients, or the size, pathological staging and lymph node metastases of the tumors (each P>0.05). Furthermore, MMP11 knockdown inhibited the proliferative activities and invasive potential of SGC-7901 GAC cells with decreased expression of IGF-1, PCNA and VEGF. Taken together, our findings demonstrated that MMP11 expression was increased in GAC tissues, but did not correlate with the clinicopathologic features. Knockdown of MMP11 expression could inhibit the proliferation and invasion of GAC cells probably through down-regulation of the IGF-1 signaling pathway, suggesting that MMP11 might be a potential therapeutic target for the treatment of gastric cancer.

KNOCKDOWN OF MMP11 INHIBITS PROLIFERATION AND INVASION OF GASTRIC CANCER CELLS

Y-B. KOU, S-Y. ZHANG, B-L ZHAO, R. DING, H. LIU and S. LI

Department of Gastroenterology, Baoshan Branch Hospital, Shuguang Hospital Affiliated with Shanghai University of Traditional Chinese Medicine, Shanghai, China







Vol. 26, no. 2, 371-381 (2013)

Asthma is an inflammatory disease of the airways, and the current treatment in managing asthma is the control of inflammation. Notch signaling pathway has been linked to T-cell imbalance. The present study aimed to explore the histone modifications of Notch1 promoter in normal and asthmatic lung CD4+ T cells. Chromatin immunoprecipitation analysis showed that the acetylation levels of total H3, H4, site-specific H3K9, H3K14, H3K27, H3K18, H4K16, and the trimethylation levels of H3K4, H3K79 of Notch1 gene promoter were increased significantly in asthmatic lung CD4+ T cells compared to the control group, which correlated with increased P300, PCAF activity and decreased HDAC1, HDAC2 activity. After intervention of garcinol, a potent inhibitor of histone acetyltransferases, in asthmatic lung CD4+ T cells, HAT activity decreased significantly and the increased Notch1 and hes-1 expression was reversed. The total H3ac, H4ac, site-specific H3K9ac, H3K14ac, H3K27ac, H3K18ac, H4K16ac and H3K79me3 levels of Notch1 gene promoter decreased significantly, and the H3K4me3, H3K9me3, H4K20me3 levels had no significant difference. We further investigated the suppressive effects of GAR on asthmatic parameters. Results showed that the levels of IL-4, IL-5 and IL-13 were significantly reduced and a small reverse trend was found in the level of IFN-g after GAR treatment. Furthermore, the expression of NF-κB and AP-1 reduced significantly. These results suggest that asthma is associated with changes in the epigenetic status of Notch1 promoter, including abnormal histone acetylation and methylation, and GAR may have applications in the treatment of asthma.

HISTONE MODIFICATIONS OF NOTCH1 PROMOTER AFFECT LUNG CD4+ T CELL DIFFERENTIATION IN ASTHMATIC RATS

Z-L. CUI, W. GU, T. DING, X-H. PENG, X. CHEN, C-Y. LUAN, R-C. HAN, W-G. XU and X-J. GUO

Department of Respiratory Medicine, XinHua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China

Received March 28, 2013 – Accepted April 22, 2013

PROOF






Vol. 26, no. 2, 383-391 (2013)

S100B, a 21kDa cytosolic calcium-binding protein of the EF-hand type, present in high abundance in the brain, stimulates inflammatory responses in different cellular types inside and outside the central nervous system. Most of extracellular S100B effects are mediated by Receptor for Advanced Glycation End-products (RAGE). RAGE is highly expressed in lung by Alveolar Type-I (AT-I) cells and its activation contributes to ALI/ARDS pathogenesis. In this in-vitro study, we tested the hypothesis that S100B (0.002µg/L, 0.02µg/L, 0.5µg/L, 5µg/L) stimulates an ATI-derived cell line (R3/1) to secrete inflammatory mediators involved in lung inflammation. Our main result is that S100B stimulates R3/1 cells to secrete TNF-alpha and IL-6 (well-known pro-inflammatory cytokines in lung inflammation and neurogenic pulmonary edema), but not sICAM-1, CINC-1 or CINC-3. Soluble RAGE (sRAGE) reduced S100B-dependent secretion of TNF-alpha but did not decrease S100B-dependent secretion of IL-6. Moreover, in absence of S100B, sRAGE enhanced IL-6 release. This study demonstrates that in vitro S100B dose-dependently stimulated R3/1 cells, to enhance the secretion of TNF-alpha and IL-6; S100B pro-inflammatory activity might be mediated at least in part by RAGE. Besides acting as decoy receptor, sRAGE could have pro-inflammatory properties.

S100B INDUCES THE RELEASE OF PRO-INFLAMMATORY CYTOKINES IN ALVEOLAR TYPE I-LIKE CELLS

O. PIAZZA1, E. LEGGIERO2, G. DE BENEDICTIS3, L. PASTORE2,3,F. SALVATORE2, R. TUFANO3 and E. DE ROBERTIS3

1Dipartimento di Medicina, Anestesiologia e Rianimazione, Università degli Studi di Salerno, Salerno, Italy; 2CEINGE, Università degli Studi di Napoli “Federico II”, Naples, Italy;

3Anestesiologia e Rianimazione, Università degli Studi di Napoli “Federico II”, Naples, Italy

Received July 3, 2012 – Accepted February 13, 2013






Vol. 26, no. 2, 393-402 (2013)

In our previous study, a relationship between low expression of D2-like dopamine receptor genes and non-small cell lung cancer (NSCLC) disease was found. In this new research, by using selective agonist of these receptors, Bromocriptine (BR), we attempted to activate D2-like expression and apoptotic induction in a selective cell line of NSCLC. In addition, the relationship of apoptotic response of human lung carcinoma cells to BR and D2- dopamine receptor genes is investigated. Human lung cancer (QU-DB) cells were treated by five doses of BR at 48 h and cell viability was determined by MTT assay. The gene expression pattern of D2-like dopamine receptor Genes was studied by Real Time PCR. Nuclear morphology of cells was monitored by DAPI florescent staining then induction of DNA fragmentation by BR was shown in an agarose gel. Finally, the detection and quantification of apoptosis and its differentiation from necrosis was carried out by using Annecxin-V-Fluos Staining. In this study, it is demonstrated that BR inhibited the proliferation of human lung cancer cells and induced apoptosis in them. In addition, the probable relationship between D2-dopamine receptor genes expression and the development of apoptosis was found. In conclusion, BR is responsible for induction of apoptosis in human lung cancer cells and can be used in treatment of these tumoric cells. In addition, normal expression of D2 dopamine receptors was associated with apoptotic effect of BR on these cells.

A NOVEL REPORT OF APOPTOSIS IN HUMAN LUNG CARCINOMA CELLS USING SELECTIVE AGONIST OF D2-LIKE DOPAMINE RECEPTORS: A NEW APPROACH

FOR THE TREATMENT OF HUMAN NON-SMALL CELL LUNG CANCER

M. SHEIKHPOUR1,2, G. AHANGARI2, M. SADEGHIZADEH1 and A. DEEZAGI3

1Department of Genetic, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran; 2Department of Medical genetic, Division of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran; 3Department of Basic Science, National Institute of

Genetic Engineering and Biotechnology, Tehran, Iran

Received November 17, 2012 – Accepted M arch 18, 2013

PROOF






Vol. 26, no. 2, 403-417 (2013)

Floctafenine, a hydroxyquinoline derivative with analgesic properties, is widely used in Thailand and many other countries. The objectives of this study were to evaluate in Thai healthy volunteers: i) the inhibition of whole blood cyclooxygenase(COX)-2 and COX-1 activity by floctafenine and its metabolite floctafenic acid in vitro and ex vivo after dosing with floctafenine; ii) the possible interference of floctafenine administration with aspirin antiplatelet effects. We performed an open-label, cross-over, 3-period study, on 11 healthy Thai volunteers, who received consecutively floctafenine(200mg/TID), low-dose aspirin(81mg/daily) or their combination for 4 days, separated by washout periods. Floctafenine and floctafenic acid resulted potent inhibitors of COX-1 and COX-2 in vitro (floctafenic acid was more potent than floctafenine) showing a slight preference for COX-1. After dosing with floctafenine alone, whole blood COX-1 and COX-2 activities were inhibited ex vivo in a time-dependent fashion which paralleled floctafenic acid plasma concentrations. Aspirin alone inhibited profoundly and persistently platelet COX-1 activity and AA-induced platelet aggregation throughout 24-h dosing interval which was affected by the co-administration of floctafenine. At 24 h after dosing with aspirin and floctafenine, the inhibition of platelet thromboxane(TX)B2 generation[73±26%(mean±SD)] and aggregation [70(2-92)%, median(range)] were significantly(P<0.05) lower than that caused by aspirin alone [97±1.9% and 87(83-89)%, respectively]. Therapeutic dosing with floctafenine profoundly inhibited prostanoid biosynthesis

CLINICAL PHARMACOLOGY OF CYCLOOXYGENASE INHIBITION AND PHARMACODYNAMIC INTERACTION WITH ASPIRIN BY FLOCTAFENINE IN THAI

HEALTHY SUBJECTS

R. MAENTHAISONG1,2,3,4, S. TACCONELLI1,2, P. SRITARA5, P. DEL BOCCIO2,6, L. DI FRANCESCO1,2, P. SACCHETTA2,6, N. ARCHARARIT7, K. ARYURACHAI7,

P. PATRIGNANI1,2 and C. SUTHISISANG3

1Department of Neuroscience and Imaging and 2Center of Excellence on Aging (CeSI), “G. d’Annunzio” University, Chieti, Italy; 3Department of Pharmacology, Faculty of Pharmacy,

Mahidol University, Bangkok, Thailand; 4Department of Clinical Pharmacy and Research, Faculty of Pharmacy, Mahasarakham University, Mahasarakham, Thailand; 5Division of Cardiology,

Department of Internal Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 6Department of Biomedical Sciences, “G. d’Annunzio” University, Chieti,

Italy; 7Research Center, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand








Vol. 26, no. 2, 419-426 (2013)

The aim of this work is to compare the results of a commercially available liquid chromatography tandem mass spectrometry (LC-MS/MS) method in a clinical pathology laboratory for routine Therapeutic Drug Monitoring (TDM) of cyclosporine (CsA) and tacrolimus (Tacr) in pediatric patients with those obtained with the current antibody-conjugated magnetic immunoassay (ACMIA). Whole blood levels of CsA (n= 135) and Tacr (n=100) were sequentially analyzed by using ACMIA and LC-MS/MS on pediatric transplanted patients. The differences were analyzed by using the Passing Bablok regression analysis and the Bland and Altman test. The LC-MS/MS method showed excellent reproducibility and lower limits of quantification compared to the ACMIA. A linear relationship between ACMIA and LC-MS/MS was obtained for both CsA (r= 0.9449; P<0.0001, 95% CI 0.9234 to 0.9605) and Tacr (r=0.9275; P<0.0001, 95% CI 0.8941 to 0.9506). No significant inter-method biases were observed. The analytical performances of the LC-MS/MS method make it suitable for the accurate measurement of CsA and Tacr in pediatric transplanted patients. However ACMIA results are also accurate and reliable. For this reason the choice of the method to be used in a routine clinical pathology laboratory can be made on the bases of non-analytical considerations such as costs, organization, availability of skilled personnel.

COMPARISON OF ANTIBODY-CONJUGATED MAGNETIC IMMUNOASSAY AND LIQUID CHROMATOGRAPHY-TANDEM MASS SPECTROMETRY FOR THE

MEASUREMENT OF CYCLOSPORINE AND TACROLIMUS IN WHOLE BLOOD

G. CANGEMI, S. BARCO, P. BONIFAZIO, A. MAFFIA, A. AGAZZI and G. MELIOLI

Laboratorio Centrale di Analisi, Istituto Giannina Gaslini, Genoa, Italy

Received December 19, 2012 – Accepted March 26, 2013

PROOF






Vol. 26, no. 2, 427-433 (2013)

Little is known on how elderly patients recover pre-operative haemoglobin, haematocrit and red blood cell levels after total hip and knee arthroplasties. In this study we aimed to evaluate blood loss and recovery blood levels in relation to gender, type of surgery and preoperative haemoglobin values. We conducted a retrospective cohort study on 187 patients over 65 years of age who underwent total knee or total hip arthroplasty between January 2008 and December 2009. Preoperative blood analysis was carried out within 40 days prior to intervention followed by a 15-day postoperative follow-up. Haemoglobin recovery values in anaemic patients versus healthy patients was also estimated. All tested values decreased significantly during the first 3-5 postoperative days. Haemoglobin levels decreased statistically significantly more in males than in females, while no significant differences were observed for haematocrit and erythrocytes. Recovery of haemoglobin values did not differ significantly between healthy patients and patients with preoperative haemoglobin below 120 g/L. Furthermore, our data showed a higher blood loss in total hip arthroplasty, whilst recovery rates showed to be higher after a total knee arthroplasty procedure. In conclusion, the type of intervention and gender played an important role in blood loss and recovery rates in total joint arthroplasty.

BEHAVIOUR OF PERIOPERATIVE VALUES OF HAEMOGLOBIN, HAEMATOCRIT AND RED BLOOD CELLS IN ELDERLY PATIENTS UNDERGOING LOWER LIMB ARTHROPLASTY: A RETROSPECTIVE COHORT STUDY ON NON-TRANSFUSED

PATIENTS

L. DRAGO1,2, E. DE VECCHI1, C.L. ROMANÒ3, C. VASSENA1 and G. BANFI4

1Laboratory of Clinical Chemistry and Microbiology, IRCCS Galeazzi Institute, Milan, Italy; 2Department of Biomedical Sciences for Health, University of Milan, Milan, Italy; 3Center for

Reconstructive Surgery and Bone and Joint Infections, IRCCS Galeazzi Orthopaedic Institute, Milan, Italy; 4Scientific Direction, IRCCS Galeazzi and School of Medicine, University of Milan, Milan, Italy

Received January 27, 2012 – Accepted February 12, 2013






Vol. 26, no. 2, 435-444 (2013)

Due to increased social awareness of allergens and population hyper-sensitization, the reported incidence of allergic reactions to food allergens has increased over the past two decades. Cow’s milk proteins (CMPs) are among the most common food allergens. The aim of this study was to use proteomics techniques to investigate cow’s milk allergens in both full-term human colostrum and in preterm newborns’ mothers – where both groups showed no prior allergen detection -- in order to understand whether cow’s milk allergens could be a cause of sensitization established through lactation. The most relevant finding was the detection of the intact bovine alpha-S1-casein in both term and preterm colostrum. Using techniques detailed in this paper and which allowed for direct protein identification, β-lactoglobulin was not detected in any of the colostrum samples. According to our results, bovine alpha 1 casein is considered a major cow’s milk allergen, is readily secreted in human milk, and so could be considered a possible cause of sensitization in exclusively breastfed infants.

DETECTION OF BOVINE ALPHA-S1-CASEIN IN TERM AND PRETERM HUMAN COLOSTRUM WITH PROTEOMIC TECHNIQUES

S. ORRÙ1, P. DI NICOLA2, F. GIULIANI2, C. FABRIS2, A. CONTI1, A. COSCIA2

and E. BERTINO2

1CNR, Institute of Science of Food Production, Turin, Italy; 2Neonatal Unit, University of Turin, Italy

Received June 5, 2012 – Accepted March 6, 2013

PROOF






Vol. 26, no. 2, 445-451 (2013)

Several studies in recent years have already reported good oncologic results with laser microsurgery in the treatment of early glottic carcinoma. We conducted a longitudinal voice evaluation, in patients with early glottic cancer who underwent transoral laser cordectomy, in order to assess the voice quality outcome and its relationship with objective and subjective (voice handicap index questionnaire and GIRBAS scale) means. Twenty-four previously untreated patients underwent transoral laser cordectomy for early glottic cancer. All patients underwent subjective and objective voice assessment according to the multidimensional voice protocol recommended by the European Laryngological Society including acoustic, perceptual and stroboscopic analysis combined to patient self assessment of voice (voice handicap index-VHI). These evaluations were performed before treatment and 6 months after the treatment. Vocal fold healing was complete in all cases by 6 months following surgery. Main voice parameters (subjective and objective) resulted improved at the 6-month control after surgery. In particular, voice handicap index (VHI) and GIRBAS scale resulted reliable for voice assessment and for the postoperative follow-up. In conclusion, VHI, GIRBAS, multidimensional voice program (MDVP) and spectroacoustic parameters showed a close trend in the present study, and this confirms the validity of the voice analysis performed by each tool.

COMPARISON OF SUBJECTIVE AND OBJECTIVE TOOLS IN TRANSORAL LASER CORDECTOMY FOR EARLY GLOTTIC CANCER: IMPORTANCE OF VOICE

HANDICAP INDEX

F. STOMEO, E. TOSIN, F. MOROLLI, C. BIANCHINI, A. CIORBA, A. PASTORE and S. PELUCCHI

ENT Department, University Hospital of Ferrara, Italy







Vol. 26, no. 2, 453-462 (2013)

Although dental implants have undergone impressive evolution in recent years, periimplantitis still remains a relevant problem and information on the susceptibility of commercial implants to bacterial colonization is insufficient. This work evaluated the susceptibility of different commercial implants to bacterial colonization, to identify key features for good performances. Twenty-four implants, produced with different technologies, were colonized with 9 bacterial strains following pre-conditioning with culture medium, or saliva or serum proteins and adherent bacteria were enumerated by Real Time quantitative PCR. The studied implants differed significantly for susceptibility to bacterial adhesion. Pre-conditioning of surfaces affected adhesion assays in a species specific manner. Although surface topography influenced bacterial adhesiveness, implants produced by different manufacturers with comparable technologies showed great variability of results. These data demonstrate that susceptibility of implants to bacterial colonization is influenced by productive technologies (in a surface topography proportional manner) and by the productive environment. In choosing an implant the clinician should rely upon specific experimental studies, because surface characteristics alone cannot predict susceptibility to colonization by pathogenic bacteria. Tests should include assays performed in the medium of culture and in the presence of serum proteins.

IN VITRO ADHESION OF COMMENSAL AND PATHOGENIC BACTERIA TO COMMERCIAL TITANIUM IMPLANTS WITH DIFFERENT SURFACES

C. PASSARIELLO1, F. PERA2 and P. GIGOLA3

1Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, Rome Italy; 2Department of Implantology and Prosthodontics, University of Turin, Turin, Italy;

3Department of Surgical Specialities, Radiologic and Medico-Forensic Sciences University of Brescia, Brescia Italy

Received July 24, 2012 – Accepted March 8, 2013

PROOF






Vol. 26, no. 2, 463-472 (2013)

We investigated the clonal relatedness of seven multi-drug-resistant (MDR) Klebsiella pneumoniae isolates, as well as three susceptible K. pneumoniae isolates collected during hospital outbreaks and outbreak-related microbiological surveillance, respectively. The relatedness among K. pneumoniae isolates was assessed by pulsed field gel electrophoresis (PFGE) and automated repetitive-sequence-based PCR (rep-PCR) genotyping and the results were compared to a proteomic phenotyping performed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). All typing methods agreed on the generation of three different clusters of K. pneumoniae isogenetic/related MDR strains. After strengthening hospital infection control measures, no other spreading events involving MDR-K. pneumoniae were reported until the end of the observation period. This preliminary investigation suggests that, in a hierarchical approach to bacterial typing, MALDI-TOF MS proteome profiling might offer a fast and valuable preliminary screening tool able to support microbiologists during nosocomial outbreak surveys.

MICROBIAL TRACKING OF MULTIDRUG-RESISTANT KLEBSIELLA PNEUMONIAE ISOLATES IN A PEDIATRIC HOSPITAL SETTING

P. BERNASCHI1, F. DEL CHIERICO2, A. PETRUCCA2,3, A. ARGENTIERI1,M. CIOFI DEGLI ATTI4, G. CILIENTO4, M. CARLETTI1, M. MURACA5,

F. LOCATELLI6,7 and L. PUTIGNANI2

1Unit of Microbiology, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy; 2Unit of Parasitology, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy; 3Department of Diagnostic

Science, Sant’Andrea Hospital, Rome, Italy; 4Medical Direction, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy; 5Laboratory Medicine, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy; 6Department of Pediatric Hematology-Oncology, Bambino Gesù Children’s Hospital,

IRCCS, Rome, Italy; 7University of Pavia, Pavia, Italy

Received January 16, 2013 – Accepted April 3, 2013






Vol. 26, no. 2, 473-478 (2013)

Systemic sclerosis (SSc) is an immune-mediated and complex genetic disease. An association of single-nucleotide polymorphisms (SNPs) in the STAT4 gene with SSc has been reported in European Caucasians, North Americans and Japanese. We undertook the current study to examine whether the STAT4 SNPs are also associated with susceptibility to SSc and SSc subsets in a Han Chinese population. A total of 453 Han Chinese patients with SSc and 534 healthy controls were examined in the study. The SNPs rs7574865, rs10168266 and rs3821236 of the STAT4 gene were examined with SNP TaqMan assays. The T-allele carriers of rs7574865 and rs10168266 were strongly associated with the presence of anti-topoisomerase I (ATA) and pulmonary fibrosis in SSc patients, as well as with diffuse cutaneous SSc (dcSSc). The presence of anti-centromere (ACA) and limited cutaneous SSc (lcSSc) did not show significant association with any of the examined SNPs. The results were consistent with previous reports in other ethnic populations in supporting the notion that polymorphisms of STAT4 may play an important role in susceptibility to SSc. It also revealed different genetic aspects of SSc subsets in a Han Chinese population.

STAT4 IS A GENETIC RISK FACTOR FOR SYSTEMIC SCLEROSIS IN A CHINESE POPULATION

L. YI1,2, J.C. WANG3,4, X.J. GUO1, Y.H. GU5, W.Z. TU6, G. GUO7, L. YANG8, R. XIAO9, L. YU6, M.D. MAYES1, S. ASSASSI1, L. JIN3, H.J. ZOU4,10 and X.D. ZHOU1

1Division of Rheumatology and Clinical Immunogenetics, University of Texas Medical School at Houston, USA; 2Gansu College of Traditional Chinese Medicine, Lanzhou, Gansu, China; 3State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, China; 4Institute of

Rheumatology, Immunology, and Allergy, Fudan University, China; 5Gansu Provincial Hospital, Lanzhou, Gansu, China; 6Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai,

China; 7YilingHospital, Shijiazhuang, Hebei Province, China; 8Teaching Hospital of Chengdu University of TCM, Chengdu, Sichuan Province, China; 9Second Xiangya Hospital, Central South

University, Changsha, Hunan Province; 10Huashan Hospital, Fudan University, China

Received April 3, 2013 – Accepted April 22, 2013

The first two authors contributed equally to the study

LETTER TO THE EDITOR

PROOF






Vol. 26, no. 2, 479-483 (2013)

Criteria from the World Health Organization (WHO) are commonly used to diagnose plasma cell myeloma (PCM), but they are complex and require several laboratory parameters. To differentiate reactive plasmacytosis from clonal plasma cell neoplasms, such as PCM, it is important to accurately determine the expression of the cytoplasmic immunoglobulin (cIg) light chain (LC). Through retrospective analyses, we selected the patients with PCM, and analyzed records of 52 PCM patients, who underwent bone biopsies, and final diagnosis of PCM was established according to WHO criteria, and 22 controls. In the present study, all samples were analyzed by flow cytometry (FC) in the side scatter vs CD38 histogram mode, and the CD38-gated plasma cell population was identified. The positive cell ratios of kappa and lambda to plasma cell populations were analyzed. PCM cells were distinguished from normal plasma cells by a cut-off level between 0.80 and 3.3, a sensitivity of 90.3%, and a specificity of 81.1%. Two-color FC analysis is simple to perform, inexpensive, and clinically relevant data are obtained soon after completion of the FC measurements. It could be one of the helpful tools in the diagnosis of PCM. The correct diagnosis of PCM can be achieved more simply, efficiently, and rapidly by combining this method.

AN APPROACH FOR PLASMA CELL MYELOMA DIAGNOSIS BY TWO-COLOR FLOW CYTOMETRY BASED ON KAPPA/LAMBDA RATIOS OF CD38-GATED

PLASMA CELLS

S. NAKAYAMA1, T. YOKOTE1, Y. HIRATA1, K. IWAKI1, T. AKIOKA1, T. MIYOSHI1, A. TAKAYAMA1, U. NISHIWAKI1, Y. MASUDA1, T. IKEMOTO2, H. TANAKA1,

Y. NISHIMURA3, M. TSUJI4 and T. HANAFUSA1

1Department of Internal Medicine (I), Osaka Medical College, Osaka, Japan; 2Central Clinical Laboratory, Osaka Medical College, Osaka, Japan; 3Division of Mathematics, Osaka Medical

College, Osaka, Japan; 4Division of Surgical Pathology, Osaka Medical College, Osaka, Japan

Received August 13, 2012 – Accepted April 23, 2013







Vol. 26, no. 2, 485-493 (2013)

The receptor for advanced glycation end products (RAGE), a pattern recognition receptor that binds multiple ligands derived from a damaged cell environment, contributes to multiple pathologies including cancer. Early growth response 1 (EGR1) is a tumor suppressor gene or a tumor promoter involved in tumorigenesis and progression of some cancers. However, there is some lack of knowledge about the expression and clinical significance of RAGE and EGR1 in human primary gastric adenocarcinoma (GAC). The present study was aimed to investigate the expression and clinical significance of RAGE and EGR1 in human GAC. One hundred and twenty cases of GAC tissues, adjacent non-cancer tissues (ANCT) and metastatic lymph node (MLN) tissues were collected. The expression of RAGE and EGR1 was assessed using immunohistochemistry (IHC) through tissue microarray procedure. The clinicopathologic characteristics of all patients were analyzed. As a result, the expression of RAGE in GAC and MLN tissues showed the positive staining mainly in the cytoplasm, with lower reactivity rate compared with the ANCT (42.5% vs 82.5%, 65.0% vs 82.5%, P<0.001), while EGR1 expression had no significant difference between GAC, MLN tissues and ANCT (P=0.565). Moreover, the positive expression of RAGE was closely associated with the N stage of GAC patients, but did not correlate with their age, gender, tumor size, tumor sites, T stage, and metastatic lymph node (each P>0.05). In addition, Spearman Rank correlation analysis showed the positive correlation of RAGE expression with EGR1 in GAC tissues (r=0.658). Taken together, the expression of RAGE is decreased in GAC and MLN tissues, and is associated with the N stage of GAC patients, suggesting that RAGE may represent a potential therapeutic target for the treatment of GAC.

CLINICAL SIGNIFICANCE OF IMMUNOGENIC CELL DEATH BIOMARKER RAGE AND EARLY GROWTH RESPONSE 1 IN HUMAN PRIMARY GASTRIC

ADENOCARCINOMA

X-C. XU, H. GAO, W-B. ZHANG, X. ABUDUHADEER and Y-H. WANG

Department of Gastrointestinal Surgery, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China


The first two authors contributed equally to this article


PROOF






Vol. 26, no. 2, 495-501 (2013)

Thermalism and spa treatments are traditionally considered effective in a number of dermatologic inflammatory conditions, yet there is scarce evidence about spring water effectiveness on psoriasis in a daily setting. We enrolled 34 patients with mild-to-moderate psoriasis in a double-blind, randomized, placebo-contralaterally-controlled trial, to evaluate Levico and Vetriolo arsenical-ferruginous water effectiveness on psoriatic lesions by daily 20-minute wet packing for 12 consecutive days. Clinical, histopathologic and immunohistochemical parameters were considered. A statistically significant difference between spa water-treated lesions and placebo-treated lesions in the same patients was demonstrated for histopathologic and immunohistochemical parameters. Since iron ions have an antiproliferative effect on epithelia, and magnesium ions have an anti-inflammatory effect, Levico and Vetriolo water effectiveness on psoriasis could be addressed to their content of these ions.

CLINICAL, PATHOLOGICAL AND IMMUNOHISTOCHEMICAL EFFECTS OF ARSENICAL-FERRUGINOUS SPA WATERS ON MILD-TO-MODERATE PSORIATIC

LESIONS: A RANDOMIZED PLACEBO-CONTROLLED STUDY

G. BORRONI1, V. BRAZZELLI1, L. FORNARA1, R. ROSSO2, M. PAULLI2,C. TINELLI3 and O. CIOCCA1

1Dermatology, 2Anatomic Pathology Section, and 3Scientific Direction, Fondazione IRCCS Policlinico San Matteo and University of Pavia, Pavia, Italy








Vol. 26, no. 2, 503-510 (2013)

Palivizumab (Synagis®) is a humanized monoclonal antibody (IgG1K) composed of 95% human and 5% murine sequences. It is directed to an epitope in the A antigenic site of the F protein of respiratory syncytial virus (RSV). Palivizumab is used for prevention of serious lower respiratory tract disease caused by RSV in pediatric patients who are at increased risk of severe disease and is administered intramuscularly (IM) for a total of 5 monthly doses. Herein, we report on the development and validation of a very sensitive enzyme-linked immunosorbent assay (ELISA) to measure serum concentrations of palivizumab by a rabbit polyclonal antibody specifically produced against the murine sequence. The method was developed and validated according to the guidelines “Guidance for Industry” (1998) and has proved suitable for the determination of palivizumab serum levels in the target infant population. The ELISA assay was successfully applied to test the serum samples in an infant population who received palivizumab intramuscularly; thus, the assay could be used to determine serum levels in palivizumab-treated infants to optimize dosing and scheduling and to study the relationship between dose and clinical response.

DEVELOPMENT AND VALIDATION OF AN ENZYME LINKED IMMUNOSORBENT ASSAY FOR PALIVIZUMAB SERUM DETERMINATION

M. MONTAGNA1, L. VISAI2,3, A. DI COMITE4, V. IOMMIELLO1, M.A. AVANZINI5, N. BLOISE3, M. STRONATI4 and M. REGAZZI1

1Clinical Pharmacokinetics and Experimental Unit, Foundation IRCCS Policlinico San Matteo, Pavia, Italy; 2Salvatore Maugeri Foundation IRCCS, Pavia, Italy; 3Department of Molecular Medicine, and UdR INSTM, and Center for Tissue Engineering (CIT), University of Pavia,

Pavia, Italy; 4Neonatal Unit and Neonatal Intensive Care Unit, Maternal, Infant Department, Foundation IRCCS Policlinico San Matteo, Pavia, Italy; 5Research Laboratory of Immunology

and Transplantation, Pediatric Onco-hematology Unit, Foundation IRCCS Policlinico San Matteo, Pavia, Italy

Received April 16, 2012 – Accepted February 27, 2013


PROOF






Vol. 26, no. 2, 511-515 (2013)

A girl who developed severe BCGitis and vaccine-derived poliovirus infection was discovered to have a novel deletion of RAG1. A neonatal screening program for SCID would identify affected infants at birth, before live vaccines are administered.

BCGITIS AND VACCINE-DERIVED POLIOVIRUS INFECTION IN A PATIENT WITH A NOVEL DELETION IN RAG1 BINDING SITE

C. CANESSA1, F. ROMANO1, F. LIPPI1, L. BIANCHI1, S. KASHEF2, N. REZAEI3,M. MORIONDO1, F. NIEDDU1, M. MARTINI4 and C. AZZARI1

1Immunology Department, Anna Meyer Children’s Hospital, Florence, Italy; 2Allergy Research Center, Division of Immunology and Allergy, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran; 3Research Center for Immunodeficiencies, Children’s Medical Center,

Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; 4Neonatal Care Unit, S.Donato Hospital, Arezzo, Italy

Received October 9, 2012 – Accepted February 18, 2013







Vol. 26, no. 2, 517-523 (2013)

Tomato cultivation farms of Southern Italy were investigated in order to evaluate the general working conditions and the levels of exposure of farm workers to pesticides, during the mixing/loading and the application of pesticides on fields. Information on working modalities, personal protective equipment, etc. was collected using a questionnaire. Inhaling and cutaneous exposure levels were measured, and the estimated pesticide total absorbed dose was compared with Admissible Daily Intakes (ADIs). Field treatments were mainly carried out by using sprayers with open cab tractors, and, in 57.9% of cases, the pesticide mixture was manually prepared by mixing pesticides in a pail, often without using gloves (59.5%). The estimated pesticides absorbed doses varied in the range 0.56-2630.31 mg (mean value, 46.9 mg), and 20% of the measured absorbed doses exceeded ADIs. The findings obtained in the 18 examined farms show a worrying situation, suggesting the investigation of many more farms, so that a statistically significant picture of tomato cultivations in Southern Italy could be formed. Besides, the planning of training courses aimed to increase workers consciousness about health risks and how they can be prevented is advisable.

EVALUATION BY ENVIRONMENTAL MONITORING OF PESTICIDE ABSORPTION IN FARM WORKERS OF 18 ITALIAN TOMATO CULTIVATIONS

P. BASILICATA1,2, A. SIMONELLI1, A. SILVESTRE1,2, M. LAMBERTI1, P. PEDATA1, D. FEOLA1, A. ACAMPORA2, M. PIERI1,2, N. SANNOLO1

and N. MIRAGLIA1

1Department of Experimental Medicine-Section of Hygiene, Occupational Medicine and Forensic Medicine, Second University of Naples, Naples, Italy; 2Department of Public Medicine and Social

Safety, University of Naples “Federico II”, Naples, Italy




PROOF






Vol. 26, no. 2, 525-528 (2013)

Chlamydiaceae is a family of obligate intracellular bacteria generally considered energy parasites. Several studies have suggested that Chlamydiae are capable of independently producing energy and, more importantly, several genes involved in the energy metabolism are up-regulated during the persistent state. Thus, it has been suggested that chlamydial persistence could be a complex and flexible metabolic strategy designed to favor a lengthy survival in the host cell by evading the immune response. In conclusion, more detailed studies on the shift in the chlamydial energy metabolism, from the active to the persistent form, may be helpful in future to determine whether chlamydial persistence observed in vitro does occur in vivo and whether chronic sequelae of chlamydial diseases may be related to the persistence.

NEW INSIGHTS INTO CHLAMYDIAE PERSISTENCE: AN ENERGY METABOLISM STRATEGY?

M. DI PIETRO, S. FILARDO, F. DE SANTIS and R. SESSA

Department of Public Health and Infectious Diseases, “Sapienza” University, Rome, Italy

Received February 6, 2013 – Accepted March 25, 2013







Vol. 26, no. 2, 529-534 (2013)

Non-cystic fibrosis bronchiectasis (nCFb) is an acquired condition of variable etiology. Medical treatment basically involves antibiotics and chest physiotherapy. An impaired mucociliary clearance seems to be one of the mechanisms behind nCFb, and inhaled therapy with mucoactive agents has frequently been used to try to correct it. The most often used mucoactive agents in this setting are N-acetylcysteine, hypertonic saline solution (HS), mannitol powder and recombinant human DNase (rhDNase). Reviewing the international medical literature on the use of these drugs for patients with nCFb from 1992 to the present day, we retrieved 88 articles, only 12 of which met our selection criteria for this analysis. We found only 2 papers and 2 reviews on the use of rhDNase in children, and in adults 3 trials on HS, 5 on mannitol powder and 2 on rhDNase. In conclusion, no observational or randomized controlled trials (RCT) have been published on the use of these drugs in children with nCFb, while the few conducted on adult patients report some evidence of their effects. Further studies are needed on inhaled mucoactive drugs for the treatment of children with nCFb.

INHALED MUCOACTIVE DRUGS FOR TREATING NON-CYSTIC FIBROSIS BRONCHIECTASIS IN CHILDREN

D. SNIJDERS, S. CALGARO, I. BERTOZZI, S. QUARTESAN, I. KOZUH, F. LUNARDI and A. BARBATO

Pediatrics Department, University of Padua, Italy



PROOF






Vol. 26, no. 2, 535-539 (2013)

Macrophage activation syndrome is a potentially fatal clinical syndrome caused by an excessive activation and proliferation of macrophages and T cells, leading to an exaggerated inflammatory reaction. It is well known that it can complicate the course of different conditions, especially autoimmune, lympho-proliferative, infectious diseases and drugs. Many infective pathogens can trigger the syndrome but the association with malaria has rarely been described, especially in children. We report a child with severe malaria complicated by MAS, in whom the clinical appearance of this syndrome could be considered as worsening of malaria itself. Furthermore, the use of steroids as first choice drugs in this complication, but arguable in malaria, has been highlighted. Clinicians should be aware of this syndrome when malaria does not respond to conventional therapy, since early diagnosis and prompt treatment may dramatically reduce the mortality associated with this condition.

MACROPHAGE ACTIVATION SYNDROME IN A CHILD AFFECTED BY MALARIA: THE CHOICE OF STEROID

S. TRAPANI, C. CANESSA, A. FEDI, G. GIUSTI, S. BARNI, C. MONTAGNANI, L. GALLI, M. RESTI and M. DE MARTINO

Department of Health Sciences, University of Florence, Anna Meyer Children’s University Hospital, Florence, Italy








Vol. 26, no. 2, 541-547 (2013)

Low frequency, high energy level ultrasound (US) induces physical effects on tissues called ultrasonic cavitation (UC). Endermic US therapy has recently been proposed as a method to reduce non-invasively the amount of adipose tissue. Very few published studies have dealt with the biological effects of such therapies on human adipose tissue. The aim of this study is to evaluate, through histopathological examination, the effects of various levels of ultrasonic radiation on supravital human adipose tissue. Four ex vivo human tissue samples were treated as follows: sample 1: no US radiation; sample 2: US radiation 2,5 W/cm2 for 15 minutes; sample 3: US radiation 5 W/cm2 for 15 minutes; sample 4: infiltration of 30 ml physiological saline and US radiation, 5 W/cm2 for 15 minutes. For lower levels of ultrasonic energy, interruption of the adipocytic membranes was evident both in the surface and in the deeper cutaneous and subcutaneous layers, with focal dissolution and homogenization of the surface dermal fascia. For higher levels of ultrasonic energy, alterations of the adipocytes and of the collagen fibers were greater, resulting in the dissolution of the cells and of the interlobular fibrous septa. Both effects were amplified by tumescent saline infiltration. The histological lesions demonstrated in adipocytes confirm the theoretical premises of a possible usefulness in the treatment of localized adiposis. The alterations observed in the connective stroma could have positive effects on the structural re–organization and consequently on the in vivo external appearance of the treated areas.

LETTER TO THE EDITORHISTOPATHOLOGICAL FEATURES OF TISSUE ALTERATIONS INDUCED BY LOW

FREQUENCY ULTRASOUND WITH CAVITATIONAL EFFECTS ON HUMAN ADIPOSE TISSUE

D. PUGLIESE1, E. MAIORANO2 and M. PASCONE3

1Internal Medicine Unit, Policlinico Universitario di Bari, Bari, Italy; 2Department of Pathology, University of Bari, Policlinico Universitario di Bari, Bari, Italy; 3Institute of Plastic, Aesthetic and

Reconstructive Surgery, University of Bari, Policlinico Universitario di Bari, Bari, Italy

Received July 7, 2012 - Accepted April 3, 2013

PROOF






Vol. 26, no. 2, 549-556 (2013)

In this article, the authors describe their experience with using cortical deantigenated equine bone sheets in sinus lift grafting procedures performed on 23 patients. The technique employed resembles that described by Tulasne but avoids the need for using harvested calvaria bone and introduces some ad-ditional operating variants. The use of heterologous cortical bone sheets effectively managed even large lacerations of the Schneiderian membrane and allowed for immediate stabilization of the heterologous bone granules. Average histomorphometric values for bone cores collected six months after grafting, at the time of implant placement, were: newly formed bone tissue 43.9±4.2%, residual bone substitute 7.4±1.4%, medullary spaces 48.7±4.0%. At seven year follow-up, clinical and radiographic examination indicated that the use of the bone sheets preserved the regenerated bone volume. In conclusion, the use of heterologous cortical bone sheets in association with granular bone graft material enabled long-term stabilization of the graft material and effective management of intra-surgical complications.

THE USE OF CORTICAL HETEROLOGOUS SHEETS FOR SINUS LIFT BONEGRAFTING: A MODIFICATION OF TULASNE’S TECHNIQUE WITH

7-YEAR FOLLOW-UP

D.A. DI STEFANO1, A. CAZZANIGA2, M. ANDREASI BASSI3,M. LUDOVICHETTI4, G. AMMIRABILE5 and R. CELLETTI6

1Department of Dentistry, Vita Salute University, San Raffaele Hospital, Milan, Italy; 2Private prac-titioner, Sammarate, Varese, Italy; 3Private practitioner, Roma, Italy; 4Private practitioner, Roma, Italy; 5Department of Biomedical Sciences, CNR Institute of Neurosciences University of Padova,

Padova, Italy; 6Dental School, University G. d’Annunzio, Chieti-Pescara, Chieti, Italy

Received June 22, 2012 – Accepted march 26, 2013







Vol. 26, no. 2, 557-563 (2013)

Elimination of microbial contamination from the root canal system is a precondition for successful root canal treatment. Teeth with immature root development, necrotic pulps and apical periodontitis present multiple challenges for successful treatment. Disinfection is achieved by irrigation followed by the placement of an intracanal medicament. A mixture of ciprofloxacin, metronidazole and minocycline (3-MIX S) has been shown to be very effective in eliminating endodontic pathogens in vitro and in vivo. Among the components of the mixture, minocycline can induce tooth discolouration after long-term oral use. Therefore, the elimination of minocycline from the above-mentioned combination has been suggested to prevent the occasion of this undesirable effect. The aim of this study was to investigate the potential antimicrobial efficacy of alternative antibiotic combinations [3-MIX C (clarithromycin); 3-MIX F (fosfomycin)] against bacteria from infected root canals. An additional objective was to evaluate their discolouration potential as possible alternatives to minocycline-based intracanal medicaments. Our in vitro results clearly demonstrated that 3-MIX C and 3-MIX F had a greater antimicrobial activity than 3-MIX S, underlying that clarithromycin still had a higher capacity to kill endodontic pathogens in vitro compared to fosfomycin. Both 3-MIX C and 3-MIX F were able to avoid the permanent staining effect of the crown.

ANTIBACTERIAL EFFICACY AND DRUG-INDUCED TOOTH DISCOLOURATION OF ANTIBIOTIC COMBINATIONS FOR ENDODONTIC REGENERATIVE PROCEDURES

N. MANDRAS1, J. ROANA1, V. ALLIZOND1, D. PASQUALINI2, P. CROSASSO3, M. BURLANDO3, G. BANCHE1, T. DENISOVA2, E. BERUTTI2 and A.M. CUFFINI1

1Department of Public Health Sciences and Paediatrics, University of Turin, Turin, Italy;2Department of Surgical Sciences, Dental School, Endodontics, University of Turin, Turin, Italy;

3Department of Pharmacy, AO Città della Salute e della Scienza of Turin, Turin, Italy

Received January 18, 2013 – Accepted April, 15, 2013


PROOF






Vol. 26, no. 2, 565-570 (2013)

Previous studies have reported a high prevalence of allergy in children with Habitual Snoring (HS), but the relationship between allergy in the early years of life and the subsequent development of this Sleep Disordered Breathing (SDB) is yet to be elucidated. The purpose of the present study was to deter-mine the role of early, under 36 months of age, allergic sensitization to food (with or without sensitization to airborne allergens) in determining the development of HS 8-10 years after. One hundred and forty-eight children (10-14 years, mean age 12 years) with a history of food allergy were selected. Under the age of 36 months, atopic status was assessed by skin prick test for a panel of airborne and food allergens. Questionnaires filled in by parents were used to collect information on children’s snoring and associ-ated symptoms. HS was defined as snoring three or more times per week. At 1-3 years of age 54 (36.5%) children were positive to food allergens alone, and 94 (63.5%) were positive also to airborne allergens. After 8-10 years of life, when patients were aged between 10 and 14 years, habitual snoring was reported in 37 (25%) children. Furthermore, among the 54 children under three years of age sensitized only to food, 8 (14.8%) became HS while of the 94 children sensitized to both food and inhalants allergens 29 (30.9%) developed HS. The difference between those two groups was statistically significant (p=0.04). We reported a significant risk of developing HS in children with early allergic sensitization. Specifically this risk was higher when food allergy was associated with inhalant allergy. The onset of upper airway inflammation due to allergic triggers in subjects under three years of age may be related to the subse-quent development of SDB after 8-10 years.

HABITUAL SNORING IN CHILDREN WITH PREVIOUS ALLERGIC SENSITIZATION

A.M. ZICARI, F. OCCASI, A. CESONI MARCELLI, V. LOLLOBRIGIDA, C. CELANI, L. INDINNIMEO, G. TANCREDI, G. DE CASTRO and M. DUSE

Policlinico Umberto I Hospital, “Sapienza” University of Rome, Rome, Italy








Vol. 26, no. 2, 571-574 (2013)

We describe herein a case of IgG4-related disease with the isolated clinical presentation of malabsorption due to pancreatic failure. Histology of an abdominal lymph node was critical for diagnosis. IgG4-related disease is increasingly recognized as an immunological disorder that can mimic various clinical entities.

IGG4: NOT ONLY FOR ALLERGISTS

C. LOMBARDI1, D. BELLI1, F. FACCHETTI2 and G. PASSALACQUA3

1Allergy and Immunology Unit, Department of Internal Medicine, Sant’Orsola-Poliambulanza Hospital, Brescia, Italy; 2Department of Pathology I; Spedali Civili-University of Brescia, Italy;

3Allergy and Respiratory Diseases, DIMI, University of Genoa, Genoa (Italy)

Received July 12, 2012 – Accepted April 18, 2013


PROOF






Vol. 26, no. 2, 575-578 (2013)

Lichen planus is an uncommon inflammatory mucocutaneous disorder affecting the skin and its appendages, as well as oral and genital mucosa. Involvement of the esophageal mucosa is rare and causes significant morbidity, with dysphagia and risk of long-term complications, such as esophageal strictures and stenosis. Esophageal lichen planus is an underreported condition in the spectrum of lichenoid tissue reactions, presenting the risk of systemic manifestations. We describe a patient with severe, long-standing esophageal lichen planus, which had led to marked weight-loss, malnutrition syndrome and chronic respiratory distress due to recurrent aspiration pneumonia. Diagnosis was confirmed by the presence of concomitant muco-cutaneous lesions and characteristic endoscopic and histological findings. Systemic therapy with cyclosporine A and micronutrient supplementation led to rapid clinical improvement. Early diagnosis of esophageal lichen planus as well as effective systemic immunosuppressive treatment is crucial in order to prevent short- and long-term complications.

SYSTEMIC COMPLICATIONS OF ESOPHAGEAL LICHEN PLANUS

R. MANNA1, S. GARCOVICH2, M. GIOVINALE1, A. MARINARO1, C. MANGANELLI3,A. ZAMPETTI2 and C. FELICIANI2

1Institute of Internal Medicine, 2Institute of Dermatology, 3Institute of Ophtalmology, Policlinico A. Gemelli, Università Cattolica del Sacro Cuore, Rome, Italy

Received January 10, 2013 - Accepted May 8, 2013


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