bluuebunny/crossref_metadata_2025 huggingface dataset:
S100B Induces the Release of Pro-Inflammatory Cytokines in Alveolar Type I-like Cells
Authors: Piazza O. , Leggiero E. , De Benedictis G. , Pastore L. , Salvatore F. , Tufano R. , De Robertis E.
Published: January 2017

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 SlOOB-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.
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
Authors: Sheikhpour M. , Ahangari G. , Sadeghizadeh M. , Deezagi A.
Published: January 2017

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.
Clinical Pharmacology of Cyclooxygenase Inhibition and Pharmacodynamic Interaction with Aspirin by Floctafenine in Thai Healthy Subjects
Authors: Maenthaisong R. , Tacconelli S. , Sritara P. , Del Boccio P. , Di Francesco L. , Sacchetta P. , Archararit N. , Aryurachai K. , Patrignani P. , Suthisisang C.
Published: January 2017

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 through the rapid conversion to floctafenic acid. Floctafenine interfered with the antiplatelet effect of aspirin. Our results suggest that floctafenine should be avoided in patients with cardiovascular disease under treatment with low-dose aspirin.
Comparison of Subjective and Objective Tools in Transoral Laser Cordectomy for Early Glottic Cancer: Importance of Voice Handicap Index
Authors: Stomeo F. , Tosin E. , Morolli F. , Bianchini C. , Ciorba A. , Pastore A. , Pelucchi S.
Published: January 2017

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.
Microbial Tracking of Multidrug-Resistant Klebsiella Pneumoniae Isolates in a Pediatric Hospital Setting
Authors: Bernaschi P. , Del Chierico F. , Petrucca A. , Argentieri A. , Atti M. Ciofi Degli , Ciliento G. , Carletti M. , Muraca M. , Locatelli F. , Putignani L.
Published: January 2017

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.
Clinical, Pathological and Immunohistochemical Effects of Arsenical-Ferruginous SPA Waters on Mild-To-Moderate Psoriatic Lesions: A Randomized Placebo-Controlled Study
Authors: Borroni G. , Brazzelli V. , Fornara L. , Rosso R. , Paulli M. , Tinelli C. , Ciocca O.
Published: January 2017

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.
Development and Validation of an Enzyme Linked Immunosorbent Assay for Palivizumab Serum Determination
Authors: Montagna M. , Visai L. , Di Comite A. , Iommiello V. , Avanzini M.A. , Bloise N. , Stronati M. , Regazzi M.
Published: January 2017

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.
Evaluation by Environmental Monitoring of Pesticide Absorption in Farm Workers of 18 Italian Tomato Cultivations
Authors: Basilicata P. , Simonelli A. , Silvestre A. , Lamberti M. , Pedata P. , Feola D. , Acampora A. , Pieri M. , Sannolo N. , Miraglia N.
Published: January 2017

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.
Inhaled Mucoactive Drugs for Treating Non-Cystic Fibrosis Bronchiectasis in Children
Authors: Snijders D. , Calgaro S. , Bertozzi I. , Quartesan S. , Kozuh I. , Lunardi F. , Barbato A.
Published: January 2017

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.
Systemic Complications of Esophageal Lichen Planus
Authors: Manna R. , Garcovich S. , Giovinale M. , Marinaro A. , Manganelli C. , Zampetti A. , Feliciani C.
Published: January 2017

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.
Ambroxol Inhibits Neutrophil Respiratory Burst Activated by Alpha Chain Integrin Adhesion
Authors: Peroni D.G. , Moser S. , Gallo G. , Pigozzi R. , Tenero L. , Zanoni L. , Boner A.L. , Piacentini G.L.
Published: January 2017

The purpose of the present study was to investigate the possible anti-oxidant effect(s) of Ambroxol on neutrophils activated by ligand-binding of the drug with membrane-associated adhesion integrin CD11a and to estimate dose-response changes in oxygen free radical production. The amount of free radical production by anti-CD11a- and anti-CD4-coated neutrophils stimulated with N-formyl-methionylleucyl-phenylalanine (FMLP) and challenged with increasing concentration of Ambroxol, was evaluated within a time frame of 90 minutes. A significant dose-dependent effect response of Ambroxol on O2− production by cells coated with anti-CD11a antibody was observed. This preliminary study opens a new perspective on the therapeutic role of Ambroxol as an antioxidant drug and for its potential use in controlling oxidative stress, particularly in leukocyte-dependent inflammation.
Cerebrospinal Fluid T-Regulatory Cells Recognize Borrelia Burgdorferi Napa in Chronic Lyme Borreliosis
Authors: Amedei A. , Codolo G. , Ozolins D. , Ballerini C. , Biagioli T. , Jaunalksne I. , Zilevica A. , D'Elios S. , De Bernard M. , D'Elios M.M.
Published: January 2017

The NapA protein of B. burgdorferi is essential for the persistence of spirochetes in ticks. One of the most intriguing aspects of NapA is its potential to interfere with the host immune system. Here, we investigated the role of the acquired immune responses induced by NapA in the cerebrospinal fluids (CSF) of patients with chronic Lyme borreliosis. We evaluated the cytokine profile induced in microglia cells and CSF T cells following NapA stimulation. We report here that NapA induced a regulatory T (Treg) response in the CSF of patients with chronic Lyme borreliosis and it is able to expand this suppressive response by promoting the production of TGF-β and IL-10 by microglia cells. Collectively, these data strongly support a central role of NapA in promoting both Treg response and immune suppression in the CSF of patients with chronic Lyme borreliosis and suggest that NapA and the Treg pathway may represent novel therapeutic targets for the prevention and treatment of the disease.
Periodontal Bacteria in the Genital Tract: Are They Related to Adverse Pregnancy Outcome?
Authors: Cassini M.A. , Pilloni A. , Condò S.G. , Vitali L.A. , Pasquantonio G. , Cerroni L.
Published: January 2017

One of the most important factors implicated in preterm birth (PTB) is acute genitourinary tract infection. The bacteria causing chronic periodontal inflammation include Gram-negative rods and anaerobes similar to those found in women with bacterial vaginosis. The aim of this prospective study is to investigate the relationship between oral and vaginal microflora and preterm low birth weight. Real-time polymerase chain reaction was used to detect both the presence and level of six periodontitis-related species: Aggregatibacter actinomycetemcomitans ( Aa), Porphyromonas gingivalis ( Pg), Tannerella forsythia ( Tf), Treponema denticola ( Td), Fusobacterium nucleatum ssp ( Fn), and Prevotella intermedia ( Pi) for both oral samples of subgingival plaque and cervical samples, obtained from 80 patients, during gynaecological examinations. The more representative oral pathogen (>60%) species in oral samples of preterm and term group were Tf, Td, and Fn. 24.4% of pregnant women presented periodontal pathogens in vaginal swab; the most representative species with a percentage over 0.1% of total bacteria in genital tract of preterm group were Tf, Td, and Pi with a positive correlation (>0.5). The presence of the bacterium T. denticola in the vagina, regardless of the amount, adversely affects preterm delivery.
Anaesthesia Management in Patients with Multiple Chemical Sensitivity Syndrome
Authors: Piroli A. , Ciccozzi A. , Petrucci E. , Paladini A. , Marsili I. , Panella L. , Santucci C. , Coaccioli S. , Marinangeli F.
Published: January 2017

Multiple Chemical Sensitivity (MCS) is characterised by the appearance of numerous and sometimes severe symptoms, when subjects are in contact with various chemicals and medicinal substances. Currently there are no useful guidelines for managing clinical issues and, specifically, anaesthesia for patients with MCS. This case report describes anaesthesia management in a patient affected by clinically documented MCS and a latex allergy, a candidate for a laparoscopic cholecystectomy operation.
Preoperative Assessment of Salivary Gland Neoplasms with Fine Needle Aspiration Cytology and Echography: A Retrospective Analysis of 357 Cases
Authors: Pastore A. , Borin M. , Malagutti N. , Di Laora A. , Beccati D. , Delazer A.L. , Bianchini C. , Stomeo F. , Ciorba A. , Pelucchi S.
Published: January 2017

Fine-needle aspiration cytology (FNAC) is a minimally invasive procedure usually well tolerated, easy to perform, quick, cheap and easy to repeat in case of doubts or non-diagnostic results. Echography is also a fast, cheap and non-invasive tool; however, the role of FNAC and echography in the diagnosis of salivary gland pathology is not universally recognised. Three hundred and fifty-seven patients with a cytological diagnosis at FNAC, and 247 of these who were also studied with echography, were enrolled for this retrospective study. The final histopathological diagnoses, obtained after surgery, were then compared to the preoperative FNAC diagnoses and echographic findings. From the analysis of our data, the overall FNAC specificity resulted 93%, sensitivity 83%, and diagnostic accuracy 92%. Echography sensibility was 57.1% specificity 98.2%, while positive and negative predictive value were respectively 80% and 94.8%. While echography can be useful in order to provide a better characterization of salivary gland lesions, FNAC can then be considered a safe diagnostic tool with reliable sensitivity and specificity for the assessment of salivary gland pathology and thus for selecting patients and indicating the best surgical treatment.
Doppler Ultrasound Study of Penis in Men with Systemic Sclerosis: A Correlation with Doppler Indices of Renal and Digital Arteries
Authors: Rosato E. , Barbano B. , Gigante A. , Cianci R. , Molinaro I. , Quarta S. , Digiulio M.A. , Messineo D. , Pisarri S. , Salsano F.
Published: January 2017

Erectile dysfunction (ED) prevalence in male systemic sclerosis (SSc) is high and its pathogenesis is unclear. The aim of the study is to assess correlation between Doppler ultrasound indices of penis and kidneys or digital arteries in male systemic sclerosis. Fourteen men with systemic sclerosis were enrolled in this study. Erectile function was investigated by the International Index of Erectile Function-5. Peak systolic velocity, end diastolic velocity, resistive index, pulsative index, and systolic/diastolic ratio were measured on the cavernous arteries at the peno-scrotal junction in the flaccid state, on the interlobar artery of both kidneys and all ten proper palmar digital arteries. Ten (71%) patients have an International Index of Erectile Function-5 <21. Reduction of penis peak systolic velocity was observed in all SSc subjects. Doppler indices of cavernous arteries correlate with the International Index of Erectile Function-5. The renal and digital arteries resistive index demonstrated a good correlation (p<0.0001) with International Index of Erectile Function-5. A positive correlation exists between penis and kidney arteries Doppler indices: end diastolic velocity (p<0.05, r=0.54), resistive index (p<0.0001, r=0.90), systolic/diastolic ratio (p<0.01, r=0.69). A positive correlation was observed between penis and digital arteries Doppler indices: peak systolic velocity (p<0.01, r=0.68), end diastolic velocity (p<0.01, r=0.75), resistive index (p<0.001, r=0.79), systolic/diastolic ratio (p<0.05, r=0.59). A correlation exists between arterial impairment of penis and renal or digital arteries.
Intranasal Administration of Hyaluronan as a Further Resource in Olfactory Performance in Multiple Chemical Sensitivity Syndrome
Authors: Alessandrini M. , Micarelli A. , Bruno E. , Ottaviani F. , Conetta M. , Cormano A. , Genovesi G.
Published: January 2017

Multiple chemical sensitivity (MCS) is a relatively common clinical diagnosis in western populations and its symptoms (i.e. dysosmia) are mainly triggered by chemical compounds, such as common odorants. The aim of this study was to test the effect of intranasal administration of hyaluronic acid (HA) on odour threshold and related quality of life in MCS syndrome. Two randomized groups of MCS patients received 30 days' administration of either a nasal spray (Ialumar®) containing HA [HA group (HAG); n=29] or only physiological solution [PS group (PG); n=30]. Both groups were investigated using the “Sniffin' Sticks” test (SST) battery, Questionnaire of Olfactory Disorder (QOD) and Zung Anxiety Scale (SAS) before randomization and after treatment. Paired t-test analysis found a statistically significant reduction in odour threshold (OT) and an improvement in QOD and SAS between pre- and post-treatment results only in the HAG. Furthermore, positive correlations were found between the OT reduction, SAS and QOD improvement. Thus, intranasal administration of HA could be suggested as a further well-tolerated resource in alleviating MCS olfactory discomfort.
Analysis of the Karyotype of Expanded Human Adipose-Derived Stem Cells for Bone Reconstruction of the Maxillo-Facial Region
Authors: Bellotti C. , Stanco D. , Ragazzini S. , Romagnoli L. , Martella E. , Lazzati S. , Marchetti C. , Donati D. , Lucarelli E.
Published: January 2017

Mesenchymal stem cells (MSC) and adipose-derived stem cells (ASC) were recently proposed for bone maxillo-facial reconstruction in association with biomaterials. For this application MSC must be ex-vivo expanded in order to obtain, for a given volume of implanted biomaterial, a relevant number of bone forming cells. Previously conducted pre-clinical studies suggested that a concentration of 6 × 108 ASC associated with 900 mg of anorganic bovine bone (ABB) could be effective for human maxillary sinus floor elevation. A keystone issue to guarantee the quality and safety of Advanced Therapy Medicinal Products containing expanded MSC and ASC is their chromosome stability in culture: this topic has been widely investigated and conflicting results have been published. Abnormal karyotype of human ex-vivo expanded MSC and ASC was found by some authors, while, at the same time, several other studies showed the MSC and ASC karyotype to be normal. It is therefore important that all the results obtained on MSC and ASC karyotype analysis be published. Given this context, the aim of this manuscript, aim of this manuscript is to verify the karyotype stability of ASC in view of their applications in clinical trials. ASC obtained from the adipose tissue of 4 donors were expanded over extended culture time. Based on previous ASC expansions we hypothesized to be able to obtain 6 × 108 cells by passage 7. Karyotype analysis of 30 metaphases was planned to be investigated at passage 2, 7, and 15 in all the cultures. No abnormalities were found in the karyotype of two donors at all the passages tested, while a translocation was found in 2 metaphases of a donor at passage 7, but not at passage 15, and in the fourth donor in 5 metaphases a trisomy was found at passage 15. Chromosomal abnormalities were detected only after extended ASC expansion. Whether these anomalies can be related to risk for the patient's safety will have to be demonstrated by in-vivo studies.
Stemness and Osteogenic and Adipogenic Potential are Differently Impaired in Subcutaneous and Visceral Adipose Derived Stem Cells (ASCs) Isolated from Obese Donors
Authors: De Girolamo L. , Stanco D. , Salvatori L. , Coroniti G. , Arrigoni E. , Silecchia G. , Russo M.A. , Niada S. , Petrangeli E. , Brini A.T.
Published: January 2017

Today adipose tissue is not just considered as the primary energy storage organ, but it is also recognized as an important endocrine tissue and an abundant source of mesenchymal stem cells (adipose-derived stem cells, ASCs). During the last decade, several studies have provided preclinical data on the safety and efficacy of ASCs, supporting their use in cell-based therapy for regenerative medicine purposes. Little is known about the effect of obesity on ASCs properties. Since ASCs differentiation and proliferation are determined by their niche, the differences in body fat distribution and the obesity-related co-morbidities may have several consequences. In this study we compared ASCs of subcutaneous adipose tissue from obese (obS-ASCs) and non-obese (nS-ASCs) donors in order to compare their immunophenotype and osteogenic and adipogenic potential. Moreover, in order to evaluate the possible difference between subcutaneous and visceral fat, obS-ASCs were also compared to ASCs derived from visceral adipose tissue of the same obese donors (obV-ASCs). Our results show that subcutaneous and visceral ASCs derived from obese donors have an impaired cell proliferation, clonogenic ability and immunophenotype. Nevertheless, obS-ASCs are able to differentiate toward osteogenic and adipogenic lineages, although to a small extent with respect to non-obese donors, whereas obV-ASCs lose most of their stem cell characteristics, including multi-differentiation potential. Taken together our findings confirm that not all ASCs present the same behavior, most likely due to their biological microenvironment in vivo. The specific stimuli which can play a key role in ASCs impairment, including the effects of the obesity-related inflammation, should be further investigated to have a complete picture of the phenomenon.
Influence on Chondrogenesis of Human Osteoarthritic Chondrocytes in Co-Culture with Donor-Matched Mesenchymal Stem Cells from Infrapatellar Fat Pad and Subcutaneous Adipose Tissue
Authors: Lopa S. , Colombini A. , Sansone V. , Preis F. W. Baruffaldi , Moretti M.
Published: January 2017

Co-culture of mesenchymal stem cells (MSCs) and articular chondrocytes (ACs) has been proposed for autologous cartilage cell-based therapies, to overcome the issues associated to limited availability of articular chondrocytes (ACs). To evaluate the potentiality of a co-culture approach in aged osteoarthritic patients, MSCs from infrapatellar fat pad (IFP-MSCs) and knee subcutaneous adipose tissue (ASCs) were co-cultured with donor-matched osteoarthritic, expanded and cryopreserved, ACs in a 75%/25% ratio. Co-cultures were prepared also from nasal chondrocytes (NCs) to evaluate their possible use as an alternative to ACs. Pellets were differentiated for 14 days, using mono-cultures of each cell type as reference. Chondrogenic genes SOX9, COL2A1, ACAN were less expressed in co-cultures compared to ACs and NCs. Total GAGs content in co-cultures did not differ significantly from values predicted as the sum of each cell type contribution corrected for the co-culture ratio, as confirmed by histology. No significant differences were observed for GAGs/DNA in mono-cultures, demonstrating a reduced chondrogenic potential of ACs and NCs. In conclusion, a small percentage of expanded and cryopreserved ACs and NCs did not lead to IFP-MSCs and ASCs chondro-induction. Our results suggest that chondrogenic potential and origin of chondrocytes may play a relevant role in the outcome of co-cultures, indicating a need for further investigations to demonstrate their clinical relevance in the treatment of aged osteoarthritic patients.
Two Bone Substitutes Analyzed in Vitro by Porcine and Human Adipose-Derived Stromal Cells
Authors: Arrigoni E. , Niada S. , Ferreira L.M. , De Girolamo L. , Brini A.T.
Published: January 2017

Nowadays, the repair of large bone defects is an important goal in orthopaedic and dental fields. Tissue engineering, applied to increase the bone regeneration process, combines suitable scaffolds with either terminally differentiated cells or Mesenchymal Stromal Cells. In vitro studies with Adipose-derived Stromal Cells (ASCs) may identify new bioactive supports, to be tested in preclinical model. In this study, we evaluated the biocompatibility and the osteoinductive properties of two bone substitutes, RegenOSS™ (RO-1) and a new generation scaffold (RO-2), on both porcine and human ASCs. Porcine ASCs need a prolonged initial phase to adapt to both substitutes; indeed, their growth was initially reduced respect to cells cultured in their absence. In contrast, human ASCs were not negatively affected. However, no toxicity of RO-1 and −2 was observed on both ASC populations which are able to stick to both biomaterials. RO-1 and −2 supported osteogenic differentiation of porcine and human ASCs in a different manner: the presence of RO-1 up-regulated both alkaline phosphatase (ALP) activity and collagen production of human ASCs, whereas in porcine ASCs, RO-2 seemed to up-regulate ALP activity, while the production of collagen is mainly stimulated by the presence of RO-1. We suggest to use not just human ASCs, but also animal ones to select suitable scaffolds to generate bio-constructs in vitro, which then need to be tested in animal model before reaching the market.
Management of Non-Melanoma Skin Cancer in Solid Organ Transplant Recipients
Authors: Specchio F. , Saraceno R. , Chimenti S. , Nisticò S.
Published: January 2017

Non-melanoma skin cancer (NMSC) is the most frequent cancer observed in solid organ transplant recipients (SOTR). Early diagnosis, patient education, and modification of immunosuppression are effective measures for reduction of NMSC incidence. Many risk factors have been identified, including age at transplantation, fair skin, type of immunosuppressive drugs, cumulative sun exposure, viral infections, and various genetic markers. Skin self-examination and photoprotection should be encouraged in all transplanted patients. Long-term skin surveillance, early diagnosis and aggressive treatment of any suspicious lesion, reduction of immunosuppressive therapy, and conversion to mammalian target-of-rapamycin (m-TOR) inhibitors can be also effective measures for reduction of NMSC incidence.
Clinical Efficacy, Safety and Anti-Inflammatory Activity of Two Sevelamer Tablet Forms in Patients on Low-Flux Hemodialysis
Authors: Tzanno-Martins C. , Biavo B.M.M. , Ferreira-Filho O. , Ribeiro-Junior E. , João-Luiz M.V.S. , Degaspari S. , Scavone C. , Kawamoto E.
Published: January 2017

Sevelamer hydrochloride is an ionic exchange resin with high affinity for phosphate. This phosphate-binding agent has few serious adverse reactions with the advantage of reducing total and low density lipoprotein (LDL) cholesterol levels. However, it is controversial as to whether sevelamer hydrochloride can modulate the inflammatory response via endotoxin reduction. Therefore, a single-center, open-label, prospective and randomized study was performed to compare the clinical efficacy, safety and anti-inflammatory activity of two sevelamer hydrochloride tablet forms – a branded tablet form, Renagel® (Genzyme manufacturer) and its generic equivalent (EMS manufacturer). Twenty-eight chronic kidney disease volunteer patients at stage 5 (CDK 5D), on chronic low-flux hemodialysis carried out in 4-hour sessions, three times a week, were studied. The serum phosphorus, ionic calcium, total cholesterol and fractions, bicarbonate, blood pH, interleukin (IL)-6, IL-10, IL-1 beta and tumor necrosis factor-alpha (TNF-α) levels were collected prior to dialysis at mid-week. The incidence of gastrointestinal adverse effects were determined at the end of the phosphate-binder washout period as well as at the end of the fourth and eighth weeks of use of both tablet forms. The same magnitude of reduction in serum phosphorus was observed with both sevelamer tablet forms. Only the Renagel® group showed lower total cholesterol and lower LDL cholesterol levels at the fourth and eighth week versus baseline. No significant differences in serum cytokine levels were identified in either drug group. However, the incidence of intestinal obstipation was higher among patients who used the generic equivalent form. In conclusion, Renagel® and its EMS generic equivalent tablet forms have a similar clinical efficacy in reducing phosphorus in CKD 5D patients on low-flux hemodialysis and a similar safety profile.
Rock Activation in Lung of Idiopathic Pulmonary Fibrosis with Oxidative Stress
Authors: Shimizu Y. , Dobashi K. , Sano T. , Yamada M.
Published: January 2017

The Rho-associated coiled-coil containing protein kinase, (Rho-kinase or ROCK) undergoes activation by oxidative stress. ROCK-II, which is an isoform of ROCK, is activated in a murine model of lung fibrosis. The present study evaluated the level of oxidative stress and activation of ROCK-II in patients with idiopathic pulmonary fibrosis (IPF). The ROCK-II level and the phosphorylation of myosin phosphatase subunit-1 (p-MYPT-1), a hallmark of ROCK activation, were examined by immunohistochemistry of lung tissue sections. The 8-iso prostaglandin-F2α (8-isoPGF2α) level, as a marker of oxidative stress, of exhaled breath condensate was significantly higher in IPF patients than in control patients. In IPF lungs, ROCK-II was predominantly expressed by bronchial epithelial cells, as well as at a lower level by airway smooth muscle cells, vascular smooth muscle cells, and the fibroblasts of fibroblastic foci (FF). In addition, there was moderate p-MYPT-1 expression in these cells of IPF lungs. In control lungs, ROCK-II was expessed by these cells. p-MYPT-1 was weakly expressed by the bronchial epithelial cells. In conclusion, ROCK-II was activated in various lung cells of IPF patients along with oxidative stress detected by 8-isoPGF2α elevation. The ROCK pathway may play a role in the development of IPF via oxidative stress.
The Significance of CA15-3 in Breast Cancer Patients and its Relationship to HER-2 Receptor Status
Authors: Hashim Z.M.
Published: January 2017

Breast cancer is estimated to be the most common malignancy affecting women in Iraq. The cancer antigen CA 15-3 has been used as a possible serum marker of occult and recurrent breast carcinoma, either alone or in combination with other tumor markers such as HER2/neu, that has evolved as a major classifier of invasive breast cancer and target of therapy for the disease. ELISA, used to evaluate serum levels of CA15-3 and immuno-histochemistry staining technique, was used to establish the HER2/neu status. The results of this study indicate an increased level of CA15-3 in breast cancer patients (29.02±1.79 IU/ml) as compared to both women with benign tumor and healthy controls (13.78±1.24 and 8.92±0.48 IU/ml, respectively), and that this increase is associated to advanced stages. Patients with HER2/neu positive malignancies show elevated serum CA15-3 (37.09±2.55 IU/ml), as well as patients who developed recurrence (40.75±2.11 IU/ml). Our data study suggests that higher levels of CA 15-3 would be a reliable prognostic marker as they were directly related to advanced stages and recurrence. In addition persistent elevation of CA 15-3 was associated to HER2/neu positivity in breast cancer patients.
Azithromycin Anaphylaxis in Children
Authors: Mori F. , Pecorari L. , Pantano S. , Rossi M.E. , Pucci N. , De Martino M. , Novembre E.
Published: January 2017

Allergic reactions associated to the use of macrolides are uncommon; in particular only two cases of anaphylaxis with erithromycin and clarithromycin have been reported to date. The aim of this study was to investigate macrolide-induced anaphylaxis. Between December 2007 and December 2011, 136 consecutive children were referred to the Allergy Unit of A. Meyer Children's Hospital because of a past history of reactions to macrolides. Allergy work-ups were carried out according to the European Network for Drug Allergy protocol. Anaphylaxis was diagnosed according to the clinical criteria proposed by Sampson et al. and graded according to Brown SGA et al. Sixty-six out of 136 patients completed the allergologic work-up and among them we investigated three cases of anaphylaxis due to azithromycin which included one child with anaphylaxis to both clarithromycin and azithromycin. In two of the children with anaphylaxis, the diagnosis was only confirmed with the skin prick test, the third was positive to the Intradermal Test. The azithromycin allergy shows a surprisingly high sensitivity to the in-vivo tests. Moreover, this study shows that cross-reactivity may occur between different macrolidic molecules; it has even been suggested that macrolide allergies are unlikely to be class allergies.
Pompholyx of the Hands after Intravenous Immunoglobulin Therapy for Clinically Isolated Syndrome: A Paediatric Case
Authors: Brazzelli V. , Grassi S. , Savasta S. , Ruffinazzi G. , Carugno A. , Barbaccia V. , Marseglia G.L. , Borroni G.
Published: January 2017

Pompholyx is a common eruption of small vesicles on the palms, soles, and/or lateral aspects of the fingers. It has a multifactorial etiology, including genetic determinants, allergy to metals, and id reaction; rarely it is a drug-related side effect. We report a paediatric case of pompholyx of the hands related to the intravenous immunoglobulin (IVIG) therapy for Clinically Isolated Syndrome (CIS). A 10-year-old boy, received an IVIG therapy (Venital®, Kedrion Spa, Italy) at a dose of 400 mg/kg daily for five days. The fifth day of IVIG infusion, a symmetrical vesicular eruption appeared on the palms of the hands and on lateral aspects of the fingers. The lesions improved with application of topical steroids in few days. The mechanism of induction of pompholyx by IVIG therapy is unknown. A review of the Literature suggests the hypothesis that dyshidrotic eczematous reactions may be related not only to the type of IVIG, to the dose and the rates of infusion, but also to an allergic response to excipients and preservatives contained in the drug, probably elicited by an underlying neurological disease in some cases.
A Subgroup of Rheumatoid Arthritis (RA) Associated with Selective Binding of Rheumatoid Factors to Antigen Structures of Cytomegalovirus (CMV)
Authors: Peichl P. , Haberhauer G. , Scriba M. , Bröll H.
Published: January 2017

We compared antibodies (Ab) with both, antiviral and anti IgG properties in patients with rheumatoid arthritis with malignant progress, short remissions and no improvement to therapy. The selective binding of Rheumatoid Factor (RF) to antigen structures of CMV were tested in 180 patients by a newly established ELISA with antiidiotypic goat antibodies of CMV neutralizing human monoclonal Ab and against the virus antigen directly. Displacement reactions on the idiotypic bindingsite as well as comparative ELISA gave proof of the special RF activity. 24,2% of the patients suffering from RA, with IgM RF, showed selective binding to antigen structures of CMV and anti IgG activity.

The evidence of the specific binding capacity of RF to the virus antigen in chronic CMV infection as well as their defined binding capacity to the Fc Fragment of IgG suggest CMV specific RF as the pathogenetic factor of malignant forms of inflammatory rheumatism.
Leukotriene B4 Production by Neutrophils from Patients with Rheumatoid Arthritis
Authors: Tawara Tohru , Shingu Masao , Ezaki Ichiko , Nobunaga Masashi
Published: January 2017

Leukotriene B4 (LTB4) production by unstimululated and stimulated neutrophils from peripheral bloods of normal persons and rheumatoid arthritis patients and from rheumatoid arthritis synovial fluids were examined. Spontaneous production of LTB4 was observed in neutrophils from rheumatoid arthritis synovial fluids but not in peripheral blood neutrophils from rheumatoid arthritis and normal persons. Synovial fluid neutrophils produced significantly higher amounts of LTB4 than peripheral neutrophils of rheumatoid arthritis patients or normal persons, whether neutrophils were stimulated or not. Recombinant human IL-1B did not stimulate LTB4 production by neutrophils. Tiopronin, a SH group-containing compound, inhibited neutrophil LTB4 production.

These results indicate that LTB4 plays an important role in rheumatoid joint inflammation.
Soluble CD4 during Human HIV-1 Infection
Authors: De Paoli P. , Basaglia G. , Gennari D. , Jus A. , Crovatto M. , Santini G.
Published: January 2017

The CD4 antigen has long been used as a surface marker for the indentification of a subset of T cells. CD4 acts also as the receptor for the Human Immunodeficiency Virus 1 HIV-1 and as a signal transducing molecule. Recently CD4 positive cells have been shown to release a soluble form of CD4 (sCD4). This molecule can interact with free gp 120 viral antigen and with serum immunoglobulins.

Because of the importance of CD4 in the natural history of HIV-1 infection, we decided to monitor it's serum levels in HIV-1 seropositive subjects. sCD4 increases, on a per cell basis, in the late stages of infection, when CD4 cell counts dramatically fall and antigenemia is frequently found. Asymptomatic patients had a mean of 6 Units/ml of sCD4 every 100 CD4 T cells, while in AIDS patients we found a mean of 51 Units/ml every 100 CD4 T cells.

These data suggest that sCD4 may be of value in monitoring the involvement of CD4 T cells during a pathological event.
Does the Selenium (SE) Level and Se-Dependent Enzyme Activity in Blood Plasma Correlate with Human Lymphocyte Subpopulations and Function?
Authors: Baj Z. , Zeman K. , Majewska Ewa , Wasowicz W. , Sklodowska Maria , Gromadzinska Jola , Tchórzewski H.
Published: January 2017

Recent literature data on the effects of Se on subpopulations of T lymphocytes, on autologous mixed lymphocyte reaction (AMLR) and on natural killer (NK) cell cytotoxicity are limited or poorly defined. In healthy volunteers we have estimated se levels, glutathione peroxidase (GSH-Px) activity and lipid peroxide levels in human plasma and simultaneously, the subpopulations of T lymphocytes, proliferation in AMLR, and activity of NK cells.

We found a significantly positive correlation between the selenium level and GSH-Px activity. The proliferative response in AMLR significantly correlated with plasma selenium levels but not with GSH-Px activity. NK cytotoxicity, subpopulations of T lymphocytes, and lipid peroxide levels did not correlate with both selenium concentration and GSH-Px activity. We suppose that the effect of Se on the proliferation of suppressor T lymphocytes (Ts) in AMLR is not mediated through GSH-Px activity and fluctuations of Se concentration within a physiological range in healthy persons do not affect NK cytotoxicity.
Immune System and Aging: Neuroimmunological Implications
Authors: Fabris N.
Published: January 2017

Intact neuroendocrine-immune interactions are essential for the development and functional maintenance of both systems. Experimental precocious disruption of such interactions causes premature aging-like phenomena affecting various body functions. Normal physiological aging appears to be, in part, dependent on age-related modifications of neuroendocrine-immune interactions. The thymus plays a major role in this context. Experimental manipulation at the thymic or neuroendocrine level may reciprocally correct the age-associated disfunctions, suggesting the reversible nature of such phenomena. Based on these observations, data are presented suggesting that the neuroendocrine-thymus network may represent a biological clock of aging.