bluuebunny/crossref_metadata_2025 huggingface dataset:
Anaphylaxis Induced by Intramuscular Betamethasone Disodium Phosphate: Reflections on a Clinical Case
Authors: Ventura M.T. , Sanapo F. , Calogiuri G.F. , Satriano F.
Published: January 2017

Glucocorticoids could be responsible for allergic symptoms correlated to an Ig-E mediated hypersensitivity mechanism. We describe the case of an anaphylactic reaction in a professional nurse, occurring after an intramuscular administration of Betamethasone. After performing skin prick tests, intramuscular tests and patch tests we concluded that the patient had Ig-E mediated sensitization. She was prescribed oral Prednisone and Deflazacort and shows good tolerance of these drugs. This demonstrates that in these patients it is possible to administrate glucocorticoids without the changes in the sites indicated by Wilkinson. Nevertheless, our patient showed a negative allergy test for Dexamethasone disodium phosphate, and in those patients sensitized to fluorinated glucocorticoids, tolerance to other glucocorticoids is not so easily predictable as in patients with hypersensitivity to first generation steroids or in corticosteroid contact dermatitis, according to the four patterns of cross-reactivity proposed by Coopman and Dooms-Goossens.
Diagnostic Value of Three Different Latex Extracts
Authors: Bernardini R. , Mistrello G. , Pucci N. , Roncarolo D. , Lombardi E. , Zanoni D. , Mori F. , De Martino M. , Novembre E. , Massai C. , Azzari C. , Vierucci A.
Published: January 2017

The diagnosis of latex allergy is made on clinical history, but a confirmatory skin prick test (SPT) or a serological assay based on a commercial latex extract is always recommendable. Different raw materials can be used in the preparation of commercial latex extracts. Such extracts can consequently show both different qualitative profiles and a different diagnostic potential. Therefore, the selection of a proper latex extract is essential for in vitro and in vivo diagnosis of latex allergy. In the present study three different latex extracts, prepared from different raw materials (ammoniated -AL-, serum -SL-, or rubber particles -RPE- latex), are compared by in vitro techniques using sera from twenty patients with latex allergy. SDS-PAGE technique was used to compare the antigenic profile of the three latex extracts. Subsequently, their allergenic profiles were evaluated by immunoblotting technique using the individual sera from the twenty latex allergic patients. The diagnostic potential of the three latex extracts was also evaluated using direct Radio-Allergo-Sorbent Test (RAST) as well as skin prick tests (SPTs). In order to establish the more appropriate latex extract in a perspective of in vivo diagnosis of latex sensitization, the same latex extracts were subsequently compared by an in vivo SPT involving ten of the above subjects. The SDS-PAGE profiles of the three latex extracts examined were quite different. SL extract showed numerous bands comprised between 10–100 kDa. RPE extract was characterized by two intense bands at 14 and 20 kDa while AL extract showed the poorer antigenic composition. Analogously, immunoblotting analysis evidenced a different profile in relation to both different patients and extracts. For only two out of the twenty sera, direct RAST results showed a same positive class in relation to the different latex extracts used. SPT with SL extract showed, in respect to the other extracts (AL, RPE), a significantly higher wheal. This study showed that SL extract is able to express the best in vitro and in vivo diagnostic potential. Thus, its use should be preferred for the diagnosis of patients affected by latex allergy.
CD1a and CD1e Allele Frequencies in an Italian Population from the Abruzzo Region
Authors: Aureli A. , Fontecchio G. , Altobelli E. , Azzarone R. , Del Beato T. , Fioroni M.A. , Caporale C.M. , Adorno D. , Papola F.
Published: January 2017

CD1 is a small family comprising 5 MHC-like genes located on chromosome 1 and encoding glycoproteins termed CD1a, CD1b, CD1c, CD1d and CD1e. They are expressed mainly on the surface of dendritic cells, monocytes and some thymocytes and are specialized in presenting lipid antigens to T lymphocytes. The structure is similar to that of MHC class I molecules with 3 globular domains and the β2-microglobulin. It has been shown that all five human CD1 genes exhibit a limited number of polymorphisms in the alpha1 domain whose effects are still unknown. CD1e results to be the most polymorphic isoform with six CD1e alleles (01, 02 in exon 2 and 03, 04, 05, 06 in ex3) described to date. At this moment, few investigations on the allele frequencies of the CD1 genes have been reported and all additional information improves our knowledge on this new class of antigen-presenting molecules. In order to study possible allelic variations of exon 2 of human CD1a and CD1e genes, we analyzed, by a sensitive technique, the sequence-based typing (SBT), 114 DNA samples from unrelated healthy Italian individuals from the Abruzzo region. Our experimental findings indicate that the allele frequency distribution of both CD1a and CD1e genes is in accordance with that observed in other geographic areas and did not identify any new allele, thus confirming a very low polymorphism.
Expression and Phosphorylation of Protein Kinase C Isoforms in Aβ1–42 Activated T Lymphocytes from Alzheimer's Disease
Authors: Ciccocioppo F. , Lanuti P. , Marchisio M. , Gambi F. , Santavenere E. , Pierdomenico L. , Bascelli A. , Velluto L. , Gambi D. , Miscia S.
Published: January 2017

The protein kinase C (PKC) family of enzymes is a regulator of transmembrane signal transduction. There is evidence demonstrating altered activity of some PKC isoforms (PKC-α, PKC-δ and PKC-ζ) in the neurons of brains of Alzheimer's Disease (AD) sufferers, but little is known about their involvement in the intracellular machinery of amyloid β protein-reactive T lymphocytes in AD. By applying a modified “split-well culture system” for Aβ1–42 reactivity, we carried out flow cytometry analysis and biochemical investigations on the possible involvement of PKC-α, PKC-δ and PKC-ζ in the signalling system activated in Aβ-reactive T cells purified from peripheral blood mononucleate cells (PBMC) from healthy subjects and patients with AD. Flow cytometry analysis of Aβ1–42 activated T lymphocytes in the majority of AD patients highlighted a distinct cellular cluster highly expressing phospho-PKC-δ (P-PKC-δ), while most full-blown AD patients highly expressed two distinct P-PKC-δ and phospho-PKC-ζ (P-PKC-ζ) bright sub-populations. The same investigation performed in freshly purified peripheral T lymphocytes, did not highlight any subpopulation, suggesting that the detection of P-PKC-δ and P-PKC-ζ bright subpopulations is specifically linked to Aβ1–42 activated T lymphocytes. The data presented here, therefore, suggest possible novel hallmarks to discriminate between healthy elderly subjects and beginning or full-blown Alzheimer's Disease patients.
Visiting a Forest, but Not a City, Increases Human Natural Killer Activity and Expression of Anti-Cancer Proteins
Authors: Li Q. , Morimoto K. , Kobayashi M. , Inagaki H. , Katsumata M. , Hirata Y. , Hirata K. , Suzuki H. , Li Y.J. , Wakayama Y. , Kawada T. , Park B.J. , Ohira T. , Matsui N. , Kagawa T. , Miyazaki Y. , Krensky A.M.
Published: January 2017

We previously reported that a forest bathing trip enhanced human NK activity, number of NK cells, and intracellular anti-cancer proteins in lymphocytes. In the present study, we investigated how long the increased NK activity lasts and compared the effect of a forest bathing trip on NK activity with a trip to places in a city without forests. Twelve healthy male subjects, age 35–56 years, were selected with informed consent. The subjects experienced a three-day/two-night trip to forest fields and to a city, in which activity levels during both trips were matched. On day 1, subjects walked for two hours in the afternoon in a forest field; and on day 2, they walked for two hours in the morning and afternoon, respectively, in two different forest fields; and on day 3, the subjects finished the trip and returned to Tokyo after drawing blood samples and completing the questionnaire. Blood and urine were sampled on the second and third days during the trips, and on days 7 and 30 after the trip, and NK activity, numbers of NK and T cells, and granulysin, perforin, and granzymes A/B-expressing lymphocytes in the blood samples, and the concentration of adrenaline in urine were measured. Similar measurements were made before the trips on a normal working day as the control. Phytoncide concentrations in forest and city air were measured. The forest bathing trip significantly increased NK activity and the numbers of NK, perforin, granulysin, and granzyme A/B-expressing cells and significantly decreased the concentration of adrenaline in urine. The increased NK activity lasted for more than 7 days after the trip. In contrast, a city tourist visit did not increase NK activity, numbers of NK cells, nor the expression of selected intracellular anti-cancer proteins, and did not decrease the concentration of adrenaline in urine. Phytoncides, such as alpha-pinene and beta-pinene were detected in forest air, but almost not in city air. These findings indicate that a forest bathing trip increased NK activity, number of NK cells, and levels of intracellular anti-cancer proteins, and that this effect lasted at least 7 days after the trip. Phytoncides released from trees and decreased stress hormone may partially contribute to the increased NK activity.
Parecoxib as an Alternative in COX-2 Hypersensitivity
Authors: Colanardi M.C. , Nettis E. , Traetta P. , Delle Donne P. , Ferrannini A. , Vacca A.
Published: January 2017

The group of non-steroidal anti-inflammatory drugs (NSAIDs) is commonly involved in hypersensitivity reactions. In clinical practice the physician is often faced with the need to choose an alternative anti-inflammatory agent for a patient who has suffered a hypersensitivity reaction to a NSAID. The most common approach to choosing the safest NSAID is to perform a challenge test. Parecoxib is the first injectable COX-2 selective inhibitor indicated for the treatment of acute postoperative pain. The authors report the case of a patient with a history of cutaneous adverse reactions to different classes of NSAIDs, including selective COX-2 inhibitors, who underwent and tolerated challenge with parecoxib.
Sinus Augmentation Procedure of the Jaw Sinus in Patients with Mucocele
Authors: Perfetti G. , Rossi F. , Massei G. , Raffaellp L. , Manicone P.F. , Paolantonio M. , Berardi D. , Neri G.
Published: January 2017

The sinus augmentation procedure of the jaw sinus (SAP) is a surgical technique which permits the prosthetic rehabilitation of the edentulous saddles by the insertion of dental implants where unfavourable conditions exist for their application. Nevertheless, apart from malignant tumors, benign pathologies exist, such as mucocele or radicular cysts, which can complicate the SAP, causing sinusal disturbances. In this study we describe our experience of SAP in patients with mucocele of the jaw sinus, and describe our surgical technique without the preventive emptying of the mucocele. Based on our experience, the SAP operation can be carried out without complications if the distance between the top of the mucocele with SAP and the osteomeatal complex (OMC) is 22 mm, or for mucocele no larger than 18 mm. In fact, these parameters guarantee that, because of the lifting of the sinusal membrane, the antral drainage (AD) duct does not alter or become obstructed.
Autism Spectrum Disorders and Mastocytosis
Authors: Theoharides Theoharis C.
Published: January 2017

Autism Spectrum Disorders (ASD) are diagnosed in early childhood and include Autism, Asperger's disorder and Pervasive neurodevelopmental disorder - not otherwise specified (PDD-NOS, or atypical autism). ASD are associated with varying degrees of dysfunctional communication and social skills, repetitive and stereotypic behaviors, as well as attention and learning disabilities. Most ASD patients also have food intolerance and other allergic symptomatology indicative of mast cell activation. The number of ASD cases have increased over the last decade to 1/100, but there is no definite pathogenesis or curative therapy. We report that the apparent prevalence of ASD in patients with mastocytosis, a rare disease occuring in 1/4,000 children and characterized by an increased number of hypersensitive mast cells in many organs, is about 1/10 or 10 times higher than the general population. A child with skin mastocytosis [urticaria pigmentosa, (UP)] and regressive autism is presented to illustrate the point. Allergic, infectious, neuroimmune and environmental triggers may activate mast cells to release vasoactive, inflammatory and neurotoxic molecules. These could disrupt the gut-blood-brain-barriers (BBB), and/or activate susceptibility genes, thus contributing to brain inflammation and ASD.
GGTI-2133, an Inhibitor of Geranylgeranyltransferase, Inhibits Infiltration of Inflammatory Cells into Airways in Mouse Experimental Asthma
Authors: Chiba Y. , Sato S. , Misawa M.
Published: January 2017

Statins have been proposed as a novel treatment of respiratory diseases including asthma. Although the mechanism of anti-inflammatory effect of statins is still unclear, an inhibition of protein prenylation by depleting the downstream metabolites of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase might be involved. To test the hypothesis, the effects of GGTI-2133, a direct inhibitor of geran ylgeranyltransferase (GGTase), on antigen-induced airway inflammation were investigated in a murine model of allergic bronchial asthma. Mice were sensitized and repeatedly challenged with ovalbumin antigen (OA). Animals were also treated with GGTI-2133 (5 mg/kg/day, i.p.) once a day before and during the antigen inhalation period. Repeated antigen inhalation caused an infiltration of inflammatory cells, especially eosinophils, into airways. Significant increases in interleukin (IL)-4, IL-13, eotaxin, thymus and activation-regulated chemokine (TARC) and leukotriene B4 (LTB4) in bronchoalveolar lavage fluids and total and OA-specific IgE in sera were also found in the antigen-exposed animals. The systemic treatments with GGTI-2133 inhibited the antigen-induced eosinophil infiltration into airways almost completely. However, interestingly, the GGTI-2133 treatment did not affect the levels of these chemotactic factors and IgE. These findings suggest that selective inhibition of GGTase is effective for eosinophilic airway inflammation such as asthma.
TNFα and its Receptors in Psoriatic Skin, before and after Treatment with Etanercept
Authors: Caldarola G. , De Simone C. , Carbone A. , Tulli A. , Amerio P. , Feliciani C.
Published: January 2017

Psoriasis is a chronic inflammatory skin condition characterized by inflammatory dermal infiltrate and hyperproliferative keratinocytes. The pathogenesis of this disease is mediated by a dysregulation of the innate immunity and cytokine production. Tumor Necrosis Factor alpha (TNFα) is considered the most important cytokine involved in the pathological mechanism of psoriasis. Recently, several therapies have been introduced for the treatment of psoriasis that try to block TNF alpha activity. Among these treatments Etanercept is a fusion protein that specifically targets TNF alpha. We performed a study on twelve psoriatic patients aimed at evaluating the effect of Etanercept treatment on the production and expression of TNFα and its receptors, in lesional and uninvolved psoriatic skin. We demonstrated that after three month of Etanercept treatment at 50 mg/wk, TNF, TNF-RI and TNF-RII immunostaining in lesional and non-lesional skin samples of patients was greatly reduced, suggesting that this treatment not only acts on stable lesional plaques, but also at a very early stage of the disease.
Sublingual Immunotherapy Affects Specific Antibody and TGF-β Serum Levels in Patients with Allergic Rhinitis
Authors: Ciprandi G. , De Amici M. , Tosca M.A. , Pistorio A. , Marseglia G.L.
Published: January 2017

Allergic rhinitis (AR) is characterized by Th2 polarized immune response, such as increased IL-4 and reduced IFN-γ production. Sublingual allergen-specific immunotherapy (SLIT) induces several immunological changes, most of which are still little known. The aim of this study is firstly to investigate the changes of allergen-specific IgE, IgG, IgG4, and IgA serum levels after SLIT. Secondly, this study aims at relating immunoglobulin (Ig) values with some Th1-, Th2-, and Treg-dependent cytokines. Twenty-three patients with pollen-induced AR were enrolled, and they assumed two pre-seasonal SLIT courses for 2 years. Serum allergen-specific IgE, IgG, IgG4 and IgA levels were determined by ELISA method at baseline and after each SLIT course. Serum IL-4, IFN-γ, IL-10, and TGF-β levels were also assessed. Allergen-specific IgE, IgG, IgG4, and IgA serum levels significantly increased after SLIT. Serum TGF-β significantly increased after SLIT. There was a significant correlation between IgA and TGF-β, both after the first and the second SLIT course. In conclusion, the present study provides the first evidence that pollen SLIT significantly affects Ig production, mainly concerning IgA; and IgA increase is related with TGF-β production. Moreover, this is the first study that measured Ig classes by using a quantitative method.
Hyperimmunoglobulinaemia in Babinga Pygmies is Present from Infancy
Authors: Meazza C. , Travaglino P. , Pagani S. , Laarej K. , Duse M. , Bozzola M.
Published: January 2017

Pygmies, a population characterized by short stature, have high immunoglobulin (Ig) concentrations. In this study, we evaluated Ig levels in Cameroon's Babinga Pygmies from infancy to adulthood and the effects of a national health program on these Ig levels. We found that IgG and IgM levels were outside the normal range for Italians of the same age and were comparable to those measured in Babinga Pygmies living in the same region by Siccardi in 1975. In conclusion, the hypergammaglobulinaemia of Babinga Pygmies is already present in infants and is not affected by sanitation improvements, suggesting that it could be partly genetically-determined.
The Economic Burden of Biological Therapy in Rheumatoid Arthritis in Clinical Practice: Cost-Effectiveness Analysis of Sub-Cutaneous Anti-TNFα Treatment in Italian Patients
Authors: Benucci M. , Li Gobbi F. , Sabadini L. , Saviola G. , Baiardi P. , Manfredi M.
Published: January 2017

Rheumatoid arthritis (RA), with a prevalence of 0.46%, is found in about 272,004 patients in Italy. The socioeconomic cost of rheumatoid arthritis in Italy in 2002 has been estimated at €1,600 million. Cost-effectiveness evaluations have been based on the concept that, with treatment, patients will not progress to the next level(s) of disease severity or will take a longer time to progress, thus avoiding or delaying the high costs and low utility associated with more severe disease. Many cost-effective studies have been based on the variation of Health Assessment Questionnaire (HAQ) in clinical trials. The objective of this study is to perform a cost-effective analysis of 86 patients with rheumatoid arthritis in therapy with adalimumab 40 mg every other week and etanercept 50 mg/week for two years in a population of patients observed in clinical practice. The group of patients in therapy with adalimumab had also taken methotrexate, mean dose 12.4±2.5 mg/week (22 patients) or leflunomide 20 mg/day (16 patients). The group of patients in therapy with etanercept had also taken methotrexate, mean dose 11.7±2.6 mg/week (24 patients) or leflunomide 20 mg/day (24 patients). Incremental costs and QALYs (quality adjusted life years) gains are calculated compared with baseline, assuming that without biologic treatment patients would remain at the baseline level through the year. Conversion HAQ scores to utility were based on the Bansback algorithm. The results after two years showed: in the group methotrexate+adalimumab the QALY gained was 0.62±0.15 with a treatment cost of €26,517.62 and a QALY/cost of €42,521.13. In the group methotrexate+etanercept the QALY gained was 0.64±0.26 with a treatment cost of €25,020.96 and a QALY/cost of €39,171.76. The result of using etanercept in association with methotrexate is cost-effectiveness with a QALY gained under the acceptable threshold of €50,000. These are important data for discussion from an economic point of view when we choose a biologic therapy for rheumatoid arthritis in clinical practice.
Erythropoiesis Equivalence, Pharmacokinetics and Immune Response following Repeat Hematide™ Administration in Cynomolgus Monkeys
Authors: Woodburn K.W. , Schatz P.J. , Fong K-L. , Beaumier P.
Published: January 2017

Hematide™ is a synthetic PEGylated peptidic erythropoiesis stimulating agent (ESA) that is presently being developed for the correction of anemia in patients with chronic renal failure. Unlike currently marketed ESAs, Hematide does not possess any sequence homology to erythropoietin (EPO) and has not elicited moribund immune responses in animal safety studies thereby allowing the generation of a robust safety package. Animals administered marketed ESAs develop anti-EPO antibodies that null the effect of the administered ESA and neutralize endogenous EPO, resulting in severe anemia that precludes the interpretation of chronic safety studies. The primary objective of this study is to determine whether Hematide-specific antibodies are generated when male monkeys are exposed to high Hematide doses (10 mg/kg, intravenous [IV] and subcutaneous [SC]) administered at frequent dosing intervals (every two weeks) for a total of 9 doses; secondary objectives are to evaluate whether developed antibodies impact pharmacokinetics (PK) and pharmacology. In this study, no Hematide-specific antibodies were detected. Hematide exhibits a prolonged plasma half-life and slow clearance by either IV or SC administration. Hematide induced significant erythropoiesis with reticulocytosis and subsequent increases in red blood cells, hematocrit and hemoglobin (Hgb) levels. No erythropoietic differences were noted between the IV and the SC dosed groups with mean ± SD Hgb levels of 20.9 ± 2.5 and 20.3 ± 2.1 g/dL, respectively, occurring on Day 48, corresponding to Hgb increases of 6.5 and 6.7 g/dL, respectively, over pre-dose levels. In conclusion, Hematide is a potent erythropoiesis stimulating agent that exhibits plasma persistence in monkeys. Similar erythropoietic responses were produced following IV and SC administration. The absence of antibody development suggests that Hematide, at the doses and regimen described, has a low immunogenic potential in cynomolgus monkeys.
Efficacy of a Spray Compound Containing a Pool of Collagen Precursor Synthetic Amino Acids (L-Proline, L-Leucine, L-Lysine and Glycine) Combined with Sodium Hyaluronate to Manage Chemo/Radiotherapy-Induced Oral Mucositis: Preliminary Data of an Open Clinical Trial
Authors: Colella G. , Cannavale R. , Vicidomini A. , Rinaldi G. , Compilato D. , Campisi G.
Published: January 2017

Oral mucositis (OM) is a very frequent and potentially severe complication experienced by patients receiving chemotherapy and/or radiotherapy, which often leads to significant morbidity and mortality, and decreased quality of life, and is very costly. Despite its severity and prevalence, there is no standard recognised management today. The aim of this open clinical trial is to evaluate the efficacy and compliance of a new spray compound containing sodium hyaluronate (SH) and a pool of collagen precursor amino acids (AAs) combined with sodium hyaluronate (SH) to manage radio/chemotherapy-induced OM. Twenty-seven consecutive patients with OM were treated according to the manufacturer's instructions. At time TO (baseline — before intervention), we evaluated the following parameters: (i) pain score (by linear visual analogue scale; 0–100) and (ii) severity of OM scored according to WHO Mucositis scale. The treatment efficacy was evaluated on i) pain score, ii) clinical resolution index (CRI) and iii) patient compliance at times T01 (after 2 hours), T1 (after 24 hours), T2 (after 72 hours), T3 (after 7 days) and T4 (after 14 days). Results showed that painful symptoms were significantly reduced after only 2 hours of spray administration compared with baseline measurements ( p<0.0001; z=−4.541). A progressive reduction of pain through the 2 weeks was also noted ( p<0.0001). Patient lesions treated with SH-AAs-based spray also significantly improved after 72 hours of treatment ( p=0.0051; z=−2.803). During the two-week observation, all patients significantly improved from the baseline ( p<0.0001) and progressively ameliorated their ability to swallow foods and liquids. The compliance of all patients to the product was very good, and at the end of the study there were no adverse effects. The results suggest that the SH-AAs-based spray accelerates lesion healing and above all helps to manage mucositis pain, especially in terms of immediate pain relief (after 2 hours from application). Although further randomized controlled studies are recommended, our findings suggest that frequent applications of this spray may offer rapid and effective pain management, aiding faster mucosal wound healing.
Lipid Metabolism Impairment in Human Gliomas: Expression of Peroxisomal Proteins in Human Gliomas at Different Grades of Malignancy
Authors: Benedetti E. , Galzio R. , Laurenti G. , D'Angelo B. , Melchiorre E. , Cifone M.G. , Fanelli F. , Muzi P. , Coletti G. , Alecci M. , Sotgiu A. , Cerù M.P. , Cimini A.
Published: January 2017

Gliomas are histologically graded by cellularity, cytological atypia, necrosis, mitotic figures, and vascular proliferation, features associated with biologically aggressive behaviour. However, abundant evidence suggests the presence of unrecognized, clinically relevant subclasses of the diffuse gliomas, both in respect to their underlying molecular phenotype and their clinical response to therapy. It is well-known that patient prognosis and therapeutic decisions rely on accurate pathological grading. Recently, it was reported that human gliomas accumulate lipid droplets during progression, suggesting a lipid metabolism impairment. Considering the crucial role of peroxisomes in lipid metabolism, in the present work we studied the expression profiles of proteins either exclusively localized to peroxisomes, such as peroxin14 (PEX14), peroxisomal membrane protein 70Kda (PMP70), acyl-CoA oxidase, thiolase, or partially associated to peroxisomes such as Hydroxymethylglutaryl-CoA reductase (HMGCoA-red) and peroxisomal-related proteins, namely PPARa, in human glioma specimens at different grades of malignancy. Moreover, Nile red staining of lipid droplets, thin layer chromatography (TLC) and proton nuclear magnetic resonance spectroscopy (NMR) were carried out in order to correlate the biochemical results with the lipid content of tumor tissues. The results obtained indicate that correlating the malignancy grade with the expression of peroxisomal genes and proteins, may constitute a sensitive tool to highlight possible subtypes not recognized by the classical histological techniques.
B Lymphocyte Subsets and Their Functional Activity in the Early Months of Life
Authors: Avanzini M.A. , Maccario R. , Belloni C. , Carrera G. , Bertaina A. , Cagliuso M. , La Rocca M. , Valsecchi C. , Mantelli M. , Castellazzi A.M. , Quinti I. , De Silvestri A. , Marconi M.
Published: January 2017

In the present study we evaluated B-cell subsets and their functional development in 74 newborns from birth to 6 months of life. Moreover, we evaluated “natural antibody” production in vitro. The results documented a predominance of naive B-lymphocytes at all time-points evaluated, decreasing from birth to 6 months (p=0.009). The percentages of CD27+IgD+ and CD27+IgDneg memory B-cells were very low at birth and significantly increased only at 6 months (p=0.02 and p<0.001, respectively). We found a significant increase only in in vitro stimulated IgG production at 6 months as compared to birth (p<0.001). Moreover, a lower secretion of anti-Pn IgM antibodies up to 6 months of age, as compared to controls was observed. Our results underline that the susceptibility and severe course of infection in the neonate can be attributed, at least in part, to the lack of pre-existing immunological memory and competent adaptive immunity.
Long-Term Anti-TNF-α Treatments Reverse the Endothelial Dysfunction in Rheumatoid Arthritis: The Biological Coherence between Synovial and Endothelial Inflammation
Authors: Capria A. , De Nardo D. , Baffetti F.R. , Barbini U. , Violo A. , Tondo T. , Fontana L.
Published: January 2017

Rheumatoid arthritis (RA) is associated with an excess cardiovascular morbidity and mortality, related to systemic inflammation with endothelial dysfunction (ED) and impaired flow-mediated vasodilation (FMD). We assessed the FMD response to anti-TNF-α treatments in 28 RA patients, aged 49.8±15.3 years: an unpaired FMD was found in 66.7% of our cases and was restored after 6 weeks of anti-TNF-a treatment (13.5±5.3% vs 4.6±4.1 %, p < 0.05). Twenty-five percent of the infliximab patients demonstrated a long term response, compared with 60% of etanercept and 100% of adalimumab patients, after 2 years (p<0.01). Infections (3 cases), myocardial ischemia (1 case) or loss of response (4 cases) were associated with a worsened FMD, restored by shifting to adalimumab. The present study confirms that ED is an RA systemic disease marker, responsive to anti-TNF-α treatment and sensitive to clinical events or to a loss of response, underlying the biological coherence between synovial and endothelial inflammation.
Evolution of and Risk Factors for Psychological Distress in Patients with Psoriasis: The Psychae Study
Authors: Colombo D. , Caputo A. , Finzi A. , Andreassi L. , Chimenti S. , Vena G.A. , Giannetti A. ,   The Psychae Study Group
Published: January 2017

Psychological distress (PD) is common in patients with psoriasis but little is known about its evolution. The aim of this study is to assess the evolution of PD in psoriasis. For this purpose, 1,505 psoriatic patients, who had been previously enrolled in the PSYCHAE study, an observational multicenter Italian study, were re-evaluated after 6 and 12 months. Minor and major PD were assessed using the General Health Questionnaire (GHQ) and Brief Symptoms Inventory (BSI) questionnaires and coping using Brief COPE questionnaire. Minor PD was present in 46% of patients but halved during the study. Female gender, surface area, topical steroids, methotrexate, self-distraction, venting and behavioral disengagement were risk factors for minor PD; cyclosporine and humor were protective. Major PD was present in 11% of patients and remained stable. Female gender, venting, religion, behavioral disengagement and emotional support were risk factors for major PD; instrumental support was protective. In conclusion, the results obtained suggest that major PD remained stable after 12 months and that coping was a predictor of its evolution.
An Uncommon Case of Systemic Mucormycosis Associated with Spinal Cord Infarction in a Recently Diagnosed Diabetic
Authors: Giuliani A. , Mettimano M. , Viviani D. , Scagliusi A. , Bruno A. , Russo A. , Rotoli M. , Savi L.
Published: January 2017

Mucormycosis is a relatively rare, opportunistic, invasive infection caused by various members of the Phycomycetes class [from Greek φvκ-, phyko- seaweed; having a plant body], an extensive taxonomy introduced in 1956 to enlarge the class of Zygomycetes. These filamentous fungi have a worldwide distribution and are capable of rapid growth and thermotolerance of human body temperature. Infection typically occurs in seriously compromised patients (i.e. diabetic ketoacidosis, hematologic malignancies, immunosuppressive disorders, end-stage renal disease, solid-organ or bone-marrow transplantation) and can be acute or fulminant, as well as indolent and chronic. In this paper we describe a case of cutaneous mucormycosis that occurred in a 54-year-old diabetic woman and evolved into a disseminated form, leading to an uncommon spinal cord infarction and consequent paraparesis. Our case suggests the importance of suspecting a mucormycosis infection in patients with decompensated diabetes mellitus, even without ketoacidosis.
Clinical, Serologic and Instrumental Data of Ten Patients Affected by Sclerodermatous Chronic Graft versus Host Disease: Similarities and Differences in Respect to Systemic Sclerosis
Authors: Barausse G. , Caramaschi P. , Scambi C. , Benedetti F. , Sorio M. , Tinelli M. , Tinazzi I. , Benini L. , Bambara L.M. , Biasi D.
Published: January 2017

Chronic graft versus host disease (cGVHD), the most common late complication of allogeneic haematopoietic stem cell transplantation (HSCT), may present with sclerodermatous lesions resembling in some cases the cutaneous involvement of systemic sclerosis (SSc). Certain pathogenetic findings connect the two diseases. In this report we describe ten subjects affected by cGVHD who underwent the examinations routinely carried out to stage SSc patients. Demographic, clinical, serologic and instrumental data were recorded. These patients showed differences in appearance, extent and progression of the sclerodermatous lesions with greater involvement of the trunk and proximal part of the limbs than the extremities. In seven subjects ANA test was positive; scleroderma-associated autoantibodies were not detected in any of the cases. Moreover, typical organ involvement of SSc was not found. Only one patient developed Raynaud's phenomenon after HSCT and only one patient demonstrated a nailfold videocapillaroscopic scleroderma pattern. Except for cutaneous involvement of cGVHD, that may resemble SSc, the clinical features of the two diseases are quite different, suggesting that the fibrotic process characterizing cGVHD and SSc has different etiologies and different initial pathobiologic events.
Evaluation of Allergenicity of Constituents of Myoga Using the Murine Local Lymph Node Assay
Authors: Wei Q.J. , Wei C.N. , Harada K. , Minamoto K. , Okamoto Y. , Otsuka M. , Ueda A.
Published: January 2017

Myoga ( Zingiber Myoga Roscoe) is a perennial plant with a pungent smell from its flower buds. It is native to East Asia and has been reported to cause allergic contact dermatitis. The purpose of this study is to assess the allergenicity of myoga related to its major chemical components, α-pinene, β-pinene, limonene, limonene oxide and β-phellandrene, which are supposed to be the causative agents of contact dermatitis among myoga cultivators. We performed a toxicity study of the volatile constituents of myoga using the local lymph node assay (LLNA), in which limonene, limonene oxide and β-phellandrene had positive responses and the EC3 was 35.8%, 8.22%, and 0.54%, respectively. EC3 for both α-pinene and β-pinene was over 100%. Both chemicals failed to induce positive responses in the LLNA. While the maximization rating of limonene, limonene oxide and phellandrene were evaluated as moderate, extreme, and extreme respectively, α-pinene and β-pinene were evaluated as weak in the previously reported GPMT. The usage of LLNA was also confirmed by comparing with previously reported GPMT results to detect the allergenicity of myoga constituents. The actual risk of humans developing an allergy to myoga constituents depends on many factors. The concentration of the compounds, the frequency and duration of exposure and the condition of the skin are supposed to be important factors.

In conclusion, limonene, limonene oxide and β-phellandrene are constituents of myoga which revealed their allergenicity by the LLNA. The usefulness of the LLNA to detect the allergenicity of myoga constituents was also confirmed when considering the differences between the LLNA in the present study and the previously reported GPMT. The actual risk of humans developing an allergy to myoga constituents depends on many factors. The concentration of the compounds, the frequency and duration of exposure and condition of the skin are all important factors.
Effects of Budesonide on P38 MAPK Activation, Apoptosis and IL-8 Secretion, Induced by TNF-α and Haemophilus Influenzae in Human Bronchial Epithelial Cells
Authors: Gallelli L. , Pelaia G. , Fratto D. , Muto V. , Falcone D. , Vatrella A. , Curto L.S. , Renda T. , Busceti M.T. , Liberto M.C. , Savino R. , Cazzola M. , Marsico S.A. , Maselli R.
Published: January 2017

Non-typeable Haemophilus influenzae (NTHi) is one of the most frequently involved pathogens in bacterial exacerbations of chronic obstructive pulmonary disease (COPD). In the airways, the main tissue target of NTHi is bronchial epithelium, where this pathogen can further amplify the inflammatory and structural changes induced by proinflammatory cytokines such as tumour necrosis factor-α (TNF-α). Therefore, the aim of this study is to investigate, in primary cultures of human bronchial epithelial cells, the effects of NTHi on signal transduction pathways, apoptotic events and chemokine production activated by TNF-α. Moreover, we also evaluated the effects exerted on such cellular and molecular phenomena by a corticosteroid drug. p38 mitogen-activated protein kinase (MAPK) phosphorylation was analyzed by Western blotting, using an anti-phospho-p38 MAPK monoclonal antibody. Apoptosis was assayed by active caspase-3 expression. Interleukin-8 (IL-8/CXCL8) was detected in cell-free culture supernatants by ELISA. TNF-α induced a significant increase in p38 MAPK phosphorylation. NTHi was able to potentiate the stimulatory actions of TNF-α on caspase-3 expression and, to a lesser extent, on IL-8 secretion. These effects were significantly ( P < 0.01) inhibited by a pharmacological pre-treatment with budesonide. These results suggest that TNF-a is able to stimulate, via activation of p38 MAPK signalling pathway, IL-8 release and airway epithelial cell apoptosis; the latter effect can be markedly potentiated by NTHi. Furthermore, budesonide can be very effective in preventing, through inhibition of p38 MAPK phosphorylation, both structural and proinflammatory changes elicited in bronchial epithelium by TNF-α and NTHi.
Effects of Phosphatidylcholine and Sodium Deoxycholate on Human Primary Adipocytes and Fresh Human Adipose Tissue
Authors: Palumbo P. , Melchiorre E. , La Torre C. , Miconi G. , Cinque B. , Marchesani G. , Zoccali V.G. , Maione M. , Macchiarelli G. , Vitale A.R. , Leocata P. , Cifone M.G. , Giuliani M.
Published: January 2017

Recent studies introduced the novel concept of chemical lipolysis where phosphatidylcholine (PC), an active component of commercial preparations, plays a pivotal role. Other studies suggested that sodium deoxycholate (DOC), an excipient contained in medical preparations, could be the real active component performing an adipocytolytic action. We investigated the effects of PC and DOC on human primary adipocyte cultures and on human fresh adipose tissue. Human adipocytes isolated by Rodbell's method, were cultured onto type I collagen-coated glass coverslips, placed into 24-well tissue culture plates. Cells were incubated with or without DOC (5–7–9%), PC (5%) or DOC/PC mixture and observed under phase contrast microscope. After incubation, cells were stained with Oil Red-O and with acridine orange/ethidium bromide to observe necrotic cells with phase contrast microscope and fluorescent microscope, respectively. Histological specimens from adipose tissue biopsies were observed with phase contrast microscopy and with scanning electron microscopy. To investigate the lipid pattern variability in the different experimental conditions, culture medium obtained from the different treatments was subjected to lipid extraction and subsequently to thin layer chromatography (TLC). Microscopic observation of adipocytes showed that DOC treatment led to a detrimental morphological effect in a dose-dependent manner. PC treatment did not significantly affect adipocyte viability. On the contrary, results from experiments aimed to analyze the effects of PC/DOC combined treatment suggested a PC protective role against the DOC harmful effects on adipocytes. Results indicated that clinical effects, observed in local treatment with pharmaceutical preparation, could be due only to DOC, a detergent inducing nonspecific lysis of cell membranes following adipocyte necrosis. On the other hand, PC could likely be incorporated in the lipid bilayer, thus strongly reducing the disruptive DOC effects.
Immunohistochemical Expression and Localization of Somatostatin Receptor Subtypes in Prostate Cancer with Neuroendocrine Differentiation
Authors: Morichetti D. , Mazzucchelli R. , Santinelli A. , Stramazzotti D. , Lopez-Beltran A. , Scarpelli M. , Bono A.V. , Cheng L. , Montironi R.
Published: January 2017

The aim of the study is to examine the tissue expression and localization of the somatostatin receptors (SSTRs) in prostate cancer (PCa) with neuroendocrine (NE) differentiation. The five SSTR subtypes (SSTR1 to 5) were evaluated immunohistochemically in the secretory cells of normal-looking epithelium (Nep), high-grade prostatic intraepithelial neoplasia (HGPIN) and PCa in 20 radical prostatectomies (RPs) with Gleason score 3+3=6 acinar PCa; 20 RPs with GS 4+4=8 and 4+5=9 PCa; and 20 RPs with PCa with NE differentiation. The basal cells were evaluated in Nep and HGPIN. In all groups the stromal smooth muscle and endothelial cells were also analyzed. Concerning the secretory cells, (i) the greatest mean proportions of cells with strong cytoplasmic staining in PCa were seen for SSTR2, mainly in the group of RP with NE differentiation, and for SSTR4 in all three groups; the mean values in HGPIN were intermediate between Nep and PCa; (ii) Membrane staining was seen for SSTR3 and SSTR4; the mean percentages of positive cells, higher in SSTR3 than in SSTR4, decreased from Nep to HGPIN and PCa in all three RP groups; in the latter two, the mean percentages were similar; and (iii) Nuclear staining was seen with SSTR4 and SSTR5; for SSTR4, the mean percentages in the PCa of the three groups were higher than in HGPIN and Nep, the highest proportion being with PCa with NE differentiation. Concerning the basal cells, in Nep the mean proportions of cells with strong staining intensity were greater for SSTR1 and SSTR3 than for the other subtypes, the lowest being with SSTR2; in HGPIN the highest mean propositions of positive cells was with SSTR3, the proportions in the three RP groups being similar. Concerning the stromal smooth muscle and endothelial cells, the highest mean values being in SSTR1 and the lowest in SSTR5; for the former subtype the highest proportion of endothelial cells with strong intensity was seen in the RP NE group. In conclusion, this immunohistochemical study expands our knowledge on the expression and localization of five SSTRs in the various tissue components in the prostate with PCa with NE differentiation, compared with conventional PCa. Typing somatostatin receptor expression in NE tumours could be of relevance to target somatostatin analogue-based diagnostic approach and treatment.
Ibuprofen and Lipoic Acid Diamide as Co-Drug with Neuroprotective Activity: Pharmacological Properties and Effects in β-Amyloid (1–40) Infused Alzheimer's Disease Rat Model
Authors: Di Stefano A. , Sozio P. , Cerasa L.S. , Iannitelli A. , Cataldi A. , Zara S. , Giorgioni G. , Nasuti C.
Published: January 2017

Both oxidative stress and inflammation are elevated in brains of Alzheimer's disease patients, but their pathogenic significance still remains unclear. Current evidence support the hypothesis that non-steroidal anti-inflammatory drugs (NSAIDs) and antioxidant therapy might protect against the development of Alzheimer's disease, and ibuprofen has the strongest epidemiological support. In the present work our attention was focused on (R)-α-lipoic acid considered as a potential neuroprotective agent in Alzheimer's disease therapy. In particular, we investigated a new co-drug (1) obtained by joining (R)-α-lipoic acid and ibuprofen via a diamide bond, for evaluating its potential to antagonize the deleterious structural and cognitive effects of β-amyloid (1–40) in an infused Alzheimer's disease rat model. Our results indicated that infusion of β-amyloid (1–40) impairs memory performance through a progressive cognitive deterioration; however, ibuprofen and co-drug 1 seemed to protect against behavioural detriment induced by simultaneous administration of β-amyloid (1–40) protein. The obtained data were supported by the histochemical findings of the present study: β-amyloid protein was less expressed in 1-treated than in ibuprofen and (R)-α-lipoic acid alone-treated cerebral cortex. Taken together, the present findings suggest that co-drug 1 treatment may protect against the cognitive dysfunction induced by intracerebroventricular infusion of β-amyloid (1–40) in rats. Thus, co-drug 1 could prove useful as a tool for controlling Alzheimer's disease-induced cerebral amyloid deposits and behavioural deterioration.
Inhibitory Activity of Cranberry Extract on the Bacterial Adhesiveness in the Urine of Women: An Ex-vivo Study
Authors: Tempera G. , Corsello S. , Genovese C. , Caruso F.E. , Nicolosi D.
Published: January 2017

Strains of uropathogenic E. coli are responsible for approximately 90% of community-acquired, uncomplicated cystitis, and fimbriae represent the adhesive factors enabling E. coli to be anchored to uroepithelial cells in the first step of the infectious process. Recently, a few studies have shown that a correlation between the consumption of cranberry ( Vaccinium macrocarpon) and prevention of UTI is related to the ability of proanthocyanidins to reduce the bacterial adhesion to uroepithelial cells. In this study we evaluate the inhibitory activity of urine of healthy women treated with tablets containing cranberry extract on the adhesiveness of E. coli to uroepithelial human cells. Two groups of 12 female volunteers each, aged between 18 and 65 years, were enrolled, one group with negative history and one group with positive history of recurrent cystitis. Subjects were treated with the active product or placebo in a random, cross-over, double-blinded sequence for one week in each of the two treatment sequences. Urine samples were collected at the beginning and the end of each study period. Tests of bacterial adhesiveness were performed with two strains of E. coli (ATCC 25922 and ATCC 35218) on HT1376 human bladder carcinoma cells. Significant reductions of bacterial adhesiveness were observed in women who received cranberry extract (−50.9%; p<0.0001), regardless of their medical history and the treatment period in the cross-over sequence. No changes were observed with placebo (−0.29%; n.s.). This ex-vivo study showed that the assumption of cranberry extract in suitable amounts can have an anti-adhesive activity on uropathogenic E. coli.
Psychological Stress and Cancer
Authors: Conti C.M. , Maccauro G. , Fulcheri M.
Published: January 2017

All the concepts reported in this editorial are based on recent literature data obtained through a PubMed search, using both Medline and manual searches, with particular reference to articles, which could be relevant to clinical practice. This paper contributes to the existing literature on depression and stress and provides important information for the development of effective strategies to manage these conditions among patients with cancer.