bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Stress on Odor Perception
Authors: Hoenen Matthias , Wolf Oliver T. , Pause Bettina M.
Published: January 2017

The olfactory system and emotional systems are highly intervened and share common neuronal structures. The current study investigates whether emotional (e.g., anger and fear) and physiological (saliva cortisol) stress responses are associated with odor identification ability and hedonic odor judgments (intensity, pleasantness, and unpleasantness). Nineteen men participated in the modified Trier Social Stress Test (TSST) and a control session (cycling on a stationary bike). The physiological arousal was similar in both sessions. In each session, participants’ odor identification score was assessed using the University of Pennsylvania Smell Identification Test, and their transient mood was recorded on the dimensions of valence, arousal, anger, and anxiety. Multivariate regression analyses show that an increase of cortisol in the TSST session (as compared with the control session) is associated with better odor identification performance (β = .491) and higher odor intensity ratings (β = .562). However, increased anger in the TSST session (as compared with the control session) is associated with lower odor identification performance (β = −.482). The study shows divergent effects of the emotional and the physiological stress responses, indicating that an increase of cortisol is associated with better odor identification performance, whereas increased anger is associated with poorer odor identification performance.
Inventing aliens: immigration control, ‘xenophobia’ and racism in Japan
Authors: Park Sara
Published: January 2017

This paper, which examines a growing problem of popular racism in Japan against ethnic minorities, especially Koreans, is critical of the way in which it is often being passed off as xenophobia. The author argues that to confront the current racism means coming to terms with Japan’s colonial past and also the immigration control system which labels all ethnic minorities, including those born in Japan during and following imperial conquest, as ‘foreign’. Since 2009, ultra-right groups, especially the Zaitokukai, have spread popular racism on the internet and attacked people on the streets. In 2013, they began demonstrations in major cities. Activists, politicians and academics, who are worried about the growing racism, have launched counter movements and demanded that new legislation regarding hate speech should be passed. However, because of the way the problem is generally being framed in relation to the rights and status of foreigners in Japan, the authorities underestimate the seriousness of the situation and its historical genesis. Continuing to use the term xenophobia trivialises the issue, suggesting it only relates to minority groups temporarily resident in Japan.
Now We Know
Authors: Corry Steve
Published: January 2017

Genocide in Paraguay ed Richard Arens Temple University Press Philadelphia 1976 171pp $10.95
Alternative Sources of Fibrinolytic, Anticoagulative, Antimicrobial and Anticancer Molecules
Authors: Cooper E. L. , Hrzenjak T. M. , Grdiša M.
Published: January 2017

The medicinal properties of earthworms in various remedies date back to 1340 A.D. and have been extended to other countries and cultures. Assays of tissue homogenates of earthworm (Eisenia foetida) have revealed a glycolipoprotein mixture referred to as G-90 that is composed of macromolecules with medical and pharmaceutical applications. There are several functions attributed to G-90: possession of several growth factors that: stimulate proliferation in cell cultures, contain an insulin like growth factor (IGF like), an immunoglobulin like growth factor (IgFG-like), possess two serine peptidases with a tyrosine code and epidermal growth factor (EGF). In contrast, G-90 exerts strong fibrinolytic and anticoagulative activity capable of lysing fibrin clots. Actions of these two properties are dependent upon concentration. Anticoagulative activity also depends upon the kind of anticoagulants (G-90, PI, PII). G-90 can also act as antioxidant, exert antimicrobial activities in vitro and in vivo. The bacteriostatic effect is significantly greater for non-pathogenic species. Finally G-90 also participates in tissue regeneration and wound healing. Taken together, components of earthworms could be tested in certain clinical trials.
Development of a Clinical Grade Procedure for Generation of mRNA Transfected Dendritic Cells from Purified Frozen CD34+ Blood Progenitor Cells
Authors: Mu L.J. , Lazarova P. , Gaudernack G. , Sæbøe-Larssen S. , Kvalheim G.
Published: January 2017

Enriched CD34+ peripheral blood progenitor cells (PBPC) are frequently used as stem cell support in cancer patients following high dose therapy. Since precursor dendritic cells (DCs) originate from haematopoietic progenitor cells, purified CD34+ cells might also serve as starting cells for ex-vivo production of DC. In the present study we developed a clinical grade procedure for ex-vivo production of DC derived from enriched CD34+ cells. Different concentrations of CD34+ cells were grown in gas-permeable Teflon bags with different serum-free and serum-containing media supplemented with GM-CSF, IL-4, TNF-α, SCF, Flt-3L and INF-α.

Serum-free CellGroSCGM medium for 7 days followed by CellGroDC medium in 7 days gave the same results as serum-containing medium. After incubation the cultured cells containing immature DCs were concentrated and transfected with tumour mRNA from human prostate cancer cell lines employing a highly efficient electroporation procedure. Thawed transfected DCs were able to elicit primary T-cell responses in vitro against antigens encoded by the prostate cancer mRNA as shown by ELISPOT assay using mock-transfected DCs as control. Our results show that frozen enriched CD34+ cells can be an alternative and efficient source for production of DCs for therapeutic purpose.
Cyclooxygenase-2 Expression in Oral Squamous Cell Carcinoma
Authors: Pannone G. , Bufo P. , Caiaffa M. F. , Serpico R. , Lanza A. , Muzio L. Lo , Rubini C. , Staibano S. , Petruzzi M. , De Benedictis M. , Tursi A. , De Rosa G. , Macchia L.
Published: January 2017

Cyclooxygenase (COX), the key enzyme in prostaglandin cascade, is expressed in two isoforms: the constitutive COX-1 and the inducible COX-2. Hyper-expression of COX-2 has been implicated in the pathogenesis of colon-rectal cancer in humans but it appears to play a significant role as a tumour progression factor also in other forms of human cancer, including oral cancer. The aim of this study was to analyze the expression of COX-2, at the protein level, in 45 cases of oral squamous cell carcinoma. Standard immunohistochemical streptavidin-biotin peroxidase analysis was carried out with a highly specific antibody against human COX-2 and cell specific markers, in 45 oral squamous cell carcinomas. Our study revealed a moderate to high COX-2 expression in 35 out of the 45 oral squamous cell carcinoma specimens (77.8%). COX-2 expression appeared particularly abundant in the superficial ulcerated layers of relatively well differentiated carcinomas. However, we were unable to assess any statistically significant association between COX-2 hyper-expression and tumor site, tumor grading, tumor size, presence of lymph node metastases, tumor stage and age at onset, respectively. Interestingly, COX-2 expression was detected not only in areas of epithelial dysplasia adjacent to the primary layers (86% of the cases) but also in normal-appearing epithelium at the boundaries of squamous cell carcinomas (77%), indicating a possible involvement in tumour progression by the apparently normal tissue surrounding the lesion. Moreover, intense COX-2 staining was observed in endothelial cells of intra-tumour vessels and extra-tumour vessels adjacent to the tumour nests, in a high proportion of cases (82%). COX-2 positivity was associated with CD34 and VEGF positivity, indicating that these vessels were probably neo-formed.

From this study, as well as from other works, it appears that COX-2 is over-expressed in this important human malignancy. However, further studies are necessary to understand the exact magnitude of this over-expression and, mostly, the possible role of COX-2 in the pathogenesis and progression of oral cancer.
Comparison between Flurbiprofen and its Nitric Oxide-Releasing Derivatives HCT-1026 and NCX-2216 on Aβ(1-42)-Induced Brain Inflammation and Neuronal Damage in the Rat
Authors: Prosperi C. , Scali C. , Barba M. , Bellucci A. , Giovannini M.G. , Pepeu G. , Casamenti F.
Published: January 2017

Brain inflammation is an underlying factor in the pathogenesis of Alzheimer's disease (AD) and epidemiological studies indicate that a sustained use of non-steroidal anti-inflammatory drugs (NSAIDs) has a protective effect on the disease. We investigated, in vivo, whether differences exist in the antiinflammatory and neuroprotective actions of flurbiprofen and its two nitric oxide-donor derivatives, HCT-1026 and NCX-2216, and the ability of these two derivatives to release nitric oxide in the brain. In adult rats injected into the nucleus basalis with preaggregated Aβ(1-42) we investigated by immunohistochemical methods glia reaction, the induction of inducible nitric oxide synthase (iNOS), the activation of p38 mitogen-activated protein kinase (p38MAPK) pathway and the number of choline acetyltransferase (ChAT)-positive neurons and, in naïve rats we investigated, by microdialysis, cortical extracellular levels of nitrite. Injection of Aβ(1-42) induced iNOS at the injection site, activated p38MAPK 7 days after injection and brought about an intense microglia and astrocyte reaction along with a marked reduction in the number of ChAT-positive neurones, persisting up to at least up to 21 days. Flurbiprofen, HCT-1026 and NCX-2216 (15 mg/kg) significantly attenuated the Aβ(1-42)-induced glia reaction, iNOS induction and p38MAPK activation 7 days after treatment and astrocytes reaction 21 days after treatment. On an equimolar basis, HCT-1026 resulted the most active agent in reducing the Aβ(1-42)-induced microglia reaction. The cholinergic cell loss was also significantly reduced by 21 days of HCT-1026 treatment. No differences in the body weight were found between the animals treated for 21 days with 15 mg/kg of either HCT-1026 or NCX-2216 and the controls. An oral administration of HCT-1026 (15 mg/kg) or NCX-2216 (100 mg/kg) to naiïve rats was followed by significant and long long -lasting increases in cortical nitrite levels. These findings indicate that the addition of a nitric oxide donor potentiates the anti-inflammatory activity of flurbiprofen in a model of brain inflammation.
Dendritic Cells Pulsed with Peptides of GP63 Induce Differential Protection against Experimental Cutaneous Leishmaniasis
Authors: Tsagozis P. , Karagouni E. , Dotsika E.
Published: January 2017

The need for a vaccine against Leishmania spp., a major cause of worldwide morbidity and mortality, is urgent. We tested the efficacy of an experimental vaccination in murine models of cutaneous leishmaniasis, using dendritic cells (DCs) pulsed with synthetic or native parasite antigens. DCs pulsed with peptide 154–169aa of gp63 or soluble promastigote lysate (SPL) triggered antigen-specific immune responses and efficiently reduced lesion formation and parasite load of genetically susceptible BALB/c mice infected with Leishmania major. This effect was accompanied by a modulation of the cellular immune response towards a Th1 profile. Vaccination of genetically resistant CBA mice with DCs pulsed with peptide 154–169aa or SPL did not affect the course of the disease, whereas pulsing with the epitope 467–482aa of gp63 resulted in disease exacerbation, accompanied by a switch to a Th2 profile. In view of our continuously growing knowledge about the immunobiology of DCs, these findings suggest that vaccination with DCs pulsed with defined peptides could be a strategy against infectious diseases. Peptide selection is a prerequisite as they can differentially regulate the type of immune response in susceptible or resistant hosts.
Ultradian Variation of Nerve Growth Factor Plasma Levels in Healthy and Schizophrenic Subjects
Authors: Bersani G. , Iannitelli A. , Massoni E. , Garavini A. , Grilli A. , Di Giannantonio M. , Conti C.M.V. , Pancheri P.
Published: January 2017

Some studies in animal models showed that several neurotrophins may be implicated in the regulation of light-dependent suprachiasmatic pacemaker and in other functions implicated in long-term memory acquisition during sleep. However, no data are known about the role played by NGF in ultradian regulation in humans. The aim of this study was to investigate whether or not there is a natural diurnal fluctuation during daytime in healthy and schizophrenic subjects with a normal light/dark cycle. In a sample of 33 subjects (10 male schizophrenics and 23 healthy subjects) an ELISA assay was used to study the ultradian NGF cycle in blood samples at 9.00, 13.00 and 20.00 hours. The study showed an ultradian rhythm of NGF in healthy subjects with a “V” trend: higher at 9:00 and 20:00 and lower at 13:00. We also show significant differences between male and female controls. No NGF ultradian rhythm among schizophrenic patients compared to healthy subjects was found. The results of this study lead to a rhythmic NGF regulation that appears altered in schizophrenics, where higher levels in the morning and lower levels in the evening were observed, compared to the controls, and support the hypothesis of a role played by NGF in schizophrenia.
Scleroderma Heart Disease
Authors: Marasini B. , Massarotti M. , Cossutta R.
Published: January 2017

Heart disease is a frequent and often severe feature of systemic sclerosis (scleroderma). Cardiomyopathy, with ventricular diastolic dysfunction and arrhythmias, is the most important form, since it is associated with a very poor prognosis. The current challenge is to define its pattern and identify individuals at risk, but evaluation in vivo may be hard to perform. The aim of this review is to provide an update on the clinical aspects of scleroderma heart disease and the early pivotal role that coronary microcirculation dysfunction plays in its development. A discussion of the diagnostic tools now available for this frequently asymptomatic condition will be provided. Treatment options will be reviewed, even though no cure for systemic sclerosis exists, and the current therapy of diastolic dysfunction remains unsatisfactory.
Iron Availability Influences Aggregation, Biofilm, Adhesion and Invasion of Pseudomonas Aeruginosa and Burkholderia Cenocepacia
Authors: Berlutti F. , Morea C. , Battistoni A. , Sarli S. , Cipriani P. , Superti F. , Ammendolia M.G. , Valenti P.
Published: January 2017

Pseudomonas aeruginosa and Burkholderia cenocepacia are predominant opportunistic pathogens in cystic fibrosis (CF) patients. In healthy humans the lower respiratory tract as well as all mucosa, contains a very low free iron concentration (10−18 M), while in CF patients' sputum iron concentration is very high, showing a median value of 63×10−6 M. Accumulation of catalytic reactive iron heavily contributes to subsequent clinical complications in the lung disorders by the production of reactive oxygen species and increases bacterial growth and virulence. The data reported in this study indicate that low iron concentration (Fe3+1 μM) induced free-living forms and motility both in P. aeruginosa and B. cenocepacia, while high iron concentrations (Fe3+ 10 and 100 μM) stimulated aggregation and biofilm formation already in the fluid phases, so demonstrating that aggregation and biofilm formation are positively iron-modulated in these bacteria. Moreover, the different morphological forms (free-living, aggregates and biofilm) showed different capabilities of adhering and invading the bronchial cell line A549. P. aeruginosa PAO1 aggregates, and mostly biofilm, exerted the highest adhesion efficiency, while B. cenocepacia PV1 aggregates or biofilm the lowest. A significant reduction in invasion efficiency by P. aeruginosa biofilm and a significant increase in cell internalization by B. cenocepacia biofilm has been reported. Therefore, the iron availability is an important signal to which P. aeruginosa and B. cenocepacia counteract by leaving the motile free-living forms and entering into a new lifestyle, i.e. biofilm. These data could contribute to explain that the iron-overload of the sputum of CF patients, inducing nonmotile forms, aggregates and biofilm, may facilitate penetration of host epithelial barriers contributing to the establishment of infection, colonization, persistence and systemic spread of these opportunistic pathogens.
Transient Transfection of Porcine Granulosa Cells after 3D Culture in Barium Alginate Capsules
Authors: Benzoni E. , Torre M.L. , Faustini M. , Stacchezzini S. , Cremonesi F. , Conte U. , Villani S. , Russo V. , Ricevuti G. , Vigo D.
Published: January 2017

Three-dimensional culture systems in barium alginate capsules can be employed to maintain primary granulosa cells in an undifferentiated state for almost 6 days. This is due to a self-organization of cells in a pseudofollicular structure. The transfection of primary granulosa cells is a necessary condition when employing these culture systems for several purposes, for example as an in vitro toxicity test or the development of oocytes or zygotes. In this work, the feasibility of two transient transfection techniques (liposome-mediated and electroporation) was assessed in primary porcine granulosa cells after a 6-day culture in an artificial extracellular matrix (barium alginate membrane). Human recombinant green fluorescent protein was chosen as a molecular readout, and protein expression was assessed after 48 hours from transfection. Liposome-mediated transfection gave low transfection levels, with increasing yields from 2 to 12 μgDNA/ml of medium; the maximum percentage (85.7%) was reached at 12 μgDNA/ml of medium. Electroporation-mediated transfection yields were higher: the best results (81.7% of transfected cells) were achieved with two 50V pulses and 12 μg/ml DNA. The application of a single or double pulse (50V) at 4 mgDNA/ml gave negligible results. These results indicate that primary granulosa cell cultured in barium alginate capsules can be transfected by electroporation with high transfection yields.
An Attempt of Specific Desensitising Treatment with Gliadin in Celiac Disease
Authors: Patriarca G. , Pogna N. , Cammarota G. , Schiavino D. , Lombardo C. , Pollastrini E. , De Pasquale T. , Buonomo A. , Nocente F. , Gazza L. , Pietrini D. , Miele L. , Nucera E. , Gasbarrini G.
Published: January 2017

Gluten-free diet is the current treatment of celiac disease. We decided to verify the occurrence of histological and serological modification and/or clinical manifestations during a gradual and progressive introduction of gliadin in the diet and if it may induce a tolerance to food, as it occurs in allergic patients. We studied the case of a celiac woman with complete clinical and histological remittance after 10 years of gluten free diet. She took increasing daily doses of gliadin, reaching the final dose of 9 g of gliadin (15 g of gluten) in 6 months. Then she started a free dietary regimen. During the 15-month follow-up period esophago-gastro-duodenoscopy showed normal Kerckring folds and villi. Anti-gliadin, anti-endomysium and anti-tissue-transglutaminase antibodies, as well as the haematological and biochemical parameters remained normal. Our results represent a new approach in the research concerning celiac disease, and could provide a future line of study for its management.
Interstitial Cystitis and Infectious Agents
Authors: Fioriti D. , Penta M. , Mischitelli M. , Degener A.M. , Pierangeli A. , Gentile V. , Nicosia R. , Gallinelli C. , Chiarini F. , Pietropaolo V.
Published: January 2017

Interstitial cystitis (IC) is a syndrome consisting of severe refractory bladder symptoms of unknown etiology. The disease tends to affect Caucasian women with a mean age of 40 years, with 25% of patients under the age of 30. Few population based epidemiological studies of IC have been performed. We analyzed a case of interstitial cystitis in a 42-year-old non-smoker woman. In two biopsy samples the presence of viral DNA of human polyomavirus BK (BKV), human herpes virus type 1 and type 2 (HHV-1 and HHV-2), adenovirus, human papillomavirus (HPV) and bacterial DNA (Chlamydia trachomatis and Mycoplasma genitalium) were evaluated by means of polymerase chain reaction (PCR). Both samples resulted positive only for BKV and HPV DNA. HPV genotyping revealed the presence of HPV-66 that is associated with a high risk of cancer development. Thus the finding of a viral co-infection could support the hypothesis of the multi-factorial origin of this pathology.
CD25high T Cells with a Prolonged Survival Inhibit Development of Diabetes
Authors: Yan Y. , Xiong Z. , Zhang S. , Song J. , Huang Y. , Thornton A.M. , Wang H. , Yang X-F.
Published: January 2017

The goal of this study is to examine a novel hypothesis that the progression of diabetes is partially due to the weakened survival of CD25high T cells, and prolonging survival of CD25high T cells inhibits the development of diabetes. Since CD28 co-stimulation is essential for the survival of CD4+CD25high T cells, we determined whether CD28-upregulated translationally controlled tumor protein (TCTP) prolongs the survival of CD4+CD25high regulatory T cells (Tregs) by a transgenic approach. The TCTP transgene prevents Tregs from undergoing apoptosis induced by interleukin-2 withdrawal-, dexamethasone-, cyclophosphamide-, and anti-Fas treatment in vitro. In addition, transgenic Tregs express higher levels of FOXP3 than wild-type counterparts and maintain suppressive activity, suggesting that TCTP promotes Tregs escape from thymic negative selection, and that prolonged survival does not attenuate Treg suppression. Moreover, TCTP transgenic Tregs inhibit the development of autoimmune diabetes due to increased survival of suppressive Tregs and decreased expression of pancreatic TNF-α. Promoting the survival of CD25high T cells leads to prolonged survival of Tregs but not activated CD25+ non-Treg T cells. Thus, we propose a new model of “two phase survival” for Tregs. Our results suggest that modulation of Treg survival can be developed as a new therapy for autoimmune diseases.
Human Colostrum T Lymphocytes and Their Effector Cytokines Actively Aid the Development of the Newborn Immune System
Authors: Ciardelli L. , Garofoli F. , Stronati M. , Mazzucchelli I. , Avanzini M.A. , Figar T. , Gasparoni A. , De Silvestri A. , Sabatino G. , Chirico G.
Published: January 2017

Colostrum contains soluble and cellular components, the latter mainly T lymphocytes. We expanded in vitro colostrum T lymphocytes (CoTL) to evaluate phenotype and capability of cytokine production. We also considered paired cord blood T-lymphocytes (CBTL) representing the newborn “virgin” immune system. CoTL showed memory phenotype while CBTL expressed mainly naïve phenotype. CoTL included a balanced percentage of helper and cytotoxic subsets. We observed higher percentages of IL-2 (p=0.003) and IL-4 (p=0.027) producing cells by helper rather than by cytotoxic T lymphocytes. The greatest percentage of IFN-γ producing cells was in cytotoxic cells (p=0.0048), while no difference was found for IL-10. Cord blood samples consisted of a statistically significant greater percentage of helper than cytotoxic cells (p<0.001), with a low percentage of cytokine producing cells, confirming the immaturity of the newborn's immune system. CBTL percentage of IL-2 producing cells was higher for helper than cytotoxic subset (p<0.001). We observed a greater percentage of IFN-γ (p=0.001), IL-4 (p=0.003) and IL-10 (p<0.001) producing cells by cytotoxic than helper T lymphocytes. CoTL demonstrated to protect the newborn through the mother's previous immune experience and to supply active cytokines, which can help the postnatal development of both T type 1/T type 2 response.
Autophagy Induction in T Cell-Independent Acute Hepatitis Induced by Concanavalin a in SCID/NOD Mice
Authors: Chang C-P. , Lei H-Y.
Published: January 2017

Concanavalin A (Con A) is known to induce acute hepatitis that is mediated by activation of NKT- and T-cell and cytokine production in immunocompetent mice. The observation of Con A-induced autophagic cell death of hepatoma cells via a Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 mediated autophagic pathway made us re-evaluate the effect of Con A-induced hepatitis in mice. Con A was administrated intravenously to BABL/c, SCID, or SCID/NOD mice at doses of 20, 30 or 40 mg/kg, respectively, to induce acute hepatitis. The levels of hepatitis and autophagy induction were both analyzed. We found that Con A can induce acute hepatitis in SCID or SCID/NOD mice with a kinetics similar to that of BALB/c, but requiring a higher dose of Con A. No lymphocyte infiltrations were found in SCID or SCID/NOD mice, and the cytokine productions were different. An autophagy with microtubule-associated protein light chain 3-II conversion was demonstrated in the liver post-Con A injection in SCID/NOD mice. Due to the mannose/glucose-specific binding on cell membrane, Con A can induce a T-cell-independent acute hepatitis with autophagy in SCID/NOD mice.
No Association of the NF-κB1 −94INS/Delattg Promoter Polymorphism with Relapse-Free and Overall Survival in Patients with Squamous Cell Carcinomas of the Head and Neck Region
Authors: Lehnerdt G.F. , Bankfalvi A. , Grehl S. , Adamzik M. , Lang S. , Schmid K.W. , Siffert W. , Riemann K.
Published: January 2017

The transcription factor, nuclear factor-κB (NF-κB) is known to play a major role in immune response, inflammation and, via apoptosis and proliferation, also in oncogenesis. Transcription of NFKB1, which encodes the subunit p50/p105 of NF-κB, seems to be influenced by an insertion/deletion polymorphism in its promoter region. Accordingly, the goal of this study is to investigate whether this polymorphism can serve as a putative prognostic marker in patients with Squamous Cell Carcinomas of the Head and Neck region (HNSCC). The prognostic value of the −94ins/delATTG NFKB1 promoter polymorphism was analyzed in an unselected series of patients treated with curative intent for HNSCC, including all tumor stages with different therapeutical regimens. Genotyping was performed by means of pyrosequencing, using DNA from paraffin-embedded tissue samples from 364 patients with a median follow-up of 61 (2-143) months. The various genotypes were correlated with relapse-free and overall survival, as well as risk, compared to healthy volunteers. The NFKB1 polymorphism was not related to risk of HNSCC. Kaplan-Meier curves revealed no significant association between the −94ins/delATTG alleles and survival or disease progression of patients with HNSCC. In conclusion, the results suggest that the investigated NFKB1 promoter polymorphism has no prognostic impact on risk or clinical course in HNSCC.
The Organophosphate Paraoxon Has No Demonstrable Effect on the Murine Immune System following Subchronic Low Dose Exposure
Authors: Fernandez-Cabezudo M.J. , Azimullah S. , Nurulain S.M. , Mechkarska M. , Lorke D.E. , Hasan M.Y. , Petroianu G.A. , Al-Ramadi B.K.
Published: January 2017

Paraoxon is the bioactive metabolite of the organophosphate pesticide parathion. Desulphuration of parathion by liver enzymes or sunlight results in the formation of paraoxon which inhibits acetylcholine esterase (AChE) activity. In the present study, we analyzed the effect of a 6-week, subchronic treatment with two different daily intraperitoneal doses (30 or 40 nmol) of paraoxon on the immune system of BALB/c mice. At a dose of 30 nmol/day, body weight of treated animals was unchanged compared to the controls. In contrast, the higher dose (40 nmol/day) induced a reduction in body growth, particularly in the first 3 weeks of treatment, peaking at week 2 when the saline group showed a 14.2-fold increase in body weight gain compared to paraoxon-treated animals. Moreover, mice treated with either dose of paraoxon had a >50% reduction in AChE activity during the first 3 weeks of treatment, but by the end of the treatment (week 6), AChE activity returned to normal. With regard to immunological parameters, there was no significant difference in either total spleen weight or in the ratios of various spleen cell populations between control and paraoxon-treated animals. Furthermore, no changes were observed in mitogen-induced cytokine secretion from splenocytes of paraoxon-treated mice. Finally, subchronic exposure to paraoxon did not alter mortality of mice exposed to a bacterial infection with Salmonella typhimurium. These data suggest that although subchronic exposure to paraoxon induced a transient inhibition in AChE activity, it had no demonstrable effect on the host immune system.
Breath Markers of Oxidative Stress and Airway Inflammation in Seasonal Allergic Rhinitis
Authors: Gratziou C. , Rovina N. , Makris M. , Simoes D.C.M. , Papapetropoulos A. , Roussos C.
Published: January 2017

Oxidative stress (OS) is well documented in asthma, but so far little data has been reported in non-asthmatic patients with Seasonal Allergic Rhinitis (SAR). The aim of this study is to investigate the degree of OS and airway inflammation in patients with SAR, with and without concomitant Asthma (SAR +A), using breath markers in exhaled air and in Exhaled Breath Condensate (EBC). In addition, the effects of natural allergen exposure and intranasal steroid treatment on these markers were evaluated. Exhaled NO (eNO) and CO, combined with measurements of 8-Isoprostane (Iso-8), Leukotriene B4 (LTB4) and nitrate/nitrite in EBC, were performed in 23 patients, 11 with SAR and 12 with SAR+A, and 16 healthy subjects. Iso-8 and LTB4 were significantly increased in both groups of patients (median values 43.6 pg/ml and 138.4 pg/ml in SAR group; 38.9 pg/ml, and 164.6 pg/ml in SAR+A group respectively; p>0.05) compared to healthy subjects (18.6 pg/ml and 7.8 pg/ml; p<0.05). Nitrate/nitrite and eNO levels were elevated in both groups compared to controls, but were significantly higher in the SAR+A compared to SAR group (nitrate/nitrite 9 μM and 3.9 μM; p=0.025; and eNO 18.5 ppb and 12.5 ppb, respectively; p>0.05). Nasal steroids caused significant reduction in LTB4 and 8-isoprostane levels in both groups of patients (p<0.05), while nitrate levels and eNO concentration were little affected by nasal treatment. OS markers were decreased at normal levels out of pollen season. Natural allergen exposure induces OS and airway inflammation, as assessed by measurements of markers in EBC and exhaled air, in patients with SAR who have no clinical signs of lower airway involvement. Besides, intranasal steroid treatment may have a regulatory role in the OS.
Can Serum TGF-BETA 1 Be Used to Evaluate the Response to Antiviral Therapy of Haemophilic Patients with HCV-Related Chronic Hepatitis ?
Authors: Tarantino G. , Coppola A. , Conca P. , Cimino E. , Di Minno G.
Published: January 2017

Congenital coagulation disorders limit the use of liver biopsy, especially when repeated assessment is needed. TGF-beta 1 plays a pivotal role in inducing fibrosis and has been proposed as its surrogate marker. Aiming at validating the clinical utility of this cytokine, fifteen haemophilic patients suffering from HCV-related chronic hepatitis were treated with Peg-IFN alpha2β plus Ribavirin. Serum TGF-beta 1, viral load and liver enzymes were analyzed at baseline and at six, twelve, and eighteen months. As expected, patients initially showed significantly higher TGF-beta 1 levels than age-matched controls (43.8 ng/mL, 28.7–46.4 vs. 26.9 ng/mL, 23.0–34.0, median and 95% CI; p=0.004). The end of therapy response rate was 67%. The main finding was a significant drop in TGF-beta 1 at six months compared to baseline values; this drop de facto predicted the levels reached in the following six months, which were fixed at lower concentrations (37.0 ng/mL, 21.9–43.8 and 27.0 ng/mL, 24.1–44.0 respectively; p<0.009), independently of treatment outcome (three patients were breakthrough, twelve were sustained virological responders (SVRs). During the treatment period none had clinical or biochemical signs of inflammation in other areas. Treatment was followed by a six-month follow-up, at the end of which TGF-beta 1 was increased compared to the previous values, reaching the initial levels in ten SVRs (45 ng/mL, 24.5–52.9). Interestingly, at a longer follow-up, two out of ten SVRs, who displayed the highest values of TGF-beta 1, relapsed. Serum TGF-beta 1 could be used to assess therapeutic outcome and short-term prognosis of HCV-related chronic hepatitis.
Low Prevalence of Selective IgA Deficiency in Infected Children Born to HIV-Seropositive Mothers: An In Vivo Model for Speculation on Selective IgA Deficiency Pathogenesis
Authors: Chiappini E. , Galli L. , Tovo P.A. , Gabiano C. , Lisi C. , Ferraris G. , Viganò A. , Giaquinto C. , Bernardi S. , Badolato R. , Genovese O. , Salvini F. , Maccabruni A. , Anzidei G. , Rosso R. , Buffolano W. , Cellini M. , Casadei A.M. , Faldella G. , Ruggeri M. , Osimani P. , Manzionna M.M. , Dodi I. , Gotta C. , Esposito S. , Gariel D. , De Martino M. ,   Italian Register for HIV Infection in Children
Published: January 2017

Anecdotal reports of restored immunoglobulin production in individuals with common variable immunodeficiency after acquiring HIV infection suggest that perturbation of the immune system occurring during HIV infection may force some underlying functional defects. These findings raise intriguing questions about the pathogenesis of common variable immunodeficiency. No study has investigated the possible influence of HIV infection on the development of selective IgA deficiency, a primary immunologic defect genetically related to common variable immunodeficiency. IgA serum levels were evaluated in a large cohort of children born to HIV-infected mothers from 1985 to 2006. To avoid differences possibly due to different follow-up durations we considered only infected and non-infected children aged over 4 years at last-follow-up. The study included 1,157 non-infected children and 964 infected children, aged ≥ 4 years at last-follow-up and with availability of two or more serum IgA determinations over six months of age. No child displayed immunoglobulin values compatible with diagnosis of common variable immunodeficiency. However, 0/964 infected children vs. 5/1157 non-infected children had selective IgA deficiency (P=0.048). It may be speculated that several immunological alterations, occurring simultaneously in perinatal HIV infection, surpass the functional defect exhibited in some children with selective IgA deficiency. Our data may shed light on the pathogenesis of selective IgA deficiency.
Systemic Lupus Erythematosus: Immunopathogenesis and Novel Therapeutic Targets
Authors: Beccastrini E. , D'Elios M.M. , Emmi G. , Silvestri E. , Squatrito D. , Prisco D. , Emmi L.
Published: January 2017

Systemic lupus erythematosus (SLE) is the prototype of autoimmune diseases with multiorgan involvement. SLE presents many genetic and epigenetic associations and the pathogenesis is characterized by a complex network of alterations affecting both adaptative and innate immunity. The disclosure of novel mechanisms of SLE pathogenesis suggested new therapeutic targets, based on interference with the cytokine pathways or on depletion of the immune cells.
Growth Factors, Their Receptor Expression and Markers for Proliferation of Endothelial and Neoplastic Cells in Human Osteosarcoma
Authors: Bianchi E. , Artico M. , Di Cristofano C. , Leopizzi M. , Taurone S. , Pucci M. , Gobbi P. , Mignini F. , Petrozza V. , Pindinello I. , Conconi M.T. , Della Rocca C.
Published: January 2017

Osteosarcoma is the most common primary malignant tumour of the bone. Although new therapies continue to be reported, osteosarcoma-related morbidity and mortality remain high. Modern medicine has greatly increased knowledge of the physiopathology of this neoplasm. Novel targets for drug development may be identified through an understanding of the normal molecular processes that are deeply modified in pathological conditions. The aim of the present study is to investigate, by immunohistochemistry, the localisation of different growth factors and of the proliferative marker Ki-67 in order to determine whether these factors are involved in the transformation of osteogenic cells and in the development of human osteosarcoma. We observed a general positivity for NGF — TrKA — NT3 — TrKC — VEGF in the cytoplasm of neoplastic cells and a strong expression for NT4 in the nuclear compartment. TGF-p was strongly expressed in the extracellular matrix and vascular endothelium. BDNF and TrKB showed a strong immunolabeling in the extracellular matrix. Ki-67/MIB-1 was moderately expressed in the nucleus of neoplastic cells. We believe that these growth factors may be considered potential therapeutic targets in the treatment of osteosarcoma, although proof of this hypothesis requires further investigation.
Acute Exposure to Essential Amino Acids (EAA) Activates MTOR/p70 Signaling in Soleus Muscle of Chronically EAA-Treated Aged Rats
Authors: Mascaro A. , Micheletti P. , D'Antona G.
Published: January 2017

Using an in vitro assay we assessed whether the acute exposure of soleus muscle of adult and aged rats to essential amino acid enriched mixture (EAAem) activates mTOR signaling pathway (mTOR and p70S6K) even after prolonged supplementation with the same mixture. A total of 20 adult (9 months of age at the end of treatment) and 20 aged (18 months of age at the end of treatment) male Wistar rats were used. Ten of each group were treated with EAAem (1.5 gr/kg/day in tap water) for 6 months. At the end of treatment the rats were grouped (n = 5 each group) as follows: adult (AD) and aged (AG) untreated controls; adult (AD_EAAem) and aged (AG_EAAem) chronically supplemented with EAAem; adult (AD+EAAem) and aged (AG+EAAem) acutely incubated with EAAem (soleus in 1% EAAem for 30 min); AD_EAAem+ and AG_EAAem+ acutely incubated with EAAem. Following treatment the activation level of mTOR and p70S6K was measured by Western blot. The basal level of mTOR and p70S6K activation appeared to be higher in AD compared with AG. In AG+EAAem a significant change in the level of p70S6K activation, unlike mTOR, was observed whereas no change was observed in AD+EAAem. In AD_EAAem muscles the basal level of p70S6K activation, unlike mTOR, was significantly lower than in AD and the acute exposure to EAAem produced a significant reduction of mTOR activation. Contrarily to AG, in AG_EAAem+ the acute exposure to EAAem produced a significant activation of mTOR, unlike p70S6K. Results in the adults indicated a higher basal level of activation and a lower responsiveness of the pathway to acute and chronic exposure to EAA-enriched mixture. On the contrary, in the aged, a lower basal level of activation was associated with a higher responsiveness to EAAem. In particular, although with a different timing, acute exposure to EAAem activated mTOR signaling even following prolonged supplementation.
Association of the Rantes Gene Promoter Polymorphisms −28C/G and −403G/A with Pneumonia in Greek Children
Authors: Doudouliaki T. , Haidopoulou K. , Pappa S. , Sakellaropoulou A. , Tsakiridis P. , Emboriadou M. , Hatzistilianou M.
Published: January 2017

Pneumonia is an inflammation of the lung caused by microbial or viral infection. It is an important factor of morbidity for children in the developed world, as well as a frequent cause of death of children in the developing world. Chemokines are a very important part of the immune system. The purpose of this study was to investigate the role of polymorphisms of chemokine RANTES (−28C/G and −403G/A) in the development of pneumonia in children. The study included two groups of children, the patient group and the control group. The patient group consisted of 60 children, who were hospitalized with the diagnosis of pneumonia from November 2009 until May 2010. The control group consisted of 135 healthy children who had no previous history of lower respiratory tract infections. According to the results, polymorphism of chemokine RANTES −28C/G was associated to the development of pneumonia in the studied population. Polymorphism of chemokine RANTES −403G/A was not associated to the development of pneumonia in the same population. Serum levels of chemokine RANTES were lower in children who were carriers of the polymorphism −28C/G compared to children who had the normal gene type. Also, serum levels of chemokine RANTES were higher in children with pneumococcal pneumonia compared to children with pneumonia caused by other pathogens.
Nephrotic Syndrome and Stroke
Authors: Gigante A. , Barbano B. , Liberatori M. , Sardo L. , Gasperini M.L. , Rosato E. , Cianci R. , Amoroso A.
Published: January 2017

The hypercoagulability of patients with nephrotic syndrome could be an important trigger for arterial and venous thrombotic events. Arterial thromboses are less frequent than venous thromboses and the most common locations are femoral arteries. The association of stroke and nephrotic syndrome is extremely rare. Here we report the case of a patient with stroke as first manifestation of nephrotic syndrome. Ischemic stroke can be the first manifestation of nephrotic syndrome and should be considered as a possible complication of the syndrome, when the commonest causes of ischemic stroke are excluded and especially in presence of pre-existing glomerular disease.
Microbiological and Molecular Characterization of Extreme Drug-Resistant Carbapenemase-Producing Klebsiella Pneumoniae Isolates
Authors: Santino I. , Bono S. , Nuccitelli A. , Martinelli D. , Petrucci C. , Alari A.
Published: January 2017

Fifteen Klebsiella pneumoniae clinical isolates showing non-susceptibility to carbapenems and resistant to colistin were collected in an Italian hospital. All isolates resulted negative to AmpC, MBL and ESBL production but positive to modified Hodge test, therefore were evaluated as KPC producers. The presence of blaKPC genes was verified by polymerase chain reaction (PCR) and sequencing. Furthermore, molecular typing was performed by multilocus sequence typing (MLST). PCR analysis and nucleotide sequencing revealed that all 15 isolates carried the blaKPC-3 gene. MLST analysis attributed the isolates from all patients to belong to the sequence type ST512. All isolates showed extensively drug-resistant (XDR) phenotype. The emergence of colistin-resistant K. pneumoniae underscores the implementation of strict control measures to prevent the dissemination of these organisms in hospitals.
Italian Study on Buckwheat Allergy: Prevalence and Clinical Features of Buckwheat-Sensitized Patients in Italy
Authors: Badiu I. , Olivieri E. , Montagni M. , Guida G. , Mietta S. , Pizzimenti S. , Caminati M. , Yacoub M.R. , Tombetti E. , Preziosi D. , Quecchia C. , Minetti S. , Facchetti S. , Fassio F. , Massaro I. , Corradi L. , Turi M.C. , Colagiovanni A. , Pascolini L. , Rossi F.W. , Losappio L. , Sansone L. , Imbesi S. , Barone S. Leto , Mistrello G. , Heffler E.
Published: January 2017

Buckwheat allergy is considered a rare food allergy outside of Asia. In Europe, buckwheat has been described mainly as a hidden allergen. Data on the prevalence of buckwheat hypersensitivity in non-Asian countries is very poor. The aim of this multicenter study was to evaluate the prevalence of buckwheat sensitization and its association with other sensitizations among patients referred to allergy clinics in different geographic areas of Italy. All patients referred to 18 Italian allergy clinics from February through April 2011 were included in the study and evaluated for sensitization to buckwheat and other allergens depending on their clinical history. A total of 1,954 patients were included in the study and 61.3% of them were atopic. Mean prevalence of buckwheat sensitization was 3.6% with significant difference between Northern (4.5%), Central (2.2%) and Southern (2.8%) regions. This is, to our knowledge, the largest epidemiological survey on buckwheat allergy reported outside of Asia. Buckwheat is an emerging allergen in Italy, being more frequently associated to sensitization in Northern regions.
Combination Therapy Including Serratiopeptidase Improves Outcomes of Mechanical-Antibiotic Treatment of Periimplantitis
Authors: Sannino G. , Gigola P. , Puttini M. , Pera F. , Passariello C.
Published: January 2017

This study was designed as a retrospective analysis of clinical outcomes of cases of periimplantitis treated by mechanical debridement and the administration of antibiotics combined or not with the administration of either the proteolytic enzyme serratiopeptidase (SPEP) or non-steroidal anti-inflammatory drugs (NSAIDs). Clinical charts of 544 partially edentulous patients treated for periimplantitis between June 1996 and December 2010 were analyzed to obtain clinical data of the affected implants just before the beginning of treatment and 12 months later to evaluate the outcomes of combined mechanical antibiotic treatment alone or in combination with the co-administration of the anti-inflammatory SPEP or NSAIDs. The comparative analysis revealed that therapeutic outcomes were significantly different in the three groups. Failure rate in the group that received SPEP (6%) was significantly lower compared to the group that received NSAIDS (16.9%; P<0.01) and to the group that received no anti-inflammatory therapy (18.9%; P<0.01). Treatment including SPEP was associated with significantly better healing also when successful treatments alone were considered. The data reported in this paper strongly support the hypothesis that SPEP is a valid addition to protocols for the combined therapy of peri-implantitis. In fact, it allows to enhance success rates significantly and also favors better tissue repair around successfully treated implants as compared to other regimens.
Sexual Distress, Sexual Dysfunction and Relationship Quality in Women with Systemic Sclerosis: Correlation with Clinical Variables
Authors: Rosato E. , Rossi C. , Molinaro I. , Digiulio M.A. , Trombetta A.C. , Marra A.M. , Gigante A. , Barbano B. , Quarta S. , Pisarri S. , Afeltra A. , Salsano F.
Published: January 2017

To assess the rate of sexual distress, sexual dysfunction and relationship quality and their association with clinical variables in women with systemic sclerosis (SSc), 102 sexually active women with SSc were recruited. Sexual distress, sexual dysfunction and dissatisfaction with relationship quality were investigated by Female Sexual Distress Scale Revised (FSDS-R), Female Sexual Function Index (FSFI) and Dyadic Adjustment Scale (DAS), respectively. The patients underwent medical examinations and nailfold videocapillaroscopy (NVC). Of the 102 patients, 37 (36%) reported sexual distress with FSDS-R score >11, 45 (44%) had sexual dysfunction with FSFI score <19 and 49 (48%) were not satisfied with relationship quality with DAS score <100. There was a negative correlation (p<0.001, R= −0.30) between FSDS-R and FSFI. No correlation was found between FSDS-R and DAS. FSFI showed a positive correlation with DAS (p<0.0001, R= 0.36). Age correlated negatively (p<0.05, R= −0.26) with FSFI, while FSDS-R and DAS did not correlate (p>0.05) with age. SSc women with digital ulcers (DU) had a reduction of FSFI and DAS compared with women without DU. In patients with late capillaroscopic pattern, mean value of FSFI was significantly lower than the other two capillaroscopic patterns. DAS decreased with progression of capillaroscopic damage. In a high percentage of women with SSc FSDS-R was increased, while FSFI and DAS were reduced. Age correlated negatively with FSFI, while skin score showed a negative correlation with DAS. Digital vascular damage negatively influenced FSFI and DAS.