bluuebunny/crossref_metadata_2025 huggingface dataset:
Urothelial Bladder Carcinoma and Viral Infections: Different Association with Human Polyomaviruses and Papilloma Viruses
Authors: Fioriti D. , Pietropaolo V. , Dal Forno S. , Laurenti C. , Chiarini F. , Degener A.M.
Published: January 2017

Bladder cancer is the second most commonly occurring genitourinary cancer in adults. The interaction of different carcinogenic and co-carcinogenic agents are responsible for bladder urothelial carcinoma: alcohol and smoking habits, Schistosoma haematobium infection, exposition to chemicals, analgesic and antineoplastic drugs prolonged use. Recently also viral infections have been associated to this pathology. In this study the correlation between viral infections and bladder carcinoma has been evaluated. A group of 32 patients affected by primary bladder neoplasia has been analysed. A control group of 20 autoptic samples of healthy bladder was analysed. The DNA of the following viruses has been searched by Polymerase chain reaction (PCR): Adenovirus, Herpes simplex virus type 1 (HSV-1), Herpes simplex virus type 2 (HSV-2), Human Papillomaviruses (HPV), Polyomaviruses (BKV and JCV). In the examined population the association bladder carcinoma-HPV, found by others, has not been confirmed. The high percentage of human polyomaviruses present in the samples is a statistically significant data (p=0.0087) and allows to presume that BKV and JCV may play a role in the aetiology of bladder tumor. In particular the polyomavirus BK, which is found in significative percentage both in single infection (p=0.0036) and in co-infections with other viral species (p=0.035), may be an important co-factor in the pathogenesis of bladder carcinoma.
Detection of Helicobacter Pylori by PCR on Gastric Biopsy Specimens Taken for CP Test: Comparison with Histopathological Analysis
Authors: Di Bonaventura G. , Neri M. , Angelucci D. , Rosini S. , Piccolomini M. , Piccolomini R.
Published: January 2017

The aims of the present study were: (i) to assess whether H. pylori could be succesfully detected by PCR from the same biopsy sample used for CPtest; and ii) to evaluate CPtest comparatively to both PCR and histology for detection of H. pylori infection in dyspeptic patients. Three antral gastric biopsies were collected from each of 80 consecutive dyspeptic patients undergoing oesophagogastroduodenoscopy. Two biopsies were for histology (gold standard), one for CPtest, scored at 20min, 1h and 24h for the presence of urease activity. Gastric biopsy was then removed from CPtest and used for ureC-targeted PCR. Fifty-five (68.7%) patients were positive for H. pylori infection by histology. CPtest yielded an overall diagnostic accuracy of 93.8% (95% CI: 91–96.4%), regardless of observation period. No erroneous categorization of H. pylori status occurred using PCR, yielding sensitivity, specificity, positive and negative predictive values, and overall diagnostic accuracy of 100%. Our results suggest that H. pylori can be detected by PCR in gastric biopsies previously taken for CPtest, so reducing the workload of the endoscopist by saving additional biopsies for culture analysis and susceptibility tests.
Neurobehavioral Functions, Serum Prolactin and Plasma Renin Activity of Manganese-Exposed Workers
Authors: Niu Q. , Shuchang H. , Sheng W. , Di Gioacchino M. , Verna N. , Volpe A. R. , Di Giampaolo L. , Carmignani M. , Boscolo P.
Published: January 2017

Objective of this study was to assess effects of manganese (Mn) exposure on 56 workers employed in a Mn welding workshop of a machine building factory in Taiyuan (Shanxi Province, P.R. China) for a mean period of 16.1 years. The mean air Mn level in the workshop was 138.4 μg/m3. Neurobehavioral Core Test Battery (NCTB), including the Profile of Mood States (POMS), was performed. Blood pressure (BP) increase following immediate stand-up (BP-IS), serum prolactin (PRL) and plasma renin activity (PRA) in supine position were also determined. Most of the NCTB scores of the Mn-exposed workers were lower than those of the controls, while the POMS scores were higher, indicating a Mn-induced impairment of neurophysiological functions and a deflection of mood towards negative emotion states. PRL values of the Mn-exposed workers were higher than those of the controls. BP-IS of Mn-exposed workers was significantly lower than that of the controls. PRA of the same workers was augmented more than 200 %. In the Mn-exposed workers, the higher PRL values are possibly due to a reduced inhibitory effect on pituitary lactotrope cells by the tubero-infundibular dopamine system; the decreased BP-IS was referred to imbalance between the sympathetic and parasympathetic activities, whereas the higher basal PRA was thought to depend on neuroendocrine changes (including increased central sympathetic tone) and/or on a direct effect of Mn on renal juxta-glomerular cells. On the whole, this study demonstrates that occupational Mn exposure is responsible for neurobehavioral changes coexisting with alterations of neuroendocrine and humoral systems.
Clastogenic but Not Apoptotic Effects on Human Artery Endothelial Cells by Concentrations of Inorganic Lead Inhibiting Their Nitric Oxide Production
Authors: Carmignani M. , Felaco M. , Boscolo P. , Di Gioacchino M. , Di Giampaolo L. , Niu Q. , Cesare P. , Volpe A. R.
Published: January 2017

Human coronary artery endothelial cells (HCAEC 5156) were cultured as monolayers and exposed to concentrations of lead (as acetate, Pb) in the culture medium similar or lower than those commonly found in the blood of human beings occupationally or environmentally exposed to this element. Only at the concentration of 200 ng/mL, Pb reduced growth rate of HCAEC 5156 cells starting from the 3rd day and up to the 5th day of incubation. On the other hand, Pb (0.2, 2 and 200 ng/mL) increased concentration-dependently micronuclei formation in binucleated HCAEC5156 cells, as it was shown by the cytokinesis-blocked micronucleus assay (CBMN assay) carried out after 48 hours of exposure to the metal. However, Pb was unable, at all the above concentrations, to induce apoptosis in HCAEC 5156 cells following a 48 hour-exposure, as shown by an electrophoretic apoptotic DNA fragmentation test. Moreover, Pb (2 and 200 ng/mL) reduced significantly the concentration of nitric oxide (NO, determined analytically as L-citrulline) in both culture medium and cytosol of HCAEC 5156 cells following a 7 day-exposure to the element. Results were discussed also in relation to evidences of other studies reporting genotoxic and/or apoptotic effects of Pb on various cell types at very elevated dosages or concentrations. The observed clastogenic effects of Pb were explained through a series of mechanisms involving interactions between oxygen reactive species and NO and/or reduced NO synthesis in the endothelium, thus leading to a depressed NO bioavailability. This research first shows that Pb is provided with clastogenic but not apoptotic effects on cultured human endothelial cells. It was emphasized that such effects are induced by Pb concentrations similar to those commonly found in blood and tissues of laboratory animals showing Pb induced cardiovascular and/or neuropsychological alterations.
Secretory Ig a in Saliva and Academic Stress
Authors: Otsuki T. , Sakaguchi H. , Hatayama T. , Takata A. , Hyodoh F. , Tsujita S. , Ueki A. , Morimoto K.
Published: January 2017

Several reports have proposed that the concentration of secretory immunoglobulin A (S-IgA) in saliva is an indicator of psychological stress. With this in mind, we decided to examine it in 10 second year medical student volunteers at Kawasaki Medical School course between May 4 and July 13, 2000 and discussed the relationship between S-IgA and the stress from academic examinations. Saliva was collected three times (on rising, at forenoon, and at bedtime) every Thursday. During this period, sporadic academic examinations were held twice and term-end examinations occurred during the last two weeks. Results showed the concentration of S-IgA significantly higher at the on rising time-point than at the other two time-points. There was also a tendency for the S-IgA level in saliva to be higher on the day before academic examinations and during them and lower on the days between these examinations. In addition, daily variations in the S-IgA concentration sometimes seemed to be disturbed by other academic stress. Therefore, it may be possible to use this measurement to monitor psychological stress in students and workers.
Genomic Organization and Cytokine-Mediated Inducibility of the Human Trim-8/Gerp Gene
Authors: Toniato E. , Flati V. , Laglia E. , Mincione G. , Martinotti S.
Published: January 2017

Cytokine signaling is negatively regulated by a set of SH2 domain-containing proteins, the Suppressors of Cytokine Signaling (SOCS) acting as intracellular modulators. Experimental evidence indicates that SOCS gene expression is induced by cytokines and pro-inflammatory stimuli and is highly controlled both at transcription and translation level. Furthermore, SOCS proteins appear rapidly degraded inside the cells, mostly controlling their stability by interacting with specific molecules such as elongin B and C. It has been shown that SOCS-1/JAB, a member of the SOCS family, interacts with TRIM-8/Gerp, a new ring protein specifically binding SOCS-1 recombinant polypeptide in-vitro and in-vivo. Trim-8/Gerp, transcribes a 3.0-kb mRNA, spans 551 AA and is highly conserved during evolution. In addition, it can be induced by IFN-γ in epithelial and lymphoid cells and is expressed mostly ubiquitously in murine and human tissues. Here in this report we present the genomic organization of this new SOCS-1 interactor, and we add new tools for extending investigation of the complex mechanism that undergoes negatively regulation of cytokine signaling.
Altered Cytokine Production in Mice Exposed to Lead Acetate
Authors: Iavicoli I. , Marinaccio A. , Castellino N. , Carelli G.
Published: January 2017

Previous investigations have shown that Pb exerts immunotoxic effects. Object of this study were Th1 and Th2-type immune responses of mice to Pb exposure. Adult Swiss male mice were administered 0, 40 and 400 mg/1 of Pb (as acetate) in drinking water for 14 days . At the end of the treatment, blood Pb was determined and two Th1 cytokines (IL-2, INF-γ) and one Th2 serum cytokine (IL-4) were measured. A significant increase in IL-4 production was observed in the mice exposed to 40 mg/1 of Pb, while a further increase in IL-4 production was associated with a decrease in IFN-γ production in mice exposed to 400 mg/1 of Pb. On the other hand, Pb exposure did not induce changes of serum IL-2 (involved also in the ThO immune pattern). Our findings indicate that low level Pb exposure enhances a Th2 response. A high Pb dose can either stimulate the Th2 immune activity or reduce the Th1 response; the result is an imbalance between Th1 and Th2 activation.
Wilson's Disease: Clinical, Genetic and Pharmacological Findings
Authors: Leggio L. , Addolorato G. , Abenavoli L. , Gasbarrini G.
Published: January 2017

Wilson's disease (WD) is an autosomal recessive disorder characterized by copper accumulation and toxicity in the liver and in other tissues. WD presents with liver disease, neurological or psychiatric disturbances or other less common clinical features. Diagnosis of WD is often difficult and may be formulated through clinical, biochemical, imaging, histochemical and genetic evaluations. Pharmacological approach in WD consists in copper chelating agents such as D-penicillamine, trientine, dimercaprol and tetrathiomolybdate. In 1997 zinc was approved for maintenance therapy of WD by the U.S. FDA. Orthotopic Liver Transplantation is indicated in fulminant hepatic failure, progressive hepatic insufficiency despite therapy, cirrhosis with complications of portal hypertension. However the most appropriate therapy, including OLT, remains controversial in WD and further studies are needed especially in order to differentiate the possibility of specific therapies for different WD phenotypes.
Amelioration of Neutrophil Membrane Function Underlies Granulocyte-Colony Stimulating Factor Action in Glycogen Storage Disease 1b
Authors: Lesma E. , Riva E. , Giovannini M. , Di Giulio A.M. , Gorio A.
Published: January 2017

Glycogen storage disease (GSD) 1b is a metabolic disorder characterized by a deficiency of glucose 6-phosphate transporter and neutrophil alterations, which are reduced in number and functionally impaired. The present study aimed at investigating neutrophil dysfunction correlating submembrane and cytoskeletal changes at different ages with or without granulocyte-colony stimulating factor (G-CSF) treatment. GSD1b neutrophils showed reduced expression and diffused localization of focal adhesion kinase (FAK) and actin. No abnormalities were observed in GSD1a patient neutrophils. Gelsolin was also slightly reduced in neutrophils of GSD1b patients. When patients were treated for at least 3 months with G-CSF, the neutrophil number and the expression of FAK and actin were significantly increased. Granulocyte colony-stimulating factor treatment was similarly effective when performed in 1 year old patients. FAK auto- and IL-8-mediated phosphorylations were already affected as early as 1 year of age. G-CSF treatment also improved this alteration. Our data suggest that neutrophil dysfunction in GSD1b patients might be related to functional impairment and disorganization of proteins of the sub-membrane apparatus, and that G-CSF treatment counteracts neutropenia and prevents the progressive alterations of neutrophil sub-membrane proteins.
IL-10 Enhances CCL2 Release and Chemotaxis Induced by CCL16 in Human Monocytes
Authors: Musso T. , Cappello P. , Stornello S. , Ravarino D. , Caorsi C. , Otero K. , Novelli F. , Badolato R. , Giovarelli M.
Published: January 2017

CCL16 is a CC chemokine originally identified as a liver-expressed chemokine. Its expression has been detected in activated monocytes where it is up-regulated by stimulation with IL-10. This is in contrast with IL-10's inhibition of the expression of most chemokines. CCL16 is chemotactic for monocytes, lymphocyte and dendritic cells. We investigated whether CCL16 displays biological activities other than chemotaxis and whether IL-10 affects monocyte response to CCL16. We show that CCL16 induces the expression of CCL2 at the mRNA and protein level, but does not affect that of CCL5, CCL18 and proinflammatory cytokines. This effect was prevented by treatment with pertussis toxin and may thus be mediated by G-protein-coupled receptors. IL-10 markedly increased CCL2 production induced by CCL16, but suppressed that of CXCL8. It also enhanced the chemotactic response to CCL16. Addition of antibodies blocking CCR1, but not CCR8, prevented this enhanced chemotactic response and suggested that CCR1 is primarily involved. We propose that IL-10 modulates the effects of CCL16 on monocytes by increasing their CCR1-dependent response. The coordinated secretion of CCL16 and IL-10 may thus enhance monocyte infiltration.
Synovial Fluid OX40T Lymphocytes of Patients with Rheumatoid Arthritis Display a TH2/TH0 Polarization
Authors: Passacantando A. , Parzanese I. , Rascente M. , Petrucci C. , Minisola G. , Tonietti G.
Published: January 2017

Rheumatoid arthritis (RA) is an autoimmune disease in which T-cell activation plays a pivotal role in the induction of articular damage. CD4+/OX40+ T cells accumulate in the synovial fluid (SF) of RA patients, which suggests that they are involved in the pathogenesis of the disease. In this study, we assessed the intracellular cytokine production of peripheral blood and SF CD4+ and CD4+/OX40+ T cells from RA patients in order to evaluate their role in this disorder. Our results show that SF CD4+ cells are predominantly interferon gamma (IFN-γ)-positive and express a Th1-like cytokine pattern. In SF, significantly more CD4+/OX40+ T cells expressed interleukin-4 (IL-4) and IL4/IFN-γ than IFN-γ alone. Our data demonstrate that SF CD4+/OX40+ T cells express a Th2/Th0 cytokine profile, which suggests that they are involved in inflammatory responses in RA joints.
In Vitro Susceptibility of Isolates of Borrelia Burgdorferi S.L. to Antimicrobial Agents
Authors: Santino I. , Scazzocchio F. , Ciceroni L. , Ciarrocchi S. , Sessa R. , Del Piano M.
Published: January 2017

In the present study, we investigate the in vitro antimicrobial activity of macrolides, β-lactams and tetracycline against Borrelia burgdorferi s.l. clinical and tick isolates. Minimal inhibitory concentrations (MICs) were determined in normal growth condition and after pre-exposure of the strains to sub-MIC of the founder of each drug family. All the classes of tested antibiotics showed good antibacterial activity against all the borreliae isolates and there were no significant susceptibility differences among clinical and tick isolates. After pre-exposure of the strains to sub-MIC of erythromycin, cefoxitin and tetracycline, we observed that some strains of B. burgdorferi s.l. showed higher MIC values to both the pre-exposed drug and drugs of the same family. The less susceptibility of borreliae, in the last growth condition in vitro, could be one of the justifications of clinical results indicating the limited efficacy of these antibiotics in treatment of B. burgdoferi infections.
In Vivo Effect of an Immunostimulating Bacterial Lysate on Human B Lymphocytes
Authors: Lanzilli G. , Falchetti R. , Cottarelli A. , Macchi A. , Ungheri D. , Fuggetta M.P.
Published: January 2017

The aim of the present study is to investigate in humans the mechanism by which the oral vaccine Polyvalent Mechanical Bacterial Lysate (PMBL) can rapidly mobilize specific immune response and evaluate the efficacy of its immunostimulating activity in preventing recurrent infections of the upper respiratory tract (URTIs) in a group of patients with a medical history of URTI recurrence. Patients received, by sublingual route, PBML, an immunostimulating lysate obtained by mechanical lysis of the most common bacteria responsible for upper respiratory tract infections. The treatment was administered for 10 consecutive days/month for 3 consecutive months. After the end of the treatment period the patients were followed up for an additional 3 months. The frequency of IgM memory B cells and the expression of the activation marker CD25 in peripheral blood lymphocytes were measured using the flow cytometric method before the start and at days 30 and 90 of the treatment cycle. To correlate clinical results to immunological parameters, the patients were monitored at different time-points during the treatment and at the end of follow-up period. The results showed that PMBL exerts a therapeutic and preventing effect in acute and recurrent infections of the upper respiratory tract and that this effect correlated with the activation and enhancement of both IgM memory B lymphocytes (CD24+/CD27+ cells) and IL2 receptor-expressing lymphocytes (CD25+ cells) involved either in humoral or cellular immunity.
Dual Effect of Methylprednsolone Pulses on Apoptosis of Peripheral Leukocytes in Patients with Renal Diseases
Authors: Stratta P. , Canavese C. , Fenoglio R. , Priolo G. , Grillo A. , Aimo G. , Quaglia M. , Pagni R.
Published: January 2017

It is well known that change in apoptosis may modulate the natural story of illness, and that many drugs may act through modulation of apoptosis, but the role of steroids in acting through apoptosis in different settings, including renal diseases, has still to be elucidated. We studied the in vivo effects of steroids by oral assumption (10 to 25 mg/deltacortene) or by intravenous pulses (300 to 1000 mg/dose) on apoptosis and cellular subsets of peripheral lymphocytes, by evaluating DNA-fragmentation and lymphocyte subsets in 79 subjects: 22 controls and 57 patients with various renal diseases (25 Lupus-GN, 19 membranous-GN (MGN), 6 rapidly progressive-GN (RPGN), 2 acute interstitial nephritis (AIN), 5 on chronic dialysis. Baseline apoptosis was present in 1/22 (4.5%) of controls, 3/25 (12%) SLE, 2/6 (33.3%) RPGN and 10/19 (52.6%) MGN. A significant decrease in CD3+CD8+ cell count and a significant increase of the CD3+CD4/CD3+CD8+ ratio were found in apoptosis-positive subjects. DNA fragmentation did not change after oral steroids, paralleling a 22 to 32% decrease in total lymphocytes. Following intravenous methylprednisolone pulses, a deeper drop of all lymphocyte subsets was observed, while DNA fragmentation turned from present to absent in 2 MGN, but not in 2 RPGN, and from absent to present in 1 ARF and 1 SLE, independently of the dosage. We demonstrated that the presence of apoptosis in renal diseases is associated with decreased CD3+CD8+ cell count. Furthermore, steroid intravenous pulses, besides inducing a profound decrease in lymphocyte subsets, do exert a dual effect on baseline leukocyte apoptosis, eventually leading to a reversal of baseline patterns, either turning from negative to positive or from positive to negative. Oral steroid therapy did not influence baseline apoptosis.
In Vitro Stem Cell Cultures from Human Dental Pulp and Periodontal Ligament: New Prospects in Dentistry
Authors: Ballini A. , De Frenza G. , Cantore S. , Papa F. , Grano M. , Mastrangelo F. , Tetè S. , Grassi F.R.
Published: January 2017

In spite of the vast knowledge of tooth development and of the various kinds of specialized bone/tooth-associated cells, the characteristics and properties of their precursor cell populations present in the postnatal organism are little known, as is their possible therapeutic use. Taken together dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PDLSCs) possess stem-cell-like qualities, including self-renewal capability and multi-lineage differentiation. Regenerative medicine is based on stem cells, signals and scaffolds. Transplantation of those cells, which can be obtained from an easily accessible tissue resource and expanded in vitro, holds promise as a therapeutic approach for reconstruction of tissues and bone in vivo.
Ulcerative Colitis Masked by Giant Urticaria
Authors: Caroselli C. , Plocco M. , Pratticò F. , Bruno C. , Antonaglia C. , Rota F. , Curreli I. , Caroselli A. , Bruno G.
Published: January 2017

The occurrence of giant urticaria and ulcerative colitis is very infrequent. A 23- year-old female reported the initial eruption of short-lived cutaneous itchy weals on her arms. Then lesions ran together and became confluent, extending to her legs, followed by undefined abdominal pain and a slight increase of body temperature. Exams showed hystologically confirmed ulcerative colitis, with perinuclear anti-neutrophil cytoplasmic antibody positivity. Ulcerative colitis therapy led not only to the remission of the colitic symptoms, but also to the prompt recovery of skin manifestations. Urticaria was the epiphenomenon of ulcerative colitis.
An IL-15 Dependent CD8 T Cell Response to Selected HIV Epitopes is Related to Viral Control in Early-Treated HIV-Infected Subjects
Authors: D'Offizi G. , Gioia C. , Corpolongo A. , Martini F. , Paganelli R. , Volpi I. , Sacchi A. , Tozzi V. , Narciso P. , Poccia F.
Published: January 2017

In some early-treated HIV+ patients, Structured Treatment Interruption (STI) is associated to spontaneous control of viral rebound. Thus, in this clinical setting, we analyzed the immunological parameters associated to viral control. Two groups of early treated patients who underwent STI were retrospectively defined, according to the ability to spontaneously control HIV replication (Controller and Non-controller). Plasma cytokine levels were analyzed by multiplex analysis. CD8 T cell differentiation was determined by polychromatic flow cytometry. Antigen-specific IFN-Γ production was analyzed by ELISpot and intracellular staining after stimulation with HIV-peptides. Long-term Elispot assays were performed in the presence or absence of IL-15. Plasma IL-15 was found decreased over a period of time in Non-Controller patients, whereas a restricted response to Gag (aa.167–202 and 265–279) and Nef (aa.86–100 and 111–138) immunodominant epitopes was more frequently observed in Controller patients. Interestingly, in two Non-Controller patients the CD8-mediated T cells response to immunodominant epitopes could be restored in vitro by IL-15, suggesting a major role of cytokine homeostasis on the generation of protective immunity. In early-treated HIV+ patients undergoing STI, HIV replication control was associated to CD8 T cell maturation and sustained IL-15 levels, leading to HIV-specific CD8 T cell responses against selected Gag and Nef epitopes.
Metabolic Syndrome and Cardiovascular Risk in HIV-Infected Patients with Lipodystrophy
Authors: Falasca K. , Ucciferri C. , Manzoli L. , Mancino P. , Pizzigallo E. , Conti P. , Vecchiet J.
Published: January 2017

In this cross-sectional study, we evaluate potential predictors of Metabolic Syndrome (MS) in a group of 54 Caucasian chronically HIV-infected patients with lipodystrophy. According to ATP-III criteria, 22 patients were affected by MS and 32 were not. The mean age of the sample was 41.2 ± 8.6 years, and most patients were males (74.1%); the two groups were homogeneous for gender, age, viro-immunologic status and the duration of antiviral therapy. The independent association between MS and several factors including demographic characteristics, type of highly-active antiviral therapy (HAART), viro-immunologic response, common cardiovascular risk factors (including Framingham scores), and selected cytokines (IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10 and IL-18), was investigated using stepwise forward logistic regression. At multivariate analysis, the only independent predictors of the metabolic syndrome were triglycerides and IL-18. A10 mg/dL increase in triglycerides corresponds to an adjusted risk ratio for MS of 1.11 (95% IC: 1.04–1.19); and patients in the top tertile of IL-18 (those with IL-18 ≥ 530 pg/L) had more than three times the likelihood of MS, as compared to the bottom and medium fertiles of IL-18 (patients with IL-18 < 530 pg/L). This relationship was not attenuated by the inclusion of any other variable in the multivariate model. However, the association between metabolic syndrome and IL-18 is no longer significant when IL-18 is treated as a continuous variable (trend p = 0.087). Our results on HIV patients with lipodystrophy confirm previous findings on a strong independent association between IL-18 and MS in the general population. Further research is needed to clarify the mechanism of this association and its role in the development of cardiovascular disease in HIV patients.
Eyelash Length in Children with Vernal Keratoconjunctivitis: Effect of Treatment with Cyclosporine Eye Drops
Authors: Pucci N. , Massai C. , Bernardini R. , Caputo R. , Mori F. , De Libero C. , Novembre E. , De Martino M. , Vierucci A.
Published: January 2017

The upper eyelashes in vernal keratoconjunctivitis (VKC) patients have been reported to be longer than in healthy age- and gender-matched subjects. Eyelash length positively correlated to the severity of the disease and negatively to the employment of cyclosporine eye drops, suggesting that specific humoral factors could be involved in both ocular inflammation and elongation of the eyelashes. The aim of the present study is to evaluate a possible relationship between eyelash length and the duration of topical cyclosporine treatment. The length of the upper eyelashes of 34 VKC patients never treated with topical cyclosporine (Cyc-NT) was matched with that of 58 VKC patients treated with cyclosporine (Cyc-T). The latter group was divided into three subgroups, depending on the duration of therapy: 1–6 months (group 1; 21 subjects), 7–12 months (group 2; 19 subjects), >12 months (group 3; 19 subjects). Cyc-NT patients' eyelashes were significantly longer than those of VKC patients treated for 1–6 months (group 1). No significant difference was found between Cyc-NT and Cyc-T patients in group 2 and group 3. The differences between Cyc-T patients and group 1 and 2, group 2 and 3, and group 1 and 3 were not statistically significant. The eyelash shortening observed seems directly related to the rapid improvement of ocular symptoms induced by the treatment. A receptor down-regulation by mediators of ocular inflammation may explain this data, although different cytokines, hormones or other humoral mediators could be expressed on the ocular surface at different stages of the disease, mainly in periods of rapid change of the clinical course.
Effect of Coronary Percutaneous Revascularization on Interferon-γ and Interleukin-10 Producing CD4+ T Cells during Acute Myocardial Infarction
Authors: Sardella G. , De Luca L. , Francavilla V. , Accapezzato D. , Di Roma A. , Gianoglio O. , Colantonio R. , Mancone M. , Fedele F. , Paroli M.
Published: January 2017

T lymphocytes play an important role in the induction and progression of acute coronary syndromes (ACS). To gain insight into how different T cell subsets can influence ACS, we analyzed the frequencies of circulating CD4+T cells producing either pro-inflammatory interferon(IFN)-γ or anti-inflammatory interleukin (IL)-10 in subjects presenting with ST-elevation myocardial infarction (STEMI). The effect of coronary bare metal (BS) and paclitaxel-eluting stent (PES) on the balance between CD4+IFN-γ+ and CD4+IL-10+ lymphocytes was also investigated. Peripheral blood mononuclear cells (PBMC) were isolated from 38 consecutive patients with STEMI before and 48 hrs or 6 days after implantation of either BS or PES. Twenty patients with no history of coronary artery disease were included as basal controls. PBMC were stimulated in vitro with anti-CD3/anti-CD28 monoclonal antibodies, and CD4+IFN-γ+ or CD4+IL-10+ T cells were detected by flow cytometry intracellular staining. The frequency of peripheral CD4+IL-10+ T cells was significantly higher in STEMI patients as compared with controls. Conversely, the frequency of CD4+IFN-γ+ T lymphocytes did not differ between STEMI and subjects without history of coronary artery disease. Six days after the revascularization procedure, the percentage of CD4+IL-10+ T cells was significantly decreased in BS but not in the PES group, whereas the relative percentage of CD4+IFN-γ+ T lymphocytes were diminished in both groups as compared with baseline levels. Our data indicate that STEMI is associated with a peripheral expansion of CD4+IL-10+T lymphocytes, and that primary coronary revascularization with implantation of either BS or PES is followed by a reduction in circulating CD4+IFN-γ+ T lymphocytes. PES implantation, however, appears to inhibit the relative decrease of the IL-10 producing lymphocyte as observed in BS implanted patients, shifting the balance between pro-inflammatory and anti-inflammatory T cell populations in favor of the latter.
Effects of a Program of Hospital-Supervised Chest Physical therapy on Lung Function Tests in Children with Chronic Respiratory Disease: 1-Year Follow-up
Authors: Indinnimeo L. , Tancredi G. , Barreto M. , De Castro G. , Zicari A.M. , Monaco F. , Duse M.
Published: January 2017

To investigate whether a hospital-supervised program of chest physical therapy improves lung function in children with chronic pulmonary diseases, twenty-four children (4 with Kartageners syndrome, 12 with common variable immunodeficiency, and 8 with primary ciliary dyskinesia) average age 11.2±3.2 years, were randomly assigned to a one-month hospital-supervised program of chest physical therapy (13 patients) or to a control group (11 patients) that continued unsupervised chest physical therapy at home. Lung function was assessed before the program, and one and twelve months after. At the one-month assessment, thoracic gas volume was significantly lower in the supervised group than in the controls. At the one-year assessment, forced expiratory volume in one second was significantly higher in the supervised group than in controls. A supervised program of chest physical therapy significantly improved lung function in children with chronic pulmonary diseases.
Inflamed Intestinal Mucosa Features a Specific Epithelial Expression Pattern of Indoleamine 2,3-Dioxygenase
Authors: Ferdinande L. , Demetter P. , Perez-Novo C. , Waeytens A. , Taildeman J. , Rottiers I. , Rottiers P. , De Vos M. , Cuvelier C. A.
Published: January 2017

Indoleamine 2,3-dioxygenase (IDO) catalyzes the first step in the degradation of tryptophan, an essential amino acid. During inflammation IDO can be induced in different cell types resulting in local tryptophan depletion. This inhibits T cell proliferation and may induce apoptosis. High expression of IDO was previously found in inflammatory bowel disease and is thought to represent a mechanism for downregulation of the local immune response. Our aim is to investigate the expression pattern of IDO in normal and inflamed murine and human intestinal mucosa. Immunohistochemical staining for IDO was performed on paraffin sections of colon of two mouse models for colitis and their controls and on paraffin sections of human ileum and colon in normal and two different inflammatory conditions, namely inflammatory bowel disease and diverticulitis. IDO immunohistochemistry showed similar results in murine and human tissue. In normal, as well as in inflamed mucosa, some mononuclear cells, fibroblasts and endothelial cells were positive for IDO. In inflamed mucosa a specific expression pattern of epithelial IDO was found where epithelial cells flanking ulcers or bordering crypt abscesses showed high IDO expression. Moreover, in human intestinal inflammation, IDO was expressed in ulcer associated cell lineage. Since bacterial invasion is more pronounced in erosions and in crypt abscesses and since IDO activity and the resulting local tryptophan depletion can cause growth arrest of several tryptophan-dependent microorganisms, IDO expression in the vicinity of interruptions of the epithelial barrier may point to a role for IDO as a local anti-infectious agent. Furthermore, expression of IDO at the margin of ulcerations and in the reparative ulcer-associated cell lineage suggests involvement of IDO in repair processes.
Allergen Specific Nasal Challenge to Latex in Children with Latex Allergy: Clinical and Immunological Evaluation
Authors: Bernardini R. , Pucci N. , Rossi M.E. , Lombardi E. , De Martino M. , Mori F. , Ciprandi G. , Novembre E. , Marcuccp F. , Massai C. , Azzari C. , Vierucci A.
Published: January 2017

There are no data concerning the significance of allergen specific nasal challenge to latex (ASNCL) in the pediatric population and the effect of mometasone furoate nasal spray [(MFNS), topic corticosteroid exerting a potent anti-inflammatory activity] in children with latex allergic rhinitis. The aims of this study are: to investigate the clinical and immune pathological effects of ASNCL in children with latex allergy; to study the effects of MFNS pre-medication on the clinical and immune pathological effects of ASNCL in children with latex allergy. Thirteen children [6 male and 7 female, mean (SD) age 9.6 (2.9) years] with latex allergy and seven children [3 male and 4 female, mean (SD) age 9.9 (3.8) years] without latex allergy underwent ASNCL. Nasal symptoms were recorded, nasal lavage fluid was collected to measure tryptase, eosinophil cationic protein (ECP), interleukin-5, interferon-γ levels, and spirometric test was performed for each patient without or with pre-medication with MFNS. ASNCL induced a clinical allergic response and increased tryptase levels only in children with latex allergy. No serious adverse events occurred after ASNCL. MFNS pre-medication reduced both tryptase and ECP levels only in children with latex allergy. ASNCL is a simple, reliable and useful tool to make or confirm the diagnosis of nasal symptoms due to latex; it allows us to study both clinical symptoms and local immunological changes. MFNS pre-medication before an ASNCL may prevent some immunological responses induced by ASNCL without clinical allergic modifications.
A Prospective Study on Children with Initial Diagnosis of Transient Hypogammaglobulinemia of Infancy: Results from the Italian Primary Immunodeficiency Network
Authors: Moschese V. , Graziani S. , Avanzini M.A. , Carsetti R. , Marconi M. , La Rocca M. , Chini L. , Pignata C. , Soresina A.R. , Consolini R. , Bossi G. , Trizzino A. , Martino S. , Cardinale F. , Bertolini P. , Marseglia G.L. , Zecca M. , Di Cesare S. , Quinti I. , Rondelli R. , Pietrogrande M.C. , Rossi P. , Plebani A. ,   IPINET (ITALIAN PRIMARY IMMUNODEFICIENCIES NETWORK)
Published: January 2017

Transient hypogammaglobulinemia of infancy (THI) is a heterogenous disorder characterized by reduced serum IgG levels in early infancy. A putative diagnosis is initially made after exclusion of other causes of hypogammaglobulinemia while a definitive diagnosis of THI can only be made a posteriori in patients with normalization of IgG levels. The aim of this study is to characterize clinical and immunological features of children with an initial diagnosis of THI in correlation to natural outcome, and to assess predictive laboratory parameters of clinical evolution for this disorder. We prospectively analysed clinical and immunological characteristics of 77 THI children at initial diagnosis and of 57 patients at follow-up. Memory B cell subsets and in vitro immunoglobulin production were evaluated. Seventy patients (91%) showed clinical symptoms. Patients suffered from infections (91%), allergies (47%) and autoimmune disease (4%). During follow-up 41/57 children (72%) normalized IgG values, mostly within 24 months of age (p<0.001), allowing the diagnosis of THI. The 16 children who did not normalize their IgG levels showed a higher frequency of severe infections and autoimmune disease (p<0.01). Moreover, they expressed a reduced frequency of IgM and switched memory B cells (p<0.01) and an inability to produce IgG in vitro (p<0.02). We conclude that most patients with an initial diagnosis of THI spontaneously recover within 24 months of age and have a benign clinical course, while a subgroup of children with undefined hypogammaglobulinemia share a clinical and immunological profile with other primary immunodeficiencies. Early recognition of children with hypogammaglobulinemia during infancy who are likely to suffer from permanent immunodeficiencies later in life would allow prompt and appropriate laboratory and clinical interventions.
Impact of Extracellular HIV-Tat on the Regulation of EDF-1 Levels in Human Endothelial Cells
Authors: Mariotti M. , Bolognese F. , Ferrè S. , Leidi M. , Maier J.A.M.
Published: January 2017

EDF-1 has been isolated by RNA fingerprinting from human endothelial cells exposed to human immunodeficiency virus type 1 (HIV-) Tat, a viral protein known to function as a cytokine in the activation of endothelial cells. Here we provide the molecular evidence that the inhibition of EDF-1 mRNA is transcriptionally regulated in human endothelial cells. Indeed, HIV-Tat inhibits the luciferase activity of endothelial cells transiently transfected with a construct containing 2300 bp of EDF-1 promoter cloned upstream of a luciferase reporter system. The decrease of EDF-1 RNA, however, does not translate into any alteration at the protein level, even when the cells are exposed to MG132 (10 μM), a proteasome inhibitor. Analogously, no modulation of the total amounts of EDF-1 by HIV-Tat has been observed in the presence of pro-inflammatory cytokine interleukin 1β, which induces endothelial responsiveness to the in vitro effects of HIV-Tat. We have previously shown that EDF-1 is cytosolic and can be translocated to the nucleus upon activation of protein kinases A and C. In response to HIV-Tat, EDF-1 is mainly in the cytosol. Since cytosolic EDF-1 binds and sequesters calmodulin, an important regulator of endothelial nitric oxide synthase, these results might explain why we do not observe any induction of nitric oxide in endothelial cells exposed to HIV-Tat.
Long-Term Evaluation of Patients with Hydatidosis Treated with Albendazole and Praziquantel
Authors: Haralabidis S. , Diakou A. , Frydas S. , Papadopoulos E. , Mylonas A. , Patsias A. , Roilides E. , Giannoulis E.
Published: January 2017

Hydatidosis is a usually asymptomatic chronic disease. In most patients who undergo surgery, hydatidosis is not resolved due to high recurrence rate. However, long-term treatment with albendazole has been found to have a significant efficacy that has been further improved when albendazole is combined with praziquantel and fat-rich diet. In this study a retrospective evaluation of the outcome of hydatidosis in 70 patients, was performed. In group A, a combined chemotherapy of albendazole plus praziquantel was given after surgical removal of cysts. In group B chemotherapy alone was administered without surgery. Sera of all patients were assayed for IgG, IgM, IgA and IgE antibodies by ELISA. In addition, ultrasonography (US) and/or computerized tomography (CT) scans were performed every 3 months for 18 months, and then, each year until the end of follow-up. The difference between the two kinds of treatment used in the present study was found to be not significant, nor was the difference of the shrinkage and extended calcification of the HCs between the two groups. However, the difference of the shrinkage of the HCs of more than 80%, as well as the extended calcifications of the cysts between the two groups were found to be statistically significant. In all patients high levels of IgG and IgA were detected, while IgE in group A and/or IgM in group B were marginally detected above the background level throughout the study. Level of IgG was strongly fluctuated and significantly decreased at 11.7 years after the end of chemotherapy, or at 8.5 years after relapses in group A, while was dramatically decreased at 3.6 years after the termination of chemotherapy in group B. Relapses occurred in 11.4% of patients within the first six months after end of chemotherapy. After additional chemotherapy with albendazole for 3–6 months, all of them were considered cured at 8.5 years of follow up.
Antibodies as Predictors of Complex Autoimmune Diseases and Cancer
Authors: Vojdani A.
Published: January 2017

The pathologic role of autoantibodies in many autoimmune diseases is widely accepted. An enzyme immunoassay was used for measurement of antibodies against disease-specific antigens and etiologic agents for cross-reactive antigens associated with them. This antibody assay was applied to a panel of antigens for the detection of different neuroautoimmune diseases that included multiple sclerosis, motor peripheral neuropathies, multifocal motor neuropathy, amyotrophic lateral sclerosis and pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection. We studied women with pregnancies complicated by neural tube defect, neuroborreliosis, autism and patients with possible somatic hypermutation. Antibodies were also measured against antigens and etiologic agents associated with primary biliary cirrhosis and chronic obstructive pulmonary disease. And, finally, antibodies were measured against several tumor antigens or peptides which are expressed in prostatic, breast and colon tissues. This panel of different autoantibodies was applied to 290 patients with neuroautoimmune disorders, cancer, and possible somatic hypermutation. The levels of these antibodies against different tissue-specific antigens and etiologic agents associated with them were significantly elevated in patients versus controls. We hope that this novel 96 antigen-specific ELISA will be used in additional studies that will prove its clinical efficacy, not only for the early diagnosis of many neuroautoimmune, liver and lung autoimmune disorders, but also for prognosis and the implementation of preventive steps for many complex diseases.
C-Reactive Protein Changes in the Uncomplicated Course of Arthroscopic Anterior Cruciate Ligament Reconstruction
Authors: Calvisi V. , Lupparelli S.
Published: January 2017

The diagnosis of septic arthritis following arthroscopic anterior cruciate ligament (ACL) reconstruction is often elusive and can only be confirmed by joint aspiration, although arthrocentesis carries a risk for superinfection. C-reactive protein (CRP) may prove a useful laboratory test to substantiate clinical suspicion. The present study investigated the post-operative variations of CRP in 58 patients (age range 15–52, median age 25) undergoing ACL reconstruction with either bone-patellar tendon-bone (BPTB) or hamstring tendon (HT) who did not develop infection at 6 months follow-up. CRP titre was determined on the 1st, 3rd, 7th, 15th, and 30th post-operative day by immunoprecipitation in patients divided according to the type of autograft (BPTB: 13 patients; HT: 45 patients). Mean CRP significantly increased on the 1st post-operative day, peaked on the 3rd day and decreased on the 7th day, while levels on the 15th and 30th days did not differ from baseline. The trend of CRP changes did not differ in relation to the type of autograft. The results of our study suggest that close clinical surveillance may be advisable when CRP levels deviate from the reference values 2 weeks after surgery. In these circumstances, suspicion of septic arthritis warrants aspiration and culturing in order to avert a diagnostic delay.
Lack of Inflammatory Cells in the Oral Mucosa of Subjects Undergoing Sublingual Immunotherapy
Authors: Marcucci F. , Incorvaia C. , Sensi L. , Di Cara G. , Cadario G. , Cavaliere A. , Moingeon P. , Puccinelli P. , Di Gioacchino M. , Frati F.
Published: January 2017

The cells involved in allergic inflammation, such as mast cells, basophils, and eosinophils, have been thoroughly studied in the nose, the lungs and the skin, demonstrating an evident increase in response to the introduction of the specific allergen, while little is known in the mucosal system and particularly in the oral mucosa. We investigated such tissue by using the model of sublingual immunotherapy (SLIT), by which high doses of the specific allergen enter the mouth. Oral biopsies were carried out on seven subjects allergic to grass pollen and treated with SLIT by a grass extract. In biopsies carried out before SLIT there was a very low number of mast cells and eosinophils both in the epithelium and subepithelium layers, and insignificant changes were detected after SLIT. These findings show the lack of allergic inflammation in the oral mucosa upon contact with the specific allergen and confirm the role of the mouth as a tolerogenic site, which is conceivable considering the different attitude of the mouth, where the antigens transit to undergo digestion, in respect to the airways or the skin, where the antigen absorption is potentially dangerous.