bluuebunny/crossref_metadata_2025 huggingface dataset:
Do Thyroid Abnormalities Detected in Patients Treated for HCV-Related Chronic Hepatitis Persist?
Authors: Tarantino G. , Gagliardi G. , Conca P.
Published: January 2017

One hundred and twenty-one patients with HCV-related chronic hepatitis and normal baseline thyroid function were studied. Forty-six patients received IFN alpha-2b, while 75 patients had Peg-IFN alpha-2b with ribavirin more recently. Thirty patients (ten belonging to the standard IFN group) were re-treated. The pre-treatment prevalence of thyroid antibodies was 3.3%. At the end of the first antiviral treatment, the prevalence of laboratory alterations (presence of antibodies and abnormal hormonal levels) of thyroid was assessed to be 20.7% (25 patients), being quite similar for standard-interferon- and pegylated-interferon-treated patients (P = 0.63). TSH level alteration was seen in eleven patients (9.1% of the overall population and 44% of the antibodies positive patients), of whom ten were females. The anti-microsomal, anti-thyroperoxidase and anti-thyroglobulin antibodies, in combined or isolated presence, were detected in all 25 patients. During the re-treatment we noticed worsening only of previous thyroid abnormalities. No patient changed the antiviral schedule after the emerging of thyroid alterations. All eleven patients remained thyroid dysfunctional at the end of the follow-up (ten with Hashimoto's thyroiditis and one with Graves' disease), meanwhile the near totality of patients with presence of antibodies remained positive. Interestingly, eight out the 14 patients who showed mood disorders after antiviral therapy, belonged to the afore-mentioned cohort.
Impact of Porcine Orexin a on Glucagon Plasma Concentrations in Pigs
Authors: Papakonstantinou P. , Tziris N. , Kesisoglou I. , Gotzamani-Psarrakou A. , Tsonidis Chr. , Patsikas M.N. , Papazoglou L.G.
Published: January 2017

In 1998, Orexin A was added to the long list of orexigenic neuropeptides of the brain's physiology. Orexin A is involved in the central control of appetite and in energy homeostasis, as well as in the regulation of many other physiological functions. It is produced by a small cluster of the brain's neurons, located mainly in and around the lateral hypothalamic area. This site is known to be involved in regulating feeding in mammals. An intracerebroventricular injection of Orexin A into the rat's brain causes an impressive increase in the consumption of food, while an intravenous injection induces changes on glucagon plasma concentrations in rats. In addition, there are signs of changes on glucagon plasma concentrations when Orexin A acts on individual pancreatic islets of rats. In this study, we investigated the potential effects of the central administration of porcine Orexin A on glucagon plasma concentrations in pigs, and examined whether these changes are associated with the possible effect of the neuropeptide on the enteroinsular axis.
Involvement of cPLA2 Inhibition in Dexamethasone-Induced Thymocyte Apoptosis
Authors: Cinque B. , Fanini D. , Di Marzio L. , Palumbo P. , La Torre C. , Donato V. , Velardi E. , Bruscoli S. , Riccardi C. , Cifone M.G.
Published: January 2017

Various molecular mechanisms have been suggested to be involved in dexamethasone induced thymocyte apoptosis. In this study we show that pharmacological inhibition of cytoplasmic PLA2 in mouse thymocytes for 18 h with arachidonyl trifluoromethyl ketone (AACOCF3) (10 μM) and palmitoyl trifluoromethyl ketone (PACOCF3) (10 μM) induced a drastic increase of thymocyte apoptosis comparable to that observed following Dex (10−7 M) treatment, while inhibition of secretory PLA2 with p-bromophenacyl bromide (pBPB) (20 μM) did not. AACOCF3-induced thymocyte apoptosis, similarly to Dex-induced thymocyte apoptosis, was eliminated by cell pre-treatment with the PI-PLCβ inhibitor, U73122, but not by the PC-PLC inhibitor D609. These observations were corroborated by the ability of AACOCF3, like Dex, to induce a rapid and transient increase in DAG generation. In addition, AACOCF3-induced apoptosis involved the activation of the acidic sphingomyelinase (aSMase) but not of the neutral sphingomyelinase (nSMase), as evaluated by measurements of enzyme activity in cell extracts following thymocyte exposure to AACOCF3 and by the ability of monensin to inhibit AACOCF3-induced thymocyte apoptosis. In addition, the AACOCF3 apoptotic effect resulted in an early increase of ceramide levels. AACOCF3-induced thymocyte apoptosis involved the activation of caspase 3, and cell pre-treatment with a caspase 3 inhibitor prevented AACOCF3-induced apoptosis. These observations suggest that cPLA2 inhibition may have a role in Dex-induced thymocyte apoptosis and highlight the importance of cPLA2 activity in thymocyte survival.
Immunohistochemical Evaluation of Global DNA Methylation and Histone Acetylation in Papillary Urothelial Neoplasm of Low Malignant Potential
Authors: Barbisan F. , Mazzucchelli R. , Santinelli A. , Stramazzotti D. , Scarpelli M. , Lopez-Beltran A. , Cheng L. , Montironi R.
Published: January 2017

A preceding study has shown that karyometry detected subvisual differences in chromatin organization status between non-recurrent and recurrent papillary urothelial neoplasm of low malignant potential (PUNLMP). The status of chromatin organization depends on epigenetic events, such as DNA methylation and histone acetylation. The aim of this study is to explore global DNA methylation and global histone acetylation in non-recurrent and recurrent PUNLMP. 5-methylcytosine (5MeC) and acetylated histone H3 lysine 9 (AcH3K9) were investigated by immunohistochemistry (IHC) in 20 PUNLMP cases (10 non-recurrent and 10 recurrent), in 5 cases of normal urothelium (NU) and in 5 cases of muscle invasive pT2 urothelial carcinoma (UC). For global DNA methylation, the mean percentage of positive nuclei in the cells adjacent to the stroma increased from NU (79%) through non-recurrent and recurrent PUNLMP (86% and 93%, respectively) to UC (97%). The percentages of positive nuclei in the intermediate cell layers and in the superficial cells in the four groups were similar to those adjacent to the stroma. The proportion of nuclei with weak-to-moderate intensity was far greater than that of those strongly stained and increased steadily from NU to UC. For global histone acetylation, the mean percentage of positive nuclei was highest in non-recurrent PUNLMP (i.e. 90%) and lowest in recurrent PUNLMP (i.e. 81%). In NU and UC the mean percentages of positive nuclei were 84% and 86%, respectively. The percentage of positive nuclei decreased from the cell layer adjacent to the stroma to the superficial cell layer. The proportion of nuclei with weak-to-moderate intensity was slightly greater than that of those strongly stained. In comparison with global DNA methylation, the proportion of strongly stained nuclei was much higher. In conclusion, there are differences in global DNA methylation and histone acetylation patterns between non-recurrent and recurrent PUNLMP. Further studies are needed to elucidate the complex interplay between chromatin structure, its modifications and recurrence of PUNLMP.
Sucralfate Modulates uPAR and EGFR Expression in an Experimental Rat Model of Cervicitis
Authors: Mannari C. , Santi S. , Migliori M. , Filippi C. , Origlia N. , Sansò M. , Boldrini E. , Giovannini L.
Published: January 2017

Sucralfate is a drug used in the treatment of gastric and duodenal ulcer; it is cytoprotective and able to increase the bioavailability of several growth factors, modulating the wound healing process. In this study we tested the possible therapeutic effect of Sucralfate in the treatment of ulcerative lesion occurring in uterine cervix; to investigate such effect we used an experimental rat model of cervicitis in which the uPAR and EGFR expression were evaluated. Cervicitis was induced in wild and ovariectomized wistar female rats by an acetic acid-soaked tampon. The animals were divided into two main groups (4 and 7 days) and Sucralfate was administered topically until the day they were sacrificed. In order to distinguish physiological and drug-induced healing, quantitative and qualitative uPAR and EGFR expression were evaluated by using Western Blot and Immunohistochemistry techniques. Western Blot analysis demonstrated an increased expression of both receptors after 4 days from wounding in wild and ovariectomized animals. In particular in ovariectomized animals the expression of uPAR and EGFR increased after 4 days while it reduced following the administration of Sucralfate. In wild rats the same was observed for uPAR expression, while EGFR was different; in fact, its expression increased significantly at day 4 in the animals treated with the drug and only at day 7 in those untreated. Immunohistochemistry highlighted a noteworthy epithelial colocalization of EGFR and uPAR after 4 days in the animals treated with Sucralfate. We conclude that Sucralfate can promote the healing of ulcerative cervicitis and moreover, it reduces the normal healing time because of its modulatory property on uPAR and EGFR expression.
Sublingual Desensitization in Patients with Wasp Venom Allergy: Preliminary Results
Authors: Patriarca G. , Nucera E. , Roncallo C. , Aruanno A. , Lombardo C. , Decinti M. , Pascolini L. , Milani M. , Buonomo A. , Schiavino D.
Published: January 2017

The aim of this paper is to assess in an open prospective pilot case-control study the tolerability, safety and efficacy of an ultra-rush sublingual immunotherapy (SLIT) protocol with Vespula venom in wasp allergic patients compared to subcutaneous immunotherapy (SCIT). Forty-one wasp allergic patients were treated with sublingual (SLIT group) or subcutaneous (SCIT group) ultrarush immunotherapy with Vespula venom extract. All patients underwent skin tests and serum specific IgE and IgG4 detection before enrolment and after 6, 12 and 24 months of immunotherapy. The SLIT group consisted of 21 (6 females and 15 males) patients who received increasing doses of Vespula venom (Aquagen, ALK-Abelló) until the final dose of 30 drops of extract in 3 hours, containing 100,000 SQ-U/ml. The maintenance dose was of 10 drops of pure venom extract 3 times a week, for a total dose of 100,000 SQ-U weekly (corresponding to 100 μg of venom extract). The SCIT group consisted of 20 patients (16 males and 4 females) who were treated with subcutaneous ultrarush immunotherapy with Vespula venom extract (Pharmalgen, Alk-Abelló). Patients received 101.1 μg of Vespula venom in 3 hours and were treated with 100 μg of wasp venom monthly. During the ultrarush sublingual treatment 2 patients (9.5%) experienced mild side-effects. Specific IgE and specific IgG to wasp venom did not show any significant modification. Four patients were field-stung by a wasp during the treatment (for a total of 6 stings). Two patients (3 stings), with a previous clinical history of a grade III and IV reaction, did not experience any reaction. One patient, with a previous grade II reaction, showed a large local reaction. The fourth patient, with a previous grade III reaction, was re-stung twice (after 12 and 24 months) with two systemic reactions (SR) (mild throat constriction). During the ultrarush SCIT phase, 3 (15%) patients experienced side-effects: 2 of them showed a large local reaction and 1 had headache and stomach ache. Specific IgE showed a significant (P=0.001) increase after 6 months of treatment and then returned to baseline levels while specific IgG showed a significant (P=0.001) increase after 6, 12 and 24 months in comparison with baseline. Nine patients were field-stung during the treatment: 8 of them experienced large local reactions; one patient (11%) experienced an SR (dizziness). Our results, even if in a small number of patients, suggest that in patients with Hymenoptera sting allergy SLIT could be efficacious with a good tolerability profile when compared to SCIT. Larger studies are needed to assess efficacy, safety and tolerability profile of wasp venom SLIT.
Comparison of Thermal Infrared and Laser Doppler Imaging in the Assessment of Cutaneous Tissue Perfusion in Scleroderma Patients and Healthy Controls
Authors: Merla A. , Di Donato L. , Romani G.L. , Proietti M. , Salsano F.
Published: January 2017

In this study we propose a non-invasive method to calculate blood flow by means of thermal infrared imaging and bio-heat transfer modeling. The method is able to provide high time-resolution series of cutaneous blood flow images with the same spatial resolution of the thermal images. The method was tested against a standard laser Doppler imaging system, which to date is considered the gold standard for non-invasive assessment of cutaneous blood flow, on both healthy subjects and patients suffering from systemic sclerosis (SSc; a pathological condition with microvessel endothelium injury). Twenty healthy subjects and twenty SSc patients simultaneously underwent laser Doppler and thermal imaging of the dorsum of the hand. A linear correlation between perfusion values obtained with the two methods was found for the healthy control group (R = 0.85, Pearson Product Moment Correlation). A significant correlation was not observed for the SSc patient group. The results of this study suggest that combined laser Doppler, thermal imaging and bio-heat transfer modeling could effectively discriminate between healthy vs. impaired conditions of the cutaneous tissue thermal properties and cutaneous vasculature. Such method, in addition to providing a potential effective imaging-based tool for a variety of biomedical and clinical applications ranging from diagnostics to treatment follow-up, may help the understanding of the morphological and functional impairment secondary to the disease. The thermal imaging-based method provided faster and better time-resolved imaging of cutaneous perfusion than standard laser Doppler techniques as the thermal cameras can provide up to 100 complete 524×524 pixel images per second, thus allowing real time monitoring of tissue perfusion rates.
The Increase of Endothelial Progenitor Cells in the Peripheral Blood: A New Parameter for Detecting Onset and Severity of Sepsis
Authors: Becchi C. , Pillozzi S. , Fabbri L.P. , Al Malyan M. , Cacciapuoti C. , Della Bella C. , Nucera M. , Masselli M. , Boncinelli S. , Arcangeli A. , Amedei A.
Published: January 2017

Sepsis is a clinical syndrome characterized by non-specific inflammatory response with evidence of profound changes in the function and structure of endothelium. Recent evidence suggests that vascular maintenance, repair and angiogenesis are in part mediated by recruitment from bone marrow (BM) of endothelial progenitor cells (EPCs). In this study we were interested in whether EPCs are increasingly mobilized during sepsis and if this mobilization is associated with sepsis severity. Our flow cytometry data demonstrate that in the CD34+ cell gate the number of EPCs in the blood of patients with sepsis had a four-fold increase (45 ± 4.5% p<0.001) compared to healthy controls (12 ± 3.6%) and that this increase was already evident at 6 hours from diagnosis (40.6 ± 4.2%), reaching its maximum at 72 hours. Also the percentage of cEPCs identified in the patients with sepsis (35 ± 4.6% of the CD34+ cell) was statistically different (p<0.001) compared to that found in the blood of patients with severe sepsis (75 ± 4.9%). In addition, we proved that at six hours after sepsis diagnosis, VEGF, CXCL8 and CXCL12 serum levels were significantly higher in septic patients compared to healthy volunteers 559 ± 82.14 pg/ml vs 2.9 ± 0.6 (p<0.0001), 189.8 ± 67.3 pg/ml 15 vs 11.9 ± 1.6 (p=0.014) and 780.5 ± 106.5 pg/ml; vs 190.2 ± 71.4 (p < 0.001). Our data suggest that the cEPC evaluation in peripheral blood, even at early times of diagnosis, in patients with sepsis can be envisaged as a valuable parameter to confirm diagnosis and suggest further prognosis.
Blood Cholesterol Concentration Measured by CR3000: Fingerstick versus Venous Sampling
Authors: Sblendorio V. , Palmieri B. , Riccioni G.
Published: January 2017

Currently, the clinical practice of desktop or Point of Care (PoC) analyzers for lipid measurements has gained wide popularity. Designed to quickly perform measurements on microlitre (μL) quantities of blood, these instruments can be used in non-laboratory settings, such as physicians' offices or field-testing sites and can provide measurements in whole blood, serum, or plasma, using either venous or capillary blood samples. The aim of this study is to examine the relationship between cholesterol determinations in venous and capillary samples using the CR3000 PoC system. The study was performed on 21 unselected adult volunteers, and no exclusion criteria was adopted. The mean cholesterol concentration for the venous blood samples measured was 164 mg/dL. The values obtained in the capillary blood samples averaged 168 mg/dL, which is only slightly higher (e.g., 2.87%) than the venous sample measurements. Moreover, the total variance was statistically similar for venous and capillary measurements (F value=1.199, where the upper critical value of the F distribution is 2.124, p<0.05). The results of our study support the concept that CR3000 total cholesterol testing can be performed safely and accurately in either venous or capillary specimens.
Autism and Immunity: Revisited Study
Authors: Castellani M.L. , Conti C.M. , Kempuraj D.J. , Salini V. , Vecchiet J. , Tetè S. , Ciampoli C. , Conti F. , Cerulli G. , Caraffa A. , Antinolfi P. , Galzio R. , Shaik Y. , Theoharides T.C. , De Amicis D. , Perrella A. , Cuccurullo C. , Boscolo P. , Felaco M. , Doyle R. , Verrocchio C. , Fulcheri M.
Published: January 2017

Autism spectrum disorder is of interest neurochemically because it represents a relatively homogeneous disorder with regard to disease development, abnormal cognitive development and intellectual development disturbance. A consistent finding in autistic children is a high number of mast cells and a high level of serotonin which is also found at elevated concentrations in the urine of autistic patients. In addition, a dysfunction of clinical conditions, such as gastrointestinal and immunological symptoms, is frequently noted in autistic children, however, IgE does not appear to be prevalent in these children but probably an increase of cytokines/chemokines produced by mast cells at an early age may play an important role. Therefore an immune hypothesis, involving also autoimmunity, is one possible pathogenetic mechanism in autism. In conclusion, mast cell activation could contribute to immune and neuroinflammatory abnormalities that are evident in patients with autism spectrum disorders.
Role of Interleukin-15 Receptor α Polymorphisms in Normal Weight Obese Syndrome
Authors: Di Renzo L. , Gloria-Bottini F. , Saccucci P. , Bigioni M. , Abenavoli L. , Gasbarrini G. , De Lorenzo A.
Published: January 2017

Previous published studies have identified a class of women, Normal Weight Obese women (NWO) with normal BMI and high fat content. An important role of Interleukin-15 (IL-15) has been documented in facilitating muscle proliferation and promoting fat depletion. Indeed the presence of three types of IL-15 receptor subunits in fat tissue suggests a direct effect on adipose tissue. We studied three single nucleotide polymorphisms (SNP) of IL-15Rα receptor gene and investigated their relationship with NWO phenotype. We considered two classes of women according to their BMI and percent fat mass (%FAT), class 1: including 72 overweight-obese women (high BMI-high fat mass) and class 2: including 36 NWO (normal BMI, high fat mass). Three sites of Interleukin-15 receptor subunit α gene were examined, located respectively in exon4, exon5 intron-exon border and exon7. Genotyping of the identified polymorphisms was performed by restriction fragment length polymorphism. Haplotype frequency estimation was performed by using the Mendel-University of Chicago program. Odds ratio analyses were calculated by EPISTAT program. Highly significant differences were observed for exon 7-exon5 intron-exon border and exon 4-exon 7 haplotype distribution between class 1 and class 2 women. These results strongly support the hypothesis that genetic variability of the IL-15 receptor has an important role in body fat composition. Our data underscore previous findings that suggest a potential role of IL-15 cytokine in NWO syndrome.
Allelic Frequencies of 3' Ig Heavy Chain Locus Enhancer HS1,2-A Associated with Ig Levels in Patients with Schizophrenia
Authors: Frezza D. , Giambra V. , Mattioli C. , Piccoli K. , Massoud R. , Siracusano A. , Di Giannantonio M. , Birshtein B.K. , Rubino I.A.
Published: January 2017

Infectious and autoimmune pathogenic hypotheses of schizophrenia have been proposed, prompting searches for antibodies against viruses or brain structures, and for altered levels of immunoglobulins. Previous experiments have shown that allele frequencies of the Ig heavy chain 3' enhancer HS1,2*A are associated with several autoimmune diseases, suggesting a possible correlation between HS1,2 alleles and Ig production. To test this, we analyzed levels of serum Igs and HS1,2*A genotypes in two independent cohorts, one of 88 schizophrenic inpatients (24 women) and a second of 133 healthy subjects (59 women). Both groups were similar in the frequency of individuals with altered serum concentration of Ig classes and IgG subclasses (schizophrenia panel-80%; controls-68%). With the possible exception of a stabilizing effect of olanzapine, no psychopharmacological drug consumed during the month prior to serum sampling in the schizophrenia group significantly affected Ig levels. In both patient and control cohorts, an increased frequency of the HS1,2*2A allele corresponded to increased Ig plasma levels, while an increased frequency of the HS1,2*1A allele corresponded to decreased Ig plasma levels. EMSA analysis with nuclear extracts from human B cells showed that the transcription factor SP1 bound to the polymorphic region of both HS1,2*1A and HS1,2*2A while NF-κB bound only to the HS1,2*2A. We predict that differences in transcription factor binding sites in the two allelic variants of the 3' IgH enhancer HS1,2 may provide a mechanism by which differences in Ig expression are affected.
In Vitro Detection of Herpes Simplex Virus −1 and −2 Infection with Immunospecific GD3+-CL6-Enhanced Magnetic Resonance Imaging
Authors: Artini M. , Papa R. , Scoarughi G.L. , Catalano C. , Palamara A.T. , Passariello R. , Selan L.
Published: January 2017

Herpes simplex virus infections are prevalent viral infections in humans. HSVs are also the most common cause of sporadic viral encephalitis (HSE). Magnetic resonance is the imaging method of choice for HSE because it provides the most sensitive method for detecting early lesions. The objective of this study is to set-up and in vitro test an experimental contrast agent specific for antigens present on HSV-infected cells, bound with a paramagnetic agent detectable by MR imaging. A selected anti-HSV HrFab was labelled with Alexa Fluor 488, 125I and Gd3+Cl6. In order to assess anti-HSV affinity and specificity, ELISA assays were performed. Vero cells infected with HSV strains were visualized by MRI using anti-HSV HrFab/Gd3+Cl6complex. Results of the ELISA tests demonstrated that the anti-HSV HrFab labelled with Gd3+Cl6 showed similar affinity for the antigens while the 125I immunoconjugate showed reduced affinity. MRI confirmed high affinity and specificity of antibody for the detection of HSV infections.
Pidotimod: A Reappraisal
Authors: Riboldi P. , Gerosa M. , Meroni P.L.
Published: January 2017

Pidotimod (Polimod ®) is a synthetic dipeptide molecule with biological and immunological activity on both the adaptive and the innate immune responses. In vitro studies, both from animal and human specimens, have documented a good activity on innate and adaptive immune responses and have been confirmed by in vivo studies. These activities have been applied in clinical studies demonstrating the efficacy of pidotimod in reducing the rate of recurrent infections of the upper respiratory and urinary tracts in children. The same results were obtained in recurrent respiratory tract infections in adults. Interestingly, these effects are more evident in the setting of immune defects such as senescence, Down's syndrome, and cancer.
Herpesviruses and Periodontal Disease: A Cautionary Tale
Authors: Passariello C. , Palamara A. , Garaci E. , Pasquantonio G.
Published: January 2017

Periodontitis is an inflammatory disease of bacterial origin, characterized by an inconstant progression of lesions affecting the tooth supporting tissues. In spite of more than half a century of research efforts, the clinician still lacks any specific molecular or microbial diagnostic tool to predict the progression of periodontal lesions. Recently, several reports have proposed a role for some herpesviruses in the etiology of destructive phases of periodontitis. This paper critically analyzes these data in the light of consolidated knowledge that was developed in the characterization of virus-bacteria cooperative interactions, and proposes new topics of investigation to clarify the role of herpesviral infections in periodontitis and their potential predictive role as markers of progression.
Pulmonary Exposure to Soluble Cell Wall β(l, 3)-Glucan of Aspergillus Induces Proinflammatory Response in MICE
Authors: Inoue K. , Koike E. , Yanagisawa R. , Adachi Y. , Ishibashi K. , Ohno N. , Takano H.
Published: January 2017

Compared to the significant immunomodulation of cell wall component(s) of bacterium such as lipopolysaccharide ( E. Coli), that of pathogenic fungi has not been well elucidated, especially in vivo. Furthermore, although it has been implied that β-(1, 3)-glucan of fungi possesses various biological activities, the impacts of the component have not been properly clarified, possibly due to its insolubility in water and alkali solutions. Previously, we isolated a soluble type of β-(1, 3) -glucan from Aspergillus (referred to as ASBG). The present study investigated the effects of a single pulmonary exposure to ASBG on the immune (proinflammatory) responses in naïve mice. ASBG (12.5–100μg/animal) exposure induced neutrophilic lung inflammation with an enhanced local expression of proinflammatory cytokines such as interleukin (IL) −1β and chemokines such as macrophage inflammatory protein −1α, and keratinocyte-derived chemoattractant in a dose-dependent fashion with overall trends. On the other hand, ASBG at relatively lower doses significantly amplified the lung expression of IL-2, IL-6, and IL-12 as compared with vehicle. ASBG significantly induced pulmonary edema. Furthermore, ASBG augmented the nuclear translocation of nuclear factor (NF)-κB and its binding capacity to the promoter site of DNA in the lung homogenate. These results suggest that pulmonary exposure to ASBG confers lung inflammation, at least partly, via the enhanced local expression of proinflammatory cytokines, likely through NF-κB-dependent pathway.
The Safety of Anti-TNF Agents in the Elderly
Authors: Migliore A. , Bizzi E. , Laganà B. , Altomonte L. , Zaccari G. , Granata M. , Canzoni M. , Marasini B. , Massarotti M. , Massafra U. , Ranieri M. , Pilla R. , Martin L.S. , Pezza M. , Vacca F. , Galluccio A.
Published: January 2017

Rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis are commonly thought of as inflammatory diseases that affect younger individuals. Although the initial presentation of these diseases is common in a patient's twenties or thirties, they usually persist for the duration of the patient's life. In addition, up to one-third of patients with RA have disease onset after 60 years of age. Anti-TNF-a therapies now have well-recognized safety profiles that have been demonstrated in the usual clinical trial populations for these diseases, but such populations under-represent patients > or =65 years of age. This retrospective study aims to determine the safety profiles for etanercept, infliximab and adalimumab in patients of 65 years or more, undergoing anti-TNF treatment for an active inflammatory disease such as rheumatoid arthritis, ankylosing spondylitis or psoriatic arthritis, or skin disease like psoriasis. Our data show that admitting elderly patients into anti-TNF therapeutic regimens is a safe option and that it grants these patients access to the best current therapeutic option, possibly leading to better disease outcome. Quality of life in elderly patients affected by arthritis or psoriasis, often reduced by comorbidities, is as important as quality of life in younger patients. Applying the recommended screening before using biological treatment helps to reduce adverse events related to the therapy, and the application of the same screening in elderly patients seems to lead to comparable results.
Amyloid β Peptides Trigger CD47-Dependent Mast Cell Secretory and Phagocytic Responses
Authors: Niederhoffer N. , Levy R. , Sick E. , Andre P. , Coupin G. , Lombard Y. , Gies J.-P.
Published: January 2017

Mast cells are found in the brain, where they contribute to immune responses. They have been implicated in multiple sclerosis, but their potential role in Alzheimer's disease (AD), another inflammatory disease of the central nervous system, remains elusive. In the present study, we examined mast cell responses to amyloid β (Aβ) peptides 1-40 and 1-42, the major components of the Alzheimer amyloid plaques. Rat peritoneal mast cells were used as experimental model for human brain serosal mast cells. Fibrillar Aβ1-40 and Aβ1-42 peptides induced concentration-dependent exocytosis, as assessed by measurement of histamine secretion; exocytosis was reduced by pre-treatment with pertussis toxin and with antibodies against the CD47 receptor and the β1-integrin subunit. Fibrillar Aβ1-40 and Aβ1-42 peptides coated on heat-inactivated yeast particles and soluble fibrillar Aβ1-40 and Aβ1-42 peptides were also recognized and phagocyted by mast cells. Uptake of the peptides was decreased in the presence of 4N1, a peptide agonist of the CD47 receptor, but remained unchanged in the presence of 4NGG, a peptide derived from 4N1 which does not bind to CD47. Non-fibrillar forms of Aβ1-40 and 1-42 peptides were unable to elicit mast cell responses. These results show that fibrillar Aβ peptides can trigger mast cells and elicit exocytosis and phagocytosis. The Aβ-induced activation of mast cells operates through a CD47/β1-integrm membrane complex coupled with Gi.-protein. The present data support the hypothesis that mast cells, similarly to microglial cells, could play a major role in AD pathogenesis.
Apicidin, the Histone Deacetylase Inhibitor, Suppresses TH1 Polarization of Murine Bone Marrow-Derived Dendritic Cells
Authors: Jung I.D. , Lee J.S. , Jeong Y-I. , Lee C-M. , Chang J.H. , Jeong S.K. , Chun S.H. , Park W.S. , Han J. , Shin Y.K. , Park Y-M.
Published: January 2017

Apicidin is a fungal metabolite shown to exhibit anti-proliferative, anti-invasive, and anti-inflammatory properties by the inhibition of histone deacetylase (HDAC). However, the effects of apicidin on the maturation and immunostimulatory function of dendritic cells (DCs) remain unknown. In this study, we investigated whether apicidin modulates surface molecule expression, cytokine production, endocytosis capacity, and underlying signaling pathways in murine bone marrow-derived DCs. We observed that apicidin significantly attenuated surface molecule expression in LPS-stimulated DCs, suppressed production of interleukin (IL)-12 and proinflammatory cytokines (IL-6 and TNF-α) by DCs, and reduced IFN-γ production by T cells. The apicidin-treated DCs were found to be highly efficient in antigen capture via mannose receptor-mediated endocytosis. Apicidin also inhibited LPS-induced MAPK activation and NF-κB nuclear translocation in DCs. Moreover, the apicidin-treated DCs were incapable of inducing Th1 responses and normal cell-mediated immune responses. These novel findings not only provide new insights into the immunopharmacological role of apicidin in terms of its effects on DCs, but also broaden current perspectives of the immunopharmacological functions of apicidin, and have implications for the development of therapeutic adjuvants for the treatment of DC-related acute and chronic diseases.
High Serum Tryptase Value in Massive Acute Myocardial Infarction with Ventricular Arrhythmia Exortion in a Cocaine Abuser
Authors: Caroselli C. , Perfetti P. , Bruno G.
Published: January 2017

A 38-year-old cocaine abuser was admitted to the Emergency Department with a one hour history of precordial chest pain associated with shortness of breath and extreme discomfort. On admission his blood pressure was 90/60 mmHg, the resting 12-lead ECG showed ventricular tachycardia at about 300 beats per minute, and oxygen saturation was 86% in room air. After electrical cardioversion, the 12-lead ECG revealed sinusal rhythm and a significative ST segment elevation in leads I, aVL and V1-V6, that was about 0.5 mV in leads I and aVL and more than 1 mV in leads V2, V3 and V4. Laboratory determinations showed elevated creatine-chinase MB (CK-MB) and troponin I. An emergency coronary angiogram was normal. Cocaine use is a major cause of acute myocardial infarction in patients with normal epicardial coronary arteries but the exact mechanism still remains unclear. We hypothesize a non-IgE mediated mast-cell activation, with a direct action played by cocaine, and consequent massive expression of several factors effecting the microcirculatory system, including pro-inflammatory cytokines and chemokines. Our hypothesis is supported by an elevated serum tryptase levels in the patient.
Safety and Efficacy of Etanercept in Children with Juvenile-Onset Behcet's Disease
Authors: Cantarini L. , Tinazzi I. , Caramaschi P. , Bellisai F. , Brogna A. , Galeazzi M.
Published: January 2017

Behçet's disease (BD) is a chronic, relapsing, multi-system inflammatory disorder, clinically characterized by recurrent oral and genital ulcers, skin lesions, and uveitis. Other manifestations include arthritis, a positive pathergy test, thrombophlebitis, central nervous system disease and gastrointestinal ulcerations. The majority of affected individuals do not have life-threatening disease, although mortality can be associated with vascular-thrombotic and neurological manifestations. Currently, treatment of BD is symptomatic and empirical, and is tailored according to the severity of clinical features. In the past few years, isolated reports and case-series have been published on adult BD patients suggesting that inhibition of TNF-α is a promising therapeutic approach for severe ocular and various extra-ocular manifestations, including central nervous system involvement. In this study we present our promising experience with Etanercept therapy in juvenile-onset BD patients, characterized by refractory multi-organ involvement.
Impairment in Cytotoxicity and Expression of NK Cell- Activating Receptors on Human NK Cells following Exposure to Asbestos Fibers
Authors: Nishimura Y. , Miura Y. , Maeda M. , Kumagai N. , Murakami S. , Hayashi H. , Fukuoka K. , Nakano T. , Otsuki T.
Published: January 2017

Asbestos is well-known for its tumorigenic activity, but its effect on anti-tumor immunity remains unclear. Therefore, we prepared a sub-line of YT-A1 human NK cells exposed to chrysotile B (CB) asbestos (YT-CB5) as an in vitro model to analyze the effect of asbestos exposure on NK cells, and examined cytotoxicity and expressions of its related molecules. The cytotoxicity of YT-CB5 against K562 cells decreased compared with the original line of YT-A1 (YT-Org). YT-CB5 exhibited significant decreases in expressions of cell surface NKG2D, 2B4 and intracellular granzyme A. YT-CB5 also exhibited a decrease in the 2B4-dependent cytotoxicity. In addition, the degranulations stimulated via cell surface NKG2D and 2B4 also decreased in YT-CB5. Therefore, peripheral blood NK cells in patients with malignant mesothelioma (MM) were examined and compared with healthy volunteers. NK cells in patients with MM also showed decreases in cytotoxicity against K562. Although the expressions of NKG2D and 2B4 did not decrease in NK cells of MM patients, the expression of cell surface NKp46 decreased. To confirm the effect of asbestos exposure on peripheral blood NK cells, PBMCs were cultured under exposure to CB. NK cells in PBMCs exposed to CB in vitro showed a significant decrease in the expression of NKp46, whereas NK cells in PBMCs exposed to glass wool did not show such a decrease. These results indicate that exposure to asbestos has the potential to impair the cytotoxicity of NK cells and alter the expression of NK cell-activating receptors including NKG2D, 2B4 and NKp46 and intracellular perforin/granzymes.
Perioperative Allergy: Uncommon Agents
Authors: Caimmi S. , Caimmi D. , Cardinale F. , Indinnimeo L. , Crisafulli G. , Peroni D.G. , Marseglia G.L.
Published: January 2017

Anesthesia may often be considered as a high-risk procedure and anaphylaxis remains a major cause of concern for anesthetists who routinely administer many potentially allergenic agents. Neuromuscular blocking agents, latex and antibiotics are the substances involved in most of the reported reactions. Besides these three agents, a wide variety of substances may cause an anaphylactic reaction during anesthesia. Basically all the administered drugs or substances may be potential causes of anaphylaxis. Among them, those reported the most in literature include hypnotics, opioids, local anesthetics, colloids, dye, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), Iodinated Contrast Media (ICM), antiseptics, aprotinin, ethylene oxyde and formaldehyde, and protamine and heparins. No premedication can effectively prevent an allergic reaction and a systematic preoperative screening is not justified for all patients; nevertheless, an allergy specialist should evaluate those patients with a history of anesthesia-related allergy. Patients must be fully informed of investigation results, and advised to provide a detailed report prior to future anesthesia.
Perioperative Allergy: Clinical Manifestations
Authors: Peroni D.G. , Sansotta N. , Bernardini R. , Cardinale F. , Paravati F. , Franceschini F. , Boner A.L.
Published: January 2017

Adverse drug reactions or side effects are usually expected, dose dependent, and occur at therapeutic doses. Anaphylactic and anaphylactoid reactions are unexpected and dose independent and can occur at the first exposure to drugs used during anesthesia. Perioperative anaphylaxis is a severe and rapid clinical condition that can be lethal even in previously healthy patients. The initial diagnosis of anaphylaxis is presumptive. A precise identification of the drug responsible for the adverse reaction is more difficult to establish in the case of anaphylactoid reaction because the adverse reaction could result from additive side effects of different drugs injected simultaneously. The timing of the reaction in relation to events, e.g. induction, start of surgery, administration of other drugs, i.v. fluids, is essential for the diagnosis. Generally, reactions are predominant in the induction and recovery phases, and manifested mainly as cutaneous symptoms. Reactions to drugs coincide with the phases when they are administered. Reactions to antibiotics are more frequent in the induction phase, to neuromuscular agents in the initiation and maintenance phases and to non-steroidal anti-inflammatory agents in the recovery phase. The differential diagnosis of any adverse reaction during or following anesthesia should include the possibility of anaphylaxis.
Tendinopathy and Inflammation: Some Truths
Authors: Del Buono A. , Battery L. , Denaro V. , Maccauro G. , Maffulli N.
Published: January 2017

Overuse tendinopathies are a common cause of pain and disability in athletes. According to histological findings, it is a “failed healing response” to overuse tendon injury. In obesity, macrophages and mast cells migrate to adipose tissue, and the resulting decreased availability of immune circulating cells should be responsible for less effective immune responses to acute tendon injury. In diabetic patients, free glucose molecules attach to collagen, alter collagen solubility, increase resistance to enzymatic degradation, and impair cross linking, contributing to the subsequent development of chronic tendinopathy secondary to a failed healing response to a tendon insult. Prolonged systemic, low-grade inflammation and impaired insulin sensitivity act as a risk factor for a “failed healing response” after an acute tendon insult, and predispose to the development of chronic overuse tendinopathies. Further studies may reveal novel therapeutic treatment approaches.
Bone Grafts and Bone Graft Substitutes in Prosthetic Hip Surgery Replacement
Authors: Vanni D. , Pantalone A. , Colucci C. , Andreoli E. , Salini V.
Published: January 2017

The need for bone grafting procedures to replace skeletal defects has become more considerable because of increased opportunities to save major bone loss. We report our experience and a critical analysis about the role of bone grafts and bone graft substitutes in prosthetic hip surgery replacement.
Platelet Rich Plasma and Tendinopathy: State of the Art
Authors: Del Buono A. , Papalia R. , Denaro V. , Maccauro G. , Maffulli N.
Published: January 2017

Platelet-rich plasma (PRP) is increasingly used in the management of tendon injury in sports, supposedly accelerating the process of healing, tissue regeneration, and return to play. However, the scientific clinical evidence to support its use is scanty, and more level I studies need to be performed to justify its widespread use.
Bone Integration of New “Stemless” Hip Implants (Proxima Vs. Nanos). A DXA Study: Preliminary Results
Authors: Logroscino G. , Ciriello V. , D'Antonio E. , De Tullio V. , Piciocco P. , Lombi G. Magliocchetti , Santori F.S. , Albanese C.V.
Published: January 2017

The development of short femoral prostheses has the advantage to preserve bone and soft tissues, restore hip geometry, permit mini-invasive techniques and allow quickly return to an active life, but very few studies described bone reaction to these new designed prostheses. The aim of the present study was to evaluate the osseointegration of two different partial neck retained stemless hip prosthesis at one year after surgery, measured by the changes of periprosthetic bone mineral density (BMD) in 5 regions of interest (ROIs) using a dual-energy X ray absorptiometry (DXA) device. The signs of stress-shielding were evaluated by standard radiographs. Thirty-two uncemented primary total hip arthroplasty (THA) patients allocated into 2 groups were evaluated. In the first group (n=19) a Proxima (De-Puy-J&J) hip stem was implanted. In the second group (n=12) a Nanos (Smith & Nephew) hip stem was used. We found that both the implants preserve metaphyseal bone stock and increase periprosthetic BMD. In Nanos prostheses a significant higher BMD values were observed in region of interest (ROI) 3 and 4 (p<0.05). No differences were found in ROIs 1, 2, and 5. Proxima stem seem to produce a physiological strain distribution in the femur. No signs of stress-shielding were present in both the implants. In conclusion, this preliminary DXA analysis showed a physiological integration of both the stems that reproduces the biomechanical stress of proximal femur. New designed short stem implants showed optimal osseointegration after one year, and therefore appears an excellent alternative to traditional long stem hip prostheses.
Trabecular Metal Cup without Augments for Acetabular Revision in Case of Extensive Bone Loss and Low Bone-Prosthesis Contact
Authors: Pierannunzii L. , Mambretti A. , d'Imporzano M.
Published: January 2017

Current evidences in revision hip arthroplasty suggest to treat severe acetabular bone loss with dedicated implants, such as anti-protrusio cages, stemmed cups, modular systems supplied with iliac flanges and obturatory hook. However recent literature is reporting satisfactory outcomes with simple elliptical Trabecular Metal cups. Purpose of the study was to evaluate mid-term results of such a surgical procedure. All hip revisions performed from 2008 to 2009 with implantation of a TMT multi-hole acetabular cup without augmentations were retrospectively reviewed. The cases with low-degree acetabular bone loss (stage I and II according to GIR classification), with surgical report poorly describing the bone defect, with inadequate pre- and post-operative x-rays were ruled out. Twenty-five cases were identified, but four were lost to follow-up. The twenty-one patients were 71 year-old on average (from 60 to 82), with stage IV bone loss in 6 cases and stage III bone loss in 15 cases. Mean interval from surgery to evaluation was 20.9 months (from 13 to 30). The evaluation included bone-prosthesis contact estimation, component position, survivorship, complications, final Harris Hip Score, presence of periprosthetic radiolucencies. Host bone-prosthesis contact was estimated to be about 35%. Only three implant were subsequently reoperated (for infection, early migration, recurrent dislocation). The HHS among non-reoperated 18 patients was 81.96 on average (from 63.44 to 95.82). Six cases showed thin radiolucencies in one of the three Charnley zones, while three cases showed radiolucencies in two. None of these images was evolutive, thus they were not considered signs of loosening. The mid-term results of this series confirm the hypothesis that a porous tantalum acetabular cup is an effective option to deal with difficult acetabular revisions. Although no extra-acetabular fixation device is available, the very high surface friction guaranteed by the material and the supplemental stability provided by trans-acetabular screws seem to be sufficient to allow satisfactory reimplantation even in severely damaged pelves.
Bioplasty for Vertebral Fractures: Preliminary Results of a Pre-Clinical Study on Goats Using Autologous Modified Skin Fibroblasts
Authors: Pola E. , Nasto L. A. , Tampieri A. , Lattanzi W. , Di Giacomo G. , Colangelo D. , Ciriello V. , Pagano E. , Spinelli S. , Robbins P. D. , Logroscino G.
Published: January 2017

The debate is still ongoing about the long term effects of the mininvasive vertebral augmentation techniques and their usefulness in treating more complex cases where a bone inducing effect more than a merely bone substitution would be suitable, such as the vertebral fractures in young patients. We previously developed a clinically relevant gene therapy approach using modified dermal fibroblasts for inducing bone healing and bone formation in different animal models. The aim of this study is to show the feasibility of a minimally invasive percutaneous intrasomatic ex vivo gene therapy approach to treat thoracolumbar vertebral fractures and anterior column bone defects in a goat model.
IL-37 (IL-1F7) the Newest Anti-Inflammatory Cytokine Which Suppresses Immune Responses and Inflammation
Authors: Tetè S. , Tripodi D. , Rosati M. , Conti F. , Maccauro G. , Saggini A. , Cianchetti E. , Caraffa A. , Antinolfi P. , Toniato E. , Castellani M.L. , Conti P. , Theoharides T.C.
Published: January 2017

Cytokines such as interleukins, chemokines and interferons are immunomodulating and inflammatory agents, characterized by considerable redundancy, in that many cytokines appear to share similar functions. Virtually all nucleated cells, but especially epithelial cells and macrophages, are potent producers of cytokines. The objective of this study is to review the detailed mechanism of action and the biological profiles of IL-37, the newest anti-inflammatory cytokine. This review focuses on IL-37, a key cytokine in regulating inflammatory responses, mainly by inhibiting the expression, production and function of proinflammatory cytokines: IL-1 family pro-inflammatory effects are markedly suppressed by IL-37.