bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementation with Essential Amino Acids in Middle Age Maintains the Health of Rat Kidney
Authors: Corsetti G. , Stacchiotti A. , D'Antona G. , Nisoli E. , Dioguardi F.S. , Rezzani R.
Published: January 2017

Chronic kidney diseases are a social and economic problem, and diet has long been recognized as a fundamental modulator of kidney health in human and experimental models. Age-dependent alterations in mitochondrial function play a crucial role in the development of diseases of aging, and mitochondrial disorders have been observed in experimental models of kidney failure. Recently, the beneficial dietary effect of a specific mixture of essential amino acids (EAA) has been studied in elderly subjects, but no data were collected from the kidney. The aim of this study was to assess whether daily supplementation of the diet with EAA at the beginning of senescence could preserve renal health. We used middle-aged (18-month-old) male Wistar rats fed a standard diet and water ad libitum (M-aged group) or a diet with added EAA (1.5 g/kg per day) dissolved in drinking water for 3 months (M-aged+EAA group). Young (2-month-old) rats fed a standard diet for 3 months were used as controls. Mitochondrial morphology and markers for collagen, cyt-c-oxidase, HSP60, GRP75, eNOS, iNOS, Bax, Bcl2 and VEGF were analyzed in glomeruli and tubules. EAA supplementation limited fibrosis and increased the capillary tuft area in the glomeruli of M-aged rats. VEGF and eNOS were enhanced in glomeruli and the peritubular space with the EAA-supplemented diet. Mitochondrial cyt-c oxidase, Bcl2, and chaperones increased in the distal tubules of the EAA group to levels similar to those observed in the young group. Mitochondrial area and density after EAA intake did not differ from young groups. The results suggest that prolonged EAA intake could represent a strategy for maintaining the healthy status of the kidney in M-aged animals.
Sublingual Allergoid Immunotherapy: A New 4-Day Induction Phase in Patients Allergic to House Dust Mites
Authors: D'Anneo R.W. , Bruno M.E. , Falagiani P.
Published: January 2017

Sublingual immunotherapy with monomeric allergoid (allergoid SLIT), given according to the standard scheme, has proved effective and safe in many clinical trials. However, its build-up phase requires a long time ranging from 16 days to 14 weeks. This study therefore investigated whether, with a four-day up-dosing, the same benefit could be achieved in a shorter time. Thirty rhinitic and/or asthmatic patients (16 M and 14 F, mean age 36±8.2 years) allergic to house dust mites (HDM) with or without other sensitizations were randomized to allergoid SLIT or standard drug therapy. The build-up phase lasted four days. The first day the patients took a 300 AU tablet, the second day two 300 AU tablets, the third day three 300 AU tablets and the fourth day four 300 AU tablets. The total amount taken during the up-dosing was 3000 AU. Patients were then treated for 12 months at the dosage of 2000 AU/week (total amount of allergen: 104,000 AU/year). The symptom score and drug consumption were recorded from November to February on monthly diary cards. At baseline and after 12 months a Visual Analogue Scale (VAS) was used to rate the patients' well-being. Skin prick test reactivity was evaluated before and after the 12-month treatment in both groups using 10 mg/mL histamine as reference. VAS scores rose significantly (about 45%) in both groups in comparison to baseline (p=0.001). In addition, there was a significantly greater reduction of the global symptoms score (about 52%) - but not in drug consumption - in the SLIT group in comparison to controls (p=0.0004). The SLIT group showed a highly significant reduction (about 39%) in skin prick test reactivity (p=0.000003) while the control group remained unchanged (p=0.5226). No severe adverse events were observed. Even with this short four-day up-dosing, the allergoid SLIT proves to be safe. In addition, it is already effective in patients allergic to HDM after 12 months, and significantly reduces allergen-specific skin reactivity.
Examination of Periodontal Pathogens in Stenotic Valve Specimens and in Whole Blood Samples in Patients Affected by Aortic Valve Stenosis and Chronic Periodontitis
Authors: Raffaelli L. , Santangelo R. , Falchetti P. , Galluccio F. , Luciani N. , Anselmi A. , Nowzari H. , Verdugo F. , Fadda G. , D'Addona A.
Published: January 2017

Periodontitis may be a risk factor for atherosclerosis and coronary heart disease. The influence of periodontal pathogens in cardiovascular diseases needs further investigation. Therefore, the aims of this clinical study are: to test the presence of periodontal bacteria DNA in aortic valves and to assess the concomitant presence of the same periodontal bacteria DNA in whole blood samples in patients affected by aortic valve stenosis and chronic periodontitis. Nineteen consecutive patients (12 males and 7 females, age: 49–85 years) were enrolled in this study after having been subjected to a complete periodontal evaluation to confirm the diagnosis of chronic periodontitis. All patients were scheduled for aortic valve replacement surgery. After clinical and microbial periodontal examination, the aortic valve tissue specimens were obtained by excision during valve replacement surgery and the patients were subjected to the whole blood sampling before the surgery. The polymerase chain reaction technology was used to detect the putative periodontal pathogens Tannerella forshytia, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Fusobacterium nucleatum, Campylobacter rectus, Eikenella corrodens and Treponema denticola. Neither the 19 aortic valve specimens nor the blood samples were positive for the genoma of the selected periodontal pathogens. The selected periodontal pathogens did not colonize the aortic valve of patients affected by stenosis and bacterial genoma was not present in whole blood samples. A high blood pressure at the aortic valve may prevent the adhesion and proliferation of bacterial colonies.
Effectiveness of a Propolis and Zinc Solution in Preventing Acute Otitis Media in Children with a History of Recurrent Acute Otitis Media
Authors: Marchisio P. , Esposito S. , Bianchini S. , Desantis C. , Galeone C. , Nazzari E. , Pignataro L. , Principi N.
Published: January 2017

Recurrent acute otitis media (rAOM) is frequently encountered in infants and children and the lack of any definitive treatment has led parents and physicians to try complementary and alternative therapies. We evaluated the efficacy of a propolis and zinc suspension in preventing AOM in 122 children aged 1–5 years with a documented history of rAOM, who were prospectively, blindly, randomized 1:1 to receive the suspension plus elimination of environmental risk factors or elimination of environmental risk factors only. AOM- and respiratory-related morbidity were assessed at study entry and every four weeks. In the 3-month treatment period AOM was diagnosed in 31 (50.8%) children given the propolis and zinc suspension and in 43 (70.5%) controls (p=0.04). The mean number of episodes of AOM per child/month was 0.23 ± 0.26 in the propolis and zinc group and 0.34 ± 0.29 in controls (reduction 32.0%, p=0.03). The administration of a propolis and zinc suspension to children with a history of rAOM can significantly reduce the risk of new AOM episodes and AOM-related antibiotic courses, with no problem of safety or tolerability, and with a very good degree of parental satisfaction. No effect can be expected on respiratory infections other than AOM.
Lactoferrin Efficacy versus Ferrous Sulfate in Curing Iron Disorders in Pregnant and Non-Pregnant Women
Authors: Paesano R. , Berlutti F. , Pietropaoli M. , Goolsbee W. , Pacifici E. , Valenti P.
Published: January 2017

Iron homeostasis in pregnancy compensates for increased iron requirements and in women of child-bearing age for iron loss in menses. Oral administration of ferrous sulfate, prescribed to cure iron deficiency (ID) and ID anemia (IDA), often fails to increase hematological parameters and causes adverse effects. Recently, we demonstrated safety and efficacy of bovine lactoferrin (bLf) in pregnant women suffering from ID/IDA. Two clinical trials were conducted on pregnant and non-pregnant women of child-bearing age suffering from ID/IDA. In both trials, women received oral administration of bLf 100 mg/twice/day (Arm A), or ferrous sulfate 520 mg/day (Arm B). Hematological parameters, serum IL-6 and prohepcidin were assayed before and after therapy. Unlike ferrous sulfate, bLf increased hematological parameters ( P<0.0001). In pregnant women, bLf decreased serum IL-6 ( P<0.0001), and increased prohepcidin ( P=0.0007). In non-pregnant women bLf did not change the low IL-6 levels while it increased prohepcidin ( P<0.0001). Ferrous sulfate increased IL-6 ( P<0.0001) and decreased prohepcidin ( P=0.093). bLf established iron homeostasis by modulating serum IL-6 and prohepcidin synthesis, whereas ferrous sulfate increased IL-6 and failed to increase hematological parameters and prohepcidin. bLf is a more effective and safer alternative than ferrous sulfate for treating ID and IDA.
Clinical Experience with Spiramycin in Bisphosphonate-Associated Osteonecrosis of the Jaw
Authors: Gasparini G. , Saponaro G. , Di Nardo F. , Moro A. , Boniello R. , Cervelli D. , Marianetti T.M. , Palazzoni G. , Pelo S.
Published: January 2017

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) consists of an exposure of the jaw bone that persists for over 8 weeks in patients with positive history for bisphosphonates. Symptomatology is characterized by dull and ceaseless pain, and in advanced stages, the exposure of necrotic bone is evident, which is frequently associated with purulent secretions and faetor oris. Despite many different studies on BRONJ, there are no general guidelines to treat this disease. In this work, the authors present their experience in BRONJ conservative therapy with spiramycin by comparing the results achieved with amoxicillin and clavulanic acid. From January 1, 2008 to June 30, 2008, our department received 25 patients who were affected by osteonecrosis secondary to bisphosphonates. Thirteen had taken bisphosphonates for osteoporosis and 12 for malignancies. We divided the 25 patients into two groups: those who had not received any treatment and those who had received treatment. The first group of 13 patients had been treated only with spiramycin (S). The results from this group were only evaluated to test the efficacy of spiramycin and were not considered in the study. The second group of 12 patients had not undergone any previous treatment. This group was further divided in two groups of 6 patients each; one group was treated with spiramycin and the other with amoxicillin and clavulanic acid (ACA). The following criteria were used to evaluate the results of the study: pain, sensibility deficits, purulent secretion and bone exposure. All group results were evaluated according to the criteria chosen, and positive results were achieved in both groups S and ACA, such as reduction or disappearance of pain, sensibility deficits and purulent secretion and healing of bone exposition, although spiramycin showed itself to be more effective than the combination of amoxicillin and clavulanic acid. Spiramycin is a macrolide antibiotic with a wide spectrum of activity against Streptococci, Pneumococci, Diplococci, Gonococci and Staphylococci, which are typical in BRONJ. No resistance was indicated. Administration of the antibiotics can be intravenous, intramuscular, rectal or oral, which remains the most frequently used since spiramycin elimination also occurs with saliva and the antibiotic reaches high concentrations in the oral cavity where BRONJ is situated. Good compliance to the spiramycin regimen was observed in all three groups, with a general improvement in all of the parameters considered. In only two cases did patients have to undergo surgical curettage. The results showed that spiramycin can be a first choice drug in the treatment of BRONJ, and it should be strongly considered for patients where previous antibiotic therapy did not prove to be effective.
Functional Infrared Imaging of Paroxysmal Ischemic Events in Patients with Raynaud's Phenomenon
Authors: Grossi G. , Mariotti A. , Di Donato L. , Amerio P. , Tulli A. , Romani G.L. , Merla A.
Published: January 2017

The use of thermal infrared (IR) imaging together with the study of the thermal recovery from a controlled cold challenge has been proposed in the diagnosis and follow-up of therapeutic response of Raynaud's Phenomenon (RP) and Systemic Sclerosis (SSc). The controlled cold challenge test usually performed during IR investigations may induce a RP in patients with the latter condition. In our Institution we routinely perform capillaroscopy and thermal IR to follow-up SSc patients. In this paper, we describe the thermal recovery patterns shown by two SSc patients (a 40 year-old male with diffuse variant of SSc and a 71 year-old female with a limited variant of SSc) who presented ischemic and paroxysmal RP attack while recovering from the routine controlled cold challenge test. During RP attack, the cutaneous temperature of some fingers continued to decrease for some minutes even after the cessation of the cold stress. To the best of our knowledge, to date, no literature report has documented the thermal behaviour of SSc patients' fingers which occasionally present ischemic and paroxysmal response. Triggering of ischemic RP attack appears to not rely only on morphological and structural finger impairment, but also upon other aspects, like the emotional attitude of the subject and the possible discomfort experienced with the proceeding of the functional cold stress test.
Successful Treatment of Schnitzler's Syndrome with Anakinra after Failure of Rituximab Trial
Authors: Cascavilla N. , Bisceglia M. , D'Arena G.
Published: January 2017

We report a 50-year-old man who presented with a 5-year history of an intermittent widespread pruritic urticarioid rash and fever, fatigue, arthralgia and a monoclonal immunoglobulin-M paraprotein. The patient was initially treated with antihistamines and corticosteroids without the disappearance of symptoms. A skin biopsy from the urticarial rash on the thorax was performed, revealing dermal mononuclear and polymorphonuclear cell infiltrate and normal epidermis. A diagnosis of Schnitzler's syndrome (SS), a rare disorder in which the simultaneous occurrence of monoclonal gammopathy and chronic urticaria is usually observed, was made. After an unsuccessful trial with rituximab at a dosage of 375 mg/sqm weekly for 4 consecutive weeks, the patient was treated with anakinra, an inhibitor of interleukin-1α that is thought to be involved in the pathogenesis of the disease, at a dose of 100 mg daily given subcutaneously. He showed a prompt response to the drug and he is still well and symptom-free after 12 months of follow-up. On the basis of both this experience and the review of the literature we conclude that anakinra may be a promising option for the treatment of SS. However, these results need to be confirmed on a larger number of patients.
Autologous Serum Skin Test Reactivity and Basophil Histamine Release Test in Patients with Nasal Polyposis: Preliminary Results
Authors: Zambetti G. , Ciofalo A. , Soldo P. , Fusconi M. , Romeo R. , Greco A. , Altissimi G. , Macri G.F. , Marinelli C. , Pagliuca G. , De Vincentiis M.
Published: January 2017

An eosinophilic inflammatory process is generally observed in patients suffering from nasal polyposis (NP), however its onset has not yet been defined. It has been suggested that immune activation of inflammatory cells may be the cause. The aim of this study is to verify whether autoantibodies and/or histamine-releasing factors are present in the serum of patients suffering from NP. In fact, we assume that autoantibodies and/or histamine-releasing factors, as already demonstrated in chronic idiopathic urticaria and asthma, may be involved in the pathogenesis of NP. In this case-control analytical study 40 patients with NP and 27 control subjects underwent the in vivo autologous serum skin test (ASST). The sera from 6 patients suffering from NP and 9 control group subjects, who had all been previously studied and randomly selected, underwent basophil histamine release assay from normal donor as a pilot study. The ASST showed positive results in 55% of patients suffering from NP versus 8% of the control group (p= .00006), the basophil histamine release test (BHRT) turned out positive in all patients tested and in 11% of the control group. We found a weak positive correlation between the percentage of histamine release and the wheal diameter. ASST reactivity is very frequent in patients suffering from NP, thus suggesting the presence of histamine-releasing factors in the blood stream. The BHRT was positive in the serum of all patients, thus suggesting the presence of anti-FcεRI, anti-IgE autoantibodies and/or other histamine-releasing factors, the presence of which can play a role in triggering and maintaining the eosinophilic inflammatory process in NP.
Safety and Efficacy of Calcium Folinate in Psoriasis: An Observational Study
Authors: Carlesimo M. , Mari E. , Arcese A. , De Angelis F. , Palese E. , Abruzzese C. , De Marco G. , Cattaruzza M.S. , Camplone G.
Published: January 2017

An association between psoriasis and cardiovascular diseases has been reported, and treatment of this condition is often considered difficult because the conventional systemic therapies often show several side effects. To assess the efficacy and tolerability of a new drug, folinate calcium, to treat psoriasis, a total of 58 patients affected by active psoriasis were enrolled in a variable period study. These patients had clinically stable, plaque psoriasis involving ≥ 6% body surface area. Thirty of these patients were treated with folinate calcium therapy, 15 mg orally once daily, for a variable period based on each patient's clinical response. The comparison was made with 28 psoriatic patients treated with conventional systemic therapies (cyclosporine, acitretin, etanercept, efalizumab, infliximab, adalimumab). A clinical improvement was observed in both group, but in the first one we did not observe any side effects, whereas some important side effects were observed in the second. These preliminary results support the effectiveness and tolerability of folinate calcium treatment in psoriasis.
The Parallel Evolution of Immunology and Pharmacology
Authors: Conti A.A.
Published: January 2017

Immunology is the systematic evaluation of the means through which human beings protect themselves and respond to the attack of internal and external agents, and Edward Jenner (1749–1823) and Louis Pasteur (1822–1895) are considered pioneers of this field. Jenner observed the protective effect of cowpox against smallpox and inoculated the cowpox in human beings to protect them from the often lethal smallpox. Pasteur developed in his laboratory a vaccine against rabies and elaborated methods for attenuating the virulence of pathogenic microorganisms while maintaining their immunogenicity. Pharmacology is the area of medical science dealing with drugs and their uses, and it was during the nineteenth century that it assumed its status of scientific specialty, mainly in German-speaking Europe, through the establishment of pharmacological institutes and dedicated laboratories. The discovery and the synthesis of drugs and the systematic evaluation of their activity have constituted through time a scientific field in which immunology and pharmacology have met and given origin to notable progress in the history of science. The development of chemotherapy, as well as of organ and tissue transplantation, in the twentieth century has been decisively promoted by both immunology and pharmacology. In the last three decades the relationship between these two scientific branches has become increasingly closer in basic research, clinical science, medical education and also editorial scientific activity, as documented by the Journal hosting this paper.
CD4+ and CD4− CD ID-Restricted Natural Killer T Cells in Perinatally HIV-1 Infected Children Receiving Highly Active Antiretroviral Therapy
Authors: Chiappini E. , Betti L. , Bonsignori F. , Azzari C. , Galli L. , De Martino M.
Published: January 2017

We conducted a cross-sectional study on 43 Italian perinatally human immunodeficiency virus-type 1 (HIV-1) infected children receiving highly active antiretroviral therapy (HAART) and 26 age-matched healthy controls to explore CD1d-restricted NKT subsets. CD4+CD1d-rectricted natural killer (NKT) cell depletion was evidenced in 26 HIV-1 infected children with active viral replication despite HAART. Conversely, no alteration was evidenced in 17 children with undetectable viral load, suggesting full recovery in both CD4+ and CD4− CDld-rectricted NKT cell subsets. The loss of CD4+ NKT cells in unresponsive children may have clinical consequences, including autoimmune disorders or cancer development. Future therapeutic perspectives are suggested.
The Role of Anti-Cyclic Citrullinated Peptide Antibody in Periodontal Disease
Authors: Ballini A. , Tetè S. , Scattarella A. , Cantore S. , Mastrangelo F. , Papa F. , Nardi G.M. , Perillo L. , Crincoli V. , Gherlone E. , Grassi F.R.
Published: January 2017

The anti-Cyclic Citrullinated Peptide Antibodies (anti-CCP) are produced locally in the inflamed synovium of Rheumatoid arthritis (RA) patients, suggesting that citrullinated proteins are located in the inflamed synovium. In scientific literature were find periodontal bacterial DNA in serum and synovial fluid of RA with PD patients. RA and adult periodontitis share common pathogenetic mechanisms and immunologic and pathological findings RA. One oral pathogen strongly implicated in the pathogenesis of periodontal disease (PD), Porphyromonas. gingivalis, possesses a unique microbial enzyme, peptidylarginine deiminase (PAD), the human equivalent of which has been identified as a susceptibility factor for RA. Under this point of view, we speculate about the presence of anti-CCP antibodies in sera of PD with RA patients. We conducted this study to evaluate and compare the diagnostic and predictive utility of anti-CCP antibodies in patients with PD and patients with PD and RA. Anti-CCP antibody was not found in 21 sera (U/ml<10), included RA controls, while only 1 patient with chronic PD and probing depth of 7,1 mm was identified positive for anti-CCP (22.2 U/ml). Our data do not support a role for anti-CCP in diagnoses of periodontal disease.
Correlations of Serum Interleukin-16, Total IgE, Eosinophil Cationic Protein and Total Eosinophil Counts with Disease Activity in Children with Atopic Dermatitis
Authors: Wu K-G. , Li T-H. , Chen C-J. , Cheng H-I. , Wang T-Y.
Published: January 2017

Several laboratory parameters have been investigated for assessing disease activity in children with atopic dermatitis (AD). Analyses of the correlation between these parameters and clinical severity can help to choose a convincing tool. This study compared the significance of serum interleukin-16 (IL-16), serum total immunoglobulin E (IgE), serum eosinophil cationic protein (ECP), and total eosinophil count (TEC) in reflecting AD severity to order to identify the most relevant objective tool for assessing AD activity and to assess the correlation between these laboratory parameters. The Severity Scoring of Atopic Dermatitis (SCORAD index) was used for the assessment of disease activity in 48 pediatric patients in the acute exacerbation phase and in the maintenance phase after improvement of clinical findings with conventional treatment for 8 weeks. Serum levels of total IgE, ECP, and IL-16 as well as TEC were measured on the same time points and compared with healthy non-atopic controls. The correlation between SCORAD and each laboratory parameter was tested for significance and compared. Serum levels of ECP and IL-16 of AD patients were significantly higher than those of controls. These serum parameters, except TEC, declined significantly after conventional treatment with clinical improvement. There was positive correlation with SCORAD for serum IgE (r=0.317, p=0.028), TEC(r=0.434, p=0.002), IL-16 (r = 0.321, p=0.026) in the acute exacerbation phase and with SCORAD for serum IgE (r=0.510, p<0.001), TEC(r=0.489, p<0.001), serum ECP (r=0.468, p=0.001) in the maintenance phase. Serum levels of total IgE, IL-16, ECP, and TEC correlated with the SCORAD index in pediatric patients with atopic dermatitis. Thus, they can serve as serum markers for monitoring disease activity in childhood atopic dermatitis.
The Sphingosine Kinase Activator K6PC-5 Stimulates C2C12 Myoblast Differentiation
Authors: Bernacchioni C. , Cencetti F. , Kwon M.J. , Gwak H.S. , Jeong S.K. , Bruni P. , Donati C.
Published: January 2017

Previously, K6PC-5, a synthetic derivative of ceramide, was demonstrated to activate sphingosine kinase (SK)-1 in keratinocytes. In this study its potential biological effect in mouse myoblasts was examined. The obtained results show that K6PC-5 promotes myogenic differentiation by enhancing myogenic marker expression, differentiation index and fusion index. Interestingly, its biological action was prevented by pharmacological inhibition of SK or S1P2 receptor, in full agreement with their recognized role in myoblast differentiation. This is the first evidence that pharmacological activation of SK accelerates myogenesis and suggests that this new therapeutic strategy could be possibly employed in skeletal muscle disorders where muscle regeneration is deficient.
Inhibition of the Complement System by Glutathione: Molecular Mechanisms and Potential Therapeutic Implications
Authors: Perricone C. , De Carolis C. , Giacomelli R. , Greco E. , Cipriani P. , Ballanti E. , Novelli L. , Perricone R.
Published: January 2017

Glutathione (GSH), a component of the antioxidant defence system, plays a role in autoimmunity and the complement system is often responsible for tissue damage in autoimmune diseases. The aim of this study is to evaluate the effects of GSH on the complement system. The complement system was examined in the normal human sera (NHS) of 30 healthy subjects. Increasing quantities of GSH (1, 2, 10, 20 mg) were incubated in 1 ml of each NHS. The mixtures were evaluated for complement activities (THC, CPA and APA) and for the presence of cleavage fragments of activation of C3 and B. GSH was also incubated with human complement in the presence of classical and alternative pathway activators. The results showed an inhibitory effect of GSH on the complement system starting from a dosage of GSH≥1 mg/ml. Indeed, when NHS was incubated with GSH at such dosage, a significant reduction of the complement activities THC, CPA, and APA was observed (P<0.0001, P<0.005, P=NS, respectively), and no cleavage fragments of C3 or B were found. Further analysis demonstrated that the inhibition was exerted on C3-9 and to a lower extent on classical and alternative pathway C3-convertases. Our results indicate that GSH is capable of inhibiting the complement system. These findings are relevant for the design of interventions aimed at modulation of GSH metabolism to inhibit complement-mediated damage in autoimmune diseases.
The Combination of Immunosuppressive Drugs with 8-Methoxypsoralen and Ultraviolet a Light Modulates the Myeloid-Derived Dendritic Cell Function
Authors: Failli A. , Legitimo A. , Mazzoni A. , Urbani L. , Scatena F. , Mosca F. , Consolini R.
Published: January 2017

The functional properties of myeloid dendritic cells (DCs) differ, depending on microenvironmental factors as well as on their stage of maturation. The main approaches for the selective enhancement of the tolerogenic properties of DCs include the induction of a pharmacological arrest of the DCs maturation and the genetical engineering of DCs expressing immunosuppressive molecules. Several immunosuppressive/anti-inflammatory agents have been discovered that potentially inhibit DC maturation and immunogenicity. Photopheresis (ECP) is an immunomodulatory therapy in which leucocytes are exposed to 8-methoxypsoralen (8-MOP) and ultraviolet (UV) A radiation (PUVA). The combination of ECP with immunosuppressive agents has demonstrated efficacy in the management of transplanted patients by reducing either the incidence of organ rejection or the pharmacological toxicity. In particular, we have observed in hepatitis C virus (HCV)-positive patients that the same combination has reduced the immunosuppressive burden and improved sustainability and efficacy of pre-emptive antiviral therapy after liver transplantation. Therefore, in our work we investigated the in vitro effects of PUVA, combined with immunosuppressive drugs (IDs), on both in vitro human DC generation and maturation, in order to contribute to understanding the immunological mechanisms underlying this pharmacological combination. Monocyte PUVA-treatment was performed by using an in vitro experimental protocol that we previously described. PUVA-treated or -untreated highly purified CD14+ cells were incubated with the association of the immunosuppressive drugs, used in the management of liver transplantation, at two different concentrations, in the presence of IL-4 and GM-CSF. The treatment with IDs at the highest concentration (corresponding to that used in clinical practice), alone or in association with PUVA, induced an immunosuppressive effect, by impairing both DC generation and maturation. Neither immunosuppressive drugs at the lowest concentration nor their combination with PUVA affected myeloid DC generation, but modified DC functions, strengthening the induction of a tolerogenic pattern. As this ID concentration was arbitrarily chosen, further experiments could highlight whether lower concentrations than those used in clinical practice would elicit the same effect on DCs and potentially improve their functional properties. This work describes an original experimental approach exploring the in vitro mechanism of action of the combined procedure of PUVA with immunosuppressive drugs, used in liver transplantation, on DCs generation and function. Our results contribute to the knowledge of the mechanisms of action of this combined procedure on DCs, suggesting useful therapeutic implications for the in vivo therapy.
Characterization of the Immune Response of Human Cord-Blood Derived γδ T Cells to Stimulation with Aminobisphosphonate Compounds
Authors: Placido R. , Auricchio G. , Gabriele I. , Galli E. , Brunetti E. , Colizzi V. , Battistini L. , Mancino G.
Published: January 2017

Vγ9Vδ2 T lymphocytes have been shown to respond to a variety of non-peptide antigens including alkylamines and phosphoantigens. Recently, aminobisphosphonates have also been shown to stimulate this subset of γδ+ T cells. In this study we analyzed the proliferative responses of freshly isolated γδ T lymphocytes obtained from human cord blood when challenged with pyrophosphomonoesters or aminobisphosphonates. Nitrogen-containing aminobisphopsphonates, in contrast to phoshoantigens, readily stimulated expansion of Vδ2Vγ9 cells in human cord blood. Expanded cells displayed an activated mature phenotype, and were capable of producing TNFα and IFNγ but not perforin following secondary stimulation, consistent with the development of a regulatory, as opposed to cytotoxic, phenotype. This approach may provide a useful strategy for a new approach to the treatment of neonatal pathologies.
Conservative Management of Canine Tracheal Collapse with Stanozolol: A Double Blinded, Placebo Control Clinical Trial
Authors: Adamama-Moraitou K.K. , Pardali D. , Athanasiou L.V. , Prassinos N.N. , Kritsepi M. , Rallis T.S.
Published: January 2017

The objective of this study is to determine the efficacy of stanozolol in the treatment of tracheal collapse (TC) in dogs, which is the analogous disease to tracheomalacia (TM) in humans. Twenty-two dogs with endoscopically confirmed and graded TC were enrolled into five groups. Groups S1 (n=5), S2 (n=5) and S3 (n=4) with grade 1, 2 and 3 TC, respectively, received stanozolol orally for 75 days, while groups P1 (n=4) and P2 (n=4) with grade 1 and 2 TC, respectively, received placebo. The clinical score was evaluated every 15 days, whereas TC grade was reassessed at the end of the experiment. Clinical improvement was detected from the 30th day in S2 and S3 group dogs and from the 45th day in S1 group dogs and continued until the end of the experiment. Also, statistically significant differences were seen between S2 and P2 dogs from the 30th day, and between S1 and P1 dogs from the 60th day, and continued until the end of the study. Amelioration of the TC grade was seen in 13 of 14 (92.9%) dogs, which received stanozolol. Of the 14 dogs, 57.1% were cured and 35.8% demonstrated a less severe TC grade, while only one dog (7.1%) did not improve at all. Stanozolol seems to be an effective drug in the management of canine TC and it may have potential for use in humans with TM.
Role of the Quantiferon-TB Test in Ruling Out Pleural Tuberculosis: A Multi-Centre Study
Authors: Losi M. , Bocchino M. , Matarese A. , Bellofiore B. , Roversi P. , Rumpianesi F. , Alma M.G. , Chiaradonna P. , Del Giovane C. , Altieri A.M. , Richeldi L. , Sanduzzi A.
Published: January 2017

Diagnosing pleural tuberculosis (plTB) might be difficult due to limited sensitivity of conventional microbiology tools. As M. tuberculosis (MTB)-specific T cells are recruited into pleural space in plTB, their detection may provide useful clinical information. To this aim, in addition to standard diagnostic tests, we used the QuantiFERON-TB Gold In-Tube (QFT-IT) test in blood and pleural effusion (PE) samples from 48 patients with clinical suspicion of plTB, 18 (37.5%) of whom had confirmed plTB. Four of them (22.2%) tested positive with a nucleic acid amplification test for MTB. The tuberculin skin test was positive in most confirmed plTB cases (88.9%). Positive QFT-IT tests were significantly more frequent in patients with confirmed plTB, as compared to patients with an alternative diagnosis, both in blood (77.7 vs 36.6%, p=0.006) and in PE samples (83.3% vs 46.6%, p=0.02). In addition, both blood and PE MTB-stimulated IFN-γ levels were significantly higher in plTB patients (p=0.03 and p=0.0049 vs non-plTB, respectively). In blood samples, QFT-IT had 77.8% sensitivity and 63.3% specificity, resulting in 56.0% positive (PPV) and 82.6% negative (NPV) predictive values. On PE, QFT-IT sensitivity was 83.3% and specificity 53.3% (PPV 51.7% and NPV 84.2%). The optimal AUC-derived cut-off for MTB-stimulated pleural IFN-γ level was 3.01 IU/mL (77.8% sensitivity, 80% specificity, PPV 68.4% and NPV 82.8%). These data suggest that QFT-IT might have a role in ruling out plTB in clinical practice.
A New Chance to Maintain Remission Induced by Anti-TNF Agents in Rheumatoid Arthritis Patients: CynAR Study II of a 12-Month Follow-up
Authors: Migliore A. , Bizzi E. , Massafra U. , Vacca F. , Martin L.S. Martin , Ferlito C. , Podestà E. , Granata M. , Laganà B.
Published: January 2017

The advent of biological therapies represented the beginning of a new era in the therapy of Rheumatoid Arthritis (RA), as demonstrated in several studies, but still many questions about their safety, especially in long term use, and correct administration time remain unanswered. Once remission is achieved, the orientation of clinicians regarding the maintenance of biological therapy or the switch to another immunosuppressive therapy is still uncertain. In our previous study 21 patients affected by RA who reached remission by the use of a combined therapy of anti-TNF drugs and methotrexate (MTX) underwent CyA-MTX combination therapy for maintaining remission state and were evaluated during a 6-month follow-up. The present study aims to investigate these data by a longer follow-up (12 months) and on a larger population. Fifty-three RA patients, with a disease duration of less than 3 years and DAS28<3.2 that reached a level of low disease activity within 6–8 months from the beginning of anti-TNF and methotrexate therapy, were enrolled in the study. By the suspension of anti-TNF therapy, patients underwent A-Cyclosporine (2–3 mg/kg/day) and methotrexate (15mg/week) therapy. DAS28, Pain VAS, Erythrosedimentation rate (ESR), C Reactive Protein (CRP) were all tested at time 0 and every 2 months after the interruption of the anti-TNF therapy and the beginning of A-Cyclosporine and methotrexate therapy, as well as liver and kidney profiles. Side effects were also recorded. Of 53 patients, 50 completed the study with a 12-month follow-up. Twenty-one (42%) patients maintained clinical parameters within low disease activity values at 12 months, while 29 (58%) patients showed an increase in DAS28 and other parameters: 16 (32%) patients at the 6-month control, 13 (26%) patients at the 12-month control. Our data show that 42% of the patients undergoing A-Cyclosporin and Methotrexate therapy maintained low disease activity parameters of rheumatoid arthritis, obtained after 6–8 months of anti-TNF therapy. Further studies on larger populations are necessary in order to confirm such results and identify predictor factors for different responses.
CD1A and CD1E Gene Polymorphisms are Associated with Susceptibility to Multiple Sclerosis
Authors: Caporale C.M. , Notturno F. , Pace M. , Aureli A. , Di Tommaso V. , De Luca G. , Farina D. , Giovannini A. , Uncini A.
Published: January 2017

Multiple sclerosis (MS) is thought to be an autoimmune T-cell-mediated disease directed at myelin antigens of the central nervous system. Besides myelin proteins, lipid components of CNS are supposed to play a role as antigens for T cells in MS. CD1 is a family of MHC-like glycoproteins specialized in capturing and presenting a variety of microbial and self lipids and glycolipids to antigen-specific T cells. CD1-restricted T cells specific for gangliosides and sulfatide have been isolated from subjects with MS and in mice with experimental allergic encephalopathy. We genotyped exon 2 of CD1A and CD1E in 205 MS patients and 223 unrelated healthy controls and determined their association with the presence of anti-ganglioside and anti-sulfatide antibodies. CD1E 01-01 is associated with a reduced risk of MS (OR 0.54, p=0.001); CD1A 02-02 (OR 1.99, p=0.012) or CD1E 02-02 (OR 2.45, p=0.000) with an increased risk. The combination of the genotypes CD1A 02-02 and CD1E 02-02 is present in 90.7% of patients but in only 9.4% controls (OR 94.16, p= 0.000). CD1A and CD1E polymorphisms contribute to the polygenic susceptibility to MS. The functional effects of CD1 polymorphisms are unknown, however changes in CD1 alleles may affect numerous immunological functions.
Aerosol Therapy with Thiamphenicol Glycinate: A Retrospective Study on Efficacy and Safety in a Group of Sixty-Six Oncological Patients
Authors: Macchi A. , Terranova P. , Macchi S. , Roselli R. , Castelnuovo P.
Published: January 2017

The purpose of this paper is to present the effectiveness of aerosol administration of TG in a group of oncological patients. Thiamphenicol is an antimicrobial agent active in the treatment of infection of different etiology and localisation due to its broad spectrum of antimicrobial activity as well as its pharmacokinetic properties. The data of the retrospective study analysis of the activity of TG, administered to oncological patients affected by infections of the respiratory tract, showed that TG administered alone or in association with other antibiotics was globally effective in more than 95% of patients. These positive results were obtained in immunologically compromised patients. The therapeutic advantages of using TG are: ease of use - aerosol therapy permits good local action; tolerability - no adverse reaction or intolerance; the possibility of using it in an ideal association with other antibiotics to combat the infectious pathology.
Change of γδTCR-Expressing T Cells in Healthy Aging
Authors: Mazzoccoli G. , Vendemiale G. , De Cata A. , Tarquini R.
Published: January 2017

A mature T-cell lineage with the capacity to proliferate in response to receptor-mediated signals and to display non-major histocompatibility complex (MHC)-restricted cytolysis expresses a CD3-associated heterodimer made up of the protein encoded by the T-cell receptor (TCR) gamma-gene. We investigated the possible differences in lymphocyte subpopulations between healthy young-middle-aged and elderly subjects, focusing attention on y8-TCR-expressing cells. The study was carried out on fifteen healthy young-middle-aged male subjects (age range 36–55 years) and fifteen healthy elderly male subjects (age range 67–79 years). Lymphocyte subpopulations were analyzed in blood samples collected every four hours for 24 hours. The presence of circadian rhythmicity on absolute counts was validated to evaluate the periodicity of variation, and the fractional variation between single time point values was calculated to evaluate the dynamics of variation. In the group of young and middle-aged subjects a clear circadian rhythm was validated for the time-qualified changes of all the lymphocyte subpopulations (CD3, CD4, CD4/CD8 ratio, CD20, CD25 and HLA-DR with acrophase at night, CD8, CD16 and TcRγδ with acrophase at noon). In the group of elderly subjects a clear circadian rhythm was validated for the nyctohemeral changes of CD3, CD8, CD4/CD8 ratio, CD 16, CD25. There was a statistically significant difference for the Midline Estimating Statistic of Rhythm (MESOR) of CD3 (p=0.001), CD25 (p=0.003) and γδ-TCR- expressing cells (p=0.004), higher in the elderly, and for the MESOR of HLA-DR (p=0.002) and CD20 (p=0.002) higher in the young and middle-aged subjects. There was a statistically significant difference between the groups in the fractional variation of TcRγδ-expressing cells between 18:00h and 22:00h values (higher in elderly subjects, p=0.007). In conclusion, specific lymphocyte subsets present different levels and different profiles of nyctohemeral changes in healthy young-middle aged in respect to elderly subjects, since B cells are decreased, whereas CD25 and γδ-TCR-bearing cells are higher in the elderly, but the rhythm and the dynamics of variation of this lymphocyte subset is severely altered and this phenomenon might contribute to the onset of age-related variations of the immune responses.
Percutaneous Steroidal Treatment in Relapses of Chronic Tendinopathies: A Pilot Study
Authors: Salini V. , Abate M.
Published: January 2017

Relapses are frequently observed in subjects with chronic tendinopathies. Corticosteroid injections are usually performed with positive results, but are uncomfortable for the patient and not free from side effects. The aim of this pilot study is to evaluate the short-term efficacy and tolerability of an occlusive Betamethasone Valerate medicated Plaster (BMVP). Fifteen subjects with relapses of chronic tendinopathies (clinical and ultrasound diagnosis) were enrolled, and treated according to RICE (Rest - Ice - Compression - Elevation) protocol. An BMVP plaster was also applied on the affected tendon. Clinical examination, at baseline and after 7, 14, 21 and 28 days, included pain (VAS at rest and during activities) and functional evaluation. Local side effects on the area and drop-outs were also recorded. Pain, both at rest and during activities, significantly decreased at 28 days (from 3.7 ± 2.7 to 1.1 ± 1.7 [p < 0.01], and from 7.3 ± 1.7 to 3.3 ± 1.4 [p < 0.0000], respectively). Moreover, the patients reported a significant improvement in the functional limitation. Five subjects dropped out of the study. No side effects were reported. The release of the steroid in pharmacologically-active concentrations over 12–24 hours and the good penetration of the drug in subcutaneous tissues explain the positive results. BMVP application may be considered a reliable first therapeutic approach in relapses of chronic tendinopathies.
Search for Genomic Sequences of Microbial Agents in Atherosclerotic Plaques
Authors: Tremolada S. , Delbue S. , Ferraresso M. , Carloni C. , Elia F. , Larocca S. , Bortolani E. , Ferrante P.
Published: January 2017

Atherosclerosis is a complex, multifactorial disease. Several studies have reported a possible association between infection with microbial agents and atherogenesis. Chlamydia pneumoniae ( C. pneumoniae), Herpes Simplex Virus 1 (HSV1), Human Cytomegalovirus (HCMV), and Epstein Barr Virus (EBV) have been widely investigated for their possible role in atherosclerosis development, but the results obtained to date are contradictory. The aim of our study is to search DNA of the aforementioned infectious agents by means of Quantitative Real Time PCR in atherosclerotic plaques from carotid arteries obtained from 17 patients. Genomic sequences of C. pneumoniae, HSV1, HCMV were not found in any atherosclerotic lesion. Therefore, our results do not support the hypothesis of an association between these infectious agents and atherosclerosis. Conversely, three patients were found to be positive for EBV DNA, thus indicating that, at least in a limited number of patients, EBV could play a role in atherogenesis.
Evaluation of the Effect of Bosentan Treatment on Proinflammatory Cytokine Serum Levels in Patients Affected by Systemic Sclerosis
Authors: Bellisai F. , Morozzi G. , Scaccia F. , Chellini F. , Simpatico A. , Pecetti G. , Galeazzi M.
Published: January 2017

Systemic sclerosis (SSc) is a connective tissue disease characterized by vascular and fibrotic changes in the skin and in internal organs. Endothelin-1 (ET-1) is a peptide that has a role in promoting both vascular injury and the fibrotic process in SSc; indeed, patients with systemic sclerosis have higher levels of ET-1 compared with healthy subjects. Moreover, ET-1 enhances expression of pro-inflammatory cytokines in animal model. Bosentan is a dual endothelin receptor antagonist approved for the treatment of pulmonary arterial hypertension and digital ulcers in scleroderma patients. In animal models and in vitro models, after treatment with Bosentan, a significant reduction of cytokine (TNFα, IFNγ, IL-8, IL-4) levels was observed. The aim of the study is to verify whether Bosentan treatment in SSc patients can reduce circulating cytokines levels. We enrolled 10 patients affected by SSc with digital ulcers and/or pulmonary hypertension, treated with Bosentan 125 mg twice daily. Patients were tested for cytokines and ET-1 level before treatment and after 12 months. The cytokines tested were IL-10, IL-2, IL-4, IL-5, IL-6, IL-8, GM-CSF, IFN-γ and TNF. Levels of ET-1, IL-10, IL-4, IL-5, GM-CSF and TNFα did not show consistent modification during treatment with Bosentan in respect to baseline, while IL-2, IL-6, IL-8 and IFN-γ were significantly decreased. Bosentan significantly reduced IL-2, IL-6, IL-8 and IFN-γ levels in SSc patients, probably slowing progression to fibrosis and vascular damage. This is the first report showing a decrease of profibrotic and proinflammatory cytokines levels in humans during treatment with Bosentan.
Allergic Inflammation: Role of Cytokines with Special Emphasis on IL-4
Authors: Saggini A. , Maccauro G. , Tripodi D. , De Lutiis M.A. , Conti F. , Felaco P. , Fulcheri M. , Galzio R. , Caraffa A. , Antinolfi P. , Felaco M. , Pandolfi F. , Sabatino G. , Neri G. , Shaik-Dasthagirisaheb Y.B.
Published: January 2017

This review examines recent articles on the relationship of cytokines to allergy and inflammation with particular emphasis on interleukin (IL)-4. The objective of this article is therefore to review published studies to identify cytokines consistently involved in allergic inflammation. Proinflammatory cytokines, including IL-4, IL-5, IL-13 and GM-CSF along with TNF-alpha play a role in allergen-induced airway leukocyte recruitment and these cytokines can be generated by T mast cells and other cells. In addition, IL-9, IL-25, IL-33, IL-17, IL-27 and IFN-γ are deeply involved in the regulation of asthma. Blocking the effect of these proinflammatory cytokines might provide new therapeutic approaches for the control of allergy and inflammation.