bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of the Compound L-Mimosine in an in Vivo Model of Chronic Granuloma Formation Induced by Potassium Permanganate (KMNO4)
Authors: Frydas S , Papazahariadou M. , Papaioannou N. , Hatzistilianou M. , Trakatellis M. , Merlitti D. , Di. Gioacchino M. , Grilli A. , Delutiis M.A. , Riccioni G. , Conti P. , Vlemmas I.
Published: January 2017

The plant amino acid L-mimosine has recently been suggested to inhibit cells at a regulatory step in late G phase before establishment of active DNA replication forks. In addition, L-mimosine is an extremely effective inhibitor of DNA replication in chromosomes of mammalian nuclei. In this work, the effect of L-mimosine on chronic inflammation induced by dorsal injections of 0.2 ml of a 1:40 saturated crystal solution of potassium permanganate in mice, was studied. Seven days afterwards, all mice developed a subcutaneous granulomatous tissue indicative of chronic inflammatory response at the site of infection. The intraperitoneal administration of L-mimosine (200 μg/dose) to the potassium permanganate treated mice for 5 consecutive days (the first at the same time of inoculation of the KMnO4), produced a significant decrease in size and weight of the granuloma when compared to mice not treated with L-mimosine (controls). In addition, in all mice treated with L-mimosine, there was a strong inhibition of tumor necrosis factor alpha that was revealed in the serum (P<0.05) and in the minced granulomas. Interleukin-6 was not detected in the serum of treated and untreated mice. These findings show for the first time, that L-mimosine may have an anti-inflammatory effect on chronic inflammation and an inhibitory effect on tumor necrosis factor alpha and interleukin-6 generation in supernatant fluids of minced granulomas.
Prevalence of Borrelia Burgdorferi Sensu Lato Genomospecies and of the Human Granulocytic Ehrlichiosis (HGE) Agent in Ixodes Ricinus Ticks Collected in the Area of Monti Lepini, Italy
Authors: Santino I. , Iori A. , Nicoletti M. , Valletta S. , Cimmino C. , Scoarughi G.L. , Santapaola D. , Sessa R. , Del Piano M.
Published: January 2017

Ticks are obligate hematophagous arthropods that are parasites in every class of vertebrates in most regions of the world. They are also considered to be important vectors for the transmission of human infectious diseases. In the present study we used polymer chain reaction (PCR) amplification analysis to determine the prevalence of Borrelia burgdorferi and Ehrlichia phagocytophila, the agents of, respectively, Lyme borreliosis and human granulocytic ehrlichiosis, among ticks inhabiting the area of Monti Lepini, a wild area located in the Latium Region of Italy. A total of 141 I. ricinus ticks (125 nymphs and 16 adults) were collected in the studied area. Total DNAs were extracted from I. ricinus nymphs (pooled in groups of five) and from individual adults. The DNA samples were examined for the presence of B. burgdorferi sensu lato and E. phagocytophila by PCR using two specific pairs of oligonucleotides that specifically amplify distinct DNA regions of the 16S rRNA genes of the two species. The prevalence of vectors infected with B. burgdorferi s. 1. was 16% in pooled nymphs samples, and 12.5% in adult ticks, while E. phagocytophila was found only in pooled nymphs samples (8%). Three genomospecies were identified, namely Borrelia afzelii, Borrelia garinii, and Borrelia valaisiana, in samples found positive for B. burgdorferi s. 1. No sample was found positive for Borrelia burgdorferi sensu stricto.
Simple Renal Cysts in Hypertensive Patients: Relation between Cyst Growing and Anti-Hypertensive Therapy
Authors: Schiavone C. , Salvatore L. , Primavera A. , Cuccurullo F. , Verna N. , Di Stefano F. , Thomson E. , Tenaglia R. , Di Gioacchino M.
Published: January 2017

The study investigates relationship between simple renal cyst enlargement studied by ultrasonography and anti-hypertensive treatment. To this purpose we enrolled 42 patients with newly diagnosed hypertension affected by simple renal cysts. Fourteen were randomly assigned to treatment with ACE-Inhibitors (group 1), twelve to diuretics (group 2) and sixteen to Ca-Antagonists (group 3). Patient performed a basal ultrasonography to evaluate basal cyst dimension before starting anti-hypertensive treatment. Following 12 months of the anti-hypertensive regimen, a new echograph was performed to evaluate changes in cyst size. A control group consisting of 15 patients with normal blood pressure and simple renal cysts was enrolled (group 0). An enlargement of cysts was detected in all patients. However, the enlargement observed in patients treated by Ca-Antagonists was significantly greater than that observed in the other groups (p<0,05). Our study supports the hypothesis that Ca-Antagonists may favor cyst enlargement by enhancing cyclic AMP production. In fact, cAMP and cAMP agonists stimulate fluid secretion by lining cells of the cyst wall, inducing cyst enlargement.
Are Thyroid Dysfunctions Related to Stress or Microwave Exposure (900 Mhz)?
Authors: Bergamaschi A. , Magrini A. , Ales G. , Coppeta L. , Somma G.
Published: January 2017

In the last decade, numerous scientific evidence suggested possible adverse health effects from exposure to electromagnetic fields (EMF'S) and the use of mobile phones. According to some studies EMF induced changes of trans-membrane Ca++ flux may lead to altered metabolism and/or secretion of neurohormones including TSH, ACTH, GH, prolactin and melatonin. The aim of this research was to analyse the effects of mobile phone use on thyroid function and to evaluate the possible role of occupational stress. 2598 employees (1355 men and 1243 women) with different duties (vendors, operators and network technicians) were included in the study. Exposure to EMF'S, generated by mobile phones, was assessed both by submitting a questionnaire directly to the employees and acquiring data regarding conversation times. The workers were divided into three groups on the basis of their personal mobile phone use. Moreover, a group of 160 workers with TSH values below 0.4 UI/1 was characterized. No statistically significant difference regarding TSH values below 0.4 UI/1 was observed among workers with different duties but there was a greater prevalence of subjects with low TSH values among 192 employees with more than 33hrs./month conversation time; this difference was statistically significant (p<0.05). On the basis of our data, it is not possible to establish whether this result is determined by exposure to EMF'S from mobile phones or by the stress of using these instruments.
Protein Kinase Cζ Regulation of Hypertrophic and Apoptotic Events Occurring during Rat Neonatal Heart Development and Growth
Authors: Centurione L. , Di Giulio C. , Santavenere E. , Cacchio M. , Sabatini N. , Rapino C. , Bianchi G. , Rapino M. , Bosco D. , Antonucci A. , Cataldi A.
Published: January 2017

The development and growth of the rat heart implies hyperplasia, which stops at birth, and hypertrophy, allowing cardiac mass to grow in response to programmed genetic events along with to haemodynamic overload. Moreover, hypertrophy is accomplished to apoptosis which controls the final number of myocardial cells, deletes vestigial structures, and takes part in remodelling the organ. Since at the basis of all these processes, which lead to the complete development of the heart, the activation of specific signalling pathways underlies, attention has been addressed to the role played in vivo by Protein Kinase Cζ (PKCζ) in regulating NF-kB signalling system and “intrinsic” mitochondrial apoptotic route at days 1, 4, 10 and 22 of rat life. In fact, a role has been assigned to PKCζ in indirectly phosphorylating IKBα, which peaks between 10 and 22 days, through a IKK determining, in turn, NF-kB activation, concomitantly to cytochrome c/Apaf 1 co-localization in the cytoplasm and caspase-9/caspase-3 activation, which leads to the occurrence of apoptosis. Thus a key role for PKCζ in regulating the hypertrophic and apoptotic events leading to establishment of complete function in rat neonatal heart is here suggested.
Identification of a Conserved N-Capping Box Important for the Structural Autonomy of the Prion α3-Helix: The Disease Associated D202N Mutation Destabilizes the Helical Conformation
Authors: Gallo M. , Paludi D. , Cicero D.O. , Chiovitti K. , Millo E. , Salis A. , Damonte G. , Corsaro A. , Thellung S. , Schettini G. , Melino S. , Florio T. , Paci M. , Aceto A.
Published: January 2017

Peptides corresponding to three alpha helices present in the C-terminal region of the human prion protein have been synthesized and their structural autonomy analyzed by circular dichroism (CD) and NMR spectroscopy. The results obtained indicate that the protein fragment corresponding to the α3-helix, in contrast to α1 and α2 peptides, shows a complete structural autonomy. The chemical shifts values found for NH and CHa resonances of the isolated α3 peptide, formed by 30 aminoacid residues, were markedly and surprisingly similar to the corresponding values of the α3-helix in the protein. The structural autonomy of the α3-helix is profoundly determined by the presence of the conserved capping box and, in part, by the ionic bond formed between Glu200 and Lys204. On the basis of these observations a novel PrP consensus pattern, centered on the α3-helix region, has been defined. The data indicate that this autonomous and highly conserved region of the PrPc likely plays a critical role in folding and stability. This gives an explanation of why many of pathogenic mutations occur in this part of the molecule, sharing relevant effects on the overall protein conformation. In particular the D202N capping mutation almost completely destabilizes the isolated α3 peptide. While it is well known that the D202N substitution is associated with a GSS disease, the possible structural basis of this fatal pathology has never been investigated. We propose that a lower α3-helical propensity leading to a major destabilization of the PrPc molecule initiates the pathogenic process associated with D202N capping mutation.
A Pilot Study of Feasibility of Ultra-Rush (20–25 Minutes) Sublingual-Swallow Immunotherapy in 679 Patients (699 Sessions) with Allergic Rhinitis and/or Asthma
Authors: Rossi R. E. , Monasterolo G.
Published: January 2017

Few studies have evaluated the occurrence of immediate adverse reactions in allergic patients after an ultra-rush regimen of different commercial allergen extracts for sublingual immunotherapy (SLIT) Methods: 679 patients took part in trials of specific ultra-rush SLIT for the treatment of IgE – mediated rhinitis and/or IgE – mediated asthma. 14 patients received two different sublingual allergen vaccines during two distinct SLIT sessions. On the whole, 699 SLIT sessions were performed. The build up ultra-rush phase involved the administration every five minutes of increasing doses of either different allergen extracts. The cumulative allergen extract solution after half an hour was several times the dose administered at the start of subcutaneous immunotherapy (range 4.7–525μg of major allergens). All patients tolerated the treatment very well. 122 (17.96%) had mild local symptoms (pruritus of the buccal cavity) that spontaneously disappeared with increasing dose. Two patients allergic to Parietaria had urticaria about three hours after the last sublingual Parietaria -extract intake. A subject allergic to Artemisia vulgaris pollen had urticaria and rhinitis two hours later than the last dose of vaccine. As reported in our previous study, no immediate severe adverse reactions were observed after that rapidly increasing doses of allergen extract were administered in a very short period to a large number of patients, showing the excellent safety profile of ultra-rush SLIT.
Timp-1 is a Key Factor of Fibrogenic Response to Bleomycin in Mouse Lung
Authors: Manoury B. , Caulet-Maugendre S. , Guénon I. , Lagente V. , Boichot E.
Published: January 2017

Pulmonary fibrosis is characterized by the excessive deposition of extracellular matrix in the interstitium, resulting in respiratory failure. The role of remodeling mediators such as metalloproteinases (MMPs) and their inhibitors (TIMPs) in the fibrogenic process remains misunderstood. We investigated MMP-9, MMP-2, TIMP-1, TIMP-2 and TIMP-3 in the fibrotic response to bleomycin of “fibrosis prone” C57BL/6J and “fibrosis resistant” BALB/c mice. Mice were administered with 0.1 mg bleomycin by intranasal administration. Either 24 h or 14 days after, the mice were anesthetized and underwent either bronchoalveolear lavage (BAL) or lung removal. Collagen deposition in lung tissue was determined by hydroxyproline measurement, MMP activity was analyzed by zymography, and others mediators were analyzed by ELISA. TIMP-1 was localized in lung sections by immunohistochemistry and real time PCR was performed to gene expression in lung. Non parametric Mann & Whitney and Spearman tests were used for statistical analysis. Fourteen days after bleomycin administration, hydroxyproline assay and histological study revealed that BALB/c mice developed significantly less fibrosis compared to C57BL/6J mice. At day 1, bleomycin enhanced TIMP-1, MMP-2 and MMP-9 protein levels in BALF, and induced corresponding genes in lung tissue of both strains. The rise of Timp-1, Mmp-9 and Mmp-2 gene levels were significantly stronger in lungs of C57BL/6J, whereas gelatinase activities of MMP-2 and MMP-9 were similar. Immunohistochemistry revealed that TIMP-1 macrophages and epithelial cells were prominent TIMP-1 producers in both strains. At day 14, neither MMP-2 nor MMP-9 levels exhibited strain-dependent protein level or gene expression, although TIMP-1 was strongly associated with fibrosis. Interestingly, bleomycin induced neither Timp-2 nor Timp-3 in lung tissue at any time of the study. The present study shows that early altered regulation of TIMP-1 following bleomycin administration may be involved in bleomycin-induced pulmonary fibrosis.
Chromium (VI)-Induced Immunotoxicity and Intracellular Accumulation in Human Primary Dendritic Cells
Authors: Burastero S.E. , Paolucci C. , Breda D. , Ponti J. , Munaro B. , Sabbioni E.
Published: January 2017

Chromium compounds, besides being occupational carcinogens, can also induce allergic contact dermatitis (ACD) and other immunomodulatory effects. In this study we investigate cell viability, uptake and intracellular distribution of chromium in human primary dendritic cells (DCs), either immature (iDCs) or driven to differentiate by a specific maturation stimulus (LPS) (mature DCs, mDCs), when exposed for 48 h to concentrations of soluble radiolabelled Na251CrO4 ranging from 5 to 0.5 μM. The modulation of the expression of membrane markers (CD80, CD86, MHC class II) correlated with the immunological functions of DCs was also measured. After 48 h of exposure the mean IC50 values in 4 donors were 36 and 31 μM in iDCs and mDC respectively, as detected by propidium iodide incorporation. Cellular uptake of chromium was nearly linear with increasing doses. At 48 h post-exposure chromium was accumulated preferentially in the nuclear and cytosolic fractions (44.1 to 66% and 13.1 to 31% of total cellular chromium, respectively). Although a high inter-individual variability was observed, an increase in the expression of CD86 and, to a lower extent, CD80 and MHC class II membrane markers was found in mDCs of single donors. These results highlight the relevance of searching for the biodistribution of trace metals in primary cells of the immune system. Moreover, they suggest that DCs differentiation markers can help in measuring the immunotoxicity of metal
Baff and Rheumatic Autoimmune Disorders: Implications for Disease Management and Therapy
Authors: Bosello S. , Pers J.-O. , Rochas C. , Devauchelle V. , De Santis M. , Daridon C. , Saraux A. , Ferraccioli G.F. , Youinou P.
Published: January 2017

Interest in B-cells has been revived due to the description of new functions. Supporting a role for B-cells in the genesis of autoimmune diseases is the fact that the B-cell activating factor of the TNF ligand family (BAFF) is essential in their physiology. However, in each disease, this is restricted to a subgroup of patients. Based on experiments in mice, and validated in humans, this new cytokine has been highlighted. Excessive production of BAFF alters immune tolerance by rescuing self-binding B-cells. Overexpression in mice leads to autoimmune manifestation, and BAFF levels are elevated in the serum of autoimmune patients. Similar abnormalities occur in chronic lymphocytic leukemia. Recent works suggest that antagonizing the protein (or competing for its receptors) is relevant to the treatment. Advances in our understanding of the BAFF system offers the opportunity to improve our therapeutic approach.
Reparixin, a Specific Interleukin-8 Inhibitor, Has No Effects on Inflammation during Endotoxemia
Authors: Leitner J.M. , Mayr F.B. , Firbas C. , Spiel A.O. , Steinlechner B. , Novellini R. , Jilma B.
Published: January 2017

Reparixin antagonizes interleukin-8 (IL-8) on the level of signal transduction in vitro. We hypothesized that IL-8 mediates some of the reactions occurring during acute inflammation and specifically that IL-8 may be a mediator of endotoxin induced neutrophilia. We therefore tested the effects of reparixin on humoral and cellular parameters in LPS-induced acute systemic inflammation. The study is a randomized (3:2 active:placebo), double-blind, placebo-controlled parallel group trial. Twenty healthy male volunteers randomly received either reparixin (12) or placebo (8) intravenously. One hour after the start of reparixin/placebo infusion a bolus of 2 ng/kg endotoxin was infused over 1–2 min. Blood samples were obtained over 24 h. Reparixin, being metabolized to ibuprofen, suppressed serum thromboxane B2 levels by 78% compared to baseline and control at 8 h. LPS-induced neutrophilia was not significantly affected by reparixin in human volunteers. Consistently, reparixin did not alter the lymphocyte or monocyte counts and had no effect on LPS-induced systemic inflammation as measured by tumor necrosis factor alpha (TNF-α) or interleukin-6 (IL-6) release. Regulation of IL-8 receptors CXCR1 and 2 and the degranulation marker CD11b showed the expected kinetics. Reparixin had no effect on thrombin formation as measured by prothrombin fragment (F1+2). In conclusion, our study showed that reparixin was safe but had no impact on endotoxin induced inflammation. In contrast to previous studies with its metabolite ibuprofen, reparixin does not enhance inflammation in this model.
Genetic Predisposition to Rheumatoid Arthritis in a Tuscan (Italy) Ancient Human Remain
Authors: Fontecchio G. , Fioroni M.A. , Azzarone R. , Battistoni C. , Cervelli C. , Ventura L. , Mercurio C. , Fornaciari G. , Papola F.
Published: January 2017

Rheumatoid arthritis (RA) is currently believed to have originated in America, and after the discovery of this continent in 1492, to have been exported to the Old World. We evaluated the genetic predisposition to RA in the “Braids Lady” from Arezzo (Italy), a partially mummified woman's body dating back to the end of 1500 AD which presents the anatomical and pathological features of this disease. The study of the polymorphic HLA-DRB1 locus, which includes alleles strongly associated with RA onset, has received much attention over recent years, especially the loci codifying for the DR1 and DR4 antigens, widely represented in the Mediterranean population, and for DR14, widespread among Native Americans. Molecular analysis was performed on extracts of DNA from the mummy, firstly from histological bone sections and then from the whole bone. Two different HLA typing techniques, PCR-sequence-specific oligonucleotides (PCR-SSO) and PCR-sequence-specific primers (PCR-SSP), were employed to identify HLA-DRB alleles. Both genotyping methods showed that the “Braids Lady” carried the DRB1*0101 allele, the serological equivalent of the DR1 antigen. Although the possession of RA risk factor genes cannot be considered a diagnostic marker, the positive result of the Italian mummy for DRB1*0101 and the RA features present, support the idea that this pathology was present in the Old World from at least the mid-16th century. A pathogenetic hypothesis of RA which might well explain its worldwide diffusion is the “molecular mimicry”, resulting from a cross-reactive antibody response between certain microbial antigens and shared epitopes of specific HLA-DR1, DR4 and DR14 susceptibility alleles, the frequency of which varies among different ethnic groups.
Penicillamine-Related Lichenoid Dermatitis and Utility of Zinc Acetate in a Wilson Disease Patient with Hepatic Presentation, Anxiety and Spect Abnormalities
Authors: Leggio L. , Ferrulli A. , Mirijello A. , Abenavoli L. , Di Giuda D , Funiciello S. , Rotoli M. , Gasbarrini G. , Addolorato G.
Published: January 2017

Wilson disease is an autosomal recessive disorder of hepatic copper metabolism with consequent copper accumulation and toxicity in many tissues and consequent hepatic, neurologic and psychiatric disorders. We report a case of Wilson disease with chronic liver disease; moreover, in our patient, presenting also with high levels of state anxiety without depression 99mTc-ECD-SPECT showed cortical hypoperfusion in frontal lobes, more marked on the left frontal lobe. During the follow-up of our patient, penicillamine was interrupted after the appearance of a lichenoid dermatitis, and zinc acetate permitted to continue the successful treatment of the patient without side-effects. In our case the therapy with zinc acetate represented an effective treatment for a Wilson disease patient in which penicillamine-related side effects appeared. The safety of the zinc acetate allowed us to avoid other potentially toxic chelating drugs; this observation is in line with the growing evidence on the efficacy of the drug in the treatment of Wilson disease. Since most of Wilson disease penicillamine-treated patients do not seem to develop this skin lesion, it could be conceivable that a specific genetic factor is involved in drug response. Further studies are needed for a better clarification of Wilson disease therapy, and in particular to differentiate specific therapies for different Wilson disease phenotypes.
A Novel Treatment of Contact Dermatitis by Topical Application of Phospholipase A2 Inhibitor: A Double-Blind Placebo-Controlled Pilot Study
Authors: Ingber A. , Cohen Y. , Krimsky M. , Yedgar S.
Published: January 2017

Phospholipase A2 hydrolyzes membrane phospholipids releasing arachidonic acid and lysophospholipids. These are key precursors of inflammatory mediators, such as prostaglandins, leukotrienes, thromboxanes and PAF, in numerous inflammatory/allergic diseases, including skin inflammation. Accordingly, inhibition of PLA2 has long been postulated as a potentially potent antiinflammatory therapy. In the present study we tested the effect of a novel PLA2 inhibitor on contact dermatitis in human subjects. A double-blind, placebo-controlled pilot study was conducted on contact dermatitis patients (n = 11) treated with the inhibitor-containing topical preparation (1% cream). Disease severity was assessed by physician's assessment before treatment (day 0) as well as after 14-days and 30-days. Patients treated with 1% PLA2 inhibitor-containing cream showed a 69.9% reduction in disease score while placebo-treated patients showed a reduction of 36.5% with p = 0.0024. The clear improvement in the disease score of inhibitor-treated patients supports the involvement of PLA2 activity in skin inflammation and the therapeutic prospective of its inhibition.
Invasive Pathway of Listeria Ivanovii in Human Amnion-Derived Wish Cells
Authors: Ammendolia M.G. , Superti F. , Bertuccini L. , Chiarini F. , Conte M.P. , Cipriani D. , Seganti L. , Longhi C.
Published: January 2017

Among Listeria genus, only two species, Listeria ivanovii and Listeria monocytogenes, are pathogenic. L. ivanovii is almost only associated with infections in animals, mainly sheep and cattle, and has rarely been associated with human infections, whereas L. monocytogenes causes severe illnesses in both humans and animals. To further investigate the pathogenetic features of L. ivanovii in humans, we undertook a study in which the intracellular behaviour of this pathogen was analysed in WISH cells, a cell line derived from human amniotic tissue, and compared to that of L. monocytogenes. Using microbiological, biochemical, and ultrastructural approaches, we demonstrate that L. ivanovii can adhere to and invade human amniotic cells, lyse the phagosomal membrane, polymerize host cell actin, and spread from cell to cell more efficiently than L. monocytogenes. However, although L. ivanovii is capable of specifically infecting and replicating in human amnion cells, its survival in cytoplasm is limited compared to that of L. monocytogenes.
The Prominent Role of P38 Mitogen-Activated Protein Kinase in Insulin-Mediated Enhancement of VCAM-1 Expression in Endothelial Cells
Authors: Madonna R. , Massaro M. , Pandolfi A. , Consoli A. , De Caterina R.
Published: January 2017

Insulin levels are a marker for cardiovascular events, but the link between hyperinsulinemia and atherosclerosis is poorly understood. We previously showed that insulin increases monocyte-endothelial interactions and the endothelial expression of the pro-atherogenic vascular cell adhesion molecule-1 (VCAM-1). The aim of this study is to examine molecular mechanisms involved in the effect of insulin on VCAM-1 expression. Human umbilical vein endothelial cells (HUVEC) were incubated with insulin (0–24 h) ± inhibitors of signaling pathways potentially involved. At pathophysiological concentrations (10−9-10−7 M), insulin selectively induced VCAM-1 expression. The p38mitogen activated protein(MAP) kinase inhibitors SB203580 and SB202190, and partially the c-Jun NH2-terminal kinase (JNK) inhibitor SP600127, decreased insulin effect on VCAM-1. Gene silencing by small interfering RNA significantly reduced the expression of p38MAP kinase, and this was accompanied by suppression of insulin-stimulated VCAM-1 expression. Treatment with insulin also led to the activation of NF-κB and induction of IκB-α phosphorylation, thus accounting for NF-κB translocation into the nucleus. Co-treatment of HUVEC with insulin and SB202190 strongly reverted the stimulatory effect of insulin on NF-κB activation, thus establishing a link between NF-κB activation and p38MAPkinase-mediated induction of VCAM-1 by insulin. In conclusion, pathophysiological insulin concentrations increase VCAM-1 expression and activate NF-κB. This mostly occurs through stimulation of p38MAP kinase.
Defective Function of the Fas Apoptotic Pathway in Type 1 Diabetes Mellitus Correlates with Age at Onset
Authors: De Franco S. , Chiocchetti A. , Ferretti M. , Castelli L. , Cadario F. , Cerutti F. , Rabbone I. , Indelicato M. , Mazzarino C. , Chessa M. , Bona G. , Dianzani U.
Published: January 2017

The Fas death receptor triggers lymphocyte apoptosis through an extrinsic and an intrinsic pathway involving caspase-8 and -9 respectively. Inherited defects of Fas function are displayed by a proportion of patients with Type 1 diabetes mellitus (T1DM) especially those with a second autoimmunity (T1DM-p). This study assesses activation of both pathways in Fas-resistant (FasR) patients to localize the defect. 21/28 (75%) T1DM-p, 14/50 (38%) T1DM, and 7/150 (5%) controls were FasR. Analysis of the 35 FasR patients and 20 Fas-sensitive (FasS) controls showed that caspase-9 activity was lower in T1DM-p and T1DM than in controls, whereas caspase-8 activity was lower in T1DM-p than in T1DM and the controls. Single patient analysis showed that 16/35 patients displayed defective activity of one (FasR1), whereas 19 displayed normal activity of both caspases (FasR2) Ages at onset of diabetes mellitus in T1DM and the second autoimmune disease in T1DM-p were lower in FasR than in FasS patients. All FasR1 patients developed diabetes mellitus before the age of 9 years, whereas a later onset was displayed by 26% FasR2 and 53% FasS patients. These data show that defective Fas function may involve both the extrinsic and intrinsic pathway in T1DM and severity correlates with the precocity of the autoimmune attack and its tissue polyreactivity.
Effects of Zafirlukast on Capsular Contracture: Controlled Study Measuring the Mammary Compliance
Authors: Scuderi N. , Mazzocchi M. , Rubino C.
Published: January 2017

Capsular contracture is a highly distressing, difficult complication after breast augmentation for both the patient and the surgeon. Although capsular contracture is a multifactorial process, one common denominator in the successful treatment of this complication is believed to be the abatement of inflammation. Leukotriene antagonists have recently emerged as effective prophylactic agents in reactive airway diseases. Anecdotal reports have indicated that zafirlukast (Accolate, AstraZeneca) effectively reverses capsular contracture. A prospective study of capsular contracture in 120 female patients in whom a total of 216 prostheses were implanted was performed. The hardness of capsular contracture was assessed by means of the mammary compliance method (Anton Paar Mammacompliance system). The patients were divided into two groups: patients in group A received zafirlukast for a 6-month period, while those in group B received vitamin E. The results show a significant decrease of the values of breast compliance after 6 months in group A but not in group B and that the variation in compliance after 6 months in group A compared to group B is statistically significant. In zafirlukast-treated patients, we observed a reduction in mammary compliance of 7.69% after 1 month, 16.78% after 3 months and 24.01% after 6 months. The present study suggests that zafirlukast may be effective in reducing pain and breast capsule distortion in patients with longstanding contracture who are either not surgical candidates or who do not wish to undergo surgery.
Long-Lasting Production of TGF-β1 by Alveolar Macrophages Exposed to Low Doses of Asbestos without Apoptosis
Authors: Nishimura Y. , Nishiike-Wada T. , Wada Y. , Miura Y. , Otsuki T. , Iguchi H.
Published: January 2017

Alveolar macrophages (AMs) exposed to asbestos are well known to produce TNF-α, which induces the production of TGF-β1, leading to lung fibrogenesis. The present study examines the production of TGF-β1 by AMs exposed to chrysotile B asbestos (CH) in vivo or in vitro and the relationship between TGF-β1 production and apoptosis in cultures of AMs. Rats instilled with CH via the trachea showed increases in TNF-α, IL-1β and IL-6 in the bronchoalveolar lavage fluid (B ALF) 1 day after the instillation, followed by increases in TGF-β1 and apoptotic cells 5 days after. The AMs from these BALFs produced a significantly increased amount of TGF-β1 in culture compared to those from the control rats. The addition of 2.5 μg/cm2 of CH augmented the production of TGF-β1 by the AMs from the control to the same level as produced by the AMs from the CH-treated rats. The apoptosis of AMs was not induced at 2.5 μg/cm2 of CH, but was drastically induced at over 12.5 μg/cm2. In contrast, the production of TGF-β1 by AMs peaked at around 2.5 μg/cm2 of CH, and it lasted for 11 days. In addition, Bcl-2 and Bcl-xL increased in the AMs surviving under the exposure to CH. Taken together, these results indicate that AMs can autonomously, without other pulmonary cells, acquire the lasting ability to produce TGF-β1 independently of apoptosis under low exposure to CH. The AMs with the lasting production of TGF-β1 may contribute not only to lung fibrosis but also to immune suppression.
N-3 Polyunsaturated Fatty Acid Effect in Periodontal Disease: State of Art and Possible Mechanisms Involved
Authors: Raffaelli L. , Serini S. , Piccioni E. , Manicone P.F. , Berardi D. , Perfetti G. , Calviello G.
Published: January 2017

Anti-inflammatory properties have been widely reported for n-3 polyunsaturated fatty acids (PUFAs) and some studies have been focalized on their possible role in the modulation of gingivitis and alveolar bone resorption in periodontal disease (PD). Increased formation of arachidonic acid-derived inflammatory eicosanoids and augmented oxidative stress are two molecular mechanisms pathogenetically involved in the progression of PD and known to be inhibited by n-3 PUFAs in PD setting. The present review will focus also on other molecular pathways and factors known to be altered in the development of PD and known to be subject to n-3 PUFA modulation in other pathological settings different from PD. Overall, the available findings strongly encourage further experimental studies on animals subject to experimental PD and treated with n-3 PUFAs, long term n-3 PUFA intervention studies on PD patients and molecular studies to identify additional potential molecular routes of n-3 PUFA action in PD.
Stability of Sirolimus and Everolimus Measured by Immunoassay Techniques in Whole Blood Samples from Kidney Transplant Patients
Authors: Capone D. , Gentile A. , Polichetti G. , Federico S. , Sabbatini M. , Acampora A. , Basile V. , Pieri M. , Tarantino G.
Published: January 2017

The measurement of blood concentration of immunosuppressive drugs is strongly recommended because of the narrow therapeutic range. An important aspect in the therapeutic monitoring of a drug is its possible degradation. This paper is aimed at investigating the stability of two widely-used immunosuppressants, sirolimus and everolimus. Short (storage at 30°C for 3 or 7 days) and long term (storage at −20°C for 0–90 days with a single freeze-thaw cycle) stability of sirolimus and everolimus in whole blood samples from kidney transplant patients were examined by using MEIA and FPIA. Sirolimus and everolimus samples stored at 30°C in light for up to a week showed a decrement in concentration of 5.2% and 6.1%, respectively. Our findings on long term stability for both sirolimus and everolimus highlight the possibility of storing samples at −20 °C for up to 90 days, without the need to use lower storage temperatures. The results have important implications for patients living far from laboratories where drug concentration is measured or when the storing of blood samples is needed for pharmacokinetic studies.
Evaluation of C-Reactive Protein and Total Serum Cholesterol in Adult Patients with Bipolar Disorder
Authors: De Berardis D. , Conti C.M. , Campanella D. , Carano A. , Scali M. , Valchera A. , Serroni N. , Pizzorno A.M. , D'Albenzio A. , Fulcheri M. , Gambi F. , Larovere R. , Cotellessa C. , Salerno R.M. , Ferro F.M.
Published: January 2017

The aim of the present study is to evaluate the role of CRP and Total Cholesterol (TC) in patients suffering from type I Bipolar Disorder (BD-I). Moreover, the goal is to elucidate possible CRP and TC differences in different phases of BD-I: acute mania, euthymia and bipolar depression. Medical records of 90 BD-I patients (30 patients with acute mania, 30 in euthymic state, full remission, and 30 in depressive phase) were reviewed to evaluate serum CRP and TC levels. Laboratory data of 30 healthy controls were also obtained. The scores of Young Mania Rating Scale (YMRS), Bech-Rafaelsen Manic Rating Scale (BRMRS) and Hamilton Rating Scale for Depression (HAM-D) were evaluated. CRP levels were higher in acute mania and depressive phase subgroups when compared to healthy controls. CRP was positively associated with BRMRS and YMRS scores in acute mania and with HAM-D in depressive phase subgroups. TC levels were lower in all clinical groups compared to controls. TC levels were negatively correlated to BRMRS, YMRS and HAM-D. In conclusion, the results of the present study support the notion that CRP and TC may be altered in patients with BP-I.
Histological and Clinical Survey of Polylactic-Polyglycolic Acid and Dextrane Copolymer in Maxillary Sinus Lift: A Pilot in Vivo Study
Authors: Martuscelli R. , Maltarello M.C. , Maraldi N.M. , Sbordone C. , Sbordone L.
Published: January 2017

Of various proposed alternatives to autogenous bone, a synthetic, degradable copolymer of PLA-GLA and dextrane seems to be a promising biomaterial for maxillary sinus lift. Consecutive partially edentulous patients showing severe monolateral posterior maxillary atrophy were treated via sinus lift using PLA-GLA-dextrane copolymer as the sole filler. Delayed implant positioning was performed and cores of regenerated tissues and native bone controls were retrieved and evaluated by light and electron microscopy, histomorphometry, microhardness and qualitative X-ray analysis. Seven sinuses in 7 patients were augmented with PLA-GLA-dextrane copolymer. Six to nine months after the copolymer ‘graft’, 17 bone cores were retrieved: all histological sections contained newly synthesized, mineralized material and new bone in various stages of development. Histomorphometry revealed average Trabecular Bone Volume (TBV) values ranging from 51% (6 months) to 77% (9 months). Backscattered scanning electron microscopy (BSE) in experimental and control samples confirmed histology findings. Microhardness values suggested newly formed bone at nine months was not as hard as native bone. Ca and P content was similar in 9-month regenerated and native bone. Seventeen implants were inserted in the second stage of surgery: resulting Implant Success (SR) and Cumulative Success (CSR) up to 3 years were 100% following Albrektsson's criteria. Sinus lift augmentation using PLA-GLA-dextrane copolymer as the sole filler resulted in uneventful surgeries. New bone formation was evident histologically and its maturation was still in progress after 9 months. Successful, staged implant positioning was achieved in regenerated tissue.
Visceral Leishmaniasis Revealing Chronic Granulomatous Disease in a Child
Authors: Finocchi A. , Palma P. , Di Matteo G. , Chiriaco M. , Lancella L. , Simonetti A. , Rana I. , Livadiotti S. , Rossi P.
Published: January 2017

We report the first description of visceral leishmaniasis (VL) infection as a harbinger of chronic granulomatous disease (CGD) in a 3-year old child. Although VL is not frequently suspected in CGD patients, our case emphasises the importance of a complete evaluation of the immune system in children presenting with VL in order to exclude underlying immunodeficiency states. As the prognosis of CGD is poor, with high morbidity and mortality, establishing an early diagnosis has important practical implications in the successful treatment of these patients. Following the diagnosis, the patient received Human Leukocyte Antigen (HLA) identical sibling bone marrow transplantation (BMT). The child is now 2 years post-transplant and is in good general conditions with normal blood counts, and evidence of full-donor chimerism in repeated fluorescence in situ hybridization (FISH) studies.
Clinical and Immunological Correlates of Pre-Co-Seasonal Sublingual Immunotherapy with Birch Monomeric Allergoid in Patients with Allergic Rhinoconjunctivitis
Authors: Burastero S.E. , Mistrello G. , Paolucci C. , Breda D. , Roncarolo D. , Zanotta S. , Falagiani P.
Published: January 2017

Sublingual immunotherapy is safe and efficacious in the treatment of patients with allergic rhinitis. The clinical and biological efficacy of modified allergens (allergoids) has not been fully clarified. We investigated in birch allergic patients the effect of a pre-co-seasonal sublingual immunotherapy regimen with a modified allergen extract on clinical parameters and on T cell proliferation and regulatory cytokine production (IL-10, TGF-beta). We found that during the birch pollen season symptoms and drug usage scores were 30 and 40% improved, respectively, in treated versus control subjects (p<0.0001 for both comparisons) whereas well days were 23.5 (33%) versus 16.9 (23%) (p=0.0024), respectively. Bet v 1 allergen specific proliferation decreased (p = 0.0010), whereas IL-10 transcription increased (p = 0.0010) in treated, but not in control patients. Moreover, TGF-beta transcription was increased, although not significantly (p=0.066), following immunotherapy. Thus, sublingual immunotherapy with modified allergen in birch-allergic subjects was safe, clinically efficacious and associated with the reduction of allergen-specific proliferation and with the increased production of the IL-10 regulatory cytokine.
Influence of the Duffy Antigen on Pharmacokinetics and Pharmacodynamics of Recombinant Monocyte Chemoattractant Protein (MCP-1, CCL-2) in Vivo
Authors: Mayr F.B. , Spiel A.O. , Leitner J.M. , Firbas C. , Schnee J. , Hilbert J. , Derendorf H. , Jilma B.
Published: January 2017

Monocyte chemoattractant protein-1 (MCP-1, CCL-2) binds to the Duffy antigen (DARC) on red blood cells, which act as a sink for several chemokines including MCP-1. In this study it is hypothesized that DARC may alter the pharmacokinetics of infused recombinant human MCP-1 (rhMCP-1). The primary aim of this first in man trial is to compare the pharmacokinetics of rhMCP-1 in Duffy positive and negative individuals. A randomized, double-blinded, placebo-controlled dose escalation trial was conducted on 36 healthy volunteers. Subjects received infusions of 0.02–2.0 μg/kg rhMCP-1 or placebo for one hour. RhMCP-1 displayed linear pharmacokinetics. Duffy negative individuals reached maximal plasma levels significantly earlier, but overall plasma concentration profiles were not altered. rhMCP-1 markedly increased monocyte counts, and estimated EC50 values were 10-fold higher in Duffy positive than in Duffy negative subjects. Increased monocyte counts were associated with decreased surface expression of intercellular adhesion molecule 1 (ICAM-1, CD54). In contrast, neither CCR-2 or CD11b expression, nor markers of platelet or endothelial activation, inflammation and coagulation were altered. RhMCP-1 is a highly selective chemoattractant for monocytes in humans. The Duffy antigen only minimally alters the pharmacokinetics of rhMCP-1 for doses up to 2 μg/kg.
Immunogenicity of Ra1A and its Tissue-Specific Expression in Hepatocellular Carcinoma
Authors: Wang K. , Chen Y. , Liu S. , Qiu S. , Gao S. , Huang X. , Zhang J. , Peng X. , Qiani W. , Zhang J.Y.
Published: January 2017

In order to understand the immunogenicity of a tumor-associated antigen (TAA), Ras family small GTP binding protein (RalA) in hepatocellular carcinoma (HCC), autoantibody responses to RalA were evaluated by enzyme-linked immunosorbent assay (ELISA), Western blotting and indirect immunofluorescence assay in sera from patients with HCC and sera from normal individuals. Immunohistochemistry (IHC) study with tissue array slides was also preformed to analyze protein expression profiles of RalA in HCC and control tissues. This study demonstrated that RalA had a relative higher frequency of autoantibody response in HCC (20.1%) compared to liver cirrhosis (3.3%), chronic hepatitis (0%), and normal individuals sera (0%). RalA also showed a stepwise increased expression from normal liver tissues (26.7%), liver cirrhosis tissues (45.0%) to HCC tissues (63.3%). Sensitivity and specificity of anti-RalA antibody in detection of HCC was 20.1% and 99.3%, respectively. The data suggested that RalA might contribute to liver malignant transformation, and could be used as a potential tumor marker in HCC detection.
Development of a New Zirconia-Toughened Alumina: Promising Mechanical Properties and Absence of In Vitro Carcinogenicity
Authors: Maccauro G. , Bianchino G. , Sangiorgi S. , Magnani G. , Marotta D. , Manicone P.F. , Raffaelli L. , Iommetti P. Rossi , Stewart A. , Cittadini A. , Sgambato A.
Published: January 2017

High purity alumina as well as zirconia ceramics have been widely used as orthopaedic implant biomaterials and dental devices displaying optimal, but sometimes exclusive, mechanical properties. In order to combine the advantages of alumina and zirconia ceramic materials different types of composites have been developed in which either zirconia is dispersed in an alumina matrix or vice versa. Orthopaedic and dental implant biomaterials are expected to be in contact with living tissues for a long period of time and their long term toxicity must be carefully evaluated. In this study we report the development of a high performance chromia-doped Zirconia Toughened Alumina (ZTA) material which displays promising mechanical properties in terms of hardness, strength and fracture toughness that make it suitable for prosthesis even for small joints. The long-term biocompatibility of this material was also evaluated, mainly in terms of DNA damage, mutagenicity and cancerogenetic potential in mammalian cells. The results obtained suggest that this new ZTA material does not display any long-term carcinogenic effect and it is suitable for biomedical applications from a cancerogenetic point of view. In conclusion, we report the development of a new chromia-doped ZTA material with interesting properties both from a mechanical and a biocompatibility point of view which warrant further studies on its suitability as a candidate biomaterial for orthopaedic implants and dental devices.
Bromhidrosis Induced by Sphingomonas Paucimobilis: A Case Report
Authors: Mancini M. , Panasiti V. , Devirgiliis V. , Pietropaolo V. , Fioriti D , Nicosia R. , Curzio M. , Roberti V. , Gobbi S. , Bottoni U. , Chiarini F. , Calvieri S.
Published: January 2017

Bromhidrosis is a clinical disorder characterized by excessive or abnormal foul axillary odour due to the interaction of apocrine glands with micro-organisms which causes a serious personal and social handicap for affected people. We present the case of a 50-year-old caucasian female with bromhidrosis. The patient referred that this symptom had begun two months previously. Her past treatments included antibacterial soap, topical antibacterial agents and perfumes, but none of these relieved the patient of the odour. A cultural examination of axillary smear was carried out and it revealed the presence of ciprofloxacin sensible Sphingomonas paucimobilis. Therefore the patient was treated with ciprofloxacin and after 1 week the infection resolved completely.
Beneficial Effects of Telmisartan in an HIV+ Diabetic Insulin-Dependent Patient
Authors: Ucciferri C. , Mancino P. , Vecchiet J. , Falasca K.
Published: January 2017

In HIV-infected patients with metabolic disorders, as in the general population, there is evidence of hypertension requiring pharmacological treatment. The presence of diabetes constitutes a cluster of particularly high cardiovascular risks in patients, both regarding diabetic damage and hypertensive damage. We used telmisartan to manage high blood pressure values in an HIV-positive patient with insulin-dependent diabetes. Surprisingly, insulin therapy had to be suspended because of hypoglycemic fits and treatment with metformin was started. In conclusion, telmisartan was effective and well-tolerated for the control of hypertension in this case and improved sensitivity to insulin. There are interesting effects of this drug in HIV-positive diabetic patients. Thus, if further studies confirm these effects, telmisartan may be the anti-hypertensive drug of first choice in HIV-infected subjects on combined antiretroviral therapy affected with diabetes and metabolic disorders.