bluuebunny/crossref_metadata_2025 huggingface dataset:
Sarcopenia: Age-Related Skeletal Muscle Changes from Determinants to Physical Disability
Authors: Di Iorio A. , Abate M. , Di Renzo D. , Russolillo A. , Battaglini C. , Ripari P. , Saggini R. , Paganelli R. , Abate G.
Published: January 2017

Human aging is characterized by skeletal muscle wasting, a debilitating condition which sets the susceptibility for diseases that directly affect the quality of life and often limit life span. Sarcopenia, i.e. the reduction of muscle mass and/or function, is the consequence of a reduction of protein synthesis and an increase in muscle protein degradation. In addition, the capacity for muscle regeneration is severely impaired in aging and this can lead to disability, particularly in patients with other concomitant diseases or organ impairment. Immobility and lack of exercise, increased levels of proinflammatory cytokines, increased production of oxygen free radicals or impaired detoxification, low anabolic hormone output, malnutrition and reduced neurological drive have been advocated as being responsible for sarcopenia. It is intriguing to notice that multiple pathways converge on skeletal muscle dysfunction, but the factors involved sometimes diverge to different pathways, thus intersecting at critical points. It is reasonable to argue that the activity of these nodes results from the net balance of regulating mechanisms, as in the case of the GH/IGF-1 axis, the testosterone and Cortisol functions, the pro- and anti-inflammatory cytokines and receptors. Both genetic and epigenetic mechanisms operate in regulating the final phenotype, the extent of muscle atrophy and reduction in strength and force generation. It is widely accepted that intervention on lifestyle habits represents an affordable and practical way to modify on a large scale some detrimental outcomes of aging, and particularly sarcopenia. The identification of the molecular chain able to reverse sarcopenia is a major goal of studies on human aging.
The Role of C-Reactive Protein in Mood Disorders
Authors: De Berardis D. , Campanella D. , Gambi F. , La Rovere R. , Carano A. , Conti C.M. , Silvestrini C. , Serroni N. , Piersanti D. , Di Giuseppe B. , Moschetta F.S. , Cotellessa C. , Fulcheri M. , Salerno R.M. , Ferro F.M.
Published: January 2017

Recently, a possible relationship between C-Reactive Protein (CRP), a marker of underlying low-grade inflammation, and mood disorders has been proposed by some researchers. The aim of this review is to elucidate the current facts and views about CRP in mood disorders such as Depressive and Bipolar Disorders. Several studies have examined the relationship between affective disorders and CRP, but the majority of the studies in literature have been limited by retrospective, case-controlled study design, and very few studies have examined the relationship between depression and CRP in large study samples. In conclusion, the role of CRP in mood disorders is, to date, intriguing but somewhat unclear. Further prospective studies are needed to introduce the CRP in clinical settings as a marker of affective states and suicidability.
Endothelial Cell Anergy is Mediated by bFGF through the Sustained Activation of p38-MAPK and NF-κB Inhibition
Authors: Flati V. , Pastore L.I. , Griffioen A.W. , Satijn S. , Tomato E. , D'Alimonte I. , Laglia E. , Marchetti P. , Gulino A. , Martinotti S.
Published: January 2017

Tumors escape from immune surveillance by, among other mechanisms, the down- regulation of endothelial adhesion molecules, such as ICAM-1, and by unresponsiveness to inflammatory signals, a process mediated by angiogenic factors that is called endothelial cell anergy. Here we present the cell biological regulation of these processes. The angiogenic basic fibroblast growth factor (bFGF/FGF-2) was found to inhibit tumor necrosis factor-α (TNF-α)- induced elevation of ICAM-1, at transcriptional level. Furthermore, we found that bFGF inhibits the TNF-mediated activation of NF-κB by blocking phosphorylation and degradation of IκBα. We also found that bFGF induces hyperphosphorylation of p38 MAPK on endothelial cells, whereas inhibition of such kinase abrogates the effect of bFGF on the TNF-mediated activation of NF-κB. Thus, we suggest that bFGF acts as an inhibitor of leukocyte adhesion in tumor vessels by decreasing the ICAM-1 expression through the sustained activation of p38-MAPK and via inhibition of NF-κB.
IL-16 Serum Level in Children with Atopic Dermatitis
Authors: Fortina A. Belloni , Tonin E. , Pigozzi B. , Romano I. , Michelotto G. , Alaibac M.
Published: January 2017

IL-16 is a natural ligand of CD4 molecules and induces Chemotaxis in CD4-expressing cells. It amplifies the inflammatory reaction by stimulating cytokine production in monocytes and activating T-cells. There is evidence that IL-16 plays a role in the pathogenesis of atopic dermatitis, and increased serum levels of IL-16 have been detected in allergic diseases. However, few data are available on IL-16 serum levels in atopic dermatitis. The aim of our study is to measure IL-16 serum levels in childhood atopic dermatitis before and after treatment and to evaluate a possible correlation between IL-16 serum levels and disease severity. IL-16 serum levels were measured by an ELISA approach in 34 children (19 males and 15 females; mean age 6.8 years) with moderate to severe atopic dermatitis, at their first visit and after 3 months of treatment, and in 10 non-atopic healthy controls of the same age group. The severity of atopic dermatitis was measured by SCORAD index. IL-16 serum levels were significantly higher in patients affected by atopic dermatitis than in controls before and after treatment with tacrolimus ointment. No clear correlation was found between IL-16 serum levels and atopic dermatitis severity. IL-16 serum levels are increased in atopic dermatitis but do not seem to correlate with disease severity.
Prostate — Specific G Protein Couple Receptor Genes and STAG1/PMEPA1 in Peripheral Blood from Patients with Prostatic Cancer
Authors: Cardillo M.R. , Di Silverio F.
Published: January 2017

We investigated whether prostate - specific G protein couple receptor genes (PSGR) and STAG1/PMEPA1 gene expression in peripheral- blood could be useful as a diagnostic or prognostic marker of prostate cancer. Circulating cells were identified by reverse transcription-polymerase chain reaction (RT-PCR) to detect PSGR and STAG1/PMEPA1 mRNA in peripheral blood (PB) from 11 patients with treated prostate cancer (CaP), 11 with newly-diagnosed untreated CaP and 20 with benign prostatic hyperplasia (BPH) (controls). RT-PCR amplified PSGR in 8 of 11 untreated and in 9 of 11 treated patients with CaP and in 16 of 20 with BPH; whereas it amplified PMEPA1 in 1 of 11 untreated and in 7 of 11 treated patients with CaP and in 4 of 20 with BPH. In our control tissues and cell lines nearly all the prostatic and non- prostatic tissues and cell lines expressed PSGR mRNA, whereas only one prostatic neoplastic tissue and the androgen-responsive (LNCaP) and androgen non-responsive (PC3) prostatic cell lines expressed PMEPA1. These findings suggest that the investigated genes are poorly specific and probably of little use as diagnostic or prognostic markers in peripheral blood for monitoring prostate cancer progression and recurrence.
Immune Recovery following Antineoplastic Chemotherapy and Highly Active Antiretroviral Therapy (Haart) in a Child with HIV-1 Infection Previously Unresponsive to Haart
Authors: Galli L. , Chiappini E. , Lippi A. , De Martino M.
Published: January 2017

We report the case of a perinatally HIV-1-infected child, previously immunologically unresponsive to antiretroviral treatments (including the highly active antiretroviral therapy), who instead developed a vigorous and long-lasting immune response after the highly active antiretroviral therapy was associated with antineoplastic chemotherapy undertaken for a B-cell non-Hodgkin bone lymphoma.
Forest Bathing Enhances Human Natural Killer Activity and Expression of Anti-Cancer Proteins
Authors: Li Q. , Morimoto K. , Nakadai A. , Inagaki H. , Katsumata M. , Shimizu T. , Hirata Y. , Hirata K. , Suzuki H. , Miyazaki Y. , Kagawa T. , Koyama Y. , Ohira T. , Takayama N. , Krensky A.M. , Kawada T.
Published: January 2017

In order to explore the effect of forest bathing on human immune function, we investigated natural killer (NK) activity; the number of NK cells, and perforin, granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields. Twelve healthy male subjects, age 37–55 years, were selected with informed consent from three large companies in Tokyo, Japan. The subjects experienced a three-day/two-night trip in three different forest fields. On the first day, subjects walked for two hours in the afternoon in a forest field; and on the second day, they walked for two hours in the morning and afternoon, respectively, in two different forest fields. Blood was sampled on the second and third days, and NK activity; proportions of NK, T cells, granulysin, perforin, and granzymes A/B-expressing cells in PBL were measured. Similar measurements were made before the trip on a normal working day as the control. Almost all of the subjects (11/12) showed higher NK activity after the trip (about 50% increased) compared with before. There are significant differences both before and after the trip and between days 1 and 2 in NK activity. The forest bathing trip also significantly increased the numbers of NK, perforin, granulysin, and granzymes A/B-expressing cells. Taken together, these findings indicate that a forest bathing trip can increase NK activity, and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins.
Subjective Symptoms of Medical Students Exposed to Formaldehyde during a Gross Anatomy Dissection Course
Authors: Wei C.N. , Harada K. , Ohmori S. , Wei Q.J. , Minamoto K. , Ueda A.
Published: January 2017

The purpose of this study is to investigate the safety of and to try to find the best plan to cope with exposure to FA for students during a gross anatomy dissection course. The FA exposure level and subjective symptoms was estimated. The relationship between exposure to FA and subjective symptoms of irritation were discussed for times; before, in the beginning period, in the middle period, and upon completion of the Anatomy Dissection Course. The geometric means of FA concentration were 32.7 ug/m3 (before), 891.3 ug/m3 (beginning), 763.3 ug/m3 (middle), and 238.9 ug/m3 (completion), respectively. Among them, FA-related symptoms were observed in 61.1%; 28.0% fell strong stress during the course, and 27.4% complained that their normal life situation was affected. Our results indicate that such subjective symptoms during the anatomy dissection course were related to the period spent in the anatomy dissection room. Our study suggests that shortening the time of each anatomy dissection practical class and reduction of the number of cadaver tables could help to reduce symptoms.
Combined Effects of Electromagnetic Fields on Immune and Nervous Responses
Authors: Boscolo P. , Di Gioacchino M. , Di Giampaolo L. , Antonucci A. , Di Luzio S.
Published: January 2017

In technologically developed countries, there is concern about hazards from electromagnetic fields (EMFs). Several studies have reported that immune and neuroendocrine systems exert an integrated response to EMF exposure. The aim of this review is to summarize the results of studies on the effect of low and high frequency EMF on immune and neuroendocrine systems on which our research group has been working for several years.
HIV-Related Acute Inflammatory Leukoencephalopathy of Undetermined Origin: Review of the Literature
Authors: Tavazzi E. , Bargiggia V. , Pichiecchio A , Delbue S. , Maserati R. , Bastianello S. , Ferrante P. , Minoli L. , Ricevuti G. , Ceroni M. , Marchioni E.
Published: January 2017

HIV-related acute inflammatory leukoencephalopathy of undetermined origin (AIL) has been anecdotally described in literature as being responsible for cognitive and motor deficits. We carried out a review of all the cases of AIL published in literature. Articles were selected according to 2 criteria: acute onset of symptoms; undetermined aetiology and non-fulfilment of multiple sclerosis diagnostic criteria. They were then analyzed in terms of clinical, biological and instrumental features, therapy, diagnostic classification and prognosis. Although rare (21 patients out of about 4,000 publications), AIL is of particular interest, as the comprehension of its mechanisms could give some insight into the direct and immune-mediated actions of HIV within the brain. All the reported patients share several clinical, histopathological, radiological and CSF features, leading to hypothesize a similar aetiopathogenetic mechanism. Conversely, we observed a high heterogeneity of treatment and diagnostic classification, which could have conditioned the broad prognostic variability. The absence of a defined aetiology leads to consider these forms as a particular subgroup of “not determined leucoencephalopathies” (NDLE), with both MRI and histological pattern dominated by inflammation as distinctive feature.
Dietary Supplementation with Fructooligosaccharides Attenuates Airway Inflammation Related to House Dust Mite Allergen in Mice
Authors: Yasuda A. , Inoue K-I. , Sanbongi C. , Yanagisawa R. , Ichinose T. , Yoshikawa T. , Takano H.
Published: January 2017

Fructooligosaccharides (FOS) are prebiotic supplements that can enhance immunological responses in the host to activate mucosal immunity, probably through regulation of gastrointestinal microflora. An area that has not been investigated, however, is the therapeutic potential of prebiotics on allergic airway diseases. The purpose of this study is to evaluate the effects of dietary supplementation with FOS on a murine model of airway inflammation induced by the house dust mite allergen Dermatophagoides farinae (Der f). Male C3H/HeN mice were intratracheally administered with Der f and were fed a diet containing 0% or 2.5% FOS ad libitum. Supplementation with FOS alleviated mite allergen-related airway inflammation characterized by eosinophilic inflammation and goblet cell hyperplasia, which was evidenced by cytological and histological examinations. In addition, the FOS-supplemented diet reduced the serum allergen-specific IgG1 level as compared with a control diet in the presence of the mite allergen. Moreover, FOS tended to suppress the expression of IL-5 and eotaxin in the lungs, which is enhanced by mite allergen. These results suggest that dietary supplementation with FOS can prevent/improve airway inflammation induced by the mite allergen. This effect can be at least partially associated with the inhibition of allergen-specific Ig production and probably with that of IL-5 and eotaxin expression.
The Role of Etanercept on the Expression of Markers of T Helper 17 Cells and Their Precursors in Skin Lesions of Patients with Psoriasis Vulgaris
Authors: Antiga E. , Volpi W. , Chiarini C. , Cardilicchia E. , Filì L. , Manuelli C. , Parronchi P. , Fabbri P. , Caproni M.
Published: January 2017

Very recently, it has been demonstrated that CD161, retinoic acid—related orphan receptor γt (RORγt) and CC-chemokin receptor 6 (CCR6) can be considered good surface markers to detect T helper 17 cells and their precursors, T cell populations that are considered to play an important role in the pathogenesis of psoriasis. In the present study, we evaluate the clinical involvement by calculating the PASI score and the number of CD4+, CD161+, RORγt+ and CCR6+ cells before and after a 12-week course with etanercept or acitretin in patients with moderate-to-severe, plaque-type psoriasis vulgaris. Ten patients were given etanercept 50 mg twice weekly and 10 patients acitretin 0.4 mg/kg per day, both for 12 weeks. At the baseline and at the end of the treatment PASI was calculated, and skin biopsies were taken to evaluate the expression of CD4, CD161, RORyt and CCR6 by immunohistochemistry. As controls, 10 patients with atopic dermatitis (AD) were included in the study. After 12 weeks, PASI was significantly lower than at the baseline for both groups. However, etanercept-treated patients showed lower PASI than acitretin-treated ones. While CD4+ cell numbers were similar in both diseases, all the other markers, that are considered more specific for Th17 cells and their precursors, were more expressed in psoriasis than in AD. Furthermore, only etanercept, but not acitretin, was able to significantly reduce CD161+, RORγt+ and CCR6+ cells in skin lesions of patients with psoriasis. Our study provides further evidence of the role of Th17 pathway in the pathogenesis of psoriasis. Furthermore, our findings suggest that etanercept is able to downregulate the expression of the recently recognized markers of Th17 cells and their precursors CD161, RORγt and CCR6, while acitretin is not. This activity on the Th17 lineage may contribute to the efficacy of etanercept in the treatment of psoriasis.
Lipopolysaccharide from Porphyromonas Gingivalis Stimulates Rat Mast Cells to Cysteinyl Leukotriene Generation and Upregulates Toll-like Receptor −2 and −4 Expression
Authors: Konopka Ł. , Wierzbicki M. , Brzezińska-Błaszczyk E.
Published: January 2017

Mast cells are found in all tissues of the oral cavity and it is suggested that they take part in the development of oral inflammation. As Porhyromonas gingivalis is widely recognized as a major pathogen in the development and progression of gingivitis and periodontitis, the aim of our study is to determine the effect of P. gingivalis lipopolysaccharide (LPS) on mast cell degranulation, cysteinyl leukotriene (cysLT) generation, and migration, as well as Toll-like receptor (TLR)−2 and −4 expression. Experiments were carried out in vitro on rat peritoneal mast cells. LPS-induced mast cell histamine release was estimated by a spectrofluorometric method and cysLT generation by ELISA test. Mast cell migration in response to this antigen was examined according to Boyden's modified method and TLR expression was determined by flow cytometry. We found that P. gingivalis LPS did not induce mast cell degranulation and histamine release. However, activation of mast cells with this bacterial antigen resulted in generation and release of significant amounts of cysLTs. We also documented that LPS from P. gingivalis did not stimulate mast cell migration, even in the presence of laminin, whereas it strongly upregulated TLR2 and TLR4 expression on mast cells. Observations that P. gingivalis LPS activates mast cells to generate and release proinflammatory mediators such as cysLTs and modulates TLR2 and TLR4 expression indicates that these cells might be involved in the emergency of inflammatory processes evolved in response to P. gingivalis infection.
Microarray Analysis of NF-κB Signaling Pathways in PBMC of Mice Infected by Trichinella Spiralis
Authors: Symeonidou I. , Pappa S. , Kourelis A. , Anogeianaki A. , Frydas I. , Karagouni E. , Hatzistilianou M.
Published: January 2017

The NF-κB pathway gene expression profiles were compared between 10, 20 and 39 days after Trichinella spiralis experimental infection in BALB/c mice. Out of 128 genes, 19 (14.8%) genes were present in non-infected and post-infected mice. The expression of 7 (36.8%) genes was downregulated 10 and 20 days post-infection while 3 (15.8%) genes were upregulated 39 days post-infection. The present study lists the candidate genes of the NF-κB signaling pathway that were commonly and differentially expressed between the specific points of T. spiralis infection, thus suggesting that these genes need to be further investigated to reveal the mechanism of the T. spiralis modulation of the NF-κB signaling pathways.
Interkeratin Peptide-Protein Interactions That Promote HPV16 E7 Gene Expression
Authors: Lucchese A. , Serpico R. , Guida A. , Crincoli V. , Scully C. , Kanduc D.
Published: January 2017

Human papillomavirus (HPV) 16 E7 gene product encodes the major transforming activity of the virus so as to induce neoplastic transformation. Continued expression of HPV16 E7 protein is required for both the establishment and maintenance of the transformed cellular phenotype. Therefore, understanding of the molecular and biochemical factors leading to the expression of E7 protein is important in relation to HPV-associated diseases. Previously, we identified a rare codon usage and a specific interaction between cytokeratin (CK) 7 and HPV16 E7 mRNA as factors modulating HPV16 E7 expression. In the present study we report that CK19, a biochemical marker of squamous oral and cervical cancer carcinogenesis, promotes the expression of HPV16 E7 oncoprotein by binding to the CK792–97SEQIKA peptide. These findings shed light on the dynamic functionality of the intermediate filament cytoskeleton, open new perspectives for investigating the role of CKs in controlling HPV16 E7 expression, and suggest new therapeutic avenues for HPV-associated carcinomas.
Pharmacological Functional MRI Assessment of the Effect of Ibuprofen-Arginine in Painful Conditions
Authors: Delli Pizzi S. , Mantini D. , Ferretti A. , Caulo M. , Salerio I. , Romani G.L. , Del Gratta C. , Tartaro A.
Published: January 2017

Pharmacological functional magnetic resonance imaging (phMRI) is a valuable tool for the investigation of pharmacological effects of a drug on pain processing. We hypothesized that the ibuprofen-arginine combination, in line with its characteristic analgesic properties, may influence the phMRI response at the central level, as compared to placebo. Ten healthy subjects underwent a double-blind, placebo-controlled, randomized, cross-over phFMRI study with somatosensory painful stimulation of the right median nerve. We measured the blood oxygen level dependent (BOLD) signal variations induced in conditions of pain after oral administration of either ibuprofen-arginine or placebo formulations. Independent component analysis (ICA) was used for the analysis of the fMRI data, without assuming a specific hemodynamic response function (HRF), which may be altered by drug administration. Median nerve electrical painful stimulation mainly activated the primary contralateral and the secondary somatosensory cortices, the insula, the supplementary motor area, and the middle frontal gyrus. Placebo and ibuprofen-arginine administration induced activation bilaterally in the premotor cortex, and an overall reduction in the other pain-related areas, which was more prominent in the left hemisphere. A task-related increase of BOLD signal between drug and placebo was observed bilaterally in the primary somatosensory area and the middle frontal gyrus without any changes in subjective pain scores. Overall, our findings show that ibuprofen-arginine, in line with the characteristic analgesic properties of ibuprofen, influences the BOLD response in specific pain-related brain areas with respect to placebo, with a vasoactive effect possibly due to arginine.
A Long-Lasting Response to Sorafenib Treatment in an Advanced Hepatocellular Carcinoma Patient
Authors: Di Lorenzo G. , Imbimbo M. , Leopardo D. , Marciano R. , Federico P. , Buonerba C. , Salvatore B. , Marinelli A. , Palmieri G.
Published: January 2017

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. No effective systemic treatment has been established, except for sorafenib chemotherapy. In fact, sorafenib has proved to provide a statistically significant survival extension of about two months in two phase III trials in the North America-Europe area and in the Asia-Pacific area, which respectively reported a median survival after treatment of 10.7 and 6.5 months, respectively. We report the case of an HCC patient, who received a four-month therapy with sorafenib with a clinical, biochemical and radiographic response, but had to interrupt treatment because of a myocardial infarction. Surprisingly, despite no antitumor treatment having been administered for about a year, the patient has shown no tumor progression and is currently on a close follow-up. Should other similar cases be presented, a subset of patients with long-lasting response to sorafenib might be identified.
Sudden Progression from Impaired Glucose Tolerance to Type 2 Diabetes after Discontinuation of Administration of Anti-Tumor Necrosis Factor-Alpha Antibody Infliximab
Authors: Ursini F. , Succurro E. , Grembiale A. , Rudi S. , Grembiale R.D. , Arturi F.
Published: January 2017

We present the case of a 45-year-old man with psoriasis and psoriatic arthritis and concomitant impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). In this patient, refractory to DMARD's, infliximab was started to control the arthritis. After achieving clinical remission of the disease, infliximab was discontinued and a 75 g- oral glucose tolerance test (OGTT) was performed. After the test, we observed a conversion from IFG/IGT glucose tolerance status to type 2 diabetes. No diet, lifestyle or therapy modifications were made during the observation period. Autoimmune diabetes was ruled out by serum antibodies determination and body weight remained constant, sustaining a protective role of infliximab in the worsening of glucose tolerance.
Etanercept Therapy in Patients with Psoriasis and Concomitant HCV Infection
Authors: Garavaglia M.C. , Altomare G.
Published: January 2017

Treatment of patients with psoriasis and/or psoriatic arthritis and concomitant hepatitis C infection remains difficult. Except for cyclosporine, other drugs have proved unacceptable because of hepatotoxicity in patients with HCV. With the advent of anti-TNF-alpha drugs, including etanercept, new therapeutic options have become available. Our study population was five patients with psoriasis and/or psoriatic arthritis and concomitant chronic HCV infection undergoing etanercept therapy. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and viral load were used as markers for liver damage and disease progression, respectively. The Psoriasis Area Severity Index (PASI) was used as a reference parameter for evaluating the therapeutic efficacy of etanercept therapy in improving the clinical skin picture. AST, ALT, viral load and PASI were monitored at 3-month intervals starting from the beginning of therapy up to two years after initiation of etanercept therapy. In four out of five patients, liver enzyme levels and viral load remained substantially unchanged during the course of therapy. In the one remaining patient, viral load and liver enzyme levels increased during etanercept therapy, and then decreased following the initiation of Peg-IFN/ribavirin in combination with anti-TNF-alpha therapy. PASI scores decreased in all five patients. Our data suggest that etanercept therapy is safe and provides an efficacious therapeutic alternative in patients with psoriasis and concomitant HCV infection.
GW0742, a High Affinity PPAR-β/δ Agonist Reduces Lung Inflammation Induced by Bleomycin Instillation in Mice
Authors: Galuppo M. , Di Paola R. , Mazzon E. , Esposito E. , Paterniti I. , Kapoor A. , Thiemermann C. , Cuzzocrea S.
Published: January 2017

Peroxisome Proliferator-Activated Receptor β/δ belongs to a family of ligand-activated transcription factors. Recent data have clarified its metabolic roles and enhanced the potential role of this receptor as a pharmacological target. Moreover, although its role in acute inflammation remains unclear, being the nuclear receptor PPAR β/δ widely expressed in many tissues, including the vascular endothelium, we assume that the infiltration of PMNs into tissues, a prominent feature in inflammation, may also be related to PPAR β/δ. Mice subjected to intratracheal instillation of bleomycin (BLEO, 1 mg/kg), a glycopeptide produced by the bacterium Streptomyces verticillus, develop lung inflammation and injury characterized by a significant neutrophil infiltration and tissue oedema. Therefore, the aim of this study is to investigate the effects of GW0742, a synthetic high affinity PPAR β/δ agonist, and its possible role in preventing the advance of inflammatory and apoptotic processes induced by bleomycin, that long-term leads to the appearance of pulmonary fibrosis. Our data showed that GW0742-treatment (0.3 mg/Kg, 10% DMSO, i.p.) has therapeutic effects on pulmonary damage, decreasing many inflammatory and apoptotic parameters detected by measurement of: 1) cytokine production; 2) leukocyte accumulation, indirectly measured as decrease of myeloperoxidase (MPO) activity; 3) IκBα degradation and NF-κB nuclear translocation; 4) ERK phosphorylation; 5) stress oxidative by NO formation due to iNOS expression; 6) nitrotyrosine and PAR localization; 7) the degree of apoptosis, evaluated by Bax and Bcl2 balance, FAS ligand expression and TUNEL staining. Taken together, our results clearly show that GW0742 reduces the lung injury and inflammation due to the intratracheal BLEO-instillation in mice.
Controversial Role of Antibodies against Linear Epitopes of Desmoglein 3 in Pemphigus Vulgaris, as Revealed by Semiquantitative Living Cell Immunofluorescence Microscopy and in-Cell Elisa
Authors: Lanza A. , Perillo L. , Landi C. , Femiano F. , Gombos F. , Cirillo N.
Published: January 2017

A novel explanation of pemphigus vulgaris (PV) pathogenesis suggests that serum autoantibodies may affect desmoglein 3 (Dsg3)-mediated adhesion by triggering depletion of Dsg3 from desmosomes. Furthermore, abrogation of Dsg3 from the cell seems to depend on anti-Dsg3 pemphigus IgG. In this study we sought to gain more insights into the role of PV IgG recognizing non-conformational epitopes of Dsg3 (anti-Dsg3-L IgG) by semi-quantitative living cell immunofluorescence (LCIF) microscopy, in-cell ELISA and morphometric analysis of acantholysis. Our data demonstrate that PV serum and PV IgG can induce acantholysis and reduce the total amount of Dsg3 in cultured keratinocytes, whereas anti-Dsg3-L IgG fail to do so when administered at concentrations comparable to those present in pathogenic PV sera. However, the Dsg3-depleting activity of such polyclonal anti-Dsg3 IgG was acquired when used at 1μg/ml. Interestingly, both PV sera and IgG, including anti-Dsg3-L IgG, caused early depletion of surface Dsg3 while slightly affecting the total cell content of Dsg3 until late acantholysis. This raises a possibility that depletion of Dsg3 from cell membrane and reduction of the total cellular levels of Dsg3 represent distinct phenomena in PV acantholysis. Taken together, our data demonstrate that anti-Dsg3 PV IgG against linear epitopes of Dsg3 can induce acantholytic changes of keratinocytes in a dose- and time-dependent manner. Specifically, both morphological and biochemical changes suggestive of acantholysis are seen only at high IgG concentrations. We conclude that anti-Dsg3L IgG play a minor role in experimental PV under physiologic conditions.
Dexamethasone Affects FAS-and Serum Deprivation-Induced Cell Death of Human Osteoblastic Cells through Survivin Regulation
Authors: Rippo M.R. , Villanova F. , Ardori F. Tomassoni , Graciotti L. , Amatori S. , Manzotti S. , Fanelli M. , Gigante A. , Procopio A.
Published: January 2017

Glucocorticoid-induced bone loss is the most prevalent form of secondary osteoporosis. Such loss could be due to the alteration of osteoclast and osteoblast lifespan through regulated apoptosis. The current study investigated the effect of dexamethasone on Fas- and starvation-induced apoptosis of mature osteoblasts and their precursors. Using the human osteoblastic hFOB1.19 and the MG63 osteosarcoma cell lines, we found that sub-lethal doses of dexamethasone act on pre-osteoblasts but not on mature cells by increasing their susceptibility to apoptosis. Apoptosis occurs in a caspase-dependent manner as both DNA fragmentation and mitochondrial transmembrane potential dissipation (ΔΨm) are inhibited by the pan-caspase inhibitor zVAD. The increased susceptibility of osteoblast precursors to apoptosis could be due to dexamethasone-mediated down-regulation of survivin expression. Dexamethasone can up-regulate survivin, and to a lesser extent Bcl-2, in mature cells but not in pre-osteoblasts. In addition, it can induce FLIP over-expression in osteosarcoma cells. All these effects are inhibited by the glucocorticoid antagonist RU486, indicating that dexamethasone action is specific and, furthermore, that it depends on glucocorticoid receptor. Finally, we have found that survivin and Bcl-2 are essential for pre- and mature osteoblast survival as their silencing is sufficient to induce spontaneous apoptosis in both cell types. In conclusion, our data outline a new molecular mechanism of glucocorticoid-mediated bone loss due to the enhanced apoptosis of precursors compared to mature osteoblasts. Furthermore, the data suggest a mechanism of dexamethasone-induced resistance of osteosarcoma cells to Fas- and stress-induced apoptosis.
Inhibition of HSV-1 Replication by Laser Diode-Irradiation: Possible Mechanism of Action
Authors: Donnarumma G. , De Gregorio V. , Fusco A. , Farina E. , Baroni A. , Esposito V. , Contaldo M. , Petruzzi M. , Pannone G. , Serpico R.
Published: January 2017

Herpes labialis are the most frequent clinical manifestations of HSV-1 infection. Epithelial cells are able to respond to HSV-1 presence inducing the expression of IL-6, IL-1, TNF-α and IL-8. These proinflammatory cytokines have a function in the acute-phase response mediation, chemotaxis, inflammatory cell activation and antigen-presenting cells. In the human epithelial cell models, it has been demonstrated that, after an early induction of proinflammatory host response, HSV-1 down-modulates the proinflammatory cytokine production through the accumulation of two viral proteins, ICP4 and ICP27, whose transcription is induced by tegument protein VP16. These viral proteins, through the decreasing of stabilizing the mRNAs of proinflammatory genes, delay cytokine production to an extent that allows the virus to replicate. Moreover, viral transactivating proteins, ICP-0 and VP-16 induce IL-10 expression. The conventional treatment of herpes labialis involves the topical and systemic use of antiviral drugs but it is necessary to find new therapies that can act in a selective and non-cytotoxic manner in viral infection. Laser diode therapy has been considered as a non-invasive alternative treatment to the conventional treatment of herpes labialis in pain therapy, in modulation of inflammation and in wound healing. This study aims to report a possible mechanism of action of laser diode irradiation in prevention and reduction of severity of labial manifestations of herpes labialis virus. We investigated, in an in vitro model of epithelial cells HaCat, the laser-effect on HSV-1 replication and we evaluated the modulation of expression of certain proinflammatory cytokines (TNF-α, IL-1β and IL-6), antimicrobial peptide HBD2, chemokine IL-8 and the immunosuppressive cytokine, IL-10. Our results lead us to hypothesize that LD-irradiation acts in the final stage of HSV-1 replication by limiting viral spread from cell to cell and that laser therapy acts also on the host immune response unblocking the suppression of proinflammatory mediators induced by accumulation of progeny virus in infected epithelial cells.
MicroRNA Expression Profiling of Oral Carcinoma Identifies New Markers of Tumor Progression
Authors: Scapoli L. , Palmieri A. , Muzio L. Lo , Pezzetti F. , Rubini C. , Girardi A. , Farinella F. , Mazzotta M. , Carinci F.
Published: January 2017

Oral squamous cell carcinoma, the most frequently occurring malignant head and neck tumour, generally exhibits poor prognosis and metastases are the main cause of death. The discovery of reliable prognostic indicators of tumour progression could greatly improve clinical practice. MicroRNAs are involved in the regulation of basic cellular processes such as cell proliferation, differentiation, and apoptosis. Since miRNAs have been shown to be abnormally expressed in different tumours their importance as potential cancer prognostic indicators is increasing. To define the role of miRNA in OSCC tumours we investigated the expression profile of 15 OSCC (8 without metastasis and 7 with lymph node metastasis) using microarray analysis. Thirteen miRNA were significantly overexpressed (miR-489, miR-129, miR-23a, miR-214, miR-23b, miR-92, miR-25, miR-210, miR-212, miR-515, miR-146b, miR-21, miR-338) and 6 miRNA were underexpressed (miR-520h, miR-197, miR-378, miR-135b, miR-224, miR-34a) in oral tumours. Underexpression of mir-155, let-7i, mir-146a was found to characterize progression to metastastatic tumours. Further investigations will elucidate whether differentially expressed miRNAs will help to better classify OSCCs, thus improving diagnoses and patient care.
Adjuvant Effect of a Probiotic Fermented Milk in the Protection against Salmonella Enteritidis Serovar Typhimurium Infection: Mechanisms Involved
Authors: De Leblanc A. De Moreno , Galdeano C. Maldonado , Dogi C.A. , Carmuega E. , Weill R. , Perdigón G.
Published: January 2017

Probiotics may offer protection against Salmonella enteritidis serovar Typhimurium infection via different mechanisms. The aim of this study is to investigate, using mouse models, the effect of the administration of fermented milk containing the probiotic bacteria L. casei DN-114 001 in the protection against Salmonella enteritidis serovar Typhimurium when this product is administered continuously before and after infection or only post-infection. The adjuvant effect of this probiotic fermented milk (PFM) against S. Typhimurium was also evaluated in newborn mice, whose mothers received the PFM during the suckling period or their offspring after weaning. The results obtained showed that PFM administration after salmonella infection was useful to decrease the severity of the infection. The best effect was obtained with continuous PFM administration. In the newborn mice model, PFM administration to the newborn mice after weaning showed the best effect against the pathogen. PFM administration to the mother during the suckling period was beneficial against this enterophatogen when their offspring did not receive probiotics after weaning. Continuous PFM administration to adult mice (before and after infection) was important to maintain the intestinal barrier and the immune surveillance in optimal conditions to diminish the pathway of entrance of salmonella and the spread of this pathogen to deeper tissues. In the newborn mice model, it was observed that PFM administration to the offspring after weaning or their mother during the suckling period had a protective effect against salmonella infection, however, in the mice from mothers that received PFM during nursing which were fed with PFM after weaning, we found a down regulated immune maturity that was not protective against this infection.
Chlamydophila Pneumoniae Infection in Patients Undergoing Carotid Artery Stent
Authors: Mancini F. , Boatta E. , Vescio M.F. , Fanelli F. , Salvatori F.M. , Passariello R. , Cassone A. , Ciervo A.
Published: January 2017

Although several reports have correlated Chlamydophila pneumoniae (CP) infection with carotid endarterectomy and coronary stent, no data have been reported on the potential relationship between this pathogen and carotid artery stenting (CAS). Hence, we evaluated 47 subjects, 27 symptomatic and 20 asymptomatic, before CAS intervention and during the follow up, for the presence of CP DNA and anti-CP antibodies, including chlamydial HSP60 (Cp-HSP60). Before stent placement, CP DNA was detected exclusively in symptomatic patients, all of whom were also positive for CP IgG and IgA and 85.7% of them also had CP-HSP60 antibodies. At the follow-up, all CP DNA positive and 11 out of the 13 symptomatic patients with Cp-HSP60 antibodies became negatives. In contrast, no change was observed for CP- IgA antibodies. Despite the small number of patients, the present study advocates an important role of CP infection in symptomatic patients with carotid artery disease. Our findings also suggest that stent placement and/or therapy might have a role in favouring resolution of inflammation, though not affecting persistence of CP infection.
Body Mass Index is Related with Bronchial Function and Reversibility in Children with Allergic Rhinitis and Asthma
Authors: Ciprandi G , Brambilla I , Tosca Ma , Arrigo T , Salpietro A , Leonardi S , La Rosa M , Marseglia Gl
Published: January 2017

Several studies have outlined a possible relationship between an increased body mass index and respiratory allergic diseases, such as asthma and rhinitis. The aim of the study was to analyse the relationship between BMI and lung function, including bronchodilation test, in allergic children. The study included 153 children (103 males, mean age 12.8 years) with allergic rhinitis and mild asthma. All subjects were evaluated performing skin prick test, spirometry, and bronchodilalation test. BMI values were in the normal range as well as lung function. BMI significantly related with FEV1, FVC values and FEV1/FVC ratio both before and after bronchodilation. In conclusion, this study provides the first evidence that BMI is negatively related with bronchial reversibility in children with allergic rhinitis and asthma. As reversibility is related with bronchial inflammation, this finding might underline a link between overweight and allergic inflammation.
Bamifylline Similar to Theophylline and Caffeine is a Competitive Inhibitor of the Cyclic Nucleotide Phosphodiesterase V
Authors: Berardi S. , Papponetti M. , Conti P. , Spoto G.
Published: January 2017

Bamifylline was found to be a poor inhibitor of 3′,5′-cyclic GMP phosphodiesterase (PDE V) as other methylxanthines such as teophylline and caffeine. The IC50 was respectively 3.24, 2.91, 1.69 mM. Inhibition decreased at higher cGMP concentrations. Lineweaver-Burk plots were linear or nearly linear. Differences in the actions of these inhibitors presumably reflect differences in the molecular requirements for effective interaction at the catalytic site on phosphodiesterase.
What Factors Contribute to Senior Psychiatry Residents' Interest in Geriatric Psychiatry? A Delphi Study
Authors: Lieff Susan J , Clarke Diana
Published: January 2017

Objective:

To generate hypotheses regarding factors that influence senior psychiatric residents, to consider treating geriatric patients in their future practices.

Method:

Using the Delphi technique, designed to generate ideas and consensus, we asked psychiatry residents at the University of Toronto who had completed, or were completing, their geriatric rotation about the factors they thought might influence residents in devoting some of their practice to geriatric patients. Residents then rated the degree of influence of these factors which had been synthesized into a questionnaire.

Results:

Twenty-six items were rated according to their degree of influence. The most influential item was positive clinical experiences with seniors. This was followed closely by supervisor characteristics such as enthusiasm, role modeling, competence, and mentoring. Interest in and comfort with the medical psychiatric and neuropsychiatric nature of the field were also felt to be influential.

Conclusions:

The factors that influence senior psychiatry resident interest in the practice of geriatric psychiatry are primarily educational and result from exposure to the field under optimal educational circumstances (positive clinical experiences and excellent supervisors). The medical and neuropsychiatric nature of the field also likely exerts a unique influence and should be considered in stimulating interest in this population.
The Misidentification of Clerambault's and Kandinsky-Clerambault's Syndromes
Authors: Lerner Vladimir , Kaptsan Alexander , Witztum Eliezer
Published: January 2017

Eponymic terms or eponyms are labels describing phenomena that reflect the name(s) of the person(s) who first described the phenomena. Using a similar term to describe different forms of pathology leads to a muddle. In this paper, we describe “Clerambault's syndrome” and “Kandinsky-Clerambault's syndrome” and discuss and clarify the confusion surrounding these different syndromes.
Attention-Deficit Hyperactivity Disorder: Critical Appraisal of Extended Treatment Studies
Authors: Schachar Russell , Jadad Alejandro R , Gauld Mary , Boyle Michael , Booker Lynda , Snider Anne , Kim Marie , Cunningham Charles
Published: January 2017

We undertook a systematic review of the literature on the long-term treatment of attention-deficit hyperactivity disorder (ADHD). We used systematic strategies to identify randomized treatment studies in which treatment was administered for 12 weeks or more. We included 14 studies involving 1379 subjects. Because of the limited number of high-quality studies and the heterogeneity of outcome measures, we did not perform metaanalysis. We rated 5 studies as adequate for methodological quality. Five studies followed children for more than 26 weeks. Pharmacologic interventions were studied more frequently than non-pharmacologic ones. Six studies permitted evaluation of the effects of combined drug and behavioural intervention. Twenty-five different outcomes were measured using 26 different tests. Stimulant medication appears to reduce ADHD (7 studies), dysfunctional social behaviour (6 studies), and internalizing symptoms (2 studies). Available studies provide little evidence for improved academic performance with stimulants (3 studies). Medications other than stimulants have not been studied extensively (3 studies). Only 1 study showed that combination therapy adds to the effects of medication. Rigorous treatment research among representative samples of ADHD individuals is needed.
Fright (Effroi) and other Peritraumatic Responses after a Serious Motor Vehicle Accident: Prospective Influence on Acute PTSD Development
Authors: Vaiva Guillaume , Brunet Alain , Lebigot François , Boss Virginie , Ducrocq François , Devos Patrick , Laffargue Philippe , Goudemand Michel
Published: January 2017

Objective:

We prospectively examined the relation between various peritraumatic responses (that is, fear, helplessness, horror, amnesia, and fright) and the development of posttraumatic stress disorder (PTSD) 2 months after a trauma.

Method:

Participants included 123 motor vehicle accident (MVA) victims consecutively hospitalized in a traumatology department for over 72 hours during a 16-month period. Between day 2 and day 5 of their hospitalization, a psychiatrist assessed the patients' peritraumatic responses and acute stress disorder (ASD). Two months after the accident, an experienced psychiatrist contacted the patients by telephone, and the PTSD symptoms and the diagnosis were assessed with a modified version of the Clinician-Administered PTSD Scale (CAPS).

Results:

Of the participants, 48 reported an immediate fright reaction when faced with the prospect of their own death. Participants who reported a fright experience had a 17 times greater risk of subsequently meeting the diagnostic criteria for PTSD (odds ratio 16.75). A fright reaction predicted PTSD development with a specificity of 0.93 and a sensitivity of 0.60.

Conclusion:

The immediate reactions described in criterion A2 of the DSM-IV (that is, fear, helplessness, and horror) did not seem to be equally relevant. An initial feeling of fright seems to be an essential qualitative factor in the clinical description of psychological trauma.