bluuebunny/crossref_metadata_2025 huggingface dataset:
Updating the Physiology, Exploration and Disease Relevance of Complement Factor H
Authors: Buhé V. , Loisel S. , Pers J.O. , Le Ster K. , Berthou C. , Youinou P.
Published: January 2017

The factor H (FH) protein (also known as β1H globulin) is the main regulator of the complement alternative pathway. It exhibits multivalent binding sites to the complement component C3b, and polyanions and one binding site to sialic acid and cell surfaces. These multiple binding sites confer to FH a decay-accelerating factor activity in the fluid phase as well as at the cell surface. A defect in FH activity or a FH protein deficiency triggers chronic inflammation and tissue injury, leading to various disorders impacting the kidney or the eye. In contrast, some pathogens, as well as cancer cells, develop various strategies to bind FH and thereby subvert a complement attack. We focus on the functions of FH, and review the main pathological conditions in which FH is involved. Since the pathogenesis is elusive, appropriate FH dosage in biological fluids and FH gene analysis may help in improving understanding of such diseases.
Challenge Tests in the Diagnosis of Latex Allergy
Authors: Nucera E. , Pollastrini E. , Sabato V. , Colagiovanni A. , Aruanno A. , Rizzi A. , Buonomo A. , Pecora V. , Lombardo C. , Astorri A.L. , Rossi G. , Patriarca G. , Schiavino D.
Published: January 2017

The aim of this study is to evaluate the sensitivity, specificity and safety of challenge tests and their usefulness in the diagnosis of latex allergy. Forty adult subjects (F/M = 34/6, aged 18–66 yrs) with a history of adverse reactions after latex exposure and positive prick test and/or specific IgE to latex were enrolled. They were compared with 20 control subjects. They underwent provocative (cutaneous, mucous-oral, sublingual, conjunctival, nasal, bronchial, vaginal) tests. Symptoms and drug scores were recorded for each patient during challenges. All patients reacted to at least one of the following: cutaneous, nasal and conjunctival tests. No systemic reactions requiring epinephrine occurred. Of the challenges, the vaginal test resulted as the safest, but it had low sensitivity and many limits related to the procedure. According to our data, bronchial and nasal tests had the highest sensitivity (76% and 82% respectively), and were more precise than other tests in determining latex exposure and symptoms, but the bronchial test also presented the highest rate of risk. Mucous and cutaneous tests resulted as the most reliable. For all the tests, specificity and positive predictive value were 100%. All control subjects resulted negative to all challenges. There were no statistically significant changes in skin and serologic tests between the first and second visits. Correlations between MIS and skin tests and between MIS and serum tests were not found. Challenges can be considered safe diagnostic procedures. Tests that most faithfully reproduce natural exposure, on the basis of a patient's history, are preferable.
Inhibiting Proliferation in KB Cancer Cells by RNA Interference-Mediated Knockdown of Nicotinamide N-Methyltransferase Expression
Authors: Pozzi V. , Mazzotta M. , Muzio L. Lo , Sartini D. , Santarelli A. , Renzi E. , Rocchetti R. , Tomasetti M. , Ciavarella D. , Emanuelli M.
Published: January 2017

The enzyme Nicotinamide N-methyltransferase (NNMT) catalyzes the methylation of nicotinamide and other pyridines, playing a pivotal role in the biotransformation and detoxification of many drugs and xenobiotic compounds. Several tumours have been associated with abnormal NNMT expression, however its role in tumour development remains largely unknown. In this study we investigated expression levels of Nicotinamide N-methyltransferase in a cancer cell line and we evaluated the effect of shRNA-mediated silencing of NNMT on cell proliferation. Cancer cells were examined for NNMT expression by semiquantitative RT-PCR and Western blot analysis. A HPLC-based catalytic assay was performed to assess enzyme activity. Cells were transfected with four shRNA plasmids against NNMT and control cells were treated with transfection reagent only (mock). The efficiency of gene silencing was detected by Real-Time PCR and Western blot analysis. MTT cell proliferation assay and the soft agar colony formation assay were then applied to investigate the functional changes in cancerous cell. NNMT mRNA was detected in cancer cells, showing a very high expression level. In keeping with the results of RT-PCR analysis, the protein level and NNMT enzyme activity were particularly high in KB cells. ShRNA vectors targeted against NNMT efficiently suppressed gene expression, showing inhibition observed at both the mRNA and protein levels. Down-regulation of NNMT significantly inhibited cell proliferation and decreased colony formation ability on soft agar. The present data support the hypothesis that the enzyme plays a role in tumour expansion and its inhibition could represent a possible molecular approach to the treatment of cancer.
Stimulation of TH1 Response by Helicobacter Pylori Neutrophil Activating Protein Decreases the Protective Role of IgE and Eosinophils in Experimental Trichinellosis
Authors: Chiumiento L. , Del Prete G. , Codolo G. , De Bernard M. , Amedei A. , Della Bella C. , Piazza M. , D'Elios S. , Caponi L. , D'Elios M.M. , Bruschi F.
Published: January 2017

Th2 responses seem to play an important role in defence against Trichinella spiralis (Ts). The Neutrophil Activating Protein of Helicobacter pylori (HP-NAP), that induces IL-12, and IL-23 expression and shifts to Th1 allergen-specific Th2 cells in vitro was used as an anti-Th2 agent in BALB/c mice infected with T. spiralis. The muscle larvae (ML) burden was lower ( p < 0.02) in untreated infected animals than those infected treated with HP-NAP. In both groups there was an inverse relationship between ML burden of each animal and total IgE level (controls: r −0.617, p = 0.0013 and HP-NAP-treated: r −0.678, P = 0.0001) or eosinophil count, evaluated in the same mouse on day 42 (r −0.390, P = 0.0592 and r −0.803, P = 0.0001, respectively). Inflammatory response around the nurse cell-parasite complex was significantly higher in HP-NAP-treated infected animals than in those untreated infected, on the contrary the number of eosinophils, counted around each complex was significantly lower in the first animal group. This study provides evidence of a powerful anti-Th2 activity in vivo by HP-NAP and for the partial protective effect of Th2 responses in T. spiralis infection.
Obstetrical, Fetal and Postnatal Effects of Gestational Antiblastic Chemotherapy: How to Counsel Cancer Patients
Authors: Del Pup L , Peccatori F , Azim Hajr , Michieli M , Moioli M , Giorda G , Tirelli U , Berretta M
Published: January 2017

At least one in a thousand pregnancies is complicated by cancer and, as the maternal age at pregnancy increases, numbers are growing. If chemotherapy cannot be postponed, both doctors and patients face complex medical and ethical issues. There is a conflict between optimal maternal therapy and fetal wellbeing. Treatment during the first trimester increases the risk of congenital malformations, spontaneous abortions and fetal death. Second and third trimester exposure is less risky, but it can cause intrauterine growth retardation and low birth weight. Other effects on pregnancy after the first trimester include premature birth, stillbirth, impaired functional development, myocardial toxicity and myelosuppression. Counseling and management of these cases are difficult, because literature is mostly represented by case reports or retrospective series while randomized prospective studies or guidelines are lacking. Moreover, personal experience is often scanty due to the rarity of the condition. This article reviews the available data regarding the different aspects of systemic treatment of cancer during pregnancy to help oncologist and obstetricians in counseling their patients and treat them accordingly.
Melkersson-Rosenthal Syndrome in a Patient with Psoriatic Arthritis Receiving Etanercept
Authors: Gaudio A. , Corrado A. , Santoro N. , Maruotti N. , Cantatore F.P.
Published: January 2017

Melkersson-Rosenthal syndrome is a rare granulomatous neuro-mucocutaneous systemic disease that is characterized by relapsing peripheral facial paralysis, orofacial edema and fissured tongue. The disease etiology is still not well known, but it has been hypothesized that a possible role is played by various causal agents such as infectious diseases, genetic causes, allergic conditions, benign lymphogranulomatosis, various associations with other pathological conditions, particularly with immune-mediated diseases and food contact allergies. In this report we describe the case of a woman, 42 years old, with psoriatic arthritis who developed neurological episodes related to MRS after treatment with anti-TNF therapy. This finding further supports the hypothesis that TNF-α blockade, and particularly the use of the TNF-α receptor, could trigger the development of granulomatous lesions in predisposed patients. The case we report further sustains the importance for the clinician to take into account this potential adverse event in patients receiving anti-TNF-α therapies.
Occurrence of Candida Species Colonization in a Population of Denture-Wearing Immigrants
Authors: Calcaterra R. , Pasquantonio G. , Vitali L.A. , Nicoletti M. , Di Girolamo M. , Mirisola C. , Prenna M. , Condò R. , Baggi L.
Published: January 2017

Infection of the oral cavity and dentures by Candida species are frequent in denture wearers. C. albicans is the most common pathogen; however, other emerging Candida species are also responsible for this condition. Few data are available about the occurrence of Candida species in the oral cavities of denture-wearing immigrants to Italy. In this study, we compare the Candida species found in the oral mucosa and on dentures from a population of denture wearing immigrants to Italy to a matched Italian group. Oral swabs were collected from dentures and the underlying mucosa of patients enrolled in the study and were then cultured to test for the presence of Candida species in each sample. Out of 168 patients enrolled (73 Italians and 95 immigrants), 51 Italians (69.8%) and 75 immigrants (78.9%) tested positive for the presence of Candida. Candida albicans was the most frequently observed species overall; however, we found a higher occurrence of C. glabrata among immigrants than among Italians. In addition, immigrants displayed a higher incidence of Candida – associated stomatitis and a lower mean age than Candida-positive individuals from the Italian group. Immigrants are more prone to longer colonization of the oral mucosa and dentures by Candida. In these patients, dentures must be checked periodically to prevent the presence of Candida.
Systemic Nickel Allergy: Oral Desensitization and Possible Role of Cytokines Interleukins 2 and 10
Authors: Ricciardi L. , Carnì A. , Loschiavo G. , Gangemi S. , Tigano V. , Arena E. , Mannucci C. , Calapai G.
Published: January 2017

Nickel ingested with food can elicit either systemic cutaneous or gastrointestinal symptoms causing a systemic nickel allergy syndrome (SNAS) that can be treated with tolerance by oral ingestion of the metal. It has been suggested that interleukins 2 (IL-2) and 10 (IL-10) are involved in the mechanisms underlying oral tolerance. We evaluated the clinical efficacy of oral desensitization therapy in SNAS consisting in the administration of nickel sulphate. Because nickel allergy prevalently affects women, only female subjects (N = 22) were recruited. Oral nickel desensitizing therapy was associated with low-nickel diet for three months. Before and after therapy, clinical conditions were evaluated, and circulating cytokines IL-2 and IL-10 were measured. After the two-year treatment, visual analogue scale (VAS) scores for symptoms were significantly reduced (P < 0.001). Patients were released by either cutaneous or gastrointestinal symptoms and by tolerating nickel-containing food. At the end of the treatment, nickel oral challenge test was negative in 18 patients, and IL-2 level in the serum was significantly reduced while IL-10 was increased, although this datum was not statistically significant. Our study confirms the clinical efficacy of nickel oral immunotherapy and focuses on the mechanisms triggered by oral tolerance indicating that reduction of IL-2 can be associated with success of oral nickel desensitizing therapy.
Impact of Capsaicin on Mast Cell Inflammation
Authors: Frydas S. , Varvara G. , Murmura G. , Saggini A. , Caraffa A. , Antinolfi P. , Tetè S. , Tripodi D. , Conti F. , Cianchetti E. , Toniato E. , Rosati M. , Speranza L. , Pantalone A. , Saggini R. , Di Tommaso L.M. , Theoharides T.C. , Conti P. , Pandolfi F.
Published: January 2017

Mast cells are inflammatory cells, and they are prominent in inflammatory diseases such as allergy and asthma. Mast cells possess high-affinity receptors for IgE (FCεRI) and the cross-linking of these receptors is essential to trigger the secretion of granules containing arachidonic acid metabolism [such as prostaglandin (PG) D2, leukotriene (LT) B4, and LTC4], histamine, cytokines, chemokines, and proteases, including mast cell-specific chymases and tryptases. Activation of mast cells provokes the secretion of cytokines and mediators that are responsible for the pathologic reaction of immediate hypersensitivity. Sensory nerve stimulation by irritants and other inflammatory mediators provokes the release of neuropeptides, causing an increase in vascular permeability, plasma extravasation and edema. Trigeminal nerve stimulation actives dura mast cells and increases vascular permeability, effects inhibited by capsaicin. Capsaicin causes release of sensory neuropeptide, catecholamines and vasodilation. Several studies have reported that capsaicin is effective in relief and prevention of migraine headaches, improves digestion, helps to prevent heart disease, and lowers blood cholesterol and blood pressure levels. The findings reported in these studies may have implications for the pathophysiology and possible therapy of neuroinflammatory disorders.
P16INK4a Immunohistochemistry for Detection of Human Papilloma Virus-Associated Penile Squamous Cell Carcinoma is Superior to in-Situ Hybridization
Authors: Aumayr K. , Susani M. , Horvat R. , Wrba F. , Mazal P. , Klatte T. , Koller A. , Neudert B. , Haitel A.
Published: January 2017

We evaluated p16INK4a as a reliable option to detect human papilloma virus (HPV) DNA in penile tumor specimens. Formalin-fixed paraffin embedded samples of 26 patients with penile cancer and another 18 cases with non-tumorigenic lesions were stained by three different widely used commercially available chromogenic in-situ hybridization assays high-risk HPV CISH Y1443 (Genpoint, DAKO), pan HPV CISH Y1404 (Genpoint, DAKO), INFORM HPV III (Ventana, Tucson, Arizona) and p16INK4a immunohistochemistry, then compared to the known gold standard polymerase chain reaction detecting HPV 16, 18, 31, and 33. Immunoreactivity for p16INK4a was evaluated by using a 4-tiered (0, 1, 2, and 3) pattern based system. 19 cases were positive for p16INK4a, 13 of which showed a continuous transepithelial staining (pattern 3). Pan HPV ISH showed positivity in 9 cases, high-risk HPV ISH in 7 cases and INFORM HPVIII ISH in 7 cases. p16INK4a IHC pattern 3 versus pattern 0, 1 and 2 exhibited a specificity and positive predictive value of 100%, with a sensitivity and negative predictive value of 72% and 62%, respectively, which was much better than all HPV in-situ hybridization methods referred to polymerase chain reaction. p16INK4a seems to be a superior marker for the detection of HPV-associated penile squamous cell carcinoma compared to CISH tests, but is not recommend for the detection of non-tumorigenic lesions, where PCR should be used for the initial assessment.
Sulphurous Thermal Water Increases the Release of the Anti-Inflammatory Cytokine IL-10 and Modulates Antioxidant Enzyme Activity
Authors: Prandelli C. , Parola C. , Buizza L. , Delbarba A. , Marziano M. , Salvi V. , Zacchi V. , Memo M. , Sozzani S. , Calza S. , Uberti D. , Bosisio D.
Published: January 2017

The beneficial effects of hot springs have been known for centuries and treatments with sulphurous thermal waters are recommended in a number of chronic pathologies as well as acute recurrent infections. However, the positive effects of the therapy are often evaluated in terms of subjective sense of wellbeing and symptomatic clinical improvements. Here, the effects of an S-based compound (NaSH) and of a specific sulphurous thermal water characterized by additional ions such as sodium chloride, bromine and iodine (STW) were investigated in terms of cytokine release and anti-oxidant enzyme activity in primary human monocytes and in saliva from 50 airway disease patients subjected to thermal treatments. In vitro, NaSH efficiently blocked the induction of pro-inflammatory cytokines and counterbalanced the formation of ROS. Despite STW not recapitulating these results, possibly due to the low concentration of S-based compounds reached at the minimum non-toxic dilution, we found that it enhanced the release of IL-10, a potent anti-inflammatory cytokine. Notably, higher levels of IL-10 were also observed in patients' saliva following STW treatment and this increase correlated positively with salivary catalase activity (r2 = 0.19, *p<0.01). To our knowledge, these results represent the first evidence suggesting that S-based compounds and STW may prove useful in facing chronic inflammatory and age-related illness due to combined anti-inflammatory and anti-oxidant properties.
Bradykinin-Forming Components in Kuwaiti Patients with Type 2 Diabetes
Authors: Sharma J.N. , Al-Shoumer K.A.S. , Matar K.M. , Al-Gharee H.Y. , Madathil N.V.
Published: January 2017

Diabetes is the most common risk factor in inducing hypertension, nephropathy and retinopathy. The bradykinin (BK)-forming system has been proposed to protect cardiovascular and renal functions. We therefore evaluated urinary active and proactive kallikrein, total kininogen, plasma tissue kallikrein, plasma creatinine, plasma glucose and plasma HbA1c in newly diagnosed untreated type 2 diabetic patients and healthy subjects. In diabetic patients, urinary and plasma tissue kallikrein concentrations were significantly increased. In addition, plasma prekallikrein levels were also significantly higher. However, urinary kininogen values were significantly reduced in diabetic patients when compared with healthy subjects. This is the first investigation among Kuwaiti Arab patients with type 2 diabetes showing abnormal activities in the BK-forming system. High levels of plasma prekallikrein may be a risk factor for developing high blood pressure as well as nephropathy. The urinary and plasma tissue kallikrein concentrations were higher in diabetic patients, which could indicate the hyperactivities of these components, and may result in increased levels of plasma glucose to induce diabetes. Furthermore, the urinary kininogen levels were reduced in diabetic patients. These alterations might reflect the utilization of urinary kininogen to form BK, a potent inflammatory agent. However, this hypothesis needs further investigation.
Usefulness of Atopy Patch Test on a Child with Milk Protein-Induced Enterocolitis Syndrome: A Case Report
Authors: Scaparrotta A. , Di Pillo S. , Consilvio N.P. , Attanasi M. , Cingolani A. , Rapino D. , Cerasa M. , Pucci N. , Di Gioacchino M. , Chiarelli F.
Published: January 2017

We describe the case of a child affected by milk-protein induced enterocolitis, in which oral challenge with corn was performed without symptoms after a negative specific Atopy Patch Test. Food protein-induced enterocolitis syndrome (FPIES) is an uncommon non-IgE-mediated gastrointestinal food hypersensitivity of infancy, characterized by severe vomiting and diarrhea arising within 1 to 3 hours after ingestion of the causative food. Little is known about the pathophysiology of FPIES. The absence of food-specific IgE as demonstrated by negative skin prick tests suggests that the disease is not caused by an early onset IgE-mediated reaction. Atopy Patch Test has been described as sensitive and predictive in this syndrome. The hypothesis on the immunological pathogenesis has been discussed on the basis of literature data.
Expression of Gelatinases (MMP-2, MMP-9) in Human Articular Cartilage
Authors: Lipari L. , Gerbino A.
Published: January 2017

Osteoarthritis (OA) is a chronic degenerative joint disorder characterized by destruction of the articular cartilage, subchondral bone alterations and synovitis. Matrix metalloproteinases (MMPs) are expressed in joint tissues of patients with osteoarthritis (OA). The objective of this study was to define the steady state levels of two different MMPs to provide more insight into the role of MMPs in cartilage destruction in OA. We investigated the expression of gelatinases through immunohistochemistry Our results show that high levels of MMP-2 and MMP-9 are present in OA and suggest that once these MMPs are fully activated they may contribute to the cartilage destruction in OA.
Increased Expression of CCL4/MIP-1β IN CD8+ Cells and CD4+ Cells in Sarcoidosis
Authors: Barczyk A. , Pierzchała E. , Caramori G. , Sozańska E.
Published: January 2017

Sarcoidosis is a granulomatous disease with an increased accumulation of T cells in lungs as a result of on-site proliferation and chemotaxis induced by chemokines. It has already been demonstrated that CCL3-5 levels were increased in BAL fluid of sarcoidosis patients. To analyze the expression of CCL3-5 chemokines by T-cell subtypes (CD4+, CD8+, Th1, Th2, Tc1 or Tc2) in the lungs of sarcoidosis patients, fifteen untreated sarcoidosis patients and eighteen control subjects were enrolled in this study. CD4+ and CD8+ cells were isolated from BAL fluid by positive magnetic selection. The expression of CCL3-5 and other cytokines in CD4+ and CD8+ cells were measured by flow cytometry. The percentage of CD4+ or CD8+ cells expressing CCL4 were significantly higher in sarcoidosis patients (22.3% and 58.1%) compared to those seen in healthy subjects (11.1% and 16.5%, P = 0.04 and P = 0.02, respectively). In addition, the expression of CCL3, CCL4 and CCL5 was significantly elevated in CD8+ cells (8.9%, 58.1% and 2.1%) compared to CD4+ cells (2.1%, 22.3% and 0.7%; P = 0.04, P = 0.009 and P = 0.04, respectively), whereas CCL4 was expressed by significantly more Tc1 than Th1 cells in sarcoidosis patients (P = 0.006). Our study shows the possible role of CD8+ cells and CD4+ cells in recruiting T cells to the site of inflammation in sarcoidosis through the release of CCL4, either alone or together with Th1/Tc1-associated cytokines.
Effect of a High Dose of Vitamin D on A Rabbit Model of Atherosclerosis
Authors: Malek H.A. , Shata A.
Published: January 2017

Multifactorial factors have been involved in atherosclerosis. An association has been shown between osteoporosis and carotid atherosclerosis. This work evaluates the effect of vitamin D on regression of atherosclerosis. Forty-eight male rabbits were divided into: Group Ia: [Standard diet + saline for 4 weeks]; Group I b: [Standard diet + a high dose of vitamin D3 daily for 4 weeks]; Group IIa: [Cholesterol–enriched diet for 4 weeks]; Group IIb: [Cholesterol–enriched diet + a single high dose of vit D3, daily for 4 weeks. At the end of 4 weeks, the rabbits were sacrificed for assay in serum lipid profile, C reactive protein (CRP), vitamin D3 metabolite, calcium, soluble adhesion molecules (sVCAM and sICAM) and nitrite (NO) and malondialdehyde (MDA) released from isolated aortic rings. Results showed that vitamin D produced a significant reduction in the sera of lipid profile, CRP, and adhesion molecules, associated with a non-significant change in serum calcium and a significant increase in the body level of vitamin D3. Addition of vitamin D to the incubated aortic rings of the atherosclerotic rabbits resulted in a significant increase in NO and decrease in MDA release. It could be concluded that vitamin D has anti-atherosclerotic effects, and may exert these effects by inhibiting lipid peroxidation and stimulation of nitric oxide, resulting in attenuation of the inflammatory atherosclerotic process.
Carcinoma Cuniculatum in Course of Etanercept: Blocking Autoimmunity but Propagation of Carcinogenesis?
Authors: Tchernev G. , Guarneri C. , Bevelacqua V. , Wollina U.
Published: January 2017

Carcinoma cuniculatum (CC) or verrucous squamous cell carcinoma is a rare variant of squamous cell carcinoma with low incidence of metastasis. It mainly affects men during the fifth-sixth decade of life, arising mostly on the weight-bearing surface of the foot, but it can also be found in other body areas. The favorable effects on the psoriatic, rheumatoid, juvenile polyarthritis as well as the ankylosing spondylitis after the application of Tumour Necrosis Factor (TNF)-alpha inhibitors, like etanercept, presume the availability of similarity between the etiopathogenetic mechanisms which are responsible for the generation of the inflammatory cascade. According to the latest studies, the sensitivity of the patients to TNF-alpha inhibitors could be genetically determined and may also be due to certain genetic polymorphisms of the NLP3 and CARD8 zones of the inflammasome. The blocking of the inflammatory reaction within the borderlines of the psoriatic arthritis could also be accepted as something of a “double edged sword”. There is a growing volume of literary data which informs us of the clinical manifestation, not only of skin, but also of other types of tumors after the application of TNF-alpha inhibitors. This inevitably generates the hypothesis that within a certain group of patients the TNF-alpha inhibitors have some additional, and currently obscure, effects on presumably key regulatory proteins of the so-called extrinsic apoptotic pathway. Other proteins of the human inflammasome could be also implicated in the regulation of the programmed cell death and the carcinogenesis - there are speculations, that the adapter protein, ASC/TMS1, could be one of these. The present study describes the case of a patient who developed a rare form of skin tumor - epithelioma cuniculatum - whilst undergoing etanercept therapy for psoriatic arthritis. Under discussion are the possible critical connections in the complex regulatory “networks” of the inflammatory processes, the programmed cell death (apoptosis) and the carcinogenesis which, in the near or distant future, could become the objects of a targeted therapy.
Granuloma Annularis Revealing Wegener's Granulomatosis
Authors: Del Porto F. , Proietta M. , Muscianese M. , Tamburi F. , Cifani N. , Ferri L. , Nisticò S. , Bottoni U. , Bruno G. , Pranteda G.
Published: January 2017

Skin manifestations are often associated with systemic autoimmune diseases (SAD). Some SAD, such as systemic lupus erythematosus, psoriatic arthritis and scleroderma display pathognomonic dermatological features, whereas other systemic diseases such as sarcoidosis, vasculitis and rheumatoid arthritis can present with non-specific skin manifestations that range from erythema nodosum to necrotic lesions. Here we report the case of a 25-year-old man with uveitis, polyarthrirtis, pulmonary involvement, nephrotic syndrome, cutaneous granuloma and pneumonia by E. coli.
Effect of an Educational Program in Primary Care: The Case of Lipid Control in Cardio-Cerebrovascular Prevention
Authors: Arcoraci V. , Santoni L. , Ferrara R. , Furneri G. , Cannata A. , Sultana J. , Moretti S. , Di Luccio A. , Tari D. U. , Pagliaro C. , Corrao S. , Tari M.
Published: January 2017

Lowering blood cholesterol levels reduces the risk of coronary heart disease. However, the effect of interventions depends on the patients' adherence to treatment. Primary care plays an important role in the detection, treatment and monitoring of disease, therefore different educational programs (EP) have been implemented to improve disease management in general practice. The present study is aimed to assess whether a general practitioner auditing and feedback EP may improve dyslipidaemia management in a primary care setting and to evaluate patients' adherence to prescribed lipid-lowering treatment. The quality of cardiovascular and cerebrovascular disease prevention before and after the implementation of an EP offered to 25 general practitioners (GPs), was evaluated. Clinical and prescription data on patients receiving at least one lipid-lowering treatment was collected. To evaluate the quality of the healthcare service provided, clinical and biochemical outcomes, and drug-utilization, process indicators were set up. Adherence was evaluated before and after the EP as the “Medication Possession Ratio” (MPR). A correlation analysis was carried out to estimate the effect of the MPR in achieving pre-defined clinical end-points. Prescription data for lipid-lowering drugs was collected in a sample of 839 patients. While no differences in the achievement of blood lipid targets were observed, a slight but significant improvement of the MPR was registered after the EP (MPR >0.8=64.2% vs 60.6%, p=0.0426). Moreover, high levels of statin adherence were associated with the achievement of total blood cholesterol target (OR=3.3 for MPR >0.8 vs MPR <0.5, 95% CI: 1.7–6.7) or LDL therapeutic goal (OR=3.3 for MPR >0.8 vs MPR <0.5,95% CI: 1.5–7.2). The EP partially improved the defined clinical targets; probably, a more patient-based approach could be more appropriate to achieve the defined target. Further studies are needed to identify how healthcare services can be improved.
Human Mesenchymal Stem Cells Produce Bioactive Neurotrophic Factors: Source, Individual Variability and Differentiation Issues
Authors: Paradisi M. , Alviano F. , Pirondi S. , Lanzoni G. , Fernandez M. , Lizzo G. , Giardino L. , Giuliani A. , Costa R. , Marchionni C. , Bonsi L. , Calzà L.
Published: January 2017

The possible use of cell therapies for neurological lesions and disorders is regarded as a very promising strategy. However, many issues related to cell type, tissue donor, expected biological action etc., are still open. In this study human mesenchymal stem cells derived from different fetal and adult tissues were examined in order to explore growth and neurotrophic factor synthesis and biological action, also considering the individual variability of the donors. Cells were derived from different human tissues and characterized according to the guidelines of the International Society for Cellular Therapy. Growth and neurotrophic factor synthesis was evaluated by real time PCR, biological assays and ELISA. It was found that human mesenchymal stem cells produce vascular endothelial-, nerve-growth factor (VEGF, NGF), brain-derived-, ciliary- and glial-derived neurotrophic factors (BDNF, CDGF, GDNF), which are neuroprotective molecules, but the source and the donor influence the synthesis rate. Accordingly, it is suggested that the source and the individual variability are key issues to be considered in the perspective of the clinical use of mesenchymal stem cells in neurological disorders.
Subglotic Malt-Lymphoma of the Larynx: An Unusual Presentation of Chronic Cough
Authors: Zapparoli M. , Trolese A.R. , Remo A. , Sina S. , Bonetti A. , Micheletto C.
Published: January 2017

Extranodal non-Hodgkin lymphomas limited to the larynx are rare, accounting for less than 1% of all laryngeal neoplasms. The most common site of development of primary laryngeal lymphomas is the supraglottic region. In most cases, the presenting symptoms are hoarseness, dysphagia, dyspnea, and cervical lymphadenopathy. They consist mainly of non-Hodgkin lymphoma, especially of diffuse large B-cell lymphoma and mucosa-associated lymphoid tissue. We report a case of a primary extranodal marginal zone of mucosa-associated lymphoid tissue (Malt Lymphoma) of the larynx in a 73-year-old non-smoker woman, presented as chronic cough, unresponsive to oral corticosteroid. We present a detailed report of her clinical and paraclinical data as well as treatment options. In patients with chronic cough, uncommon causes should be considered when the cough persists after evaluation for common causes. If a cough persists after consideration of the most common causes, CT scan and a bronchoscopic evaluation are fundamental for the diagnosis of tumors of the upper and lower respiratory tract.
Immunopathological and Antimicrobial Effect of Black Pepper, Ginger and Thyme Extracts on Experimental Model of Acute Hematogenous Pyelonephritis in Albino Rats
Authors: Nassan M.A. , Mohamed E.H.
Published: January 2017

Recent studies showed prominent antimicrobial activity of various plant extracts on certain pathogenic microorganisms, therefore we prepared crude aqueous extracts of black pepper, ginger and thyme and carried out an in vitro study by measuring antimicrobial activity of these extracts using the agar well diffusion method. An in vivo study was carried out on 50 adult healthy male albino rats which were divided into 5 groups, 10 rats each. Group 1: negative control group which received saline solution intragastrically daily; Group 2: Positive control group, injected with mixed bacterial suspension of S.aureus and E.coli as a model of pyelonephritis, then received saline solution intragastrically daily; Group 3: injected with the same dose of mixed bacterial suspension, then received 100 mg/kg/day black pepper extract intragastrically; Group 4: injected with mixed bacterial suspension then received 500 mg/kg/day ginger extract intragastrically. Group 5: injected with mixed bacterial suspension then received 500 mg/kg/day thyme extract intragastrically. All groups were sacrificed after either 1 or 4 weeks. Serum and blood samples were collected for lysozyme activity estimation using agarose lysoplate, measurement of nitric oxide production, and lymphocyte transformation test as well as for counting both total and differential leukocytes and erythrocytes. Kidney samples were tested histopathologically. Both in vivo and in vitro results confirm the efficacy of these extracts as natural antimicrobials and suggest the possibility of using them in treatment procedures.
In Silico Modeling of the Molecular Interactions of Antacid Medication with the Endothelium: Novel Therapeutic Implications in Head and Neck Carcinomas
Authors: Matossian M. , Vangelderen C. , Papagerakis P. , Zheng L. , Wolf G.T. , Papagerakis S.
Published: January 2017

Pathological acid reflux is a common event in patients afflicted with head and neck squamous cell carcinomas (HNSCCs), known to play a role in HNSCC etiology and contribute to complications after surgery or during radiation and chemotherapy. Antacid medications are commonly prescribed in HNSCC patients as part of their cancer treatment, and consist of two classes: histamine 2 receptor antagonist class (H2RA, with cimetidine as its prototypical drug) and proton pump inhibitors class (PPI, with omeprazole as its prototypical drug). Clinical evidence revealed a significant survival benefit of antacid usage in a large cohort of HNSCC patients treated in our Otolaryngology Department, with a median follow-up of over 5 years. Therefore, we postulate that one mechanism by which antacid intake enhances patient survival could involve modulation of tumor cell adhesion to endothelium, critical in the initiation of the metastatic dissemination. This study investigates the potential physical interactions between cimetidine and omeprazole with the endothelial E-selectin (E-sel) and its ligand sialyl Lewis X (sLex) using a molecular visualization energy-based program (AutoDock). Docking results were further analyzed with the PyMOL program, which allowed for measurements of the distances between the drugs and the closest interacting atoms or residues on E-sel and sLex molecules. Our model predicts that omeprazole displays a stronger interaction with E-sel than cimetidine, as extrapolated from the calculated overall binding energies. However, the shorter distances existing between interacting atoms in the proposed E-sel/cimetidine complex are suggestive of more stable interactions. Neither antacid/E-sel complex overcame the stronger Autodock-calculated sLex/E-sel interaction, suggesting competitive inhibition was not involved. This study provides the first in silico evidence of omeprazole and cimetidine ability to bind to adhesion molecules involved in tumor dissemination, underlining their therapeutic potential in the HNSCC clinical management.
Anti-TNF Agents as Therapeutic Choice in Immune-Mediated Inflammatory Diseases: Focus on Adalimumab
Authors: Armuzzi A. , Lionetti P. , Blandizzi C. , Caporali R. , Chimenti S. , Cimino L. , Gionchetti P. , Girolomoni G. , Lapadula G. , Marchesoni A. , Marcellusi A. , Mennini F.S. , Salvarani C. , Cimaz R.
Published: January 2017

The complex pathogenesis of immune-mediated inflammatory diseases (IMIDs) has been extensively investigated and dysregulation of cytokines, such as tumour necrosis factor (TNF), has been shown to play a dominant role in the pathogenesis of various IMIDs, such as rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, psoriasis and psoriatic arthritis. The subsequent development of biological agents capable of blocking TNF has led to important advances in the pharmacotherapy of such diseases and confirmed the concept of a common pathophysiology among IMIDs with TNF having a predominant role. Five TNF inhibitors have currently been approved for treatment of one or more IMIDs; these include infliximab, etanercept, adalimumab, golimumab and certolizumab pegol. Given the similarities in the pathogenic background of IMIDs, one could expect that anti-TNF agents be similarly effective and with comparable tolerability profiles; however, this may not be the case. Structural and pharmacological differences among the anti-TNF drugs are likely to result in differences in efficacy and tolerability among the agents in the different IMIDs, together with differences in potency, therapeutic dose ranges, dosing regimens, administration routes, and propensity for immunogenicity. Among the five TNF inhibitors approved for treatment of IMIDs, adalimumab has the widest range of indications. Data from controlled clinical trials of adalimumab, showing its excellent efficacy and tolerability in a wide range of indications, are supported by real-world long-term data from observational studies, which confirm the value of adalimumab as a suitable choice in the management of IMIDs.
Cytokine Levels in Whole Blood Cell Cultures of Oral Contraceptive Users and Pregnant Women
Authors: Elsässer-Beile Ursula , Von Kleist Sabine , Hölsch P. , Mönting J. Schulte , Werner Inna
Published: January 2017

The production of the cytokines IFN-gamma, IL-2, IL-1-alpha and TNF-alpha was investigated in the supernatants of mitogen-stimulated whole blood cell cultures from 52 oral contraceptive users, 33 pregnant women and 75 female controls. Cells from women taking oral contraceptives produced significantly less IFN-gamma (p≤0.05) and TNF-alpha (p≤0.05) compared to the controls. In the cultures of the pregnant women significantly lower levels of IFN-gamma (p≤0.01), IL-2 (p ≤0.001) and TNF-alpha (p≤0.01) were found than in those of the controls. Total and differential leukocyte counts were almost identical in all three groups of women. It is suggested, that lymphocyte and monocyte function as measured by cytokine production is altered in women taking oral contraceptives and in pregnant women.
γ/δ T Cells are not Involved in the Natural and Antibody-Dependent Cytotoxicity of Peripheral blood Mononuclear Cells in Inflammatory Bowel Disease
Authors: Giacomelli R. , Passacantando A. , Parzanese I. , Cucinelli F. , Klidara N. , Lattanzio R. , Santori E. , Paolini F. , Manetti L.L. , D'Alo S. , Cipriani P. , Cifone M.G. , Tonietti G.
Published: January 2017

In a previous study, we showed an imbalance in the cytotoxic phenotype of circulating PBMC of IBD patients, possibly related to an alteration in the cytotoxic activity, which might play a role in the immunopathogenesis of IBD. γ/δ T cells, which are increased in the PBMC of IBD patients, represent a minor population of peripheral lymphocytes displaying cytolytic potential and showing both MHC and non-MHC cytotoxicity. This study was performed in order to verify their role in the cytotoxic activity of PBMC from IBD patients and correlate this activity to UC and CD, respectively. We observed a decreased NK cytotoxicity of PBMC in both UC and CD patients and this findings was unrelated to γ/δ T lymphocytes. In fact, both total and γ/δ-depleted PBMC of IBD patients, showed comparable lytic activity. On the contrary, the ADCC lytic activity was within normal range in our patients, ad was not modified by removal of γ/δ cells. The increase of Vδ1+ T cells, previously observed in our patients, seems to be unrelated to this functional impairment, because of a low cytotoxic activity displayed by this subset. Alternatively, the expanded Vδ1+ T cells could be involved in the pathogenesis of the autoimmune phenomena observed in IBD, by a mechanism different from cytotoxicity, such as autoantibodies production and/or loss of tolerance.
Controlling the Environment to Prevent Suicide: International Perspectives
Authors: Leenaars Antoon , Cantor Chris , Connolly John , EchoHawk Marlene , Gailiene Danute , He Zhao Xiong , Kokorina Natalia , Lester David , Lopatin Andrew A , Rodriguez Mario , Schlebusch Lourens , Takahashi Yoshitomo , Vijayakumar Lakshmi , Wenckstern Susanne
Published: January 2017

Background:

Suicide and suicidal behaviour are multifaceted events requiring complex solutions. Controlling the environment is a neglected solution, despite strong support for this approach from the World Health Organization (WHO).

Method

To discuss this approach from a global view, this review is written by authors from various cultures: American, Australian, Canadian, Chinese, Cuban, Dutch, Indian, Irish, Japanese, Lithuanian, Native North American, Russian, and South African.

Results

We examine gun control to illustrate the environmental control approach; however, the worldwide diversity of suicide methods calls for diverse responses. Further, controlling the environment encompasses more than restricting the means of suicide, which we illustrate with examples of toned-down media reports and restricted medicine availability.

Conclusions

Controlling the environment may be a viable strategy for preventing suicide, although research shows that few clinicians implement such approaches.
First-Episode Psychosis: A Comparative Review of Diagnostic Evolution and Predictive Variables in Adolescents versus Adults
Authors: Menezes Natasja M , Milovan Eduard
Published: January 2017

Objective:

To review the diagnostic evolution and predictive variables of diagnosis and outcome in first-episode psychosis in adolescents (age 13–19 years) and adults.

Method

Literature was reviewed through MEDLINE, Psycinfo, and PubMed, and supplemented by selected bibliographies.

Results

First-episode psychosis in the adolescent population has greater diagnostic instability than in adults. We identified trends in the predictive variables of diagnosis and outcome: 1) Premorbid adjustment (that is, personality) in adolescents and Global Assessment of Functioning (GAF) both before and after first-episode psychosis in adolescents and adults are the best predictors of diagnosis; 2) GAF (before and after) is the best predictor of outcome in both adolescents and adults.

Conclusion

Adolescent-onset psychosis appears to be in continuity with adult-onset psychosis. The greater diagnostic instability in adolescents and the absence of significant data on predictive variables suggest a need for specialized and continuous care and research in the adolescent population.
Childhood Anxiety Disorders: Lessons from the Literature
Authors: Manassis Katharina
Published: January 2017

Studies of childhood anxiety disorders have increased in recent years, but the clinical implications of the work are sometimes difficult to discern. This paper reviews salient findings (related to the assessment and management of anxious children) published in the last 5 years. The high comorbidity among disorders, the occurrence of different disorders in the same child over time, recent changes in diagnostic categories, the availability of new anxiety measures, and poor correspondence between parent and child reports of symptoms all underscore the need for thorough assessment. Increasing evidence supports cognitive-behavioural treatments for anxiety disorders, alone or in combination with pharmacotherapy. Other important aspects of management suggested by developmental studies of anxious children include psychoeducation about constitutional factors in the development of anxiety, interventions to address parental anxiety, parenting advice regarding behaviour management and reduction of family conflict, and treatment of child impairment to decrease the risk of depression. Questions requiring further research are identified.
Anxiety Disorders in Suicidal Youth
Authors: Strauss John , Birmaher Boris , Bridge Jeffrey , Axelson David , Chiappetta Laurel , Brent David , Ryan Neal
Published: January 2017

Objective:

To test the hypothesis that anxiety disorders are associated with suicidal ideation and suicide attempts in a child and adolescent sample referred to a clinic.

Method

The sample comprised 1979 patients aged 5 to 19 years who were assessed using the Schedule for Affective Disorders and Schizophrenia for School Aged Children – Present Episode (K-SADS-P) at an outpatient mood and anxiety disorders clinic. Subjects were stratified by age and categorized into mutually exclusive groups as being non-suicidal (n = 817), having suicidal ideation (n = 768), or having attempted suicide (n = 394) in the current episode. Psychiatric diagnoses based on DSM-IV criteria were compared to determine if anxiety disorders were a risk factor for suicidal ideation and suicide attempts. Logistic regression was used to control for significant demographic characteristics and comorbid disorders.

Results

After stratifying by age, we found no differences across the 3 groups (ideators, attempters, and nonsuicidal youth) in rates of an anxiety disorder in general or in specific rates of panic disorder, agoraphobia, social phobia, simple phobia, and obsessive-compulsive disorder. Two salient findings involving anxiety disorders were noted with regression analysis. In younger children (age ≤ 15 years), attempters had a signficantly lower prevalence of separation anxiety disorder (SAD), compared with ideators (OR = 0.30; 95%CI, 0.11 to 0.80; P = 0.006) and nonsuicidal youngsters (OR = 0.14; 95%CI, 0.05 to 0.39; P < 0.0001). In older children (age >15 years), generalized anxiety disorder (GAD) was more prevalent in ideators (OR = 1.65; 95%CI, 1.03 to 2.66; P = 0.03) than in nonsuicidal patients.

Conclusions

Based on this clinical sample, the relation between pediatric anxiety disorder and suicidal ideation and suicide attempts is not straightforward. However, further studies in nonreferred samples are warranted.