bluuebunny/crossref_metadata_2025 huggingface dataset:
Advanced Glycation End Products: Possible Link between Metabolic Syndrome and Periodontal Diseases
Authors: Pietropaoli D. , Monaco A. , Del Pinto R. , Cifone M.G. , Marzo G. , Giannoni M.
Published: January 2017

On a planetary scale, Metabolic Syndrome (MetS) is the third cause of inability after malnutrition and nicotinism, even higher than water shortage and sedentariness. In the USA, the prevalence is estimated at over 25% of the population; in Italy, it involves approximately 25% of men and even 27% of women. These are very high figures, corresponding to approximately 14 million affected individuals. The prevalence is alarming and must not be underestimated, particularly in the dental field, where more than one patient out of four sitting in a dentist's chair is affected. The etiology of periodontal disease has not yet been clarified, and recently the idea to consider it as a multifactor pathology has been developed. Cofactors such as the formation of free radicals of oxygen (ROS), oxidative stress, lipid peroxidation, and formation of glycation end-products (AGEs) probably play an important role in the onset of periodontal disease. The AGEs are compounds physiologically produced by the cells. However, they accumulate and cause pro-inflammatory conditions, when the cellular clearance fails, or in hyperglycemic and oxidative states. All these conditions can be clinically summarized as Metabolic Syndrome. The purpose of this literature review is to establish a relationship between two pathologies with very high prevalence: Metabolic Syndrome and Periodontal Disorder. The literature seems to have clarified that MetS involves a pro-oxidation status, which induces AGE formation. AGEs play a very important role in the course and severity of periodontal diseases.
Is There a Role for Prostate Tumour Overexpressed-1 in the Diagnosis of HGPIN and of Prostatic Adenocarcinoma? A Comparison with α-Methylacyl CoA Racemase
Authors: Scarpelli M. , Mazzucchelli R. , Barbisan F. , Santinelli A. , Lopez-Beltran A. , Cheng L. , Montironi R.
Published: January 2017

Prostate Tumour Overexpressed-1 (PTOV1) was recently identified as a novel gene and protein during a differential display screening for genes overexpressed in prostate cancer (PCa). α-Methyl-CoA racemose (AMACR) mRNA was identified as being overexpressed in PCa. PTOV1 and racemase were immunohistochemically evaluated in PCa, high-grade prostatic intraepithelial neoplasia (HGPIN), atrophy and normal-looking epithelium (NEp) in 20 radical prostatectomies (RPs) with pT2a Gleason score 6 prostate cancer with the aim of analyzing the differences in marker expression between PTOV1 and AMACR. The level of expression of PTOV1 and AMACR increased from NEp and atrophy through HGPIN, away from and adjacent to prostate cancer, to PCa. With the ROC curve analysis the overall accuracy in distinguishing PCa vs HGPIN away from and adjacent to cancer was higher for AMACR than for PTOV1. In conclusion, AMACR can be considered a more accurate marker than PTOV1 in the identification of HGPIN and of PCa. However, PTOV1 may aid in the diagnosis of PCa, at least to supplement AMACR as another positive marker of carcinoma and to potentially increase diagnostic accuracy.
Endothelial Progenitor Cell-Derived Microvesicles Improve Neovascularization in a Murine Model of Hindlimb Ischemia
Authors: Ranghino A. , Cantaluppi V. , Grange C. , Vitillo L. , Fop F. , Biancone L. , Deregibus M.C. , Tetta C. , Segoloni G.P. , Camussi G.
Published: January 2017

Paracrine mediators released from endothelial progenitor cells (EPCs) have been implicated in neoangiogenesis following ischemia. Recently, we demonstrated that microvesicles (MVs) derived from EPCs are able to activate an angiogenic program in quiescent endothelial cells by a horizontal transfer of RNA. In this study we aim to investigate whether EPC-derived MVs are able to induce neoangiogenesis and to enhance recovery in a murine model of hindlimb ischemia. Hindlimb ischemia was induced in severe combined immunodeficient (SCID) mice by ligation and resection of the left femoral artery and mice were treated with EPC-derived MVs (MVs), RNase-inactivated MVs (RnaseMVs), fibroblast-derived MVs or vehicle alone as control (CTL). Since MVs contained the angiogenic miR-126 and miR-296, we evaluated whether microRNAs may account for the angiogenic activities by treating mice with MVs obtained from DICER-knock-down EPC (DICER-MVs). The limb perfusion evaluated by laserdoppler analysis demonstrated that MVs significantly enhanced perfusion in respect to CTL (0.50±0.08 vs 0.39±0.03, p < 0.05). After 7 days, immunohistochemical analyses on the gastrocnemius muscle of the ischemic hindlimb showed that MVs but not fibroblast-MVs significantly increased the capillary density in respect to CTL (MVs vs CTL: 24.7±10.3 vs 13.5±6, p < 0.0001) and (fibroblast-MVs vs CTL: 10.2±3.4 vs 13.5±6, ns); RNaseMVs and DICER-MVs significantly reduced the effect of MVs (RNaseMVs vs CTL: 15.7±4.1 vs 13.5±6, ns) (MVs vs DICER-MVs 24.7±10.3 vs 18.1±5.8, p < 0.05), suggesting a role of RNAs shuttled by MVs. Morphometric analysis confirmed that MVs enhanced limb perfusion and reduced injury. The results of the present study indicate that treatment with EPC-derived MVs improves neovascularization and favors regeneration in severe hindlimb ischemia induced in SCID mice. This suggests a possible use of EPCs-derived MVs for treatment of peripheral arterial disease.
AvidinOX® for Tissue Targeted Delivery of Biotinylated Cells
Authors: Nucera E. , Nicoletti C. , Chiapparino C. , Pacello M.L. , D'Alessio V. , Musarò A. , De Santis R.
Published: January 2017

AvidinOX® a product containing aldehyde groups, generated by ligand-assisted sugar oxidation of avidin by sodium periodate, maintains the capacity to bind biotin with very high affinity and exhibits the property to chemically link cellular and tissue proteins through Schiff's base formation thus residing in tissues for weeks. In recent studies, we have shown that AvidinOX exhibits much higher persistency in the skeletal muscle than native avidin. The aim of the present study is to evaluate whether AvidinOX-biotin interaction might be exploited to target biotinylated cells to an AvidinOX pre-treated muscle. To accomplish this we performed the following experiments: 1) The proliferation and differentiation properties of biotinylated C2C12 myoblasts were tested in vitro upon linkage to AvidinOX; 2) Bone marrow-derived cells (BMDC) were isolated from GFP positive transgenic mice [strain C57 BL/6-tg (UBC-GFP)] and after biotinylation (bBMDC) were intravenously administered to naive and MAVA+ (Mouse anti Avidin Antibody) C57/B6 mice previously injected with AvidinOX in a tibial muscle (TM). Localization efficiency of GFP+ bBMDC was evaluated on serial sections of the AvidinOX- and vehicle-treated (contra lateral limb) TM, 5 days after transplantation. Results show that biotinylated C2C12 cells, once linked to AvidinOX, maintain their proliferation and differentiation capacity, in vitro. Intravenous injection of biotinylated GFP+ bone marrow-derived cells leads to their specific and efficient localization in the AvidinOX-pre-treated, but not contra lateral muscle of both naive and MAVA+ mice. The present data suggest a potential use of AvidinOX to improve tissue targeted delivery of biotinylated cells.
Switch to Icatibant in a Patient Affected by Hereditary Angioedema with High Disease Activity: A Case Report
Authors: Firinu D. , Barca M.P. , Serusi L. , Lorrai M.M. , Peralta M.M. , Manconi P.E. , Del Giacco S.R.
Published: January 2017

Icatibant, an antagonist of the bradykinin B2 receptor, was approved for the treatment of acute attacks of hereditary angioedema in the EU in 2008. This paper presents the case of a 65-year-old woman affected by frequent acute attacks of hereditary angioedema who benefitted from a change of therapy to icatibant, following years of treatment with C1-inhibitor.
Hepatitis C Virus-Related Arthtitis and Rheumatoid Arthritis: Could They Be Different Aspects of the Same Disease?
Authors: Riccio A. , Tarantino G.
Published: January 2017

The role played by HCV in the genesis of many autoimmune disorders has been reported in several studies. In particular, the onset of arthritis has been described in about 2–3% of HCV infection cases. At present, this HCV-related arthritis is classified as a reactive arthritis, but a real distinction of this form from classical rheumatoid arthritis is often difficult. In this presentation, the Authors distinguish two arthritic forms observed in HCV-related arthritis patients: one, characterized by asymmetrical oligoarticular-involvement, and another, with poly-articular symmetrical involvement. The Authors suggest that the latter can be considered as a form of rheumatoid arthritis, because of the similarity of the main clinical aspects and laboratory findings (rheumatoid factor, anti-cyclic citrullinated peptide antibodies) to those of classical rheumatoid arthritis, which make the two forms indistinguishable. Therefore, HCV could be considered the etiologic agent of a limited number of cases of rheumatoid arthritis.
Platelet Rich Plasma in Tendinopathies: How to Explain the Failure
Authors: Abate M. , Di Gregorio P. , Schiavone C. , Salini V. , Tosi U. , Muttini A.
Published: January 2017

Tendinopathies are very common in athletes and in people practicing sport activities. The experimental evidence that Growth Factors (GFs), present in platelets, enhance the recruitment, proliferation and differentiation of cells involved in tissue regeneration, has prompted the use of Platelet Rich Plasma (PRP) preparations in the treatment of these diseases. However, at present, a sound demonstration of the clinical efficacy of PRP is still lacking. Several theoretical and practical reasons can explain the failure of the treatment: a) animal experiments have been carried out on “normal tendons” submitted to surgical lesions, and it is questionable whether these models may best mimic human pathology; b) the pathway of chronic tendinopathies is very complex, involving, besides GFs, many other pathogenetic factors, which operate at different stages of the disease; c) several methods have been used to produce PRP, which can result in a large variation in GF content, and in kinetics of release. Therefore, further research is desirable. As a preliminary step, it is necessary to standardize PRP preparation, and to establish the modalities of its activation and administration. Secondly, prospective, randomized, double-blind studies are needed, selecting subjects with homogenous forms of tendinopathies: load-bearing and non-load-bearing tendons, midportion and insertional tendinopathies, with or without neovascularization. Finally, new strategies in PRP use should be exploited: among them, the association of PRP with autologous stem cells or the administration of selective GFs (fibroblast growth factor, vascular endothelial growth factor, or anti-angiogenic factors), which could be better options in specific situations.
Effects of 4-Nonylphenol and/or Diisononylphthalate on THP-1 Cells: Impact of Endocrine Disruptors on Human Immune System Parameters
Authors: Bennasroune A. , Rojas L. , Foucaud L. , Goulaouic S. , Laval-Gilly P. , Fickova M. , Couleau N. , Durandet C. , Henry S. , Falla J.
Published: January 2017

The aim of the present work is to investigate the link between two endocrine disruptor compounds (EDCs), which are chemicals that interfere with the hormone system in human and wildlife, and the human immune response through a study of their effects on the THP-1 human cell line which was used as a model for macrophages. We used two EDCs, diisononylphthalate (DiP) and 4-n-nonylphenol (NP) alone or in combination in order to evaluate the effects of these compounds on several parameters of the immune response - cytokine secretion, phagocytosis and the putative implication of the estrogen receptors - by studying the level of MAPK activation. NP and DiP strongly reduced phagocytosis and modify cytokine secretions. Indeed, differentiated THP-1 cell exposures (i) to 5 and 10 μM of combination of NP and DiP induced an IL-8 level in the medium respectively of 28.9 and 45% higher than the level obtained for the control (untreated cells), (ii) to combination of NP and DiP at 10 μM induced an increase of IL-1β level in comparison to the control level, (iii) to combination of NP and DiP induced an increase of TNF-α level whatever the concentration of EDCs tested (between 0 and 10 μM). Lastly, differentiated THP-1 cell exposure to NP, DiP alone or in combination (2 μM for each condition) induced a decrease of ERK1/2 phosphorylation in comparison to ERK1/2 phosphorylation level of the control. Moreover, differentiated THP-1 cell treatments by ICI-182780 (an estrogen receptor antagonist) supressed the EDC effects on ERK1/2 phosphorylation level which indicates an estrogen receptor-dependent pathway. These results suggest that EDCs have the ability to alter the human immune function, maybe by interfering with endocrine balance.
Acquired Peripheral Neuropathy: A Report on 20 Children
Authors: Pavone P. , Praticò A.D. , Ruggieri M. , Verrotti A. , Castellano-Chiodo D. , Greco F. , Falsaperla R. , Pavone L.
Published: January 2017

Guillain—Barré syndrome (GBS) is an inflammatory polyneuropathy characterized by acute onset, rapid progression, symmetric muscular weakness, pain, and paresthesias. The incidence of GBS in the pediatric age group is 0.8 cases per 100,000; 50%-70% of the cases are preceded by respiratory or gastrointestinal infectious episodes or vaccination. The etiopathogenesis of GBS has been hypothesized to involve a direct immune-mediated mechanism against the peripheral nerves. A series of 20 patients managed in the Department of Pediatrics of the University of Catania between 2003 and 2011 and evaluated according to epidemiologic, clinical, and therapeutic features is reported.
Effects of Oral Hyposensitization Therapy with Nickel on Haemoglobin and Haematocrit Values in Sensitized Patients
Authors: Tammaro A. , Narcisi A. , Di Russo P.P. , Abruzzese C. , Caperchi C. , Persechino F. , Parisella F.R. , Persechino S.
Published: January 2017

Nickel deficiency leads to reduced iron content in organs and to reduced hemoglobin levels and haematocrit counts. We carried out a clinical trial of oral hyposensitization therapy with low doses of nickel on a group of 20 patients affected by systemic allergy to this sensitizer element and with a chronic relapsing low hemoglobin level and haematocrit count. We obtained interesting results en maintaining these values in treated patients.
Gut Microbiota and the Immune System: An Intimate Partnership in Health and Disease
Authors: Iebba V. , Nicoletti M. , Schippa S.
Published: January 2017

In recent years there have been increased rates of autoimmune diseases, possibly associated to altered intestinal microflora. In this brief review article, after a description of the structure and function of the gut microbiota organ and its cross-talk with the human host, we give a report on findings indicating how the host immune system responds to bacterial colonization of the gastrointestinal tract. The disturbances in the bacterial microbiota will result in the deregulation of adaptive immune cells, which may underlie autoimmune disorders. The mammalian immune system, which seems to be designed to control microorganisms, could be instead influenced by microorganisms, as suggested in recent literature. Alterations in both the structure and function of intestinal microbiota could be one of the ‘common causative triggers’ of autoimmune and/or autoinflammatory disorders.
Impact and Neuropeptide Substance Pan Inflammatory Compound on Arachidonic Acid Compound Generation
Authors: Nicoletti M. , Neri G. , Maccauro G. , Tripodi D. , Varvara G. , Saggini A. , Potalivo G. , Castellani M.L. , Fulcheri M. , Rosati M. , Toniato E. , Caraffa A. , Antinolfi P. , Cerulli G. , Pandolfi F. , Galzio R. , Conti P. , Theoharides T.C.
Published: January 2017

There is much evidence that neuropeptide substance P is involved in neurogenic inflammation and is an important neurotransmitter and neurmodulator compound. In addition, substance P plays an important role in inflammation and immunity. Macrophages can be activated by substance P which provokes the release of inflammatory compounds such as interleukins, chemokines and growth factors. Substance P is involved in the mechanism of pain through the trigeminal nerve which runs through the head, temporal and sinus cavity. Substance P also activates mast cells to release inflammatory mediators such as arachindonic acid compound, cytokines/chemokines and histamine. The release of these chemical mediators is crucial for inflammatory response. Among these mediators there are prostoglandins and leukotrines. Here we review the impact of substance P on inflammatory compounds.
Combined Blockade and Akt/Mtor Pathway Inhibits Growth of Human Hemangioma via Downregulation of Proliferating Cell Nuclear Antigen
Authors: Ou J-M. , Qiu M-K. , Dai Y-X. , Dong Q. , Shen J. , Dong P. , Wang X-F. , Liu Y-B. , Fei Z-W.
Published: January 2017

Protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway plays a crucial role in the tumorigenesis and progression of multiple tumors, and has been shown to be important therapeutic targets for cancer. The present study aimed to explore the role and molecular mechanisms of AKT/mTOR pathway in human hemangioma (HA). Twenty-five cases of human HA tissues were collected. The expression of AKT, mTOR and proliferating cell nuclear antigen (PCNA) proteins was evaluated using semi-quantitative immunohistochemistry in biopsy samples in different phases of HA. AKT/mTOR pathway was blocked by recombinant small hairpin RNA adenovirus vector rAd5-AKT+mTOR (rAd5-Am), used for infecting proliferating phase HA-derived endothelial cells (HDEC). The expression of AKT, mTOR and PCNA was detected by Real-time PCR and Western blot assays. Cell proliferative activities were determined by MTT assay, and cell cycle distribution and apoptosis were analyzed by flow cytometry. As a consequence, the expression of AKT, mTOR and PCNA was significantly increased in proliferative phase HA, while that was decreased in involutive phase. Combined blockade of AKT/mTOR pathway by rAd5-Am diminished cell proliferative activities, and induced cell apoptosis and cycle arrest with the decreased expression of AKT, mTOR and PCNA in proliferative phase HDEC. In conclusion, the activity of AKT/mTOR pathway was increased in proliferative phase HA, while it was decreased in involutive phase. Combined blockade of AKT/mTOR pathway might suppress cell proliferation via down-regulation of PCNA expression, and induce apoptosis and cycle arrest in proliferative phase HDEC, suggesting that AKT/mTOR pathway might represent the important therapeutic targets for human HA.
Immunogenetics and Hplc Analyses Contribute to Understanding the Etiopathology of Rheumatoid Arthritis through Studies on Ancient Human Remains
Authors: Poma A. , Carlucci G. , Fontecchio G.
Published: January 2017

Genetic investigations on ancient human remains affected by rheumatological pathologies are a research field of particular interest for identifying origins and the etiopathology of diseases, especially those having an autoimmune background such as rheumatoid arthritis (RA). We wish to demonstrate how reliable studies concerning this topic require collaboration between multiple disciplines, usually starting from paleopathologic observations up to immunogenetic screening, even involving analytical chemistry. Here, we focused our investigation on the skeleton of Cardinal Carlo de'Medici (1595–1666) for whom RA and psoriatic arthritis (PsA) were postulated after paleopathologic examination. RA susceptibility is linked to specific HLA alleles belonging to DRB1*04 locus, such as DRB1*0401, while Cw*0602 and DRB1*07 predispose to PsA. Thus, we genotyped the Cardinal's remains to search for RA or PsA “risk genes”. Ancient DNA is often subjected to hydrolysis followed by fragmentation. For this reason, all immunogenetic tests were preceded by an original RP-HPLC-FL method able to inform on the ancient DNA preservation and the extent of contamination, with the purpose of avoiding the risk of false positive results. After DNA isolation from a piece of bone from the Cardinal, PCR-SSP and reverse-SSO hybridization assays were applied to perform genomic HLA-typing. RP-HPLC-FL analysis revealed a good preservation of DNA without contamination by exogenous genomes. Molecular tests assigned to the Cardinal the genotype DRB1*0401/*1102 for HLA-DRB locus and Cw*04/*12 for HLA-C locus, data that support a genetic predisposition for RA but not for PsA. This multidisciplinary study has allowed us: (i) to ascertain that the remains undoubtledy belonged to the specific subject, Cardinal Carlo de'Medici; (ii) to sustain that the subject suffered from RA rather then that PsA, and (iii) to state that RA was already widespread in Europe at the Renaissance age, despite some authors claiming that the disease was introduced to the Old Continent from America after colonization during the 18th century
Systemic Lupus Erythematosus Patients with and without Neuropsychiatric Manifestations: A Neck and Transcranial Duplex Sonography Study
Authors: Zardi E.M. , Vernieri F. , Navarini L. , Taccone A. , Sambataro G. , Alemanno P. , Margiotta D. , Afeltra A.
Published: January 2017

Neuropsychiatric manifestations are not rarely associated with systemic lupus erythematosus (SLE). Magnetic resonance angiography and positron emission tomography can provide excellent images of cerebral perfusion and metabolism whereas information is still lacking on a possible diagnostic role of ultrasound. In this study we aim to assess whether duplex sonography of neck and intracranial vessels may be useful in distinguishing patients with and without neuropsychiatric SLE (NPSLE). Neck and transcranial duplex sonography was performed by a single operator on 33 women affected by SLE (mean age ± SD: 47.69±8.17 years) and on 15 healthy control subjects. Nineteen patients presented NPSLE. Pulsatility and resistivity indices (PI and RI) were automatically calculated by the ultrasound instrument in internal carotid (ICA) and middle cerebral artery (MCA), on both sides, according to standard methods. No significant haemodynamic differences were found in mean and median PI and RI values of ICA and MCA comparing SLE with NPSLE patients and with healthy control subjects. No correlation was found between MCA and ICA parameters in the same group of patients. Duplex sonography of cerebral vessels is unable to distinguish SLE and NPSLE patients. Heterogeneity of causes in the pathogenesis of NPSLE and the different vascular adaptation of cerebral macrocirculation as opposed to cerebral microcirculation may represent possible reasons that explain the inability of ultrasound to differentiate SLE patients from NPSLE patients.
STAT4 is a Genetic Risk Factor for Systemic Sclerosis in a Chinese Population
Authors: Yi L. , Wang J.C. , Guo X.J. , Gu Y.H. , Tu W.Z. , Guo G. , Yang L. , Xiao R. , Yu L. , Mayes M.D. , Assassi S. , Jin L. , Zou H.J. , Zhou X.D.
Published: January 2017

Systemic sclerosis (SSc) is an immune-mediated and complex genetic disease. An association of single-nucleotide polymorphisms (SNPs) in the STAT4 gene with SSc has been reported in European Caucasians, North Americans and Japanese. We undertook the current study to examine whether the STAT4 SNPs are also associated with susceptibility to SSc and SSc subsets in a Han Chinese population. A total of 453 Han Chinese patients with SSc and 534 healthy controls were examined in the study. The SNPs rs7574865, rs10168266 and rs3821236 of the STAT4 gene were examined with SNP TaqMan assays. The T-allele carriers of rs7574865 and rs10168266 were strongly associated with the presence of anti-topoisomerase I (ATA) and pulmonary fibrosis in SSc patients, as well as with diffuse cutaneous SSc (dcSSc). The presence of anti-centromere (ACA) and limited cutaneous SSc (lcSSc) did not show significant association with any of the examined SNPs. The results were consistent with previous reports in other ethnic populations in supporting the notion that polymorphisms of STAT4 may play an important role in susceptibility to SSc. It also revealed different genetic aspects of SSc subsets in a Han Chinese population.
An Approach for Plasma Cell Myeloma Diagnosis by Two-Color Flow Cytometry Based on Kappa/Lambda Ratios of CD38-Gated Plasma Cells
Authors: Nakayama S. , Yokote T. , Hirata Y. , Iwaki K. , Akioka T. , Miyoshi T. , Takayama A. , Nishiwaki U. , Masuda Y. , Ikemoto T. , Tanaka H. , Nishimura Y. , Tsuji M. , Hanafusa T.
Published: January 2017

Criteria from the World Health Organization (WHO) are commonly used to diagnose plasma cell myeloma (PCM), but they are complex and require several laboratory parameters. To differentiate reactive plasmacytosis from clonal plasma cell neoplasms, such as PCM, it is important to accurately determine the expression of the cytoplasmic immunoglobulin (cIg) light chain (LC). Through retrospective analyses, we selected the patients with PCM, and analyzed records of 52 PCM patients, who underwent bone biopsies, and final diagnosis of PCM was established according to WHO criteria, and 22 controls. In the present study, all samples were analyzed by flow cytometry (FC) in the side scatter vs CD38 histogram mode, and the CD38-gated plasma cell population was identified. The positive cell ratios of kappa and lambda to plasma cell populations were analyzed. PCM cells were distinguished from normal plasma cells by a cut-off level between 0.80 and 3.3, a sensitivity of 90.3%, and a specificity of 81.1%. Two-color FC analysis is simple to perform, inexpensive, and clinically relevant data are obtained soon after completion of the FC measurements. It could be one of the helpful tools in the diagnosis of PCM. The correct diagnosis of PCM can be achieved more simply, efficiently, and rapidly by combining this method.
Tanshinone VI Inhibits the Expression of Intercellular Adhesion Molecule-1 and Vascular Cell Adhesion Molecule-1
Authors: Nicolin V. , Bossi F. , Viggiano A. , Valentini R. , Nori S.L.
Published: January 2017

This study investigated the possible antitumor mechanisms of action of Tanshinone VI, one of the components of Salvia miltiorrhiza Bunge, which is used in traditional Chinese herbal medicine. To this end, the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), were evaluated in-vitro in tumor necrosis factor-α (TNF-α)-stimulated endothelial cells, with, or without the addition of Tanshinone VI (10, 20, 30, or 40 mM) in the culture medium; the effects of Tanshinone VI on angiogenesis was also evaluated with an epithelial cell tube formation assay and its toxicity was evaluated with a colorimetric (MTT) cell viability assay. The results showed that the up-regulation of ICAM-1 and VCAM-1 induced by TNF-α was dose-dependently inhibited by Tanshinone VI, with restoration of control levels at the dose of 40 mM; Tanshinone VI also had a remarkable anti-angiogenesis effect, already at the dose of 10 mM, while none of the doses tested had significant effects on cell viability. These results indicate that the antitumor properties of Tanshinone VI can be ascribed to the inhibition of cell adhesion, due to blockage of the up-regulation of cell adhesion molecules, with the consequent inhibition of metastases formation and/or angiogenesis. The lack of toxic effects at the dosage used makes Tanshinone VI a good candidate for its therapeutic use in humans.
Management of Biofilm Control in an Elderly Patient Suffering from Rheumatoid Arthritis: A Case Report
Authors: Nardi G.M. , Sabatini S. , Lauritano D. , Denisi C. , Grassi F.R.
Published: January 2017

The increase in the average age of the population forces dentists and dental hygienists to deal with clinical scenarios typical of the elderly. In old people deep changes present both in systemic and oral health. These changes affect the anatomical and functional integrity of many tissues, such as the mouth. Impairment of patients' oral hygiene becomes manifested by local infections and promotes the pathogenesis of periodontal diseases. There is also a significant increase in autoimmune diseases, which are defined as disorders of the immune system that result in abnormal immune responses. Among the autoimmune diseases of medical interest we report a case of rheumatoid arthritis (RA) strictly related to periodontal disease.
Adipose Tissue-Derived Stromal Cells Primed in Vitro with Paclitaxel Acquire Anti-Tumor Activity
Authors: Bonomi A. , Coccè V. , Cavicchini L. , Sisto F. , Dossena M. , Balzarini P. , Portolani N. , Ciusani E. , Parati E. , Alessandri G. , Pessina A.
Published: January 2017

Many strategies, including those based on genetically modified Mesenchymal Stromal Cells (MSCs), have been developed in recent years in order to obtain high concentrations of anticancer drugs effective on tumor mass. In previous studies, we showed that human and murine bone marrow-derived MSCs (BM-MSCs) and human skin-derived stromal fibroblasts (hSDFs) acquired strong anti-tumor capacity, both in vitro and in vivo, once primed with Paclitaxel (PTX). In this report we investigate whether adipose tissue-derived MSCs (AT-MSCs) behave similarly to BM-MSCs in their uptake and release of PTX in sufficient amounts to inhibit tumor proliferation in vitro. According to a standardized procedure, PTX primed AT-MSCs (AT-MSCsPTX) were washed and then subcultured to harvest their conditioned medium, which was then tested to evaluate its in vitro anti-tumor potential. We observed that AT-MSCsPTX were able to uptake PTX and release it in a time-dependent manner and that the released drug was active in vitro against proliferation of leukemia, anaplastic osteosarcoma, prostatic carcinoma and neuroblastoma cell lines. These data confirm that AT-MSCs, as well as BM-MSCs, can be loaded in vitro with anti-cancer drugs. While the harvesting of BM-MSCs requires invasive procedures, AT-MSCs can be prepared from fat samples taken with little patient discomfort. For this reason, this source of stromal cells represents an important alternative to BM-MSCs in developing new tools for carrying and delivering anti-cancer drugs into tumor microenvironments.
Cutaneous Manifestations in Patients with Chronic Renal Failure on Hemodialysis
Authors: Specchio F. , Carboni I. , Chimenti S. , Tamburi F. , Nisticò S.
Published: January 2017

Patients with chronic renal failure (CRF) may exhibit various cutaneous abnormalities, including changes in skin colour, pruritus, xerosis, hair, nail and oral changes, metastatic calcinosis, and bullous dermatosis. These changes have a considerable negative effect on the patient's quality of life. Early recognition of cutaneous signs and prompt initiation of treatment can dramatically alter their course and decrease morbidity.
Vasoactive Role for Angiotensin II Type 2 Receptors in Human Radial Artery
Authors: Zulli A. , Hare D.L. , Buxton B.F. , Widdop R.E.
Published: January 2017

Angotensin II type 2 receptors are believed to counter the effects of the angiotensin type 1 receptors and there is no data relating to the co-localisation of either receptor in human diseased arteries. We sought to determine whether AT2R counter the effects of AT1R and immunolocalise both receptors to cells in human diseased arteries. Human radial arteries (RA, n=11) were placed in organ bath chambers and preincubated with the AT2R antagonist PD123319 for twenty minutes before an angiotensin II dose response curve. Immunohistochemistry was performed to identify receptors and pathology was quantified by image analysis software. We observed both receptors in human arteries. Angiogenic blood vessels within occluded arteries expressed both receptors. PD123319 impaired angiotensin II mediated vasoconstriction by 20% (n=5, p<0.05), however in other arteries, PD123319 exacerbated angiotensin II-mediated vasoconstriction by 60% (n=6, p<0.01), respectively. We conclude that inhibition of AT2R can enhance or reduce angiotensin II-mediated vasoconstriction. These data indicate that the role of AT2R in human diseased arteries is divergent although the AT2R-mediated vasorelaxation prevails.
Cytokine Profiles and Hepatic Injury in Occult Hepatitis C Versus Chronic Hepatitis C Virus Infection
Authors: Mousa N. , Eldars W. , Eldegla H. , Fouda O. , Gad Y. , Abousamra N. , Elmasry E. , Arafa M.
Published: January 2017

Occult hepatitis C virus (HCV) infection is a new entity that should be considered when diagnosing patients with abnormal liver functions of unknown origin. This work was carried out to evaluate T-helper 1/T-helper 2 (Th1/Th2) cytokine profiles in patients with occult HCV infection versus chronic hepatitis C (CHC) infection, also to investigate any association between theses cytokines and liver histological features in both groups. Serum levels of Th1 cytokines (IL-2, IFN-γ) and Th2 (IL-4 and IL-10) were measured in 35 patients with occult HCV infection compared to 50 patients with chronic hepatitis C infection and 30 healthy controls. We have found that Th1 cytokines were significantly increased in patients with CHC infection than in both occult HCV infection and control groups (p<0.001). On the other hand, serum IL-4 levels were higher in occult HCV infection than in CHC and control groups (p<0.001). Furthermore, serum IL-10 levels were higher in both patient groups vs control group (p<0.001), with no significant difference between CHC and occult HCV groups. Finally, only serum IL-10 levels were significantly higher among patients with high activity (A2-A3) than those with low activity (A0-A1) in both CHC and occult HCV groups (p=0.038, p=0.025, respectively). Patients with occult HCV infection exhibited a distinct immunoregulatory cytokine pattern that is shifted towards the Th2 arm.
Multiple Cytokine-Producing Testicular Malignant Lymphoma with Clinical Symptoms Resembling Infectious Signs
Authors: Nakayama S. , Yokote T. , Tsuji M. , Hirata Y. , Iwaki K. , Takayama A. , Nishiwaki U. , Hiraoka N. , Akioka T. , Miyoshi T. , Masuda Y. , Hanafusa T.
Published: January 2017

We present the case of a 64-year-old male with painful swelling of the bilateral testes and epididymides, high fever, leukocytosis, and an elevated C-reactive protein (CRP) level. This is the first case report of testicular diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS) immunostained for multiple cytokines and their receptors, which clearly demonstrates that tumor cells express multiple cytokines [interleukin-6 (IL-6) and granulocyte colony-stimulating factor (G-CSF)] and their receptors [IL-6 receptor (IL-6R) and G-CSF receptor (G-CSFR)]. The clinical course showed that the reduction in tumor size was accompanied by a corresponding improvement in clinical symptoms and peripheral blood findings. Such clinical investigation may lead clinicians to misdiagnose inflammatory disease rather than neoplastic disease. Recognizing this paraneoplastic phenomenon associated with some cases of testicular DLBCL, NOS is important. In addition, this case suggests that the growth of tumor cells may be promoted through autocrine mechanisms of IL-6 and G-CSF, which are produced by tumor cells. The possibility that these cytokines can be produced by tumor cells and can accelerate tumor proliferation should be considered to be a cause of severe clinical symptoms, an aggressive clinical course, and an indication of the necessity of treatment. Certain cytokines may be used as tumor markers in some cases of DLBCL, NOS.
Analysis of T Lymphocytes Cloned from Rejected Kidney Allograft: High Frequency of Cytotoxic T Cell Precursor
Authors: Benvenuto R. , Bachetoni A. , Franco A. , Cinti P. , Sallusto F. , Balsano C. , Malajoni E. Renna , Barnaba V.
Published: January 2017

A high proportion of CD8 positive cells and inverted CD4/CD8 ratio were found in peripheral blood mononuclear cells and in freshly isolated kidney-graft infiltrating cells in two patients who underwent irreversible acute rejection.

Seventy seven T cell clones were generated from the T cell blasts infiltrating rejected kidney allografts. The majority of T cell clones obtained showed CD8 phenotype in accordance to uncloned graft infiltrating cells. All clones (both CD8 and CD4) displayed cytolytic activity evaluated by lectin-dependent cell-mediated cytotoxicity and natural killer (NK) activities. None of the clones presented lymphokine activated killer phenomenon.

These data suggest that the graft infiltrate is characterized by T cell clones with cytolytic potential and that these T cell clones may be responsible for the killing of graft cells by a CTL or NK type mechanism.
Differential Sensitivity of CD4+ and CD8+ T Lymphocytes to Phorbol Myristate Acetate upon Anti-CD3 Stimulation: Evidence for a Distinct Signaling Pathway
Authors: Chouaib S. , Mahe Yann , Mechri Salah , Andreeff M. , Welte K.
Published: January 2017

The effects of suboptimal concentrations of Phorbol Myristate Acetate (PMA) in combination with submitogenic concentrations of OKT3 antibody on CD4+ and CD8+ cell activation were investigated. Upon stimulation with OKT3 (25 pg/ml) and PMA (0.25 – 0.75 ng/ml), the majority of CD4+ cells entered the cell cycle whereas most of CD8+ cells remained in G0/G1 phase. Under the same conditions of OKT3 stimulations, both CD4+ and CD8+ cells failed to produce IL2 in the absence of PMA. In the presence of PMA (0,25 ng/ml), CD4+ produced measurable amounts of IL2 (0,5 – 2,3 U/ml) whereas IL2 production by CD8+ cells remained below the detection limit. Expression of TAC antigen (CD25) was found to parallel IL2 production and cell proliferation in both subsets whereas changes in [Ca2+] mobilization following OKT3 stimulation were similar in both subsets.

Interestingly, the elevation of intracellular cyclic adenosine 3':5' monophosphate (cAMP) was not equally distributed between CD4+ and CD8+ subpopulations. Furthermore, the kinetics of protein kinase (PKC) translocation was markedly prolonged in membranes of CD4+ cells compared with CD8+ cells suggesting a differential involvement that may operate under distinct regulatory signaling mechanisms.
The Cytokine Network: Their Role in Physiopathology and Therapeutic Implications
Authors: Ricevuti G. , Mazzone A. , Pasotti D. , Notario A.
Published: January 2017

Lymphocytes, accessory-endothelial-and inflammatory-cells produce a variety of soluble factors termed cytokines. These are regulatory molecules which appear after the immune response at all stages of lymphocyte development. They also have important regulatory influences on other haematopoietic cells. Rapid progress is being made through the use of gene cloned cytokines in understanding the complex interactions of these factors with many different cell types. New factors have been added to the cytokine network, and new functions reported for existing cytokines. The clinical implications in disease and the application of cytokines or their inhibitors in human disorders, cancer, infection and autoimmunity, has met with some success and many trials are currently in progress which should lead to more successful therapeutic strategies.
Possible Role of Cytokines in the Pathogenesis of Non-Organ Specific Autoimmunity
Authors: Zupo S. , Dono M. , Azzoni L. , Chiorazzi N. , Ferrarini M.
Published: January 2017

This paper describes the experiments conducted in our laboratory on the mode of activation of CD5 + B cells. The data show that these cells are stimulated in a manner that is less dependent of T cell help as compared to CD5- cells and define IL-2 as the major growth and differentiation factor for CD5 + cells. These data are discussed in the light of the supposed function of CD5 + cells that seem represented by the capacity to release polyspecific antibodies reacting with a multiplicity of antigens from various pathogens. These antibodies, also called natural antibodies, probably represent one of the first line of defense against invading microrganisms.
Influence of Neuroleptics on Cytotoxic Activity of Rat Natural Killer Cells
Authors: Madej A.J. , Kowalski J. , Belowski D. , Herman Z. S.
Published: January 2017

The aim of the study was to evaluate the in vivo and in vitro effects of three neuroleptics (chlorpromazine, haloperidol, and sulpiride) on the activity of rat spleen NK cells. In the in vivo experiment, rats were injected with different intraperitoneal doses of neuroleptics given once, for 14 or 28 days. In the in vitro experiment rat spleen NK cells were cultured in medium containing two different concentrations of neuroleptics for three days. The cytotoxic activity of NK cells was evaluated by measuring 51Cr release from YAC-1 target cells after 4-hour incubation. We also measured, using fluorescein-labelled anti-NK monoclonal antibody, the percentage of NK cells in the splenocyte population before and after single intraperitoneal injections of neuroleptics. In the in vitro experiment, both haloperidol (1×10−5 M and 1×10−6 M) and sulpiride (1.5×10−3 M and 1.5×10−4 M) induced a statistically significant decrease in the cytotoxic activity of NK cells. The lower dose of chlorpromazine (6×10−6 M) decreased the cytotoxic activity of NK cells, while the higher dose (6×10−5 M) did not. In the in vivo experiment, both single and repeated doses of chlorpromazine (2 mg /kg /day), haloperidol (0.5 mg/kg/day) and sulpiride (50 mg/kg/day) increased NK cell activity. That effect reflected an increase in NK cell activity but not in the number of NK cells. The study has shown that the immunomodulatory effect of neuroleptics on NK cell activity depends mainly on drug concentrations and experimental conditions.
Specific IgG and IgA Antibodies and Related Subclasses in the Diagnosis of Gastrointestinal Disorders or Atopic Dermatitis Due to Cow's Milk and Egg
Authors: Lucarelli S. , Frediani T. , Corbi S. , Del Guercio I. , Ranauro E. , Barbato M. , Cardi E.
Published: January 2017

Today the only investigation considered valid for the diagnosis of reactions to food is the oral stimulation test following a period of diet during which the suspected food item has been withdrawn. This test is, however, not without a certain risk, due to the possibility of the onset of an unexpected anaphylactic reaction. Researchers are therefore focusing attention on new, more reliable and less risky diagnostic techniques. The aim of this investigation was to evaluate, by means of ELISA, the serum levels of specific IgG and IgA antibodies and of their subclasses for casein, alpha lactalbumin, bovine beta-lactoglobulin and ovalbumin in 72 children with gastointestinal disorders or atopic dermatitis due to food. The diagnosis of food intolerance was made following a double blind oral stimulation test: 16 healthy age-matched children were used as controls. The results of the investigation demonstrated that specific IgA levels for all the food antigens were statistically higher compared with those of controls, irrespective of the clinical features, whereas the IgG class antibodies were statistically higher only for casein in the children with atopic dermatitis. Studies on the antibody subclasses, showed a statistically significant increase particulary of IgG, but also of IgA1, especially in children with gastointestinal disorders. In conclusion, the results show that total specific IgA may play a role, although modest, in the diagnosis of food intolerance. The IgG subclasses, and to a lesser extent the IgA subclasses, appear to be useful in the diagnostic work-up, particularly in children with gastrointestinal symptoms.
Influence of Losartan Therapy on Tubular Sodium Kinetics in Mild to Moderate Hypertension
Authors: Consolo F. , Monardo P. , Consolo P.
Published: January 2017

Losartan is a selective antagonist of angiotensin II and it is useful in the therapy of tubular sodium kinetics in mild to moderate hypertension. In this study 30 subjects with mild to moderate hypertension were treated for 2 months with Losartan and were compared to control group of 30 normotensive subjects. Inulin and para aminohippuric acid (PAH) were administered intravenously to both groups, and blood and urine samples were collected every 30 minutes to determine baseline levels of inulin, PAH, lithium, sodium and potassium. A protein meal was given without salt, cereals nor vegetables. After 4 clearance periods were determined. Glomerular filtration rate data from treated and control subjects were not statistically significant. However, lithium clearance, fractional excretion, absolute distal reabsorption of sodium, as well as filtration fraction from Losartan treated and untreated subjects were highly significant at all minutes studied (30-60-90-120, and 180). In this paper we confirm that Losartan can be identified as a drug with high tollerability compared to other compounds of the same class that act on receptor inhibition for the managment of hypertension.
Comorbidity in Juvenile Obsessive—Compulsive Disorder: A Report from India
Authors: Reddy YC Janardhan , Reddy P Srinivas , Srinath S , Khanna S , Sheshadri SP , Girimaji SC
Published: January 2017

Objective:

Using minimal exclusion criteria, to assess systematically the psychiatric comorbidity in children and adolescents with obsessive–compulsive disorder (OCD) and compare the findings with those of previous studies.

Method:

Fifty-four children and adolescents who satisfied DSM-III-R criteria for OCD were assessed using a structured interview schedule, the Children's version of the Yale-Brown Obsessive Compulsive Scale (CY-BOCS), and the questionnaire for tic disorders. All 54 subjects were recruited from the Child and Adolescent Psychiatry (CAP) services of the National Institute of Mental Health and Neuro Sciences (NIMHANS), Bangalore, South India. Diagnoses were determined consensually after a review of all the available data.

Results:

Comorbidity was found in 69% of the sample: 22% were diagnosed with disruptive disorders; 20% met criteria for mood disorders; 19% had anxiety disorders; and 17% had tic disorders. Only 1 subject had bipolar disorder, and none had psychosis. The rates for individual diagnoses—in particular, the rates for disruptive disorders, bipolar disorder, and psychosis—were considerably lower than those reported in previous studies.

Conclusions:

Patterns of comorbidity in this study differed from those previously reported. Novel patterns of comorbidity with disruptive disorders, bipolar disorder, and psychosis reported in a few recent studies were not replicated in this study. These differences are probably due to different ascertainment methods. Comorbidity needs to be assessed in large epidemiological samples before definite associations can be made between certain comorbid disorders and juvenile OCD.
Measuring Depression in Canada's Elderly Chinese Population: Use of a Community Screening Instrument
Authors: Lai Daniel WL
Published: January 2017

Objective:

To assess the reliability and validity of a 15-item Chinese Geriatric Depression Scale (GDS) to measure depression in Canada's elderly Chinese population.

Method

A random sample of 96 elderly Chinese in a Canadian city was surveyed by telephone. The measure of depression used was the 15-item Chinese version of the GDS. In addition, the physical and mental health of the respondents was assessed by a Chinese version of the SF-12, questions on self-perceived general health, and questions on self-reported illnesses and health concerns.

Results

The prevalence rate of depression in the elderly Chinese who participated in this study is approximately 20%, which is much lower than that of elderly Chinese in the United States (US). Cronbach's alpha and split-half reliability coefficients were 0.88 and 0.89 respectively. GDS scores are significantly correlated with the mental health component (r = −0.74) of the SF-12, indicating a strong convergent validity. GDS scores are also correlated with the physical health component of the SF-12 (r = −0.41), self-perceived general health (r = −0.26), and illnesses (r = 0.52), demonstrating concurrent validity.

Conclusions:

The 15-item Chinese GDS has good internal consistency and both convergent and concurrent validity. It can help to identify depression among the elderly Chinese, allowing early identification and prevention of this problem. Further research is required to support its use in clinical settings.