Transplantation of SNAP-treated adipose tissue-derived stem cells improves cardiac function and induces neovascularization after myocardium infarct in rats

Stem cell therapy has been considered a promise for damaged myocardial tissue. We have previously shown that S-nitroso-N-acetyl-D,L-penicillamine (SNAP) increases the expression of several muscular markers and VEGF in mesenchymal stem cells, indicating that transplantation of SNAP-treated cells could provide better functional outcomes. Here, we transplanted SNAP-treated adipose tissue-derived stem cells (ADSCs) in rat infarcted myocardium. After 30 days, we observed a significant improvement of the ejection fraction in rats that received SNAP-treated ADSCs, compared with those that received untreated cells (p = 0.008). Immunohistochemical reactions showed an increased expression of troponin T–C and von Willebrand factor, and organized vascular units in the infarcted area of tissue transplanted with treated ADSCs. SNAP exposure induced intracellular S-nitrosation, a decreased GSH/GSSG ratio, but did not increase cGMP levels. Collectively, these results indicate that SNAP alters the redox environment of ADSCs, possibly associated with a pre-differentiation state, which may improve cardiac function after transplantation.     

Ganglioside-exposed dendritic cells inhibit T-cell effector function by promoting regulatory cell activity

Tumour pathogenesis is characterized by an immunosuppressive microenvironment that limits the development of effective tumour‐specific immune responses. This is in part the result of tumour‐dependent recruitment and activation of regulatory cells, such as myeloid‐derived suppressor cells and regulatory T cells in the tumour microenvironment and draining lymph nodes. Shedding of gangliosides by tumour cells has immunomodulatory properties, suggesting that gangliosides may be a critical factor in initiating an immunosuppressive microenvironment. To better define the immunomodulatory properties of gangliosides on antigen‐specific T‐cell activation and development we have developed an in vitro system using ganglioside‐treated murine bone‐marrow‐derived dendritic cells to prime and activate antigen‐specific CD4⁺ T cells from AND T‐cell receptor transgenic mice. Using this system, ganglioside treatment promotes the development of a dendritic cell population characterized by decreased CD86 (B7‐2) expression, and decreased interleukin‐12 and interleukin‐6 production. When these cells are used as antigen‐presenting cells, CD4 T cells are primed to proliferate normally, but have a defect in T helper (Th) effector cell development. This defect in Th effector cell responses is associated with the development of regulatory T‐cell activity that can suppress the activation of previously primed Th effector cells in a contact‐dependent manner. In total, these data suggest that ganglioside‐exposed dendritic cells promote regulatory T‐cell activity that may have long‐lasting effects on the development of tumour‐specific immune responses.     

Motive-oriented therapeutic relationship in brief psychodynamic intervention for patients with depression and personality disorders

Motive-Oriented Therapeutic Relationship (MOTR, also called Complementary Therapeutic Relationship) has already shown itself to be related to therapeutic outcome in several studies. The present study aims to test MOTR in a 4-session Brief Psychodynamic Intervention for patients presenting with major depressive disorder (MDD) and comorbid personality disorder (PD). In total, N = 20 patients were selected; n = 10 had MDD, n = 10 had MDD with comorbid PD. The first therapy session was videotaped and analyzed by means of Plan Analysis and the MOTR scale. Results suggest a differential effect on outcome: only the nonverbal component of MOTR is related to symptomatic change in patients presenting with MDD and comorbid PD; no such effect was found for patients with MDD alone. These results are discussed in line with the generalization and refinement of the conclusions of previous findings on the MOTR.     

Botulinum Toxin Injection in Long-Standing Facial Paralysis Patients: Improvement of Facial Symmetry Observed up to 6 Months

Background  Despite modern reanimation surgical techniques, facial paralysis presents with functional and aesthetic deficits. We evaluated facial symmetry after treating with botulinum toxin the healthy side of the face of 25 patients with long-standing facial paralysis who had previously been treated by surgical methods, with 6 months follow-up. Methods  Evaluation consisted of a clinical score, the two subscales of the Facial Disability Index, and surface electromyography. The mean botulinum toxin dose was 38 ± 5 U (range = 15–69 U). Results  The clinical score showed significant reduction of asymmetry of 48.4% at 1 month and 16.8% after 6 months. The initial result was a consequence of reduced motion on the treated side combined with better motion on the paralyzed side. At 6 months, the treated side returned to basal scores. The residual effect seen in symmetry was due to an increase (18%) of motion in the paralyzed side. There was a significant decrease in the action potential of muscles on the nonparalyzed side 1 month post injection but completely reverted after 6 months. The Physical Function Index increased, but not significantly. The Social/Well-Being Function Index showed a significant increase at 6 months compared to pretreatment. Conclusion  The proposed treatment improved facial symmetry for up to 6 months. Even after the end of the clinical effect of the drug, the paralyzed side’s clinical score was 18% higher than pretreatment, with an increased quality of life.     

Restless legs syndrome in multiple sclerosis: A case‐control study

The aim of our study was to explore restless legs syndrome (RLS) frequency in multiple sclerosis (MS)‐patients and establish whether RLS could be a symptom of MS. Over a period of 1 year, we consecutively enrolled 202 MS‐patients and 212 healthy controls, matched for sex and age, in a case‐control study. All of them filled in a structured questionnaire according to IRLSSG criteria. Those patients who fit the diagnostic criteria were subsequently examined by a neurologist to verify the effective presence of RLS. A total of 91 MS‐patients (45%) responded positively to the questionnaires. The diagnosis of RLS was carried out in 29subjects (14.4%). Among the healthy controls, a definite diagnosis of RLS was achieved only in 6 subjects (2.8%). The risk of MS patients to present RLS was significantly higher (OR.5.76 P:0.00002) than the general population. None of them was affected by other medical conditions related to RLS developing. The 62 remaining patients presented numbness and weakness of the legs not suggestive of RLS. Our findings confirm a significant correlation between MS and RLS. In our opinion, MS must be definitively included among RLS causes. © 2008 Movement Disorder Society     

Psychometric properties of the Screen for Child Anxiety Related Emotional Disorders (SCARED) in the general Italian adolescent population: A validation and a comparison between Italy and The Netherlands

In this study examination is given to the psychometric properties of the Italian version of the Screen for Child Anxiety Related Emotional Disorders (SCARED) in a large community sample of adolescents. Additionally, a comparison was made between the anxiety scores of this Italian adolescent cohort (N = 1975) and a comparative Dutch adolescent cohort (N = 1115).Findings revealed that a five-factor structure of the SCARED applied not only to the Italian adolescents from the general community, but also to boys and girls, and to early and middle adolescents. Moreover, sex and age differences on anxiety scores within the Italian sample were found to be consistent with previous studies of adolescent anxiety disorders. Finally, Italian adolescents reported higher anxiety scores than their Dutch peers.Findings of this study highlight that the SCARED is a valid screening instrument to rate anxiety symptoms of Italian adolescents.     

The complex interaction between APOE promoter and AD: an Italian case�Ccontrol study

The single nucleotide polymorphisms (SNPs) rs449647, rs769446 and rs405509 in the promoter region of the APOE gene have been variously suggested to be ɛ4-independent risk factors for Alzheimer''s disease (AD). A previous Italian study found that the rs449647 was significantly associated with late-onset AD. The aim of this study was to verify whether these APOE promoter SNPs are genetic risk factors for AD and to investigate their interaction with the common APOE polymorphism. A total of 169 clinically diagnosed AD patients and 99 cognitively intact age-matched controls were included in the study. Significant associations with AD independent from sex, age and APOE/ɛ4 status were found for rs449647 A/A and rs405509 G/G genotypes (positive), and rs449647 A/T and rs405509 T/T genotypes (negative). Haplotype frequency estimation at the APOE locus showed significant associations for the ATG4, ATT4 and ACG3 (positive) and ATT2, ATT3 and TCG3 (negative) haplotypes. Therefore this study confirms the role of the rs449647 A/A genotype as risk factor for AD in Italy and suggests that promoter genotypes and APOE haplotypes might have a complex function in AD-associated genetic risk factors.