Cognitive functions and psychological symptoms in migraine: a study on patients with and without aura

Aim: Migraine is neurological disorder with a complex pathophysiology. We described the neuropsychological profile of 100 migraineurs (50 with visual aura and 50 without aura), in interictal phase, compared to 50 matched healthy controls.

Materials and methods: A battery of standardized neuropsychological tests was used to assess attention, memory and executive functions. Beck Depression Inventory and Hamilton Rating Scale for Anxiety were used to evaluate anxiety and depressive symptoms. Severity of disability during daily activities was assessed by Migraine Disability Assessment.

Results: Migraine without aura showed a significant difference in comparison to healthy controls in semantic verbal fluency (p?=?0.02), delayed memory (p?<?0.001) and set-shifting (p?<?0.001). Migraine with aura showed a significant difference in delayed memory (p?=?0.001) and set-shifting (p?=?0.005) if compared to healthy controls. No significant correlation between cognitive functions and mood was found (HAM-A p?=?0.67) (BDI-II p?=?0.42).

Conclusions: Our data showed isolate and specific cognitive deficit during interictal phase in migraine patients. Future studies are need to identify if specific migraine characteristics may affect cognitive functions.     

Development of a Novel Formulation with Hypericin To Treat Cutaneous Leishmaniasis Based on Photodynamic Therapy in In Vitro and In Vivo Studies

An evaluation of the leishmanicidal activity in vitro and in vivo of hypericin, an expanded-spectrum photosensitizer found in Hypericum perforatum, is presented. Hypericin was evaluated against intracellular amastigotes in vitro of Leishmania (Viannia) panamensis. A topical formulation containing 0.5% hypericin was developed and assayed in vivo in a hamster model of cutaneous leishmaniasis. Results demonstrate that hypericin induces a significant antiamastigote effect in vitro against L. panamensis by decreasing the number of parasites inside infected cells. The topical formulation of 0.5% hypericin allows healing of L. panamensis-induced lesions upon a topical application of 40 mg/day plus visible-light irradiation (5 J/cm², 15 min), twice a week for 3 weeks.     

Lower proportion of CD19+IL-10+ and CD19+CD24+CD27+ but not CD1d+CD5+CD19+CD24+CD27+ IL-10+ B cells in children with autoimmune thyroid diseases

Abstract

Introduction: As it is generally known, regulatory B cells (Bregs) control inflammation and autoimmunity. The significance of Bregs in the population of children with autoimmune thyroid diseases (AITD) still offers plenty of potential to explore. The aim of this study was to estimate the expression of Bregs (phenotype CD19⁺CD24⁺CD27⁺IL-10⁺, CD19⁺IL-10⁺, CD1d⁺CD5⁺CD19⁺IL-10⁺ and CD1d⁺CD5⁺CD19⁺CD24⁺CD27⁺) in a paediatric cohort with AITD and in health controls.

Materials and methods: A total of 100 blood samples were obtained from 53 paediatric patients with Graves’ disease (GD) (N?=?12 newly diagnosed, mean age 12.5?±?3.5 and N?=?17 during methimazole therapy, mean age 12.7?±?4.4), Hashimoto’s thyroiditis (HT) (N?=?10 newly diagnosed, mean age 13.3?±?2.9 and N?=?10 during L-thyroxine therapy, mean age 13.7?±?3.4) and compared with healthy controls (C) (N?=?15, mean age 13.1?±?3.1). The expressions of the immune cell populations were analysed by four-color flow cytometry using a FASC Canto II cytometer (BD Biosciences).

Results: There was a decreasing tendency in the number of lymphocytes B producing IL-10 (B10) cells among all B lymphocytes and more widely, also among all lymphocytes, in each study group, as compared to C. We reported a reduction in IL-10 production in Bregs with the expression of CD19⁺CD24⁺CD27⁺IL-10 and CD1d⁺CD5⁺CD19⁺IL-10⁺ in both untreated and treated AITD.

Conclusions: Our data demonstrate that the reduction in the number of Bregs with CD19⁺CD24⁺CD27⁺IL-10⁺ and CD19⁺IL-10⁺ expression could be responsible for breaking immune tolerance and for AITD development in children.     

Downregulation of inflammatory markers by conjugated linoleic acid isomers in human cultured astrocytes

Objectives: Conjugated linoleic acid (CLA) isomers have been shown to possess anti-inflammatory activity in the central nervous system. In this study, we aimed to evaluate whether modulation of the fatty acid profile by the CLA isomers c9,t11 or t10,c12CLA was associated with changes in the expression of pro-inflammatory molecules in human astrocytes.

Methods: Cultured astrocytes were treated for 6 days with 100?µM fatty acids (c9,t11CLA or t10,c12CLA or oleic acid). Following the treatment, the fatty acid profile of the cell and pro-inflammatory molecule expression were assessed.

Results: Only the t10,c12CLA isomer induced a significant decrease in arachidonic acid and increased the ratio of docosahexaenoic acid/eicosapentaenoic acid, which constitutes indirect evidence of peroxisome proliferator-activated receptor alpha activation. Inhibition of tumour necrosis factor-α, interleukin-1β, and RANTES expression was observed in astrocytes treated with c9,t11CLA and t10,c12CLA.

Discussion: Current data demonstrate that CLA isomers, particularly t10,c12, may affect neuroinflammation by reducing the pro-inflammatory molecules in cultured astrocytes, suggesting a potential nutritional role of CLA isomers in modulating the astrocyte inflammatory response.     

CD44 Presence in inflamed pulp tissue

Inflammation of pulp tissue appears as a consequence of caries progression. Its main characteristic is inflamed infiltrate whose cells contain lymphocytes. CD44 is a widely expressed adhesion molecule present in several body cells such as leukocytes and parenchymatous cells, including endothelial cells, epithelial cells, and unstriated muscle cells. It interacts with hyaluronic acid, collagen, laminin, and fibronectin, and there are data that indicate an important role in the migration of leukocytes from the bloodstream toward inflammation areas. This project, which applied the immunologic assay method of agglutination inhibition of the CD44-hyaluronate system, evaluated the presence of CD44 in inflamed pulp tissue in both asymptomatic and symptomatic processes, as well as in healthy pulp tissue. The results demonstrated significant differences between both groups of pulp inflammatory processes with strong presence of the receptor. Moreover, healthy pulp had low to nondetectable levels of CD44. These results suggest that the expression of the CD44 molecule is higher during the initiation or maintenance of inflammatory processes.     

Divergent effects of anandamide transporter inhibitors with different target selectivity on social play behavior in adolescent rats

The endocannabinoid system plays an important role in the modulation of affect, motivation, and emotion. Social play behavior is a natural reinforcer in adolescent rats, and we have recently shown that interacting endocannabinoid, opioid, and dopamine systems modulate social play. In the present study, we tested the hypothesis that, in contrast to administration of exogenous cannabinoid agonists, increasing local endocannabinoid signaling through anandamide transporter inhibition enhances social play. To this aim, we tested the effects of two anandamide transporter inhibitors with different target selectivity on social play behavior in adolescent rats. Interestingly, we found that the prototypical anandamide transporter inhibitor N-(4-hydroxyphenyl)-arachidonamide (AM404) reduced social play, whereas its more selective analog N-arachidonoyl-(2-methyl-4-hydroxyphenyl)amine (VDM11) enhanced it. The effects of AM404 were not mediated through its known pharmacological targets, since they were not blocked by the CB(1) cannabinoid receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride (SR141716A), the CB(2) cannabinoid receptor antagonist N-(1,3,3-trimethylbicyclo(2.2.1)heptan-2-yl)-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)pyrazole-3-carboxamide (SR144528), or by the transient receptor potential vanilloid 1 receptor antagonist capsazepine. In contrast, the increase in social play induced by VDM11 was dependent on cannabinoid, opioid, and dopaminergic neurotransmission, since it was blocked by the CB(1) cannabinoid receptor antagonist SR141716A, the opioid receptor antagonist naloxone, and the dopamine receptor antagonist alpha-flupenthixol. These findings support the notion that anandamide plays an important role in the modulation of social interaction in adolescent rats, and they suggest that selective anandamide transporter inhibitors might be useful for the treatment of social dysfunctions. Furthermore, these results suggest that off-target effects may be responsible for some of the conflicting effects of anandamide transporter inhibitors on behavior.