Tumores Odontogénicos Queratoquísticos Múltiplos em Síndrome de Gorlin-Goltz

Introdução: A síndrome de Gorlin‐Goltz ou síndrome dos basaliomas nevoides múltiplos é uma patologia autossómica dominante, provocada por uma mutação no gene de supressão tumoral PTCH, localizado no cromossoma 9 (q22,3‐q31). As principais manifestações clínicas são o aparecimento de múltiplos carcinomas de células basais, associado a alterações osteoesqueléticas e a tumores odontogénicos queratoquísticos. Estes últimos estão presentes em 80% dos casos e podem ser diagnosticados nas primeiras décadas de vida, constituindo geralmente a primeira manifestação da síndrome. São habitualmente indolores, podem ser múltiplos, afetando qualquer região dos maxilares e estando quase sempre relacionados com alterações da erupção dentária. É frequente a presença de outras anomalias craniofaciais, nomeadamente fenda lábio‐palatina, bosseladura frontal e temporoparietal, macrocefalia e hipertelorismo. Descrição do caso clínico: Rapaz de 13 anos, proveniente dos Açores, referenciado a consulta hospitalar por múltiplas lesões hipertransparentes dos maxilares; antecedentes de parto pré‐termo, macrocefalia, pectus carinatus, hipercifose dorsal e atrofia dos músculos da cintura escapular. Objetivamente, apresentava bosseladura frontal e temporoparietal, face assimétrica, implantação baixa dos pavilhões auriculares e tumefação mandibular bilateral. No exame objetivo, reconhecia‐se marcado abaulamento vestibular do 3.° e 4.° quadrantes. A ortopantomografia revelou 5 lesões hipertransparentes, 4 na mandíbula e uma na maxila. Pela suspeita de síndrome de Gorlin‐Goltz foram também pedidas radiografias do crânio, tórax e extralongo da coluna, reforçando a suspeita diagnóstica inicial, pela presença de calcificação da foice cerebral, costelas aplanadas e bífidas e múltiplas alterações vertebrais. Tendo em conta a idade, a dimensão das lesões e a probabilidade de recidiva, optou‐se por uma abordagem conservadora inicial, pela descompressão pré‐cirúrgica das lesões com tubos acrílicos, para posterior enucleação. Discussão e conclusões: A suspeita desta síndrome deve desencadear uma avaliação sistémica que permita o diagnóstico precoce e um seguimento apropriado, de modo a reduzir a morbilidade e a mortalidade associadas às lesões potencialmente malignas. Desconhece‐se a prevalência real desta síndrome em Portugal, não deixando de ser curioso que alguns dos doentes diagnosticados nesta unidade sejam oriundos do arquipélago dos Açores, sugerindo um possível cluster genético.info:eu-repo/semantics/publishedVersio

Identification of a cytokine network sustaining neutrophil and Th17 activation in untreated early rheumatoid arthritis

© 2010 Cascão et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by sustained synovitis. Recently, several studies have proposed neutrophils and Th17 cells as key players in the onset and perpetuation of this disease. The main goal of this work was to determine whether cytokines driving neutrophil and Th17 activation are dysregulated in very early rheumatoid arthritis patients with less than 6 weeks of disease duration and before treatment (VERA). Methods: Cytokines related to neutrophil and Th17 activation were quantified in the serum of VERA and established RA patients and compared with other very early arthritis (VEA) and healthy controls. Synovial fluid (SF) from RA and osteoarthritis (OA) patients was also analyzed. Results: VERA patients had increased serum levels of cytokines promoting Th17 polarization (IL-1b and IL-6), as well as IL-8 and Th17-derived cytokines (IL-17A and IL-22) known to induce neutrophil-mediated inflammation. In established RA this pattern is more evident within the SF. Early treatment with methotrexate or corticosteroids led to clinical improvement but without an impact on the cytokine pattern. Conclusions: VERA patients already display increased levels of cytokines related with Th17 polarization and neutrophil recruitment and activation, a dysregulation also found in SF of established RA. 0 Thus, our data suggest that a cytokine-milieu favoring Th17 and neutrophil activity is an early event in RA pathogenesis.This work was supported by a grant from Sociedade Portuguesa de Reumatologia/Schering-Plough 2005. RAM and RC were funded by Fundação para a Ciência e a Tecnologia (FCT) SFRH/BD/30247/2006 and SFRH/BD/40513/2007, respectively. MMS-C was funded by Marie Curie Intra-European Fellowship PERG-2008-239422 and a EULAR Young Investigator Award

CD45RA, CD8β, and IFNγ Are Potential Immune Biomarkers of Human Cognitive Function

There is increasing evidence that in humans the adaptive immunological system can influence cognitive functions of the brain. We have undertaken a comprehensive immunological analysis of lymphocyte and monocyte populations as well as of HLA molecules expression in a cohort of elderly volunteers (age range, 64-101) differing in their cognitive status. Hereby, we report on the identification of a novel signature in cognitively impaired elderly characterized by: (1) elevated percentages of CD8+ T effector-memory cells expressing high levels of the CD45RA phosphate receptor (Temra hi); (2) high percentages of CD8+ T cells expressing high levels of the CD8β chain (CD8βhi); (3) augmented production of IFNγ by in vitro activated CD4+ T cells. Noteworthy, CD3+CD8+ Temra hi and CD3+CD8βhi cells were associated with impaired cognition. Cytomegalovirus seroprevalence showed that all volunteers studied but one were CMV positive. Finally, we show that some of these phenotypic and functional features are associated with an increased frequency of the HLA-B8 serotype, which belongs to the ancestral haplotype HLA-A1, Cw7, B8, DR3, DQ2, among cognitively impaired volunteers. To our knowledge, this is the first proof in humans linking the amount of cell surface CD45RA and CD8β chain expressed by CD8+ Temra cells, and the amount of IFNγ produced by in vitro activated CD4+ T cells, with impaired cognitive function in the elderly.info:eu-repo/semantics/publishedVersio

Areas of natural occurrence of melipona scutellaris Latreille, 1811(Hymenoptera: Apidae) in the state of Bahia, Brazil.

The bee Melipona scutellaris is considered the reared meliponine species with the largest distribution in the North and Northeast regions of Brazil, with records from the state of Rio Grande do Norte down to the state of Bahia. Considering the importance of this species in the generation of income for family agriculture and in the preservation of areas with natural vegetation, this study aimed at providing knowledge on the distribution of natural colonies of M. scutellaris in the state of Bahia. Literature information, interviews with stinglessbee beekeepers, and expeditions were conducted to confirm the natural occurrence of the species. A total of 102 municipalities showed records for M. scutellaris, whose occurrence was observed in areas ranging from sea level up to 1,200-meter height. The occurrence of this species in the state of Bahia is considered to be restricted to municipalities on the coastal area and the Chapada Diamantina with its rainforests. Geographic coordinates, elevation, climate and vegetation data were obtained, which allowed a map to be prepared for the area of occurrence in order to support conservation and management policies for the species

Cognitive impairment induced by delta9-tetrahydrocannabinol occurs through heteromers between cannabinoid CB1 and serotonin 5-HT2A receptors

Delta-9-tetrahydrocannabinol (THC), the main psychoactive compound of marijuana, induces numerous undesirable effects, including memory impairments, anxiety, and dependence. Conversely, THC also has potentially therapeutic effects, including analgesia, muscle relaxation, and neuroprotection. However, the mechanisms that dissociate these responses are still not known. Using mice lacking the serotonin receptor 5-HT2A, we revealed that the analgesic and amnesic effects of THC are independent of each other: while amnesia induced by THC disappears in the mutant mice, THC can still promote analgesia in these animals. In subsequent molecular studies, we showed that in specific brain regions involved in memory formation, the receptors for THC and the 5-HT2A receptors work together by physically interacting with each other. Experimentally interfering with this interaction prevented the memory deficits induced by THC, but not its analgesic properties. Our results highlight a novel mechanism by which the beneficial analgesic properties of THC can be dissociated from its cognitive side effects