RESUMO
Shank3 is a structural protein found predominantly at the postsynaptic density. Mutations in the SHANK3 gene have been associated with risk for autism spectrum disorder (ASD). We generated induced pluripotent stem cells (iPSCs) from control individuals and from human donors with ASD carrying microdeletions of SHANK3. In addition, we used Zinc finger nucleases to generate isogenic SHANK3 knockout human embryonic stem (ES) cell lines. We differentiated pluripotent cells into either cortical or olfactory placodal neurons. We show that patient-derived placodal neurons make fewer synapses than control cells. Moreover, patient-derived cells display a developmental phenotype: young postmitotic neurons have smaller cell bodies, more extensively branched neurites, and reduced motility compared with controls. These phenotypes were mimicked by SHANK3-edited ES cells and rescued by transduction with a Shank3 expression construct. This developmental phenotype is not observed in the same iPSC lines differentiated into cortical neurons. Therefore, we suggest that SHANK3 has a critical role in neuronal morphogenesis in placodal neurons and that early defects are associated with ASD-associated mutations.
Assuntos
Transtorno do Espectro Autista/genética , Proteínas do Tecido Nervoso/genética , Células-Tronco Neurais/patologia , Transtorno do Espectro Autista/patologia , Diferenciação Celular/fisiologia , Linhagem Celular , Células Cultivadas , Deleção Cromossômica , Potenciais Pós-Sinápticos Excitadores/genética , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/patologia , Mutação , Células-Tronco Neurais/metabolismo , Neurônios/metabolismo , Neurônios/patologia , Densidade Pós-Sináptica/patologia , Sinapses/metabolismo , Sinapses/patologia , Transmissão SinápticaRESUMO
The chemistry of chromones is very well known. This system is widely used in organic chemistry as an intermediate compound for the synthesis of numerous hetrocycles. On the other hand, chromones were extensively studied as bioactive compounds. They possess remarkable biological activities, such as antimicrobial, antiviral, anticancer, anti-inflammatory, antioxidant, etc. This comprehensive review describes the current status and knowledge of natural occurrence, and biological activities of chromones. Recent advances made over the last decade i.e. January 1999 to December 2009 are critically discussed and we have covered about 176 references and more than 350 compounds reported during this period.
Assuntos
Cromonas/química , Cromonas/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Plantas/química , Animais , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Cromonas/isolamento & purificação , Cromonas/uso terapêutico , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Humanos , Neoplasias/tratamento farmacológico , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/uso terapêuticoRESUMO
AIM: To present the successful endodontic and periodontal management of a two rooted maxillary lateral incisor tooth with a complex radicular lingual groove and severe periodontal destruction using spiral computed tomography as a diagnostic aid. SUMMARY: A 30-year-old male patient presented with a chief complaint of mobility and discharge of pus in an upper front tooth. Clinical examination revealed a sinus tract on the labial gingival surface and a 10-mm-deep periodontal pocket associated with maxillary left lateral incisor tooth. On the lingual side, a groove emerging from cingulum, continuing mesioapically down the lingual aspect of tooth was found. Intraoral periapical radiographs demonstrated a lateral periodontal defect around the mesial aspect and a diffuse radiolucency at the apex of maxillary left lateral incisor tooth. The sinus tract was traced with gutta-percha to the maxillary left lateral incisor that showed an accessory root surrounded by a large radiolucent area. A spiral computed tomographic scan for better understanding of the complicated root canal morphology of the tooth was performed. Based on the clinical, radiographic and spiral computed tomographic findings, a diagnosis of an endo-perio lesion in tooth 22 was made. Management consisted of conventional root canal treatment, radiculoplasty, root resection of accessory root and surgical curettage of the periodontal defect. Follow-up with radiographic examination at 3 months and 1 year was performed. At 1-year recall, the patient was asymptomatic, there was no evidence of the sinus tract and a 3-mm nonbleeding pocket was present in relation to tooth 22. Progression of hard tissue healing was observed in the periapical radiograph taken 1 year postoperatively. KEY LEARNING POINTS: The key to achieving favourable results in this particular type of developmental anomaly is accurate diagnosis and treatment planning. The health of the periapical osseous tissues appears to be the provital factor for tooth retention. A favourable outcome can only be achieved with a comprehensive treatment approach that effectively manages all local factors that are contributing to the disease process.
