RESUMO
Serotonin acts through its receptors (5-HTRs) to shape brain networks during development and modulates essential functions in mature brain. The 5-HT1AR is mainly located at soma of hippocampal neurons early during brain development and its expression gradually shifts to dendrites during postnatal development. The 5-HT7R expressed early during hippocampus development, shows a progressive reduction in its expression postnatally. Considering these changes during development, we evaluated in cultured hippocampal neurons whether the 5-HT1AR and 5-HT7R change their expression, modulate dendritic growth, and activate signaling pathways such as ERK1/2, AKT/GSK3ß and LIMK/cofilin, which may sustain dendrite outgrowth by controlling cytoskeleton dynamics. We show that mRNA levels of both receptors increase between 2 and 7 DIV; however only protein levels of 5-HT7R increase significantly at 7 DIV. The 5-HT1AR is preferentially distributed in the soma, while 5-HT7R displays a somato-dendritic localization at 7 DIV. Through stimulation with 5-HT at 7 DIV during 24h and using specific antagonists, we determined that 5-HT1AR decreases the number of primary and secondary dendrites and restricts the growth of primary dendrites. The activation of 5-HT1AR and 5-HT7R promotes the growth of short secondary dendrites and triggers ERK1/2 and AKT phosphorylation through MEK and PI3K activation respectively; without changes in the phosphorylation of LIMK and cofilin. We conclude that 5-HT1AR restricts dendritogenesis and outgrowth of primary dendrites, but that both 5-HT1AR and 5-HT7R promote secondary dendrite outgrowth. These data support the role of 5-HT in neuronal outgrowth during development and provide insight into cellular basis of neurodevelopmental disorders.
Assuntos
Dendritos/efeitos dos fármacos , Dendritos/metabolismo , Receptor 5-HT1A de Serotonina/metabolismo , Receptores de Serotonina/metabolismo , Serotonina/farmacologia , Animais , Células Cultivadas , Hipocampo/metabolismo , Neurogênese/fisiologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
The human papillomavirus (HPV) was detected in 20 (29%) out of 69 lung carcinomas (LCs) in Chile, by PCR and Southern blot, and was more frequently detected in squamous cell carcinoma (SQC) than in adenocarcinomas (46 vs 9%, P=0.001). HPV-16, positive in 11 cases, was the most frequently detected HPV genotype determined by DNA sequencing. HPV-16 E2/E6 ratio, estimated from real-time PCR analysis, was much lower than the unity, suggesting that at least a partial HPV-16 genome was integrated in all but one HPV-16-positive SQCs. The remaining one case was suspected to have only episomal HPV-16. Although the viral load was low in most of the LCs, a case showed the HPV-16 copy number as high as 8479 per nanogram DNA, which was even a few times higher than the minimum viral load of seven cervical carcinomas (observed viral load: 3356-609 392 per nanogram DNA). The expression of the HPV-16/18 E6 protein was found in only two HPV-16-positive SQCs (13%) but not in the case with the highest viral load. Although the viral load was in general very low and HPV E6 expression is none or weak, further studies seem warranted to examine aetiological involvement of high-risk HPV in lung carcinogenesis.
Assuntos
Adenocarcinoma/virologia , Carcinoma de Células Escamosas/virologia , Papillomavirus Humano 16/isolamento & purificação , Neoplasias do Colo do Útero/virologia , Adenocarcinoma/metabolismo , Idoso , Carcinoma de Células Escamosas/metabolismo , Chile , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/virologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Proteína Supressora de Tumor p53/metabolismo , Carga Viral , Integração ViralRESUMO
BACKGROUND: The traditional methods to distinguish Chronic Follicular Gastritis and Primary Gastric Lymphoma do not allow an adequate definitive diagnosis in a significant number of cases. The molecular Biology diagnostic methods are based on the rearrangement of immunoglobulin genes. The polymerase chain reaction (PCR) specifically amplifies this rearrangement and allows molecular analysis of minimal tissue samples obtained with endoscopical biopsies. AIM: To test the usefulness of this PCR method in the differential diagnosis between Chronic Follicular Gastritis and Primary Gastric Lymphoma. MATERIAL AND METHODS: We analyzed the endoscopical biopsies of six Chronic Follicular Gastritis cases and eight surgically treated Primary Gastric Lymphoma cases, six with the correct diagnosis in the endoscopical biopsies and two with a diagnosis of Chronic Follicular Gastritis. RESULTS: A policlonal immunoglobulin rearrangement was found in the six cases with Chronic Follicular Gastritis. A monoclonal arrangement was found in 5 of 6 biopsies with the diagnosis of Primary Gastric Lymphoma. The same monoclonal rearrangement was observed in the two biopsies incorrectly diagnosed as Chronic Follicular Gastritis. CONCLUSIONS: PCR analysis of immunoglobulin rearrangement is a useful method in the differential diagnosis between Chronic Follicular Gastritis and Primary Gastric Lymphoma.
Assuntos
Gastrite Hipertrófica/diagnóstico , Imunoglobulinas/genética , Linfoma/diagnóstico , Neoplasias Gástricas/diagnóstico , Doença Crônica , Diagnóstico Diferencial , Eletroforese em Gel de Ágar , Gastrite Hipertrófica/genética , Gastrite Hipertrófica/imunologia , Humanos , Linfoma/genética , Linfoma/imunologia , Reação em Cadeia da Polimerase , Neoplasias Gástricas/genética , Neoplasias Gástricas/imunologiaRESUMO
This study aims to establish the frequency of diabetic retinopathy (DR) in patients with diabetes mellitus (DM) type II in Leon, Guanajuato, Mexico, as well as the opportunity for their diagnosis. A prospective study was carried out in a sample of 100 patients. DR was stratified using the classification of the Early Treatment Diabetic Retinopathy Study Research Group and diagnosed in 42 per cent of the sample. The evolution time of diabetes in this group was different from that of the group without RD (p < 0.0001). A direct proportional and significant relationship between the duration of DM and an increasing severity of DR was found. Opportune diagnosis was made in 70 per cent of the cases with DR. In 81 per cent of the 42 patients with DR, no previous diagnosis was made. This study shows a high proportion of RD without diagnosis. The intensification of educational strategies for the opportune detection and early treatment of DR is recommended.