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1.
Mol Psychiatry ; 23(1): 143-153, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-27956747

RESUMO

The bed nucleus of the stria terminalis (BNST) is a brain region important for regulating anxiety-related behavior in both humans and rodents. Here we used a chemogenetic strategy to investigate how engagement of G protein-coupled receptor (GPCR) signaling cascades in genetically defined GABAergic BNST neurons modulates anxiety-related behavior and downstream circuit function. We saw that stimulation of vesicular γ-aminobutyric acid (GABA) transporter (VGAT)-expressing BNST neurons using hM3Dq, but neither hM4Di nor rM3Ds designer receptors exclusively activated by a designer drug (DREADD), promotes anxiety-like behavior. Further, we identified that activation of hM3Dq receptors in BNST VGAT neurons can induce a long-term depression-like state of glutamatergic synaptic transmission, indicating DREADD-induced changes in synaptic plasticity. Further, we used DREADD-assisted metabolic mapping to profile brain-wide network activity following activation of Gq-mediated signaling in BNST VGAT neurons and saw increased activity within ventral midbrain structures, including the ventral tegmental area and hindbrain structures such as the locus coeruleus and parabrachial nucleus. These results highlight that Gq-mediated signaling in BNST VGAT neurons can drive downstream network activity that correlates with anxiety-like behavior and points to the importance of identifying endogenous GPCRs within genetically defined cell populations. We next used a microfluidics approach to profile the receptorome of single BNST VGAT neurons. This approach yielded multiple Gq-coupled receptors that are associated with anxiety-like behavior and several potential novel candidates for regulation of anxiety-like behavior. From this, we identified that stimulation of the Gq-coupled receptor 5-HT2CR in the BNST is sufficient to elevate anxiety-like behavior in an acoustic startle task. Together, these results provide a novel profile of receptors within genetically defined BNST VGAT neurons that may serve as therapeutic targets for regulating anxiety states and provide a blueprint for examining how G-protein-mediated signaling in a genetically defined cell type can be used to assess behavior and brain-wide circuit function.


Assuntos
Ansiedade/genética , Ansiedade/patologia , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/metabolismo , Neurônios/fisiologia , Núcleos Septais/patologia , Transdução de Sinais/fisiologia , Animais , Ansiolíticos/uso terapêutico , Ansiedade/tratamento farmacológico , Mapeamento Encefálico , Antagonistas de Receptores de Canabinoides/farmacologia , Clozapina/análogos & derivados , Clozapina/farmacologia , Adaptação à Escuridão/efeitos dos fármacos , Adaptação à Escuridão/genética , Modelos Animais de Doenças , Estrenos/farmacologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/genética , Comportamento Exploratório/efeitos dos fármacos , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Técnicas In Vitro , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurônios/efeitos dos fármacos , Inibidores de Fosfodiesterase/farmacologia , Piperazinas/farmacologia , Pirrolidinonas/farmacologia , RNA Mensageiro/metabolismo , Receptores de Droga/efeitos dos fármacos , Receptores de Droga/fisiologia , Rimonabanto/farmacologia , Núcleos Septais/metabolismo , Agonistas do Receptor de Serotonina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Bloqueadores dos Canais de Sódio/farmacologia , Tetrodotoxina/uso terapêutico , Proteínas Vesiculares de Transporte de Aminoácidos Inibidores/genética , Proteínas Vesiculares de Transporte de Aminoácidos Inibidores/metabolismo
3.
Eval Health Prof ; 23(4): 397-408, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11139867

RESUMO

Medicaid managed care can improve access to prevention services, such as immunization, for low-income children. The authors studied immunization rates for 7,356 children on Medicaid in three managed care programs: primary care case management (PCCM; n = 4,605), a voluntary HMO program (n = 851), and a mandatory HMO program (n = 1,900). Immunization rates (3:3:1 series) in PCCM (78%) exceeded rates in the voluntary HMO program (71%), which in turn exceeded those in the mandatory HMO program (67%). Adjusting for race, urban residence, and gender, compared to children in PCCM, children in the voluntary HMO program were less likely to complete the 3:3:1 series (OR = 0.75, CI = 0.63, 0.90), and children in the mandatory HMO program were even less likely to complete the series (OR = 0.59, CI = 0.51, 0.68). Results differed by individual HMOs. Monitoring of outcomes for all types of managed care by Medicaid agencies is imperative to assure better disease prevention for low-income children.


Assuntos
Sistemas Pré-Pagos de Saúde/organização & administração , Acessibilidade aos Serviços de Saúde/organização & administração , Imunização/estatística & dados numéricos , Medicaid/organização & administração , Serviços Preventivos de Saúde/estatística & dados numéricos , Pré-Escolar , Estudos Transversais , Humanos , Pobreza , Estados Unidos
4.
Pediatr Dent ; 20(5): 327-30, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9803432

RESUMO

PURPOSE: The purpose of this study was to examine the occlusion of children younger than 6 years with a diagnosis of otitis media. METHODS: The study consisted of 112 children diagnosed with otitis media by their pediatrician. Parents were surveyed regarding their child's history of pacifier use, thumb/finger-sucking habit, mouthbreathing habit, method of feeding, day care attendance, snoring, allergies, asthma, upper respiratory infections, otitis media in the family, and the number of people who smoke in the home. The children's occlusions were examined. RESULTS: In this study, 52% of the population presented with some type of malocclusion, with anterior open bite (17%) and an overbite measuring greater than 70% (17%) being the most prominent. This study showed that the following factors were common in children with otitis media: bottle feeding, smoking in the home, day care attendance, upper respiratory infection, history of otitis media with a sibling, pacifier habit, snoring, and mouthbreathing habit. CONCLUSION: A logistic regression analysis showed no significant association between malocclusion and factors related to otitis media.


Assuntos
Má Oclusão/complicações , Otite Média/complicações , Asma/complicações , Alimentação com Mamadeira , Aleitamento Materno , Cuidado da Criança , Pré-Escolar , Saúde da Família , Feminino , Sucção de Dedo/efeitos adversos , Humanos , Hipersensibilidade/complicações , Lactente , Cuidado do Lactente , Modelos Logísticos , Masculino , Má Oclusão/classificação , Respiração Bucal/complicações , Infecções Respiratórias/complicações , Fumar , Ronco/complicações
5.
South Med J ; 82(11): 1344-6, 1989 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-2814620

RESUMO

The topical anesthetic solution TAC (tetracaine, adrenaline, cocaine) has gained widespread acceptance as the preferred local anesthetic for repairing skin lacerations in children. Despite this popularity, there are no universally accepted guidelines for its application. We report the case of a 6-month-old infant who had respiratory distress and seizures after TAC administration. In addition, we surveyed emergency departments within the state of Virginia regarding their guidelines for TAC application in children. Of the 91 hospitals surveyed, 32 (35%) currently administer TAC, and 14 (44%) of these have no guidelines regarding its use. Among the 20 (63%) with restrictions, there is wide variability in the way it is prescribed. TAC solution is a highly potent anesthetic agent with significant toxicity potential. Research into appropriate dosages, absorption, and actions needs to be undertaken before its widespread acceptance as the drug of choice for providing local anesthesia in children.


Assuntos
Anestésicos Locais/administração & dosagem , Cocaína/administração & dosagem , Epinefrina/administração & dosagem , Tetracaína/administração & dosagem , Administração Tópica , Cocaína/efeitos adversos , Combinação de Medicamentos/administração & dosagem , Combinação de Medicamentos/efeitos adversos , Epinefrina/efeitos adversos , Humanos , Lactente , Masculino , Tetracaína/efeitos adversos
6.
Pediatrics ; 74(2): 250-3, 1984 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-6462823

RESUMO

Fifty infants less than 1 year of age with rotavirus gastroenteritis were studied with regard to the protective effect of breast-feeding. The initial incidence of breast-feeding was 64% in the patients infected with rotavirus and 70% in a matched control population. Seven patients were breast-fed at the time of infection, 25 patients had stopped breast-feeding prior to infection, and 18 patients were exclusively formula-fed. There were no significant differences between groups in the average age of infection, mean duration of diarrhea, mean number of bowel movements in 24 hours, or in the frequency of fever or irritability. The only apparent difference between groups was that the frequency of vomiting was significantly decreased in the breast-fed children. The results of this study suggest that breast-feeding offers little protection against rotavirus gastroenteritis.


Assuntos
Aleitamento Materno , Gastroenterite/prevenção & controle , Infecções por Rotavirus/prevenção & controle , Fatores Etários , Alimentação com Mamadeira , Diarreia/etiologia , Estudos de Avaliação como Assunto , Feminino , Gastroenterite/etiologia , Humanos , Lactente , Recém-Nascido , Estudos Prospectivos , Infecções por Rotavirus/complicações , Vômito/etiologia
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