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1.
J Exp Bot ; 75(1): 364-390, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37712879

RESUMO

The mechanisms underlying susceptibility to and defense against Pseudomonas syringae (Pph) of the common bean (Phaseolus vulgaris) have not yet been clarified. To investigate these, 15-day-old plants of the variety Riñón were infected with Pph and the transcriptomic changes at 2 h and 9 h post-infection were analysed. RNA-seq analysis showed an up-regulation of genes involved in defense/signaling at 2 h, most of them being down-regulated at 9 h, suggesting that Pph inhibits the transcriptomic reprogramming of the plant. This trend was also observed in the modulation of 101 cell wall-related genes. Cell wall composition changes at early stages of Pph infection were associated with homogalacturonan methylation and the formation of egg boxes. Among the cell wall genes modulated, a pectin methylesterase inhibitor 3 (PvPMEI3) gene, closely related to AtPMEI3, was detected. PvPMEI3 protein was located in the apoplast and its pectin methylesterase inhibitory activity was demonstrated. PvPMEI3 seems to be a good candidate to play a key role in Pph infection, which was supported by analysis of an Arabidopsis pmei3 mutant, which showed susceptibility to Pph, in contrast to resistant Arabidopsis Col-0 plants. These results indicate a key role of the degree of pectin methylesterification in host resistance to Pph during the first steps of the attack.


Assuntos
Arabidopsis , Phaseolus , Arabidopsis/genética , Arabidopsis/metabolismo , Phaseolus/genética , Phaseolus/metabolismo , Hidrolases de Éster Carboxílico/genética , Hidrolases de Éster Carboxílico/metabolismo , Pseudomonas syringae/fisiologia , Pectinas/metabolismo , Parede Celular/metabolismo
2.
Dermatol. argent ; 27(2): 64-68, abr-jun 2021. il, graf
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1366212

RESUMO

Introducción: El liquen plano (LP) es una enfermedad inflamatoria crónica, de etiología desconocida, que puede afectar la piel, los anexos y las mucosas. Objetivo: Describir las características epidemiológicas y clínicas y el tratamiento realizado en los pacientes con diagnóstico clínico e histopatológico de LP, valorados en el Servicio de Dermatología del Hospital de Pediatría "Prof. Dr. Juan P. Garrahan" en los últimos 33 años. Diseño:Estudio descriptivo, retrospectivo y transversal. Materiales y métodos: Se revisaron las historias clínicas de los pacientes con diagnóstico histopatológico de LP atendidos en el Hospital desde agosto de 1987 hasta febrero de 2020 y se analizaron las variables epidemiológicas, clínicas y de tratamiento. Resultados: Se incluyeron datos de 26 pacientes, 18 de los cuales eran varones (69,3%). La media de edad en el momento del diagnóstico fue de 9,6 años. Presentaron la variedad de LP clásico 24 pacienes (93%). El compromiso ungueal y de la mucosa bucal se observó en 2 pacientes (7,7%). Ninguno tuvo asociación a fármacos ni a infecciones. En cuanto al tratamiento recibido, 4 pacientes (15,4%) tuvieron pérdida del seguimiento; 13 (50%) realizaron tratamiento tópico; 6 (23%), tratamiento sistémico y 3 (11,5%), tratamiento combinado. El promedio de seguimiento fue de 6 meses y se obtuvo una respuesta favorable en el 68% de los pacientes. Conclusiones: El LP es una patología de baja frecuencia en la infancia. No se encontró asociación a medicamentos ni a enfermedades infecciosas como se describe en la población adulta. Su curso es crónico y, en los pacientes que tuvieron un adecuado seguimiento, se obtuvo una buena respuesta al tratamiento indicado.


Introduction: Lichen planus (LP) is a chronic, inflammatory disease of unknown etiology, which can affect skin, adnexal tissues and mucosa. Objective: to describe the clinical, epidemiological characteristics and the treatment received by patients with clinical and histopathological diagnosis of LP, seen at the Dermatology Service of Pediatric Hospital "Prof. Dr. Juan P. Garrahan" in the last 33 years. Design: Descriptive, retrospective and cross-sectional study. Materials y methods: We reviewed the clinical history of patients with histopathological diagnosis of LP that were treated at our hospital from August 1987 to February 2020 and analysed the epidemiological, clinical and treatment variables. Results: Data of 26 patients were included in this study 18 of which are males (69.3%). The mean age of diagnosis was 9.6 years. 24 patients (93%) presented the classical type of LP. Ungual and mucosal compromise were observed in 2 patients (7.7%) and none had associations with infections or drugs. Regarding treatment, 4 patients (15.4%) did not continue follow-ups, 13 patients (50%) had topical treatment, 6 (23%) had systemic treatment and 3 patients (11.5%) received combined treatment. The average follow-up time was 6 months and 68% of patients had favorable outcome. Conclusions: LP is an uncommon pathology in children. During this study we did not find any etiologic relations with use of drugs or infectious diseases as is described in de adult population. Its course is chronic and in the patients that had a proper follow-up a good response to the indicated treatment was obtained.


Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Líquen Plano/epidemiologia , Fototerapia , Argentina/epidemiologia , Estudos Transversais , Estudos Retrospectivos , Corticosteroides/uso terapêutico , Líquen Plano/diagnóstico , Líquen Plano/patologia , Líquen Plano/terapia
3.
Neurology ; 95(17): e2427-e2441, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-32847951

RESUMO

OBJECTIVE: To investigate the functional correlates of recurrent secondarily generalized seizures in temporal lobe epilepsy (TLE) using task-based fMRI as a framework to test for epilepsy-specific network rearrangements. Because the thalamus modulates propagation of temporal lobe onset seizures and promotes cortical synchronization during cognition, we hypothesized that occurrence of secondarily generalized seizures, i.e., focal to bilateral tonic-clonic seizures (FBTCS), would relate to thalamic dysfunction, altered connectivity, and whole-brain network centrality. METHODS: FBTCS occur in a third of patients with TLE and are a major determinant of disease severity. In this cross-sectional study, we analyzed 113 patients with drug-resistant TLE (55 left/58 right), who performed a verbal fluency fMRI task that elicited robust thalamic activation. Thirty-three patients (29%) had experienced at least one FBTCS in the year preceding the investigation. We compared patients with TLE-FBTCS to those without FBTCS via a multiscale approach, entailing analysis of statistical parametric mapping (SPM) 12-derived measures of activation, task-modulated thalamic functional connectivity (psychophysiologic interaction), and graph-theoretical metrics of centrality. RESULTS: Individuals with TLE-FBTCS had less task-related activation of bilateral thalamus, with left-sided emphasis, and left hippocampus than those without FBTCS. In TLE-FBTCS, we also found greater task-related thalamotemporal and thalamomotor connectivity, and higher thalamic degree and betweenness centrality. Receiver operating characteristic curves, based on a combined thalamic functional marker, accurately discriminated individuals with and without FBTCS. CONCLUSIONS: In TLE-FBTCS, impaired task-related thalamic recruitment coexists with enhanced thalamotemporal connectivity and whole-brain thalamic network embedding. Altered thalamic functional profiles are proposed as imaging biomarkers of active secondary generalization.


Assuntos
Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/fisiopatologia , Tálamo/diagnóstico por imagem , Tálamo/fisiopatologia , Adulto , Mapeamento Encefálico , Estudos Transversais , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/fisiopatologia , Epilepsia do Lobo Temporal/psicologia , Epilepsia Tônico-Clônica/diagnóstico por imagem , Epilepsia Tônico-Clônica/fisiopatologia , Feminino , Lateralidade Funcional , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Testes Neuropsicológicos , Desempenho Psicomotor , Curva ROC , Comportamento Verbal
4.
Arch. argent. pediatr ; 117(5): 340-343, oct. 2019. ilus, tab
Artigo em Inglês, Espanhol | LILACS, BINACIS | ID: biblio-1054963

RESUMO

El pilomatrixoma es un tumor benigno cutáneo, de frecuente aparición en los niños, que se origina en las células de la matriz del folículo piloso. Se presenta como un nódulo o tumor, aproximadamente, de 0,5 a 3 cm de tamaño, de consistencia cálcica, de bordes facetados, con piel suprayacente eritematoazulada. En ocasiones, la piel puede atrofiarse, dar la apariencia de una ampolla e, incluso, extruir material cálcico. El diagnóstico se sospecha por la presentación clínica característica y los estudios de imágenes complementarios. El diagnóstico definitivo es por los hallazgos histológicos. La extirpación quirúrgica es el tratamiento de elección. Se presentan los datos epidemiológicos, clínicos, estudios complementarios y técnicas quirúrgicas empleadas de 149 pilomatrixomas resecados en 137 pacientes tratados en los Servicios de Dermatología de los hospitales de pediatría Dr. Pedro de Elizalde y Prof. Dr. Juan P. Garrahan.


A pilomatrixoma is a benign skin tumor common in children, which develops from the matrix cells of hair follicles. It presents as a nodule or tumor of approximately 0.5-3 cm in size, with calcium-like consistency, faceted edges, and blue erythematous overlying skin. Sometimes, the skin may atrophy and look like a blister or even extrude calcium. Diagnosis is suspected based on the typical clinical presentation and supplementary imaging tests. The definite diagnosis is made according to histological findings. Surgical removal is the treatment of choice. Here we describe the epidemiological and clinical data, supplementary tests, and surgical techniques in relation to 149 pilomatrixomas resected in 137 patients treated at the Departments of Dermatology of two children's hospitals: Dr. Pedro de Elizalde and Prof. Dr. Juan P. Garrahan.


Assuntos
Humanos , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Procedimentos Cirúrgicos Operatórios , Criança , Pilomatrixoma , Neoplasias de Anexos e de Apêndices Cutâneos
5.
Arch Argent Pediatr ; 117(5): 340-343, 2019 10 01.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31560492

RESUMO

A pilomatrixoma is a benign skin tumor common in children, which develops from the matrix cells of hair follicles. It presents as a nodule or tumor of approximately 0.5-3 cm in size, with calcium-like consistency, faceted edges, and blue erythematous overlying skin. Sometimes, the skin may atrophy and look like a blister or even extrude calcium. Diagnosis is suspected based on the typical clinical presentation and supplementary imaging tests. The definite diagnosis is made according to histological findings. Surgical removal is the treatment of choice. Here we describe the epidemiological and clinical data, supplementary tests, and surgical techniques in relation to 149 pilomatrixomas resected in 137 patients treated at the Departments of Dermatology of two children's hospitals: Dr. Pedro de Elizalde and Prof. Dr. Juan P. Garrahan.


El pilomatrixoma es un tumor benigno cutáneo, de frecuente aparición en los niños, que se origina en las células de la matriz del folículo piloso. Se presenta como un nódulo o tumor, aproximadamente, de 0,5 a 3 cm de tamaño, de consistencia cálcica, de bordes facetados, con piel suprayacente eritematoazulada. En ocasiones, la piel puede atrofiarse, dar la apariencia de una ampolla e, incluso, extruir material cálcico. El diagnóstico se sospecha por la presentación clínica característica y los estudios de imágenes complementarios. El diagnóstico definitivo es por los hallazgos histológicos. La extirpación quirúrgica es el tratamiento de elección. Se presentan los datos epidemiológicos, clínicos, estudios complementarios y técnicas quirúrgicas empleadas de 149 pilomatrixomas resecados en 137 pacientes tratados en los Servicios de Dermatología de los hospitales de pediatría Dr. Pedro de Elizalde y Prof. Dr. Juan P. Garrahan.


Assuntos
Doenças do Cabelo/diagnóstico , Pilomatrixoma/diagnóstico , Neoplasias Cutâneas/diagnóstico , Adolescente , Criança , Pré-Escolar , Feminino , Doenças do Cabelo/epidemiologia , Doenças do Cabelo/cirurgia , Hospitais Pediátricos , Humanos , Lactente , Masculino , Pilomatrixoma/epidemiologia , Pilomatrixoma/cirurgia , Estudos Retrospectivos , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/cirurgia
6.
Epilepsia ; 59(1): 226-234, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29150855

RESUMO

OBJECTIVE: Patients with genetic generalized epilepsy (GGE) have subtle morphologic abnormalities of the brain revealed with magnetic resonance imaging (MRI), particularly in the thalamus. However, it is unclear whether morphologic abnormalities of the brain in GGE are a consequence of repeated seizures over the duration of the disease, or are a consequence of treatment with antiepileptic drugs (AEDs), or are independent of these factors. Therefore, we measured brain morphometry in a cohort of AED-naive patients with GGE at disease onset. We hypothesize that drug-naive patients at disease onset have gray matter changes compared to age-matched healthy controls. METHODS: We performed quantitative measures of gray matter volume in the thalamus, putamen, caudate, pallidum, hippocampus, precuneus, prefrontal cortex, precentral cortex, and cingulate in 29 AED-naive patients with new-onset GGE and compared them to 32 age-matched healthy controls. We subsequently compared the shape of any brain structures found to differ in gray matter volume between the groups. RESULTS: The thalamus was the only structure to show reduced gray matter volume in AED-naive patients with new-onset GGE compared to healthy controls. Shape analysis revealed that the thalamus showed deflation, which was not uniformly distributed, but particularly affected a circumferential strip involving anterior, superior, posterior, and inferior regions with sparing of medial and lateral regions. SIGNIFICANCE: Structural abnormalities in the thalamus are present at the initial onset of GGE in AED-naive patients, suggesting that thalamic structural abnormality is an intrinsic feature of GGE and not a consequence of AEDs or disease duration.


Assuntos
Epilepsia Generalizada , Tálamo/diagnóstico por imagem , Adolescente , Adulto , Estudos de Casos e Controles , Córtex Cerebral/diagnóstico por imagem , Criança , Epilepsia Generalizada/diagnóstico por imagem , Epilepsia Generalizada/genética , Epilepsia Generalizada/patologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Adulto Jovem
7.
Hum Brain Mapp ; 38(1): 221-236, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27543883

RESUMO

Patients with focal epilepsy have been shown to have reduced functional connectivity in intrinsic connectivity networks (ICNs), which has been related to neurocognitive development and outcome. However, the relationship between interictal epileptiform discharges (IEDs) and changes in ICNs remains unclear, with evidence both for and against their influence. EEG-fMRI data was obtained in 27 children with focal epilepsy (mixed localisation and aetiologies) and 17 controls. A natural stimulus task (cartoon blocks verses blocks where the subject was told "please wait") was used to enhance the connectivity within networks corresponding to ICNs while reducing potential confounds of vigilance and motion. Our primary hypothesis was that the functional connectivity within visual and attention networks would be reduced in patients with epilepsy. We further hypothesized that controlling for the effects of IEDs would increase the connectivity in the patient group. The key findings were: (1) Patients with mixed epileptic foci showed a common connectivity reduction in lateral visual and attentional networks compared with controls. (2) Having controlled for the effects of IEDs there were no connectivity differences between patients and controls. (3) A comparison within patients revealed reduced connectivity between the attentional network and basal ganglia associated with interictal epileptiform discharges. We also found that the task activations were reduced in epilepsy patients but that this was unrelated to IED occurrence. Unexpectedly, connectivity changes in ICNs were strongly associated with the transient effects of interictal epileptiform discharges. Interictal epileptiform discharges were shown to have a pervasive transient influence on the brain's functional organisation. Hum Brain Mapp 38:221-236, 2017. © 2016 Wiley Periodicals, Inc.


Assuntos
Mapeamento Encefálico , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Epilepsias Parciais/patologia , Epilepsias Parciais/fisiopatologia , Estimulação Acústica , Adolescente , Criança , Eletroencefalografia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Modelos Estatísticos , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Testes Neuropsicológicos , Oxigênio/sangue , Estimulação Luminosa
8.
Chemosphere ; 156: 150-162, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27174828

RESUMO

BACKGROUND AND AIMS: Rapeseed (Brassica napus L.) is a Cd/Zn-accumulator whereas soil conditioners such as biochars may immobilize trace elements. These potentially complementary soil remediation options were trialed, singly and in combination, in a pot experiment with a metal(loid)-contaminated technosol. METHODS: The technosol [total content in mg kg(-1) Zn 6089, Cd 9.4, Cu 110, and Pb 956] was either amended (2% w/w) or not with a poultry manure-derived biochar. Rapeseed was cultivated for both soil treatments during 24 weeks up to harvest under controlled conditions. RESULTS: Biochar incorporation into the technosol promoted the As, Cd, Cu, Mo, Ni, Pb and Zn solubility. It decreased foliar B, Cu and Mo concentrations, and Mo concentration in stems, pericarps and seeds. But, it did not impact neither the biomass of aerial rapeseed parts (except a decrease for seeds), nor their C (except a decrease for stems), seed fatty acid, seed starch and soluble sugar contents, and antioxidant capacity in both leaves and seeds. Biochar amendment increased the phytoextraction by aerial plant parts for K, P, and S, reduced it for N, Ca, B, Mo, Ni and Se, whereas it remained steady for Mg, Zn, Fe, Mn, Cu, Cd and Co. CONCLUSIONS: The biochar incorporation into this technosol did not promote Cd, Cu and Zn phytoextraction by rapeseed and its potential oilseed production, but increased the solubility of several metal(loid)s. Here Zn and Cd concentrations in the soil pore water were decreased by rapeseed, showing the feasibility to strip available soil Zn and Cd in combination with seed production.


Assuntos
Compostos de Amônio/toxicidade , Biodegradação Ambiental , Brassica napus/crescimento & desenvolvimento , Carvão Vegetal/química , Sementes/química , Poluentes do Solo/toxicidade , Oligoelementos/metabolismo , Disponibilidade Biológica , Biomassa , Brassica napus/efeitos dos fármacos , Brassica napus/metabolismo , Esterco , Metais/metabolismo , Fotoquímica , Poluentes do Solo/análise
9.
PLoS One ; 10(2): e0116787, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25658912

RESUMO

The cloning, expression and characterization of three cellulosomal pectinolytic enzymes viz., two variants of PL1 (PL1A and PL1B) and PL9 from Clostridium thermocellum was carried out. The comparison of the primary sequences of PL1A, PL1B and PL9 revealed that these proteins displayed considerable sequence similarities with family 1 and 9 polysaccharide lyases, respectively. PL1A, PL1B and PL9 are the putative catalytic domains of protein sequence ABN54148.1 and ABN53381.1 respectively. These two protein sequences also contain putative carbohydrate binding module (CBM) and type-I dockerin. The associated putative CBM of PL1A showed strong homology with family 6 CBMs while those of PL1B and PL9 showed homology with family 35 CBMs. Recombinant derivatives of these three enzymes showed molecular masses of approximately 34 kDa, 40 kDa and 32 kDa for PL1A, PL1B and PL9, respectively. PL1A, PL1B and PL9 displayed high activity toward polygalacturonic acid and pectin (up to 55% methyl-esterified) from citrus fruits. However, PL1B showed relatively higher activity towards 55% and 85% methyl-esterified pectin (citrus). PL1A and PL9 showed higher activity on rhamnogalacturonan than PL1B. Both PL1A and PL9 displayed maximum activity at pH 8.5 with optimum temperature of 50°C and 60°C respectively. PL1B achieved highest activity at pH 9.8, under an optimum temperature of 50°C. PL1A, PL1B and PL9 all produced two or more unsaturated galacturonates from pectic substrates as displayed by TLC analysis confirming that they are endo-pectate lyase belonging to family 1 and 9, respectively. This report reveals that pectinolytic activity displayed by Clostridium thermocellum cellulosome is coordinated by a sub-set of at least three multi-modular enzymes.


Assuntos
Celulose/metabolismo , Clostridium thermocellum/enzimologia , Polissacarídeo-Liases/genética , Polissacarídeo-Liases/metabolismo , Sequência de Bases , Cromatografia em Camada Fina , Primers do DNA/genética , Escherichia coli , Concentração de Íons de Hidrogênio , Cinética , Estrutura Molecular , Pectinas/metabolismo , Reação em Cadeia da Polimerase , Alinhamento de Sequência , Análise de Sequência de DNA , Homologia de Sequência , Temperatura
10.
J Agric Food Chem ; 60(48): 11850-8, 2012 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-23101762

RESUMO

Stem byproducts from 10 different grape (Vitis vinifera L.) varieties were evaluated in terms of their total phenolic and total proanthocyanidin contents, flavan-3-ol and proanthocyanidin profiles, and antioxidant capacity measured by ABTS, CUPRAC, FRAP, and ORAC assays, with a view to the recovery of their natural bioactive compounds. Stems from Callet, Syrah, Premsal Blanc, Parellada, and Manto Negro varieties yielded the highest total phenolic and total proanthocyanidin contents and showed the greatest antioxidant capacities, whereas Chardonnay and Merlot stems presented the lowest values. Varieties differed significantly (p<0.05) with regard to both the phenolic composition and antioxidant capacity of their stems. However, no significant differences (p>0.05) were observed when stems from red and white varieties were considered separately. For the 10 grape varieties investigated, this is the first study presenting a detailed description of their stem flavan-3-ol composition determined by HPLC-UV-fluo. All of the analyses confirmed the stem byproducts as a potential polyphenol-rich source, especially promising in the case of the Callet variety.


Assuntos
Antioxidantes/farmacologia , Caules de Planta/química , Proantocianidinas/análise , Proantocianidinas/farmacologia , Vitis/química , Vinho , Benzotiazóis/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Flavonoides/análise , Indústria de Processamento de Alimentos , Hidroxibenzoatos/análise , Polifenóis/análise , Polifenóis/isolamento & purificação , Proantocianidinas/química , Ácidos Sulfônicos/metabolismo
11.
Endocrinology ; 152(11): 4138-47, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21914774

RESUMO

Evidence shows that neuropeptide Y (NPY) neurons are involved in mediating the anorexigenic action of leptin via neuronal circuits in the hypothalamus. However, studies have produced limited data on the cellular processes involved and whether hypothalamic NPY neurons are susceptible to cellular leptin resistance. To investigate the direct regulation of NPY secretion by leptin, we used novel NPY-synthesizing, immortalized mHypoA-NPY/green fluorescent protein and mHypoA-59 hypothalamic cell lines derived from adult hypothalamic primary cultures. We report that leptin treatment significantly suppressed NPY secretion in the cells by approximately 20%. We found a decrease in c-fos expression upon leptin exposure, indicating deactivation or hyperpolarization of the neurons. Protein analysis indicated that leptin inhibits AMP-activated protein kinase (AMPK) activity and activates acetyl-coenzyme A carboxylase in NPY neurons, supporting the hypothesis of an AMPK-dependent mechanism. Inhibiting both AMPK with Compound C or phosphatidylinositol 3 kinase (PI3K) with 2-(4-morpholinyl)-8-phenyl-1(4H)-1-benzopyran-4-one hydrochloride prevented the leptin-mediated decrease in NPY secretion, indicating both AMPK- and PI3K-mediated mechanisms. Further, NPY secretion was stimulated by 30% by the AMPK activator, aminoimidazole carboxamide ribonucleotide. Importantly, prolonged leptin exposure in the mHypoA-NPY/green fluorescent protein cells prevented leptin-induced changes in AMPK phosphorylation and suppression of NPY secretion, indicating that NPY neurons are susceptible to leptin resistance. Our studies indicate that AMPK and PI3K pathways are involved in leptin action in NPY neurons and that leptin resistance blocks the feedback response likely required to maintain energy homeostasis.


Assuntos
Hipotálamo/metabolismo , Leptina/metabolismo , Neurônios/metabolismo , Neuropeptídeo Y/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Linhagem Celular , Camundongos , Fosforilação
12.
FASEB J ; 23(12): 4256-65, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19703933

RESUMO

The distinct lack of cell lines derived from the adult brain is evident. Ciliary neurotrophic factor (CNTF) triggers neurogenesis in primary culture from adult mouse hypothalamus, as detected by bromodeoxyuridine and Ki67 immunostaining. Using SV-40 T-antigen, we immortalized dividing neurons and generated clonal cell lines expressing neuropeptides and receptors involved in neuroendocrine function. We hypothesized that proglucagon-derived peptides may be the mechanistic downstream effectors of CNTF due to documented neuroprotective and proliferative effects. Indeed, proglucagon gene expression was induced by CNTF, and exposure of primary cells to glucagon-like peptide-1 receptor (GLP-1) agonist, exendin-4, induced cell proliferation. Intracerebroventricular injection of CNTF into adult mice caused increased expression of proglucagon peptide in the hypothalamus. Using a specific GLP-1-receptor antagonist, we found that neurogenesis was significantly attenuated and primary culture from GLP-1-receptor-knockout mice lacked CNTF-mediated neuronal proliferation, thus linking the induction of neurogenesis in the hypothalamus to GLP-1-receptor signaling.


Assuntos
Fator Neurotrófico Ciliar/farmacologia , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Hipotálamo/citologia , Neurogênese/fisiologia , Neurônios/citologia , Animais , Linhagem Celular , Proliferação de Células , Fator Neurotrófico Ciliar/metabolismo , Regulação da Expressão Gênica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proglucagon/genética , Proglucagon/metabolismo , Transdução de Sinais
13.
Mol Neurobiol ; 38(3): 199-230, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18931961

RESUMO

It is now well accepted that stress can precipitate mental and physical illness. However, it is becoming clear that given the same stress, some individuals are very vulnerable and will succumb to illness while others are more resilient and cope effectively, rather than becoming ill. This difference between individuals is called stress sensitivity. Stress sensitivity of an individual appears to be influenced by genetically inherited factors, early life (even prenatal) stress, and by the presence or absence of factors that provide protection from stress. In comparison to other stress-related diseases, the concept of sensitivity versus resilience to stress-induced reproductive dysfunction has received relatively little attention. The studies presented herein were undertaken to begin to identify stable characteristics and the neural underpinnings of individuals with sensitivity to stress-induced reproductive dysfunction. Female cynomolgus macaques with normal menstrual cycles either stop ovulating (stress sensitive) or to continue to ovulate (stress resilient) upon exposure to a combined metabolic and psychosocial stress. However, even in the absence of stress, the stress-sensitive animals have lower secretion of the ovarian steroids, estrogen and progesterone, have higher heart rates, have lower serotonin function, have fewer serotonin neurons and lower expression of pivotal serotonin-related genes, have lower expression of 5HT2A and 2C genes in the hypothalamus, have higher gene expression of GAD67 and CRH in the hypothalamus, and have reduced gonadotropin-releasing hormone transport to the anterior pituitary. Altogether, the results suggest that the neurobiology of reproductive circuits in stress-sensitive individuals is compromised. We speculate that with the application of stress, the dysfunction of these neural systems becomes exacerbated and reproductive function ceases.


Assuntos
Inibição da Ovulação , Reprodução , Estresse Fisiológico , Estresse Psicológico , Animais , Hormônio Liberador da Corticotropina/genética , Hormônio Liberador da Corticotropina/metabolismo , Feminino , Expressão Gênica , Hormônio Liberador de Gonadotropina/metabolismo , Hormônios/metabolismo , Sistema Hipotálamo-Hipofisário/fisiologia , Hipotálamo/fisiologia , Imuno-Histoquímica , Macaca fascicularis , Sistema Hipófise-Suprarrenal/fisiologia , Pró-Opiomelanocortina/genética , Pró-Opiomelanocortina/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Serotonina/genética , Receptores de Serotonina/metabolismo , Serotonina/genética , Serotonina/fisiologia , Ácido gama-Aminobutírico/metabolismo
14.
Brain Res ; 1142: 1-12, 2007 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-17320837

RESUMO

Like women, female cynomolgus monkeys show differential sensitivity to stress-induced reproductive dysfunction. A combined social and metabolic stress (mild diet+moderate exercise+relocation) will rapidly induce anovulation in a third of female cynomolgus monkeys (stress-sensitive; SS); a third will ovulate once and then become anovulatory (medium stress-resilient; MSR) and a third are highly stress-resilient (HSR) and exhibit normal menstrual cycles through two stressed menstrual cycles. In a non-stressed menstrual cycle, SS animals have lower levels of estrogen and progesterone, lower activity of the serotonin system and lower expression of genes related to the serotonin system in the dorsal raphe nucleus. In this study, we examined the expression of 5HT1A, 5HT2A, 5HT2C receptors and GAD67 in the hypothalamus of SS, HSR and MSR monkeys using in situ hybridization. SS monkeys exhibited higher expression of 5HT2A mRNA in the paraventricular nucleus (PVN), higher expression of 5HT2C and GAD67 in the infundibulum, as well as higher expression of GAD67 in the posterior hypothalamus (PH), compared with HSR monkeys. However, the expression of 5HT1A mRNA in the ventromedial nucleus (VMN) was not different between groups. We speculate that the serotonin and GABA systems may be altered in the stress-response and reproductive-related circuits of SS monkeys, and may be participating in altering the sensitivity of the reproductive system to stress in these individuals.


Assuntos
Regulação da Expressão Gênica/fisiologia , Glutamato Descarboxilase/metabolismo , Hipotálamo/metabolismo , Isoenzimas/metabolismo , Receptores de Serotonina/metabolismo , Estresse Psicológico/patologia , Análise de Variância , Animais , Feminino , Glutamato Descarboxilase/genética , Hibridização In Situ/métodos , Isoenzimas/genética , Macaca fascicularis , RNA Mensageiro/metabolismo , Receptores de Serotonina/genética , Estresse Psicológico/metabolismo , Fatores de Tempo
15.
Eur J Pharmacol ; 555(1): 67-75, 2007 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-17112509

RESUMO

Estrogen and progesterone act on gene and protein expression in serotonin neurons in a manner that suggests serotonin neurotransmission should increase. However, measurement of extracellular serotonin in macaques was lacking. Elevated prolactin secretion can be an indicator of increased serotonergic function and prolactin is increased by combined estrogen and progesterone treatment. We examined extracellular serotonin by microdialysis in a well-characterized macaque model of steroid-induced prolactin secretion. Monkeys were fitted with 2 guide tubes directed to the arcuate nucleus of the hypothalamus. Samples (75 microl/15-minute interval) were obtained via a tether-swivel device through sample lines into an adjoining room. Serotonin was measured with a modified commercial enzyme linked immunoassay (ELISA) kit. Fenfluramine infused through the probe (300 microM for 2 h; n=2 trials) or administered intravenously (2.5 mg/kg; n=2 trials) caused a marked increase in extracellular serotonin and verified the efficacy of the procedure. Three monkeys were maintained with an estrogen implant for 2 weeks. Each monkey was injected with 20 mg of progesterone s.c. in oil at 1500 h; microdialysis was initiated the next morning and samples were obtained for 24 h. There was a significant increase in serotonin between 40 and 43 h after the progesterone injection (P<0.001, ANOVA). Serotonin averaged 59+/-1 pg/sample from 18-30 h post-progesterone injection, and averaged 76+/-2 pg/sample from 30-48 h post-progesterone injection (P<0.0001; t-test). Since the increase in serotonin is delayed by approximately 40 h after progesterone-injection, we speculate that the action of progesterone may involve either nuclear progestin receptors or membrane progestin receptors.


Assuntos
Estradiol/administração & dosagem , Hipotálamo/efeitos dos fármacos , Progesterona/farmacologia , Serotonina/metabolismo , Animais , Feminino , Fenfluramina/farmacologia , Hipotálamo/metabolismo , Macaca mulatta , Microdiálise , Prolactina/sangue , Serotoninérgicos/farmacologia
16.
Cad. saúde coletiva ; 3(5): 8-48, 1987. tab
Artigo em Português | LILACS | ID: lil-59242

RESUMO

Os objetivos do presente estudo foram: a) verificar se as idéias de "quente" e "frio" existiam na comunidade goianiense, b) conhecer quais os alimentos/remédios "quentes" e "frios" definidos pela populaçäo, relacionando-se com os problemass de saúde a que se aplicavam, e c) conhecer as regras de uso (prescriçöes e proibiçöes), e as consequências pela violaçäo e/ou desconhecimento das regras. Foram realizadas reuniöes em grupos com estudantes de medicina, entrevistas abertas com 11 informantes e entrevistas através de questionário com 39 senhoras, sendo que 36 delas informaram 348 indicaçöes para alimentos "quentes" e "frios" tendo predominado a categoria "quente" (197 indicaçöes), a categoria alimentar frutas (38,5%) seguida de ervas e condimentos (27%) e a origem vegetal das indicaçöes (87,9%). Os alimentos/remédios "quentes" foram indicados preferencialmente para problemas do trato respiratório (58,1%) e os "frios" para os problemass gastrointestinais e gênito-urinários (58,2%). A regra de uso (dos termos opostos) näo se apresentou de forma clara no grupo estudado. Em 75% dos casos a família foi o veículo de transmissäo da idéia desde a infância


Assuntos
Medicina Tradicional , Brasil
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