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1.
Med J Malaysia ; 76(1): 114-117, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33510122

RESUMO

Xanthogranulomatous inflammation is an uncommon form of chronic inflammatory process. Only a few isolated case reports of xanthogranulomatous appendicitis (XA) have been published. XA has nonspecific imaging findings and cannot be reliably differentiated on imaging from locally advanced malignancy. XA however follows a benign course and can potentially be treated with surgical resection.


Assuntos
Apendicite , Xantomatose , Apendicite/diagnóstico por imagem , Apendicite/cirurgia , Feminino , Granuloma/diagnóstico por imagem , Granuloma/cirurgia , Humanos , Pelve/diagnóstico por imagem , Pelve/cirurgia , Xantomatose/diagnóstico por imagem , Xantomatose/cirurgia
4.
Sleep Med ; 16(9): 1109-15, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26298787

RESUMO

STUDY OBJECTIVE: Working memory deficits in children with obstructive sleep apnea (OSA) have been reported in previous studies, but the results were inconclusive. This study tried to address this issue by delineating working memory functions into executive processes and storage/maintenance components based on Baddeley's working memory model. METHODS: Working memory and basic attention tasks were administered on 23 OSA children aged 8-12 years and 22 age-, education-, and general cognitive functioning-matched controls. Data on overnight polysomnographic sleep study and working memory functions were compared between the two groups. Associations between respiratory-related parameters and cognitive performance were explored in the OSA group. RESULTS: Compared with controls, children with OSA had poorer performance on both tasks of basic storage and central executive components in the verbal domain of working memory, above and beyond basic attention and processing speed impairments; such differences were not significant in the visuo-spatial domain. Moreover, correlational analyses and hierarchical regression analyses further suggested that obstructive apnea-hypopnea index (OAHI) and oxygen saturation (SpO2) nadir were associated with verbal working memory performance, highlighting the potential pathophysiological mechanisms of OSA-induced cognitive deficits. CONCLUSIONS: Verbal working memory impairments associated with OSA may compromise children's learning potentials and neurocognitive development. Early identification of OSA and assessment of the associated neurocognitive deficits are of paramount importance. Reversibility of cognitive deficits after treatment would be a critical outcome indicator.


Assuntos
Transtornos da Memória/etiologia , Transtornos da Memória/fisiopatologia , Memória de Curto Prazo/fisiologia , Apneia Obstrutiva do Sono/psicologia , Estudos de Casos e Controles , Criança , China , Feminino , Humanos , Masculino , Transtornos da Memória/diagnóstico , Testes Neuropsicológicos , Polissonografia , Testes de Função Respiratória , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/fisiopatologia
5.
Neuroscience ; 278: 105-12, 2014 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-25130560

RESUMO

5-Hydroxytrytamine (serotonin) type 3A receptors (5-HT3ARs), as the only ligand-gated ion channels in the serotonin receptor family, are known to regulate neuronal excitation and release of GABA in hippocampal interneurons. However, their physiological role in glutamatergic synaptic plasticity remains unclear. Here, we show that deletion of the 5-HT3AR gene in transgenic mice abolished N-methyl-d-aspartate (NMDA) receptor (NMDAR)-dependent long-term depression (LTD) induced by low-frequency stimulation (LFS) in hippocampal CA1 synapses in slices, whereas the metabotropic glutamate receptor (mGluR)-dependent LTD did not change in the 5-HT3AR knockout mice. In addition, 5-HT3ARs disruption inhibited α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) internalization, without altering basal surface levels of AMPARs. However, the deletion of 5-HT3ARs did not lead to loss of synapses and structural alteration of dendritic spines. Furthermore, the concentrations of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in the hippocampus were not affected by the deletion of 5-HT3ARs. These observations revealed an important role of 5-HT3ARs in NMDAR-dependent long-term depression, which is critical for learning behaviors.


Assuntos
Região CA1 Hipocampal/fisiologia , Depressão Sináptica de Longo Prazo , Receptores de AMPA/metabolismo , Receptores de N-Metil-D-Aspartato/fisiologia , Receptores 5-HT3 de Serotonina/fisiologia , Animais , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transporte Proteico , Células Piramidais/fisiologia , Receptores de Glutamato Metabotrópico/fisiologia , Receptores 5-HT3 de Serotonina/genética , Serotonina/análise
6.
ACS Chem Neurosci ; 3(1): 22-30, 2012 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-22860178

RESUMO

Parkinson's disease is caused by the degeneration of dopaminergic neurons in substantia nigra. There is no current promising treatment for neuroprotection of dopaminergic neurons. Ceftriaxone is a beta-lactam antibiotic and has been reported to offer neuroprotective effects (Rothstein, J.-D., Patel, S., Regan, M.-R., Haenggeli, C., Huang, Y.-H., Bergles, D.-E., Jin, L., Dykes, H.-M., Vidensky, S., Chung, D.-S., Toan, S.-V., Bruijn, L.-I., Su, Z.-Z., Gupta, P., and Fisher, P.-B. (2005) Beta-lactam antibiotics offer neuroprotection by increasing glutamate transporter expression Nature433, 73-77). In the present study, efficacy of ceftriaxone in neuroprotection of dopaminergic neurons and amelioration of motor deficits in a rat model of Parkinson's disease were investigated. Ceftriaxone was administrated in 6-hydroxydopamine-lesioned rats. Using behavioral tests, grip strength and numbers of apomorphine-induced contralateral rotation were declined in the ceftriaxone-treated group. More importantly, cell death of dopaminergic neurons was found to decrease. In addition, both the protein expression and immunoreactivity for GLT-1 were up-regulated. The present results strongly indicate that ceftriaxone is a potential agent in the treatment of Parkinson's disease.


Assuntos
Encéfalo/efeitos dos fármacos , Ceftriaxona/farmacologia , Atividade Motora/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Transtornos Parkinsonianos/tratamento farmacológico , Animais , Comportamento Animal/efeitos dos fármacos , Western Blotting , Encéfalo/patologia , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/patologia , Feminino , Oxidopamina/toxicidade , Transtornos Parkinsonianos/patologia , Ratos , Ratos Sprague-Dawley
7.
Hong Kong Med J ; 18(1): 40-5, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22302910

RESUMO

OBJECTIVE: To compare the relative efficacy of the green pit viper antivenom from Thailand and Agkistrodon halys antivenom from China. DESIGN. In-vivo experimental study. SETTING: A wildlife conservation organisation, a university, a poison information centre, and a regional hospital in Hong Kong. MAIN OUTCOME MEASURES: Pre- and post-antivenom lethal dose 50 (LD50) of the Cryptelytrops albolabris venom, median effective dose (ED50) of green pit viper antivenom and Agkistrodon halys antivenom against a lethal dose of the venom. SUBJECTS. Adult mice. RESULTS: The intraperitoneal LD50 of the venom from locally caught Cryptelytrops albolabris was 0.14 microL. After post-exposure treatment with 10 microL of antivenom, it was elevated to 0.36 microL and 0.52 microL by the green pit viper antivenom and the Agkistrodon halys antivenom, respectively. The ED50 was 32.02 microL for green pit viper antivenom and 6.98 microL for Agkistrodon halys antivenom. Both green pit viper antivenom and Agkistrodon halys antivenom ameliorated the lethality of Cryptelytrops albolabris venom in mice. CONCLUSION: The overall superior neutralisation capacity of Agkistrodon halys antivenom over green pit viper antivenom may be related to the geographic proximity of the venoms used for antivenom preparation. The results point towards the need for further comparison of the two antivenoms on protein or immunoglobulin weight basis, and with respect to non-lethal clinically significant toxicities.


Assuntos
Antivenenos/farmacologia , Venenos de Crotalídeos/antagonistas & inibidores , Mordeduras de Serpentes/complicações , Animais , Antivenenos/administração & dosagem , China , Relação Dose-Resposta a Droga , Hong Kong , Dose Letal Mediana , Camundongos , Camundongos Endogâmicos C57BL , Centros de Controle de Intoxicações , Tailândia
8.
Proc Natl Acad Sci U S A ; 106(37): 15961-6, 2009 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-19805236

RESUMO

Hypothalamic magnocellular neurons express either one of the neurohypophysial hormones, vasopressin or oxytocin, along with different neuropeptides or neuromodulators. Axonal terminals of these neurons are generally accepted to release solely the two hormones but not others into the circulation. Here, we show that secretin, originally isolated from upper intestinal mucosal extract, is present throughout the hypothalamo-neurohypophysial axis and that it is released from the posterior pituitary under plasma hyperosmolality conditions. In the hypothalamus, it stimulates vasopressin expression and release. Considering these findings together with our previous findings that show a direct effect of secretin on renal water reabsorption, we propose here that secretin works at multiple levels in the hypothalamus, pituitary, and kidney to regulate water homeostasis. Findings presented here challenge previous understanding regarding the neurohypophysis and could provide new concepts in treating disorders related to osmoregulation.


Assuntos
Água Corporal/fisiologia , Neuro-Hipófise/fisiologia , Secretina/fisiologia , Animais , Sequência de Bases , Primers do DNA/genética , Expressão Gênica , Homeostase/fisiologia , Sistema Hipotálamo-Hipofisário/fisiologia , Imuno-Histoquímica , Rim/fisiologia , Modelos Neurológicos , Sistemas Neurossecretores/fisiologia , Neurotransmissores/genética , Neurotransmissores/fisiologia , Concentração Osmolar , Ratos , Secretina/sangue , Secretina/genética , Vasopressinas/genética , Vasopressinas/fisiologia
9.
Neuroscience ; 151(2): 439-51, 2008 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-18082329

RESUMO

Anatomical and neurochemical studies indicated that the globus pallidus receives serotonergic innervation from raphe nuclei but the membrane effects of 5-HT on globus pallidus neurons are not entirely clear. We address this question by applying whole-cell patch-clamp recordings on globus pallidus neurons in immature rat brain slices. Under current-clamp recording, 5-HT depolarized globus pallidus neurons and increased their firing rate, an action blocked by both 5-HT(4) and 5-HT(7) receptor antagonists and attributable to an increase in cation conductance(s). Further experiments indicated that 5-HT enhanced the hyperpolarization-activated inward conductance which is blocked by 5-HT(7) receptor antagonist. To determine if 5-HT exerts any presynaptic effects on GABAergic and glutamatergic inputs, the actions of 5-HT on synaptic currents were studied. At 10 microM, 5-HT increased the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) but had no effect on both the frequency and amplitude of miniature inhibitory postsynaptic currents (mIPSCs). However, 5-HT at a higher concentration (50 microM) decreased the frequency but not the amplitude of the mIPSCs, indicating an inhibition of GABA release from the presynaptic terminals. This effect was sensitive to 5-HT(1B) receptor antagonist. In addition to the presynaptic effects on GABAergic neurotransmission, 5-HT at 50 microM had no consistent effects on glutamatergic neurotransmission, significantly increased the frequency of miniature excitatory postsynaptic currents (mEPSCs) in 4 of 11 neurons and decreased the frequency of mEPSCs in 3 of 11 neurons. In conclusion, we found that 5-HT could modulate the excitability of globus pallidus neurons by both pre- and post-synaptic mechanisms. In view of the extensive innervation by globus pallidus neurons on other basal ganglia nuclei, this action of 5-HT originated from the raphe may have a profound effect on the operation of the entire basal ganglia network.


Assuntos
Globo Pálido/citologia , Neurônios/efeitos dos fármacos , Receptores de Serotonina/efeitos dos fármacos , Serotonina/farmacologia , Animais , Cátions/metabolismo , Eletrofisiologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Globo Pálido/efeitos dos fármacos , Técnicas In Vitro , Canais Iônicos/efeitos dos fármacos , Masculino , Técnicas de Patch-Clamp , Pindolol/análogos & derivados , Pindolol/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores Pré-Sinápticos/efeitos dos fármacos , Receptores de Serotonina/fisiologia , Receptores 5-HT4 de Serotonina/efeitos dos fármacos , Receptores 5-HT4 de Serotonina/fisiologia , Antagonistas da Serotonina/farmacologia , Sinapses/efeitos dos fármacos , Sinapses/fisiologia , Transmissão Sináptica/efeitos dos fármacos
10.
Ann N Y Acad Sci ; 1070: 27-50, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16888148

RESUMO

Secretin holds a unique place in the history of endocrinology and gastrointestinal physiology, as it is the first peptide designated as a hormone. During the last century since its first discovery, the hormonal effects of secretin in the gastrointestinal tract were extensively studied, and its principal role in the periphery was found to stimulate exocrine secretion from the pancreas. Recently, a functional role of secretin in the brain has also been substantiated, with evidence suggesting a possible role of secretin in embryonic brain development. Given that secretin and its receptors are widely expressed in multiple tissues, this peptide should therefore exhibit pleiotrophic functions throughout the body. The present article reviews the current knowledge on the central and peripheral effects of secretin as well as its therapeutic uses.


Assuntos
Secretina/metabolismo , Animais , Doença , Humanos , Receptores Acoplados a Proteínas G/metabolismo , Receptores dos Hormônios Gastrointestinais/metabolismo , Secretina/uso terapêutico , Transdução de Sinais
11.
Ann N Y Acad Sci ; 1070: 196-200, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16888165

RESUMO

Previous studies demonstrated that secretin could be released from the cerebellum, where it exerts a facilitatory action on the GABAergic inputs into the Purkinje neurons. In the present article, we provide evidence of the endogenous release of secretin in the hypothalamus and the mechanisms underlying this release. Incubation of the hypothalamic explants with KCl induces the release of secretin to 4.35 +/- 0.45-fold of the basal level. This K+-induced release was tetrodotoxin and cadmium sensitive, suggesting the involvement of voltage-gated sodium and calcium channels. The use of specific blockers further revealed the involvement of L-, N-, and P-type high voltage-activated (HVA) calcium channels. Results present in the current article provide further and more solid evidence of the role of secretin as a neuropeptide in the mammalian central nervous system.


Assuntos
Hipotálamo/metabolismo , Secretina/metabolismo , Animais , Masculino , Cloreto de Potássio/farmacologia , Ratos , Ratos Endogâmicos WF , Receptores Acoplados a Proteínas G/metabolismo , Receptores dos Hormônios Gastrointestinais/metabolismo
12.
Neuroscience ; 141(4): 1871-8, 2006 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-16814931

RESUMO

The tridecapeptide neurotensin has been demonstrated to modulate neurotransmission in a number of brain regions. There is evidence that neurotensin receptors exist in globus pallidus presynaptically and postsynaptically. Whole-cell patch-clamp recordings were used to investigate the modulatory effects of neurotensin on glutamate and GABA transmission in this basal ganglia nucleus in rats. Neurotensin at 1 microM significantly increased the frequency of glutamate receptor-mediated miniature excitatory postsynaptic currents. In contrast, neurotensin had no effect on GABA(A) receptor-mediated miniature inhibitory postsynaptic currents. The presynaptic facilitation of neurotensin on glutamatergic transmission could be mimicked by the C-terminal fragment, neurotensin (8-13), but not by the N-terminal fragment, neurotensin (1-8). The selective neurotensin type-1 receptor antagonist, SR48692 {2-[(1-(7-chloro-4-quinolinyl)-5-2(2,6-dimethoxyphenyl)pyrazol-3-yl)carbonylamino]-tricyclo(3.3.1.1.(3.7))-decan-2-carboxylic acid}, blocked this facilitatory effect of neurotensin, and which itself had no effect on miniature excitatory postsynaptic currents. The specific phospholipase C inhibitor, U73122 {1-[6-[[17beta-3-methoyyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione}, significantly inhibit neurotensin-induced facilitation on glutamate release. Taken together with the reported postsynaptic depolarization of neurotensin in globus pallidus, it is suggested that neurotensin excites the globus pallidus neurons by multiple mechanisms which may provide a rationale for further investigations into its involvement in motor disorders originating from the basal ganglia.


Assuntos
Globo Pálido/citologia , Ácido Glutâmico/metabolismo , Neurônios/efeitos dos fármacos , Neurotensina/farmacologia , Transmissão Sináptica/efeitos dos fármacos , Anestésicos Locais/farmacologia , Animais , Animais Recém-Nascidos , Bicuculina/farmacologia , Relação Dose-Resposta à Radiação , Interações Medicamentosas , Estimulação Elétrica/métodos , Inibidores Enzimáticos/farmacologia , Estrenos/farmacologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Potenciais Pós-Sinápticos Excitadores/efeitos da radiação , Antagonistas GABAérgicos/farmacologia , Técnicas In Vitro , Inibição Neural/efeitos dos fármacos , Inibição Neural/fisiologia , Inibição Neural/efeitos da radiação , Neurônios/metabolismo , Neurotensina/antagonistas & inibidores , Técnicas de Patch-Clamp/métodos , Pirazóis/farmacologia , Pirrolidinonas/farmacologia , Quinolinas/farmacologia , Ratos , Ratos Sprague-Dawley , Tetrodotoxina/farmacologia
13.
Neuroscience ; 134(2): 377-86, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15963647

RESUMO

Previous studies demonstrated that secretin could modulate synaptic transmission in the rat cerebellum. In the present report, we provide evidence for the endogenous release of secretin in the cerebellum and further characterize the actions of secretin in this brain area. First, to show that secretin is released endogenously, blocks of freshly dissected cerebella were challenged with a high concentration of KCl. Incubation with KCl almost doubled the rate of secretin release. This KCl-induced release was sensitive to tetrodotoxin and cadmium suggesting the involvement of voltage-gated sodium and calcium channels. The use of specific channel blockers further revealed that L-type and P/Q-type calcium channels underlie both basal and KCl-evoked secretin release. In support of this, depolarization of Purkinje neurons in the presence of NMDA, group II mGluR and cannabinoid CB1 receptor blockers resulted in increased inhibitory postsynaptic current frequency. Second, we found that the previously reported facilitatory action of secretin on GABAergic inputs to Purkinje neurons is partly dependent on the release of endogenous glutamate. In the presence of CNQX, an AMPA/kainate receptor antagonist, the facilitatory effect of secretin on GABA release was significantly reduced. In support of this idea, application of AMPA, but not kainate receptor agonist, facilitated GABA release from inhibitory terminals, an action that was sensitive to AMPA receptor antagonists. These data indicate that a direct and an indirect pathway mediate the action of secretin in the basket cell-Purkinje neuron synapse. The results provide further and more solid evidence for the role of secretin as a neuropeptide in the mammalian CNS.


Assuntos
Cerebelo/fisiologia , Agonistas de Aminoácidos Excitatórios/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Receptores de AMPA/fisiologia , Secretina/fisiologia , 6-Ciano-7-nitroquinoxalina-2,3-diona/farmacologia , Animais , Canais de Cálcio/efeitos dos fármacos , Canais de Cálcio/fisiologia , Cerebelo/efeitos dos fármacos , Técnicas In Vitro , Técnicas de Patch-Clamp , Cloreto de Potássio/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores de AMPA/efeitos dos fármacos , Secretina/metabolismo , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico/farmacologia
14.
Neuroreport ; 16(3): 219-22, 2005 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-15706223

RESUMO

The expression and spatial distribution of secretin and its receptor in human cerebellum were investigated by in situ hybridization and immunohistochemical techniques. Secretin mRNAs are found in Purkinje cells whereas secretin receptor transcripts are present in Purkinje cells and basket cells in the molecular cell layer. In addition, secretin-immunoreactivities are localized in both the soma and dendrites of Purkinje cells. These data are the first demonstration of the spatial distribution of secretin and its receptor in distinct neurons within the human cerebellum. The cellular localizations of this ligand-receptor pair are consistent with the proposed actions of secretin in the cerebellum of rodents and hence suggest that secretin also serves specific neural functions in the human cerebellum.


Assuntos
Cerebelo/metabolismo , Regulação da Expressão Gênica/fisiologia , Receptores dos Hormônios Gastrointestinais/metabolismo , Secretina/metabolismo , Cerebelo/citologia , Dendritos/genética , Dendritos/metabolismo , Humanos , Imuno-Histoquímica/métodos , Hibridização In Situ/métodos , Microscopia Confocal/métodos , Células de Purkinje/citologia , Células de Purkinje/metabolismo , RNA Mensageiro/metabolismo , Receptores Acoplados a Proteínas G , Receptores dos Hormônios Gastrointestinais/genética , Secretina/genética
15.
Neurosignals ; 14(6): 303-16, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16772733

RESUMO

In the present study, a twenty-mer antisense oligonucleotide specific for N-methyl-D-aspartate receptor one (ANR1) was applied to striatal neurons in primary cell culture. The ANR1 was found to be specific and nontoxic. Significant reductions in expression of NR1 mRNA and proteins were resulted after a single dose of ANR1 transcripts. Interestingly, there were reductions in total NR1 proteins but two phosphorylated forms of NR1 proteins at serine 896 and 897 residues were not reduced. There was also no change in the pattern of distribution of NR1 immunoreactivity in the striatal neurons. In addition, significant reductions of NMDA-mediated peak inward current were found after application of a higher concentration of ANR1 (20-100 microM) by patch clamp recordings. The present results indicate that ANR1 is a useful agent in reducing NMDA receptor functions. The present data thus provide detailed cellular and molecular mechanisms to explain our previous findings of amelioration of motor symptoms in a rat model of Parkinson's disease. More importantly, application of ANR1 was also found to display neuroprotective effects of striatal neurons against NMDA-induced excitotoxic cell death. The findings have implications in development of new approach in prevention of cell death in neurodegenerative diseases and new treatments for these diseases.


Assuntos
Expressão Gênica/efeitos dos fármacos , Neostriado/metabolismo , Neurônios/fisiologia , Oligonucleotídeos Antissenso/farmacologia , Receptores de N-Metil-D-Aspartato/genética , Animais , Animais Recém-Nascidos , Western Blotting , Células Cultivadas , Agonistas de Aminoácidos Excitatórios/toxicidade , Imunofluorescência , Imuno-Histoquímica , N-Metilaspartato/toxicidade , Neostriado/citologia , Neostriado/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Técnicas de Patch-Clamp , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa
16.
J Glaucoma ; 13(6): 479-85, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15534473

RESUMO

PURPOSE: To evaluate the effect of varying the scanning resolution of optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) measurement on diagnostic sensitivity and functional correlation in glaucoma. PATIENTS AND METHODS: 314 eyes from 182 subjects including 107 normal eyes, 83 glaucoma suspect eyes, and 124 glaucoma eyes were included in this cross-sectional study. Standard automated perimetry and OCT measurement of RNFL thickness were performed. Each individual underwent two scanning protocols: (1) fast RNFL thickness (3.4) scan (with resolution of 256 scan points) and (2) RNFL thickness (3.4) scan (with resolution of 512 scan points). RNFL thickness was compared among the groups. Diagnostic sensitivity was evaluated with Receiver Operating Characteristic (ROC) Curve. Relationship between RNFL thickness and visual field mean deviation was examined using linear regression analysis. RESULTS: Measured RNFL thickness using fast RNFL thickness (3.4) scan was significantly higher compared with RNFL thickness (3.4) scan in average, superior, nasal and inferior RNFL in all diagnostic groups. Comparing normal and glaucoma groups, RNFL thickness (3.4) scan produced the largest area under the ROC curve (0.912) based on average RNFL thickness. A stronger correlation between average RNFL and visual field mean deviation was found in RNFL thickness (3.4) scan (R = 0.75, R = 0.56). CONCLUSIONS: Higher resolution RNFL scan provides better diagnostic sensitivity in glaucoma detection and a stronger correlation with visual function.


Assuntos
Glaucoma/diagnóstico , Fibras Nervosas/ultraestrutura , Retina/ultraestrutura , Tomografia de Coerência Óptica/normas , Adulto , Estudos de Casos e Controles , Feminino , Glaucoma/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Sensibilidade e Especificidade , Campos Visuais
17.
Neuroscience ; 125(4): 853-9, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15120846

RESUMO

The globus pallidus is a major component in the indirect pathway of the basal ganglia. There is evidence that neurotensin receptors exist in this nucleus. To determine the electrophysiological effects of neurotensin on pallidal neurons, whole-cell patch-clamp recordings were performed in the acutely prepared brain slices. Under current-clamp recordings, neurotensin at 1 microM depolarized pallidal neurons. Voltage-clamp recordings also showed an inward current induced by neurotensin. The depolarizing effect of neurotensin could be mimicked by the C-terminal fragment, neurotensin (8-13), but not by the N-terminal fragment, neurotensin (1-8). Both SR 142948A, a non-selective neurotensin receptor type-1 and type-2 antagonist, and SR 48692, a selective type-1 receptor antagonist, blocked the depolarizing effect of neurotensin, and which themselves had no effect on membrane potential. Thus, neurotensin type-1 receptors appear to mediate the effect of neurotensin. The depolarization evoked by neurotensin persisted in the presence of tetrodotoxin, ionotropic and metabotropic glutamate and GABA receptor antagonists, indicating that neurotensin excited the pallidal neurons by activating the receptor expressed on the neurons recorded. Current-voltage relationship revealed that both the suppression of a potassium conductance and the activation of a cationic conductance are involved in the neurotensin-induced depolarization. Based on the action of neurotensin in the globus pallidus we hypothesize that alterations of the striatopallidal neurotensin system contribute to symptoms of basal ganglia motor disorders.


Assuntos
Potenciais de Ação/fisiologia , Adamantano/análogos & derivados , Globo Pálido/fisiologia , Neurônios/fisiologia , Neurotensina/metabolismo , Receptores de Neurotensina/metabolismo , Potenciais de Ação/efeitos dos fármacos , Adamantano/farmacologia , Anestésicos Locais/farmacologia , Animais , Eletrofisiologia , Globo Pálido/efeitos dos fármacos , Imidazóis/farmacologia , Neurônios/efeitos dos fármacos , Técnicas de Cultura de Órgãos , Técnicas de Patch-Clamp , Fragmentos de Peptídeos/metabolismo , Pirazóis/farmacologia , Quinolinas/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores de Neurotensina/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Transmissão Sináptica/fisiologia , Tetrodotoxina/farmacologia
18.
Brain Res Mol Brain Res ; 120(1): 9-21, 2003 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-14667572

RESUMO

Developmental expression of N-methyl-D-aspartate (NMDA) receptor subunits were determined and compared in striatal and nigral neurons in neonatal primary cell cultures. In striatal neurons, NR1, NR2A and NR2B mRNAs and immunoreactivity, and NR2D mRNA were found and the maximal levels of NR1 mRNA and immunoreactivity expression were found at 6 day-in-vitro (DIV). NMDA receptors found at this stage in striatal neurons are likely to contain NR1 plus NR2A, NR2B and NR2D subunits. In nigral neurons, NR1 and NR2B mRNAs and immunoreactivity, and NR2D mRNA were found and the maximal level of NR1 immunoreactivity expression was found at 10 DIV. Unlike striatal neurons, NMDA receptors found in nigral neurons are likely to contain NR1 plus NR2B and NR2D subunits only. NMDA-induced toxicity assays showed that striatal neurons were most susceptible to cell death at around 10 DIV but nigral neurons were not susceptible to NMDA-induced cell death at all stages. In addition, patch clamp analysis revealed that functional NMDA receptors could only be found in striatal neurons but not in nigral dopaminergic neurons in vitro. The present results indicate that striatal and nigral neurons are programmed to express distinct NMDA receptor subunits during their endogenous development in cell cultures. Despite dopaminergic neurons in culture display NMDA receptor subunits, functional NMDA receptors are not assembled. The present findings have demonstrated that dopaminergic neurons in vitro may behave very differently to their counterparts in vivo in terms of NMDA receptor-mediated responses. Our results also have implications in transplantations using dopaminergic neurons in vitro in treatments of Parkinson's disease.


Assuntos
Dopamina/metabolismo , Neostriado/citologia , Neurônios/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Substância Negra/citologia , Animais , Animais Recém-Nascidos , Antígenos de Diferenciação Mielomonocítica/farmacologia , Contagem de Células , Células Cultivadas , Imunofluorescência/métodos , Glutamato Descarboxilase/metabolismo , Isoenzimas/metabolismo , Potenciais da Membrana/efeitos dos fármacos , Neostriado/metabolismo , Neurônios/efeitos dos fármacos , Técnicas de Patch-Clamp , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo , RNA Mensageiro/biossíntese , Ratos , Receptores de N-Metil-D-Aspartato/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Substância Negra/metabolismo , Fatores de Tempo , Fatores de Transcrição/farmacologia , Tirosina 3-Mono-Oxigenase/metabolismo
19.
Mol Neurobiol ; 26(1): 97-107, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12392059

RESUMO

The role of secretin as a classical hormone in the gastrointestinal system is well-established. The recent debate on the use of secretin as a potential therapeutic treatment for autistic patients urges a better understanding of the neuroactive functions of secretin. Indeed, there is an increasing body of evidence pointing to the direction that, in addition to other peptides in the secretin/glucagon superfamily, secretin is also a neuropeptide. The purpose of this review is to discuss the recent data for supporting the neurocrine roles of secretin in rodents. By in situ hybridization and immunostaining, secretin was found to be expressed in distinct neuronal populations within the cerebellum and cerebral cortex, whereas the receptor transcript was found throughout the brain. In the rat cerebellum, secretin functions as a retrograde messenger to facilitate GABA transmission, indicating that it can modulate motor and other functions. In summary, the recent data support strongly the neuropeptide role of secretin, although the secretin-autism link remains to be clarified in the future.


Assuntos
Neuropeptídeos/fisiologia , Secretina/fisiologia , Sequência de Aminoácidos , Animais , Transtorno Autístico/tratamento farmacológico , Cerebelo/metabolismo , Córtex Cerebral/metabolismo , Estimulação Elétrica , Evolução Molecular , Humanos , Mucosa Intestinal/metabolismo , Mamíferos/metabolismo , Modelos Neurológicos , Dados de Sequência Molecular , Proteínas do Tecido Nervoso/fisiologia , Neurônios/metabolismo , Ratos , Receptores Acoplados a Proteínas G , Receptores dos Hormônios Gastrointestinais/fisiologia , Secretina/uso terapêutico , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Ácido gama-Aminobutírico/fisiologia
20.
Neuroscience ; 114(2): 417-25, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12204211

RESUMO

GABA is the major neurotransmitter used in the globus pallidus and there is evidence that GABA(B) receptors exist in this nucleus. Here we show that unilateral microinjection of baclofen, a GABA(B) receptor agonist, induced ipsilateral turning in Sprague-Dawley rats. This effect was prevented by preinjection of the GABA(B) receptor antagonist CGP55845A, which itself did not cause rotation. Thus, activation of GABA(B) receptor may suppress the activity of globus pallidus neurons, which is in line with the finding that the glutamate receptor antagonists (+/-)-2-amino-5-phosphonopentanoic acid and 6-cyano-7-nitroquinoxaline-2,3-dione also caused similar ipsilateral turning when injected into globus pallidus. Furthermore, in the presence of these glutamate receptor antagonists, injection of baclofen resulted in fewer rotations. To test the possibility that baclofen reduced glutamate release onto globus pallidus neurons, the effects of baclofen on miniature excitatory postsynaptic currents were studied in rat brain slices. Patch-clamp recordings showed that baclofen at 30 microM significantly reduced the frequency of the miniature excitatory postsynaptic currents. However, baclofen induced a weak outward current only in a minority of globus pallidus neurons. These pre- and postsynaptic effects of baclofen were reversed or prevented by CGP55845A. These results suggest that GABA(B) receptor in globus pallidus plays an important role in the regulation of movement by modulating glutamatergic inputs at a presynaptic site.


Assuntos
Globo Pálido/metabolismo , Ácido Glutâmico/metabolismo , Atividade Motora/fisiologia , Vias Neurais/metabolismo , Terminações Pré-Sinápticas/metabolismo , Receptores de GABA-B/metabolismo , Transmissão Sináptica/fisiologia , Animais , Baclofeno/farmacologia , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Relação Dose-Resposta a Droga , Antagonistas de Aminoácidos Excitatórios/farmacologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Agonistas GABAérgicos/farmacologia , Antagonistas GABAérgicos/farmacologia , Globo Pálido/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Vias Neurais/efeitos dos fármacos , Terminações Pré-Sinápticas/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Receptores de GABA-B/efeitos dos fármacos , Receptores de Glutamato/efeitos dos fármacos , Receptores de Glutamato/metabolismo , Rotação , Membranas Sinápticas/efeitos dos fármacos , Membranas Sinápticas/metabolismo , Transmissão Sináptica/efeitos dos fármacos
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