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1.
QJM ; 112(11): 847-853, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31297519

RESUMO

BACKGROUND: Sarcopenia is emerging as an important public health problem, and evidences have determined that poor sleep is associated with muscle strength, but the potential effects of excessive daytime sleepiness (EDS), snoring and witnessed apnea on handgrip strength have not been evaluated. AIM: We aimed to examine the association between EDS, snoring, witnessed apnea and muscle strength in an adult population. DESIGN: Cross-sectional study. METHODS: This cross-sectional study comprised 19 434 adults. Handgrip strength was measured using a handheld digital dynamometer. EDS was assessed by Epworth Sleepiness Scale, snoring and witnessed apnea during sleep were reported through simple yes/no questions. Analysis of covariance was carried out to determine the association between EDS with snoring or witnessed apnea and muscle strength. RESULTS: The means (95% confidence interval) for average handgrip strength/body weight (kg/kg) across symptoms categories were 0.396 (0.333-0.472), 0.393 (0.330-0.467), 0.396 (0.333-0.471) and 0.386 (0.325-0.460) (P < 0.0001), respectively. Similar results were observed with maximal handgrip strength/body weight (kg/kg). CONCLUSIONS: Self-reported EDS accompanied with snoring or apnea is associated with lowest handgrip strength, independently of confounding factors. Whether improvement of EDS, snoring and apnea, can ameliorate age-associated decline in muscle strength warrants further studies.


Assuntos
Distúrbios do Sono por Sonolência Excessiva/epidemiologia , Distúrbios do Sono por Sonolência Excessiva/etiologia , Força da Mão , Ronco/complicações , Adulto , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Dinamômetro de Força Muscular , Fatores de Risco , Autorrelato
2.
J Burn Care Res ; 34(6): 649-58, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23817000

RESUMO

To evaluate the clinical impact of multiple-drug resistance in burn patients with Pseudomonas aeruginosa (Pa) bacteremia. A retrospective cohort study in a 10-bed burn intensive care unit (BICU) was performed. Univariate and multivariate analyses were used to analyze the influence of multiple-drug resistance on mortality and length of BICU stay in Pa bacteremic patients. During a 21-year study period (1989-2009), 87 patients with Pa bacteremia were identified; 45 patients had multiple-drug resistant (MDR) strains and 42 susceptible strains. On comparison of the two populations, one with multiple-drug resistant strains and the other with the susceptible strains, the following parameters were found to be significantly different in the univariate analysis: age (32.7 vs 43.6 years; P = .013), sex (males: 91.1 vs 66.7%; P = .005), intubation status on admission (75.6 vs. 54.8%; P = .041), escharotomy (57.8 vs 33.3%; P = .022), burn size (51.0 vs 35.3% of TBSA; P = .002) and Abbreviated Burn Severity Index score (9.2 vs 8.1; P = .048). In terms of outcome parameters, multiple-drug resistance was not significantly related to mortality (adjusted odds ratio 1.076; 95% confidence interval [CI] 0.356-3.254; P = .897) and length of BICU stay after Pa bacteremia (Kaplan-Meier analysis log-rank test P = .945; Cox's proportional hazards regression hazards ratio, 0.994; 95% CI 0.513-1.925; P = .985) in the univariate and multivariate analyses. The data from this study suggest that multiple-drug resistance is not associated with significant increases in mortality and length of BICU stay among burn patients with Pa bacteremia.


Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Queimaduras/microbiologia , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/isolamento & purificação , Adulto , Bacteriemia/mortalidade , Unidades de Queimados , Queimaduras/mortalidade , Infecção Hospitalar/mortalidade , Farmacorresistência Bacteriana Múltipla , Feminino , Alemanha/epidemiologia , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Infecções por Pseudomonas/mortalidade , Estudos Retrospectivos , Resultado do Tratamento
3.
J Virol Methods ; 179(1): 8-16, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21704081

RESUMO

Japanese encephalitis virus (JEV) is a human pathogenic, mosquito-borne flavivirus that is endemic/epidemic in Asia. JEV is rarely detected or isolated from blood or cerebrospinal fluid (CSF), and detection of IgM is generally diagnostic of the infection. The flavivirus nonstructural glycoprotein NS1 is released transiently during flavivirus replication. The aim of this study was to set up a quantitative JEV NS1 antigen capture assay. A soluble hexameric form of JEV NS1 protein was produced in a stable Drosophila S2 cell clone and purified from supernatant fluids. Two IgG1 monoclonal antibodies (MAbs) with high affinity against two different epitopes of JEV NS1 antigen were used to develop an antigen-capture assay with a limit of detection of 0.2ngml(-1) NS1. Up to 1µgml(-1) JEV NS1 protein was released in supernatants of mammalian cells infected with JEV but <10ngml(-1) was released in sera of virus-infected mice before the onset of encephalitis and death. Moreover, NS1 protein was detected at low levels (<10ngml(-1)) in 23.8% of sera and in 10.5% of CSF of patients diagnosed as IgM-positive for JEV. This quantitative test of NS1 protein is proposed for highly specific diagnosis of acute infection with JEV genotypes I to IV.


Assuntos
Antígenos Virais/análise , Técnicas de Laboratório Clínico/métodos , Encefalite Japonesa/diagnóstico , Proteínas não Estruturais Virais/sangue , Proteínas não Estruturais Virais/líquido cefalorraquidiano , Virologia/métodos , Proteína Agouti Sinalizadora , Animais , Anticorpos Monoclonais , Anticorpos Antivirais , Análise Química do Sangue , Proteínas de Ligação ao Cálcio , Linhagem Celular , Líquido Cefalorraquidiano/química , Proteínas Quinases Dependentes de GMP Cíclico , Drosophila , Proteínas de Drosophila , Feminino , Infecções por Flavivirus , Proteínas de Ligação ao GTP , Humanos , Imunoensaio/métodos , Imunoglobulina G , Proteínas de Membrana , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H
4.
Bull Soc Pathol Exot ; 104(4): 313-20, 2011 Oct.
Artigo em Francês | MEDLINE | ID: mdl-21643648

RESUMO

Dengue has emerged in Vietnam 50 years ago and since has become endemo-epidemic throughout the whole country. Each year, major epidemics of dengue fever (DF) and dengue hemorrhagic fever (DHF) hit South Vietnam during the rainy season, causing significant morbidity and mortality, especially among young children. The only preventive measure is vector control, but it is often implemented too late or indiscriminately. The aim of this study was to investigate, in the pre-epidemic stage, the existence of significant changes in vector indices, which will predict DF/DHF outbreaks. We conducted a descriptive transversal study, repeated once a month for four months (March to June) in the village of Locthuan (province Ben Tre) in the Mekong's delta. Adult mosquitoes were caught in 30 houses, and larvae were collected in water holding containers of 50 houses. The houses were randomly selected. Vector densities were calculated according to the indices recommended by WHO. Virological analysis was carried out on lots of female Aedes and larvae in order to determine viral infection rates. Catches of adult mosquitoes collected 496 specimens including 329 Aedes, 139 Culex and 28 Anopheles. Aedes aegypti was present in 63% of visited homes that is an average density of 1.8 mosquitoes per house. The increase in imaginal indices during the 4 months was not significant. The survey of breeding sites of Ae. aegypti identified 1292 water containers in which 71,569 larval specimens were collected. The values of house index, container index [CI] and Breteau index [BI] increased each month, the latter from 166 to 442. This increase was significant for CI and BI. Breeding sites were mostly intra-home, mainly consisting of large and small ceramic jars. Larval density of Ae. aegypti in the containers also increased significantly over the 4 months. It was correlated with the lack of cover and predators such as Mesocyclops spp., Micronecta spp. and larvivorous fishes. Cultivation of 15 pools of 10 adult females and 29 pools of larvae (ie 1088 specimens) of Ae. aegypti failed to isolate dengue virus. The high Stegomyia indices measured in this South Vietnamese village and their increase before the rainy season reflect a situation at high risk of epidemics but cannot predict the occurrence of an outbreak in the absence of virus isolation from mosquitoes. They justify conducting an integrated vector control throughout the year.


Assuntos
Dengue/epidemiologia , Dengue/transmissão , Insetos Vetores , Controle de Mosquitos/métodos , Aedes/virologia , Animais , Culex/virologia , Dengue/prevenção & controle , Vírus da Dengue/isolamento & purificação , Feminino , Humanos , Larva/virologia , Densidade Demográfica , Chuva , Estações do Ano , Vietnã/epidemiologia
5.
Ann Plast Surg ; 66(4): 339-43, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21301290

RESUMO

Self-immolation constitutes a rare form of suicide in developed countries, though it accounts for unique injury characteristics in the burn intensive care unit. The aim of this study was to present the epidemiological and clinical features of patients burned during a suicidal attempt seen in a North Rhine-Westphalia burn intensive care unit (BICU). To address this aim, we undertook a 21-year retrospective study involving patients with thermal injuries admitted to the largest burn unit in Germany. A total of 125 suicide-related burn victims were identified in the study period (9.4%). Comparing the self-immolation group with the rest burn patient cohort, suicide victims were more likely to be single and to act under the influence of alcohol. The suicidal group had a larger extent of burns, higher incidence of inhalation injury, required more surgical procedures, catecholamines, blood transfusions, and a longer BICU stay. Their clinical course was complicated by prolonged intubation period, higher rate of multiple drug-resistant bacteria acquisition and sepsis, leading to a higher mortality rate. Although the proportion of self-immolation victims among all burned patients is not high, the markedly higher severity of their burns and their poorer quality of outcomes makes them an important clinical subgroup for further study.


Assuntos
Queimaduras/mortalidade , Queimaduras/terapia , Procedimentos de Cirurgia Plástica/estatística & dados numéricos , Comportamento Autodestrutivo/mortalidade , Comportamento Autodestrutivo/terapia , Lesão por Inalação de Fumaça/mortalidade , Adulto , Unidades de Queimados/estatística & dados numéricos , Feminino , Seguimentos , Alemanha/epidemiologia , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Motivação , Prevalência , Estudos Retrospectivos , Fatores de Risco , Suicídio/classificação , Adulto Jovem
6.
Bull Soc Pathol Exot ; 100(1): 43-7, 2007 Feb.
Artigo em Francês | MEDLINE | ID: mdl-17402695

RESUMO

The dengue shock syndrome (DSS) is primarily a complication of dengue haemorrhagic fever (DHF) among children in South East Asia. A case-control study was carried out at the children hospital no 1 (Ho-Chi-Minh City, Vietnam) in May-July 2005, to identify the predictive factors of the DSS among 1-15 year patients with DHE Forty consecutive admitted cases and forty controls were studied. The associated features of DSS were the 7-12 year age group and the re-infection by the dengue virus. The vaccination against the Japanese encephalitis B was not associated statistically significantly with the shock syndrome. The clinical predictors of DSS gathered an abdominal tenderness, an hepatomegaly, a lethargy, a cold extremity presentation. DSS associated laboratory features were a value of hematocrit a 50 % and a platelet cell count < or = 75,000/mm3.


Assuntos
Dengue Grave/epidemiologia , Dor Abdominal/etiologia , Adolescente , Fatores Etários , Estudos de Casos e Controles , Criança , Pré-Escolar , Progressão da Doença , Feminino , Hematócrito , Hepatomegalia/etiologia , Hospitais Urbanos/estatística & dados numéricos , Humanos , Imunocompetência , Lactente , Vacinas contra Encefalite Japonesa/imunologia , Masculino , Recidiva , Fatores de Risco , Dengue Grave/sangue , Dengue Grave/complicações , Dengue Grave/diagnóstico , População Urbana , Vacinação , Vietnã/epidemiologia
7.
J Cell Biol ; 153(2): 295-305, 2001 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-11309411

RESUMO

Oligodendrocyte-specific protein (OSP)/claudin-11 is a major component of central nervous system myelin and forms tight junctions (TJs) within myelin sheaths. TJs are essential for forming a paracellular barrier and have been implicated in the regulation of growth and differentiation via signal transduction pathways. We have identified an OSP/claudin-11-associated protein (OAP)1, using a yeast two-hybrid screen. OAP-1 is a novel member of the tetraspanin superfamily, and it is widely expressed in several cell types, including oligodendrocytes. OAP-1, OSP/claudin-11, and beta1 integrin form a complex as indicated by coimmunoprecipitation and confocal immunocytochemistry. Overexpression of OSP/claudin-11 or OAP-1 induced proliferation in an oligodendrocyte cell line. Anti-OAP-1, anti-OSP/claudin-11, and anti-beta1 integrin antibodies inhibited migration of primary oligodendrocytes, and migration was impaired in OSP/claudin-11-deficient primary oligodendrocytes. These data suggest a role for OSP/claudin-11, OAP-1, and beta1 integrin complex in regulating proliferation and migration of oligodendrocytes, a process essential for normal myelination and repair.


Assuntos
Divisão Celular/fisiologia , Movimento Celular/fisiologia , Integrina beta1/metabolismo , Proteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Oligodendroglia/metabolismo , Sequência de Aminoácidos , Animais , Anticorpos/imunologia , Anticorpos/metabolismo , Northern Blotting , Encéfalo/citologia , Encéfalo/metabolismo , Linhagem Celular , Claudinas , Fibronectinas/metabolismo , Hibridização In Situ , Substâncias Macromoleculares , Proteínas de Membrana/química , Proteínas de Membrana/genética , Camundongos , Camundongos Knockout , Microscopia de Fluorescência , Dados de Sequência Molecular , Proteínas do Tecido Nervoso/genética , Oligodendroglia/química , Oligodendroglia/citologia , Oligodendroglia/ultraestrutura , Alinhamento de Sequência , Tetraspaninas , Junções Íntimas/metabolismo , Técnicas do Sistema de Duplo-Híbrido
8.
Clin Neuropharmacol ; 24(1): 58-61, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11290883

RESUMO

The objective of the study was to investigate the effects of estrogen on severity and duration of myoclonus in the rat cardiac arrest model of posthypoxic myoclonus. Female sex hormones affect a variety of movement disorders and alter dopaminergic and serotonergic pharmacology. Although women represented three-fourths of patients from the original report of Lance and Adams and 80% of the largest published series, the impact of estrogens on myoclonus has never been studied. Twelve previously ovariectomized female rats underwent 8 minutes of mechanically induced cardiac arrest and were resuscitated according to a standardized protocol. On the same day, they were randomly assigned to subcutaneous treatment with a 21-day, 0.5-mg, 17 beta-estradiol or matching placebo pellet. Animals were tested daily with 7 sets of 45 auditory stimuli for 10 days, and myoclonus scores were obtained using a 5-point interval scale. Comparisons were based on two-sample Wilcoxon rank-sum tests. Estrogen treatment significantly enhanced myoclonus intensity and duration: mean peak myoclonus score, 210.2 +/- 18.0 versus 180 +/- 28.5 (p = 0.031); mean number of days above baseline, 9.2 +/- 0.4 versus 5.7 +/- 2.3 (p = 0.004); mean score on day 10, 90.7 +/- 38.7 versus 27.0 +/- 20.6 (p = 0.016). All estrogen-treated animals were above baseline on day 10 compared with none in the placebo group. Estrogen enhances and prolongs posthypoxic myoclonus, suggesting that female gender and estrogen status may play a pivotal role as a risk factor for human posthypoxic myoclonus.


Assuntos
Estrogênios/administração & dosagem , Hipóxia Encefálica/fisiopatologia , Mioclonia/fisiopatologia , Animais , Implantes de Medicamento , Estradiol/administração & dosagem , Estradiol/efeitos adversos , Estrogênios/efeitos adversos , Feminino , Parada Cardíaca/fisiopatologia , Ovariectomia , Ratos , Ratos Sprague-Dawley
9.
Bull World Health Organ ; 79(1): 15-21, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11217661

RESUMO

OBJECTIVE: A cross-sectional survey was conducted in three districts of Quang Ninh province, Viet Nam, to find out what proportion of the people who lived there engaged in behaviour that put them at risk of becoming infected with HIV, and to measure their knowledge about HIV infection and AIDS. METHODS: The survey was conducted in a rural district, Yen Hung; a mountainous district inhabited primarily by ethnic minority groups, Binh Lieu; and an urban district, Ha Long. Participants aged 15-45 years were randomly selected from the general population to be interviewed. FINDINGS: A total of 630 people from 707 households were interviewed; 8% were not home despite repeated visits and 3% refused to participate. The prevalence of premarital intercourse ranged from 9% to 16% among married men and 4% to 7% among married women. Among single men the proportion who had ever had intercourse ranged from 6% to 16%. Fewer than 3% reported having ever had sex with a sex worker. The median number of extramarital sex partners was 1. Knowledge about HIV/AIDS was high in the urban and rural areas but low in the mountainous area. Being male and being 20-29 years old were associated with having multiple sex partners. CONCLUSION: The low prevalence of individuals reporting that they had had intercourse with sex workers and partners other than their spouse may explain the low rates of HIV infection among the heterosexual population; these rates are in contrast to the high rates of HIV infection found among injecting drug users. The association between having extramarital partners and being a younger man suggests that the tendency to have more sexual partners may increase in the future. If this happens, the potential for HIV to be spread through heterosexual sex will increase.


Assuntos
Infecções por HIV/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Comportamento Sexual , Adolescente , Adulto , Estudos Transversais , Feminino , Infecções por HIV/epidemiologia , Humanos , Modelos Logísticos , Masculino , Grupos Minoritários/estatística & dados numéricos , Razão de Chances , População Rural/estatística & dados numéricos , População Urbana/estatística & dados numéricos , Vietnã/epidemiologia
11.
J Neural Transm (Vienna) ; 107(2): 159-76, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10847557

RESUMO

The D3 preferring dopamine agonist pramipexole has been shown to attenuate the cell loss induced by levodopa in vitro. Pramipexole was herein evaluated in the 6-hydroxydopamine lesion model to determine its in vivo effect. Rats were treated with pramipexole or saline before and after an intracerebroventricular 6-hydroxydopamine injection. In the preliminary study, 6-hydroxydopamine produced a 68% reduction in striatal dopamine and a 62% loss in tyrosine hydroxylase immunoreactive (THir) cell counts in the substantia nigra. Pramipexole treated animals exhibited a 29% and a 27% reduction in striatal dopamine and THir cell counts, respectively. THir cell counts and striatal dopamine were significantly correlated. In the stereological study, 6-hydroxydopamine reduced THir cell counts by 47% in saline treated animals and 26% in pramipexole treated animals. These data demonstrate that pramipexole attenuates the biochemical and THir cell changes normally produced by 6-hydroxydopamine consistent with its neuroprotective actions in vitro.


Assuntos
Morte Celular/efeitos dos fármacos , Agonistas de Dopamina/farmacologia , Dopamina/metabolismo , Degeneração Neural/tratamento farmacológico , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Tiazóis/farmacologia , Animais , Benzotiazóis , Contagem de Células , Morte Celular/fisiologia , Masculino , Neostriado/efeitos dos fármacos , Neostriado/metabolismo , Neostriado/fisiopatologia , Degeneração Neural/induzido quimicamente , Degeneração Neural/fisiopatologia , Neurônios/metabolismo , Neurônios/patologia , Oxidopamina , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/tratamento farmacológico , Transtornos Parkinsonianos/fisiopatologia , Pramipexol , Ratos , Ratos Sprague-Dawley , Substância Negra/efeitos dos fármacos , Substância Negra/patologia , Substância Negra/fisiopatologia
13.
Brain Res ; 856(1-2): 301-9, 2000 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-10677639

RESUMO

Our previous studies demonstrated that the survival of a mesencephalic graft was reduced in aged animals suggesting an age-related decline in target-derived neurotrophic activity. We tested this hypothesis by examining dopamine (DA) and trophic activities from the striatum of intact or unilateral 6-hydroxydopamine (6-OHDA) lesioned rats of increasing age. Fisher 344 rats were 4, 12, 18, and 23 months old (m.o.) at sacrifice. Half the animals had received unilateral 6-OHDA lesions of the mesostriatal DA pathway 8 weeks earlier. Striatal tissue punches were analyzed for DA, homovanillic acid (HVA), and DA activity (HVA/DA) using HPLC. The remainder of the striatal tissue was homogenized to generate tissue extracts which were added to E14.5 ventral mesencephalic cultures to test trophic activity. In the non-lesioned animals, striatal DA was reduced and striatal DA activity was increased in the 18 and 23 m.o. animals relative to the 4 and 12 m.o. animals. Striatal trophic activity was inversely related to age. In the lesioned animals, striatal DA ipsilateral to 6-OHDA infusion was below detection limits while the contralateral striatum exhibited age-related changes in DA similar to those seen in the non-lesioned animals. In 4 m.o. lesioned rats, striatal trophic activity ipsilateral to 6-OHDA infusion was elevated by 26% relative to the contralateral side. The ipsi/contra-lateral differences in striatal trophic activity were reduced in 12 m.o. animals and absent in the 18 and 23 m.o. groups. These data suggest that advancing age is associated with a reduction in striatal DA as well as trophic activity. Moreover, the aged striatum loses its ability to biochemically and trophically compensate for DA reduction and therefore may represent a more challenging environment for the survival, growth, and function of a fetal graft.


Assuntos
Envelhecimento/fisiologia , Encéfalo/fisiologia , Corpo Estriado/fisiologia , Dopamina/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/crescimento & desenvolvimento , Células Cultivadas , Cromatografia Líquida de Alta Pressão , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/crescimento & desenvolvimento , Embrião de Mamíferos , Lateralidade Funcional , Ácido Homovanílico/metabolismo , Mesencéfalo/fisiologia , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Oxidopamina/toxicidade , Ratos , Ratos Endogâmicos F344 , Extratos de Tecidos/farmacologia
14.
J Neurosci ; 20(4): 1414-23, 2000 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-10662832

RESUMO

The processing of signals by integrative neurons in the retina and CNS relies strongly on inhibitory synaptic inputs, principally from GABAergic and glycinergic neurons that serve primarily to hyperpolarize postsynaptic neurons. Recent evidence indicates that the neuron-specific K-Cl cotransporter 2 (KCC2) is the major chloride extrusion system permitting hyperpolarizing inhibitory responses. It has been hypothesized that depolarizing GABA responses observed in immature neurons are converted to hyperpolarizing responses in large part by the expression of KCC2 during the second week of postnatal development. The cell-specific localization and developmental expression of KCC2 protein have been examined in relatively few neural tissues and have never been studied in retina, of which much is known physiologically and morphologically about inhibitory synaptic circuits. We examined the localization of KCC2 in adult rat retina with immunohistochemical techniques and determined the time course of its postnatal expression. KCC2 expression was localized in horizontal cells, bipolar cells, amacrine cells, and, most likely, ganglion cells, all of which are known to express GABA receptor subtypes. Developmentally, KCC2 expression in the retina increased gradually from postnatal day 1 (P1) until P14 in the inner retina, whereas expression was delayed in the outer plexiform layer until P7 but reached its adult level by P14. These data support the hypothesis that the function of KCC2 is intimately involved in GABAergic synaptic processing. Furthermore, the delayed temporal expression of KCC2 in the outer plexiform layer indicates that GABAergic function may be differentially regulated in retina during postnatal development and that GABA may produce depolarizing responses in the outer plexiform layer at times when it generates hyperpolarizing responses in the inner plexiform layer.


Assuntos
Envelhecimento/metabolismo , Proteínas de Transporte/genética , Regulação da Expressão Gênica no Desenvolvimento , Retina/metabolismo , Simportadores , Animais , Animais Recém-Nascidos , Proteínas de Transporte/análise , Cloretos/metabolismo , Imuno-Histoquímica , Neurônios/citologia , Neurônios/metabolismo , Potássio/metabolismo , Ratos , Ratos Long-Evans , Receptores de GABA/análise , Receptores de Glicina/análise , Retina/citologia , Retina/crescimento & desenvolvimento , Cotransportadores de K e Cl-
15.
Brain Res Dev Brain Res ; 118(1-2): 231-5, 1999 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-10611525

RESUMO

Glial cell line-derived neurotrophic factor (GDNF) is a glycosylated, disulfide-bonded homodimer, and a member of the transforming growth factor-beta superfamily. GDNF has been shown to promote the survival and morphological differentiation of dopamine (DA) neurons and increase their high-affinity dopamine uptake. In order to determine whether the mechanism for our previously observed cocaine-induced DA reductions in brain and carotid body were GDNF-mediated, we exposed Sprague-Dawley rat fetuses to cocaine via maternal subcutaneous injections (30 mg/kg b.i.d., E7-E19). Brains and carotid bodies of fetuses were excised and processed for assessment of GDNF levels using an Enzyme-Linked ImmunoadSorbent Assay (ELISA). ANOVA indicated that cocaine reduced carotid body GDNF by 36% (F((1,5))=28. 11, p<0.05) and striatal GDNF by 41% (F((1,5))=41.77, p<0.01). Although there was no interaction between drug exposure and fetal uterine position, post-hoc pairwise comparisons indicated that reductions in GDNF in the cocaine groups were due to differences at more distal positions (positions 4-8). The magnitude of the reductions in striatal GDNF (but not carotid body GDNF) in both cocaine-exposed and control fetuses followed a cervical (smallest GDNF reductions) to ovarian (greatest GDNF reductions) uterine position gradient. This pattern was similar to that which we observed in prior studies examining DA reductions in brain following prenatal cocaine exposure. The finding that cocaine reduces GDNF levels in striatum and carotid body support the hypothesis that cocaine's ability to reduce striatal and carotid body DA may be indirect through its ability to reduce GDNF. These data along with previous findings support the hypothesis that cocaine's effects on DA neurons are at least partially due to its indirect effects on trophic activity. The possible mechanisms whereby cocaine affects trophic activity are discussed.


Assuntos
Corpo Carotídeo/embriologia , Cocaína/farmacologia , Corpo Estriado/embriologia , Inibidores da Captação de Dopamina/farmacologia , Dopamina/metabolismo , Fatores de Crescimento Neural , Proteínas do Tecido Nervoso/antagonistas & inibidores , Animais , Encéfalo/embriologia , Desenvolvimento Embrionário e Fetal/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Feminino , Feto/efeitos dos fármacos , Feto/metabolismo , Feto/fisiologia , Fator Neurotrófico Derivado de Linhagem de Célula Glial , Gravidez , Ratos , Ratos Sprague-Dawley
16.
Neurology ; 52(1): 16-21, 1999 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-9921842

RESUMO

OBJECTIVE: To study specific serotonin (5-hydroxytryptamine [5-HT]) receptor subtype antagonists in an animal model of posthypoxic myoclonus. BACKGROUND: Although serotonergic system dysfunction is implicated in posthypoxic myoclonus, anatomic specificity and linkage to receptor subtypes are not delineated. METHODS: The authors performed a pharmacologic study to identify specific serotonin receptor subtype antagonists effective in inhibiting myoclonus in posthypoxic rats. Sprague-Dawley rats underwent cardiac arrest for 8 minutes and were resuscitated. On the day of pharmacologic testing, animals were rated every 10 minutes at -30 minutes to time 0 (drug injection) and from +60 to +150 minutes. Using a blinded methodology, animals were injected with normal saline, vehicle, or one of seven serotonin antagonists given at a dose that maintains serotonin receptor subtype specificity: WAY100135 (5-HT1A), methiothepin mesylate (5-HT1B/1D/2), mesulergine hydrochloride (5-HT2A/2B), GR 127935 (5-HT1D), SR 46349 (5-HT2), ondansetron (5-HT3), or GR 125487 (5-HT4). Drugs that produced a significant decrease in myoclonus compared with the control were studied in a dose-response study with six doses across a range from the original dose studied to 10% of that dose. RESULTS: Two drugs were significantly different from placebo: methiothepin mesylate and mesulergine hydrochloride. GR 127935 showed a trend toward reducing myoclonus. Dose-response studies showed that all doses of methiothepin mesylate and the three highest doses of mesulergine hydrochloride inhibited myoclonus effectively. CONCLUSIONS: 5-HT1B, 5-HT2A/2B, and possibly 5-HT1D receptor subtypes likely play a role in posthypoxic myoclonus. More specific 5-HT antagonists that affect these receptor subtypes are candidates for future testing in this model and in Lance-Adams syndrome.


Assuntos
Hipóxia Encefálica/complicações , Hipóxia/complicações , Mioclonia/tratamento farmacológico , Mioclonia/etiologia , Antagonistas da Serotonina/farmacologia , Estimulação Acústica , Animais , Química Encefálica/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Ergolinas/farmacologia , Parada Cardíaca/complicações , Masculino , Metiotepina/farmacologia , Oxidiazóis/farmacologia , Piperazinas/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores de Serotonina/fisiologia
17.
J Physiol ; 505 ( Pt 1): 193-204, 1997 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-9409482

RESUMO

1. We examined signal, noise and response properties of salamander rod photoreceptors by measuring: (a) the circulating current of rods which were adapted to darkness and to a wide range of backgrounds; (b) contrasts of natural environments; (c) the effect of adaptation on the linear response range of rods; and (d) the behaviour of rods responding to dynamically modulated stimuli having a range of contrasts found in nature. 2. In the dark, the circulating current contained two noise components analogous to those described in toad. A discrete noise component consisted of events occurring at a rate of 1 event per 32 s (21 degrees C) and had a variance of 0.036 pA2. A continuous noise component contributed 0.022 pA2 to the dark current, roughly equal to the discrete noise variance. 3. Exposure to a wide range of steady backgrounds (suppressing up to 80% of the circulating current), elicited a sustained fluctuating photocurrent having a power spectrum which resembled those of single photon responses and was consistent with the linear summation of single photon events; this indicates that the primary source of noise in the current is caused by the light. 4. Eighty-nine per cent of the contrasts (C) measured in natural environments had magnitude of C < 50%, where C = magnitude of I - Imean/magnitude of Imean. The linear response range elicited by brief flashes expanded with brighter backgrounds, well-encompassing flash contrasts of 100%. 5. Dynamically modulated stimuli and incremental flashes having contrasts similar to those in natural scenes elicited small currents which deviated by a few picoamps about the mean and the transfer functions computed from each type of stimulus-response pair closely corresponded to one another. These results indicate that in natural environments, rods behave as linear small-signal transducers of light.


Assuntos
Adaptação Ocular/fisiologia , Adaptação à Escuridão/fisiologia , Células Fotorreceptoras Retinianas Bastonetes/fisiologia , Visão Ocular/fisiologia , Ambystoma , Animais , Eletrofisiologia , Luz , Fótons
18.
Brain Res ; 759(1): 1-8, 1997 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-9219856

RESUMO

The neuroprotective effects of (R)-HA-966 and (S)-HA-966 (3-amino-1-hydroxy-2-pyrrolidinone) were examined in an MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced animal model of Parkinson's disease. Systemic pretreatment of C57 black mice with the strychnine-insensitive glycine site antagonist, (R)-HA-966 (3-30 mg/kg, i.p.), dose-dependently attenuated MPTP-induced depletion of striatal dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC). Pretreatment with (R)-HA-966 also significantly protected the degeneration of tyrosine hydroxylase-positive neurons in the substantia nigra of mice treated with MPTP and alleviated the acute behavioral changes caused by the neurotoxin. In contrast, the other racemic form, (S)-HA-966, neither prevented the neurochemical depletions nor the neuronal injury caused by MPTP. These results indicate that excitatory mechanisms of neurodegeneration are involved in the pathophysiology of Parkinson's disease, and that strychnine-insensitive glycine site NMDA antagonists may serve as dopaminoprotective agents which intervene in the progressive neurodegeneration in Parkinson's disease.


Assuntos
Agonistas de Aminoácidos Excitatórios/uso terapêutico , N-Metilaspartato/antagonistas & inibidores , Fármacos Neuroprotetores/uso terapêutico , Doença de Parkinson Secundária/tratamento farmacológico , Pirrolidinonas/uso terapêutico , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Dopamina/metabolismo , Dopaminérgicos/farmacologia , Resistência a Medicamentos , Glicinérgicos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Neurônios/patologia , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/psicologia , Estereoisomerismo , Estricnina/farmacologia
19.
Cancer Lett ; 104(2): 183-92, 1996 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-8665486

RESUMO

The cyclin dependent kinase inhibitors p16 and p18 were investigated in neuroblastoma. Only one of 19 neuroblastoma cell lines, an adriamycin-resistant variant, and none of 5 primary neuroblastoma, was deleted for p16 while its parental drug sensitive cell line is p16 intact. The region of deletion minimally extended centromeric to include p15, and telomeric to interferon-beta. This is the first report of a p16 gene alteration in neuroblastoma. No p16 gene hypermethylation or mutations were found. No homozygous deletions of p18 in these samples were found, although several instances of loss of heterozygosity are suspected. No p18 point mutations were detected. We conclude that (1) neither p16 nor p18 are likely involved in the pathogenesis of neuroblastoma; and (2) the role of p16, or another 9p21 gene, in the development of drug resistance warrants further investigation.


Assuntos
Proteínas de Transporte/genética , Proteínas de Ciclo Celular , Inibidores Enzimáticos , Genes Supressores de Tumor , Neuroblastoma/genética , Inibidores de Proteínas Quinases , Proteínas Supressoras de Tumor , Sequência de Bases , Deleção Cromossômica , Mapeamento Cromossômico , Cromossomos Humanos Par 9 , Inibidor p16 de Quinase Dependente de Ciclina , Inibidor de Quinase Dependente de Ciclina p18 , Humanos , Dados de Sequência Molecular , Células Tumorais Cultivadas
20.
Eur J Pharmacol ; 297(3): 219-24, 1996 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-8666053

RESUMO

The antimyoclonic property of the novel antiepileptic drug, gabapentin (1-(aminomethyl) cyclohexane acetic acid), was tested in cardiac arrest-and p,p'-DDT(1,1,1-trichloro-2,2-bis (p-chlorophenyl)ethane)-induced animal models of myoclonus. Gabapentin dose-dependently attenuated myoclonus in posthypoxic rats for more than 3 h. The drug was also found to be effective in controlling the early stages of seizures following the anoxic insult. In contrast, the drug was ineffective in controlling either myoclonus or seizures in p,p'-DDT-treated animals. These results suggest that gabapentin can be used used as an effective therapeutic agent in an acute hypoxia/ischemia-induced neurological disorder. The data further indicate that distinct neurological mechanisms may be operating in the expression of myoclonus among posthypoxic and p,p'-DDT-induced animal models.


Assuntos
Acetatos/farmacologia , Aminas , Anticonvulsivantes/farmacologia , Ácidos Cicloexanocarboxílicos , Mioclonia/prevenção & controle , Ácido gama-Aminobutírico , Estimulação Acústica , Animais , DDT/toxicidade , Modelos Animais de Doenças , Gabapentina , Hipóxia , Masculino , Mioclonia/induzido quimicamente , Ratos , Ratos Sprague-Dawley , Convulsões/induzido quimicamente , Convulsões/prevenção & controle
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