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1.
Neuroscience ; 259: 214-22, 2014 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-24316470

RESUMO

Neuronal loss is the most common and critical feature of a spectrum of brain traumas and neurodegenerative disorders such as Alzheimer's disease (AD). The capacity to generate new neurons in the central nervous system diminishes early during brain development and is restricted mainly to two brain areas in the mature brain: subventricular zone and subgranular zone. Extensive research on the impact of brain injury on endogenous neurogenesis and cognition has been conducted primarily using young animals, when neurogenesis is most active. However, a critical question remains to elucidate the effect of brain injury on endogenous neurogenesis and cognition in older animals, which is far more relevant for age-related neurodegenerative disorders such as AD. Therefore, we examined the impact of neuronal loss on endogenous neurogenesis in aged animals using CaM/Tet-DTA mice, a transgenic model of hippocampal cell loss. Additionally, we investigated whether the upregulation of adult neurogenesis could mitigate cognitive deficits following substantial hippocampal neuronal loss. Our findings demonstrate that aged CaM/Tet-DTA mice that sustain severe neuronal loss exhibit an upregulation of endogenous neurogenesis. However, despite this significant upregulation, neurogenesis alone is not able to mitigate the cognitive deficits observed. Our studies suggest that the aged brain has the capacity to stimulate neurogenesis post-injury; however, multiple therapeutic approaches, including upregulation of endogenous neurogenesis, will be necessary to recover brain function after severe neurodegeneration.


Assuntos
Envelhecimento , Transtornos Cognitivos/etiologia , Hipocampo/lesões , Hipocampo/patologia , Neurogênese/fisiologia , Neurônios/fisiologia , Técnicas de Ablação , Animais , Astrócitos/metabolismo , Proteína Quinase Tipo 1 Dependente de Cálcio-Calmodulina/genética , Contagem de Células , Toxina Diftérica/genética , Proteína 4 Homóloga a Disks-Large , Proteína Duplacortina , Regulação da Expressão Gênica/fisiologia , Guanilato Quinases/metabolismo , Aprendizagem em Labirinto/fisiologia , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Transgênicos , Fragmentos de Peptídeos/genética , Fosfopiruvato Hidratase/metabolismo , Subunidade beta da Proteína Ligante de Cálcio S100/metabolismo , Sinaptofisina/metabolismo
2.
Food Addit Contam ; 20(12): 1105-13, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14726273

RESUMO

About 400 food samples, mainly Asian foods available in Hong Kong, were tested for acrylamide by an LC-MS/MS method using [1, 2, 3-(13)C(3)]-acrylamide as surrogate. The acrylamide levels in the more commonly consumed food items in the food groups such as rice and rice products, noodles, bakery and batter-based products, were generally less than 60 microg kg(-1). Higher levels were found in the food groups such as biscuit-related products and crisps. The highest levels were detected in potato crisps (1500-1700 microg kg(-1)). Lower levels were found in rye flour-based crisps (440 microg kg(-1)), followed by corn-based (65 to 230 microg kg(-1)) and wheat flour-based crisps (61-200 microg kg(-1)), and then rice flour-based crisps (15-42 microg kg(-1)). The acrylamide formation during deep frying of a wheat flour-based product, Chinese fried fritter, was studied. Deep-frying at 170 degrees C resulted in gentle but steady rise in acrylamide content. A steep rise for frying at 210 degrees C was recorded. The moisture content of the product decreased with frying time, but the fat content increased. It is proposed that the reaction for the formation of acrylamide was initiated on the surface and then penetrated into the interior of the food matrix by heat transfer via radiation/conduction and diffusion of hot oil.


Assuntos
Acrilamida/análise , Contaminação de Alimentos/análise , Mutagênicos/análise , Acrilamida/metabolismo , Culinária , Hong Kong , Humanos , Mutagênicos/metabolismo , Temperatura
6.
Lancet ; 337(8745): 816-8, 1991 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-1672914

RESUMO

A non-invasive exercise method was used to look for myocardial damage in apparently normal children who had received moderate doses of anthracyclines for treatment of cancer. 19 children (mean [SD] age 10.6 [4.3] years) who had received anthracyclines (mean total dose 230 [119] mg/m2) and 10 who had received other cytotoxic drugs (mean age 13.3 [4.9] years) were selected from 263 children attending routine follow-up examinations. They underwent measurement of heart rate, blood pressure, and left ventricular dimensions by echocardiography before and after exercise on a bicycle for a maximum of 10 min. All 29 were in remission. All the subjects showed normal fractional shortening (FS = left ventricular end-diastolic minus end-systolic diameter as a percentage of the end-diastolic diameter) at rest, but the increase in FS on exercise was significantly lower in the children who had received anthracyclines than in those who had not (3 [16]% vs 23 [17]%; p less than 0.05). This difference remained significant after adjustment for age and drug exposure. However, there were no significant differences between the groups in the adjusted mean percentage changes on exercise in heart rate or systolic or diastolic blood pressure. Disease type had no effect on the cardiological indices. Thus, many children who have received anthracyclines may have suffered subclinical myocardial damage. Post-exercise echocardiography seems a useful non-invasive method for detecting such damage. Long-term cardiological follow-up of these patients is needed.


Assuntos
Daunorrubicina/efeitos adversos , Contração Miocárdica/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Função Ventricular/efeitos dos fármacos , Adolescente , Pressão Sanguínea/efeitos dos fármacos , Criança , Pré-Escolar , Daunorrubicina/administração & dosagem , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Esquema de Medicação , Quimioterapia Combinada , Teste de Esforço , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Neoplasias/fisiopatologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/fisiopatologia
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