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1.
Medimay ; 26(1)ene. 2018. tab
Artigo em Espanhol | CUMED | ID: cum-74705

RESUMO

Introducción: la evaluación de impacto se asocia con potenciales de efectos positivos o negativos en una investigación. El uso de indicadores permite la obtención de evidencias cualitativas y cuantitativas sobre determinantes de salud para evitar posibles resultados adversos, sobre todo si las intervenciones están dirigidas a modificar factores de riesgos en adultos mayores, a partir de la aplicación de programas o proyectos. Objetivo: determinar los indicadores para evaluación de impacto en intervenciones de promoción de salud con adultos mayores en la atención primaria. Métodos: se realizó un estudio de enfoque bimodal. Se utilizó el método de análisis documental y técnica de triangulación de la información. Fueron revisados los fundamentos de promoción de salud de referencia nacional e internacional y se sistematizaron ideas expresadas en documentos legales y políticas públicas cubanas. Se tuvo en cuenta el criterio de 15 expertos a partir de una selección entre 20 candidatos. El método Delphi conllevó a secuencia de acciones en tres rondas, entre abril y noviembre de 2017, en San José de las Lajas, Mayabeque. Resultados: se seleccionaron 15 expertos con alto coeficiente de competencia. Los profesionales llegaron al consenso de 15 indicadores científicos, 19 sociales y 10 económicos. Se estableció el porciento que debían alcanzar los indicadores para evaluar el impacto como positivo. Conclusiones: los indicadores establecidos contribuyen al desarrollo de instrumentos para evaluación de impacto en intervenciones de promoción de salud con adultos mayores en la atención primaria, asegurando solidez metodológica y calidad de resultados en este tipo de investigaciones gerontológicas(AU)


Introduction: the evaluation of impact is associated to different potentials with positive or negative properties in one investigation. By means of the use of indicators, the investigators can obtain the qualitative and quantitative evidences to avoid possible adverse reactions, after all if the interventions are guided to modify risk factors in elderly adults since the application of programs and projects. Objective: to determine the indicators for the impact evaluation in promotional interventions of the elders' primary health care. Methods: a study of bimodal approach was performed. Documental analysis and triangulation technique of information were used. The promotional basics of health about national and international reference came under review and ideas came under a system expressed in legal documents and Cubans' political publics. Opinions by 15 experts, starting from a selection among 20 candidates were taken into account. The Delphi method was applied in three sequences from April to November, 2017, in San José de las Lajas, Mayabeque. Results: they selected 15 experts with high competitive coefficient. The professionals agreed with 15 scientific indicators, 19 social and 10 economic ones.The percentage that the indicators should have reached to evaluate the impact as positivewas established. Conclusions: the establishments of indicators for the impact evaluation in promotional interventions of the elders' primary health care contribute with the development of instruments assuring methodological solidity and quality of results in this gerontological investigation(AU)


Assuntos
Humanos , Masculino , Feminino , Idoso , Geriatria , Envelhecimento , Atenção Primária à Saúde , Avaliação do Impacto na Saúde/métodos , Promoção da Saúde
3.
Pharmacol Res ; 110: 205-215, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27013280

RESUMO

Cannabinoids have emerged as promising neuroprotective agents due to their capability to activate specific targets, which are involved in the control of neuronal homeostasis and survival. Specifically, those ligands that selectively target and activate the CB2 receptor may be useful for their anti-inflammatory and neuroprotective properties in various neurological disorders, with the advantage of being devoid of psychotropic effects associated with the activation of CB1 receptors. The aim of this work has been to investigate the neuroprotective properties of 7-(1,1-dimethylheptyl)-4,4-dimethyl-9-methoxychromeno[3,4-d]isoxazole (PM226), a compound derived from a series of chromeno-isoxazoles and -pyrazoles, which seems to have a promising profile related to the CB2 receptor. The compound binds selectively to this receptor with an affinity in the nanomolar range (Ki=12.8±2.4nM). It has negligible affinity for the CB1 receptor (Ki>40000nM) and no activity at the GPR55. PM226 was also evaluated in GTPγS binding assays specific to the CB2 receptor showing agonist activity (EC50=38.67±6.70nM). In silico analysis of PM226 indicated that it has a good pharmacokinetic profile and a predicted ability to cross the blood-brain barrier. Next, PM226 was investigated in an in vitro model to explore its anti-inflammatory/neuroprotective properties. Conditioned media were collected from LPS-stimulated cultures of BV2 microglial cell line in the absence or presence of different doses of PM226, and then media were added to cultured M213-2O neuronal cells to record their influence on cell viability evaluated using MTT assays. As expected, cell viability was significantly reduced by the exposure to these conditioned media, while the addition of PM226 attenuated this reduction in a dose-dependent manner. This effect was reversed by co-incubating with the CB2 antagonist SR144528, thus confirming the involvement of CB2 receptors, whereas the addition of PM226 to neuronal cultures instead cultured BV2 cells was not effective. PM226 has also been studied in an in vivo model of mitochondrial damage generated by intrastriatal application of malonate in rats. MRI analysis showed that PM226 administration decreased the volume of the striatal lesion caused by malonate, effect that was confirmed after the histopathological evaluation (Nissl staining, Iba-1 immunostaining and TUNEL assay) of striatal sections derived from malonate-lesioned rats in the absence or presence of PM226. Again, the beneficial effects of PM226 were dependent on the activation of CB2 receptors as they were reversed by blocking these receptors with AM630. Overall, PM226 has shown to have a promising neuroprotective profile derived from its ability to selectively activate CB2 receptor, so that it could be a useful disease-modifying agent in those neurodegenerative pathologies in which the activation of these receptors may have therapeutic value.


Assuntos
Lesões Encefálicas/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Agonistas de Receptores de Canabinoides/farmacologia , Isoxazóis/farmacologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Receptor CB2 de Canabinoide/agonistas , Animais , Sítios de Ligação , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Lesões Encefálicas/metabolismo , Lesões Encefálicas/patologia , Agonistas de Receptores de Canabinoides/síntese química , Agonistas de Receptores de Canabinoides/metabolismo , Agonistas de Receptores de Canabinoides/farmacocinética , Linhagem Celular , Modelos Animais de Doenças , Humanos , Isoxazóis/síntese química , Isoxazóis/metabolismo , Isoxazóis/farmacocinética , Masculino , Malonatos , Camundongos , Modelos Biológicos , Degeneração Neural , Neurônios/metabolismo , Neurônios/patologia , Fármacos Neuroprotetores/síntese química , Fármacos Neuroprotetores/metabolismo , Fármacos Neuroprotetores/farmacocinética , Permeabilidade , Ligação Proteica , Ratos Wistar , Receptor CB2 de Canabinoide/química , Receptor CB2 de Canabinoide/genética , Receptor CB2 de Canabinoide/metabolismo , Transfecção
4.
Cell Death Differ ; 22(3): 433-44, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25257175

RESUMO

Over recent years, accumulated evidence suggests that autophagy induction is protective in animal models of a number of neurodegenerative diseases. Intense research in the field has elucidated different pathways through which autophagy can be upregulated and it is important to establish how modulation of these pathways impacts upon disease progression in vivo and therefore which, if any, may have further therapeutic relevance. In addition, it is important to understand how alterations in these target pathways may affect normal physiology when constitutively modulated over a long time period, as would be required for treatment of neurodegenerative diseases. Here we evaluate the potential protective effect of downregulation of calpains. We demonstrate, in Drosophila, that calpain knockdown protects against the aggregation and toxicity of proteins, like mutant huntingtin, in an autophagy-dependent fashion. Furthermore, we demonstrate that, overexpression of the calpain inhibitor, calpastatin, increases autophagosome levels and is protective in a mouse model of Huntington's disease, improving motor signs and delaying the onset of tremors. Importantly, long-term inhibition of calpains did not result in any overt deleterious phenotypes in mice. Thus, calpain inhibition, or activation of autophagy pathways downstream of calpains, may be suitable therapeutic targets for diseases like Huntington's disease.


Assuntos
Autofagia/efeitos dos fármacos , Calpaína/antagonistas & inibidores , Doença de Huntington/metabolismo , Doença de Huntington/patologia , Peptídeos/metabolismo , Animais , Proteínas de Ligação ao Cálcio/biossíntese , Calpaína/genética , Calpaína/metabolismo , Modelos Animais de Doenças , Drosophila , Proteínas de Drosophila/antagonistas & inibidores , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Feminino , Técnicas de Silenciamento de Genes , Doença de Huntington/enzimologia , Doença de Huntington/terapia , Endogamia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais
5.
CNS Neurol Disord Drug Targets ; 12(5): 665-79, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23469842

RESUMO

Hipericum perforatum is a well-known herbal for its antidepressant property. Recently, it has been shown to have nootropic effects against neurodegenerative disorders. The aim of the present study was to evaluate the protective role of chronic administration of two standardized extract of Hypericum perforatum SHP1 rich in hyperforin (6%) and SHP2 extract poor in hyperforin (0.2%) on the neurodegeneration induced by chronic administration of rotenone in rats. Quercetin in liposomes, one active constituent, was tested in the same experimental conditions. The animals received pretreatments with SHP1 (4 mg/Kg, ip), SHP2 (4 mg/Kg, ip) or quercetin liposomes (25 and 100 mg/kg, ip) 60 min before of rotenone injection (2.5 mg/kg) for 45 days. Pretreatment of the animals with SHP1 and SHP2 efficiently halted deleterious toxic effects of rotenone, revealing normalization of catalepsy in addition to amelioration of neurochemical parameters. Also, SHP1 reduced neuronal damage, diminishing substantia nigra dopaminergic cell death caused by the pesticide, indicating benefit of neuroprotective therapy. In general, the SHP1 was more active than SHP2. In addition, SHP1 inhibited the apoptotic cascade by decreasing Bax levels. The results presented here indicate that mainly hyperforin and quercetin, may be involved in the neuroprotective action of Hypericum standardized extracts. Combination of dietary antioxidants could provide better therapeutic advantage for the management of Parkinson, and possibly other neurodegenerative disorders. Therefore H. perforatum standardized extract enriched in hyperforin, could be a better alternative for depressed elderly patients with degenerative disorders exhibiting elevated oxidative stress status.


Assuntos
Hypericum/química , Fármacos Neuroprotetores/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Fitoterapia/métodos , Quercetina/uso terapêutico , Análise de Variância , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Catalepsia/tratamento farmacológico , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Corpo Estriado/patologia , Modelos Animais de Doenças , Dopamina/metabolismo , Relação Dose-Resposta a Droga , Fluordesoxiglucose F18 , Inseticidas/toxicidade , Lipossomos/uso terapêutico , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/patologia , Doença de Parkinson/etiologia , Doença de Parkinson/patologia , Doença de Parkinson/fisiopatologia , Tomografia por Emissão de Pósitrons , Ratos , Ratos Wistar , Rotenona/toxicidade , Natação
6.
Med. prev ; 17(3): 21-28, jul.-sept. 2011. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-110256

RESUMO

Objetivo: Queremos conocer de modo general la cartera de servicios, el rendimiento y la organización de la consulta en los servicios de Medicina Preventiva (CMP) en la Comunidad Valenciana en el periodo referido al año 2008. Material y métodos: Se utiliza una encuesta realizada en 23 hospitales de la Comunidad Valenciana (CV). Diseñamos un cuestionario específico telefónico dirigido a informadores clave, estructurado en 4 bloques de información y 8 áreas de actividad de la CMP. Resultados: Los médicos y enfermeras dedicaron, respectivamente, el 32,8% y el 34,1% de su tiempo a la CMP. Las vacunaciones de grupos de riesgo y las vacunaciones al viajero (97,5%) fueron las actividades más realizadas. Se contabilizaron un total de 49.440 CMP (primeras y sucesivas) en 2008 en la CV. Conclusiones: Los datos sugieren que la CMP es una actividad consolidada, creciente en número y claramente orientada a mejorar el rendimiento de otras consultas y a colaborar en programas prioritarios para la Salud Pública (AU)


Objetive: Aim of this study was to know portfolio of services, output results and organization of specific-consultations of Hospitalary Preventive Medicine services in Spain (PMC). Methods: We use a opinion poll, performed in 2008 between 23 Valencian-Community hospitals. We design a questionary that was pointed to key informers and that was divided into 4 information sections and 8 activity areas. Results: Physicians and nurses devoted, respectively, 32.8% and 34.1% of his time to PMC. Risk-groups vaccinations (97.5%) and traveller vaccinations (97.5%) were the more frequent done activities. We estimated a overall 49.440 consultations (first and successive ones) in 2008 in Valencian Community. Conclusions: Data suggest that PMC is a consolidated activity, increasing to time and clearly pointed to improve output results and to collaborate in prioritary public health programs (AU)


Assuntos
Humanos , Serviços Preventivos de Saúde/estatística & dados numéricos , Prevenção de Doenças , Visita a Consultório Médico/estatística & dados numéricos , 24419 , Atenção à Saúde/estatística & dados numéricos
7.
Br J Pharmacol ; 163(7): 1495-506, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21323909

RESUMO

BACKGROUND AND PURPOSE: Previous findings have indicated that a cannabinoid, such as Δ(9)-THCV, which has antioxidant properties and the ability to activate CB(2) receptors but to block CB(1) , might be a promising therapy for alleviating symptoms and delaying neurodegeneration in Parkinson's disease (PD). EXPERIMENTAL APPROACH: The ability of Δ(9)-THCV to reduce motor inhibition and provide neuroprotection was investigated in rats lesioned with 6-hydroxydopamine and in mice lesioned with lipopolysaccharide (LPS). KEY RESULTS: Acute administration of Δ(9)-THCV attenuated the motor inhibition caused by 6-hydroxydopamine, presumably through changes in glutamatergic transmission. Moreover, chronic administration of Δ(9)-THCV attenuated the loss of tyrosine hydroxylase-positive neurones caused by 6-hydroxydopamine in the substantia nigra, through an effect related to its antioxidant properties (it was reproduced by cannabidiol -enriched botanical extract). In addition, CB(2) receptor-deficient mice responded to 6-hydroxydopamine in a similar manner to wild-type animals, and CB(2) receptors were poorly up-regulated in the rat substantia nigra in response to 6-hydroxydopamine. By contrast, the substantia nigra of mice that had been injected with LPS exhibited a greater up-regulation of CB(2) receptors. In these animals, Δ(9)-THCV also caused preservation of tyrosine hydroxylase-positive neurones. This effect probably involved CB(2) receptors as it was also elicited by the selective CB(2) receptor agonist, HU-308, and CB(2) receptor-deficient mice were more vulnerable to LPS lesions. CONCLUSIONS AND IMPLICATIONS Given its antioxidant properties and its ability to activate CB(2) but to block CB(1) receptors, Δ(9)-THCV has a promising pharmacological profile for delaying disease progression in PD and also for ameliorating parkinsonian symptoms.


Assuntos
Dronabinol/farmacologia , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/tratamento farmacológico , Receptor CB1 de Canabinoide/antagonistas & inibidores , Receptor CB1 de Canabinoide/metabolismo , Receptor CB2 de Canabinoide/metabolismo , Animais , Antioxidantes/farmacologia , Canabinoides/farmacologia , Cicloexanóis/farmacologia , Modelos Animais de Doenças , Dopamina/metabolismo , Ácido Glutâmico/metabolismo , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Oxidopamina/farmacologia , Doença de Parkinson/metabolismo , Ratos , Ratos Sprague-Dawley , Receptor CB2 de Canabinoide/agonistas , Receptor CB2 de Canabinoide/deficiência , Substância Negra/efeitos dos fármacos , Substância Negra/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo
8.
Chemosphere ; 56(11): 1157-67, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15276729

RESUMO

An experimental study on the formation and transport of ozone in ambient air was performed in Tenerife (Canary Islands) in order to investigate the processes affecting ozone levels and air quality. The special features of Tenerife (prevalence of the trade wind pattern (NE), orography and the specific location of the local ozone sources) permit to quantify the role of the 'long-range transport from northern latitudes' versus the 'formation and transport of ozone downwind of the main urban areas' of Tenerife. Levels of O(3), NO(2) and O(X) were monitored in different types of environments to achieve this purpose. The results showed that: (1) upwind of the urban areas ozone is mainly transported from the ocean by trade winds, (2) local ozone titration (by NO) and ozone replenishment from the ocean are the main causes of ozone variations in urban and suburban areas, and (3) photochemical ozone production occurs downwind of the urban areas. Photochemical production causes daylight O(3) and O(X) levels downwind of urban areas to be frequently (60% and 35% days/year, respectively) higher than upwind of the urban sites (O(3) and O(X) excess frequently in the range 5-20 ppbv). Due to the above processes, different daily ozone cycles occur in short distances (<30 km), with maximum O(3) levels during daylight or night depending on the site. Ozone phytotoxicity was assessed by calculating the AOT40 index upwind and downwind of the main urban areas. The critical value for the 5-day-AOT40 index was simultaneously exceeded at the two sites (few times/year) during long-range transport events. During the additional exceedances of the critical value downwind of the urban area, relatively high 5-day-AOT40 values were recorded upwind of the urban site. Thus, long-range transport from northern latitudes may produce relatively high 5-days-AOT40 levels in the oceanic boundary layer. These results are important for the protection of the large number of endemic plants in the Canaries. The conceptual model discussed in this study may be qualitatively applied to other islands which possess features similar to those of Tenerife.


Assuntos
Poluentes Atmosféricos/análise , Modelos Teóricos , Oxidantes Fotoquímicos/análise , Ozônio/análise , Movimentos do Ar , Geografia , Fotoquímica , Plantas , Espanha
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