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1.
Int J Exp Pathol ; 98(3): 147-157, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28849621

RESUMEN

The aim of this study was to better understand the role of apoptosis in a retinal ischaemia-reperfusion injury model and to determine whether sildenafil citrate treatment can prevent retinal cell apoptosis. Thirty-six rats were divided into a control group (n = 6) and two experimentally induced ischaemia-reperfusion groups (7 and 21 days; n = 15 per group). The induced ischaemia-reperfusion groups were treated with sildenafil for 7 and 21 days (n = 10 per group), and 10 animals were treated with a placebo for the same period (n = 5 per group). Paracentesis of the anterior chamber was performed with a 30-G needle attached to a saline solution (0.9%) bag positioned at a height of 150 cm above the eye for 60 min. Intraocular pressure was measured by rebound tonometer (TonoVet® ). The eyes were analysed by histology and morphometry, and by immunohistochemistry and qRT-PCR for expression of Caspase-7, Caspase-6, Caspase-9, Tnf-r2, Fas-l, Bcl-2 and Bax. Sildenafil-treated animals showed lower levels of histopathological changes (inflammatory, cellular and tissue) than their placebo-treated counterparts at both 7 and 21 days. The retinal ganglion cell layer (RGC) was preserved in the sildenafil groups (SG), with a cell count closer to control than in the placebo groups (PG). Caspase-7 expression was significantly higher in both treated groups at 7 days compared to controls. Gene expression levels in both treatment groups differed from the controls, but in SG Bax and Caspase-6 expression levels were similar to control animals. These results suggest that the main mechanism of retinal cell death in this model is apoptosis, as there is an increase in pro-apoptotic factors and decrease in the anti-apoptotic ones. Also, sildenafil seems to protect the retinal ganglion cell layer from apoptosis. Cell survival was evident in the histological and morphometric analyses, and sildenafil treatment had a protective effect in the apoptosis pathways, with gene expression levels in SG similar to the controls.


Asunto(s)
Daño por Reperfusión/prevención & control , Enfermedades de la Retina/prevención & control , Vasos Retinianos/patología , Citrato de Sildenafil/uso terapéutico , Vasodilatadores/uso terapéutico , Animales , Apoptosis/efectos de los fármacos , Evaluación Preclínica de Medicamentos/métodos , Proteínas del Ojo/biosíntesis , Proteínas del Ojo/genética , Regulación de la Expresión Génica/efectos de los fármacos , Presión Intraocular/efectos de los fármacos , Masculino , Nervio Óptico/efectos de los fármacos , Nervio Óptico/patología , Ratas Endogámicas Lew , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Daño por Reperfusión/fisiopatología , Enfermedades de la Retina/metabolismo , Enfermedades de la Retina/patología , Enfermedades de la Retina/fisiopatología , Células Ganglionares de la Retina/efectos de los fármacos , Células Ganglionares de la Retina/patología
2.
Clinics (Sao Paulo) ; 63(3): 375-80, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18568249

RESUMEN

OBJECTIVES: The pharmacological effects of methylprednisolone (MP) and ganglioside GM-1 on spinal injuries have been thoroughly investigated, but only a few studies have evaluated the interaction between these two drugs. METHODS: Twenty-four Wistar rats were subjected to contusive injury of the spinal cord produced by the NYU system. These animals were divided into four groups: group I was injected with MP; group II was injected with GM-1; group III was injected with MP together with GM-1; and group control received physiological serum. The animals were evaluated with regard to their recovery of locomotive function by means of the BBB test on the second, seventh and fourteenth days after receiving the contusive injury to the spinal cord. They were sacrificed on the fourteenth day. RESULTS: This study demonstrated that the MP and GM-1 groups presented functional results that were better than those of the control group, although the enhanced recovery of group II (GM-1) relative to the control group was not statistically significant (p>0.05). The most notable recovery of locomotive function was observed in the group that received MP alone (p<0.05). The group that received MP together with GM-1 presented results that were better than those of the control group (p<0.05). CONCLUSION: Administration of methylprednisolone alone or with GM-1 was shown to be effective for recovery of locomotive function. Combined administration of these drugs resulted in better outcomes than administration of methylprednisolone alone.


Asunto(s)
Antiinflamatorios/uso terapéutico , Gangliósido G(M1)/uso terapéutico , Metilprednisolona/uso terapéutico , Actividad Motora/efectos de los fármacos , Traumatismos de la Médula Espinal/tratamiento farmacológico , Animales , Antiinflamatorios/farmacología , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Quimioterapia Combinada , Gangliósido G(M1)/farmacología , Masculino , Metilprednisolona/farmacología , Ratas , Ratas Wistar , Recuperación de la Función/efectos de los fármacos , Estadísticas no Paramétricas , Resultado del Tratamiento
3.
Clinics ; 63(3): 375-380, 2008. ilus, graf, tab
Artículo en Inglés | LILACS | ID: lil-484764

RESUMEN

OBJECTIVES: The pharmacological effects of methylprednisolone (MP) and ganglioside GM-1 on spinal injuries have been thoroughly investigated, but only a few studies have evaluated the interaction between these two drugs. METHODS: Twenty-four Wistar rats were subjected to contusive injury of the spinal cord produced by the NYU system. These animals were divided into four groups: group I was injected with MP; group II was injected with GM-1; group III was injected with MP together with GM-1; and group control received physiological serum. The animals were evaluated with regard to their recovery of locomotive function by means of the BBB test on the second, seventh and fourteenth days after receiving the contusive injury to the spinal cord. They were sacrificed on the fourteenth day. RESULTS: This study demonstrated that the MP and GM-1 groups presented functional results that were better than those of the control group, although the enhanced recovery of group II (GM-1) relative to the control group was not statistically significant (p>0.05). The most notable recovery of locomotive function was observed in the group that received MP alone (p<0.05). The group that received MP together with GM-1 presented results that were better than those of the control group (p<0.05). CONCLUSION: Administration of methylprednisolone alone or with GM-1 was shown to be effective for recovery of locomotive function. Combined administration of these drugs resulted in better outcomes than administration of methylprednisolone alone.


Asunto(s)
Animales , Masculino , Ratas , Antiinflamatorios/uso terapéutico , Gangliósido G(M1)/uso terapéutico , Metilprednisolona/uso terapéutico , Actividad Motora/efectos de los fármacos , Traumatismos de la Médula Espinal/tratamiento farmacológico , Antiinflamatorios/farmacología , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Quimioterapia Combinada , Gangliósido G(M1)/farmacología , Metilprednisolona/farmacología , Ratas Wistar , Recuperación de la Función/efectos de los fármacos , Estadísticas no Paramétricas , Resultado del Tratamiento
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