RESUMEN
Hypovitaminosis D has been identified as a possible new cardiovascular risk factor. However, the results of studies correlating serum vitamin D levels with markers of subclinical atherosclerosis have been conflicting. The aim of this study was to correlate serum levels of 25-hydroxyvitamin D [25(OH)D] with carotid intima-media thickness (C-IMT) and conventional cardiovascular risk factors in Afro-descendants. A cross-sectional analysis was performed on a sample of 382 individuals from a cohort of descendants of African slaves, inhabitants of "Quilombola" communities, with a mean age of 57.79 ±15.3 years, 54.5% of whom were women. Socio-demographic and clinical data were collected and biochemical tests were performed, including serum levels of 25(OH)D by electrochemiluminescence and urinary albumin excretion, evaluated by the albumin/creatinine ratio (ACR) in a spot urine sample. All participants underwent high-resolution ultrasonography for C-IMT measurement. Hypovitaminosis D was defined as serum 25(OH)D levels <30 ng/mL. The mean serum 25(OH)D levels were 50.4±13.5 ng/mL, with a low prevalence of hypovitaminosis D (4.86%). By simple linear correlation, a significant inverse association between 25(OH)D levels and C-IMT (r=-0.174, P=0.001) was observed. However, after multiple linear regression analysis, the significance of the association between serum levels of 25(OH)D and C-IMT measurement was lost (ß=-0.039, P=0.318) and only male gender, age, smoking, systolic blood pressure, glucose and low density lipoprotein (LDL)-cholesterol remained significantly associated with C-IMT. Levels of 25(OH)D were independently and positively associated with HDL-cholesterol and inversely associated with age and ACR. In conclusion, no independent association between 25(OH)D levels and C-IMT was observed in this population. On the other hand, there was an inverse association with albuminuria, a marker of endothelial lesion.
Asunto(s)
Aterosclerosis/sangre , Población Negra , Grosor Intima-Media Carotídeo , Deficiencia de Vitamina D/epidemiología , Vitamina D/análogos & derivados , Adolescente , Adulto , Anciano , Albuminuria , Aterosclerosis/etiología , Presión Sanguínea , Brasil/epidemiología , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Factores Socioeconómicos , Vitamina D/sangre , Adulto JovenRESUMEN
Hypovitaminosis D has been identified as a possible new cardiovascular risk factor. However, the results of studies correlating serum vitamin D levels with markers of subclinical atherosclerosis have been conflicting. The aim of this study was to correlate serum levels of 25-hydroxyvitamin D [25(OH)D] with carotid intima-media thickness (C-IMT) and conventional cardiovascular risk factors in Afro-descendants. A cross-sectional analysis was performed on a sample of 382 individuals from a cohort of descendants of African slaves, inhabitants of "Quilombola" communities, with a mean age of 57.79 ±15.3 years, 54.5% of whom were women. Socio-demographic and clinical data were collected and biochemical tests were performed, including serum levels of 25(OH)D by electrochemiluminescence and urinary albumin excretion, evaluated by the albumin/creatinine ratio (ACR) in a spot urine sample. All participants underwent high-resolution ultrasonography for C-IMT measurement. Hypovitaminosis D was defined as serum 25(OH)D levels <30 ng/mL. The mean serum 25(OH)D levels were 50.4±13.5 ng/mL, with a low prevalence of hypovitaminosis D (4.86%). By simple linear correlation, a significant inverse association between 25(OH)D levels and C-IMT (r=-0.174, P=0.001) was observed. However, after multiple linear regression analysis, the significance of the association between serum levels of 25(OH)D and C-IMT measurement was lost (β=-0.039, P=0.318) and only male gender, age, smoking, systolic blood pressure, glucose and low density lipoprotein (LDL)-cholesterol remained significantly associated with C-IMT. Levels of 25(OH)D were independently and positively associated with HDL-cholesterol and inversely associated with age and ACR. In conclusion, no independent association between 25(OH)D levels and C-IMT was observed in this population. On the other hand, there was an inverse association with albuminuria, a marker of endothelial lesion.
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Anciano , Adulto Joven , Población Negra , Aterosclerosis/sangre , Grosor Intima-Media Carotídeo , Deficiencia de Vitamina D/epidemiología , Vitamina D/análogos & derivados , Albuminuria , Aterosclerosis/etiología , Presión Sanguínea , Brasil/epidemiología , Estudios Transversales , Factores de Riesgo , Factores Socioeconómicos , Vitamina D/sangreAsunto(s)
Dopamina/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/antagonistas & inhibidores , Neuronas/enzimología , Neuronas/trasplante , Enfermedad de Parkinson/enzimología , Enfermedad de Parkinson/patología , Animales , Antracenos/farmacología , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Supervivencia de Injerto/efectos de los fármacos , Mesencéfalo/citología , Mesencéfalo/efectos de los fármacos , Neuronas/citología , Neuronas/efectos de los fármacos , Ratas , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
Persephin (PSP) is a neurotrophic factor of the GDNF family that has been found to promote the survival of multiple populations of neurons. In the present study we have examined: (1) the mechanism of action and the function of PSP on nigrostriatal dopamine neurons and (2) the therapeutic potential of PSP, delivered by neural stem cells (NSCs) in a model of Parkinson's disease. Interestingly we found that the prenatal ventral mesencephalon and the newborn striatum express high levels of PSP mRNA. Moreover, midbrain dopamine neurons express its preferred receptor GFRalpha4, allowing a cis type of action of PSP on dopamine neurons. Primary culture studies showed that PSP is as potent and efficacious as GDNF at promoting both survival and neuritogenesis of midbrain dopamine neurons. To study the function and therapeutic potential of PSP in vivo we engineered NSCs to overexpress PSP. PSP-c17.2 cells were found to stably express PSP mRNA and protein for at least 3 months in vivo, to disperse within the striatum, and to give rise to neurons, astrocytes, and a large proportion of oligodendrocytes that integrated within white matter tracts in the striatum. Moreover, PSP-c17.2 cells enhanced dopamine-dependent behavioral parameters in unlesioned mice and prevented the loss of dopamine neurons and the behavioral impairment of mice receiving intrastriatal 6-OHDA injections. Thus, our findings are consistent with a direct action of PSP on developing and adult midbrain dopamine neurons and suggest that the delivery of PSP by NSCs may constitute a very useful strategy in the treatment of Parkinson's disease.