Erythropoietin （Epo） is a fundamental hormone in the regulation of hematopoiesis, and other secondary roles mediated by the binding of the hormone to its specific receptor （EpoR）, which leads to an activation of k...Erythropoietin （Epo） is a fundamental hormone in the regulation of hematopoiesis, and other secondary roles mediated by the binding of the hormone to its specific receptor （EpoR）, which leads to an activation of key signaling pathways that induce an increase in cell differentiation, apoptosis control and neuroprotection. It has been suggested that their ftmction depends on final conformation of glycosylations, related with affinity to the receptor and its half-life. The presence of EpoR has been reported in different tissues including central nervous system, where it has been demonstrated to exert a neuroprotective function against oxidative stress conditions, such as ischemic injury and neurodegenerative diseases. There is also evidence of an increase in EpoR expression in brain cell lysates of Alzheimer＇s patients with respect to healthy patients. These results are related with extensive in vitro experimental data of neuroprotection obtained from cell lines, primary cell cultures and hippocampal slices. Additionally, this data is correlated with in vivo experiments （water maze test） in mouse models of Alzheimer＇s disease where Epo treatment improved cognitive function. These stud- ies support the idea that receptor activation induces a neuroprotective effect in neurodegenerative disorders including dementias, and especially Alzheimer＇s disease. Taken together, available evidence suggests that Epo appears to be a central element for EpoR activation and neuroprotective properties in the central nervous system. In this review, we will describe the mechanisms associated with neuroprotection and its relation with the activation of EpoR in order with identify new targets to develop pharmacological strategies.展开更多
The study was carried out in healthy Chilean volunteers in order to compare the pharmacokinetics （rate and extent absorption） of two commercial oral formulations of 50 mg hydrochlorothiazide. Thirty nine subjects we...The study was carried out in healthy Chilean volunteers in order to compare the pharmacokinetics （rate and extent absorption） of two commercial oral formulations of 50 mg hydrochlorothiazide. Thirty nine subjects were administered hydrochlorothiazide tablets of test （T） and reference （R） formulation in a single blind, randomized, fasting, 2 × 2 crossover study, seven washout days. Blood samples were taken during a 48 h period after drug administration. Plasma concentrations were quantified by HPLC-MS/MS. The primary parameters log-transformed Cmax （maximum plasma concentration）, A UC0-t and A UC0-∞ （area under the plasma concentration-time curve from zero to the last time and zero to infinity） were tested for bioequivalence considering the ratios of geometric means （test/reference）; whereas tmax （the time of maximum plasma concentration） was analyzed nonparametrically. The 90% confidence intervals for the geometric mean values of test/reference ratios for Cmax, A UCo.t and A UC0-∞ were 95.37%, 93.59% and 96.34%, respectively, and were located within the bioequivalence acceptance range of 80-125%, as were tmax and elimination constants. Together, we conclude that the test formulation of the hydrochlorothiazide 50 mg tablet is bioequivalent to the reference product and suitable for generic prescription.展开更多
基金supported by the Innova Proyect,No.13IDL218688Fondecyt Proyect,No.1130747,1161078PhD CONICYT Grant,No.21130386
文摘Erythropoietin （Epo） is a fundamental hormone in the regulation of hematopoiesis, and other secondary roles mediated by the binding of the hormone to its specific receptor （EpoR）, which leads to an activation of key signaling pathways that induce an increase in cell differentiation, apoptosis control and neuroprotection. It has been suggested that their ftmction depends on final conformation of glycosylations, related with affinity to the receptor and its half-life. The presence of EpoR has been reported in different tissues including central nervous system, where it has been demonstrated to exert a neuroprotective function against oxidative stress conditions, such as ischemic injury and neurodegenerative diseases. There is also evidence of an increase in EpoR expression in brain cell lysates of Alzheimer＇s patients with respect to healthy patients. These results are related with extensive in vitro experimental data of neuroprotection obtained from cell lines, primary cell cultures and hippocampal slices. Additionally, this data is correlated with in vivo experiments （water maze test） in mouse models of Alzheimer＇s disease where Epo treatment improved cognitive function. These stud- ies support the idea that receptor activation induces a neuroprotective effect in neurodegenerative disorders including dementias, and especially Alzheimer＇s disease. Taken together, available evidence suggests that Epo appears to be a central element for EpoR activation and neuroprotective properties in the central nervous system. In this review, we will describe the mechanisms associated with neuroprotection and its relation with the activation of EpoR in order with identify new targets to develop pharmacological strategies.
文摘The study was carried out in healthy Chilean volunteers in order to compare the pharmacokinetics （rate and extent absorption） of two commercial oral formulations of 50 mg hydrochlorothiazide. Thirty nine subjects were administered hydrochlorothiazide tablets of test （T） and reference （R） formulation in a single blind, randomized, fasting, 2 × 2 crossover study, seven washout days. Blood samples were taken during a 48 h period after drug administration. Plasma concentrations were quantified by HPLC-MS/MS. The primary parameters log-transformed Cmax （maximum plasma concentration）, A UC0-t and A UC0-∞ （area under the plasma concentration-time curve from zero to the last time and zero to infinity） were tested for bioequivalence considering the ratios of geometric means （test/reference）; whereas tmax （the time of maximum plasma concentration） was analyzed nonparametrically. The 90% confidence intervals for the geometric mean values of test/reference ratios for Cmax, A UCo.t and A UC0-∞ were 95.37%, 93.59% and 96.34%, respectively, and were located within the bioequivalence acceptance range of 80-125%, as were tmax and elimination constants. Together, we conclude that the test formulation of the hydrochlorothiazide 50 mg tablet is bioequivalent to the reference product and suitable for generic prescription.
