Over the last decade,remarkable developments in nanotechnology have powered medical research,unveiling new approaches for the solution of public health issues such as the treatment of traumatic peripheral neuropathies.
M ultiple sclerosis is a chro nic central nervous system demyelinating disease whose onset and progression are driven by a combination of immune dysregulation,genetic predisposition,and environmental fa ctors.The acti...M ultiple sclerosis is a chro nic central nervous system demyelinating disease whose onset and progression are driven by a combination of immune dysregulation,genetic predisposition,and environmental fa ctors.The activation of microglia and astrocytes is a key player in multiple sclerosis immunopathology,playing specific roles associated with anatomical location and phase of the disease and controlling demyelination and neurodegeneration.Even though reactive mic roglia can damage tissue and heighten deleterious effects and neurodegeneration,activated microglia also perform neuroprotective functions such as debris phagocytosis and growth fa ctor secretion.Astrocytes can be activated into pro-inflammato ry phenotype A1 through a mechanism mediated by activated neuroinflammatory microglia,which could also mediate neurodegeneration.This A1 phenotype inhibits oligodendrocyte prolife ration and differe ntiation and is toxic to both oligodendrocytes and neurons.Howeve r,astroglial activation into phenotype A2 may also take place in response to neurodegeneration and as a protective mechanism.A variety of animal models mimicking specific multiple sclerosis features and the associated pathophysiological processes have helped establish the cascades of events that lead to the initiation,progression,and resolution of the disease.The colonystimulating facto r-1 receptor is expressed by myeloid lineage cells such as peripheral monocytes and macrophages and central nervous system microglia.Importantly,as microglia development and survival critically rely on colony-stimulating factor-1 receptor signaling,colony-stimulating factor-1 receptor inhibition can almost completely eliminate microglia from the brain.In this context,the present review discusses the impact of microglial depletion through colo ny-stimulating factor-1 receptor inhibition on demyelination,neurodegeneration,astroglial activation,and behavior in different multiple sclerosis models,highlighting the diversity of microglial effects on the progression of demyelinating diseases and the strengths and weaknesses of microglial modulation in therapy design.展开更多
Given the relevance of vitamin D in calcium metabolism homeostatic control, as well as its role as differentiation and cell proliferation modulator, it is important to study its circulating level in patients considere...Given the relevance of vitamin D in calcium metabolism homeostatic control, as well as its role as differentiation and cell proliferation modulator, it is important to study its circulating level in patients considered at risk, in order to develop prevention strategies. We studied 77 postmenopausal women with no history of osteoactive drug therapy, corticosteroid intake or diseases that could alter bone metabolism, attending the Menopause Center at the Hospital Provincial del Centenario, Rosario, Argentina. A medical history was taken, and a food consumption frequency questionnaire was applied in order to estimate daily calcium intake. To assess daily physical exercise, work and sports activities were investigated. Serum parathyroid hormone (PTH) and 25(OH)D were measured, and a hip DXA scan was performed in every patient. An inappropriate level of 25(OH)D was observed in 86.3% of patients. The 25(OH)D average value was found within the insufficiency range (<30 ng/ml) whereas PTH average concentration fell within the normal range, and bone mineral density average value was found within the osteopenic category. A statistically significant negative logarithmic association was observed between serum PTH level and vitamin D status (p = 0.01). Mean 25(OH)D concentration among patients who had reported fractures was significantly lower than the corresponding to women who had not suffered this type of event. Patients with vitamin D deficiency had significantly wider mean Cobb angle;higher sum of wedge angles of T4 - T12 vertebral bodies mean values, and higher uncompromised vertebrae wedge angle values than non-deficient women. This study shows high hypovitaminosis D occurrence among these postmenopausal women.展开更多
文摘Over the last decade,remarkable developments in nanotechnology have powered medical research,unveiling new approaches for the solution of public health issues such as the treatment of traumatic peripheral neuropathies.
文摘M ultiple sclerosis is a chro nic central nervous system demyelinating disease whose onset and progression are driven by a combination of immune dysregulation,genetic predisposition,and environmental fa ctors.The activation of microglia and astrocytes is a key player in multiple sclerosis immunopathology,playing specific roles associated with anatomical location and phase of the disease and controlling demyelination and neurodegeneration.Even though reactive mic roglia can damage tissue and heighten deleterious effects and neurodegeneration,activated microglia also perform neuroprotective functions such as debris phagocytosis and growth fa ctor secretion.Astrocytes can be activated into pro-inflammato ry phenotype A1 through a mechanism mediated by activated neuroinflammatory microglia,which could also mediate neurodegeneration.This A1 phenotype inhibits oligodendrocyte prolife ration and differe ntiation and is toxic to both oligodendrocytes and neurons.Howeve r,astroglial activation into phenotype A2 may also take place in response to neurodegeneration and as a protective mechanism.A variety of animal models mimicking specific multiple sclerosis features and the associated pathophysiological processes have helped establish the cascades of events that lead to the initiation,progression,and resolution of the disease.The colonystimulating facto r-1 receptor is expressed by myeloid lineage cells such as peripheral monocytes and macrophages and central nervous system microglia.Importantly,as microglia development and survival critically rely on colony-stimulating factor-1 receptor signaling,colony-stimulating factor-1 receptor inhibition can almost completely eliminate microglia from the brain.In this context,the present review discusses the impact of microglial depletion through colo ny-stimulating factor-1 receptor inhibition on demyelination,neurodegeneration,astroglial activation,and behavior in different multiple sclerosis models,highlighting the diversity of microglial effects on the progression of demyelinating diseases and the strengths and weaknesses of microglial modulation in therapy design.
文摘Given the relevance of vitamin D in calcium metabolism homeostatic control, as well as its role as differentiation and cell proliferation modulator, it is important to study its circulating level in patients considered at risk, in order to develop prevention strategies. We studied 77 postmenopausal women with no history of osteoactive drug therapy, corticosteroid intake or diseases that could alter bone metabolism, attending the Menopause Center at the Hospital Provincial del Centenario, Rosario, Argentina. A medical history was taken, and a food consumption frequency questionnaire was applied in order to estimate daily calcium intake. To assess daily physical exercise, work and sports activities were investigated. Serum parathyroid hormone (PTH) and 25(OH)D were measured, and a hip DXA scan was performed in every patient. An inappropriate level of 25(OH)D was observed in 86.3% of patients. The 25(OH)D average value was found within the insufficiency range (<30 ng/ml) whereas PTH average concentration fell within the normal range, and bone mineral density average value was found within the osteopenic category. A statistically significant negative logarithmic association was observed between serum PTH level and vitamin D status (p = 0.01). Mean 25(OH)D concentration among patients who had reported fractures was significantly lower than the corresponding to women who had not suffered this type of event. Patients with vitamin D deficiency had significantly wider mean Cobb angle;higher sum of wedge angles of T4 - T12 vertebral bodies mean values, and higher uncompromised vertebrae wedge angle values than non-deficient women. This study shows high hypovitaminosis D occurrence among these postmenopausal women.
基金funded by the Agencia Estatal de Investigación(AEI)and Fondo Europeo de Desarrollo Regional(FEDER)(BIO2016-76063-R,AEI/FEDER,UE),AGAUR(2017SGR229)CIBER-BBN(project VENOM4CANCER)granted to Villaverde A,ISCIII(PI15/00272 co-founding FEDER)+2 种基金supported by predoctoral fellowship from AGAUR(2018FI_B2_00051)supported by a predoctoral fellowship from the Government of Navarrasupported by PERIS program from the health department of la Generalitat de Catalua