RESUMEN
OBJECTIVES: To evaluate the effects of combined treatment with granulocyte colony-stimulating factor (G-CSF) and methylprednisolone in rats subjected to experimental spinal cord injury. METHODS: Forty Wistar rats received a moderate spinal cord injury and were divided into four groups: control (no treatment); G-CSF (G-CSF at the time of injury and daily over the next five days); methylprednisolone (methylprednisolone for 24 h); and G-CSF/Methylprednisolone (methylprednisolone for 24 h and G-CSF at the time of injury and daily over the next five days). Functional evaluation was performed using the Basso, Beattie and Bresnahan score on days 2, 7, 14, 21, 28, 35 and 42 following injury. Motor-evoked potentials were evaluated. Histological examination of the spinal cord lesion was performed immediately after euthanasia on day 42. RESULTS: Eight animals were excluded (2 from each group) due to infection, a normal Basso, Beattie and Bresnahan score at their first evaluation, or autophagy, and 32 were evaluated. The combination of methylprednisolone and G-CSF promoted greater functional improvement than methylprednisolone or G-CSF alone (p<0.001). This combination also exhibited a synergistic effect, with improvements in hyperemia and cellular infiltration at the injury site (p<0.001). The groups displayed no neurophysiological differences (latency p=0.85; amplitude p=0.75). CONCLUSION: Methylprednisolone plus G-CSF promotes functional and histological improvements superior to those achieved by either of these drugs alone when treating spinal cord contusion injuries in rats. Combining the two drugs did have a synergistic effect.
Asunto(s)
Factor Estimulante de Colonias de Granulocitos/farmacocinética , Metilprednisolona/farmacocinética , Fármacos Neuroprotectores/farmacocinética , Traumatismos de la Médula Espinal/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Combinación de Medicamentos , Masculino , Distribución Aleatoria , Ratas Wistar , Recuperación de la Función/efectos de los fármacos , Valores de Referencia , Reproducibilidad de los Resultados , Traumatismos de la Médula Espinal/patología , Traumatismos de la Médula Espinal/rehabilitación , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVES: To evaluate the effects of combined treatment with granulocyte colony-stimulating factor (G-CSF) and methylprednisolone in rats subjected to experimental spinal cord injury. METHODS: Forty Wistar rats received a moderate spinal cord injury and were divided into four groups: control (no treatment); G-CSF (G-CSF at the time of injury and daily over the next five days); methylprednisolone (methylprednisolone for 24 h); and G-CSF/Methylprednisolone (methylprednisolone for 24 h and G-CSF at the time of injury and daily over the next five days). Functional evaluation was performed using the Basso, Beattie and Bresnahan score on days 2, 7, 14, 21, 28, 35 and 42 following injury. Motor-evoked potentials were evaluated. Histological examination of the spinal cord lesion was performed immediately after euthanasia on day 42. RESULTS: Eight animals were excluded (2 from each group) due to infection, a normal Basso, Beattie and Bresnahan score at their first evaluation, or autophagy, and 32 were evaluated. The combination of methylprednisolone and G-CSF promoted greater functional improvement than methylprednisolone or G-CSF alone (p<0.001). This combination also exhibited a synergistic effect, with improvements in hyperemia and cellular infiltration at the injury site (p<0.001). The groups displayed no neurophysiological differences (latency p=0.85; amplitude p=0.75). CONCLUSION: Methylprednisolone plus G-CSF promotes functional and histological improvements superior to those achieved by either of these drugs alone when treating spinal cord contusion injuries in rats. Combining the two drugs did have a synergistic effect.
Asunto(s)
Animales , Masculino , Traumatismos de la Médula Espinal/tratamiento farmacológico , Metilprednisolona/farmacocinética , Factor Estimulante de Colonias de Granulocitos/farmacocinética , Fármacos Neuroprotectores/farmacocinética , Valores de Referencia , Traumatismos de la Médula Espinal/patología , Traumatismos de la Médula Espinal/rehabilitación , Factores de Tiempo , Distribución Aleatoria , Reproducibilidad de los Resultados , Resultado del Tratamiento , Ratas Wistar , Recuperación de la Función/efectos de los fármacos , Modelos Animales de Enfermedad , Combinación de MedicamentosRESUMEN
In this work, microparticles were prepared by spray-drying using albumin, chondroitin sulfate, and hyaluronic acid as excipients to create a controlled-release methylprednisolone system for use in inflammatory disorders such as arthritis. Scanning electron microscopy demonstrated that these microparticles were almost spherical, with development of surface wrinkling as the methylprednisolone load in the formulation was increased. The methylprednisolone load also had a direct influence on the mean diameter and zeta potential of the microparticles. Interactions between formulation excipients and the active drug were evaluated by x-ray diffraction, differential scanning calorimetry, and thermal gravimetric analysis, showing limited amounts of methylprednisolone in a crystalline state in the loaded microparticles. The encapsulation efficiency of methylprednisolone was approximately 89% in all formulations. The rate of methylprednisolone release from the microparticles depended on the initial drug load in the formulation. In vitro cytotoxic evaluation using THP-1 cells showed that none of the formulations prepared triggered an inflammatory response on release of interleukin-1ß, nor did they affect cellular viability, except for the 9.1% methylprednisolone formulation, which was the maximum test concentration used. The microparticles developed in this study have characteristics amenable to a therapeutic role in inflammatory pathology, such as arthritis.
Asunto(s)
Química Farmacéutica/métodos , Desecación/métodos , Portadores de Fármacos/química , Metilprednisolona/química , Línea Celular , Membrana Celular/efectos de los fármacos , Membrana Celular/patología , Supervivencia Celular/efectos de los fármacos , Sulfatos de Condroitina/química , Portadores de Fármacos/toxicidad , Humanos , Ácido Hialurónico/química , Interleucina-1beta/análisis , Metilprednisolona/farmacocinética , Tamaño de la Partícula , Difracción de Rayos XRESUMEN
Oral corticosteroids are as effective as intravenous therapy for treating acute exacerbations of asthma. They are available in tablets that can be crushed and mixed with soft food or syrup, and in a variety of liquid formulations that differ in volume required, palatability, patient acceptance, and cost. The most important consideration in product selection for a young child is that the doses can be easily swallowed and retained.
Asunto(s)
Antiinflamatorios/administración & dosificación , Asma/tratamiento farmacológico , Dexametasona/administración & dosificación , Metilprednisolona/administración & dosificación , Prednisolona/administración & dosificación , Prednisona/administración & dosificación , Enfermedad Aguda , Administración Oral , Antiinflamatorios/farmacocinética , Asma/prevención & control , Disponibilidad Biológica , Niño , Dexametasona/farmacocinética , Glucocorticoides/administración & dosificación , Humanos , Metilprednisolona/farmacocinética , Prednisolona/farmacocinética , Prednisona/farmacocinética , Ensayos Clínicos Controlados Aleatorios como Asunto , GustoRESUMEN
The target cellular response to glucocorticoids is proportional to the concentration or affinity of specific receptors to these substances. To look for a correlation between glucocorticoid receptors concentrations in synovial wall cells and the clinical response to steroidal treatment in patients with rheumatoid arthritis. Twenty eight patients with rheumatoid arthritis were studied. Each subject was subjected to a synovial biopsy in which a dry radioautographic technique for diffusable compounds was used. Patients were treated afterwards with 3 500mg iv pulses of methilprednisolone. A mean of 44.8 percent of synovial cells (range 30.1-62.8 percent) had binding sites for 3H dexamethasone. All patients had a significant clinical improvement after methilprednisolone. Multiple regression analysis did not show a correlation between clinical response and glucocorticoid receptor concentration. The lack of association between glucocorticoid receptor concentration and clinical response could be due to the large steroid dose used, that saturated all available receptors
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Artritis Reumatoide/tratamiento farmacológico , Glucocorticoides/farmacocinética , Antiinflamatorios/farmacocinética , Membrana Sinovial/efectos de los fármacos , Membrana Sinovial/patología , Metilprednisolona/farmacocinéticaRESUMEN
Rapid glucocorticoid clearance and abnormal glucocorticoid receptor binding have been described as factors that contribute to an inadequate response to treatment with glucocorticoids in patients with asthma. We report the coexistence of these abnormalities in children with severe asthma who respond poorly to systemic glucocorticoid therapy.
Asunto(s)
Asma/tratamiento farmacológico , Metilprednisolona/farmacocinética , Prednisolona/farmacocinética , Receptores de Glucocorticoides , Adolescente , Asma/metabolismo , Niño , Femenino , Humanos , Masculino , Tasa de Depuración Metabólica , Metilprednisolona/uso terapéutico , Prednisolona/uso terapéuticoRESUMEN
Deflazacort (DFC) is a heterocyclic glucocorticoid with anti-inflammatory activity but with decreased side effects. In this study, we have evaluated the capacity of DFC and other glucocorticoids to reach the central nervous system (CNS) in vivo by measuring changes of [3H]dexamethasone (DEX) binding to glucocorticoid receptors (GR) in vitro. GR occupation was effected by DEX in the cerebral cortex, hippocampus, pituitary, liver and thymus, with DFC showing a similar profile except for the cerebral cortex. In contrast, corticosterone weakly occupied GR in the thymus, pituitary and hippocampus and methyl-prednisolone was active only in peripheral tissues. Furthermore, IC50 for DEX in vitro amounted to 15-17 nM in the hippocampus and liver, whereas IC50 for the active metabolite 21-deacetyl-DFC (21-OH-DFC) was 4 times higher. 21-OH-DFC bound to type II and was absent from type I GR. When tested in equipotent doses based on IC50 analysis, DFC and DEX similarly induced in vivo ornithine decarboxylase activity in hippocampus and liver, although body weight loss after chronic treatment was significantly less for DFC. The results show that DFC distributes on the CNS similarly to DEX, induces ornithine decarboxylase activity but presents less intensive catabolic effects, making it suitable for use as an anti-inflammatory steroid during chronic therapeutic regimes.