RESUMEN
Tumor Necrosis Factor-alpha (TNF-α) is an immunomodulatory and proinflammatory cytokine implicated in neuro-inflammation and neuronal damage in response to cerebral ischemia. The present study tested the hypothesis that anti-TNF-α agents may be protective against cerebral infarction. Transient focal ischemia was artificially induced in anesthetized adult male Wistar rats (300-350 g) by middle cerebral artery occlusion (MCAO) with an intraluminal suture. TNF-α function was interfered with either a chimeric monoclonal antibody against TNF-α (infliximab-7 mg/kg) aiming to TNF-α soluble and membrane-attached form; or a chimeric fusion protein of TNF-α receptor-2 with a fragment crystallizable (Fc) region of IgG1 (etanercept-5 mg/kg) aiming for the TNF-α soluble form. Both agents were administered intraperitoneally 0 or 6 h after inducing ischemia. Infarct volume was measured by 2,3,5-triphenyltetrazolium chloride staining. Cerebral infarct volume was significantly reduced in either etanercept or infliximab-treated group compared with non-treated MCAO rats 24 h after reperfusion. These results suggest that anti-TNF-α agents may reduce focal ischemic injury in rats.
Asunto(s)
Lesiones Encefálicas/prevención & control , Etanercept/uso terapéutico , Infliximab/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Factor de Necrosis Tumoral alfa/metabolismo , Animales , Infarto Encefálico/etiología , Infarto Encefálico/prevención & control , Lesiones Encefálicas/etiología , Modelos Animales de Enfermedad , Infarto de la Arteria Cerebral Media/complicaciones , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Masculino , Ratas , Ratas Wistar , Factores de Tiempo , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
Vitamin D deficiency affects the lipid composition and Ca2+ uptake of intestinal basolateral membranes from chick intestine. The increased cholesterol content causes an increase in the molar ratio cholesterol/phospholipid. Phospholipid classes remain unchanged, but the percentages of arachidonic acid from the from the major phospholipid fractions are increased. After 24 hours of oral administration of 2,000 IU of cholecalciferol to vitamin D-deficient chicks, the cholesterol values do not change, but the amount of arachidonic acid returns to normal values. Ca2+ uptake driven by ATP is diminished in vesicles from intestinal basolateral membranes of vitamin D-deficient chicks. Cholecalciferol treatment returns these values to the controls which might be due mainly to the increased number of Ca2+ pump units. In conclusion, changes in lipid composition and in Ca2+ pump caused by vitamin D deficiency seems to play a role in the decrease of vesicular Ca2+ transport. A single dose of cholecalciferol restores only partially the lipid-protein changes produced by vitamin D deficiency.
Asunto(s)
Calcio/metabolismo , Membrana Celular/metabolismo , Mucosa Intestinal/metabolismo , Lípidos/química , Deficiencia de Vitamina D/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Transporte Biológico , Calcio/farmacocinética , Membrana Celular/química , Membrana Celular/efectos de los fármacos , Pollos , Colecalciferol/farmacología , Colesterol/metabolismo , Duodeno/efectos de los fármacos , Duodeno/metabolismo , Ácidos Grasos/análisis , Ácidos Grasos/metabolismo , Intestinos/efectos de los fármacos , Metabolismo de los Lípidos , Fosfatidilinositoles/análisis , Fosfatidilinositoles/metabolismo , Deficiencia de Vitamina D/tratamiento farmacológicoRESUMEN
The effect of diet phosphate content and cholecalciferol on intestinal phosphate secretion and absorption was investigated in rachitic chicks. Phosphate absorption was determined by the in situ ligated loop technique. Phosphate secretion was estimated by a method proposed by the authors. Hydroxyapatite, placed in the lumen of a ligated loop, acts as trapping agent of 32P leaving the intestinal tissue. The fraction of rapid exchangeability of tissue phosphate was taken as the precursor pool of secreted phosphate. Control chicks fed diets containing 0.3% P (group 1) or 1.0% (group 2) showed similar Pi absorption; the secretion was larger for group 2. After cholecalciferol treatment for 2 or 4 consecutive days an increment of Pi absorption with simultaneous reduction of Pi secretion was evident for both groups of animals. Chicks treated for 7 days gave values similar to those of controls. It is concluded that the regulation of intestinal phosphate absorption and secretion could be one important mean of homeostatic control. Intestinal phosphate movement is adapted to dietary phosphate and is partially independent of cholecalciferol.
Asunto(s)
Colecalciferol/farmacología , Dieta , Absorción Intestinal/efectos de los fármacos , Secreciones Intestinales/efectos de los fármacos , Fosfatos/metabolismo , Animales , Pollos , Íleon/metabolismo , Fosfatos/farmacología , Fósforo/metabolismo , Raquitismo/metabolismoAsunto(s)
Animales , Absorción Intestinal , Colecalciferol , Dieta , Fosfatos , Secreciones IntestinalesRESUMEN
The effect of diet phosphate content and cholecalciferol on intestinal phosphate secretion and absorption was investigated in rachitic chicks. Phosphate absorption was determined by the in situ ligated loop technique. Phosphate secretion was estimated by a method proposed by the authors. Hydroxyapatite, placed in the lumen of a ligated loop, acts as trapping agent of 32P leaving the intestinal tissue. The fraction of rapid exchangeability of tissue phosphate was taken as the precursor pool of secreted phosphate. Control chicks fed diets containing 0.3
P (group 1) or 1.0
(group 2) showed similar Pi absorption; the secretion was larger for group 2. After cholecalciferol treatment for 2 or 4 consecutive days an increment of Pi absorption with simultaneous reduction of Pi secretion was evident for both groups of animals. Chicks treated for 7 days gave values similar to those of controls. It is concluded that the regulation of intestinal phosphate absorption and secretion could be one important mean of homeostatic control. Intestinal phosphate movement is adapted to dietary phosphate and is partially independent of cholecalciferol.
Asunto(s)
Animales , Colecalciferol , Dieta , Absorción Intestinal , Secreciones Intestinales , FosfatosRESUMEN
Administration of vitamin D3 or 1,25 (OH)2D3 to rachitic chicks produces a decrease of 45Ca uptake by mitochondria from intestinal mucosa. This effect of vitamin D3 shows tissue specificity, since it was not observed in liver mitochondria from the same animals. The Km values were similar (about 10 microM) for intestinal mitochondria from rachitic and treated animals. The Ca2+ efflux in previously loaded mitochondria was not changed by treatment. The Ca content of recently isolated mitochondria was strikingly lower after vitamin D3 administration. It is concluded that vitamin D3 may participate in the mechanism which regulates the intramitochondrial Ca concentration.
Asunto(s)
Calcio/metabolismo , Colecalciferol/farmacología , Mucosa Intestinal/metabolismo , Mitocondrias/metabolismo , Animales , Pollos , Mitocondrias Hepáticas/metabolismoRESUMEN
Administration of vitamin D3 or 1,25 (OH)2D3 to rachitic chicks produces a decrease of 45Ca uptake by mitochondria from intestinal mucosa. This effect of vitamin D3 shows tissue specificity, since it was not observed in liver mitochondria from the same animals. The Km values were similar (about 10 microM) for intestinal mitochondria from rachitic and treated animals. The Ca2+ efflux in previously loaded mitochondria was not changed by treatment. The Ca content of recently isolated mitochondria was strikingly lower after vitamin D3 administration. It is concluded that vitamin D3 may participate in the mechanism which regulates the intramitochondrial Ca concentration.
RESUMEN
The effects of vitamin D3 and the aqueous extract of Solanum malacoxylon on intestinal alkaline phosphatase and tissue phosphate content were studied on rachitic chicks treated with large doses of ethane-1-hydroxy-1,1 diphosphonate (EHDP). The EHDP treatment blocks the increase of intestinal calcium or phosphate absorption induced by the vitamin D3, while it has no effects on the rise of intestinal alkaline phosphatase activity or the increment in tissue phosphate content. The lack of correlation between the increment of alkaline phosphatase and that of Ca or phosphate absorption in vitamin D3 plus EHDP treated chicks excludes a participation of the alkaline phosphatase in the mechanism of Ca or P intestinal absorption. The Ca or phosphorus absorption are elicited specifically by 1,25-(OH)2-D3, while alkaline phosphatase activity and phosphate tissue concentration respond to a broader spectrum of stimuli.
Asunto(s)
Fosfatasa Alcalina/metabolismo , Calcio/metabolismo , Colecalciferol/farmacología , Intestinos/enzimología , Animales , Pollos , Colecalciferol/antagonistas & inhibidores , Ácido Etidrónico/farmacología , Absorción Intestinal , Fosfatos/metabolismoAsunto(s)
Absorción Intestinal , Calcio , Fosfatasa Alcalina , Fosfatos , Ácido Etidrónico , Vitamina DRESUMEN
The effects of vitamin D3 and the aqueous extract of Solanum malacoxylon on intestinal alkaline phosphatase and tissue phosphate content were studied on rachitic chicks treated with large doses of ethane-1-hydroxy-1,1 diphosphonate (EHDP). The EHDP treatment blocks the increase of intestinal calcium or phosphate absorption induced by the vitamin D3, while it has no effects on the rise of intestinal alkaline phosphatase activity or the increment in tissue phosphate content. The lack of correlation between the increment of alkaline phosphatase and that of Ca or phosphate absorption in vitamin D3 plus EHDP treated chicks excludes a participation of the alkaline phosphatase in the mechanism of Ca or P intestinal absorption. The Ca or phosphorus absorption are elicited specifically by 1,25-(OH)2-D3, while alkaline phosphatase activity and phosphate tissue concentration respond to a broader spectrum of stimuli.
Asunto(s)
Fosfatasa Alcalina , Calcio , Absorción Intestinal , Fosfatos , Ácido Etidrónico , Vitamina DRESUMEN
Intestinal Ca and P absorption was investigated on rachitic chicks raised on diets with a 1% Ca and 0.3% or 1% P contents. 45Ca and 32P absorption was determined by the technique of the isolated gut sac in vivo. In addition, 32P transport was also measured by the everted gut sac procedure in vitro. Treatment with vit. D3 during 7 days increased the 45Ca absorption in animals fed diets containing 0.3% or 1% P. 32P absorption showed an increase after 2 days of treatment and a decrease afterwards. The reduction of 32P absorption was larger in animals fed diet with 1% P. Study of 32P transport with the everted gut sac technique showed an increase after vit. D3 and a loss of intracellular P, regardless the duration of treatment.
Asunto(s)
Calcio/metabolismo , Dieta , Absorción Intestinal/efectos de los fármacos , Fosfatos/metabolismo , Animales , Huesos/análisis , Radioisótopos de Calcio , Pollos , Colecalciferol/administración & dosificación , Colecalciferol/farmacología , Mucosa Intestinal/análisis , Fosfatos/administración & dosificación , Radioisótopos de Fósforo , Raquitismo/tratamiento farmacológico , Raquitismo/fisiopatologíaRESUMEN
Intestinal Ca and P absorption was investigated on rachitic chicks raised on diets with a 1
Ca and 0.3
P contents. 45Ca and 32P absorption was determined by the technique of the isolated gut sac in vivo. In addition, 32P transport was also measured by the everted gut sac procedure in vitro. Treatment with vit. D3 during 7 days increased the 45Ca absorption in animals fed diets containing 0.3
P. 32P absorption showed an increase after 2 days of treatment and a decrease afterwards. The reduction of 32P absorption was larger in animals fed diet with 1
P. Study of 32P transport with the everted gut sac technique showed an increase after vit. D3 and a loss of intracellular P, regardless the duration of treatment.
RESUMEN
Intestinal Ca and P absorption was investigated on rachitic chicks raised on diets with a 1
Ca and 0.3
or 1
P contents. 45Ca and 32P absorption was determined by the technique of the isolated gut sac in vivo. In addition, 32P transport was also measured by the everted gut sac procedure in vitro. Treatment with vit. D3 during 7 days increased the 45Ca absorption in animals fed diets containing 0.3
or 1
P. 32P absorption showed an increase after 2 days of treatment and a decrease afterwards. The reduction of 32P absorption was larger in animals fed diet with 1
P. Study of 32P transport with the everted gut sac technique showed an increase after vit. D3 and a loss of intracellular P, regardless the duration of treatment.