RESUMEN
PURPOSE: We present the case of a fifty-year-old male who presented at the Neurology Service. During the previous months he had noticed progressive cognitive deterioration, and particularly a loss of memory and executive abilities, as well as proximal weakness of the four limbs and lumbar tenderness. He had lost ten centimetres of height. A bone densitometry was performed, which showed early osteoporosis. RESULTS/CONCLUSIONS: The laboratory results showed an increase in urine cortisol excretion (1725 g/24h), with detectable plasma ACTH concentration (89 pg/ml), suggesting ACTH-dependent Cushing's syndrome, Additional tests were run in order to determine a hypothalamic or ectopic location of the syndrome. To this end, a bilateral inferior petrosal sinus sample (BIPSS) was performed for ACTH determination. BIPSS is the test that has been proven to have the best sensitivity to achieve differential diagnosis of ACTH-dependent Cushing's syndrome.
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Osteoporosis/diagnóstico , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND & AIMS: Dietary fiber has been proven to be beneficial in maintaining remission in human ulcerative colitis, an effect related with an increased luminal production of short-chain fatty acids (SCFA). The aim of the present study was to further investigate the mechanisms involved in the intestinal anti-inflammatory effects of dietary fiber in an experimental model of rat colitis. METHODS: HLA-B27 transgenic rats (8-10 weeks old) were fed a fiber-supplemented diet (5% Plantago ovata seeds) for 13 weeks before evaluation of the colonic inflammatory status, both histologically and biochemically. The luminal colonic production of SCFA was quantified. In vitro studies were also performed to test the interaction between two SCFA (butyrate and propionate) as inhibitors of cytokine production in THP-1 cells. RESULTS: Dietary fiber supplementation ameliorated the development of colonic inflammation in transgenic rats as evidenced by an improvement of intestinal cytoarchitecture. This effect was associated with a decrease in some of the pro-inflammatory mediators involved in the inflammatory process: nitric oxide, leukotriene B(4), tumor necrosis factor alpha (TNFalpha). The intestinal contents from fiber-treated colitic rats showed a significant higher production of SCFA, butyrate and propionate, than non-treated colitic animals. In vitro studies revealed a synergistic inhibitory effect of butyrate and propionate on TNFalpha production. CONCLUSIONS: Dietary fiber supplementation ameliorated colonic damage in HLA-B27 transgenic rats. This effects was associated with an increased production of SCFA, which can act synergistically in inhibiting the production of pro-inflammatory mediators.
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Colitis Ulcerosa/dietoterapia , Fibras de la Dieta/uso terapéutico , Ácidos Grasos Volátiles/biosíntesis , Mediadores de Inflamación , Animales , Células Cultivadas , Colitis Ulcerosa/metabolismo , Colon/citología , Colon/patología , Modelos Animales de Enfermedad , Ácidos Grasos Volátiles/farmacología , Femenino , Antígeno HLA-B27/genética , Organismos Modificados Genéticamente , Plantago , Psyllium , Distribución Aleatoria , Ratas , Ratas Endogámicas F344 , Semillas , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
We used the trinitrobenzenesulphonic acid (TNBS) rat model of experimental colitis to study the alterations in electrogenic ion transport in the inflamed distal colon. The distal colon exhibited decreased basal transport and reduced short-circuit current responses to carbachol and isobutylmethylxanthine (IBMX). The concentration/response curve for IBMX was also shifted to the right. Ion substitution experiments indicated that electrogenic transport was attributable chiefly to Cl(-) secretion. The mucosal layer of the inflamed distal colon (devoid of the submucosa) exhibited normal maximal responses to carbachol and IBMX, although the concentration/response curve for the latter was again shifted to the right. Tetrodotoxin markedly increased the response of the normal distal colon to both secretagogues and nullified the inhibition of the response to carbachol, but not that to IBMX, in the inflamed colon. The response of the mucosal preparation to 8-bromoadenosine 3',5'-cyclic monophosphate was similar in the normal and inflamed intestine, while the G protein activator NaF had a greater effect in the latter. The expression of the cystic fibrosis transmembrane conductance regulator (CFTR), as assessed by Northern blotting, was unchanged. cAMP levels in isolated colonocytes were markedly reduced by inflammation. We conclude that colonic inflammation produces disturbances of the enteric nervous system resulting in defective mucosal cAMP production and inhibition of ionic secretion.
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Colitis/metabolismo , Colon/inervación , Colon/metabolismo , AMP Cíclico/metabolismo , Sistema Nervioso Entérico/fisiología , 1-Metil-3-Isobutilxantina/farmacología , Anestésicos Locales/farmacología , Animales , Transporte Biológico/efectos de los fármacos , Carbacol/farmacología , Agonistas Colinérgicos/farmacología , Colitis/inducido químicamente , Colitis/inmunología , Colon/inmunología , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Femenino , Expresión Génica , Mucosa Intestinal/inmunología , Mucosa Intestinal/inervación , Mucosa Intestinal/metabolismo , Iones/metabolismo , Inhibidores de Fosfodiesterasa/farmacología , Ratas , Ratas Wistar , Tetrodotoxina/farmacología , Ácido TrinitrobencenosulfónicoRESUMEN
The effect of the flavonoid rutoside on acetic acid-induced rat colitis was studied. Rats were pretreated orally with different doses of the flavonoid (10, 25, and 100 mg/kg) 48, 24, and 1 hour prior to colitis induction and examined for colonic damage 24 hours later. Colonic inflammation was characterized by gross and microscopical injury, bowel wall thickening, abolition of fluid absorption, glutathione depletion, enhanced leukotriene B4 synthesis, and increased levels of myeloperoxidase and alkaline phosphatase activities. Rutoside treatment (25 and 100 mg/kg) reduced histologic injury and prevented the increase in alkaline phosphatase activity, but it had no effect on myeloperoxidase levels or leukotriene B4 synthesis. In addition, glutathione depletion was effectively counteracted at the dose of 25 mg/kg, whereas fluid absorption was achieved at the highest dose assayed. It is concluded that rutoside has an acute anti-inflammatory activity in this model which may be related to a putative direct protective effect on intestinal cells, mainly enterocytes, in which the antioxidative properties of the flavonoid may play a role.
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Colitis/prevención & control , Mucosa Intestinal/efectos de los fármacos , Rutina/análogos & derivados , Ácido Acético , Administración Oral , Animales , Colitis/inducido químicamente , Colitis/patología , Colon/efectos de los fármacos , Colon/patología , Colon/fisiopatología , Absorción Intestinal/efectos de los fármacos , Mucosa Intestinal/patología , Peroxidasa/metabolismo , Ratas , Ratas Wistar , Rutina/administración & dosificación , Rutina/farmacologíaRESUMEN
The antidiarrhoeic activity of the Euphorbia hirta whole plant was investigated. The lyophilized decoction demonstrated antidiarrhoeic activity in experimental models of diarrhoea induced by castor oil, arachidonic acid, and prostaglandin E2. It showed no activity when magnesium sulphate was used to provoke the diarrhoea. The lyophilized decoction delayed small intestinal transit when this was accelerated by castor oil but not in normal conditions. A flavonoid, quercitrin, with antidiarrhoeic activity was isolated from this crude drug.