RESUMEN
AIM: To investigate the effect of 4,5-dichloro-1,3-diethyl-1,3-dihydro-benzoimidazol-2-one (NS4591), a novel SK/IK channels positive modulator, on human myometrial activity. METHODS: Organ bath studies were performed on myometrial preparations obtained from women undergoing elective caesarean section at term (N = 11) or hysterectomy (N = 11). NS4591 was added cumulatively in the concentration range of 0.3-30 µm. In separate experiments, the effects of pre-incubation of muscle preparation with the SK or IK channel blockers apamin (1 µm) and TRAM34 (10 µm) on the outcomes of NS4591 were evaluated. Simultaneous vehicle controls were performed for all experiments. The effects of drugs were studied on spontaneous contractions. RESULTS: NS4591 exerted an inhibitory effect on myometrial contractions in muscle strips from non-pregnant and pregnant women. The contractility in non-pregnant and pregnant myometrium was reduced to the following values respectively: amplitude 20.65 ± 7.38% (P < 0.001) and 42.85 ± 11.04% (P < 0.05) and area under the curve 11.72 ± 7.39% (P < 0.001) and 34.84 ± 10.50% (P < 0.001) and are reflective of 30 µm NS4591 compared to vehicle control. In non-pregnant tissue, apamin partially reduced the inhibitory effects of NS4591, but we observed relaxation mediated by NS4591 despite pre-incubation with TRAM34. In contrast, in pregnant tissue, neither apamin nor TRAM34 could reverse the relaxatory effects of NS4591. CONCLUSION: Our findings imply that SK/IK channels are present and functional in myometrium from pregnant and non-pregnant women. The SK/IK channel-positive modulator NS4591 exerts relaxation of human myometrium in vitro, and this may have implications for the clinical management of preterm labour.
Asunto(s)
Bencimidazoles/farmacología , Miometrio/efectos de los fármacos , Canales de Potasio Calcio-Activados/agonistas , Contracción Uterina/efectos de los fármacos , Adulto , Cesárea , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Histerectomía , Persona de Mediana Edad , Miometrio/fisiología , Embarazo , Contracción Uterina/fisiologíaRESUMEN
Hartmann's procedure in humans results in a closed rectum deprived of its natural short-chain fatty acid source. This induces atrophy of the entire rectal wall. Ki-67 is a monoclonal antibody directed towards proteins in the cell nucleus that are present only during cell proliferation. This study investigated the effects of short-chain fatty acids on mucosal cell proliferation in the human rectum after Hartmann's procedure by means of Ki-67. Eight patients in whom Hartmann's procedure was performed were treated with placebo and then short-chain fatty acids for 14 days. Biopsies specimens were taken from the rectum before and after treatment; these were prepared with Ki-67 and labeling index was determined. The treatment was found significantly to increase proliferative activity in the rectal mucosa (P<0.01); the increase was principally in the middle (P<0.01) and upper crypt (P<0.05) compartments.