Altered spontaneous contractions of the ileum by anesthetic agents in rats exposed to peritonitis

AIM:To investigate in vitro effects of propofol,midazolam and dexmedetomidine,which are commonly used anaesthesic or sedatives,on spontaneous contractions of the ileum both in normal rats and those exposed to hyperdynamic peritonitis.METHODS:Spontaneous contractions of isolated ileum muscle segments from sham operated rats and those exposed to peritonitis,were studied in vitro.The amplitude and the frequency of spontaneous contractions of ileum muscle segments were studied after adding dexmetetomidine,propofol,and midazolam to the organ bath in a cumulative manner.RESULTS:Both amplitude(85.2±6.6 vs 47.4±7.1)and frequency(32.8±4.6 vs 20.2±3.9)of spontaneous contractions in ileum smooth muscle segments were decreased significantly in the peritonitis group compared to the control group(P<0.05).Dexmedetomidine significantly increased the amplitude of spontaneous contractions(85.2±6.6 vs 152.0±5.4,P<0.05)whereas,propofol(85.2±6.6 vs 49.6±4.8,P<0.05)and midazolam(85.2±6.6 vs 39.2±4.5,P<0.05)decreased it in both control and peritonitis groups.The frequency of spontaneous contractions were significantly decreased by propofol in both control(32.8±4.6 vs 18.2±3.4,P<0.05)and peritonitis groups 20.2±3.9 vs 11.6±3.2,P<0.05).Dexmedetomidine and midazolam did not cause significant changes in the number of spontaneous contractions in both control and the peritonitis groups(P>0.05).CONCLUSION:Propofol,midazolam and dexmedetomidine have various in vitro effects on spontaneous contractions of the rat ileum.While dexmedetomidine augments the spontaneous contraction of the rat ileum,propofol attenuates it.However,the effects of these compounds were parallel in both control and peritonitis groups.

Effects of tyrosine kinase inhibitor E7080 and eNOS inhibitor L-NIO on colorectal cancer alone and in combination

Objective：To investigate the effects of E7080 and N5-（1-iminoethyl）-L-ornithine dihydrochloride （L-NIO）on colorectal cancer alone and in combination.Methods：HT29 colorectal cancer cell line from Sap Institute was used.Real-time cell analysis （xCELLigence system） was performed to determine the effects of E7080 and L-NIO on colorectal cell proliferation.While apoptosis was determined with Annexin V staining,and the effect of agents on angiogenesis was determined with chorioallantoic membrane （CAM） model.Results：We found that E7080 has a strong antiproliferative effect with an half maximum inhibition of concentration （IC50） value of 5.60×10-8 mol/L.Also it has been observed that E7080 showed antiangiogenic and apoptotic effects on HT29 colorectal cancer cells.Antiangiogenic scores of E7080 were 1.2,t.0 and 0.6 for 100,10 and 1 nmol/L E7080 concentrations,respectively.Furthermore,apoptosis has been detected in 71％ of HT29 colorectal cancer cells after administration of 100 nmol/L E7080 which may indicate strong apoptotic effect.Meanwhile administration of L-NIO alone did not show any effect,but the combination of E7080 with L-NIO increased the antiproliferative,antiangiogenic and apoptotic effects of E7080.Conclusions：Results of this study indicate that E7080 may be a good choice in treatment of colorectal tumors.Furthermore the increased effects of E7080 when combined with L-NIO raise the possibility to use a lower dose of E7080 and therefore avoid/minimize the side effects observed with E7080.