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.

Midkine secretion protects Hep3B cells from cadmium induced cellular damage

AIM: To evaluate role of midkine secretion during Cadmium (Cd) exposure in the human hepatocyte cell line Hep3B cells. METHODS: Different dosages of Cd (0.5-1-5-10 μg/mL) were applied to Hep3B cells and their effects to apoptosis, lactate dehydrogenase (LDH) leakage and midkine secretion were evaluated as time dependent manner. Same experiments were repeated with exogenously applied midkine (250-5000 pg/mL) and/or 5 μg/mL Cd.RESULTS: Cd exposure induced prominent apoptosis and LDH leakage beginning from lower dosages at the 48th h. Cd induced midkine secretion with higher dosages (P < 0.001), (control, Cd 0.5-1-5-10 μg/mL respectively: 1123 ± 73, 1157 ± 63, 1242 ± 90, 1886 ± 175, 1712 ± 166 pg/mL). Exogenous 500-5000 pg/mL midkine application during 5 μg/mL Cd toxicity prevented caspase-3 activation (control, Cd toxicity, 250, 500, 1000, 2500, 5000 pg/mL midkine+ Cd toxicity, respectively: 374 ± 64, 1786 ± 156, 1545 ± 179, 1203 ± 113, 974 ± 116, 646 ± 56, 556 ± 63 cfu) LDH leakage and cell death in Hep3B cells (P < 0.001). CONCLUSION: Our results showed that midkine secretion from Hep3B cells during Cd exposure protects liver cells from Cd induced cellular damage. Midkine has anti-apoptotic and cytoprotective role during Cd toxicity. Further studies are needed to explain the mechanism of midkine secretion and cytoprotective role of midkine during Cd exposure. Midkine may be a promising theurapatic agent in different toxic hepatic diseases.

Effects of contrast media on the hepato-pancreato-biliary system

AIM:To determine the effects of high osmolarity contrast media (HOCM) and iso-osmolar contrast media (CM) application, with or without pressure, on hepato-pancreato-biliary (HPB) system.METHODS: Sixty rats were divided into six equal groups as follows: Group 1: (0.9% NaCl, control), Group 2: (diatrizoate meglumine Na, ionic HOCM, Urographin?), Group 3: (iodixanol, iso-osmolar non-ionic CM, Visipaque?); each of which was applied without pressure, whereas the animals of the remaining three groups (1p, 2p, 3p) were subjected to the same CM with pressure. We performed a duodenal puncture and introduced a catheter into the ampulla. After the catheterization, 0.2 mL CM or 0.9% NaCl was injected with or without pressure. Blood samples were taken for biochemical evaluations. The histopathological examinations of liver, common bile duct, and pancreas were performed.RESULTS: There were no significant differences between the six groups for blood amylase, alanine aminotransferases, aspartate aminotransferases, bilirubin levels (P>0.05). Alkaline phosphatase and γ glutamyl transaminase levels were higher (P < 0.05) in the Urographin? groups (2, 2p) than the Visipaque? groups (3, 3p), or control groups (1, 1p). Hepatocyte necrosis, portal area inflammation, and Kupffer's cell hyperplasia were higher (P<0.05) in the study groups than the control group. However, there were no significant differences (P>0.05) between HOCM (2,2p) and iso-osmolar CM (3,3p) groups. Bile duct proliferation and regeneration in the Urographin groups (2, 2p) were significantly higher (P<0.05) than the Visipaque groups (3, 3p) or the control groups (1,1p). Although CM caused minor damage to the pancreas, there were no statistically significant differences (P>0.05) between the groups. Application of the CM with pressure did not cause additional damage to the HPB system.CONCLUSION: Iso-osmolar, non-ionic CM could be more reliable than the ionic HOCM, whereas the application of pressure during the CM application had no effect on the HPB system.

Lack of nitrate tolerance in isosorbid dinitrate- and sodium nitroprusside-induced relaxation of rabbit internal anal sphincter

AIM: To investigate the tolerance development against the relaxant effect of nitric oxide donating drug isosorbide dinitrate (ISDN) and sodium nitropruside (SNP) in internal anal sphincter (IAS) smooth muscle. METHODS: Relaxation responses of ISDN, and electrical fi eld stimulation (EFS) were obtained before and after tolerance induction by ISDN incubation. RESULTS: ISDN (10-7-10-4 mol/L) and SNP (10-8-10-4 mol/L) caused a concentration-dependent relaxation on the basal tonus of the isolated rabbit IAS strips. After a period of 2 h incubation of the 6 x 10-4 mol/L ISDN the relaxation effects of ISDN and SNP did not change compared to control strips. EFS evoked frequency-dependent relaxation in internal anal sphincter smooth muscle and Emax obtained from control strips were not changed in ISDN tolerance-inducing condition. In this study nitrate tolerance was not observed in rabbit IAS smooth muscle. CONCLUSION: This result shows that nitric oxide donating drugs relaxes the internal anal sphincter of the rabbits without the development of tolerance.