Idiopathic mesenteric phlebosclerosis associated with long-term oral intake of geniposide.

BACKGROUND: Idiopathic mesenteric phlebosclerosis (IMP) is a rare disease, and its etiology and risk factors remain uncertain. AIM: To investigate the possible influence of Chinese herbal liquid containing geniposide on IMP. METHODS: The detailed formula of herbal liquid prescriptions of all patients was studied, and the herbal ingredients were compared to identify the toxic agent as a possible etiological factor. Abdominal computed tomography (CT) and colonoscopy images were reviewed to determine the extent and severity of mesenteric phlebosclerosis and the presence of findings regarding colitis. The disease CT score was determined by the distribution of mesenteric vein calcification and colon wall thickening on CT images. The drinking index of medicinal liquor was calculated from the daily quantity and drinking years of Chinese medicinal liquor. Subsequently, Spearman's correlation analysis was conducted to evaluate the correlation between the drinking index and the CT disease score. RESULTS: The mean age of the 8 enrolled patients was 75.7 years and male predominance was found (all 8 patients were men). The patients had histories of 5-40 years of oral Chinese herbal liquids containing geniposide and exhibited typical imaging characteristics (e.g., threadlike calcifications along the colonic and mesenteric vessels or associated with a thickened colonic wall in CT images). Calcifications were confined to the right-side mesenteric vein in 6 of the 8 patients (75%) and involved the left-side mesenteric vein of 2 cases (25%) and the calcifications extended to the mesorectum in 1 of them. The thickening of colon wall mainly occurred in the right colon and the transverse colon. The median disease CT score was 4.88 (n = 7) and the median drinking index was 5680 (n = 7). After Spearman's correlation analysis, the median CT score of the disease showed a significant positive correlation with the median drinking index (r = 0.842, P < 0.05). CONCLUSION: Long-term oral intake of Chinese herbal liquid containing geniposide may play a role in the pathogenesis of IMP.

Role of CCL20/CCR6 and the ERK signaling pathway in lung adenocarcinoma.

Previous studies have revealed that carcinoma-associated fibroblasts communicate microenvironment-derived signals through chemokine/chemokine receptor interaction, resulting in carcinogenesis. C-C motif chemokine ligand 20 (CCL20)/C-C motif chemokine receptor 6 (CCR6) interactions are involved in the pathogenesis of colonic malignancies. The present study aimed to characterize the roles of CCL20/CCR6 and the extracellular signal-regulated kinase (ERK) signaling pathway in lung adenocarcinoma growth. Lung adenocarcinoma samples obtained at surgery were assessed for the expression, tissue localization and production of CCL20/CCR6. In addition, colony formation, ERK signaling and chemokine production were measured to assess the responsiveness of the A549 cell line to CCL20 stimulation. CCL20 and CCR6 were found to be highly expressed in the majority of samples in the recurrence group (76 and 66%, respectively). The staining indexes of CCL20 and CCR6 in the recurrence group were 149.3 and 134.4, respectively, which were significantly higher than those in the non-recurrence group (57.2 and 58.0, respectively); the protein and mRNA expression levels determined by western blot and reverse transcription-quantitative polymerase chain reaction were also found to be high in the recurrence group For A549 cells, the colony-forming capacity was increased by CCL20 stimulation, and this effect was dependent in part on ERK phosphorylation. Collectively, the findings suggest that CCR6 and CCL20 may serve a role in lung adenocarcinoma, leading to proliferation and migration via autocrine or paracrine mechanisms. The disruption of CCL20/CCR6 interactions may be a promising strategy for the treatment of cancer.

[Effects of adsorbents on partitioning of Cd and Pb in MSW incineration].

An incineration experiment using simulated municipal solid waste (MSW) in the tubular furnace was performed to study the effects of SiO2, Al2o3 and CaO on the partitioning of Cd and Pb under different operating conditions which included adsorbents percentage, furnace temperature and residence time. The results indicated that the increasing of SiO2, AL2O3, CaO concentration were favorable for Cd to partition in the bottom ash. And for Pb, SiO2 and Al2O3 had the same effects. However, the condition with CaO showed an opposite tendency of increasing Pb distribution in fly ash. While all of these adsorbents increasing, the effects were also enhanced. When the temperature of the tubular furnace was 850 degrees C, the adsorption efficiencies of these adsorbents for Cd were in the sequence of CaO > Al, O3 > SiO2, and for Pb, Al2O3 > SiO2 > CaO. In addition,with increasing of tubular furnace temperature and residence time, there would be more Cd and Pb compounds moving to the fly ash.

Cholecystokinin octapeptide improves cardiac function by activating cholecystokinin octapeptide receptor in endotoxic shock rats.

AIM: To explore the effect of sulfated cholecystokinin octapeptide (sCCK-8) on cardiac functions and its receptor mechanism in endotoxic shock (ES) rats. METHODS: The changes of the mean arterial pressure (MAP), heart rate (HR), the left ventricular pressure (LVP) and the maximal/minimum rate of LVP (+/-LVdp/dt(max))) were measured by using physiological record instrument in eight groups of rats. The expression of cholecystokinin-A receptor (CCK-AR) and cholecystokinin-B receptor (CCK-BR) mRNA of myocardium in ES rats was examined by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: (1) Low doses of sCCK-8 (0.4 microg/kg) caused tachycardia (441+/-27, normal control 391+/-22 s/min) and slight increase in MAP, LVP and +/-LVdp/dt(max) (16.96+/-1.79, 18.21+/-1.69 and +768.85+/-31.28/-565.04+/-27.71 kPa, respectively, all P<0.01), while medium doses (4.0 microg/kg) and high doses of sCCK-8 (40 microg/kg) elicited bradycardia and marked increase in MAP, LVP and +/-LVdp/dt(max) (17.29+/-1.63, 19.46+/-2.57 and +831.46+/-22.57/-606.08 +/-31.32; 17.46+/-1.08, 19.83+/-2.91 and +914.52+/-35.95/-639.15+/-30.23 kPa, respectively, all P<0.01). Proglumide (1.0 mg/kg), a nonselective antagonist of CCK-receptor (CCK-R), significantly inhibited the pressor effects of sCCK-8 (15.96+/-1.38, 17.36+/-0.66 and +748.18+/-19.29/-512.12+/-14.39 kPa, respectively, all P<0.01), whilst reversing the bradycardiac responses. (2) High doses of LPS (8 mg/kg) elicited marked decrease in MAP, LVP and +/-LVdp/dt(max). (7.16+/-0.59, 7.6+/-0.68 and +298.01+/-25.52/-166.96+/-19.25 kPa, respectively, all P<0.01). Pretreatment with sCCK-8 (40 microg/kg) could reverse the decline of cardiac functions (10.71+/-0.45, 11.7+/-1.26 and +446.04+/-67.18/-347.90+/-36.98 kPa, respectively, all P<0.01), while proglumide could cause further decline of cardiac function in ES rats (4.71+/-0.67, 5.58+/-1.25 and +226.48+/-15.84/-142.83+/-20.23 kPa, respectively, all P<0.01). (3) CCK-A/BR mRNAs were expressed in myocardium of control rats. Gene expression of CCK-AR and CCK-BR significantly increased in myocardium of ES rats. The increase of CCK-AR mRNA induced by LPS began at 0.5 h, peaked at 2 h, kept a high level at 6 h and declined at 12 h, respectively. Similar to CCK-AR mRNA, the expression of CCK-BR mRNA peaked at 2 h and kept a high level at 6 h, but it did not change at the first 0.5 h and was stable at a high level at 12 h. CONCLUSION: The above results indicate that endogenous and exogenous sCCK-8 may significantly improve cardiac function and intractable hypotension of ES rats, which was likely related to high expression of CCK-A/BR in myocardium induced by LPS.

[Melatonin improves vascular reactivity of endotoxemia rats].

The purpose of the present study was to investigate the effect of melatonin (MT) on the abnormal reactivity of thoracic aorta and pulmonary artery induced by lipopolysaccharide (LPS) in rats. Sprague-Dawley rats were divided into four groups randomly: (1) Vehicle group; (2) LPS group: LPS (4 mg/kg, i.p.); (3) LPS+MT group: MT (5 mg/ml, i.p.) was given 30 min before LPS and 60 min after LPS (4 mg/kg ,i.p); (4) MT group: received two doses of MT, 90 min after the first injection of MT another dose of MT was given. Six hours after LPS injection,the rats were killed and both thoracic aortic rings (TARs) and pulmonary artery rings (PARs)were prepared. The reactivity of TARs and PARs in the four subgroups was tested separately. The contraction response to phenylephrine (PE) and the endothelium-dependent relaxation response (EDRR) to ACh were observed with the isolated artery ring technique. Concentration-response curves were generated with ACh or PE (1 x 10(-8) - 1 x 10(-5) mol/L). Superoxide dismutes (SOD) activity and the content of malondialhyde (MDA) in artery tissues were detected. For TARs, LPS significantly reduced the contraction response to PE compared with the vehicle group (P<0.01) and the curve of cumulative dose responses to PE in the LPS group shifted downward. Although EDRR to ACh in the LPS group had the tendency to decrease but still showed no significant difference compared with the vehicle group (P>0.05). For PARs, EDRR to ACh was depressed significantly in the LPS group (P<0.01), while no effect on contraction response to PE in the LPS group was observed, compared with the vehicle group (P> 0.05). Compared with the LPS group, TARs in the LPS+MT group exhibited an increased contraction response to PE, but were still lower than that in the vehicle group. Similarly, EDRR to ACh of PARs in the LPS+MT group was improved significantly and there was no difference between the LPS+MT group and the vehicle group. The vascular reactivity was unaffected in MT group compared with the vehicle group in both TARs and PARs. SOD activity in the LPS +MT group increased significantly and the content of MDA decreased markedly compared with the LPS group. These results suggest that MT may improve the vascular reactivity in endotoxemia rats due to its antioxidant properties.

[Effect of peroxynitrite on the reactivity of rabbit pulmonary arteries in vitro].

To investigate the effect of peroxynitrite (ONOO(-)) on the reactivity of rabbit pulmonary artery, the responses of rabbit pulmonary artery rings (PARs) pre-incubated with ONOO(-) to endothelium-dependent and receptor-dependent relaxants ACh and ADP, endothelium-dependent and receptor-independent relaxant calcium ionophore A23187, endothelium-independent relaxant sodium nitroprusside (SNP) and alpha(1)-adrenoceptor agonist phenylephrine (PE) were observed in vitro in an accumulative manner. (1) Relaxations of PARs to ACh, calcium ionophore A23187 and ADP were markedly impaired with shift of accumulative dose-response curve of each agonist to the right. Inhibition of endothelium-dependent and receptor-dependent or independent relaxation by ONOO(-) was dose-dependent. (2) ONOO(-) incubation inhibited SNP-induced relaxation in a dose-dependent manner. (3) Contractile response of PARs to PE varied with the different doses of ONOO(-). In PARs pre-incubated with 0.5 mmol/L ONOO(-), contractile response was significantly enhanced with shift of PE accumulative dose-response curve to the left, whereas in PARs pre-incubated with 1.0 mmol/L or 2.0 mmol/L ONOO(-), it was markedly reduced with right shift of PE accumulative dose-response curve. (4) Vehicle of ONOO(-) had no effect on responses to each agonist.Decomposed ONOO(-) had minimal effect on the response to PE and ADP, in contrast, relaxation of PARs to ACh, A23187 and SNP were enhanced. These results indicate that ONOO(-) may contribute to regulatory disorder of pulmonary artery reactivity.

Anti-inflammatory effect of cholecystokinin and its signal transduction mechanism in endotoxic shock rat.

AIM: To study the anti-inflammatory effects of cholecystokinin-octapeptide (CCK-8) on lipopolysaccharide (LPS)-induced endotoxic shock (ES) and further investigate its signal transduction pathways involving p38 mitogen-activated protein kinase (MAPK) and IkappaB-alpha. METHODS: Eighty-four rats were divided randomly into four groups: LPS (8 mg.kg(-1), iv) induced ES; CCK-8 (40 microg.kg(-1), iv) pretreatment 10 min before LPS (8 mg.kg(-1)); CCK-8 (40 microg.kg(-1), iv) or normal saline (control) groups. The inflammatory changes of lung and spleen, phagocytic function of alveolar macrophage, quantification of inflammatory cells in bronchoalveolar lavage (BAL) were investigated in rats by using hematoxylin and eosin (HE) staining, phagocytosis of Candida albicans and differential cell counting. Nitric oxide (NO) production in serum, lung and spleen was measured with the Griess reaction. The mechanism involving p38 MAPK and IkappaB-alpha signal pathways was investigated by Western blot. RESULTS: Inflammatory changes of lung and spleen induced by LPS were alleviated by CCK-8, the increase of NO induced by LPS in serum, lung and spleen was significantly inhibited and the neutrophil infiltration in BAL was significantly reduced by CCK-8. The number of neutrophils was (52+/-10)X10(6) cells. (-1) in LPS group, while it decreased to (18+/-4)X10(6) cells. (-1) in CCK-8+LPS (P<0.01). The phagocytic rate of CCK-8 group increased to (62.49+/-9.49) %, compared with control group (48.16+/-14.20) %, P<0.05. The phagocytosis rate was (85.14+/-4.64) % in LPS group, which reduced to (59.33+/-3.14) % in CCK-8+LPS group (P<0.01). The results of phagocytosis indexes showed similar changes. CCK-8 may play an important role in increasing the expression of p38 MAPK and decreasing the degradation of IkappaB-alpha in lung and spleen of ES rats. CONCLUSION: CCK-8 can result in anti-inflammatory effects, which may be related to activation of p38 MAPK and inhibition on the degradation of IkappaB-alpha.

Effects of cholecystokinin octapeptide on rat cardiac function and the receptor mechanism.

The aim of this study was to explore the effects of cholecystokinin octapeptide (CCK-8) on cardiac function and the receptor mechanism in anesthetized rats. The mean arterial pressure (MAP), heart rate (HR), the left ventricle systolic pressure (LVP) and the maximal/minimum rate of LVP (+/-LV dp/dt(max)) were measured. The results obtained are as follows. (1) Low dose of CCK-8 (0. 4 microgram/kg i.v.) caused tachycardia and slight increase in MAP, LVP and LV dp/dt(max) (P<0.01), while medium dose (4.0 microgram/kg i.v.) and high dose of CCK-8 (40 microgram/kg i.v.) elicited a bradycardia and marked increase in MAP, LVP and LV dp/dtmax (P<0.01). (2) Proglumide (1.0 mg/kg i.v.), a CCK-receptor (CCK-R) antagonist, significantly inhibited the pressor effects of CCK-8, whilst it reversed the bradycardic responses (P<0.01). (3) Using reverse transcription polymerase chain reaction (RT-PCR), CCK-A receptor (CCK-AR) and CCK-B receptor (CCK-BR) mRNA were expressed in myocardium of rats. The above results indicate that CCK-8 may enhance cardiac function in a dose-dependent manner and elicit a change in HR, which is likely induced by the activation of CCK-R on myocardium.

[Inhibitory effect of cholecystokinin-octapeptide on production of cytokines in the lung of endotoxic shock rats].

To study the effect of cholecystokinin-octapeptide (CCK-8) on systemic hypotension and cytokine production in serum and lung of endotoxic shock (ES) rats induced by lipopolysaccharide (LPS) and investigate its signal transduction mechanism of p38 mitogen-activated protein kinase (MAPK), the changes in mean arterial pressure (MAP) were observed by using a polygraph in four groups of SD rats: group of LPS (8 mg/kg i.v.) induced ES, group of CCK-8 (40 microg/kg i.v.) pretreatment 10 min before LPS (8 mg/kg) administration, group of CCK-8 (40 microg/kg i.v.) only, and normal saline (control) group; the contents of proinflammatory cytokines (TNF-alpha, IL-1 beta and IL-6) in the lung and serum were assayed using ELISA kits; and p38 MAPK was detected by Western blot. The results showed that CCK-8 alleviated LPS-induced decrease in MAP of rats; compared with the control, LPS elevated the levels of TNF-alpha, IL-1 beta and IL-6 in serum and lung significantly, while CCK-8 significantly inhibited the LPS-induced increases in TNF-alpha, IL-1 beta and IL-6 in serum and lung. The activation of p38 MAPK in the lung of ES rats was enhanced by CCK-8 pretreatment. These results suggest that CCK-8 can alleviate the LPS-induced decrease in MAP of ES rats and exert an inhibitory effect on the overproduction of proinflammatory cytokines, and that p38 MAPK may be involved in its signal transduction mechanisms.

CCK-8 inhibits expression of TNF-alpha in the spleen of endotoxic shock rats and signal transduction mechanism of p38 MAPK.

AIM: To study the effect of sulfated cholecystokinin-octapeptide (CCK-8) on systemic hypotension, gene and protein expression of TNF-alpha in the spleen of lipopolysaccharide (LPS)-induced endotoxic shock (ES) rats, and further investigate the signal transduction mechanism of p38 mitogen-activated protein kinase (MAPK). METHODS: The changes of blood pressure were observed using physiological record instrument in the four groups of rats: LPS (8 mg x kg(-1), iv), CCK-8 (40 microg x kg(-1), iv) pretreatment 10 min before LPS (8 mg x kg(-1)), CCK-8 (40 microg x kg(-1), iv) or normal saline (control) group. The content of TNF-alpha in the spleen was assayed 2 h after LPS administration using ELISA kit and the expression of TNF-alpha mRNA was examined 30 min, 2 h and 6 h after LPS administration by reverse transcribed polymerase chain reaction (RT-PCR). Activation of p38 MAPK was detected with Western blot 30 min after LPS administration. RESULTS: CCK-8 reversed LPS-induced decrease of mean arterial pressure (MAP) in rats. The content of TNF-alpha in the spleen was (282+/-30) ng x L(-1) in control group, while it increased to (941+/-149) ng x L(-1) in LPS group, P<0.01. CCK-8 significantly inhibited the LPS-induced increase of TNF-alpha content in spleen. It decreased to (462 +/-87) ng x L(-1) in CCK-8+LPS group, P<0.01. The expression of TNF-alpha mRNA 30 min and 2 h after treatment was stronger in LPS group, while it was lowered after CCK-8 pretreatment. The p38 MAPK expression increased significantly in LPS group (5.84 times of control) and CCK-8 increased the activation of p38 MAPK in ES rats (10.74 times of control). CONCLUSION: CCK-8 reverses the decrease of MAP in ES rats and has inhibitory effect on the gene and protein expression of TNF-alpha in spleen, and p38 MAPK may be involved in its signal transduction mechanisms.