Comparison of postpolypectomy bleeding between epinephrine and saline submucosal injection for large colon polyps by conventional polypectomy:A prospective randomized,multicenter study

AIM:To evaluate and compare the clinical outcomes of prophylactic submucosal saline-epinephrine injection and saline injection alone for large colon polyps by conventional polypectomy. METHODS:A prospective study was conducted from July 2003 to July 2004 at 11 tertiary endoscopic centers. Large colon polyps (> 10 mm in diameter) wererandomized to undergo endoscopic polypectomy with submucosal saline-epinephrine injection (epinephrine group) or normal saline injection (saline group). Endoscopic polypectomy was performed by the conventional snare method,and early (< 12 h) and late bleeding complications (12 h-30 d) were observed. RESULTS:A total of 561 polyps in 486 patients were resected by endoscopic polypectomy. Overall,bleeding complications occurred in 7.6% (37/486) of the patients,including 4.9% (12/244) in the epinephrine group,and 10.3% (25/242) in the saline group. Early and late postpolypectomy bleeding (PPB) occurred in 6.6% (32/486) and 1% (5/486) of the patients,respectively,including 4.5% (11/244),0.4% (1/244) in the epinephrine group,and 8.7% (21/242),1.7% (4/242) in the saline group. No significant differences in the rates of overall,early and late PPB were observed between the 2 groups. Multivariate stepwise logistic regression analysis revealed that large size (> 2 cm) and neoplastic polyps were independently and significantly associated with the presence of PPB. CONCLUSION:The prophylactic submucosal injection of diluted epinephrine does not appear to provide an additional advantage over the saline injection alone for the prevention of PPB.

The Role of β3-adrenergic Receptor Gene in Neuropeptide Y Y5Receptor Antisense Gene Therapy of Diet-induced Obese Rats

Objective: To study the role of β3-adrenergic receptor gene in neuropeptide Y(NPY) Y5 receptor antisense gene therapy of diet-induced obese rats.Methods: The diet-induced obese rats were prepared by feeding a high-nutrition diet. Lateral ventricular was cannulated in obese rats which then received an intraventricular injection of either 5 μg/μl NPY Y5 receptor antisense or 10 μl missense oligodeoxynucleotide or saline of 10 μl respectively in every rat. When the rats were killed, the wet weight of abdominal adipose tissue, the level of serum lipid and lipoprotein were measured. Total RNA from the retroperitoneal adipose tissue was extracted and the level of β3-adrenergic receptor gene mRNA expression was evaluated by RT-PCR.Results: ①The wet weight of abdominal adipose tissue, the levels of serum lipids were greatly higher in diet-induced obese rats than those in normal rats. However, there were much lower β3-adrenergic receptor gene mRNA expression levels in retroperitoneal adipose tissue in diet-induced obese rats as compared with those in normal rats. ②After the diet-induced obese rats were intraventricularly administered with NPY Y5 receptor antisense oligodeoxynucleotide, the levels of β3-adrenergic receptor gene mRNA expression in retroperitoneal adipose tissue of diet-induced obese rats were strikingly up-regulated, whereas the wet weight of abdominal adipose tissue, the levels of serum lipids were markedly reduced.Conclusion: Intraventricular administration of antisense oligodeoxynucleotide to NPY Y5 receptor could significantly reduce the abdominal adipose tissue and the levels of serum lipids in diet-induced obese rats by up-regulating the level of β3-adrenergic receptor gene mRNA expression in retroperitoneal adipose tissue.

Effect of ryanodine on adrenergic stimulation in rat smooth muscle cells

Norepinephrine(NE)endogenously released following electrical field stimulation(prazosin and TTX sensitive responses),produced a biphasic contraction of the rat vas deferens(RVD).The initial transient contraction was decreased by 30μmol/L ryanodine andμmol/L nifedipine while the secondary component was abolished by 2μmol/L nifedipine but increased by 30μmol/L ryanodine.Exogenously added NE produced biphasic contractions of the RVD.These contractions were inhibited by 2μmol/L nifedipine.Ryanodine(30μmol/L)decreased both phases by about 50%.We conclude that ryanodine binding sites reside in RVD endoplasmic reticulum(ER).There was a lack of uniformity in the effect of ryanodine against different phases of alpha-adrenergic stimulation may be indicative of two modes of stimulation-contraction coupling process related to this stimulation.

Expressions of cardiac sympathetic norepinephrine transporter and β_1-adrenergic receptor decreased in aged rats

Evidence suggests that the deterioration of communication between the sympathetic nervous system and cardiovascular system always accompanies the aging of human and animals. Cardiac sympathetic norepinephrine(NE) transporter(NET) on presynaptic membrane is a predominant component to eliminate released NE in the synaptic cleft and maintains the sensitivity of the β-adrenergic receptor(β-AR). In the present study,we investigated NET and β1-AR mRNA levels and sympathetic nerve density in cardiac sympathetic ganglion and left ventricular myocardium in 2-and 16-month-old rats with Northern blot analysis and immunohistochemistry. The expression levels of NET mRNA,NET protein and β1-AR mRNA in the ganglia or myocardia of 16-month-old rats were markedly reduced by 67%,26%,and 43%,respectively,in comparison with those in 2-month-old rats. Our results also show that aging induces a strong decrease of the catecholaminergic nerve fiber density.

Enhanced vasoconstriction to α_1 adrenoceptor autoantibody in spontaneously hypertensive rats

Autoimmune activities have been implicated in the pathogenesis of hypertension.High levels of autoantibodies against the second extracellular loop of α1-adrenoceptor(α1-AR autoantibody,α1-AA) are found in patients with hypertension,and α1-AA could exert a α1-AR agonist-like vasoconstrictive effect.However,whether the vasoconstrictive effect of α1-AA is enhanced in hypertension is unknown.Using aortic rings of spontaneously hypertensive rats(SHR) and normotensive Wistar-Kyoto(WKY) rats,we observed the vasoconstrictive responses to α1-AA with phenylephrine(α1-AR agonist) as a positive control drug.Aortic nitrotyrosine levels were also measured by ELISA and immunohistochemistry.The results showed that the aortic constrictive responses to α1-AA and phenylephrine(both 1 nmol L-1-10 μmol L-1) were greater in SHR than in WKY rats.Endothelial denudation or L-NAME(a non-selective NOS inhibitor)(100 μmol L-1) increased α1-AA- or phenylephrine-induced vasoconstrictions both in SHR and WKY.However,selective iNOS inhibitor 1400W(10 μmol L-1) enhanced the α1-AA-induced aortic constriction in WKY,but not in SHR.The aortic nitrotyrosine level was significantly higher in SHR than WKY,as shown by both ELISA and immunohistochemistry.These results indicate that the vasoconstrictive response to α1-AA is enhanced in SHR,and this altered responsiveness is due to endothelial dysfunction and decreased NO bioavailability.The study suggests an important role of α1-AR autoimmunity in the pathogenesis and management of hypertension especially in those harboring high α1-AA levels.

Effect of Qilongtoutong granule on calcitonin gene-related peptide,beta-endorphin, serotonin, dopamine, and noradrenalin in migraine model rats and mice

OBJECTIVE： To study the effect of Qilongtoutong granule （QLTT） on plasma calcitonin gene-related peptide （CGRP）, beta-endorphin （I[3-EP）, 5-HT, dopa- mine （DA）, noradrenalin （NE）, and blood viscosity in migraine model rats and mice. METHODS： Both the acute blood stasis model group and nitroglycerin-induced migraine model group included 60 Sprague-Dawley rats. The reser- pine-reduced model group had 60 Kunming mice. Rats from each test were grouped into normal con- trol group, model group, Zhengtian pill （ZTP） group, and high, moderate, or low-dose QLTT groups. In the acute blood stasis model test, after gavage for 7 days, rats were given 0.8 mL/kg adren- aline hydrochloride subcutaneously twice, and kept in ice water for 5 min. After fasting for 12 h, rats were anesthetized and blood samples were collected for detection of blood viscosity. In the nitro- glycerin-induced migraine group, after gavage for 7 days, rats were intraperitoneally injected nitro- glycerin （10 mg/kg）, and 4 h later, blood samples were collected from postcava for measuring the plasma CGRP and 13-EP levels. In the reserpine-re- duced model test, except the normal control group, mice were administered reserpine （0.25 mg/ kg, i.h.） for 9 days. Mice received intragastric admin- istration from the third day to the ninth day. One hour after the last gavage, blood and brain tissue samples were obtained. Then, blood clotting time and the contents of neurotransmitters were deter- mined. RESULTS： QLTT- （3.6, 1.8, and 0.9 g/kg） and ZTP-treated rats had lower blood viscosity than that in model rats under different shear rates （P〈 0.01）. QLTT- （3.6, 1.8 g/kg） and ZTP-treated rats had significantly lower plasma CGRP levels and higher plasma 13-EP levels than those in model rats （P〈 0.01）. QLTT treatment at dose of 0.9 g/kg had lower plasma CGRP levels as well （P〈0.05）. QLTT- （5.2, 2.6 g/kg） and ZTP-treated mice had longer blood clotting time than that in model mice （P〈0.01）. QLTT- （2.6 g/kg） and ZTP-treated mice had higher plasma serotonin （5-HT） levels than those in model mice （P〈0.05）. CONCLUSION： QLTT-treated animals had lower plasma CGRP level, higher plasma 13-EP, 5-HT, high- er brain tissue 5-HT, NE, DA levels, and lower blood viscosity than those in the migraine model animals.

Protein and RNA expression of acid-sensing ion channels 2 and 3 in myocardial ischemia rats induced by isoproterenol

OBJECTIVE:To investigate the impact of electro-acupuncture at the Neiguan(PC 6) acupoint on protein and RNA expression of acid-sensing ion channel 2(ASIC2) and ASIC3 in myocardial ischemia rats.METHODS:Fifty male Sprague-Dawley rats were used,weighing(230 ± 50) g.The rats were randomized into a normal group A,model group B,Neiguan(PC 6) group C,Lieque(LU 7) group D,and A-shi points group E.There were 10 rats in each group.Rats were continuously administered 85 mg/kg intravenous isoproterenol daily to establish the model.Successfully modeled rats in groups C,D,and E were given electro-acupuncture treatment.Each group of rats was sacrificed with chloral hydrate(1 mL/100 g) intraperitoneal injection.The left ventricular myocardium was extracted and placed at- 70 ℃ until use.Western blot analysis and real-time PCR were performed to assay protein and RNA expressions of ASIC2 and ASIC3,respectively.Fold changes in RNA expression were quantified with the 2~^(-△△Ct) method.Blood samples were drawn from the aorta abdominalis and tested for creatine kinase-MB(CK-MB) and lactate dehydrogenase(LDH) levels using enzyme-linked immunosorbent assay.RESULTS:Myocardial ischemia rats given electro-acupuncture at the Neiguan(PC 6) acupoint had significantly lower protein and RNA expression of ASIC2 and ASIC3,and CK-MB and LDH levels,compared with model rats(P < 0.01).CONCLUSION:Electro-acupuncture at the Neiguan(PC 6) acupoint can not only decrease the protein and RNA expression of ASIC2 and ASIC3,but also inhibit the opening of ASICs and reduce the cardiomyocyte damage in myocardial ischemia rats.

Effect of tribulus terrestris saponins on behavior and neuroendocrine in chronic mild stress depression rats

OBJECTIVE： To observe the effect of tribulus terres- tris saponins （TTS） on behavior and neuroendo- crine of chronic mild stress （CMS） depression rats. METHODS：ThirtymaleSprague-Dawleyratswereran- domly allocated to six groups： vehicle group, CMS group, CMS ＋ fluoxetine group and CMS ＋ TTS of low-dosage （0.375 g/kg）, medium-dosage （0.75 g/kg） and high-dosage （2.25 g/kg） groups. All rats except the vehicle group singly housed and exposed an unpredicted sequence of mild stressors. The behav- ior of rats was detected by open-field test （OFT） and sucrose preference test （SPT）. The concentra- tion of corticotropin-releasing factor （CRF） and ad- renocorticotropic hormone （ACTH） in serum of the rats were detected by radioimmunoassay. The con- centration of cortisol （CORT） in serum was detected by enzyme immunoassay.RESULTS： CMS procedure not only significantly de- creased the scores of crossing, rears and grooming in OFI： and the sucrose preference in SPT （all P〈 0.01）, but also markedly increased serum CRH and CORT levels （both P〈0.05）. Treatment with TTS （0.75 and 2.25 g/kg） could significantly prevent all of these abnormalities induced by CMS （P〈0.05, P〈 0.01）. CONCLUSION： CMS can affect rat behavior and neuroendocrine and cause depression. TTS has the antagonism on CMS and produce antidepressive ef- fects.

Effect of Chaihushugan San on expression of the Raf/mitogen-activated protein kinase/extracellular signal-regulated kinase pathway in the hippocampi of perimenopausal rats induced by immobilization stress

OBJECTIVE: We wished to study the impact of Chaihushugan San(CSS) on the behavior of perimenopausal rats with liver-Qi stagnation(LQS) and to investigate the effect of CSS on signal transduction of the Raf/mitogen-activated protein kinase(MEK)/extracellular signal-regulated kinase(ERK) cascade in the hippocampi of rats induced by immobilization.METHODS: Twenty 52-week-old female rats were divided into two groups by the random number table method: model control group(MCG) and CSS group(CSSG), with 10 rats in each group.Ten-week-old female rats were used as the normal control group(NCG). CSS effects were assessed using rats exposed to immobilization stress by measuring body weight and sucrose consumption, serum hormone levels, and observing performance in the open field test(OFT). Molecular mechanisms were examined by measuring the effect of CSS on expression of Raf1, MEK1/2 and ERK1/2 m RNA in hippocampi using quantitative real-time polymerase chain reaction and by measuring levels of these proteins and related phospho-proteins using Western blotting.RESULTS: Perimenopausal rats with LQS had decreased locomotor activity; reduced sucrose consumption; and increased serum levels of corticotropin releasing hormone(CRH) and corticosterone(CORT). Activation of hippocampal Raf/MEK/ERK cascade was suppressed significantly in the MCG,and activation was increased after 21 days of CSS treatment.CONCLUSION: CSS has significant effects upon relief of the symptoms of LQS in immobilization-induced rats. The mechanism underlying this action might(at least in part) be mediated by reversal of disruption of the Raf/MEK/ERK pathway.