β-Receptor blocker enhances the anabolic effect of PTH after osteoporotic fracture

The autonomic nervous system plays a crucial role in regulating bone metabolism,with sympathetic activation stimulating bone resorption and inhibiting bone formation.We found that fractures lead to increased sympathetic tone,enhanced osteoclast resorption,decreased osteoblast formation,and thus hastened systemic bone loss in ovariectomized(OVX)mice.However,the combined administration of parathyroid hormone(PTH)and theβ-receptor blocker propranolol dramatically promoted systemic bone formation and osteoporotic fracture healing in OVX mice.The effect of this treatment is superior to that of treatment with PTH or propranolol alone.In vitro,the sympathetic neurotransmitter norepinephrine(NE)suppressed PTH-induced osteoblast differentiation and mineralization,which was rescued by propranolol.Moreover,NE decreased the PTH-induced expression of Runx2 but enhanced the expression of Rankl and the effect of PTH-stimulated osteoblasts on osteoclastic differentiation,whereas these effects were reversed by propranolol.Furthermore,PTH increased the expression of the circadian clock gene Bmal1,which was inhibited by NE-βAR signaling.Bmal1 knockdown blocked the rescue effect of propranolol on the NE-induced decrease in PTHstimulated osteoblast differentiation.Taken together,these results suggest that propranolol enhances the anabolic effect of PTH in preventing systemic bone loss following osteoporotic fracture by blocking the negative effects of sympathetic signaling on PTH anabolism.

β-receptor blocker influences return of spontaneous circulation and chemical examination in rats during cardiopulmonary resuscitation

Objective:We investigated the influence of β-receptor blocker metoprolol on return of spontaneous circulation(ROSC) during cardiopulmonary resuscitation(CPR) in rats with induced myocardial infarction(MI).Methods:Male Sprague-Dawley rats were randomly divided into three groups:the sham-operated group,the MI group without metoprolol,which was fed the vehicle,and the MI+metoprolol group receiving intragastric metoprolol.Each group was further divided randomly into three subgroups,depending on the dosage of epinephrine administered during subsequent CPR applied after the induction of asphyxial cardiac arrest.Results:The ROSC rate was significantly decreased in the low dose subgroup of MI group,unchanged in the medium dose subgroup of MI group,and significantly decreased in the high dose subgroup of MI group,compared with the same dose subgroup of sham-operated group.MI+metoprolol group had a lower ROSC rate than MI group in the medium dose subgroup,and a higher ROSC rate than MI group in the high dose subgroup.There was no difference in blood K+ values of successful rats between MI group and MI+metoprolol group.The rats with successful CPR had lower blood K+ values than rats with unsuccessful CPR in each of the three treatment groups.Conclusions:Metoprolol administered to MI rats over a long period significantly improved ROSC rates under an appropriate dose of epinephrine during CPR.An increasing high blood K+ value would attenuate the rate of a successful CPR.

Treatment of Helicobacter pylori with potassium competitive acid blockers:A systematic review and meta-analysis

BACKGROUND Helicobacter pylori(H.pylori)infects over half the global population,causing gastrointestinal diseases like dyspepsia,gastritis,duodenitis,peptic ulcers,GMALT lymphoma,and gastric adenocarcinoma.Eradicating H.pylori is crucial for treating and preventing these conditions.While conventional proton pump inhibitor(PPI)-based triple therapy is effective,there’s growing interest in longer acid suppression therapies.Potassium competitive acid blocker(P-CAB)triple and dual therapy are new regimens for H.pylori eradication.Initially used in Asian populations,vonoprazan(VPZ)has been recently Food and Drug Administration-approved for H.pylori eradication.AIM To assess the efficacy of regimens containing P-CABs in eradicating H.pylori infection.METHODS This study,following PRISMA 2020 guidelines,conducted a systematic review and meta-analysis by searching MEDLINE and Scopus libraries for randomized clinical trials(RCTs)or observational studies with the following command:[("Helicobacter pylori"OR"H pylori")AND("Treatment"OR"Therapy"OR"Eradication")AND("Vonaprazan"OR"Potassium-Competitive Acid Blocker"OR"P-CAB"OR"PCAB"OR"Revaprazan"OR"Linaprazan"OR"Soraprazan"OR"Tegoprazan")].Studies comparing the efficacy of P-CABs-based treatment to classical PPIs in eradicating H.pylori were included.Exclusion criteria included case reports,case series,unpublished trials,or conference abstracts.Data variables encompassed age,diagnosis method,sample sizes,study duration,intervention and control,and H.pylori eradication method were gathered by two independent reviewers.Meta-analysis was performed in R software,and forest plots were generated.RESULTS A total of 256 references were initially retrieved through the search command.Ultimately,fifteen studies(7 RCTs,7 retrospective observational studies,and 1 comparative unique study)were included,comparing P-CAB triple therapy to PPI triple therapy.The intention-to-treat analysis involved 8049 patients,with 4471 in the P-CAB intervention group and 3578 in the PPI control group across these studies.The analysis revealed a significant difference in H.pylori eradication between VPZ triple therapy and PPI triple therapy in both RCTs and observational studies[risk ratio(RR)=1.17,95%confidence interval(CI):1.11-1.22,P<0.0001]and(RR=1.13,95%CI:1.09-1.17,P<0.0001],respectively.However,no significant difference was found between tegoprazan(TPZ)triple therapy and PPI triple therapy in both RCTs and observational studies(RR=1.04,95%CI:0.93-1.16,P=0.5)and(RR=1.03,95%CI:0.97-1.10,P=0.3),respectively.CONCLUSION VPZ-based triple therapy outperformed conventional PPI-based triple therapy in eradicating H.pylori,positioning it as a highly effective first-line regimen.Additionally,TPZ-based triple therapy was non-inferior to classical PPI triple therapy.

Use of Beta-Blocker in Acute ST-Elevation Myocardial Infarction

This paper reported beta-blocker use in 21 STEMI patients over four years. The patients were between 50 - 65 years of age presenting with anterior, lateral, and inferior STEMI (ST-Elevation Myocardial Infarction). Seven of the patients were female, and 14 were male. They presented to an emergency room of a rural hospital that did not provide emergency percutaneous coronary angioplasty/stenting (PTCA/stenting). The hospital is about 70 minutes from a facility that provided PTCA/ stenting—all the patients presented with typical angina chest pain with ST elevation. They are hemodynamic stable. Most patients received Lopressor 35 mg IVP, with one receiving 115 mg in a 5 mg increment. They were chest pain-free and hemodynamically before leaving the ER for the transfer for PTCA/stent. The results demonstrated that beta-blockers are effective in relieving pain in STEMI patients. Further study is needed to determine its efficacy, safety, and how to use it.

水中β受体阻滞剂类心血管药物污染研究进展

随着心血管药物使用量的逐年上升,各种环境介质中已普遍检测到心血管药物的存在。由于其生物累积性与潜在毒性,如何有效控制水中心血管类药物污染物及评估其生态风险是目前研究的热点。文章以β受体阻滞剂为典型心血管药物,主要阐述其在环境中的分布、迁移、转化和生态毒性,目前已在各类环境样品中检测到多达12种β受体阻滞剂,相关研究多集中于废水和地表水,地下水中的研究较少。文章总结了其污染控制技术,提出重点研究方向:(1)加强不同环境基质中的监测、深入调查其在中国不同地区的环境分布状况;(2)深入研究β受体阻滞剂的代谢途径、代谢物及其生态效应,以及混合药物的协同生物学效应,以期为水中心血管药物的治理和风险控制提供参考。

钠离子通道阻滞剂药物治疗颞叶癫痫相关的脑功能复杂网络的变化

目的 探讨钠离子通道阻滞剂(SCB)治疗相关的脑功能复杂网络的变化以及对执行控制功能影响的神经机制。方法 将21例服用SCB的颞叶癫痫患者(TLE-SCB)和12例未服用SCB的颞叶癫痫患者(TLE-N)与18例健康对照(HC)一起纳入研究。完成行静息态功能磁共振成像(rs-fMRI)和注意网络测试(ANT),应用图论方法研究3组受试者脑功能复杂网络的变化,研究脑网络变化与执行功能的关系。结果 TLE-SCB组和TLE-N组相比HC组均出现执行功能损害。脑网络拓扑属性分析结果显示,TLE-SCB组与TLE-N组相比,多个节点介数中心性降低(均Bonferroni校正,P <0.017);右侧杏仁核节点聚类系数、左侧枕下回局部效率都降低(t=-2.953,P=0.006;t=-2.597,P=0.0142)。TLE-SCB相比于HC组,多个节点介数中心性降低(均Bonferroni校正,P <0.017);左侧眶部额中回节点聚类系数增加(t=2.861,P=0.007);左侧颞下回局部效率降低(t=-2.870,P=0.007)。TLE-N组相比于HC组,右侧中央旁小叶介数中心性、局部效率增加(t=2.644,P=0.013;t=3.464,P=0.002);右侧杏仁核节点聚类系数增加(t=2.884,P=0.007)。相关分析显示:TLE-SCB组左侧枕下回介数中心性降低与执行效率呈负相关(P=0.045,r=-0.441)。结论 使用SCB药物患者出现相关脑功能网络拓扑属性的改变,可能是SCB认知障碍的网络基础。左侧枕下回可能在使用SCB的癫痫患者执行控制功能损害中发挥重要作用。

星状神经节阻滞联合尼麦角林对脑卒中后吞咽困难的疗效观察

目的探讨星状神经节阻滞(SGB)联合尼麦角林对脑卒中后吞咽困难的治疗效果。方法选取卒中后吞咽困难患者104例,随机分为观察组和对照组。观察组采用尼麦角林联合SGB治疗,对照组采用功能性电刺激治疗。比较2组总有效率、吞咽情况、炎性因子水平及不良事件。结果治疗后,观察组总有效率高于对照组(92.31%vs.73.08%,P<0.05);观察组标准吞咽功能评价量表(SSA)评分、白细胞介素-6(IL-6)水平、肿瘤坏死因子α(TNF-α)水平低于对照组(P<0.05),曼恩吞咽能力评估量表(MASA)评分高于对照组(P<0.05);且2组声门关闭、喉痉挛等不良反应发生率差异无统计学意义(P>0.05)。结论脑卒中后吞咽困难患者采用SGB联合尼麦角林治疗可有效改善吞咽功能,安全性良好,效果较为理想,临床应用价值较高。

A 3D-QSAR Study on a Novel Chromanol Class of I_ (Ks) Potassium Channel Blockers

Aim and Method A novel three-dimensional quantitative structure-activityrelationship (3D-QSAR) method, self-organizing molecular field analysis (SOMFA) , was used toinvestigate the correlation between the molecular properties and a class of chromanol analogs asI_(Ks) blockers. Results The cross-validated correlation coefficient q^2 values (0.698) and noncross-validated correlation coefficient r^2 values (0.701) proved a good conventional statisticalcorrelation. Conclusion The final SOMFA model has therefore good predictive activity for the furthermolecular design of chromanol I_(Ks) potassium channel blockers.

支气管封堵器与双腔气管导管用于成人胸科手术气道管理安全性的Meta分析

目的利用Meta分析的方法评价支气管封堵器与双腔气管导管用于成人胸科手术气道管理安全性。方法检索PubMed、MedLine、the Cochrane Library、中国知网数据库、万方数据库、维普数据库,收集2024年7月前关于支气管封堵器与双腔气管导管用于成人胸科手术的随机对照试验,按改良Jadad量表评价研究质量,提取相关数据后采用Stata 18.0进行Meta分析。结果共纳入14篇文献,883例研究对象(其中封堵器组445例,双腔管组438例)。Meta分析结果显示,封堵器的首次插管成功率高于双腔管(RR=1.10,95%CI:1.03~1.16,P=0.002);封堵器的气道峰压低于双腔管(SMD=-4.67,95%CI:-5.11~4.24,P<0.001);封堵器的围术期并发症少于双腔管(RR=0.53,95%CI:0.44~0.65,P<0.001)。封堵器和双腔管的插管定位时间、肺萎陷质量差异无统计学意义。结论支气管封堵器用于成人胸科手术气道管理的安全性好,同时并发症少。

Antineoplastic Effect of Calcium Channel Blocker-Verapamil and 5-Fluorouracil Intraperitoneal Chemotherapy on Hepatocarcinoma-Bearing Rats

Objective To study the antineoplastic effect of the calcium channel blocker verapamil and 5-fluorouracil intraperitoneal chemotherapy onhepatocarcinoma-bearing rats, and examine the action between calcium channel blockers and cytotoxic drugs.Methods We adopted the method of subcapsular implantation of carcinoma tissues of walker-256 in the left liver lobe as a model of livercarcinoma-bearing rats. All experimental animals were divided into four groups. On the sixth day post implantation, in group A (controlgroup) 6 ml of saline was injected intraperitoneally once a day for 3 days. In group B (single chemotherapy group) 6 ml of 5-Fu 75 mg/kg was injected intraperitoneally once a day for 3 days. In group C (combination of treatment group) both 5-Fu (75 mg/kg) and verapamil(25 mg/kg) were administered simultaneously as in A and B. In group D (simple verapamil group) only 6 ml of verapamil (25 mg/kg)was administered as above.Results Compared with groups A, B and D, The volume of cancer and the contents of liver cancer DNA and protein were significantlyreduced. The rates of inhibiting cancer (89.9% in group C and 35.4% in group B) were significantly increased in group C. Group C hadsignificantly long survival time compared to groups A, B and D ( P < 0.05) . By light microscopy, a number of focal necroses were foundin cancer tissue in group C.Conclusion Calcium channel blockers can enhance the antineoplastic effect of 5-Fu intraperitoneal chemotherapy to liver cancer ; Theuse of verapamil can not increase the toxicity of 5-Fu.

Bax channel blocker逆转衰老骨髓间充质干细胞生物学行为的研究

目的:探讨Bax channel blocker(BCB)对自然衰老大鼠骨髓间充质干细胞(aged-BMSCs)生物学功能的影响。方法:全骨髓贴壁培养法获得22月龄(老年)和2周龄(年青)大鼠BMSCs,β-gal染色鉴定aged-BMSCs,用BCB对实验组细胞进行干预,以Nanog和Oct-4为靶标,RT-PCR筛选最佳作用浓度。使用RT-PCR和Western Blot分别检测细胞衰老水平及成骨分化的关键基因及蛋白的表达;对细胞药物干预同时进行成骨分化诱导,培养14 d后进行碱性磷酸酶(ALP)染色,21 d后茜素红染色。结果:BCB对aged-BMSCs最佳实验浓度为10μmol/L。BCB能明显降低aged-BMSCs细胞内β-gal含量,在mRNA水平和蛋白水平降低衰老相关基因p53和p21WAF1/cip1表达;明显提升干细胞标记物Nanog、Oct-4。成骨分化诱导后,成骨分化标志基因表达上调,ALP和茜素红染色水平提升。结论:BCB能够逆转aged-BMSCs的衰老,促进其骨向分化。

Risks of anti-Helicobacter therapy and long-term therapy with antisecretory drugs

Helicobacter pylori(H.pylori)infection has a protective effect on gastroesophageal reflux disease(GERD).Both of these diseases have a very high incidence and prevalence.As a result,GERD often recurs after anti-Helicobacter therapy.The problem of effective treatment of H.pylori infection and GERD is that the main groups of drugs[proton pump inhibitors(PPIs)and potassium-competitive acid blockers]have the possibility of side effects with use.Such supposed side effects have no evidence in randomized controlled trials that comply with the principles of evidence-based medicine.Morphological changes in the gastric mucosa after long-term use of antisecretory drugs should be considered as compensatory mechanisms of sanogenesis.The greatest concern for doctors who treat patients with antisecretory drugs is the risk of gastric carcinogenesis.This article presents an analysis of morphological and pathophysiological changes that occur after long-term use of antisecretory drugs(PPIs).Hypertrophy(hyperplasia)of G cells,enterochromaffin-like cells and possible fundic gland polyps(hyperplasia)are compensatory mechanisms of sanogenesis during long-term treatment with PPIs.These mechanisms are of primary importance for rehabilitation and prevention of complications in patients with GERD,non-steroidal anti-inflammatory drugsgastropathy and other diseases during long-term treatment with PPIs.Understanding the pathophysiological and morphological mechanisms of compensation and adaptation,the mechanisms of sanogenesis and carcinogenesis will increase the number of indications for long-term use of PPIs with a high level of efficiency and safety of treatment.In addition,understanding the pathophysiological and morphological mechanisms of compensation and adaptation,the mechanisms of sanogenesis will allow us to forecast the side effects of long-term use of potassium-competitive acid blockers.

大罐笼载胶轮车用液压自动阻车器的开发

针对传统大罐笼内的胶轮车阻车器多为手动阻车,提出了一种无轨胶轮车用液压自动阻车器。该液压阻车器采用液压自动控制,无须工人进罐操作,安全、可靠,为立井大罐笼载无轨胶轮车的运输安全提供了保障。

Long-term clinical outcome between beta-blocker with ACEI or ARB in patients with NSTEMI who underwent PCI with drug-eluting stents

Background Because limited comparative data are available,we decided to compare 2-year major clinical outcomes between beta-blockers (BB) with angiotensin converting enzyme inhibitors (ACEI) and BB with angiotensin receptor blockers (ARB) therapy in patients with non-ST-segment elevation myocardial infarction (NSTEMI) after percutaneous coronary intervention (PCI) with drug-eluting stents (DES).Methods A total 11,288 NSTEMI patients who underwent PCI with DES were enrolled and they were divided into two groups,the BB with ACEI group (n = 7600) and the BB with ARB group (n = 3688).The major clinical endpoint was the occurrence of major adverse cardiac events (MACE) defined as all-cause death,recurrent myocardial infarction (re-MI),total revascularization [target lesion revascularization (TLR),target vessel revascularization (TVR),non-TVR] rate during the 2-year follow-up period.Results After propensity score-matched (PSM) analysis,two PSM groups (3317 pairs,n = 6634,C-statistic = 0.695) were generated.Although the cumulative incidences of all-cause death,cardiac death,TLR,and non-TVR were similar between the two groups,MACE (HR = 0.832,95% CI: 0.704?0.982,P = 0.030),total revascularization rate (HR = 0.767,95% CI: 0.598?0.984,P = 0.037),and TVR rate (HR = 0.646,95% CI: 0.470?0.888,P = 0.007) were significantly lower in the BB with ACEI group after PSM.Conclusions In this study,we suggest that the combination of BB with ACEI may be beneficial for reducing the cumulative incidences of MACE,total revascularization rate,and TVR rather than the BB with ARB after PCI with DES in NSTEMI patients.

改良Blocker PCR检测EGFR-TKI耐药后非小细胞肺癌血浆EGFR T790M突变的价值

目的探讨改良PCR(Blocker PCR)方法在晚期非小细胞肺癌(non-small-cell lung cancer,NSCLC)患者血浆游离DNA(cell free DNA,cfDNA)中检测继发EGFR T790 M突变的应用价值。方法采用Blocker PCR方法对127例表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitor,EGFR-TKI)耐药后肺癌患者的血浆标本行EGFR敏感突变和T790 M突变检测,统计T790 M突变的检出率;为验证Blocker PCR血浆检测的可靠性,部分患者血浆标本行二代测序(next generation sequencing,NGS)和Blocker PCR配对比较;获得配对血浆和组织的病例行Blocker PCR配对检测。结果在127例采用Blocker PCR方法检测的EGFR-TKI耐药NSCLC患者中,T790 M耐药突变的检出率为40.15%(51/127),其中21.56%(11/51)为单纯T790 M耐药突变,78.44%(40/51)为T790 M合并原有EGFR敏感突变。组织与血浆配对检测中,EGFR-TKI耐药后二次活检组织标本T790 M的检出率为54.54%(6/11),血浆T790 M的检出率为43.75%(14/32)。在同时行Blocker PCR和二代测序基因检测的18例患者中,敏感突变位点及T790 M突变位点在两种检测方法中的一致率均为100%。结论在EGFR-TKI耐药后的NSCLC患者中使用Blocker PCR检测血浆T790 M突变是对组织活检的重要补充。

Calcium channel blocker monotherapy versus combination with reninangiotensin system inhibitors on the development of new-onset diabetes mellitus in hypertensive Korean patients

Background In real practice, two or more antihypertensive drugs are needed to achieve target blood pressure. We investigated the comparative beneficial actions of combination therapy of renin-angiotensin system inhibitors (RASI), with calcium channel blockers (CCB) over CCB monotherapy on the development of new-onset diabetes mellitus (NODM) in Korean patients during four-year follow-up periods. Methods A total of 3208 consecutive hypertensive patients without a history of diabetes mellitus who had been prescribed CCB were retrospectively enrolled from January 2004 to December 2012. These patients were divided into the two groups according to the additional use of RASI (the RASI group, n = 1221 and the no RASI group, n = 1987). Primary endpoint was NODM, defined as a fasting blood glucose ≥ 126 mg/dL or hemoglobin A1c ≥ 6.5%. Secondary endpoint was major adverse cardiac events (MACE) defined as total death, myocardial infarction (MI) and percutaneous coronary intervention (PCI). Results After propensity score-matched (PSM) analysis, two propensity- matched groups (939 pairs, n = 1878, C-statistic = 0.743) were generated. The incidences of NODM (HR = 1.009, 95% CI: 0.700–1.452, P = 0.962), MACE (HR = 0.877, 95% CI: 0.544–1.413, P = 0.589), total death, MI, PCI were similar between the two groups after PSM during four years. Conclusions The use of RASI in addition to CCB showed comparable incidences of NODM and MACE compared to CCB monotherapy in non-diabetic hypertensive Korean patients during four-year follow-up period. However, large-scaled randomized controlled clinical trials will be required for a more definitive conclusion.

Rethinking the role of non-selective beta blockers in patients with cirrhosis and portal hypertension

Non-selective beta blockers(NSBB) are commonly used to prevent portal hypertensive bleeding in cirrhotics.Nevertheless, in the last years, the use of NSBB in critically decompensated patients, especially in those with refractory ascites, has been questioned, mainly for an increased risk of mortality and worsening of systemic hemodynamics. Moreover, even if NSBB have been reported to correlate with a higher risk of renal failure and severe infection in patients with advanced liver disease and hypotension, their use has been associated with a reduction of risk of spontaneous bacterial peritonitis, modification of gut permeability and reduction of bacterial translocation. This manuscript systematically reviews the published evidences about harms and benefits of the use of NSBB in patients with decompensated cirrhosis.

Effect of angiotensin Ⅱ type 1 receptor blocker and angiotensin converting enzyme inhibitor on the intraocular growth factors and their receptors in streptozotocin-induced diabetic rats

AIM： To investigate the effect of angiotensin II type 1 receptor blocker （ARB） and angiotensin converting enzyme inhibitor （ACEI） on intraocular growth factors and their receptors in streptozotocin-induced diabetic rats. METHODS： Forty Sprague-Dawley rats were divided into 4 groups： control, diabetes mellitus （DM）, candesartan- treated DM, and enalapril-treated DM （each group, n---10）. After the induction of DM by streptozotocin, candesartan [ARB, 5 mg/（kg · d）] and enalapril [ACEI, 10 mg/（kg · d）] were administered to rats orally for 4Wko Vascular endothelial growth factor （VEGF） and angiotensin II （Ang II） concentrations in the vitreous were measured using enzyme-linked immunosorbent assays, and VEGF receptor 2 and angiotensin II type 1 receptor （ATIR） levels were assessed at week 4 by Western blotting. RESULTS： Vitreous Ang II levels were significantly higher in the DM group and candesartan-treated DM group than in the control （P=0.04 and 0.005, respectively）. Vitreous ATIR increased significantly in DM compared to the other three groups （P〈0.007）. Candesartan-treated DM rats showed higher vitreal ATIR concentration than the enalapril-treated DM group and control （P〈0.001 and P=0.005, respectively）. No difference in vitreous Ang II and ATIR concentration was found between the enalapril- treated DM group and control. VEGF and its receptor were below the minimum detection limit in all 4 groups. CONCLUSION： Increased Ang II and ATIR in the hyperglycemic state indicate activated the intraocular renin-angiotensin system, which is inhibited more effectively by systemic ACEI than systemic ARB.

Experimental Study on AT1-receptor-peptide-induced Myocardial Immune Damage in Rat

In order to investigate the immunological damage in rat immunized with AT1-receptor peptide, 18 male Wistar rats were divided into two groups: immunized-group (n=12), each rat was immunized with 150 μg AT 1-receptor petide coupled to bovine serum albumin, together with Freund's adjuvant. Control group (n=6), sham-immunized, 'immunized liquid' was same as immunized-group except AT1-receptor peptide. Systolic blood pressure (SBP) was measured by using the tail-cuff technique, antibody against AT1-receptor peptide detected by using ELISA method, and left ventricular myocardium and renal cortex sections were observed under light and electron microscopy. There was no significant difference in SBP and light microscopic observation of the tissue sections between the immunized-group and control group. The O.D. value of anti-AT1-receptor peptide antiserum was significantly higher in the immunized-group than in the rats before immunization and control group (P<0.01). Positive rate in the immunized-group was 100 %, while 0 % in the control group. Ultramicroscopic morphology showed potential myocardial injury, including: increase in number of mitochondria, swelling of many mitochondria with reduction in number or absence of their cristae and cristolysis, disorder of the cardiac myofibrils, and myofibrillar disruption and myocytolysis. And lysosomes were increased in renal tubular epithelia. The AT1-receptor peptide could induce to generate the antibody against AT1-receptor peptide and lead to myocardial and renal damage in rats.

The gap junction blocker carbenoxolone enhances propofol and sevoflurane-induced loss of consciousness

General anesthetics induce loss of consciousness by inhibiting ascending arousal pathways, and they interfere with gap junction electrical coupling. The present study aimed to determine whether inhibition of gap junction-mediated signaling could influence general anesthetic-induced loss of consciousness. The general anesthetics sevoflurane and propofol were used. Intracerebroventricular administration of carbenoxolone, a gap junction blocker, significantly decreased the time to loss of the righting reflex （P 0.05）, but prolonged the time to recovery of the reflex （P 0.05）. Moreover, intracerebroventricular administration of carbenoxolone increased the sensitivity to sevoflurane, with a leftward shift of the loss of righting reflex dose-response curve, and decreased the 50% effective concentration of sevoflurane. These results suggest that the gap junction blocker carbenoxolone enhances propofol and sevoflurane-mediated general anesthesia.