BACKGROUND The use of proton pump inhibitors(PPIs)with the intent of reducing gastric acidity to the desired therapeutic level for treating bleeding peptic ulcer still has several limitations.AIM To compare intravenou...BACKGROUND The use of proton pump inhibitors(PPIs)with the intent of reducing gastric acidity to the desired therapeutic level for treating bleeding peptic ulcer still has several limitations.AIM To compare intravenous PPIs and oral potassium competitive acid blockers(PCABs)administered prior to endoscopic treatment of bleeding peptic ulcers.METHODS This retrospective study involved 105 consecutive patients with non-variceal upper gastrointestinal bleeding(treated August 2023 to February 2024).Prior to emergency endoscopy,patients received either intravenous PPI(pantoprazole 80 mg bolus)or oral PCAB(tegoprazan 50 mg single-dose).Severity of bleeding was assessed using the Glasgow-Blatchford,Rockall,and AIMS65 scoring systems.Patients with severe comorbidities were excluded.Primary outcomes included need for therapeutic endoscopic intervention and occurrence of re-bleeding.Multivariate logistic regression was performed to adjust for potential confounding factors.RESULTS Total of the 105 patients,61 received intravenous PPI injection and 44 received oral PCAB prior to emergency endoscopy.To minimize selection bias,bleeding severity was assessed using the Glasgow-Blatchford,Rockall and AIMS65 scores,with no statistically significant differences observed between the two groups.During emergency endoscopy performed within 48 hours,ulcer bed status was classified according to the Forrest classification.The proportion of lesions graded IIa or higher was significantly lower in the PCAB group(P<0.001),as was the frequency of therapeutic endoscopy intervention(odds ratio=0.272,95%confidence interval:0.111-0.665,P=0.004).The frequency of re-bleeding events was statistically significantly higher in the PPI group(odds ratio=0.141,95%confidence interval:0.024-0.844,P=0.032).CONCLUSION Pre-endoscopic PCAB administration is more effective than PPI injection for upper gastrointestinal bleeding and may reduce ulcer bleeding mortality.展开更多
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 sympathet...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.展开更多
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...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.展开更多
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). Sev...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.展开更多
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 re...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.展开更多
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 pr...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.展开更多
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 bloc...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.展开更多
AIM:To explore effects of nonselective beta-blockers(NSBBs) in cirrhotic patients with no or small varices.METHODS:The Pub Med,EMBASE,Science Direct,and Cochrane library databases were searched for relevant papers.A m...AIM:To explore effects of nonselective beta-blockers(NSBBs) in cirrhotic patients with no or small varices.METHODS:The Pub Med,EMBASE,Science Direct,and Cochrane library databases were searched for relevant papers.A meta-analysis was performed using ORs with 95%CI as the effect sizes.Subgroup analysis was conducted according to the studies including patients without varices and those with small varices.RESULTS:Overall,784 papers were initially retrieved from the database searches,of which six randomized controlled trials were included in the meta-analysis.The incidences of large varices development(OR = 1.05,95%CI:0.25-4.36;P = 0.95),first upper gastrointestinal bleeding(OR = 0.59,95%CI:0.24-1.47;P = 0.26),and death(OR = 0.70,95%CI:0.45-1.10;P = 0.12) were similar between NSBB and placebo groups.However,the incidence of adverse events was significantly higher in the NSBB group compared with the placebo group(OR = 3.47,95%CI:1.45-8.33;P = 0.005).The results of subgroup analyses were similar to those of overall analyses.CONCLUSION:The results of this meta-analysis indicate that NSBBs should not be recommended for cirrhotic patients with no or small varices.展开更多
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 inhibi...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.展开更多
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 diabet...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.展开更多
AIM: To determine whether the association of β-blockers with endoscopic treatment is superior to endoscopic treatment alone for the secondary prophylaxis of oesophageal variceal bleeding. METHODS: Randomised controll...AIM: To determine whether the association of β-blockers with endoscopic treatment is superior to endoscopic treatment alone for the secondary prophylaxis of oesophageal variceal bleeding. METHODS: Randomised controlled trials comparing sclerotherapy (SCL) with SCL plus β-blockers (BB) or banding ligation (BL) with BL plus BB were identif ied.Main outcomes were overall and 6, 12 and 24 mo rebleeding rates, as well as overall and 6, 12 and 24 mo mortality. Two statistical methods were used: Yusuf-Peto, and Der Simonian and Laird. Inter-trial heterogeneity was systematically taken into account. RESULTS: Seventeen randomised controlled trials were included, 14 with SCL and 3 with BL. Combination β-blocker and endoscopic treatment signif icantly reduced rebleeding rates at 6, 12 and 24 mo and overall [odds ratio (OR): 2.20, 95% conf idence interval (CI): 1.69-2.85, P<0.0001] compared to endoscopic treatment alone. Mortality at 24 mo was signif icantly lower for the combined treatment group (OR: 1.83, 95% CI:1.16-2.90, P= 0.009), as well as overall mortality (OR: 1.43, 95% CI:1.03-1.98, P= 0.03). CONCLUSION: Combination therapy should thus be recommended as the fi rst line treatment for secondary prophylaxis of oesophageal variceal bleeding.展开更多
Proton pump inhibitors(PPIs),the most commonly used antisecretory medications in the management of reflux illness,virtually eliminate elective surgery for ulcer disease,and relegate anti-reflux surgery to patients wit...Proton pump inhibitors(PPIs),the most commonly used antisecretory medications in the management of reflux illness,virtually eliminate elective surgery for ulcer disease,and relegate anti-reflux surgery to patients with gastroesophageal reflux disease(GERD)who are inadequately managed by medical therapy.However,PPI medications still leave some therapeutic demands of GERD unmet.Furthermore,up to 40%-55%of daily PPI users have chronic symptoms,due to PPI refractoriness.Potassium-competitive acid blockers(P-CABs)transcend many of the problems and limits of PPIs,delivering quick,powerful,and extended acid suppression and allowing for treatment of numerous unmet needs.Recently,it has become clear that compromised mucosal integrity plays a role in the etiology of GERD.As a result,esophageal mucosal protection has emerged as a novel and potential treatment approach.An increasing body of research demonstrates that when P-CABs are used as primary drugs or add-on drugs(to regular treatment),they provide a considerable extra benefit,particularly in alleviating symptoms that do not respond to PPI therapy.展开更多
AIM To investigate usefulness of triple therapy with vonoprazan,a potassium ion-competitive acid blocker and antibiotics,for Helicobacter pylori(H.pylori) eradication.METHODS The H.pylori eradication rate was examined...AIM To investigate usefulness of triple therapy with vonoprazan,a potassium ion-competitive acid blocker and antibiotics,for Helicobacter pylori(H.pylori) eradication.METHODS The H.pylori eradication rate was examined in 2507 patients(2055 undergoing primary eradication and 452 undergoing secondary eradication,excluding patients with subtotal gastrectomy) at the Japanese Red Cross Kyoto Daiichi Hospital from March 2013 to September 2015.For patients treated from March 2013 to February 2015,a proton pump inhibitor(PPI) was used to reduce acid secretion,while vonoprazan was used after March 2015.The success rates of the 2 regimens(PPI + amoxicillin + clarithromycin/metronidazole,or vonoprazan + amoxicillin + clarithromycin/metronidazole) were compared.RESULTS The success rate of primary H.pylori eradication was significantly higher in the vonoprazan group.When stratified by the underlying disease,a significant increase of the H.pylori eradication rate was observed in patients with chronic gastritis.A significantly lower H.pylori eradication rate was observed in younger patients compared to older patients in the PPI group,but there was no difference according to age in the vonoprazan group.On the otherhand,the success rate of secondary eradication was similar at approximately 90% in both groups.CONCLUSION Vonoprazan is very useful for primary eradication of H.pylori,and may become a first-line acid secretion inhibitor instead of PPIs.展开更多
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:Mal...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.展开更多
Aldosterone mediates many of the physiological and pathophysiological/cardio-toxic effects of angiotensin II(Ang II). Its synthesis and secretion from the zona glomerulosa cells of the adrenal cortex, elevated in chro...Aldosterone mediates many of the physiological and pathophysiological/cardio-toxic effects of angiotensin II(Ang II). Its synthesis and secretion from the zona glomerulosa cells of the adrenal cortex, elevated in chronic heart failure(HF), is induced by Ang II type 1 receptors(AT1Rs). The AT1R is a G protein-coupled receptor, mainly coupling to Gq/11 proteins. However, it can also signal through β-arrestin-1(βarr1) or-2(βarr2), both of which mediate G protein-independent signaling. Over the past decade, a second, Gq/11 proteinindependent but βarr1-dependent signaling pathway emanating from the adrenocortical AT1R and leading to aldosterone production has become appreciated. Thus, it became apparent that AT1R antagonists that block both pathways equally well are warranted for fully effective aldosterone suppression in HF. This spurred the comparison of all of the currently marketed angiotensin receptor blockers(ARBs, AT1R antagonists or sartans) at blocking activation of the two signaling modes(G protein-, and βarr1-dependent) at the Ang IIactivated AT1R and hence, at suppression of aldosterone in vitro and in vivo. Although all agents are very potent inhibitors of G protein activation at the AT1R, candesartan and valsartan were uncovered to be the most potent ARBs at blocking βarr activation by Ang II and at suppressing aldosterone in vitro and in vivo in post-myocardial infarction HF animals. In contrast, irbesartan and losartan are virtually G protein-"biased" blockers at the human AT1R, with very low efficacy for βarr inhibition and aldosterone suppression. Therefore, candesartan and valsartan(and other, structurally similar compounds) may be the most preferred ARB agents for HF pharmacotherapy, as well as for treatment of other conditions characterized by elevated aldosterone.展开更多
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...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.展开更多
The modern lifestyle caters to an increase in the incidence of peptic ulcer disease,gastroesophageal reflux disease and several other acid-related conditions of the gut. The drugs to prevent these conditions work eith...The modern lifestyle caters to an increase in the incidence of peptic ulcer disease,gastroesophageal reflux disease and several other acid-related conditions of the gut. The drugs to prevent these conditions work either through H2 receptor blockade or inhibition of the H^+, K^+ ATPase enzyme. Although proton pump inhibitors have been proven to be efficacious, they have a slow onset of action with limited resolution of symptoms in most patients. Potassium-competitive acid blockers(P-CABs) are novel drugs that bind reversibly to K^+ ions and block the H^+, K^+ ATPase enzyme, thus preventing acid production. P-CABs have a fast onset of action and have dose-dependent effects on acid production. Animal studies exist that differentiate the better results of P-CABs from proton pump inhibitors; further human trials will give a comprehensive picture of the results and will help to elucidate the therapeutic benefits of this new group of drugs.展开更多
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 junct...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.展开更多
文摘BACKGROUND The use of proton pump inhibitors(PPIs)with the intent of reducing gastric acidity to the desired therapeutic level for treating bleeding peptic ulcer still has several limitations.AIM To compare intravenous PPIs and oral potassium competitive acid blockers(PCABs)administered prior to endoscopic treatment of bleeding peptic ulcers.METHODS This retrospective study involved 105 consecutive patients with non-variceal upper gastrointestinal bleeding(treated August 2023 to February 2024).Prior to emergency endoscopy,patients received either intravenous PPI(pantoprazole 80 mg bolus)or oral PCAB(tegoprazan 50 mg single-dose).Severity of bleeding was assessed using the Glasgow-Blatchford,Rockall,and AIMS65 scoring systems.Patients with severe comorbidities were excluded.Primary outcomes included need for therapeutic endoscopic intervention and occurrence of re-bleeding.Multivariate logistic regression was performed to adjust for potential confounding factors.RESULTS Total of the 105 patients,61 received intravenous PPI injection and 44 received oral PCAB prior to emergency endoscopy.To minimize selection bias,bleeding severity was assessed using the Glasgow-Blatchford,Rockall and AIMS65 scores,with no statistically significant differences observed between the two groups.During emergency endoscopy performed within 48 hours,ulcer bed status was classified according to the Forrest classification.The proportion of lesions graded IIa or higher was significantly lower in the PCAB group(P<0.001),as was the frequency of therapeutic endoscopy intervention(odds ratio=0.272,95%confidence interval:0.111-0.665,P=0.004).The frequency of re-bleeding events was statistically significantly higher in the PPI group(odds ratio=0.141,95%confidence interval:0.024-0.844,P=0.032).CONCLUSION Pre-endoscopic PCAB administration is more effective than PPI injection for upper gastrointestinal bleeding and may reduce ulcer bleeding mortality.
基金supported by the National Natural Science Foundation of China(Grant Nos.82330078,81874010)the National Key Research and Development Program(Grant Nos.2020YFC2009004,2021YFC2501700).
文摘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.
文摘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.
文摘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.
基金supported by Research of Korea Centers for Disease Control and Prevention (2016-ER6304-02)
文摘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.
文摘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.
文摘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.
文摘AIM:To explore effects of nonselective beta-blockers(NSBBs) in cirrhotic patients with no or small varices.METHODS:The Pub Med,EMBASE,Science Direct,and Cochrane library databases were searched for relevant papers.A meta-analysis was performed using ORs with 95%CI as the effect sizes.Subgroup analysis was conducted according to the studies including patients without varices and those with small varices.RESULTS:Overall,784 papers were initially retrieved from the database searches,of which six randomized controlled trials were included in the meta-analysis.The incidences of large varices development(OR = 1.05,95%CI:0.25-4.36;P = 0.95),first upper gastrointestinal bleeding(OR = 0.59,95%CI:0.24-1.47;P = 0.26),and death(OR = 0.70,95%CI:0.45-1.10;P = 0.12) were similar between NSBB and placebo groups.However,the incidence of adverse events was significantly higher in the NSBB group compared with the placebo group(OR = 3.47,95%CI:1.45-8.33;P = 0.005).The results of subgroup analyses were similar to those of overall analyses.CONCLUSION:The results of this meta-analysis indicate that NSBBs should not be recommended for cirrhotic patients with no or small varices.
文摘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.
基金Supported by Biomedical Research Institute Grant(PNU-2013-0373),Pusan National University Hospital
文摘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.
文摘AIM: To determine whether the association of β-blockers with endoscopic treatment is superior to endoscopic treatment alone for the secondary prophylaxis of oesophageal variceal bleeding. METHODS: Randomised controlled trials comparing sclerotherapy (SCL) with SCL plus β-blockers (BB) or banding ligation (BL) with BL plus BB were identif ied.Main outcomes were overall and 6, 12 and 24 mo rebleeding rates, as well as overall and 6, 12 and 24 mo mortality. Two statistical methods were used: Yusuf-Peto, and Der Simonian and Laird. Inter-trial heterogeneity was systematically taken into account. RESULTS: Seventeen randomised controlled trials were included, 14 with SCL and 3 with BL. Combination β-blocker and endoscopic treatment signif icantly reduced rebleeding rates at 6, 12 and 24 mo and overall [odds ratio (OR): 2.20, 95% conf idence interval (CI): 1.69-2.85, P<0.0001] compared to endoscopic treatment alone. Mortality at 24 mo was signif icantly lower for the combined treatment group (OR: 1.83, 95% CI:1.16-2.90, P= 0.009), as well as overall mortality (OR: 1.43, 95% CI:1.03-1.98, P= 0.03). CONCLUSION: Combination therapy should thus be recommended as the fi rst line treatment for secondary prophylaxis of oesophageal variceal bleeding.
文摘Proton pump inhibitors(PPIs),the most commonly used antisecretory medications in the management of reflux illness,virtually eliminate elective surgery for ulcer disease,and relegate anti-reflux surgery to patients with gastroesophageal reflux disease(GERD)who are inadequately managed by medical therapy.However,PPI medications still leave some therapeutic demands of GERD unmet.Furthermore,up to 40%-55%of daily PPI users have chronic symptoms,due to PPI refractoriness.Potassium-competitive acid blockers(P-CABs)transcend many of the problems and limits of PPIs,delivering quick,powerful,and extended acid suppression and allowing for treatment of numerous unmet needs.Recently,it has become clear that compromised mucosal integrity plays a role in the etiology of GERD.As a result,esophageal mucosal protection has emerged as a novel and potential treatment approach.An increasing body of research demonstrates that when P-CABs are used as primary drugs or add-on drugs(to regular treatment),they provide a considerable extra benefit,particularly in alleviating symptoms that do not respond to PPI therapy.
文摘AIM To investigate usefulness of triple therapy with vonoprazan,a potassium ion-competitive acid blocker and antibiotics,for Helicobacter pylori(H.pylori) eradication.METHODS The H.pylori eradication rate was examined in 2507 patients(2055 undergoing primary eradication and 452 undergoing secondary eradication,excluding patients with subtotal gastrectomy) at the Japanese Red Cross Kyoto Daiichi Hospital from March 2013 to September 2015.For patients treated from March 2013 to February 2015,a proton pump inhibitor(PPI) was used to reduce acid secretion,while vonoprazan was used after March 2015.The success rates of the 2 regimens(PPI + amoxicillin + clarithromycin/metronidazole,or vonoprazan + amoxicillin + clarithromycin/metronidazole) were compared.RESULTS The success rate of primary H.pylori eradication was significantly higher in the vonoprazan group.When stratified by the underlying disease,a significant increase of the H.pylori eradication rate was observed in patients with chronic gastritis.A significantly lower H.pylori eradication rate was observed in younger patients compared to older patients in the PPI group,but there was no difference according to age in the vonoprazan group.On the otherhand,the success rate of secondary eradication was similar at approximately 90% in both groups.CONCLUSION Vonoprazan is very useful for primary eradication of H.pylori,and may become a first-line acid secretion inhibitor instead of PPIs.
基金Project (No. 2009K16-02) supported by the Shaanxi Provincial Science and Technology Program of China
文摘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.
文摘Aldosterone mediates many of the physiological and pathophysiological/cardio-toxic effects of angiotensin II(Ang II). Its synthesis and secretion from the zona glomerulosa cells of the adrenal cortex, elevated in chronic heart failure(HF), is induced by Ang II type 1 receptors(AT1Rs). The AT1R is a G protein-coupled receptor, mainly coupling to Gq/11 proteins. However, it can also signal through β-arrestin-1(βarr1) or-2(βarr2), both of which mediate G protein-independent signaling. Over the past decade, a second, Gq/11 proteinindependent but βarr1-dependent signaling pathway emanating from the adrenocortical AT1R and leading to aldosterone production has become appreciated. Thus, it became apparent that AT1R antagonists that block both pathways equally well are warranted for fully effective aldosterone suppression in HF. This spurred the comparison of all of the currently marketed angiotensin receptor blockers(ARBs, AT1R antagonists or sartans) at blocking activation of the two signaling modes(G protein-, and βarr1-dependent) at the Ang IIactivated AT1R and hence, at suppression of aldosterone in vitro and in vivo. Although all agents are very potent inhibitors of G protein activation at the AT1R, candesartan and valsartan were uncovered to be the most potent ARBs at blocking βarr activation by Ang II and at suppressing aldosterone in vitro and in vivo in post-myocardial infarction HF animals. In contrast, irbesartan and losartan are virtually G protein-"biased" blockers at the human AT1R, with very low efficacy for βarr inhibition and aldosterone suppression. Therefore, candesartan and valsartan(and other, structurally similar compounds) may be the most preferred ARB agents for HF pharmacotherapy, as well as for treatment of other conditions characterized by elevated aldosterone.
文摘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.
文摘The modern lifestyle caters to an increase in the incidence of peptic ulcer disease,gastroesophageal reflux disease and several other acid-related conditions of the gut. The drugs to prevent these conditions work either through H2 receptor blockade or inhibition of the H^+, K^+ ATPase enzyme. Although proton pump inhibitors have been proven to be efficacious, they have a slow onset of action with limited resolution of symptoms in most patients. Potassium-competitive acid blockers(P-CABs) are novel drugs that bind reversibly to K^+ ions and block the H^+, K^+ ATPase enzyme, thus preventing acid production. P-CABs have a fast onset of action and have dose-dependent effects on acid production. Animal studies exist that differentiate the better results of P-CABs from proton pump inhibitors; further human trials will give a comprehensive picture of the results and will help to elucidate the therapeutic benefits of this new group of drugs.
基金supported by the Natural Science Foundation of Hubei Province, No. 2010CHB01001
文摘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.
