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
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 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
Currently, nonselective β-blockers (NSBBs) are commonly used for the prevention of variceal bleeding in liver cirrhosis. The beneficial effects of NSBBs are primarily attributed to the reduction in cardiac...Currently, nonselective β-blockers (NSBBs) are commonly used for the prevention of variceal bleeding in liver cirrhosis. The beneficial effects of NSBBs are primarily attributed to the reduction in cardiac output by blockade of β1 receptors and vasoconstriction of the splanchnic circulation by the blockade of β2 receptors. The prognostic value of occlusive portal vein thrombosis (PVT) in cirrhotic patients has been increasingly recognized. The most important risk factor for the development of PVT in liver cirrhosis is the decreased portal vein inflow velocity. Collectively, we propose that the use of NSBBs potentially increases the development of portal vein thrombosis by reducing portal vein inflow velocity. The hypothesis should be confirmed by prospective cohort studies, in which cirrhotic patients without prior PVT treated with and without NSBBs are enrolled, and the development of PVT during follow-up is compared between the two groups. Additionally, subgroup analyses should be performed according to the dosage of NSBBs and the reduction of portal inflow velocity after use of NSBBs.展开更多
Background β-blocker (BB) therapy is a cornerstone for the treatment of coronary heart disease (CHD).The evidence of the benefit from long-term BB therapy in diabetic patients with stable CHD is scarce.This meta-anal...Background β-blocker (BB) therapy is a cornerstone for the treatment of coronary heart disease (CHD).The evidence of the benefit from long-term BB therapy in diabetic patients with stable CHD is scarce.This meta-analysis summarizes the evidence relating to the BB therapy in diabetic patients with stable CHD.Methods A meta-analysis was performed according to PRISMA and MOOSE guidelines for reporting of systematic reviews of observational studies.PubMed,Embase,and Cochrane central were searched and two authors independently screened studies for eligibility.The quality of studies was assessed with the Newcastle Ottawa scale.The primary outcome of interest was all-cause mortality,cardiovascular (CV) mortality and major adverse cardiovascular events (MACE) in diabetic patients with and without BB therapy.A generic inverse variance model was used to pool odds ratio or hazards ratio from included studies to calculate the overall effect estimate.The significance threshold was set at P-value < 0.05.Heterogeneity was assessed by I2.Results Four non-randomized studies with 9515 participants were selected for the analyses.Four studies were post-hoc analyses of randomized controlled trials,and one article was an analysis of a nationally representative survey.In a fixed effects model,BB therapy in diabetic patients with stable CHD was found to be associated with increased risk of CV mortality,and MACE (27% and 32% respectively;P-value < 0.05) and was not associated with a reduction in all-cause mortality (HR 1.12;95% CI: 0.94–1.33;P-value = 0.22).Conclusion BB therapy in diabetic patients with stable CHD appears to be linked to higher mortality.Large randomized trials are needed in this population to confirm these findings.展开更多
Aim: To investigate the effect of substituting β-blockers with nebivolol on the erectile function of patients suffering from essential hypertension. Methods: Forty-four young and middle-aged men (31-65 years) wit...Aim: To investigate the effect of substituting β-blockers with nebivolol on the erectile function of patients suffering from essential hypertension. Methods: Forty-four young and middle-aged men (31-65 years) with essential hypertension visited our outpatient clinic and took β-blocker treatment (atenolol, metoprolol or bisoprolol) for more than 6 months. All the patients completed a questionnaire regarding erectile function (International Index for Erectile Function). Patients were then switched to an equipotent dose of nebivolol for 3 months and, at the end of this time period, filled out the same questionnaire. Results: Twenty-nine out of the 44 (65.9%) patients who took p-blockers (atenolol, metoprolol or bisoprolol) had exhibited erectile dysfunction (ED). Their systolic and diastolic blood pressure did not change significantly with the treatment switch. In 20 out of these 29 (69%) patients, a significant improvement in the erectile function score was exhibited after 3 months of nebivolol administration, and in 11 of these 20 patients, erectile function was normalized. Conclusion: Nebivolol seems to have a beneficial effect on ED (possibly due to increased nitric oxide availability); however, further prospective, randomized, placebo-controlled studies are needed to confirm the beneficial effects of nebivolol. (Asian J Androl 2006 Mar; 8: 177-182)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
Alzheimer's disease is characterized by two pathological hallmarks: amyloid plaques and neurofibrillary tangles. In addition, calcium homeostasis is disrupted in the course of human aging Recent research shows that ...Alzheimer's disease is characterized by two pathological hallmarks: amyloid plaques and neurofibrillary tangles. In addition, calcium homeostasis is disrupted in the course of human aging Recent research shows that dense plaques can cause functional alteration of calcium signals in mice with Alzheimer's disease. Calcium channel blockers are effective therapeutics for treating Alzheimer's disease. This review provides an overview of the current research of calcium channel blockers involved in Alzheimer's disease theraov.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
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
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
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
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
Objective: To evaluate the association between hypertension and β-blocker (BB) use and antepartum depression risk. Patients and Methods: We conducted a retrospective cohort study of women who delivered within our int...Objective: To evaluate the association between hypertension and β-blocker (BB) use and antepartum depression risk. Patients and Methods: We conducted a retrospective cohort study of women who delivered within our integrated health system between 2009 and 2015, and completed an Edinburgh Postnatal Depression Scale (EPDS) during pregnancy. Increased depression risk was defined as EPDS score ≥ 10, or an affirmative answer to question ten, endorsing self-harm. Antepartum hypertension was determined by blood pressure measurements and provider ICD-9 codes. Regression analyses examined the independent associations of BB use and hypertension on antepartum depression risk. Results: Of 9192 deliveries during the study time frame, 5% were hypertensive. Within the hypertensive group, 103 (22%) used a single agent BB (BB Group), 325 (68%) required no antihypertensive medication (No-Med Group), and 48 (10%) used a non-BB single agent or multi-agent therapy (All-Other Group). After adjusting for covariates, compared to normotensive pregnancies, antepartum hypertension was significantly associated with both EPDS score ≥ 10 (adjusted odds ratio [aOR] 1.61, 95% confidence interval [CI] 1.17 - 2.21) and endorsement of self-harm (aOR 1.76, 95% CI 1.05 - 2.95). In further analyses of depression risk in hypertensive pregnancies, there was no difference between the BB Group and No-Med Group (EPDS score ≥ 10, aOR 1.22, 95% CI 0.56 - 2.63;self-harm, aOR 0.84, 95% CI 0.32 - 2.21), or between the All-Other Group and No-Med Group (EPDS ≥ 10, aOR 1.42, 95% CI 0.57 - 3.54;self-harm, aOR 1.04, 95% CI 0.29 - 3.74). Conclusion: Women with antepartum hypertension have increased risk for depression and thoughts of self-harm. β-Blocker use is not associated with further increased risk.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
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.
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 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Currently, nonselective β-blockers (NSBBs) are commonly used for the prevention of variceal bleeding in liver cirrhosis. The beneficial effects of NSBBs are primarily attributed to the reduction in cardiac output by blockade of β1 receptors and vasoconstriction of the splanchnic circulation by the blockade of β2 receptors. The prognostic value of occlusive portal vein thrombosis (PVT) in cirrhotic patients has been increasingly recognized. The most important risk factor for the development of PVT in liver cirrhosis is the decreased portal vein inflow velocity. Collectively, we propose that the use of NSBBs potentially increases the development of portal vein thrombosis by reducing portal vein inflow velocity. The hypothesis should be confirmed by prospective cohort studies, in which cirrhotic patients without prior PVT treated with and without NSBBs are enrolled, and the development of PVT during follow-up is compared between the two groups. Additionally, subgroup analyses should be performed according to the dosage of NSBBs and the reduction of portal inflow velocity after use of NSBBs.
文摘Background β-blocker (BB) therapy is a cornerstone for the treatment of coronary heart disease (CHD).The evidence of the benefit from long-term BB therapy in diabetic patients with stable CHD is scarce.This meta-analysis summarizes the evidence relating to the BB therapy in diabetic patients with stable CHD.Methods A meta-analysis was performed according to PRISMA and MOOSE guidelines for reporting of systematic reviews of observational studies.PubMed,Embase,and Cochrane central were searched and two authors independently screened studies for eligibility.The quality of studies was assessed with the Newcastle Ottawa scale.The primary outcome of interest was all-cause mortality,cardiovascular (CV) mortality and major adverse cardiovascular events (MACE) in diabetic patients with and without BB therapy.A generic inverse variance model was used to pool odds ratio or hazards ratio from included studies to calculate the overall effect estimate.The significance threshold was set at P-value < 0.05.Heterogeneity was assessed by I2.Results Four non-randomized studies with 9515 participants were selected for the analyses.Four studies were post-hoc analyses of randomized controlled trials,and one article was an analysis of a nationally representative survey.In a fixed effects model,BB therapy in diabetic patients with stable CHD was found to be associated with increased risk of CV mortality,and MACE (27% and 32% respectively;P-value < 0.05) and was not associated with a reduction in all-cause mortality (HR 1.12;95% CI: 0.94–1.33;P-value = 0.22).Conclusion BB therapy in diabetic patients with stable CHD appears to be linked to higher mortality.Large randomized trials are needed in this population to confirm these findings.
文摘Aim: To investigate the effect of substituting β-blockers with nebivolol on the erectile function of patients suffering from essential hypertension. Methods: Forty-four young and middle-aged men (31-65 years) with essential hypertension visited our outpatient clinic and took β-blocker treatment (atenolol, metoprolol or bisoprolol) for more than 6 months. All the patients completed a questionnaire regarding erectile function (International Index for Erectile Function). Patients were then switched to an equipotent dose of nebivolol for 3 months and, at the end of this time period, filled out the same questionnaire. Results: Twenty-nine out of the 44 (65.9%) patients who took p-blockers (atenolol, metoprolol or bisoprolol) had exhibited erectile dysfunction (ED). Their systolic and diastolic blood pressure did not change significantly with the treatment switch. In 20 out of these 29 (69%) patients, a significant improvement in the erectile function score was exhibited after 3 months of nebivolol administration, and in 11 of these 20 patients, erectile function was normalized. Conclusion: Nebivolol seems to have a beneficial effect on ED (possibly due to increased nitric oxide availability); however, further prospective, randomized, placebo-controlled studies are needed to confirm the beneficial effects of nebivolol. (Asian J Androl 2006 Mar; 8: 177-182)
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.
基金supported by the National Natural Science Foundation of China, No. 81171206
文摘Alzheimer's disease is characterized by two pathological hallmarks: amyloid plaques and neurofibrillary tangles. In addition, calcium homeostasis is disrupted in the course of human aging Recent research shows that dense plaques can cause functional alteration of calcium signals in mice with Alzheimer's disease. Calcium channel blockers are effective therapeutics for treating Alzheimer's disease. This review provides an overview of the current research of calcium channel blockers involved in Alzheimer's disease theraov.
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.
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.
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.
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.
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.
文摘Objective: To evaluate the association between hypertension and β-blocker (BB) use and antepartum depression risk. Patients and Methods: We conducted a retrospective cohort study of women who delivered within our integrated health system between 2009 and 2015, and completed an Edinburgh Postnatal Depression Scale (EPDS) during pregnancy. Increased depression risk was defined as EPDS score ≥ 10, or an affirmative answer to question ten, endorsing self-harm. Antepartum hypertension was determined by blood pressure measurements and provider ICD-9 codes. Regression analyses examined the independent associations of BB use and hypertension on antepartum depression risk. Results: Of 9192 deliveries during the study time frame, 5% were hypertensive. Within the hypertensive group, 103 (22%) used a single agent BB (BB Group), 325 (68%) required no antihypertensive medication (No-Med Group), and 48 (10%) used a non-BB single agent or multi-agent therapy (All-Other Group). After adjusting for covariates, compared to normotensive pregnancies, antepartum hypertension was significantly associated with both EPDS score ≥ 10 (adjusted odds ratio [aOR] 1.61, 95% confidence interval [CI] 1.17 - 2.21) and endorsement of self-harm (aOR 1.76, 95% CI 1.05 - 2.95). In further analyses of depression risk in hypertensive pregnancies, there was no difference between the BB Group and No-Med Group (EPDS score ≥ 10, aOR 1.22, 95% CI 0.56 - 2.63;self-harm, aOR 0.84, 95% CI 0.32 - 2.21), or between the All-Other Group and No-Med Group (EPDS ≥ 10, aOR 1.42, 95% CI 0.57 - 3.54;self-harm, aOR 1.04, 95% CI 0.29 - 3.74). Conclusion: Women with antepartum hypertension have increased risk for depression and thoughts of self-harm. β-Blocker use is not associated with further increased risk.
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.