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

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

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

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

Impact of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers on the mortality in sepsis: A meta-analysis

BACKGROUND The effect of angiotensin-converting enzyme inhibitors(ACEIs)or angiotensin receptor blockers(ARBs)on the mortality of patients with sepsis is not well characterized.AIM To elucidate the association between prior ACEI or ARB exposure and mortality in sepsis.METHODS The PubMed,EMBASE,Web of Science,and Cochrane Library databases were searched for all studies of premorbid ACEI or ARB use and sepsis mortality until November 302019.Two reviewers independently assessed,selected,and ab-stracted data from studies reporting ACEIs or ARBs,sepsis,and mortality.The primary extracted data consisted of premorbid ACEI or ARB exposure,mortality,and general patient data.Two reviewers independently assessed the risk of bias and quality of evidence.RESULTS A total of six studies comprising 281238 patients with sepsis,including 49799 cases with premorbid ACEI or ARB exposure were eligible for analysis.Pre-morbid ACEIs or ARBs exposure decreased the 30-d mortality in patients with sepsis.Moreover,the use of ACEIs or ARBs was associated with approximately a 6%decreased risk of 30-d mortality.CONCLUSION The results of this systematic review suggest that ACEI or ARB exposure prior to sepsis may be associated with reduced mortality.Further high-quality cohort studies and molecular mechanism experiments are required to confirm our results.

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

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

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

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

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

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

Potassium-competitive acid blockers-are they the next generation of proton pump inhibitors?

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.

Calcium channel blockers and Alzheimer's disease

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.

Hyperkalemia of Angiotensin-converting Enzyme Inhibitors or Angiotensin Receptor Blockers in Hemodialysis: A Meta-analysis

The safety of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) used in hemodialysis (HD) patients was evaluated.Medline,Embase,the Cochrane Library,some databases of clinical trial registries,grey literatures,other reference lists of eligible articles and review articles for the randomized clinical trials (RCTs) on comparison of ACEIs/ARBs or placebo in HD patients were retrieved.RCTs reporting the risk of hyperkalemia by using ACEIs/ARBs in HD patients were selected.Eight articles met the eligibility criteria and were subjected to meta-analysis by using the Cochrane Collaboration’s RevMan 4.2 software package.The results showed that there was no significant difference in hyperkalemia in HD patients between ACEIs or ARBs group and control group (ACEIs vs.control:RD=0.03,95% CI=-0.13?0.18,Z=0.34,P=0.73;ARBs vs.control:RD=-0.02,95% CI=-0.07?0.03,Z=0.75,P=0.45).However,there was no significant difference in the serum potassium between ACEIs or ARBs group and control group in HD patients (ACEIs vs.control:WMD=0.10,95% CI=0.06?0.15,Z=4.64,P<0.00001;ARBs vs.control:WMD=-0.24,95% CI=-0.37--0.11,Z=3.58,P=0.0003).The use of ACEIs or ARBs could not cause an increased risk of hyperkalemia in HD patients,however the serum potassium could be increased with use of ACEIs in HD patients.Therefore the serum potassium concentration should still be closely monitored when ACEIs are taken during the maintenance HD.

Nonselective beta-blockers in cirrhotic patients with no or small varices:A meta-analysis

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.

Role of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in cryoballoon ablation outcomes for paroxysmal atrial fibrillation

BACKGROUND Cryoballoon ablation(CBA)is recommended for patients with paroxysmal atrial fibrillation(AF)refractory to antiarrhythmic drugs.However,only 80%of patients benefit from initial CBA.There is growing evidence that pretreatment with angiotensin-converting enzyme inhibitors(ACEIs)and angiotensin receptor blockers(ARBs)decreases the recurrence of AF postablation,particularly in nonparoxysmal AF undergoing radiofrequency ablation.The role of ACEIs and ARBs in patients with paroxysmal AF in CBA remains unknown.We decided to investigate the role of ACEIs and ARBs in preventing the recurrence of atrial arrhythmia(AA)following CBA for paroxysmal AF.AIM To investigate the role of ACEIs and ARBs in preventing recurrence of AA following CBA for paroxysmal AF.METHODS We followed 103 patients(age 60.6±9.1 years,29%women)with paroxysmal AF undergoing CBA 1-year post procedure.Recurrence was assessed by documented AA on electrocardiogram or any form of long-term cardiac rhythm monitoring.A multivariable Cox proportional hazard model was used to assess if ACEI or ARB treatment predicted the risk of AA recurrence.RESULTS After a 1-year follow-up,19(18.4%)participants developed recurrence of AA.Use of ACEI or ARB therapy was noted in the study population.Patients on ACEI/ARB had a greater prevalence of hypertension and coronary artery disease.On a multivariate model adjusted for baseline demographics and risk factors for AF,ACEI or ARB therapy did not prevent recurrence of AA following CBA(P=0.72).Similarly,on Kaplan–Meier analysis pretreatment with ACEI/ARB did not predict the time to first recurrence of AA(P=0.2173).CONCLUSION In our study population,preablation treatment with an ACEI or ARB had no influence on the recurrence of AA following CBA for paroxysmal AF.

Potassium-competitive acid blockers and gastroesophageal reflux disease

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.

Awake fiberoptic intubation and use of bronchial blockers in ankylosing spondylitis patients

BACKGROUND Patients with ankylosing spondylitis(AS)combined with severe cervical fusion deformity have difficult airways.Awake fiberoptic intubation is the standard treatment for such patients.Alleviating anxiety and discomfort during intubation while maintaining airway patency and adequate ventilation is a major challenge for anesthesiologists.Bronchial blockers(BBs)have significant advantages over double-lumen tubes in these patients requiring one-lung ventilation.AIM To evaluate effective drugs and their optimal dosage for awake fiberoptic nasotracheal intubation in patients with AS and to assess the pulmonary isolation effect of one-lung ventilation with a BB.METHODS We studied 12 AS patients(11 men and one woman)with lung or esophageal cancer who underwent thoracotomy with a BB.Preoperative airway evaluation found that all patients had a difficult airway.All patients received an intramuscular injection of penehyclidine hydrochloride(0.01 mg/kg)before anesthesia.In the operating room,dexmedetomidine(0.5μg/kg)was infused intravenously for 10 min,with 2%lidocaine for airway surface anesthesia,and a 3%ephedrine cotton swab was used to contract the nasal mucosa vessels.Before tracheal intubation,fentanyl(1μg/kg)and midazolam(0.02 mg/kg)were administered intravenously.Awake fiberoptic nasotracheal intubation was performed in the semi-reclining position.Intravenous anesthesia was administered immediately after successful intubation,and a BB was inserted laterally.The pre-intubation preparation time,intubation time,facial grimace score,airway responsiveness score during the fiberoptic introduction,time of end tracheal catheter entry into the nostril,and lung collapse and surgical field score were measured.Systolic blood pressure(SBP),diastolic blood pressure(DBP),and heart rate(HR)were recorded while entering the operation room(T1),before intubation(T2),immediately after intubation(T3),2 min after intubation(T4),and 10 min after intubation(T5).After surgery,all patients were followed for adverse reactions such as epistaxis,sore throat,hoarseness,and dysphagia.RESULTS All patients had a history of AS(20.4±9.6 years).They had a Willson's score of 5 or above,grade III or IV Mallampati tests,an inter-incisor distance of 2.9±0.3 cm,and a thyromental(T-M)distance of 4.8±0.7 cm.The average pre-intubation preparation time was 20.4±3.4 min,intubation time was 2.6±0.4 min,facial grimace score was 1.7±0.7,airway responsiveness score was 1.1±0.7,and pulmonary collapse and surgical exposure score was 1.2±0.4.The SBP,DBP,and HR at T5 were significantly lower than those at T1-T4(P<0.05).While the values at T1 were not significantly different from those at T2-T4(P>0.05),they were significantly different from those at T5(P<0.05).Seven patients had minor epistaxis during endotracheal intubation,two were followed 24 h after surgery with a mild sore throat,and two had hoarseness without dysphagia.CONCLUSION Patients with AS combined with severe cervical and thoracic kyphosis should be intubated using fiberoptic bronchoscopy under conscious sedation and topical anesthesia.Proper doses of penehyclidine hydrochloride,dexmedetomidine,fentanyl,and midazolam,combined with 2%lidocaine,administered prior to intubation,can provide satisfactory conditions for tracheal intubation while maintaining the comfort and safety of patients.BBs are safe and effective for onelung ventilation in such patients during thoracotomy.

Nonselective β-blockers may induce development of portal vein thrombosis in cirrhosis

Currently, nonselective &#x003b2;-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 &#x003b2;1 receptors and vasoconstriction of the splanchnic circulation by the blockade of &#x003b2;2 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.

Potential protective role of ACE-inhibitors and AT1 receptor blockers against levodopa-induced dyskinesias:a retrospective case-control study

Growing evidence has highlighted that angiotensin-converting enzyme(ACE)-inhibitors(ACEi)/AT1 receptor blockers(ARBs)may influence the complex interplay between dopamine and the renin-angiotensin system in the nigrostriatal pathway,thus affecting the development of levodopa-induced dyskinesia in Parkinson’s disease(PD).In the present study,we analyzed whether the use of this class of medication was associated with a reduced occurrence of levodopa-induced dyskinesia,using electronically-stored information of idiopathic PD patients enrolled at Novara University Hospital“Maggiore della Carità”.We conducted a retrospective case-control study identifying PD patients with dyskinesias(PwD;n=47)as cases.For each PwD we selected a non-dyskinetic control(NoD),nearly perfectly matched according to sex,Unified Parkinson’s Disease Rating Scale(UPDRS)part III score,and duration of antiparkinsonian treatment.Binary logistic regression was used to evaluate whether dyskinesias were associated with ACEi/ARBs use.Ninety-four PD patients were included,aged 72.18±9 years,with an average disease duration of 10.20±4.8 years and 9.04±4.9 years of antiparkinsonian treatment.The mean UPDRS part III score was 18.87±7.6 and the median HY stage was 2.In the NoD group,25(53.2%)were users and 22(46.8%)non-users of ACEi/ARBs.Conversely,in the PwD group,11(23.4%)were users and 36 non-users(76.6%)of this drug class(Pearson chi-square=8.824,P=0.003).Concerning general medication,there were no other statistically significant differences between groups.After controlling for tremor dominant phenotype,levodopa equivalent daily dose,HY 3-4,and disease duration,ACEi/ARBs use was a significant predictor of a lower occurrence of dyskinesia(OR=0.226,95%CI:0.080-0.636,P=0.005).Therefore,our study suggests that ACEi/ARBs may reduce levodopa-induced dyskinesia occurrence and,thanks to good tolerability and easy management,represent a feasible choice when dealing with the treatment of hypertension in PD patients.The study was approved by the Ethics Committee of Novara University Hospital“Maggiore della Carità”(CE 65/16)on July 27,2016.

Beneficial effects of switching from β-blockers to nebivolol on the erectile function of hypertensive patients

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）

Effects of angiotensin receptor blockers and angiotensin-converting enzyme inhibitors on COVID-19

BACKGROUND The World Health Organization reported that 28637952 people worldwide had been infected with severe acute respiratory syndrome coronavirus 2,the causative agent of coronavirus disease 2019(COVID-19),by September 13.AIM The aim was to investigate whether long-term use of renin-angiotensin-aldosterone system(RAAS)inhibitors for the treatment of hypertension aggravates the performance of COVID-19 patients with hypertension.METHODS This was a retrospective analysis of lung computed tomography(CT)data and laboratory values of COVID-19 patients with hypertension who were admitted to Huoshenshan Hospital,Wuhan,Hubei Province,between February 18 and March 31,2020.Patients were divided into two groups.Group A included 19 people who were long-term users of RAAS inhibitors for hypertension;and group B included 28 people who were randomly selected from the database and matched with group A by age,sex,basic diseases,and long-term use of other antihypertensive drugs.All patients underwent a series of CT and laboratory tests.We compared the most severe CT images of the two groups and the laboratory examination results within 2 d of the corresponding CT images.RESULTS The time until the most severe CT images from the onset of COVID-19 was 30.37±14.25 d group A and 26.50±11.97 d in group B.The difference between the two groups was not significant(t=1.01,P=0.32).There were no significant differences in blood laboratory values,C-reactive protein,markers of cardiac injury,liver function,or kidney function between the two groups.There was no significant difference in the appearance of the CT images between the two groups.The semiquantitative scores of each involved lobe were 11.84±5.88 in group A and 10.36±6.04 group B.The difference was not significantly different(t=0.84,P=0.41).CONCLUSION Chest CT is an important imaging tool to monitor the characteristics of COVID-19 and the degree of lung injury.Chronic use of RAAS inhibitors is not related to the severity of COVID-19,and it does not worsen the clinical process.

Angiotensin converting enzymes inhibitors or angiotensin receptor blockers should be continued in COVID-19 patients with hypertension

BACKGROUND Recent studies have revealed that sustained ingestion of angiotensin converting enzymes inhibitors or angiotensin receptor blockers(ACEIs/ARBs)had no harmful effects on coronavirus disease 2019(COVID-19)patients complicated with hypertension.AIM To investigate the impact on COVID-19 patients complicated with hypertension who discontinued using ACEIs/ARBs.METHODS All COVID-19 patients complicated with hypertension admitted to our isolated unit were consecutively recruited in this study.Some patients switched from ACEIs/ARBs to calcium channel blocker(CCBs)after admission,while others continued using non-ACEIs/ARBs.We compared characteristics and clinical outcomes between these two groups of patients.RESULTS A total of 53 patients were enrolled,27 patients switched from ACEIs/ARBs to CCBs while 26 patients continued with non-ACEIs/ARBs.After controlling potential confounding factors using the Cox proportional hazards model,hospital stay was longer in patients who discontinued ACEIs/ARBs,with a hazard ratio of 0.424(95%confidence interval:0.187-0.962;P=0.040),upon discharge than patients using other anti-hypertensive drugs.A sub-group analysis showed that the effect of discontinuing use of ACEIs/ARBs was stronger in moderate cases[hazard ratio=0.224(95%confidence interval:0.005-0.998;P=0.0497)].CONCLUSION Patients in the discontinued ACEIs/ARBs group had longer hospital stays.Our findings suggest that COVID-19 patients complicated with hypertension should continue to use ACEIs/ARBs.

THE PROTECTIVE EFFECT OF Na^+ CHANNEL BLOCKERS AGAINST CELL DAMAGE CAUSED BY ISCHEMIA

In order to observe it blockers of sodium channel obsesses the neuroprotective effect on hippocampal CA 1 pyramidal cell under the condition of transient brain ischemia, the present experiment used 24 male Wistar rats aged 9 months and divided them into four groups. Lidocaine and/or furosemide were injected introcerebroventicularlly (I.C.V). Stained with H E and accounted the CA 1 pyramidal cell numbers by computer in each group suggested following findings: Although 5 μl of 2% lidocaine was injected I.C.V, the results indicated lidocaine didn't have any blockade to pyramidal cell injuries in hippocampal CA 1 area (P<0 05). In the group medicated with 2 5μl of both 2% lidocaine and 2% furosemide, the results showed that the combined approach had a blockade to injuries of pyramidal cells compared with control group (P<0 01). The present experiment indicates that the combined blockade of lidocaine and furosemide injected I.C.V. to Na + channel can prevent the injuries from hippocampal neurons owing to ischemia.

Renin-angiotensin system blockers-SGLT2 inhibitorsmineralocorticoid receptor antagonists in diabetic kidney disease:A tale of the past two decades!

Several pharmacological agents to prevent the progression of diabetic kidney disease(DKD)have been tested in patients with type 2 diabetes mellitus(T2DM)in the past two decades.With the exception of renin-angiotensin system blockers that have shown a significant reduction in the progression of DKD in 2001,no other pharmacological agent tested in the past two decades have shown any clinically meaningful result.Recently,the sodium-glucose cotransporter-2 inhibitor(SGLT-2i),canagliflozin,has shown a significant reduction in the composite of hard renal and cardiovascular(CV)endpoints including progression of end-stage kidney disease in patients with DKD with T2DM at the top of reninangiotensin system blocker use.Another SGLT-2i,dapagliflozin,has also shown a significant reduction in the composite of renal and CV endpoints including death in patients with chronic kidney disease(CKD),regardless of T2DM status.Similar positive findings on renal outcomes were recently reported as a top-line result of the empagliflozin trial in patients with CKD regardless of T2DM.However,the full results of this trial have not yet been published.While the use of older steroidal mineralocorticoid receptor antagonists(MRAs)such as spironolactone in DKD is associated with a significant reduction in albuminuria outcomes,a novel non-steroidal MRA finerenone has additionally shown a significant reduction in the composite of hard renal and CV endpoints in patients with DKD and T2DM,with reasonably acceptable side effects.