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BACKGROUND: While folic acid (FA) is widely used to treat elevated total homocysteine (tHcy), promoting vascular health by reducing vascular oxidative stress and modulating endothelial nitric oxide synthase, the optimal daily dose and individual variation by MTHFR C677T genotypes have not been well studied. Therefore, this study aimed to explore the efficacy of eight different FA dosages on tHcy lowering in the overall sample and by MTHFR C677T genotypes. METHODS: This multicentered, randomized, double-blind, controlled clinical trial included 2697 eligible hypertensive adults with elevated tHcy (≥ 10 mmol/L) and without history of stroke and cardiovascular disease. Participants were randomized into eight dose groups of FA combined with 10 mg enalapril maleate, taken daily for 8 weeks of treatment. RESULTS: The intent to treat analysis included 2163 participants. In the overall sample, increasing FA dosage led to steady tHcy reduction within the FA dosing range of 0-1.2 mg. However, a plateau in tHcy lowering was observed in FA dose range of 1.2-1.6 mg, indicating a ceiling effect. In contrast, FA doses were positively and linearly associated with serum folate levels without signs of plateau. Among MTHFR genotype subgroups, participants with the TT genotype showed greater efficacy of FA in tHcy lowering. CONCLUSIONS: This randomized trial lent further support to the efficacy of FA in lowering tHcy; more importantly, it provided critically needed evidence to inform optimal FA dosage. We found that the efficacy of FA in lowering tHcy reaches a plateau if the daily dosage exceeds 1.2 mg, and only has a small gain by increasing the dosage from 0.8 to 1.2 mg. GOV IDENTIFIER: NCT03472508 (Registration Date: March 21, 2018).

Background: Angiotensin-converting enzyme inhibitors, such as enalapril, are foundational in treating pediatric heart failure. However, they are often administered off-label to young children using extemporaneous formulations. This study, conducted as part of the EU-funded Labeling of Enalapril from Neonates up to Adolescents (LENA) project, aimed to evaluate the acceptability and palatability of an age-appropriate enalapril orodispersible minitablet (ODMT). These factors are critical for ensuring adherence, efficacy, and safety in pediatric patients. Methods: An 8-week trial was conducted in children with heart failure caused by dilated cardiomyopathy or congenital heart disease. Enalapril ODMTs (0.25 mg or 1.0 mg) were dose-titrated and administered to 38 children aged 0–6 months and 22 children aged 6 months to 6 years. This study aimed to assess its acceptability and palatability, key factors contributing to adherence, and therefore, efficacy and safety. Results: Across all 169 assessments in 38 children aged 0–6 months and 22 aged 6 months to 6 years, complete or partial swallowability was observed, and the acceptability rate was 100%. There were no cases of choking, inhalation/coughing, or spitting out. A favorable or neutral rating was observed in 96% of palatability assessments based on observations of facial expressions. Acceptability and palatability were higher in subjects aged 6 months–6 years than 0–6 months, with no significant influence from repeated administration. Conclusions: Enalapril ODMTs are widely accepted and well-tolerated among young children, including neonates, with heart failure. These findings suggest that ODMTs are a suitable and effective method for administering pediatric medicinal products. [ABSTRACT FROM AUTHOR]

Objective To investigate the efficacy of levosimendan combined with enalapril on acute anterior wall myocardial infarction complicated with cardiac dysfunction after emergency percutaneous coronary intervention (PCI). Methods Ninety-eight patients with acute anterior wall myocardial infarction who underwent emergency PCI surgery and developed heart failure were prospectively selected, and randomly divided into the single group and the combined group, 49 patients in each group. The single group received enalapril at a dose of 5 mg/(times · day). The combined group received levosimendan on the basis of the single group, with an initial dose of 6 µg/kg within 10 minutes after the start of intravenous injection, and the adjusted dose was 0.1 µg/(kg·min) after 10 minutes. The infusion lasted for 24 hours. The effects, improvement in Killip heart function classification, cardiac remodeling indicators [left atrial diameter (LAD), left ventricular ejection fraction (LVEF), interventricular septal thickness (IVST) and left ventricular end-diastolic diameter (LVEDD)], serological indicators [creatine kinase isoenzyme (CK-MB), cystatin C (Cys C) and cardiac troponin I (cTnI)], 6-minute walk distance and incidence of adverse reactions were compared between the two groups. Results The overall effective rate was higher in the combined group than that of the single group (P＜0.05). After treatment, the cardiac function was better in the combined group than that of the single group. Data of LAD, IVST, LVEDD, CK-MB, Cys C and cTnI were lower in the combined group than those of the single group, and LVEF was higher in the combined group than those of the single group (P＜0.05). The distance of the 6MWT was longer in the combined group than that in the single group (P＜0.05). There was no significant difference in the total incidence of adverse reactions between the two groups. Conclusion Levosimendan in combination with enalapril is effective in treating patients with acute anterior wall myocardial infarction complicated with cardiac insufficiency after emergency PCI, which can effectively reduce myocardial injury, improve cardiac and renal functions, and has high safety [ABSTRACT FROM AUTHOR]

Background: Numerous clinical studies have demonstrated that the therapeutic efficacy of combining nifedipine and enalapril in treating hypertension with coronary heart disease surpasses that of nifedipine as a stand-alone treatment. However, the current evidence is not yet sufficient due to limitations in the sample size, and further validation is needed. To analyze and assess the clinical impact of nifedipine combined with enalapril on hypertension complicated with coronary heart disease, and provide evidence for rational drug use in clinic. Methods: We employed a revised version of the Jadad scale to assess the quality of the research literature following a rigorous screening process. The statistical analysis was performed utilizing the software RevMan 5.4.1 for data analysis. Heterogeneity in the studies was evaluated based on the results of the Q test (P value), and the OR value of the combined effect was calculated using either the model with fixed effects orthe one with random effects, with the results presented in a forest plot. Furthermore, a sensitivity analysis was conducted by excluding articles with the highest impact, and potential bias in publication was assessed through the utilization of a funnel plot. Results: A total of 183 articles were initially identified, and after a comprehensive review, 14 clinical randomized controlled trials were chosen for analysis. The meta-analysis findings revealed that the trial group displayed a significantly higher overall effectiveness rate compared to the control group (OR=3.47, 95%CI 2.40-5.03). Additionally, the trial group exhibited a more pronounced reduction in blood pressure and greater enhancement in cardiac function (OR=5.55, 95%CI). Conversely, the control group had a lower occurrence of ischemic events compared to the trial group (OR=0.35, 95%CI 0.24-0.50). Sensitivity analysis confirmed the stability and reliability of the combined effect size results (OR=3.91, 95%CI 2.51-6.09, P<0.00001). However, based on an assessment using funnel plot results suggested potential bias in publication. Conclusions: The combined administration of nifedipine and enalapril exhibits enhanced effectiveness compared to the sole use of nifedipine in individuals diagnosed with hypertension and coronary heart disease, rendering it a valuable alternative for clinical application. [ABSTRACT FROM AUTHOR]

BACKGROUND: Effects of the renin-angiotensin-aldosterone system (RAAS) inhibitors enalapril and telmisartan on circulating RAAS in dogs with proteinuric chronic kidney disease (pCKD) are undescribed. OBJECTIVES: To characterize the RAAS in untreated dogs with pCKD compared to healthy, life-stage- and sex-matched controls, and in dogs with pCKD after 30 days of treatment with enalapril or telmisartan. ANIMALS: Dogs with pCKD (n = 36) and healthy controls (n = 20). METHODS: Retrospective study of banked samples and previously collected data. Day 0 serum equilibrium concentrations of angiotensin I, II, III, IV, 1-5, and 1-7, and aldosterone, and urinary aldosterone-to-creatinine ratio (UACR) from pCKD dogs were compared to values on day 30 of treatment with enalapril (0.5 mg/kg PO q12) or telmisartan (1 mg/kg PO q24h) and to those of healthy dogs. Data were analyzed using linear mixed models. RESULTS: Compared with healthy dogs, pCKD dogs had significantly higher Ang I, III, 1-5, and 1-7 concentrations, and UACR. Relative to pretreatment values, day 30 Ang II concentrations were significantly increased and decreased in telmisartan- and enalapril-treated pCKD dogs, respectively (both P

Background: The aim of this study was to evaluate the efficacy of 1-year treatment in children with IgAN and IgAVN using azathioprine, prednisone, and enalapril (AZA+PRED+E) combined with a control kidney biopsy. Methods: This study consists of 68 children diagnosed via kidney biopsy with Oxford classification. The study group included 36 children (15 IgAN, 21 IgAVN) treated with AZA+PRED+E (according to the protocol with a control kidney biopsy); and the control group included 32 children (21 IgAN, 11 IgAVN) who were treated with enalapril alone during one year after kidney biopsy. Results: After 1 year of combined therapy, a significant reduction in both proteinuria (proteinuria = 0 in 35 patients from the study group) and hematuria in the study group was found. It was confirmed that the Δ proteinuria between the start and end of treatment in IgAN and IgAVN patients from the study group was significantly higher than the Δ proteinuria between the start and end of treatment in the control IgAN and IgAVN group treated with enalapril (30.7 ± 43.6 vs. 8.7 ± 8.7; p = 0.015; 68.2 ± 58.3 vs. 19.3 ± 20.3; p = 0.008 respectively). In the Oxford classification a high frequency of improvement in E and T in the study group after treatment was observed. Conclusions: Patients with higher proteinuria and a higher MESTC score require consideration of the strategy of immunosuppressive treatment so that therapy with AZA+PRED+E may be used as a personal treatment plan for children with these diseases. [ABSTRACT FROM AUTHOR]

BACKGROUND: Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), is an established treatment for heart failure (HF) with reduced left ventricular ejection fraction. It has not been rigorously compared with angiotensin-converting enzyme inhibitors in children. PANORAMA-HF (Prospective Trial to Assess the Angiotensin Receptor Blocker Neprilysin Inhibitor LCZ696 Versus Angiotensin-Converting Enzyme Inhibitor for the Medical Treatment of Pediatric HF) is a randomized, double-blind trial that evaluated the pharmacokinetics and pharmacodynamics (PK/PD), safety, and efficacy of sacubitril/valsartan versus enalapril in children 1 month to <18 years of age with HF attributable to systemic left ventricular systolic dysfunction (LVSD). METHODS: Children with HF attributable to LVSD were randomized to sacubitril/valsartan versus enalapril to assess the efficacy and safety of sacubitril/valsartan at 52 weeks of follow-up. The primary end point of the study was to determine whether sacubitril/valsartan was superior to enalapril for the treatment of pediatric patients with HF attributable to systemic LVSD, assessed using a primary global rank end point consisting of ranking patients from worst to best on the basis of clinical events such as death, listing for urgent heart transplant, mechanical life support requirement, worsening HF, New York Heart Association (NYHA)/Ross class, Patient Global Impression of Severity (PGIS), and Pediatric Quality of Life Inventory physical functioning domain. The change from baseline to 52 weeks in NT-proBNP (N-terminal pro–B-type natriuretic peptide) was an exploratory end point. RESULTS: A total of 375 children (mean age, 8.1±5.6 years; 52% female) were randomized to sacubitril/valsartan (N=187) or enalapril (N=188). At week 52, no significant difference was observed between the 2 treatment arms in the global rank end point (Mann-Whitney probability, 0.52 [95% CI, 0.47–0.58]; Mann-Whitney odds, 0.91 [95% CI, 0.72–1.14]; P =0.42). At week 52, clinically meaningful reductions were observed in both treatment arms in NYHA/Ross, PGIS, Patient Global Impression of Change, and NT-proBNP, without significant differences between groups. Adverse events were similar between treatment arms (incidence: sacubitril/valsartan, 88.8%; enalapril, 87.8%), and the safety profile of sacubitril/valsartan was acceptable in children. CONCLUSIONS: In this study, sacubitril/valsartan did not show superiority over enalapril in the treatment of children with HF attributable to systemic LVSD using the prespecified global rank end point. However, both treatment arms showed clinically meaningful improvements over 52 weeks. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02678312. [ABSTRACT FROM AUTHOR]

Background: Elevated blood pressure is a major risk factor for severe medical conditions. Adherence to antihypertensive medication, especially in free-dose combinations, poses a significant challenge. This study aims to develop a novel method for assessing co-exposure to free-dose antihypertensive medications using secondary data sources. Methods: A register-based cohort study was conducted on individuals aged 65 years or older in Denmark who initiated antihypertensive therapy from 1996 to 2016 and followed for 730 days from the index date. A new method was developed to assess co-exposure to antihypertensive medications through redeemed prescriptions, treatment episodes, and overlapping medication events. The method's accuracy was evaluated using a random sample of 400 individuals. Results: A total of 1,021,819 individuals were included in the study, with a mean age of 68.8 years, and 53.7% were women. The method achieved 100% accuracy in identifying co-exposure periods. During the early stage of the follow-up (0–180 days), 54.1% of individuals were co-exposed to at least two antihypertensive medications, while 37.5% were co-exposed during the late stage of the follow-up period (181–730 days). The most frequent antihypertensive combinations included bendroflumethiazide and potassium with either amlodipine or enalapril in the early (13.2% and 12.5% of patients, respectively) and late stages (16.9% and 15.0% of patients, respectively). Conclusions: The newly developed method effectively assesses co-exposure to antihypertensive medications, overcoming previous limitations. The findings reveal common co-exposure combinations and evolving trends in antihypertensive medication use among older individuals, reflecting changes in clinical practice and guidelines over two decades. [ABSTRACT FROM AUTHOR]

Ventricular remodeling (VR) after acute ST-elevation myocardial infarction (STEMI) is an important predictor for medium- and long-term prognosis. This study focuses on the relevant indexes of VR in patients with AMI, in which, the intervention effects of sacubitril/valsartan and enalapril were compared, guiding the clinical treatment. 58 patients with acute STEMI treated with PCI were divided into research group and control group. UCG was performed at 1 week, 1 month and 3 months after MI, and the patients' indexes were collected to compare VR and adverse reactions in the two groups. The test results showed that there was no statistical difference in the baseline data of patients in the two groups, which were comparable. In the blood biochemical index examination, no statistical difference was found in cTnI and NT-proBNP between the two groups. At 1 week after operation, the levels of cTnI and NT-proBNP in research group were lower than those in the control group. In ECG examination, there was no statistical significance in the levels of LVEF, LVEDD and LVESD at admission between the two groups. After 1 week, the results of LVEF, LVEDD, LVESD in the research group were higher than those in the control group. The results of this study show that sacubitril/valsartan can be used in patients with AMI instead of enalapril. Sacubitril/valsartan improves cardiac function in patients with emergency percutaneous coronary intervention (PCI) for AMI, inhibits ventricular remodeling, and has a low incidence of adverse cardiac events and adverse drug reactions. [ABSTRACT FROM AUTHOR]

The article focuses on an 8-year-old girl diagnosed with atypical hemolytic uremic syndrome (aHUS) after presenting with non-bloody diarrhea, hemolytic anemia, and thrombocytopenia. Topics include her clinical presentation with elevated blood pressure and kidney involvement, the negative tests for shiga toxin and the normal ADAMTS-13 activity, and her subsequent treatment with plasma exchange and eculizumab, leading to improved kidney function and the cessation of dialysis.

Objective • Heart failure is a common cardiovascular disease, and its prevalence is increasing year by year. For patients with heart failure combined with non-valvular reduced ejection fraction, drug therapy has always been a key treatment. This study aimed to explore the clinical efficacy of sacubitril valsartan sodium and enalapril in such patients. Methods • Study design: This study used a prospective observational design. From February 2020 to February 2022, we included 123 patients with non-valvular heart failure and reduced ejection fraction who were treated in Xingtai Third Hospital. Patients were divided into two groups according to the treatment plan: Group A (n=61) received enalapril, and Group B (n=62) received nifedipine. All patients received conventional treatment. We compared the efficacy of the two groups of patients 8 weeks after treatment. During the study, the laboratory indicators, echocardiographic indicators, cardiovascular markers, and possible adverse reactions of the two groups of patients before and after treatment were recorded. Results • After 8 weeks of treatment, the effective rate of group B was higher than group A (P < .05). There were no differences in the levels of total protein, total bilirubin, total cholesterol and serum creatinine between the two groups before and after treatment (P > .05). The serum creatinine level in the two groups after treatment was higher than that before treatment, and the level in group B was lower than that in group A (P < .05). There were no statistically significant differences in the levels of total protein, total bilirubin and total cholesterol between the two groups before and after treatment (P > .05), and there was no statistically significant difference in the level of serum creatinine between the two groups before treatment (P > .05), and the level of serum creatinine after treatment was higher than that before treatment, and the level of group B was lower than that of group A (P < .05). Before treatment, there was no significant difference in the levels of high-sensitive troponin T and n-terminal brain natriuretic peptide and cyclic guanosine phosphate between the two groups (P > .05). After treatment, the levels of high- sensitive troponin T and N-terminal brain natriuretic peptide in the two groups were lower than those before treatment, and those in group B were lower than those in group A. The level of cyclic guanosine phosphate in group A was lower than that before treatment, the level of cyclic guanosine phosphate in group B was higher than that before treatment, and the level of group B was higher than that of group A (P < .05). The incidence of adverse cardiovascular events in group B was lower than that in group A (P < .05). In this study, the effective rate of treatment group B was significantly higher than that of treatment group A, indicating that treatment group B had a better therapeutic effect. In addition, there were no significant differences between the two groups in a series of biochemical parameters, but it is worth noting that after treatment, the serum creatinine level of group B was significantly lower than that of group A, which may indicate that the treatment of group B is not only more effective but also Reduces the risk of certain adverse cardiovascular events. Conclusion • The main findings of the study showed that Sacubitril valsartan sodium showed better clinical efficacy than enalapril in patients with heart failure and non-valvular reduced ejection fraction. Specifically, the drug significantly improved patients’ kidney function, reduced cardiovascular marker levels, and reduced the incidence of adverse cardiovascular events. These findings have important clinical implications for guiding treatment selection in patients with heart failure. [ABSTRACT FROM AUTHOR]

The Angiotensin Converting Enzyme 2 (ACE2) is a key drug target for treating hypertension, kidney, lung and heart disease. We used a ligand-based strategy to identify Enalapril analogs as novel potent and selective ACE2 inhibitors. These analogs were screened from ChEBI database using Swisssimilarity tool. Pharmacokinetics and drug likeliness properties of screened analogs were predicted by SwissADME tool. Further, screened analogs of Enalapril were docked within binding pocket of angiotensin-converting enzyme 2 using MTiAutoDock server. Compounds CHEBI: 3698, CHEBI: 161620, CHEBI: 161824 and CHEBI: 161817 were qualifying all the ADME parameters. In the AutoDock programme, the binding energy of these analogs, CHEBI: 3698, CHEBI: 161620, CHEBI: 161824 and CHEBI: 161817 had low binding affinity -8.52, -8.70, -8.11 and -8.15 kcal/mol with ACE2, respectively. The outcome of this work confirms the importance of these analogs as promising drug candidates for the treatment of hypertension and cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Objective: Apelin and visfatin are adipokines secreted from adipose tissue that play important roles in regulating blood pressure. Therefore, the current study aimed to investigate the effects of candesartan versus enalapril on apelin, visfatin, and lipid profiles in hypertensive patients. Methods: In this case-control study, 120 participants were enrolled in four groups; Healthy people, newly diagnosed hypertensive patients, and enalapril- and candesartan-treated patients. Results: Serum apelin levels were significantly lower and visfatin levels were significantly higher in newly diagnosed hypertensive patients compared with the control group (p=0.0015, p=0.0175 respectively). Moreover, apelin levels were higher and visfatin levels were lower in the candesartan-treated patients compared with the newly diagnosed group (p=0.0487, p

Objectives. Visfatin and apelin are two adipokines that recently gained a special interest in hypertension research as they may have a role in the pathogenesis of hypertension and are closely related to the renin-angiotensin system. This study aimed to evaluate the serum levels of apelin and visfatin in uncontrolled newly diagnosed hypertensive patients, controlled hypertensive patients managed by enalapril and controlled hypertensive patients managed by telmisartan. Patients and methods. The study population included 126 participants, who were divided into four groups established as healthy participants, newly diagnosed hypertensive patients, hypertensive patients managed by enalapril and hypertensive patients managed by telmisartan. Outcomes. Serum apelin levels reduced significantly in newly diagnosed hypertensive patients, with a significant increase in visfatin levels compared with control group. Enalapril-treated patients expressed significantly higher apelin levels with a significant reduction in visfatin levels compared with newly diagnosed. Apelin levels were significantly increased in enalapril-treated patients compared telmisartan-treated group. Additionally, a significant reduction in visfatin levels were found in telmisartan group compared with newly diagnosed hypertensive patients. Moreover, a significant positive correlation was found between HDL and visfatin in patients receiving treatment. Additionally, visfatin was negatively correlated with triglycerides and VLDL in the same patient group. Conclusions. In light of the data collected so far, whether visfatin and apelin play roles in the pathophysiology of hypertension remains unclear and further research is still required to fully understand its relevance. Nevertheless, high visfatin and low apelin levels appear to be intrinsic characteristics of uncontrolled hypertension, indicating that these adipokines could be potential biomarkers for this disease.

Abstract Background Mucous membrane pemphigoid (MMP) is an autoimmune blistering disease (AIBD). Some reports suggest that it has a drug-related pathogenesis especially anti-hypertensive drug. Case presentation A 67-year-old man with a 7-year history of essential hypertension was prescribed enalapril maleate for 5 months. He presented at our department with pain, ulcers, and blisters on the oral mucosa. We performed clinical, histopathology, and direct immunofluorescence examinations, and findings were consistent with the diagnostic criteria for MMP. Consequently, we consulted with the cardiovascular physician and agreed to discontinue the enalapril maleate replacing it with irbesartan/hydrochlorothiazide tablets and topical corticosteroid therapies instead. The lesions healed without recurrence. Conclusions ABID induced by antihypertensive drugs have been reported, and enalapril maleate has been implicated as an antihypertensive agent that may trigger AIBDs, such as MMP. This case highlights the potential relationship between antihypertensive drugs and MMP, of which clinicians should be aware to accurately diagnose and promptly relieve patients’ pain.

Background: Mucous membrane pemphigoid (MMP) is an autoimmune blistering disease (AIBD). Some reports suggest that it has a drug-related pathogenesis especially anti-hypertensive drug. Case presentation: A 67-year-old man with a 7-year history of essential hypertension was prescribed enalapril maleate for 5 months. He presented at our department with pain, ulcers, and blisters on the oral mucosa. We performed clinical, histopathology, and direct immunofluorescence examinations, and findings were consistent with the diagnostic criteria for MMP. Consequently, we consulted with the cardiovascular physician and agreed to discontinue the enalapril maleate replacing it with irbesartan/hydrochlorothiazide tablets and topical corticosteroid therapies instead. The lesions healed without recurrence. Conclusions: ABID induced by antihypertensive drugs have been reported, and enalapril maleate has been implicated as an antihypertensive agent that may trigger AIBDs, such as MMP. This case highlights the potential relationship between antihypertensive drugs and MMP, of which clinicians should be aware to accurately diagnose and promptly relieve patients' pain. [ABSTRACT FROM AUTHOR]

Background: The angiotensin-converting enzyme inhibitor (ACEI) enalapril is often administered to infants and young children with heart failure (HF) in various dosing regimens and formulations not adapted for their age. Methods: This prospective, two-center, open-label 8-week study evaluated an age-appropriate formulation of orodispersible minitablets (ODMTs) of enalapril (0.25 mg and 1 mg) in children aged 0 to 6 years with HF due to congenital heart disease. An age/weight-based dosing schedule was followed. Measures of echocardiographic parameters, blood pressure, heart rate, modified Ross score, and biochemistry were obtained over the 8-week period. The following two groups were assessed: ACEI-naïve and ACEI-pretreated patients. Results: In total, 53 children (age range of 0.05 to 4.8 years) were enrolled and 29 were ACEI-naïve. The average enalapril dose was 0.098 mg/kg (0.06–0.17 mg/kg) in the naïve group and 0.15 mg/kg (0.07–0.3 mg/kg) in pretreated patients. After 8 weeks, the modified Ross score and left ventricular diastolic dimension (LVD) z-score showed a significant decrease in both groups (p < 0.005). During 8 weeks follow-up, there were no difference in the z-scores for the systolic blood pressure (p = 0.071) or heart rate (p = 0.146). Conclusions: Pediatric patients treated with ODMTs of enalapril for 8 weeks had favorable improvements in LVD and HF symptoms. [ABSTRACT FROM AUTHOR]

Enalapril is an orally administered angiotensin-converting enzyme inhibitor which is widely prescribed to treat hypertension, chronic kidney disease, and heart failure. It is an ester prodrug that needs to be activated by carboxylesterase 1 (CES1). CES1 is a hepatic hydrolase that in vivo biotransforms enalapril to its active form enalaprilat in order to produce its desired pharmacological impact. Several single nucleotide polymorphisms in CES1 gene are reported to alter the catalytic activity of CES1 enzyme and influence enalapril metabolism. G143E, L40T, G142E, G147C, Y170D, and R171C can completely block the enalapril metabolism. Some polymorphisms like Q169P, E220G, and D269fs do not completely block the CES1 function; however, they reduce the catalytic activity of CES1 enzyme. The prevalence of these polymorphisms is not the same among all populations which necessitate to consider the genetic panel of respective population before prescribing enalapril. These genetic variations are also responsible for interindividual variability of CES1 enzyme activity which ultimately affects the pharmacokinetics and pharmacodynamics of enalapril. The current review summarizes the CES1 polymorphisms which influence the enalapril metabolism and efficacy. The structure of CES1 catalytic domain and important amino acids impacting the catalytic activity of CES1 enzyme are also discussed. This review also highlights the importance of pharmacogenomics in personalized medicine. [ABSTRACT FROM AUTHOR]

Copyright of Medeniyet Medical Journal is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: The objective of this meta-analysis is to determine how sacubitril/valsartan (SV) compares to equivalent and sub-equivalent angiotensin receptor blockers (ARB) or angiotensin-converting enzyme inhibitors (ACEI) in patients with heart failure with reduced ejection fraction (HFrEF). Methods: The databases of PubMed and EMBASE were used to identify those randomized controlled trials which compared SV to ARB/ACEI in patients with HFrEF. Only those trials that reported outcomes regarding total mortality, cardiovascular mortality, and worsening heart failure were considered. Meta-analysis was performed separately in those patients receiving equivalent doses of ARB/ACEI and those receiving sub-equivalent doses. Equivalent doses were SV 97/103 = valsartan 160 mg twice daily = enalapril 20 mg twice daily = ramipril 5 mg twice daily. Meta-analyses were performed using Review Manager 5.4. Results: Twelve randomized trials were identified involving 17,484 patients: 11,291 in the sub-equivalent group (8 trials) and 6193 in the equivalent group (4 trials). Meta-analyses showed there were no statistical differences regarding the outcomes of total mortality, cardiovascular mortality, and worsening heart failure in the equivalent dosing group. However, SV reduced total mortality (risk ratio (RR) = 0.85, 95% confidence interval (CI) = 0.78–0.93, p < 0.001), cardiovascular mortality (RR = 0.81, 95% CI = 0.73–0.90, p ≤ 0.001) and worsening heart failure (RR = 0.77, 95% CI = 0.64–0.92, p = 0.005) in the sub-equivalent group. Conclusion: When compared to equivalent doses of ARB/ACEI, SV is not superior in reducing mortality and worsening heart failure. SV is superior when compared to sub-equivalent doses of ACEI. [ABSTRACT FROM AUTHOR]

Introduction: Intestinal colitis, also known as ulcerative colitis, is an inflammatory bowel disease characterized by long-term inflammation and ulcers in the gastrointestinal tract. It has been suggested that the mucosal expression of angiotensin II (AT-II) is increased in colitis. This study aimed to examine the potential therapeutic effects of combination therapy with Enalapril, an angiotensin-converting enzyme inhibitor, and sulfasalazine (SSZ) in a murine colitis model. Methods: Male C57BL/6 mice were divided into five groups: control group (distilled water), dextran sulphate sodium (DSS) group (colitis group) (1% DSS), SSZ group (positive control group) with 100 mg/kg/day, Enalapril alone group with 4 mg/kg/day, and Enalapril (4 mg/kg/day) + SSZ (100 mg/kg/day) group. Results: There was a significant reduction in the disease activity index among the mice receiving the combination of Enalapril and SSZ compared to the colitis group. Enalapril and SSZ treatment was associated with a lower reduction in colon length, decreased colon weight, spleen weight, and spleen-to-body weight in mice with colitis. Following DSS administration, Enalapril and SSZ also significantly decreased MDA levels, an oxidant marker, and increased total thiol, SOD, and CAT levels, as antioxidants. Additionally, mucosal damage, crypt loss, pathological changes, and inflammation scores decreased after treatment with Enalapril and SSZ in comparison with the colitis group. The combination of Enalapril and SSZ reduced colon collagen content and caused a decrease in fibrosis compared to the colitis group. Conclusion: The results of this study indicated that Enalapril alone and in combination with SSZ decreased inflammation and clinical symptoms of colitis induced by DSS. [ABSTRACT FROM AUTHOR]

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Abstract Background Adult nephrotic syndrome is a well-known kidney disease that causes heavy proteinuria, hypoalbuminemia, hypercholesterolemia, edema, and hypertension. The treatment varies according to its underlying cause but often faces medication resistance or adverse drug effects. Case presentation A Japanese woman in her 80s presented with nephrotic syndrome after a 3 year latent period of urinary protein and occult blood. She did not have any secondary causes of nephrotic syndrome. Renal biopsy revealed thin glomerular basement membrane, partial foot process fusion on electron microscopy with minor glomerular change on light microscopy, and slight coarse immunoglobulin M deposition in the mesangium on immunofluorescence microscopy, which was inconsistent with any other glomerular diseases. Without steroid treatment, she dramatically remitted from proteinuria after the administration of the renal protective agents enalapril, ezetimibe, rosuvastatin, and dapagliflozin. Recurrence after 8 months of follow-up subsided with the administration of additional doses of the agents. Conclusions This case illustrated the novel outcomes of combining medical treatment without steroid use for nephrotic syndrome with thin glomerular basement membrane disease. At the time of writing this report, the patient’s renal function was stable and she was free of edema, although moderate proteinuria and occult hematuria persisted. The final diagnosis was uncertain because of the lack of genetic investigation; however, the response to the aforementioned medical treatment suggests the effectiveness of the supportive therapy.

Muscle atrophy due to limb immobilization and inactivity is a common consequence of many diseases and treatment processes. One of the systems activated in inflammatory conditions is the renin-angiotensin system (RAS). The present study was conducted with the aim of investigating the effects of one of the angiotensin-converting enzyme (ACE) inhibitors, enalapril, on improving muscle atrophy caused by immobility. The study was conducted in three groups: a control, an atrophy, and an atrophy group treated with enalapril on Balb/c mice. After tying a splint to cause atrophy in one of the legs, daily treatment with enalapril intraperitoneally (dissolved in DMSO) at a dose of 10 mg/kg/day was done for 7 days. On the eighth day, the splint was opened and half of the mice were evaluated. Then, in the recovery phase, treatment with enalapril was continued in the remaining mice for 10 days without a splint. At the end of each phase, the mice were examined for the muscle strength of the lower limb muscles, and histological and biochemical analyses were subsequently carried out. The tissue level of the oxidative stress index MDA was evaluated, which showed a significantly lower level in the enalapril group compared to the atrophy group (*P

Acute post-streptococcal glomerulonephritis (APSGN) is the most common glomerulonephritis of childhood, and clinical presentation can vary widely. This case report presents an atypical manifestation of APSGN in an 8-year-old female patient with pleuritic chest pain and elevated troponin-I, despite lacking classical kidney symptoms. Imaging studies showed cardiomegaly and interstitial lung opacities. Further investigations revealed hematuria and proteinuria, and the diagnosis was confirmed through elevated antistreptolysin-O (ASO) titers and low complement 3 (C3) levels. The patient was successfully managed with fluid restriction, diuretics, and antihypertensives, resulting in the resolution of symptoms and normalization of laboratory values. This case highlights the significance of recognizing atypical manifestations of APSGN for ensuring prompt diagnosis and proper management in the pediatric population. [ABSTRACT FROM AUTHOR]