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Background: The PARADIGM HF trial showed sacubitril/valsartan (SV) to be superior to enalapril in patients with reduced ejection fraction (HFrEF). Since its publication, several other randomized trials have compared SV to either an angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) in HFrEF which showed conflicting results regarding mortality, hospitalizations, and quality of life scoring. Objective: To review randomized comparative trials of SV to either ACEI or ARB in patients with HFrEF. Methods: PubMed and Embase databases were used to identify randomized comparative trials. The text terms sacubitril, angiotensin neprilysin, and LCZ696 were used for both searches. Meta-analysis, retrospective, adhoc, and cohort studies were excluded. Results: 1476 and 3983 citations were reviewed on PubMed and Embase, respectively. Of these, 11 randomized comparative trials to either ACEI or ARB were included for analysis. The mortality/quality of life benefits of SV over enalapril in the PARADIGM HF were not corroborated in any of the other trials. The effect of hospitalizations for heart failure was inconsistent among trials. Exercise tolerance was not improved with SV versus enalapril. Conclusion: The results of the PARADIGM HF trial have largely not been confirmed in subsequent randomized comparative trials. [ABSTRACT FROM AUTHOR]

Objectives: To assess the impact of prior chronic treatment with angiotensin-converting enzyme inhibitors (ACEIs)/ angiotensin-receptor blockers (ARBs), both as a group and by active ingredient, on severity (risk of hospitalization and mortality), progression of and susceptibility to COVID-19. Methods: We conducted a multiple population-based case–control study in Galicia (north-west Spain). The study data were sourced from medical, administrative and clinical databases. We assessed: (1) risk of hospitalization, by selecting all patients hospitalized due to COVID-19 with PCR + as cases, and a random sample of subjects without a PCR + as controls; (2) COVID-19 mortality risk; (3) risk of disease progression; and (4) susceptibility to SARS-CoV-2, considering all patients with PCR + as cases, and the same subjects used in the previous model as controls. Adjusted odds ratios (aORs) were calculated. Results: ACEIs and ARBs were shown to decrease the risk of hospitalization (aOR = 0.78 [95%CI 0.69–0.89] and aOR = 0.80 [95%CI 0.72–0.90] respectively), risk of mortality (aOR = 0.71 [95%CI 0.52–0.98] and aOR = 0.69 [95%CI 0.52–0.91] respectively), and susceptibility to the virus (aOR = 0.88 [95%CI 0.82–0.94] and aOR = 0.92 [95%CI 0.86–0.97] respectively). By active ingredient: use of enalapril was associated with a significantly lower risk of hospitalization (aOR = 0.72 [95%CI 0.61–0.85]), mortality (aOR = 0.59 [95%CI 0.38–0.92]) and susceptibility to COVID-19 (aOR = 0.86 [95%CI 0.79–0.94]); and use of candesartan was associated with a decreased risk of hospitalization (aOR = 0.76 [95%CI 0.60–0.95]), mortality (aOR = 0.36 [95%CI 0.17–0.75]) and disease progression (aOR = 0.73 [95%CI 0.56–0.95]). Conclusion: This large-scale real-world data study suggest that enalapril and candesartan are associated with a considerable reduction in risk of severe COVID19 outcomes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Obesity over‐activates the classical arm of the renin‐angiotensin system (RAS), impairing skeletal muscle remodeling. We aimed to compare the effect of exercise training and enalapril, an angiotensin‐converting enzyme inhibitor, on RAS modulation in the skeletal muscle of obese animals. Thus, we divided C57BL/6 mice into two groups: standard chow (SC) and high‐fat (HF) diet for 16 weeks. At the eighth week, the HF‐fed animals were divided into four subgroups—sedentary (HF), treated with enalapril (HF‐E), exercise training protocol (HF‐T), and combined interventions (HF‐ET). After 8 weeks of treatment, we evaluated body mass and index (BMI), body composition, exercise capacity, muscle morphology, and skeletal muscle molecular markers. All interventions resulted in lower BMI and attenuation of overactivation in the classical arm, while favoring the B2R in the bradykinin receptors profile. This was associated with reduced apoptosis markers in obese skeletal muscles. The HF‐T group showed an increase in muscle mass and expression of biosynthesis markers and a reduction in expression of degradation markers and muscle fiber atrophy due to obesity. These findings suggest that the combination intervention did not have a synergistic effect against obesity‐induced muscle remodeling. Additionally, the use of enalapril impaired muscle's physiological adaptations to exercise training. [ABSTRACT FROM AUTHOR]

Simple Summary: The most common heart disease in dogs is a leaky mitral valve. This disease is incurable and slowly progressive. However, with appropriate therapy, prolonged longevity and improved quality of life can be reached. International guidelines are available to help veterinarians treat these dogs according to the latest insights. However, these guidelines might become outdated because scientific evidence can only be reviewed until about a year before their publication. Moreover, disagreements among the panelists who prepare the guidelines, and newer study results challenging the guidelines can make it difficult for practicing veterinarians to choose the right treatment. Our study aimed to investigate, using a survey, how Dutch and Belgian veterinary practitioners treat dogs with a leaky mitral valve. From the 363 responses, we concluded that the more advanced the disease stage is, the more variation there is among the recommended drug regimes. The earliest asymptomatic stage of the disease was treated correctly by 93% of the respondents, whereas the more advanced asymptomatic stage was treated by 67% of the respondents correctly. For the treatment of the symptomatic stage of the disease, 16 various drug combinations were reported, of which only 2 are considered correct, recommended by 48%. No respondents recommended surgery. Background: Myxomatous mitral valve degeneration is the most common canine heart disease. Several clinical trials have investigated various treatments. The latest recommendations are published in the ACVIM consensus guidelines (2019). Our study aimed to investigate how closely veterinary practitioners apply the treatment recommendations of these guidelines and the latest clinical trials. Methods: An online survey was sent to Dutch and Belgian veterinary practices via digital channels. Results: The data from 363 fully completed surveys were analyzed. For stage B1 disease, 93% recommended, correctly, no treatment. For stage B2 disease, 67% of the respondents recommended starting pimobendan as monotherapy. For chronic treatment of stage C disease, 16 different drug combinations were mentioned, but nobody recommended surgery. Only 48% of the respondents recommended the only evidence-based drug combination: a loop diuretic with pimobendan. A concerning finding was the simultaneous prescription of two loop diuretics, by 19% of the respondents. Conclusions: Treatment recommendations showed an increasing variation with more advanced disease stages from B1 through B2 to C. This reflects the increasing disagreement among the panelists who prepared the ACVIM consensus guidelines. Practitioners of our study seem to practice more evidence-based medicine than veterinary cardiologists, as it was reported in a recent survey-based study. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is an autoimmune disease that can involve multiple organ systems. The most common form of vasculitis seen in SLE is small vessel vasculitis. Aortitis in SLE or antiphospholipid syndrome is an extremely rare complication. Here, we present a 32-year-old female who presented with a history of prolonged abdominal pain, who was evaluated and diagnosed to have aortitis as an unusual involvement in SLE with secondary antiphospholipid antibody syndrome. [ABSTRACT FROM AUTHOR]

Objective: To assess the efficacy of left bundle branch pacing (LBBP) combined with either sacubitril/valsartan or enalapril in the treatment of chronic heart failure (CHF). Methods: We retrospectively reviewed the records of 138 patients with CHF admitted to Dazhou Central Hospital between June 2020 and June 2022 to extract clinical data. We divided the data into two treatment groups for the analysis: 71 patients received LBBP combined with sacubitril/valsartan treatment (sacubitril/valsartan group), and 67 received LBBP combined with enalapril treatment (enalapril group). The levels of cardiac and cardiopulmonary function indicators, levels of myocardial injury markers, and the scores of the Minnesota Living with Heart Failure Questionnaire (MLHFQ) before and after the treatment were compared between the two groups. Results: After six months of treatment, patients in the sacubitril/valsartan group had lower myocardial injury markers, higher cardiopulmonary function indicators, and lower MLHFQ scores (P<0.05). Conclusions: In CHF patients, the combination of LBBP with sacubitril/valsartan had a better therapeutic effect compared to LBBP with enalapril, with more effective improvement of the cardiopulmonary function, reduction of myocardial injury, and improvement in quality of life. [ABSTRACT FROM AUTHOR]

Objective: In this study, we aimed to investigate the effects of the concurrent exercise training (CET) associated with the enalapril maleate on blood pressure variability (BPV) and renal profile in an experimental model of arterial hypertension (AH) and postmenopause. Methods: Female ovariectomized spontaneously hypertensive rats (SHR) were distributed into 4 groups (n = 8/group): sedentary (SO), sedentary + enalapril (SOE), trained (TO) and trained + enalapril (TOE). Both enalapril (3mg/kg) and CET (3 days/week) were conducted during 8 weeks. Blood pressure (BP) was directly recorded for BPV analyses. Renal function, morphology, inflammation and oxidative stress were assessed. Results: The SOE, TO e TOE groups presented decreased systolic BP compared with SO. Both trained groups (TO and TOE) presented lower BPV and increased baroreflex sensitivity (TO: 0.76 ± 0.20 and TOE: 1.02 ± 0.40 vs. SO: 0.40 ± 0.07 ms/mmHg) compared with SO group, with additional improvements in TOE group. Creatinine and IL-6 levels were reduced in SOE, TO and TOE compared with SO group, while IL-10 was increased only in TOE group (vs. SO). Enalapril combined with CET promote reduction in lipoperoxidation (TOE: 1.37 ± 0.26 vs. SO: 2.08 ± 0.48 and SOE: 1.84 ± 0.35 μmol/mg protein) and hydrogen peroxide (TOE: 1.89 ± 0.40 vs. SO: 3.70 ± 0.19 and SOE: 2.73 ± 0.70 μM), as well as increase in catalase activity (vs. sedentary groups). The tubulointerstitial injury was lower in interventions groups (SOE, TO and TOE vs. SO), with potentialized benefits in the trained groups. Conclusions: Enalapril combined with CET attenuated BPV and baroreflex dysfunctions, probably impacting on end-organ damage, as demonstrated by attenuation in the AH-induced renal inflammations, oxidative stress and morphofunctional impairments in postmenopausal rats. [ABSTRACT FROM AUTHOR]

Objectives: The key objective of this work is to establish a stability-indicating UHPLC technique for measuring amlodipine and enalapril maleate in bulk and pharmaceutical formulations Materials and Methods: The mobile phase consisted of 0.02M KH2PO4 buffer: Methanol (70:30 v/v). The chromatographic separation was carried out using an Analytical Technologies UHPLC-3000 equipment in conjunction with a variable wavelength programmable UV identifier and a Rheodyne injector equipped with a 5 µL fixed circle. Detection was done at 224 nm with the flow rate of 0.3 mL/min. Results: Amlodipine's retention time was determined to be 0.7 min, while Enalapril's was 1.2 min. The linearity range for Amlodipine and Enalapril was discovered to be 5-25 µg/mL. The technique has been examined in accordance with ICH (International Conference on Harmonisation) standards. A procedure is precise and accurate if the %RSD is less than two. Amlodipine's limit of detection and quantitation ranges are 0.12-0.37 µg/mL and Enalapril's range is 0.10-0.30 µg/mL, respectively. The procedure proved to be simple, linear, swift, exact, accurate, repeatable, and reliable. The drug was prone to acid, basic, and oxidation conditions, according to the stress degradation research. Conclusion: Even in actual samples, the techniques clearly distinguished between the drugs and degradation products. The method was proved as a stability indicating method and can be used in practice for bulk and the dosage forms and also to evaluate the shelf life. [ABSTRACT FROM AUTHOR]

BACKGROUND: Angioneurotic edema is the most dangerous complication in angiotensin-converting enzyme inhibitors (ACEIs) therapy. Based on the current data, the clinical and genetic predictors of angioedema development are still understudied, which demonstrates the relevance of this study. OBJECTIVE: To reveal the pharmacogenetic predictors of the angioedema as a secondary side effect to enalapril in patients with essential arterial hypertension. METHODS: The study enrolled 111 subjects randomized into two groups: study group, patients with the angioedema as a secondary side effect to enalapril; and control group, patients without adverse drug reaction. All patients underwent pharmacogenetic testing. RESULTS: An association between the development of the angioneurotic edema and the genotypes AA rs2306283 of gene SLCO1B1, TT rs4459610 of gene ACE, and CC rs1799722 of gene BDKRB2 in patients was revealed. CONCLUSION: The findings justify further investigations of the revealed genetic predictors of angioedema with larger-size patient populations. [ABSTRACT FROM AUTHOR]

Introduction: During the design and formulation of pharmaceutical forms, or in case of any transformation due to the need to adjust the dose or adapt it to the patient's condition, it is necessary to verify the chemical, physical and biological characteristics of all the components that will be part of the formulation in the final product. The above in order to ensure that the compounding it is stable, effective, safe, easy to administer and well tolerated. Objective: To study the physical and chemical properties of an extemporaneous (compounding) liquid preparation of enalapril maleate for peroral administration, prepared from tablets commercially available in the Colombian market, using common practices in hospital centers for its preparation. Materials and methods: The following were used as vehicles: a 1:1 solution of dextrose in 5% water and distilled water (vehicle 1) and a solution of the same composition of vehicle 1 adjusted to pH 3.0 with ascorbic acid (vehicle 2). Samples were packaged in amber or transparent bottles and stored at 5±2 °C and 25±2 °C for 360 hours. Enalapril maleate was quantified at 0, 12, 24, 36, 48, 72, 120, 168, 240 and 360 hours, using a validated methodology, which proved to be selective, linear, precise and exact. Results: The results indicate that pH is a factor that affects the shelf life of extemporaneous liquid preparations of enalapril maleate. The stability of the extemporaneous preparation was preserved up to 240 hours using vehicle 1 and storing it at a temperature of 5±2°C in an amber bottle. [ABSTRACT FROM AUTHOR]

The article explores chronic constipation in Parkinson's disease (PD) patients, emphasizing its prevalence, impact on quality of life, and multifaceted causes, including medication effects and neurological factors. Topics include the prevalence and impact of chronic constipation in PD, treatment options ranging from dietary adjustments to neuromodulation therapies and the need for further research to validate the effectiveness of these treatments, particularly in neurological disorders like PD.

Parkinson's disease (PD) is characterised by severe movement defects and the degeneration of dopaminergic neurones in the midbrain. The symptoms of PD can be managed with dopamine replacement therapy using L-3, 4-dihydroxyphenylalanine (L-dopa), which is the gold standard therapy for PD. However, long-term treatment with L-dopa can lead to motor complications. The central renin–angiotensin system (RAS) is associated with the development of neurodegenerative diseases in the brain. However, the role of the RAS in dopamine replacement therapy for PD remains unclear. Here, we tested the co-treatment of the angiotensin-converting enzyme inhibitor (ACEI) with L-dopa altered L-dopa-induced dyskinesia (LID) in a 6-hydroxydopamine (6-OHDA)-lesioned mouse model of PD. Perindopril, captopril, and enalapril were used as ACEIs. The co-treatment of ACEI with L-dopa significantly decreased LID development in 6-OHDA-lesioned mice. In addition, the astrocyte and microglial transcripts involving Ccl2, C3, Cd44 , and Iigp1 were reduced by co-treatment with ACEI and L-dopa in the 6-OHDA-lesioned striatum. In conclusion, co-treatment with ACEIs and L-dopa, such as perindopril, captopril, and enalapril, may mitigate the severity of L-DOPA-induced dyskinesia in a mouse model of PD. • Perindopril, captopril, and enalapril attenuate LID in 6-OHDA-induced mouse model. • ACEIs + L-dopa decrease microglial Ccl2 transcription in dopamine-depleted striata. • ACEIs + L-dopa reduce C3 , Cd44, and Iigp1 transcripts in dopamine-depleted striata. [ABSTRACT FROM AUTHOR]

In this work, a TiO 2 -decorated electrode was fabricated by dip coating activated carbon fibers (ACF) with TiO 2 , which were then used as a cathode for the photoelectro-Fenton (PEF) treatment of the pharmaceutical enalapril, an angiotensin-converting enzyme inhibitor that has been detected in several waterways. The TiO 2 coating was found to principally improve the electrocatalytic properties of ACF for H 2 O 2 production via the 2-e- O 2 reduction, in turn increasing enalapril degradation by PEF. The effect of the current density on the mineralization of enalapril was evaluated and the highest TOC removal yield (80.5% in 3 h) was obtained at 8.33 mA cm−2, in the presence of 0.5 mmol L−1 of Fe2+ catalyst. Under those conditions, enalapril was totally removed within the first 10 min of treatment with a rate constant k = 0.472 min−1. In contrast, uncoated ACF only achieved 60% of TOC removal in 3 h at 8.33 mA cm−2. A degradation pathway for enalapril mineralization is proposed, based on the degradation by-products identified during treatment. Overall, the results demonstrate the promises of TiO 2 cathodes for PEF, a strategy that has often been overlooked in favor of photoelectrocatalysis (PEC) based on TiO 2 -modified photoanodes. [Display omitted] • TiO 2 coating improved H 2 O 2 cathodic generation on activated carbon fibers (ACF). • TOC removal reached 80.5% after 3 h of photoelectro-Fenton treatment. • Enalapril was totally removed within 10 min with a rate constant k = 0.472 min−1. • Electrocatalysis was the dominant mechanism, followed by photolysis. • First report of enalapril treatment and of its electrochemical degradation pathway. [ABSTRACT FROM AUTHOR]