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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]

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. ClinicalTrials.gov Identifier: NCT03472508 (Registration Date: March 21, 2018). [ABSTRACT FROM AUTHOR]

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]

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

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]

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]

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]

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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]

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]

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]

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]

Abstract 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.

Background: As the impacts of diabetes-induced reproductive damage are now evident in young people, we are now in urgent need to devise new ways to protect and enhance the reproductive health of diabetic people. The present study aimed to evaluate the protective effects of enalapril (an ACE inhibitor) and paricalcitol (a vitamin D analog), individually or in combination, on streptozotocin (STZ)-diabetes-induced testicular dysfunction in rats and to identify the possible mechanisms for this protection. Material and methods: This study was carried out on 50 male Sprague-Dawley rats; 10 normal rats were allocated as a non-diabetic control group. A total of 40 rats developed diabetes after receiving a single dose of STZ; then, the diabetic rats were divided into four groups of equivalent numbers assigned as diabetic control, enalapril-treated, paricalcitol-treated, and combined enalapril-and-paricalcitol-treated groups. The effects of mono and combined therapy with paricalcitol and enalapril on testicular functions, sperm activity, glycemic state oxidative stress, and inflammatory parameters, as well as histopathological examinations, were assessed in comparison with the normal and diabetic control rats. Results: As a result of diabetes induction, epididymal sperm count, sperm motility, serum levels of testosterone, follicle-stimulating hormone (FSH) as well as luteinizing hormone (LH), and the antioxidant enzyme activities, were significantly decreased, while abnormal sperm (%), insulin resistance, nitric oxide (NO), malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were significantly increased, along with severe distortion of the testicular structure. Interestingly, treatment with paricalcitol and enalapril, either alone or in combination, significantly improved the sperm parameters, increased antioxidant enzyme activities in addition to serum levels of testosterone, FSH, and LH, reduced insulin resistance, IL-6, and TNF-α levels, and finally ameliorated the diabetes-induced testicular oxidative stress and histopathological damage, with somewhat superior effect for paricalcitol monotherapy and combined therapy with both drugs compared to monotherapy with enalapril alone. Conclusions: Monotherapy with paricalcitol and its combination therapy with enalapril has a somewhat superior effect in improving diabetes-induced testicular dysfunction (most probably as a result of their hypoglycemic, antioxidant, anti-inflammatory, and anti-apoptotic properties) compared with monotherapy with enalapril alone in male rats, recommending a synergistic impact of both drugs.

Abstract Background Angiotensin‐converting enzyme inhibitors (ACEi) are a recommended treatment for glomerular proteinuria. Frequency of response to ACEi and the association of achieving proposed urine protein‐to‐creatinine ratio (UPC) targets on survival is unknown. Objectives To determine response rates to ACEi therapy and whether a positive response is associated with improved survival. Animals Eighty‐five dogs with proteinuria (UPC > 2.0). Methods Retrospective study including dogs (UPC > 2.0) prescribed an ACEi for treatment of proteinuria. Baseline creatinine, albumin, cholesterol, UPC, and systolic blood pressure were recorded, and cases reviewed to track UPC. Treatment response was defined as achieving a UPC of 2.0, achieving recommended UPC targets within 3 months appears to be associated with a significant survival benefit. Response to treatment is still associated with survival benefit in dogs with less severe disease (no azotemia or hypoalbuminemia).

Abstract Background Pimobendan, diuretics, and an angiotensin-converting enzyme inhibitor (ACEi) are widely used for the management of chronic valvular heart disease in dogs; however, the effects of that combination on heart rate variability (HRV) are unknown. The purpose of this study was to assess the HRV of symptomatic myxomatous mitral valve degeneration (MMVD) dogs in response to therapy with a combination of pimobendan, diuretics, and ACEi. Results MMVD stage C (n = 17) dogs were enrolled and a 1-hour Holter recording together with echocardiography, blood pressure measurement, and blood chemistry profiles were obtained before and 1, 3, and 6 months after oral treatment with pimobendan (0.25 mg/kg), enalapril (0.5 mg/kg), and furosemide (2 mg/kg) twice daily. The results revealed that MMVD stage C dogs at the baseline had lower values of time-domain indices, low frequency (LF), high frequency (HF), and total power, as well as higher value of LF/HF. Triple therapy significantly increases these parameters in MMVD stage C dogs (P

Background Diabetes Mellitus (DM) is a prominent health care issue worldwide. One of the most prevalent comorbidities of DM is cardiovascular disease (CVD). The objective of this study was to assess the utilization patterns of cardiovascular medications in patients with DM in Iran from 2013 to 2017. Methods This retrospective cross-sectional study was undertaken using prescription claims data from 2013 to 2017 in Iran. Epidemiological data elements used in this study were obtained from the Global Burden of Disease (GBD) 2019 study. In addition, data on total medication sales were obtained from the national regulatory authority database. The data on medication utilization were analyzed according to the Anatomical Therapeutic Chemical Classification (ATC) /Defined Daily Doses (DDD) international system. Results Based on the findings, Acetylsalicylic acid was the mainstay of treatment with a utilization rate of 191.7 DDD/ patient/ year in 2017, followed by Atorvastatin with 170.0 and Losartan with 115.1. Although there was an increasing trend in the utilization rate of the medications, the rate of Atenolol and Enalapril was constantly declining during the 2013-17 period. On the other hand, Valsartan and Metoprolol were attracting attention. Almost all medication utilization rates increased from the 30--39 age group up to the 80 + age group. Females had a higher utilization rate in each age group during the whole study period. Conclusion The present study reflects that medication utilization patterns were rational, according to the standard treatment guidelines. Utilization patterns of medications that are recommended for both prevention and treatment of CVD in diabetes were observed to be the highest. Implementation of further policies is needed to minimize cardiovascular complications of diabetes. [ABSTRACT FROM AUTHOR]