Comparison of Angioedema in Heart Failure Patients Treated with Sacubitril/Valsartan or Enalapril in the PARADIGM-HF Study
Background: The PARADIGM-HF study showed that sacubitril/valsartan (LCZ696) is beneficial in heart failure (HF) patients with reduced ejection fraction. Inhibition of neprilysin, angiotensin-converting enzyme (ACE) or aminopeptidase may lead to bradykinin elevation and increased risk of angioedema. Therefore, this was considered an adverse event of special interest in the PARADIGM-HF study. Methods: PARADIGM-HF included 10513 eligible class II-IV HF patients (ejection fraction  ≤ 40%, and mildly elevated NT-proBNP/BNP) in the enalapril run-in phase. (Source: Journal of Cardiac Failure)
Source: Journal of Cardiac Failure - July 23, 2016 Category: Cardiology Authors: Alan Kaplan, Hendrik Streefkerk, Christine Thorburn, Victor Shi, Wenchun Zhou, Heike Schwende, Milton Packer Source Type: research

Efficacy of Sacubitril/Valsartan Relative to  a Prior Decompensation
Conclusions Patients with recent HF decompensation requiring hospitalization were more likely to experience cardiovascular death or HF hospitalization than those who had never been hospitalized. Patients who were clinically stable, as shown by a remote HF hospitalization (>3 months prior to screening) or by lack of any prior HF hospitalization, were as likely to benefit from sacubitril/valsartan therapy as more recently hospitalized patients. (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF]; NCT01035255) (Source: JACC: Heart Failure)
Source: JACC: Heart Failure - July 21, 2016 Category: Cardiology Source Type: research

Intrauterine growth restriction programs an accelerated age-related increase in cardiovascular risk in male offspring
Placental insufficiency programs an increase in blood pressure associated with a twofold increase in serum testosterone in male growth-restricted offspring at 4 mo of age. Population studies indicate that the inverse relationship between birth weight and blood pressure is amplified with age. Thus, we tested the hypothesis that intrauterine growth restriction programs an age-related increase in blood pressure in male offspring. Growth-restricted offspring retained a significantly higher blood pressure at 12 but not at 18 mo of age compared with age-matched controls. Blood pressure was significantly increased in control offs...
Source: AJP: Renal Physiology - July 21, 2016 Category: Urology & Nephrology Authors: Dasinger, J. H., Intapad, S., Backstrom, M. A., Carter, A. J., Alexander, B. T. Tags: ARTICLES Source Type: research

Postoperative Case Study: A Collaborative Approach to Symptomatic Bradycardia
A 64 year old female patient arrived to PACU after right total hip replacement surgery. Preoperative vital signs were 110-120/70’s, heart rate 59-60 beat per minute (bpm), respirations 16 per minute, and pule ox 100% on room air. Home meds included aspirin, carvedilol, furosemide, hydralazine, atorvastatin, metformin, amlodipine, and enalapril. The case was done under general anesthesia with no significant intraoperative events. Postoperatively, vitals were 80-90’s/60’s, 40’s/sinus bradycardia, 15, and 99% on room air. (Source: Journal of PeriAnesthesia Nursing)
Source: Journal of PeriAnesthesia Nursing - July 19, 2016 Category: Nursing Authors: Delsene Hanner, Patricia Mefford, Mark Neuman, Julie Thomas, Donna Bernard, Jennifer Fraccaroli Source Type: research

Study of Copolymer Composition on Drug Loading Efficiency of Enalapril in Polymersomes and Cytotoxicity of Drug Loaded Nanoparticles
Drug Res (Stuttg)DOI: 10.1055/s-0042-110931Enalapril was used for hypertension and congestive heart failure. Di-block mPEG-PCL copolymers were synthesized and used to prepare of polymersomes for controlled release of enalapril as a hydrophilic drug. The various methods such as HNMR, FTIR, GPC, DSC, PCS and AFM performed for characterization of the polymersomes. The results of AFM showed that the polymersomes had spherical structure and the size of nanoparticles was 97 nm. Drug-loading efficiency of nanoparticles from copolymers with compositions of mPEG1-PCL1, mPEG2-PCL2, and mPEG3-PCL3 were 14.43%, 19.8%, and 12.3...
Source: Drug Research - July 19, 2016 Category: Drugs & Pharmacology Authors: Danafar, H.Manjili, H. K.Najafi, M. Tags: Original Article Source Type: research

Influence of Sacubitril/Valsartan (LCZ696) on 30-Day Readmission After Heart Failure Hospitalization
ConclusionsCompared with enalapril, treatment with LCZ696 reduces 30-day readmissions for any cause following discharge from HF hospitalization. (Source: Journal of the American College of Cardiology)
Source: Journal of the American College of Cardiology - July 11, 2016 Category: Cardiology Source Type: research

Efficacy of Sacubitril/Valsartan Relative to a Prior Decompensation
Conclusions Patients with recent HF decompensation requiring hospitalization were more likely to experience cardiovascular death or HF hospitalization than those who had never been hospitalized. Patients who were clinically stable, as shown by a remote HF hospitalization (>3 months prior to screening) or by lack of any prior HF hospitalization, were as likely to benefit from sacubitril/valsartan therapy as more recently hospitalized patients. (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF]; NCT01035255) (Source: JACC: Heart Failure)
Source: JACC: Heart Failure - July 11, 2016 Category: Cardiology Source Type: research

Enhancement of anti-OVA IgG2c production in vivo by enalapril.
In this study, we investigated the effect of enalapril treatment on ovalbumin (OVA)-specific IgG1 and IgG2c production in mice determined by ELISA. Two groups of 8-week-old C57BL/6 females mice (3-4/group) were subcutaneously immunized with OVA (10 μg/animal) in presence of Alhydrogel (1 mg/mouse) and boosted at day 21. The mice were treated with enalapril (5 mg/kg daily, po) or were left without treatment for one month. The animals were bled from the orbital plexus on days 0, 7, 14, 21, and 28 after the first immunization and the sera were stored at -20°C until usage. OVA-specific serum IgG1 and IgG2c were determin...
Source: Braz J Med Biol Res - July 11, 2016 Category: Research Authors: Almeida LC, Muraro LS, Albuquerque DA Tags: Braz J Med Biol Res Source Type: research

A case of survival following intake of a potentially lethal dose of enalapril
10.1080/15569543.2016.1201841Xiao-Wei Liu (Source: Toxin Reviews)
Source: Toxin Reviews - July 8, 2016 Category: Toxicology Authors: Xiao-Wei LiuYan JinZhi Liu Source Type: research

Effects of dipeptidyl peptidase-4 inhibitor in insulin-resistant rats with myocardial infarction
Adverse cardiac remodeling after myocardial infarction (MI) leads to progressive heart failure. Obese-insulin resistance increases risks of MI and heart failure. Although dipeptidyl peptidase-4 (DPP4) inhibitor is known to exert cardioprotection, its effects on adverse remodeling after MI in obese-insulin-resistant rats are unclear. We hypothesized that DPP4 inhibitor reduces adverse left ventricular (LV) remodeling and LV dysfunction in obese-insulin-resistant rats with MI. Rats were fed either normal diet (ND) or high-fat diet (HFD) for 12 weeks to induce obese-insulin resistance, followed by left anterior descending cor...
Source: Journal of Endocrinology - June 23, 2016 Category: Endocrinology Authors: Apaijai, N., Inthachai, T., Lekawanvijit, S., Chattipakorn, S. C., Chattipakorn, N. Tags: Research Source Type: research

Role of Angiotensin Receptor-Neprilysin Inhibition in Heart Failure
Abstract Purpose of Review Numerous evidence-based medical and device therapies proven to reduce morbidity and mortality have advanced care for heart failure with reduced ejection fraction (HFrEF). The primacy of this approach has now been superseded by striking new data resulting in the approval of the combination of valsartan and sacubitril, a neprilysin inhibitor (also known as LCZ696), in 2015 for the treatment of HFrEF. LCZ696 is a novel heart failure drug that simultaneously inhibits the renin-angiotensin system and potentiates the natriuretic peptide system. ...
Source: Current Atherosclerosis Reports - June 20, 2016 Category: Cardiology Source Type: research

Factors Associated With Noncompletion During the Run-In Period Before Randomization and Influence on the Estimated Benefit of LCZ696 in the PARADIGM-HF Trial [Original Article]
Conclusions— Patients with lower blood pressure, lower glomerular filtration rate, and more severe heart failure were at higher risk for noncompletion during the run-in period of PARADIGM-HF. Weighted analysis of key study outcomes accounting for the effect of run-in noncompletion did not alter the benefit of LCZ696 over enalapril. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255. (Source: Circulation: Heart Failure)
Source: Circulation: Heart Failure - June 13, 2016 Category: Cardiology Authors: Desai, A. S., Solomon, S., Claggett, B., McMurray, J. J. V., Rouleau, J., Swedberg, K., Zile, M., Lefkowitz, M., Shi, V., Packer, M. Tags: Heart Failure, Mortality/Survival Original Article Source Type: research

Partial podocyte replenishment in experimental FSGS derives from nonpodocyte sources
The current studies used genetic fate mapping to prove that adult podocytes can be partially replenished following depletion. Inducible NPHS2-rtTA/tetO-Cre/RS-ZsGreen-R reporter mice were generated to permanently label podocytes with the ZsGreen reporter. Experimental focal segmental glomerulosclerosis (FSGS) was induced with a cytotoxic podocyte antibody. On FSGS day 7, immunostaining for the podocyte markers p57, synaptopodin, and podocin were markedly decreased by 44%, and this was accompanied by a decrease in ZsGreen fluorescence. The nuclear stain DAPI was absent in segments of reduced ZsGreen and podocyte marker stai...
Source: AJP: Renal Physiology - June 7, 2016 Category: Urology & Nephrology Authors: Kaverina, N. V., Eng, D. G., Schneider, R. R. S., Pippin, J. W., Shankland, S. J. Tags: ARTICLES Source Type: research

Anxiolytic- and antidepressant-like effects of angiotensin-(1-7) in hypertensive transgenic (mRen2)27 rats
Angiotensin-(1-7) [Ang-(1-7)], a counter-regulatory peptide of the renin-angiotensin system (RAS) exerts its effects through the G-protein-coupled receptor Mas, which is expressed in different tissues, including the brain.  Ang-(1-7) has a broad range of effects beyond the well-described cardiovascular and renal actions, including the modulation of emotional and behavioral responses.  In the present study we tested the hypothesis that Ang-(1-7) could attenuate the anxiety- and depressive-like behaviors observed in transgenic hypertensive (mRen2)27 (TGR) rats.  We also hypothesized that Ang-(1-7) co...
Source: Clinical Science - June 6, 2016 Category: Biomedical Science Authors: Santos Almeida, A. F., Kangussu, L. M., Moreira, F. A., Santos, R. A. S., Aguiar, D. C., Campagnole-Santos, M. J. Tags: PublishAheadOfPrint Source Type: research

Pharmacokinetic–pharmacodynamic modelling of acute N‐terminal pro B‐type natriuretic peptide after doxorubicin infusion in breast cancer
ConclusionThe relationship between doxorubicin concentration and the acute NT‐proBNP response was successfully described with a population PK‐PD model. This model will serve as a valuable framework for future studies to identify clinical factors associated with the acute response to doxorubicin. Future studies are warranted to examine the relationship between this acute response and subsequent heart failure. Should such a relationship be established, this model could provide useful information on patients' susceptibility to doxorubicin‐induced long‐term cardiotoxicity. (Source: British Journal of Clinical Pharmacology)
Source: British Journal of Clinical Pharmacology - June 3, 2016 Category: Drugs & Pharmacology Authors: Shuang Liang, Richard C. Brundage, Pamala A. Jacobson, Anne Blaes, Mark N. Kirstein Tags: Clinical Trials Source Type: research

Pharmacokinetic –pharmacodynamic modelling of acute N‐terminal pro B‐type natriuretic peptide after doxorubicin infusion in breast cancer
ConclusionThe relationship between doxorubicin concentration and the acute NT‐proBNP response was successfully described with a population PK‐PD model. This model will serve as a valuable framework for future studies to identify clinical factors associated with the acute response to doxorubicin. Future studies are warranted to examine the relationship between this acute response and subsequent heart failure. Should such a relationship be established, this model could provide useful information on patients' susceptibility to doxorubicin‐induced long‐term cardiotoxicity. (Source: British Journal of Clinical Pharmacology)
Source: British Journal of Clinical Pharmacology - June 3, 2016 Category: Drugs & Pharmacology Authors: Shuang Liang, Richard C. Brundage, Pamala A. Jacobson, Anne Blaes, Mark N. Kirstein Tags: Clinical Trials Source Type: research

Angiotensin-Converting Enzyme Inhibition as an Adjunct to Pulmonary Rehabilitation in COPD.
Abstract RATIONALE: Epidemiological studies in older individuals have found an association between use of ACE-inhibition (ACE-I) therapy and preserved locomotor muscle mass, strength and walking speed. ACE-I therapy might therefore have a role in the context of pulmonary rehabilitation. OBJECTIVES: We investigated the hypothesis that enalapril, an ACE-inhibitor, would augment the improvement in exercise capacity seen during pulmonary rehabilitation. METHODS: We performed a double-blind, placebo-controlled, parallel-group randomised controlled trial. COPD patients, with at least moderate airflow obstructi...
Source: American Journal of Respiratory and Critical Care Medicine - June 1, 2016 Category: Respiratory Medicine Authors: Curtis KJ, Meyrick VM, Mehta B, Haji GS, Li K, Montgomery H, Man WD, Polkey MI, Hopkinson NS Tags: Am J Respir Crit Care Med Source Type: research

Study of the effect of formulation variables on the characteristics of combination tablets containing enalapril maleate and indapamide as active substances using experimental design.
;si I, Kovács B, Zöldi K, Sipos E Abstract To evaluate the influence of different variables on tablet formulations containing enalapril maleate and indapamide as active substances, two separate experimental designs were employed: one for evaluating powder properties and the other for tablet characteristics. Because of the low active pharmaceutical ingredient content, it was hypothesized that both powder and tablet properties could be determined only by the characteristics of excipients. In order to test this assumption, both experimental designs were done with placebo mixtures. The optimized formulatio...
Source: Acta Pharmaceutica - June 1, 2016 Category: Drugs & Pharmacology Authors: Szabó ZI, Székely-Szentmiklósi B, Deák B, Székely-Szentmiklósi I, Kovács B, Zöldi K, Sipos E Tags: Acta Pharm Source Type: research

PS076 The Increased States of Cardiac Autonomic Nervous Activity at Late Night and the Effect of Enalapril in Patients With Essential Hypertension
Cardiac autonomic nervous activity at late night in patients with essential hypertension is unknown. (Source: CVD Prevention and Control)
Source: CVD Prevention and Control - June 1, 2016 Category: Global & Universal Authors: Y. Liu, X. Liu, Y. Fan Tags: Poster Abstract Source Type: research

Early Treatment with Enalapril and Later Renal Injury in Programmed Obese Adult Rats
ABSTRACT Obesity‐related kidney disease should be prevented or retarded. We aimed to investigate whether early treatment with enalapril ameliorates later renal injury induced by early postnatal overnutrition. Three or ten male pups per mother were assigned to either the Obese or Lean group during the first 21 days of life. These pups were treated with enalapril (Obese enalapril, OE; Lean enalapril, LE) or vehicle (Obese control, OC; Lean control, LC) for 15–28 days. Body weight, blood pressure (BP), and renal alterations were determined at 3 months. Enalapril decreased body weight only in the Lean group at 3 months (P 
Source: Journal of Cellular Physiology - May 30, 2016 Category: Cytology Authors: Hyung Eun Yim, Kee Hwan Yoo, In Sun Bae, Young Sook Hong Tags: Original Research Article Source Type: research

Effects of xanthine oxidase inhibition with febuxostat on the development of nephropathy in experimental Type 2 diabetes.
ConclusionsFBX is protective and enhances actions of ENL in experimental DN. Multiple mechanisms might contribute, such as reduction of UA, renal OS and inhibition of profibrotic signaling. (Source: British Journal of Pharmacology)
Source: British Journal of Pharmacology - May 30, 2016 Category: Drugs & Pharmacology Authors: Radko Komers, Bei Xu, Jennifer Schneider, Terry T. Oyama Tags: RESEARCH PAPER Source Type: research

PS076 The Increased States of Cardiac Autonomic Nervous Activity at Late Night and the Effect of Enalapril in Patients With Essential Hypertension
Cardiac autonomic nervous activity at late night in patients with essential hypertension is unknown. (Source: CVD Prevention and Control)
Source: CVD Prevention and Control - May 27, 2016 Category: Cardiology Authors: Y. Liu, X. Liu, Y. Fan Tags: Poster Abstract Source Type: research

A Systematic Approach to Assess the Burden of Drug Interactions in Adult Kidney Transplant Patients.
Abstract AIM: Renal transplant patients are frequently subject to polypharmacy and drug-drug interactions. However, no previous study has systematically assessed the risk of drug interactions and Adverse Drug Reactions (ADRs) in this population. METHODS: A total of 138 consecutive adult kidney transplant recipients admitted to our hospital between August 2010 and February 2012 were prospectively and systematically assessed by our pharmacovigilance team, within 24 hours of admission, to identify potential drug-drug interactions and probable ADRs. RESULTS: As a consequence of the high number of medications...
Source: Current Drug Safety - May 21, 2016 Category: Drugs & Pharmacology Authors: Bril F, Castro V, Centurion IG, Espinosa J, Keller GA, Gonzalez CD, Riera MC, Saubidet CL, Di Girolamo G, Pujol GS, Alvarez PA Tags: Curr Drug Saf Source Type: research

An additive effect of eplerenone to ACE inhibitor on slowing the progression of diabetic nephropathy in the db/db mice.
Authors: Zhou G, Johansson U, Peng XR, Bamberg K, Huang Y Abstract Although blockade of the renin-angiotensin-system (RAS) has become standard therapy for diabetic nephropathy (DN), decline in kidney function towards end-stage renal disease is seen in many patients. Elevated plasma aldosterone often accompanies RAS blockade by a phenomenon known as "aldosterone escape" and activates the mineralocorticoid receptor (MR). We therefore examined whether addition of the MR antagonist eplerenone to an ACEI would enhance the efficacy in slowing the progression of DN. Untreated uninephrectomized diabetic db/db mic...
Source: American Journal of Translational Research - May 19, 2016 Category: Research Tags: Am J Transl Res Source Type: research

Chronic Blockade of the Androgen Receptor Abolishes Age-Dependent Increases in Blood Pressure in Female Growth-Restricted Rats [Intrauterine Growth Restriction and Androgen Receptor]
Intrauterine growth restriction induced via placental insufficiency programs a significant increase in blood pressure at 12 months of age in female growth-restricted rats that is associated with early cessation of estrous cyclicity, indicative of premature reproductive senescence. In addition, female growth-restricted rats at 12 months of age exhibit a significant increase in circulating testosterone with no change in circulating estradiol. Testosterone is positively associated with blood pressure after menopause in women. Thus, we tested the hypothesis that androgen receptor blockade would abolish the significant increase...
Source: Hypertension - May 11, 2016 Category: Cardiology Authors: Dasinger, J. H., Intapad, S., Rudsenske, B. R., Davis, G. K., Newsome, A. D., Alexander, B. T. Tags: ACE/Angiotensin Receptors/Renin Angiotensin System, Animal Models of Human Disease, Basic Science Research, Physiology Intrauterine Growth Restriction and Androgen Receptor Source Type: research

Popular pharmaceutical residues in hospital wastewater: quantification and qualification of degradation products by mass spectroscopy after treatment with membrane bioreactor.
Abstract The occurrence of drugs in wastewater has been considered an imminent risk to the population, for the treatments used are usually ineffective. The presence of four popular drug residues (metformin, paracetamol, tetracycline, and enalapril) in hospital effluents, by using ultra-fast liquid chromatography tandem mass spectrometry (UFLC-MS/MS) with electrospray (ESI) ionization, and removal/degradation by membrane bioreactor (MBR) system are investigated in this study. For analysis method, all standard calibration curves showed satisfactory linearity (R (2) ≥ 0.993) within a relatively wide ...
Source: Environmental Science and Pollution Research International - May 5, 2016 Category: Environmental Health Authors: Chiarello M, Minetto L, Giustina SV, Beal LL, Moura S Tags: Environ Sci Pollut Res Int Source Type: research

Intrauterine growth restriction programs accelerated age-related increased cardiovascular risk in male offspring.
INTRAUTERINE GROWTH RESTRICTION PROGRAMS ACCELERATED AGE-RELATED INCREASED CARDIOVASCULAR RISK IN MALE OFFSPRING. Am J Physiol Renal Physiol. 2016 May 4;:ajprenal.00123.2016 Authors: Dasinger JH, Intapad S, Backstrom MA, Carter AJ, Alexander BT Abstract Placental insufficiency programs an increase in blood pressure associated with a two-fold increase in serum testosterone in male growth-restricted offspring at 4 months of age. Population studies indicate that the inverse relationship between birth weight and blood pressure is amplified with age. Thus, we tested the hypothesis that intrauterine growth ...
Source: Am J Physiol Renal P... - May 4, 2016 Category: Urology & Nephrology Authors: Dasinger JH, Intapad S, Backstrom MA, Carter AJ, Alexander BT Tags: Am J Physiol Renal Physiol Source Type: research

Suppression of connective tissue growth factor mediates the renoprotective effect of Sitagliptin rather than Pioglitazone in type 2 diabetes mellitus
Publication date: 15 May 2016 Source:Life Sciences, Volume 153 Author(s): Samia M. Ali, Hoda Khalifa, Dalia K. Mostafa, Amal El sharkawy Aim Diabetic nephropathy (DN) is a leading cause of end-stage renal disease, and thus, the ability of antidiabetic drugs to ameliorate renal microvascular disease may be as important as their ability to control blood glucose. Therefore, we investigated the reno-protective effect of the antidiabetic drugs, Sitagliptin and Pioglitazone, versus combined Metformin/Enalapril in a rat model of type 2 diabetes. Method Male Wistar rats were randomly assigned to be either normal control or ...
Source: Life Sciences - May 3, 2016 Category: Biology Source Type: research

Anxiolytic- and antidepressant-like effects of angiotensin-(1-7) in hypertensive transgenic (mRen2)27 rats
Angiotensin-(1-7) [Ang-(1-7)], a counter-regulatory peptide of the renin-angiotensin system (RAS) exerts its effects through the G-protein-coupled receptor Mas, which is expressed in different tissues, including the brain.  Ang-(1-7) has a broad range of effects beyond the well-described cardiovascular and renal actions, including the modulation of emotional and behavioral responses.  In the present study we tested the hypothesis that Ang-(1-7) could attenuate the anxiety- and depressive-like behaviors observed in transgenic hypertensive (mRen2)27 (TGR) rats.  We also hypothesized that Ang-(1-7) co...
Source: Clinical Science - May 3, 2016 Category: Biomedical Science Authors: Santos Almeida, A. F. J., Kangussu, L. M., Moreira, F. A., Santos, R. A. S., Aguiar, D. C., Campagnole-Santos, M. J. Tags: PublishAheadOfPrint Source Type: research

Efficacy of sacubitril/valsartan vs. enalapril at lower than target doses in heart failure with reduced ejection fraction: the PARADIGM‐HF trial
Abstract AimsIn this analysis, we utilized data from PARADIGM‐HF to test the hypothesis that participants who exhibited any dose reduction during the trial would have similar benefits from lower doses of sacubitril/valsartan relative to lower doses of enalapril. Methods and resultsIn a post‐hoc analysis from PARADIGM‐HF, we characterized patients by whether they received the maximal dose (200 mg sacubitril/valsartan or 10 mg enalapril twice daily) throughout the trial or had any dose reduction to lower doses (100/50/0 mg sacubitril/valsartan or 5/2.5/0 mg enalapril twice daily). The treatment effect for the primary o...
Source: European Journal of Heart Failure - May 1, 2016 Category: Cardiology Authors: Orly Vardeny, Brian Claggett, Milton Packer, Michael R. Zile, Jean Rouleau, Karl Swedberg, John R. Teerlink, Akshay S. Desai, Martin Lefkowitz, Victor Shi, John J.V. McMurray, Scott D. Solomon, Tags: Original Article Source Type: research

Pharmacokinetic‐pharmacodynamic modeling of acute N‐terminal pro B‐type natriuretic peptide after doxorubicin infusion in breast cancer
ConclusionThe relationship between doxorubicin concentration and acute NT‐proBNP response was successfully described with a population PK‐PD model. This model will serve as a valuable framework for future studies to identify clinical factors associated with acute response to doxorubicin. Future studies are warranted to examine the relationship between this acute response and subsequent heart failure. Should such relationship be established this model could provide useful information of patients’ susceptibility to doxorubicin‐induced long‐term cardiotoxicity. This article is protected by copyright. All rights ...
Source: British Journal of Clinical Pharmacology - April 30, 2016 Category: Drugs & Pharmacology Authors: Shuang Liang, Richard C. Brundage, Pamala A. Jacobson, Anne Blaes, Mark N. Kirstein Tags: Clinical Trials Source Type: research

Lercanidipine/enalapril combination in the management of obesity-related hypertension
Guido Grassi1,2 1Internal Medicine, Department of Health Science, Università Milano-Bicocca, Milano, Italy; 2Istituto di Ricerche a Carattere Scientifico (IRCCS) Multimedica, Sesto San Giovanni, Milano, ItalyAbstract: Obesity-related hypertension represents a condition frequently observed in current clinical practice characterized by a complex pathophysiological background and a very high cardiovascular risk profile, particularly in severely obese individuals. This explains, on the one hand, the difficulty in reducing elevated blood pressure values in this pathological state and, on the other, the need to achieve th...
Source: Integrated Blood Pressure Control - April 26, 2016 Category: Cardiology Tags: Integrated Blood Pressure Control Source Type: research

Lercanidipine enalapril in obese hypertensives
Grassi G (Source: Integrated Blood Pressure Control)
Source: Integrated Blood Pressure Control - April 25, 2016 Category: Cardiology Source Type: research

Anxiolytic- and antidepressant-like effects of angiotensin-(1-7) in hypertensive transgenic (mRen2)27 rats
Angiotensin-(1-7) [Ang-(1-7)], a counter-regulatory peptide of the renin-angiotensin system (RAS) exerts its effects through the G-protein-coupled receptor Mas, which is expressed in different tissues, including the brain.  Ang-(1-7) has a broad range of effects beyond the well-described cardiovascular and renal actions, including the modulation of emotional and behavioral responses.  In the present study we tested the hypothesis that Ang-(1-7) could attenuate the anxiety- and depressive-like behaviors observed in transgenic hypertensive (mRen2)27 (TGR) rats.  We also hypothesized that Ang-(1-7) co...
Source: Clinical Science - April 20, 2016 Category: Biomedical Science Authors: Almeida-Santos, A. F. J., Kangussu, L. M., Moreira, F. A., Santos, R. A. S., Aguiar, D. C., Campagnole-Santos, M. J. Tags: PublishAheadOfPrint Source Type: research

Reflection on the Pharmaceutical Formulation Challenges Associated with a Paediatric Investigation Plan for an Off-Patent Drug.
This article provides an overview of some of the key formulation challenges that were faced during the product development programme and PIP process, including selection of dosage form and excipients, methodology for administration of the product and evaluation of patient acceptability. PMID: 27097815 [PubMed - as supplied by publisher] (Source: AAPS PharmSciTech)
Source: AAPS PharmSciTech - April 20, 2016 Category: Drugs & Pharmacology Authors: Walsh J Tags: AAPS PharmSciTech Source Type: research

Importance of Clinical Worsening of Heart Failure Treated in the Outpatient Setting: Evidence from the Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial (PARADIGM-HF).
CONCLUSIONS: -Focusing only on HFh underestimates the frequency of worsening and the serious implications of all manifestations of worsening. For clinical trials conducted in an era of heightened efforts to avoid HFh, inclusion of episodes of outpatient treatment intensification (and ED visits) in a composite outcome adds an important number of events and shortens the time taken to accrue a target number of endpoints in an event-driven trial. Clinical Trial Registration Information-www.clinicaltrials.gov. Identifier: NCT01035255. PMID: 27143684 [PubMed - as supplied by publisher] (Source: Circulation)
Source: Circulation - April 20, 2016 Category: Cardiology Authors: Okumura N, Jhund PS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Swedberg K, Zile MR, Solomon SD, Packer M, McMurray JJ, PARADIGM-HF Investigators and Committees Tags: Circulation Source Type: research

Cost-Effectiveness of Sacubitril-Valsartan Combination Therapy Compared With Enalapril for the Treatment of Heart Failure With Reduced Ejection Fraction
Conclusions Sacubitril-valsartan may be a cost-effective treatment option depending on the willingness-to-pay threshold. Future investigations should incorporate real-world evidence with sacubitril-valsartan to further inform decision making. (Source: JACC: Heart Failure)
Source: JACC: Heart Failure - April 19, 2016 Category: Cardiology Source Type: research

Partial Podocyte Replenishment in Experimental FSGS Derives from Non-Podocyte Sources.
Abstract The current studies used a genetic fate mapping approach to prove that adult podocytes can be partially replenished, following depletion. Inducible NPHS2-rtTA/tetO-Cre/RS-ZsGreen-R reporter mice were generated in order to permanently label podocytes with the ZsGreen reporter. Experimental FSGS was induced with a cytotoxic podocyte antibody. On FSGS d7, immunostaining for the podocyte markers p57, synaptopodin and podocin were markedly decreased by 44%, accompanied by a decrease in ZsGreen fluorescence. The nuclear stain DAPI was absent in segments of reduced ZsGreen and podocyte marker staining, consisten...
Source: American Journal of Physiology. Renal Physiology - April 13, 2016 Category: Physiology Authors: Kaverina NV, Eng DG, Schneider RR, Pippin JW, Shankland SJ Tags: Am J Physiol Renal Physiol Source Type: research

Endothelial nitric oxide synthase tagSNPs influence the effects of enalapril in essential hypertension
We examined whether the NOS3 tagSNPs rs3918226, rs3918188, and rs743506, and their haplotypes, affect the antihypertensive responses to enalapril in 101 patients with essential hypertension. Subjects were prospectively treated only with enalapril for 8 weeks. Genotypes were determined by Taqman® allele discrimination assay and real-time polymerase chain reaction (PCR) and haplotype frequencies were estimated. We compared the effects of NOS3 tagSNPs on changes in blood pressure after enalapril treatment. To confirm our findings, multiple linear regression analysis was performed adjusting for age, gender, ethnicity, and ...
Source: Nitric Oxide - April 6, 2016 Category: Chemistry Source Type: research

Diuretics for Hypertension: A Review and Update.
Abstract This review and update focuses on the clinical features of hydrochlorothiazide (HCTZ), the thiazide-like agents chlorthalidone (CTDN) and indapamide (INDAP), potassium-sparing ENaC inhibitors and aldosterone receptor antagonists, and loop diuretics. Diuretics are the second most commonly prescribed class of antihypertensive medication, and thiazide-related diuretics have increased at a rate greater than that of antihypertensive medications as a whole. The latest hypertension guidelines have underscored the importance of diuretics for all patients, but particularly for those with salt-sensitive and resista...
Source: American Journal of Hypertension - April 5, 2016 Category: Cardiology Authors: Roush GC, Sica DA Tags: Am J Hypertens Source Type: research

Diabetic hypertensive patients, get better glycaemic and blood pressure control with imidapril than with other angiotensin-converting enzyme inhibitors
Imidapril data are favorable, showing that presents an appropriate metabolic profile in patients with metabolic syndrome or glucose intolerance. However, there are few data in real-life treatments with imidapril compared with other angiotensin-converting enzyme inhibitors (ACE I). In this paper, we compared a group of diabetic hypertensive patients receiving imidapril with another group receiving enalapril for the treatment of hypertension and value the impact on glycosylated haemoglobin (Hb A1c) over several months. (Source: Journal of the American Society of Hypertension)
Source: Journal of the American Society of Hypertension - April 1, 2016 Category: Cardiology Authors: Ricardo Cabrera-Sole, Caridad Turpin Lucas, Liliana Urrego Rivera, Manuel Aguilera Saldana Tags: Metabolic Syndrome (Diabetes/Glycemic Control; Dysglycemic Drugs; Insulin Resistance) Source Type: research

Effect of Enalapril on Preventing Anthracycline-Induced Cardiomyopathy.
Abstract Anthracycline (ANT) is a topoisomerase-interacting agent that is used in most malignancy treatments. We investigated the efficacy of enalapril (angiotensin-converting enzyme inhibitor) in the prevention of ANT-induced cardiomyopathy. In this randomized, single-blind, and placebo-controlled study, 69 patients with a newly diagnosed malignancy for which ANT therapy was planned were randomly assigned to either a group receiving enalapril (n = 34) or placebo (n = 35). Echocardiography studies were performed before chemotherapy and at 6 months after randomization. Additionally, troponi...
Source: Cardiovascular Toxicology - March 22, 2016 Category: Cardiology Authors: Janbabai G, Nabati M, Faghihinia M, Azizi S, Borhani S, Yazdani J Tags: Cardiovasc Toxicol Source Type: research

Pearls & Oy-sters: Symptomatic innominate artery disease
A 64-year-old man presented to the emergency department with left-sided weakness and speech impairment upon awakening. He had a history of multiple myocardial infarctions and had undergone coronary angioplasty and coronary artery bypass graft surgery 1 year previously. He was a heavy smoker and had arterial hypertension. He was taking aspirin 100 mg QD, clopidogrel 75 mg QD, simvastatin 40 mg QD, and enalapril 5 mg BID. (Source: Neurology)
Source: Neurology - March 21, 2016 Category: Neurology Authors: Guedes, B. F., Valeriano, R. P., Puglia, P., Arantes, P. R., Conforto, A. B. Tags: RESIDENT AND FELLOW SECTION Source Type: research

Effect of folic acid supplementation on cancer risk among adults with hypertension in China: A randomized clinical trial
Abstract The relationship of folic acid supplementation with the risk of cancer remains inconclusive. We aimed to evaluate the effects of folic acid supplementation on cancer incidence among adults with hypertension without history of stroke or myocardial infarction(MI) in the China Stroke Primary Prevention Trial(CSPPT). A total of 20,702 hypertensive adults without history of stroke or MI, stratified by MTHFR C677T genotypes(CC, CT, and TT), were randomly assigned to receive double‐blind daily treatment with a single pill containing 10mg enalapril and 0.8 mg folic acid(n=10,348) or a pill containing 10mg enalapril alon...
Source: International Journal of Cancer - March 17, 2016 Category: Cancer & Oncology Authors: Xianhui Qin, Lin Shen, Rong Zhang, Youbao Li, Xiaobin Wang, Binyan Wang, Xiaodong Jiang, Hua Jiang, Yu Lei, Fan Fan Hou, Jin Gu, Yong Huo Tags: Research Article Source Type: research

Combined Angiotensin Receptor Antagonism and Neprilysin Inhibition.
Abstract Heart failure affects ≈5.7 million people in the United States alone. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, and aldosterone antagonists have improved mortality in patients with heart failure and reduced ejection fraction, but mortality remains high. In July 2015, the US Food and Drug Administration approved the first of a new class of drugs for the treatment of heart failure: Valsartan/sacubitril (formerly known as LCZ696 and currently marketed by Novartis as Entresto) combines the angiotensin receptor blocker valsartan and the neprilysin inhibitor...
Source: Circulation - March 15, 2016 Category: Cardiology Authors: Hubers SA, Brown NJ Tags: Circulation Source Type: research

Chemometric optimization and validation of a novel dispersive liquid–liquid microextraction–HPLC method for gliclazide, glibenclamide and glimepiride quantitation in serum samples
Publication date: July 2016 Source:Microchemical Journal, Volume 127 Author(s): Celina M. Monzón, Carla M. Teglia, Mario R. Delfino, Héctor C. Goicoechea A dispersive liquid–liquid micro extraction (DLLME) liquid chromatographic method that allows extraction and separation of gliclazide, glibenclamide and glimepiride from serum was developed and optimized with the use of experimental design. The analyzed factors in optimization were type of extracting solvent, extracting solvent volume, dispersing solvent volume, pH and protein precipitation. The selected conditions for DLLME were dichloromethane ...
Source: Microchemical Journal - March 10, 2016 Category: Chemistry Source Type: research

Angioedema With Renin Angiotensin System Drugs and Neutral Endopeptidase Inhibitors
In the PARADIGM-HF study, sacubitril-valsartan (LCZ696) was found to be superior to enalapril in reducing the risks of death and hospitalization for heart failure.1 The medication was approved by the FDA for use in patients with chronic NYHA Class II-IV heart failure and reduced ejection fraction. However, questions remain about the use of sacubitril-valsartan across the spectrum of patients with heart failure and on the occurrence of angioedema.2 (Source: Journal of the American Society of Hypertension)
Source: Journal of the American Society of Hypertension - March 7, 2016 Category: Cardiology Authors: John B. Kostis, Abel E. Moreyra, William J. Kostis Tags: Commentary Source Type: research

Clinically Relevant Doses of Enalapril Mitigate Multiple Organ Radiation Injury.
Abstract Angiotensin-converting enzyme inhibitors (ACEi) are effective mitigators of radiation nephropathy. To date, their experimental use has been in fixed-dose regimens. In clinical use, doses of ACEi and other medication may be escalated to achieve greater benefit. We therefore used a rodent model to test the ACEi enalapril as a mitigator of radiation injury in an escalating-dose regimen. Single-fraction partial-body irradiation (PBI) with one hind limb out of the radiation field was used to model accidental or belligerent radiation exposures. PBI doses of 12.5, 12.75 and 13 Gy were used to establish multi-org...
Source: Radiation Research - March 2, 2016 Category: Physics Authors: Cohen EP, Fish BL, Moulder JE Tags: Radiat Res Source Type: research

Renin-Angiotensin-Aldosterone Signaling Inhibitors-Losartan, Enalapril, and Cardosten-Prevent Infarction-induced Heart Failure Development in Rats.
Conclusions • The study was the first to have demonstrated that preventive treatment with losartan, enalapril, or cardosten can attenuate pathological hypertrophy in infarction-induced heart failure in rats. PMID: 27036051 [PubMed - as supplied by publisher] (Source: Alternative Therapies in Health and Medicine)
Source: Alternative Therapies in Health and Medicine - March 1, 2016 Category: Complementary Medicine Authors: Kiss K, Fekete V, Pálóczi J, Sárközy M, Murlasits Z, Pipis J, Kheyfets IA, Dugina JL, Sergeeva SA, Epstein OI, Csonka C, Csont T, Ferdinandy P, Bencsik P Tags: Altern Ther Health Med Source Type: research

Influence of Ejection Fraction on Outcomes and Efficacy of Sacubitril/Valsartan (LCZ696) in Heart Failure with Reduced Ejection Fraction: The Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) Trial [Original Articles]
Background— The angiotensin receptor neprilysin inhibitor sacubitril/valsartan (LCZ696) reduced cardiovascular morbidity and mortality compared with enalapril in patients with heart failure (HF) and reduced ejection fraction (EF) in the Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial. We evaluated the influence of EF on clinical outcomes and on the effectiveness of sacubitril/valsartan compared with enalapril. Methods and Results— Eight thousand three hundred ninety-nine patients with New York Heart Association class II to IV H...
Source: Circulation: Heart Failure - February 25, 2016 Category: Cardiology Authors: Solomon, S. D., Claggett, B., Desai, A. S., Packer, M., Zile, M., Swedberg, K., Rouleau, J. L., Shi, V. C., Starling, R. C., Kozan, O., Dukat, A., Lefkowitz, M. P., McMurray, J. J. V. Tags: Heart Failure Original Articles Source Type: research