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Sample records for enalapril

  1. Enalapril

    Science.gov (United States)

    ... or pharmacist if you are taking valsartan and sacubitril (Entresto) or if you have stopped taking it ... enalapril, if you are also taking valsartan and sacubitril. Also, tell your doctor if you have diabetes ...

  2. 21 CFR 520.804 - Enalapril tablets.

    Science.gov (United States)

    2010-04-01

    ... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.804 Enalapril tablets. (a...). Enalapril maleate is administered as conjunctive therapy with furosemide and digoxin in the treatment of...

  3. ADVERSE PREGNANCY OUTCOMES ASSOCIATED WITH MATERNAL ENALAPRIL ANTIHYPERTENSIVE TREATMENT

    Science.gov (United States)

    Enalapril, one of several antihypertensive drugs that act as angiotensin-converting enzyme (ACE) inhibitors, is often used for treatment of hypertension in women of reproductive age. Adverse birth outcomes following the use of ACE inhibitors, including enalapril, during pregnanc...

  4. Enalapril dosage in progressive chronic nephropathy

    DEFF Research Database (Denmark)

    Elung-Jensen, Thomas; Heisterberg, Jens; Sonne, Jesper

    2005-01-01

    OBJECTIVE: In chronic renal failure, clearance of enalapril is reduced. Hence, a renoprotective effect may be achieved with lower doses than conventionally used. Since marked inter-patient variation in concentrations of enalaprilat has been shown in patients with renal failure despite equivalent...... dosage of enalapril, a direct comparison of the effect of high versus low plasma concentrations of enalaprilat on the progression of renal failure was undertaken. METHODS: Forty patients with a median glomerular filtration rate (GFR) of 17 (6-35) ml/min/1.73 m2 were studied in an open-label, randomised...... intervals by the plasma clearance of 51Cr-EDTA, and the individual rates of progression of renal failure were calculated as the slope of GFR versus time plot. RESULTS: In the high-concentration group, the median enalaprilat trough concentration was 92.9 ng/ml (21.8-371.0 ng/ml) and in the low...

  5. Buccal Transmucosal Delivery System of Enalapril for Improved ...

    African Journals Online (AJOL)

    Purpose: To prepare and characterize buccal transmucosal delivery system of enalapril maleate for overcoming its low bioavailability, and hence provide improved therapeutic efficacy and patient compliance. Methods: Transmucosal drug delivery systems of enalapril maleate were formulated as buccal films by solvent ...

  6. Higher persistence with valsartan compared with enalapril in daily practice

    Directory of Open Access Journals (Sweden)

    Satu J Siiskonen

    2008-01-01

    Full Text Available Satu J Siiskonen1, Nancy S Breekveldt-Postma1, Gábor Vincze2, Zeba M Khan3, Joëlle A Erkens1, Ron MC Herings11PHARMO Institute for Drug Outcomes Research, Utrecht, The Netherlands; 2Novartis Pharma AG, Basel, Switzerland; 3Novartis Pharmaceuticals Corporation, East Hanover, NJ, USAObjective: To compare persistence with valsartan and enalapril in daily practice.Methods: The PHARMO Record Linkage System includes various data registries including drug dispensing and hospitalizations for ≥2 million subjects in the Netherlands. Patients newly treated with valsartan or enalapril in the period of 1999–2002 were selected. Persistence was calculated by summing up the number of days of continuous treatment. Patients who remained on therapy with valsartan or enalapril for 12 or 24 months were defined as persistent at 1 or 2 years, respectively.Results: 3364 patients received valsartan and 9103 patients received enalapril. About 62% of patients treated with valsartan and 55% of patients treated with enalapril remained on therapy at 12 months after the initial dispensing, while 48% of patients treated with valsartan and 43% of patients treated with enalapril were persistent at 24 months. Patients treated with valsartan were about 20% more likely to stay on treatment than patients treated with enalapril (1 year RRadj: 1.23, 95% CI: 1.16–1.32; 2 years RRadj: 1.16, 95% CI: 1.11–1.23.Conclusions: Real-life persistence is higher with valsartan than with enalapril. The results of this and other studies on persistence in daily practice should be taken into account when deciding upon drug treatment for hypertension.Keywords: persistence, antihypertensive, valsartan, enalapril, angiotensin-converting enzyme inhibitors, angiotensin-2-receptor blockers

  7. Buccal Transmucosal Delivery System of Enalapril for Improved ...

    African Journals Online (AJOL)

    Methods: Transmucosal drug delivery systems of enalapril maleate were ... Index Medicus, JournalSeek, Journal Citation Reports/Science Edition, Directory of Open Access Journals. (DOAJ) ... investigated for various drugs including protein.

  8. Aliskiren alone or in combination with enalapril vs. enalapril among patients with chronic heart failure with and without diabetes

    DEFF Research Database (Denmark)

    Kristensen, Søren L; Mogensen, Ulrik M; Tarnesby, Georgia

    2017-01-01

    AIMS: Because of concerns about the safety of aliskiren in patients with diabetes, study treatment was stopped prematurely in the Aliskiren Trial of Minimizing OutcomeS for Patients with HEart failuRE (ATMOSPHERE). We examined outcomes and treatment effect in these patients compared with those...... without diabetes. METHODS AND RESULTS: ATMOSPHERE included 7016 patients with heart failure and a reduced ejection fraction (HFrEF) randomly assigned to enalapril plus aliskiren, aliskiren alone, or enalapril. At baseline, 1944 (27.7%) patients had diabetes. Median follow-up was shorter in patients...... with diabetes compared with those without (24 months vs. 46 months). Among patients with diabetes, the primary endpoint of cardiovascular death or hospitalization for heart failure occurred in 216 patients (33.1%) in the enalapril group (reference), 172 (27.4%) in the aliskiren group [hazard ratio (HR) 0.82, 95...

  9. Synergistic therapy of enalapril and Cordyceps sinensis in the ...

    African Journals Online (AJOL)

    Chronic allograft nephropathy (CAN) still remains an important factor that affects the long-term survival of renal recipients. The aim of the study was to investigate synergistic effect of enalapril (an angiotensin converting enzyme inhibitor, ACEI) and Cordyceps sinensis (Bailing capsule, fermented agent of C. sinensis) on ...

  10. ENALAPRIL: PHARMACOKINETIC/DYNAMIC INFERENCES FOR COMPARATIVE DEVELOPMENTAL TOXICITY

    Science.gov (United States)

    Enalapril is an antihypertensive drug of the class of angiotensin-converting enzyme inhibitors (ACEI) used in pregnancy for treatment of pre-existing or pregnancy-induced hypertension. The use of ACE inhibitors (drugs that act directly on the renin-angiotensin system) during the ...

  11. Fixed-dose lercanidipine/enalapril for hypertension.

    Science.gov (United States)

    Menne, Jan; Haller, Hermann

    2008-04-01

    The dihydropyridine calcium channel blocker lercanidipine and the ACE inhibitor enalapril are frequently used in the treatment of hypertensive patients. In April 2007, a fixed-dose combination of the two drugs was approved in Germany for the treatment of patients not responding to monotherapy. It is expected that the drug will soon be available in the other European Union markets. In this review the present literature is summarized. Two doses will be available with 10 mg lercanidipine each and 10 or 20 mg enalapril. The medication should be taken once daily, optimally =15 minutes before a meal and the consumption of grapefruit juice should be avoided. The fixed-dose combination of the two drugs has a stronger blood pressure-lowering effect than monotherapy with 20 mg enalapril or 10 mg lercanidipine. The combination is well tolerated and few patients stopped the treatment because of side effects. As expected, the most common side effects reported are cough, peripheral edema, flushing, dizziness and vertigo, occurring in 1-5% of patients. This new fixed-dose combination is a useful adjunct to the present treatment and should increase compliance and help reduce hypertension-related costs. 2008 Prous Science, S.A.U. or its licensors

  12. Biowaiver Monographs for Immediate-Release Solid Oral Dosage Forms: Enalapril.

    Science.gov (United States)

    Verbeeck, Roger K; Kanfer, Isadore; Löbenberg, Raimar; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, D W; Langguth, Peter; Polli, James E; Parr, Alan; Shah, Vinod P; Mehta, Mehul; Dressman, Jennifer B

    2017-08-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence testing for the marketing authorization of immediate-release, solid oral dosage forms containing enalapril maleate are reviewed. Enalapril, a prodrug, is hydrolyzed by carboxylesterases to the active angiotensin-converting enzyme inhibitor enalaprilat. Enalapril as the maleate salt is shown to be highly soluble, but only 60%-70% of an orally administered dose of enalapril is absorbed from the gastrointestinal tract into the enterocytes. Consequently, enalapril maleate is a Biopharmaceutics Classification System class III substance. Because in situ conversion of the maleate salt to the sodium salt is sometimes used in production of the finished drug product, not every enalapril maleate-labeled finished product actually contains the maleate salt. Enalapril is not considered to have a narrow therapeutic index. With this background, a biowaiver-based approval procedure for new generic products or after major revisions to existing products is deemed acceptable, provided the in vitro dissolution of both test and reference preparation is very rapid (at least 85% within 15 min at pH 1.2, 4.5, and 6.8). Additionally, the test and reference product must contain the identical active drug ingredient. Copyright © 2017 American Pharmacists Association®. All rights reserved.

  13. Enalapril and ASS inhibit tumor growth in a transgenic mouse model of islet cell tumors.

    Science.gov (United States)

    Fendrich, V; Lopez, C L; Manoharan, J; Maschuw, K; Wichmann, S; Baier, A; Holler, J P; Ramaswamy, A; Bartsch, D K; Waldmann, J

    2014-10-01

    Accumulating evidence suggests a role for angiotensin-converting enzymes involving the angiotensin II-receptor 1 (AT1-R) and the cyclooxygenase pathway in carcinogenesis. The effects of ASS and enalapril were assessed in vitro and in a transgenic mouse model of pancreatic neuroendocrine neoplasms (pNENs). The effects of enalapril and ASS on proliferation and expression of the AGTR1A and its target gene vascular endothelial growth factor (Vegfa) were assessed in the neuroendocrine cell line BON1. Rip1-Tag2 mice were treated daily with either 0.6 mg/kg bodyweight of enalapril i.p., 20 mg/kg bodyweight of ASS i.p., or a vehicle in a prevention (weeks 5-12) and a survival group (week 5 till death). Tumor surface, weight of pancreatic glands, immunostaining for AT1-R and nuclear factor kappa beta (NFKB), and mice survival were analyzed. In addition, sections from human specimens of 20 insulinomas, ten gastrinomas, and 12 non-functional pNENs were evaluated for AT1-R and NFKB (NFKB1) expression and grouped according to the current WHO classification. Proliferation was significantly inhibited by enalapril and ASS in BON1 cells, with the combination being the most effective. Treatment with enalapril and ASS led to significant downregulation of known target genes Vegf and Rela at RNA level. Tumor growth was significantly inhibited by enalapril and ASS in the prevention group displayed by a reduction of tumor size (84%/67%) and number (30%/45%). Furthermore, daily treatment with enalapril and ASS prolonged the overall median survival compared with vehicle-treated Rip1-Tag2 (107 days) mice by 9 and 17 days (P=0.016 and P=0.013). The AT1-R and the inflammatory transcription factor NFKB were abolished completely upon enalapril and ASS treatment. AT1-R and NFKB expressions were observed in 80% of human pNENs. Enalapril and ASS may provide an approach for chemoprevention and treatment of pNENs. © 2014 Society for Endocrinology.

  14. Blood pressure response to conventional and low-dose enalapril in chronic renal failure

    DEFF Research Database (Denmark)

    Elung-Jensen, Thomas; Heisterberg, Jens; Kamper, Anne-Lise

    2003-01-01

    AIMS: In chronic renal failure, the clearance of most ACE inhibitors including enalapril is reduced. Hence, with conventional dosage, plasma enalaprilat may be markedly elevated. It is unclear whether this excess of drug exposure affords an improved control of blood pressure. The aim of the present...... study was to evaluate short-term blood pressure response to two different plasma levels of enalaprilat. METHODS: As part of an open, randomized, controlled trial of the effect of high and low dosage of enalapril on the progression of renal failure, short-term blood pressure response was evaluated. Data...... potassium concentrations at day 90 and patients in the low group experienced a slight increase in GFR. CONCLUSIONS: In moderate to severe chronic renal insufficiency the same degree of blood pressure control was achieved on low as well as moderate daily doses of enalapril. This was irrespective...

  15. Effects of enalapril on urinary protein excretion of essential and renal parenchymal hypertensive patients

    International Nuclear Information System (INIS)

    Mazzucca, N.; Falciani, C.; Morini, V.; Bigazzi, R.; Paparatto, P.; Setti, G.P.; Bianchi, S.; Baldari, G.; Valteriani, C.; Chiapponi, I.

    1988-01-01

    Angiotensin converting enzyme (ACE) inhibiting drugs are able to reduce urinary protein excretion in experimental hypertension and in hypertensive patients with diabetes. Fifteen essential (group I) and six renal parenchymal (group II) mild or moderate hypertensive patients were treated with the ACE inhibitor Enalapril in monotherapy or in combination with a diuretic. Twenty-four hour urinary protein excretion was measured by means of colorimetric and RIA methods. All patients of group I had a significant decrease of arterial pressure with Enalapril alone and this reduction was dosage dependent. Three out of six patients of group II required the addition of diuretic to achieve a good pressure control. Serum creatinine values were stable in group I, while one patient of group II, who already had high baseline creatinine levels, showed an impairment of renal function requiring discontinuation of therapy. Twenty-four hour urinary protein excretion did not change in group I, while after two months of therapy a significant decrease was observed in group II (P<0.05), which was even more evident after 4 months (P<0.03). In this group a good correlation between MAP and proteinuria was observed. Finally, compared to the colorimetric method, RIA method seems to be more sensitive to assess the variations under Enalapril treatment. In conclusion, Enalapril is an effective drug in patients with moderate or mild hypertension. Caution must be exercised in administering Enalapril to patients with severe renal failure. Also in hypertensive patients with mild renal failure ACE inhibition appears to induce an antiproteinuric effect during long term therapy. This fact could be related to an improved hemodynamic intraglomerular status due to the renal effects of the drug. Finally urinary albumin RIA method seems to be more sensitive than colorimetric evaluation to follow-up the variations of proteinuria under Enalapril treatment

  16. Blood pressure response to conventional and low-dose enalapril in chronic renal failure

    DEFF Research Database (Denmark)

    Elung-Jensen, Thomas; Heisterberg, Jens; Kamper, Anne-Lise

    2003-01-01

    AIMS: In chronic renal failure, the clearance of most ACE inhibitors including enalapril is reduced. Hence, with conventional dosage, plasma enalaprilat may be markedly elevated. It is unclear whether this excess of drug exposure affords an improved control of blood pressure. The aim of the present...... study was to evaluate short-term blood pressure response to two different plasma levels of enalaprilat. METHODS: As part of an open, randomized, controlled trial of the effect of high and low dosage of enalapril on the progression of renal failure, short-term blood pressure response was evaluated. Data...

  17. COMPARISON OF PHARMACOKINETICS AND PHARMACODYNAMICS OF THE ORIGINAL AND GENERIC ENALAPRIL IN THE ELDERLY PATIENTS WITH ARTERIAL HYPERTENSION

    Directory of Open Access Journals (Sweden)

    O. P. Bobrova

    2015-12-01

    Full Text Available Aim. To study the pharmacokinetic, pharmacodynamic and pharmacoeconomic parameters of the original and generic enalaprils in the treatment of the elderly patients with hypertension (HT. Material and Methods. Patients (n=40 75–90 years with HT were included in the open randomized comparative study. Patients were randomized into two groups. Patients of the group 1 received generic enalapril, patients of the group 2 — the original enalapril consisting of combined therapy. Pharmacokinetic single-dose study of original and generic enalapril were carried out with high-performance liquid chromatography. Pharmacodynamic study was carried out in single-dose administration as well as after 2 and 4 weeks of treatment with original and generic enalapril. Pharmacoeconomic evaluation of antihypertensive drugs was carried out on the basis of cost minimization analysis. Results. Original enalapril dose necessary to achieve the target blood pressure (BP was 10 mg/day as a part of two-component therapy. This for generic enalapril was 20 mg/day consisting of three- or four-component therapy. Both drugs have shown an acceptable safety profile. Pharmacokinetic differences were revealed between original and generic enalapril: area under pharmacokinetic curve 204.14 (202.25–206.05 vs 136.23 (134.17–137.65 ng*h/ml, respectively; time of the drug retention in the blood plasma 5.42 (5.26–5.76 vs 4.88 (4.86–4.94 hours, respectively; p<0.001. Original enalapril demonstrated more stable 24-hour antihypertensive effect in once daily administration in comparison with this in generic enalapril: trough/peak ratio 78.67% (47.61–91.35% vs 44.96% (32.44–55.49%, respectively , p<0.01. The average daily cost of combined therapy containing generic enalapril was 15.91 rubles per patient, while this in combined therapy containing original enalapril — 13.78 rubles per patient. Conclusion. Medicines on the basis of original and generic enalapril have pharmacokinetic

  18. ESTUDIO EX VIVO DE LA LIBERACIÓN TRANSDÉRMICA DE ENALAPRIL

    Directory of Open Access Journals (Sweden)

    Lucía Lhez

    2010-01-01

    Full Text Available En el presente trabajo se estudió el comportamiento ex vivo de una formulación de enalapril maleato para su administración por vía transdérmica, utilizando piel de oreja de cerdo. Los experimentos se realizaron en celdas de difusión vertical tipo Franz. El principio activo fue formulado en una dispersión de carbopol. A partir de las cantidades acumuladas de enalapril en el compartimento receptor, se evaluó el flujo y el coeficiente de permeabilidad. Con el fin de optimizar la penetración del principio activo, se investigó el efecto de L-mentol como potenciador de la permeabildiad. Se determinó que este compuesto contribuye favorablemente a la penetración de enalapril a través de la piel y que los parámetros de permeabilidad, flujo y coeficiente de permeabilidad, alcanzan sus máximos valores cuando L-mentol está presente en un 3,82% en la formulación enalapril/carbopol.

  19. The effect of renal diet in association with enalapril or benazepril on ...

    African Journals Online (AJOL)

    Whether different ACE-inhibitors have distinct kidney protective effects is unknown; it is therefore hypothesized that renal diets and enalapril or benazepril have different beneficial effects in proteinuric CKD dogs. Forty-four dogs with proteinuric CKD (IRIS stages 1-4) were enrolled in the study and were fed renal diet for 30 ...

  20. EFFECTS OF ENALAPRIL ON ENDOTHELIUM FUNCTION IN PATIENTS WITH ISCHEMIC HEART DISEASE

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    L. I. Katelnizkaya

    2006-01-01

    Full Text Available Aim. To study endothelium vasomotor function (EF in patients with ischemic heart disease (IHD and the influence of angiotensin converting enzyme inhibitor enalapril (Enam, Dr .Reddy’s, India on it. Material and methods. 87 patients were examined totally. 49 patients were suffering from IHD: 18 patients were younger than 60 years old and 31 patients were older . The combination of arterial hypertension (HT and IHD were registered in 38 patients: 18 patients were below and 20 patients were above 60 years old. All patients additionally to basic IHD therapy took enalapril in dose 2,5-30 mg/daily during 12 weeks. Before the beginning and in the end of treatment cuff test, test with nitroglycerine, bicycle exercise test and Holter monitoring were made, the thickness of intima-media complex of carotid artery and the level of endothelin-1 in blood plasma were defined. Results. EF disorders were shown in IHD, maximal disorders were determined in patients with combination of IHD and HT. EF disorders were also more expressive in patients of elder group. Enalapril restored of cuff tests results, nitroglycerine tests results, reduced a number of myocardial ischemia episodes and provided target blood pressure in 60, 5% patients with HT. Conclusion. Enalapril improves endothelium vasomotor function, endothelium reaction on nitroglycerine and clinical course of IHD and HT.

  1. A Liquid Chromatography-Tandem Mass Spectrometry Method for Evaluation of Two Brands of Enalapril 20 mg Tablets in Healthy Human Volunteers

    Directory of Open Access Journals (Sweden)

    Wael Abu Dayyih

    2017-01-01

    Full Text Available Enalapril is an angiotensin-converting enzyme inhibitor used for treatment of hypertension and chronic heart disease. Enalaprilat is its active metabolite responsible for the activity. This study aimed to develop and validate a method for enalapril and enalaprilat analysis and to determine the bioequivalence of two tablet formulae of enalapril. LC-MS/MS bioanalytical method was developed and validated and then applied to evaluate the bioavailability of two enalapril formulae. Antihyperglycemic sitagliptin was used as internal standard (IS. The method was accurate for the within- and between-days analysis, and precise CV% was 85% and the LOD was 0.907 and 0.910 ng/ml for enalapril and enalaprilat, respectively, and LLOQ was 1 ng/ml. The pharmacokinetic parameters Cmax, tmax, AUC0–72, and AUC0–∞ values of enalapril and enalaprilat of the two formulae were calculated and nonsignificant differences were found. A linearity, specific, accurate, and precise method was developed and applied for the analysis of enalapril and enalaprilat in human plasma after oral administration of two formulae of enalapril 20 mg tablets in healthy volunteers. Depending on the statistical analysis it was concluded that the two enalapril formulae were bioequivalent.

  2. A Study to Assess the Therapeutic Effect of Enalapril on Olanzapine Induced Metabolic Syndrome in Wistar Rats.

    Science.gov (United States)

    Arivazhahan, Avinash; Bairy, Laxminarayana Kurady; Nayak, Veena; Kunder, Sushil Kiran

    2017-02-01

    Metabolic Syndrome (MS) is a complex of risk factors for the development of cardiovascular complications and Type 2 Diabetes Mellitus (DM). Pharmacological management of the condition is complex, as multiple drug groups have to be used, as the syndrome itself is multi faceted. Angiotensin Converting Enzyme Inhibitors (ACEIs) are chiefly used to manage the hypertensive component of the syndrome. However, recent studies have shown that these drugs may have a role in the non hypertensive aspects of the syndrome as well. To evaluate the therapeutic effect of enalapril on total body weight, random blood glucose and serum lipid profile in a rodent model of olanzapine induced MS. Three different dosages (1 mg/kg/day, 10 mg/kg/day and 20 mg/kg/day) of oral enalapril were administered (for three weeks) in albino wistar rats, which received prior intra peritoneal olanzapine (for three weeks), and compared against control (normal saline) and standard (olanzapine only and enalapril only) groups. Parameters like total body weight, random blood glucose and serum lipid profile were measured at baseline, at three weeks and at six weeks. Enalapril at 20 mg/kg/day was found to be effective in reversing the weight gain, hyperglycaemia and hypercholesterolaemia, without any changes in triglycerides, High Density Lipoprotein (HDL) and Low Density Lipoprotein (LDL). 10 mg/kg/day of enalapril prevented any further rise in body weight, blood glucose, total cholesterol and serum triglycerides, after olanzapine was stopped. 1 mg/kg/day of enalapril was ineffective. High dose of enalapril may be considered as a component of therapeutic regimens to combat weight gain, hyperglycaemia and dyslipidaemia seen in MS, in addition to its antihypertensive utility. Further rodent and clinical studies may be required to ascertain the same.

  3. Clinical evaluation of enalapril maleate and furosemide usage in dogs with degenerative myxomatous mitral valve, CHF functional class Ib

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    Rodrigo P. Franco

    2011-09-01

    Full Text Available Degenerative myxomatous mitral valve (DMMV is a heart disease of high incidence in small animal clinical medicine, affecting mainly older dogs and small breeds. Thus, a scientific investigation was performed in order to evaluate the clinical use of the medicines furosemide and enalapril maleate in dogs with this disease in CHF functional class Ib before and after the treatment was established. For this purpose 16 dogs with the given valve disease were used, separated into two groups: the first received furosemide (n=8 and the second received enalapril maleate (n=8 throughout 56 days. The dogs were evaluated in four stages (T0, T14, T28 and T56 day in relation to clinical signs, hematological, biochemical and serum assessment, which included serum angiotensin converting enzyme (ACE and aldosterone, as well as radiography, electrocardiography, Doppler-echocardiography and blood pressure. The results regarding the clinical, hematological and serum chemistry evaluations revealed no significant changes in both groups, but significant reductions in the values of ACE and aldosterone in the group receiving enalapril maleate were verified. The radiographic examination revealed reductions of VHS values and variable Pms wave of the electrocardiogram in both groups, but no changes in blood pressure values were identified. The echocardiogram showed a significant decrease of the variables LVDd/s in the studied groups and the FS% in animals that received only enalapril. Therefore, analysis of results showed that monotherapy based on enalapril maleate showed better efficiency of symptoms control in patients with CHF functional class Ib.

  4. Stability and in vitro release profile of enalapril maleate from different commercially available tablets: possible therapeutic implications.

    Science.gov (United States)

    Lima, Dione Marçal; dos Santos, Leandro Dias; Lima, Eliana Martins

    2008-08-05

    Stability of enalapril maleate formulations can be affected when the product is exposed to higher temperature and humidity, with the formation of two main degradation products: enalaprilat and a diketopiperazine derivative. In this work, stability and drug release profiles of 20 mg enalapril maleate tablets (reference, generic and similar products) were evaluated. After 180 days of the accelerated stability testing, most products did not exhibit the specified amount of drug. Additionally, drug release profiles were markedly different from that of the reference product, mainly due to drug degradation. Changes in drug concentration and drug release profile of enalapril formulations are strong indicators of a compromised bioavailability, with possible interferences on the therapeutic response for this drug.

  5. Angioedema in heart failure patients treated with sacubitril/valsartan (LCZ696) or enalapril in the PARADIGM-HF study.

    Science.gov (United States)

    Shi, Victor; Senni, Michele; Streefkerk, Hendrik; Modgill, Vikas; Zhou, Wenchun; Kaplan, Allen

    2018-08-01

    PARADIGM-HF demonstrated significant clinical benefits for sacubitril/valsartan (LCZ696, an angiotensin receptor neprilysin inhibitor) versus the angiotensin-converting enzyme inhibitor (ACEI) enalapril in patients with heart failure with reduced ejection fraction. As inhibition of ACE, and co-inhibition of ACE and neprilysin, may increase the risk of angioedema, this was an adverse event of special interest. Following sequential enalapril and sacubitril/valsartan run-ins, patients were randomized to twice-daily sacubitril/valsartan 200 mg or enalapril 10 mg. The study design incorporated two wash-out periods (~36 h each) to minimize any potential risk of angioedema due to overlapping ACE and neprilysin inhibition. Suspected cases of angioedema were reported to, and blindly adjudicated by, an independent angioedema adjudication committee (AAC). Of the 10,513 patients entering the enalapril run-in, 9419 entered the sacubitril/valsartan run-in and 8432 received double-blind treatment. Overall, 148 suspected angioedema events occurring in 144 patients were reported to AAC, with one event reported during screening period. Of the remaining 147 events, 54 were confirmed as angioedema by AAC. A confirmed event was experienced by 15 (0.14%) and 10 (0.11%) patients, during the enalapril and sacubitril/valsartan run-ins, respectively, and by 10 (0.24%) and 19 (0.45%) patients in the corresponding randomized arms during the double-blind phase. The frequency of confirmed angioedema was higher in black patients. Most events were mild. Only five patients required hospitalization and none required mechanical airway support. The number of confirmed angioedema events in PARADIGM-HF was low and there was no-marked excess risk of angioedema with sacubitril/valsartan versus enalapril. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  6. Comparative Evaluation of Enalapril and Losartan in Pharmacological Correction of Experimental Osteoporosis and Fractures of Its Background

    Science.gov (United States)

    Rajkumar, D. S. R.; Faitelson, A. V.; Gudyrev, O. S.; Dubrovin, G. M.; Pokrovski, M. V.; Ivanov, A. V.

    2013-01-01

    In the experiment on the white Wistar female rats (222 animals), the osteoprotective effect of enalapril and losartan was studied on experimental models of osteoporosis and osteoporotic fractures. It was revealed that in rats after ovariectomy, the endothelial dysfunction of microcirculation vessels of osteal tissue develops, resulting in occurrence of osteoporosis and delay of consolidation of experimental fractures. Enalapril and losartan prevented the reduction of microcirculation in bone, which was reflected in slowing the thinning of bone trabeculae and in preventing the occurrence of these microfractures, as well as increasing quality of experimental fractures healing. PMID:23401845

  7. Comparative Evaluation of Enalapril and Losartan in Pharmacological Correction of Experimental Osteoporosis and Fractures of Its Background

    Directory of Open Access Journals (Sweden)

    D. S. R. Rajkumar

    2013-01-01

    Full Text Available In the experiment on the white Wistar female rats (222 animals, the osteoprotective effect of enalapril and losartan was studied on experimental models of osteoporosis and osteoporotic fractures. It was revealed that in rats after ovariectomy, the endothelial dysfunction of microcirculation vessels of osteal tissue develops, resulting in occurrence of osteoporosis and delay of consolidation of experimental fractures. Enalapril and losartan prevented the reduction of microcirculation in bone, which was reflected in slowing the thinning of bone trabeculae and in preventing the occurrence of these microfractures, as well as increasing quality of experimental fractures healing.

  8. Enalapril alters the formation of the collagen matrix in spontaneously hypertensive rats

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    Alfredo de Souza Bomfim

    2003-07-01

    Full Text Available OBJECTIVE: To assess the effect of the inhibition of the angiotensin-converting enzyme on the collagen matrix (CM of the heart of newborn spontaneously hypertensive rats (SHR during embryonic development. METHODS: The study comprised the 2 following groups of SHR (n=5 each: treated group - rats conceived from SHR females treated with enalapril maleate (15 mg. kg-1.day-1 during gestation; and nontreated group - offspring of nontreated females. The newborns were euthanized within the first 24 hours after birth and their hearts were removed and processed for histological study. Three fields per animal were considered for computer-assisted digital analysis and determination of the volume densities (Vv of the nuclei and CM. The images were segmented with the aid of Image Pro Plus® 4.5.029 software (Media Cybernetics. RESULTS: No difference was observed between the treated and nontreated groups in regard to body mass, cardiac mass, and the relation between cardiac and body mass. A significant reduction in the Vv[matrix] and a concomitant increase in the Vv[nuclei] were observed in the treated group as compared with those in the nontreated group. CONCLUSION: The treatment with enalapril of hypertensive rats during pregnancy alters the collagen content and structure of the myocardium of newborns.

  9. Effect of enalapril on the progression of chronic renal failure. A randomized controlled trial

    DEFF Research Database (Denmark)

    Kamper, A L; Strandgaard, S; Leyssac, P P

    1992-01-01

    In order to study the influence of angiotensin converting enzyme (ACE) inhibition on the progression of chronic nephropathy, 70 patients with a median glomerular filtration rate (GFR) of 15 (range, 6 to 54) mL/min/1.73 m2 were randomized in an open study to basic treatment with enalapril or conve......In order to study the influence of angiotensin converting enzyme (ACE) inhibition on the progression of chronic nephropathy, 70 patients with a median glomerular filtration rate (GFR) of 15 (range, 6 to 54) mL/min/1.73 m2 were randomized in an open study to basic treatment with enalapril...... or conventional antihypertensive treatment. The patients were followed for at least 2 years or until they needed dialysis. The groups were comparable with respect to age and sex distribution, etiology of renal diseases, initial levels of renal function and arterial blood pressure (BP), and protein intake.......18 to -7.11) mL/min/1.73 m2/month and in the control group it was -0.31 (+0.01 to -1.97) mL/min/1.73 m2/month (P less than .05). There was no significant difference in blood pressure or plasma lipid levels between the groups. Thus, the progression of moderate to severe chronic nephropathy was slower...

  10. Angiotensin I konverteringshaemmeren enalapril til behandling af progredierende kronisk nefropati. En åben randomiseret kontrolleret undersøgelse

    DEFF Research Database (Denmark)

    Kamper, A L; Strandgaard, S; Leyssac, P P

    1993-01-01

    In order to study the influence of angiotensin converting enzyme (ACE) inhibition on the progression of chronic nephropathy, 70 patients with a median glomerular filtration rate (GFR) of 15 (range, 6 to 54) mL/min/1.73 m2 were randomised in an open study to basic treatment with enalapril or conve...

  11. Effects of nitrendipine and enalapril on left ventricular mass in patients with non-insulin-dependent diabetes mellitus and hypertension

    NARCIS (Netherlands)

    Gerritsen, TA; Bak, AAA; Stolk, RP; Jonker, JJC; Grobbee, DE

    Objective To compare the effects of a calcium antagonist (nitrendipine) and an angiotensin converting enzyme inhibitor (enalapril) with those of placebo on left ventricular mass in patients with non-insulin-dependent diabetes mellitus and hypertension, Design A double-blind randomized,

  12. Study of Copolymer Composition on Drug Loading Efficiency of Enalapril in Polymersomes and Cytotoxicity of Drug Loaded Nanoparticles.

    Science.gov (United States)

    Danafar, H; Manjili, H K; Najafi, M

    2016-09-01

    Enalapril 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 12.33% respectively. The release profile of enalapril for drug loaded nanoparticles prepared from mPEG3-PCL3 was very fast and release profile for the nanoparticles prepared from mPEG1-PCL1 and mPEG2-PCL2 was sustained. The IC 50 value of enalapril was determined to be 8 μM while EPM/m-PEG-PCL nanoparticles did not show significant toxicity at equal concentrations in comparison with enalapril drug. Therapeutic preparations of mPEG-PCL micelle are calibrated by the mouse LD 50 assay. A dose-finding scheme of the polymeric micelle showed a safe dose of mPEG-PCL micelles was approximately 330 mg/kg in mice. The relationship between the numbers of animals, number of doses, duration of the assay used to estimate the LD 50 and the precision of the assay were investigated. Overall, the results was showed that m-PEG-PCL polymersomes can be considered as a promising carrier for hydrophilic drugs. © Georg Thieme Verlag KG Stuttgart · New York.

  13. Cost-effectiveness Analysis of Sacubitril/Valsartan vs Enalapril in Patients With Heart Failure and Reduced Ejection Fraction.

    Science.gov (United States)

    Gaziano, Thomas A; Fonarow, Gregg C; Claggett, Brian; Chan, Wing W; Deschaseaux-Voinet, Celine; Turner, Stuart J; Rouleau, Jean L; Zile, Michael R; McMurray, John J V; Solomon, Scott D

    2016-09-01

    The angiotensin receptor neprilysin inhibitor sacubitril/valsartan was associated with a reduction in cardiovascular mortality, all-cause mortality, and hospitalizations compared with enalapril. Sacubitril/valsartan has been approved for use in heart failure (HF) with reduced ejection fraction in the United States and cost has been suggested as 1 factor that will influence the use of this agent. To estimate the cost-effectiveness of sacubitril/valsartan vs enalapril in the United States. Data from US adults (mean [SD] age, 63.8 [11.5] years) with HF with reduced ejection fraction and characteristics similar to those in the PARADIGM-HF trial were used as inputs for a 2-state Markov model simulated HF. Risks of all-cause mortality and hospitalization from HF or other reasons were estimated with a 30-year time horizon. Quality of life was based on trial EQ-5D scores. Hospital costs combined Medicare and private insurance reimbursement rates; medication costs included the wholesale acquisition cost for sacubitril/valsartan and enalapril. A discount rate of 3% was used. Sensitivity analyses were performed on key inputs including: hospital costs, mortality benefit, hazard ratio for hospitalization reduction, drug costs, and quality-of-life estimates. Hospitalizations, quality-adjusted life-years (QALYs), costs, and incremental costs per QALY gained. The 2-state Markov model of US adult patients (mean age, 63.8 years) calculated that there would be 220 fewer hospital admissions per 1000 patients with HF treated with sacubitril/valsartan vs enalapril over 30 years. The incremental costs and QALYs gained with sacubitril/valsartan treatment were estimated at $35 512 and 0.78, respectively, compared with enalapril, equating to an incremental cost-effectiveness ratio (ICER) of $45 017 per QALY for the base-case. Sensitivity analyses demonstrated ICERs ranging from $35 357 to $75 301 per QALY. For eligible patients with HF with reduced ejection fraction, the Markov

  14. Losartan and enalapril decrease viral absorption and interleukin 1 beta production by macrophages in an experimental dengue virus infection.

    Science.gov (United States)

    Hernández-Fonseca, Juan Pablo; Durán, Anyelo; Valero, Nereida; Mosquera, Jesús

    2015-11-01

    The role of angiotensin II (Ang II) in dengue virus infection remains unknown. The aim of this study was to determine the effect of losartan, an antagonist of the angiotensin II type 1 receptor (AT1 receptor), and enalapril, an inhibitor of angiotensin I-converting enzyme (ACE), on viral antigen expression and IL-1β production in peritoneal macrophages infected with dengue virus type 2. Mice treated with losartan or enalapril and untreated controls were infected intraperitoneally with the virus, and macrophages were analyzed. Infection resulted in increased IL-1β production and a high percentage of cells expressing viral antigen, and this was decreased by treatment with anti-Ang II drugs, suggesting a role for Ang II in dengue virus infection.

  15. Cost-effectiveness of sacubitril/valsartan versus enalapril in patients with heart failure and reduced ejection fraction.

    Science.gov (United States)

    Liang, Lin; Bin-Chia Wu, David; Aziz, Mohamed Ismail Abdul; Wong, Raymond; Sim, David; Leong, Kui Toh Gerard; Wei, Yong Quek; Tan, Doreen; Ng, Kwong

    2018-02-01

    Sacubitril/valsartan reduces cardiovascular death and hospitalizations for heart failure (HF). However, decision-makers need to determine whether its benefits are worth the additional costs, given the low-cost generic status of traditional standard of care. To evaluate the cost-effectiveness of sacubitril/valsartan compared to enalapril in patients with HF and reduced ejection fraction, from the Singapore healthcare payer perspective. A Markov model was developed to project clinical and economic outcomes of sacubitril/valsartan vs enalapril for 66-year-old patients with HF over 10 years. Key health states included New York Heart Association classes I-IV and deaths; patients in each state incurred a monthly risk of hospitalization for HF and cardiovascular death. Sacubitril/valsartan benefits were modeled by applying the hazard ratios (HRs) in PARADIGM-HF trial to baseline probabilities. Primary model outcomes were total and incremental costs and quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER) for sacubitril/valsartan relative to enalapril Results: Compared to enalapril, sacubitril/valsartan was associated with an ICER of SGD 74,592 (USD 55,198) per QALY gained. A major driver of cost-effectiveness was the cardiovascular mortality benefit of sacubitril/valsartan. The uncertainty of this treatment benefit in the Asian sub-group was tested in sensitivity analyses using a HR of 1 as an upper limit, where the ICERs ranged from SGD 41,019 (USD 30,354) to SGD 1,447,103 (USD 1,070,856) per QALY gained. Probabilistic sensitivity analyses showed the probability of sacubitril/valsartan being cost-effective was below 1%, 12%, and 71% at SGD 20,000, SGD 50,000, and SGD 100,000 per QALY gained, respectively. At the current daily price sacubitril/valsartan may not represent good value for limited healthcare dollars compared to enalapril in reducing cardiovascular morbidity and mortality in HF in the Singapore healthcare setting. This study

  16. Beneficial effect of perindopril on cardiac sympathetic nerve activity and brain natriuretic peptide in patients with chronic heart failure. Comparison with enalapril

    International Nuclear Information System (INIS)

    Tsutamoto, Takayoshi; Tanaka, Toshinari; Sakai, Hiroshi

    2008-01-01

    In patients with chronic heart failure (CHF), it remains unclear whether perindopril is more cardioprotective than enalapril. Forty-five stable CHF outpatients undergoing conventional therapy including enalapril therapy were randomized to 2 groups [group I (n=24): continuous enalapril treatment; group II (n=21): enalapril was changed to perindopril]. Cardiac sympathetic nerve activity was evaluated using cardiac 123 I-metaiodobenzylguanidine (MIBG) scintigraphy, hemodynamic parameters and neurohumoral factors before and 6 months after treatment. There was no difference in baseline characteristics between the 2 groups. In group I, there were no changes in MIBG parameters, left ventricular ejection fraction (LVEF) or plasma level of brain natriuretic peptide (BNP). In contrast, in group II delayed heart/mediastinum count ratio was significantly increased (2.0±0.07 vs 2.15±0.07, p=0.013) and the washout rate was significantly decreased (33.0±1.4 vs 30.5±1.2, p=0.030) after 6 months compared with the baseline value. In addition, LVEF was significantly increased and the plasma BNP level was significantly decreased. These findings suggest that for the treatment of CHF, perindopril is superior to enalapril with respect of cardiac sympathetic nerve activity and BNP. (author)

  17. Impact of angiotensin-converting enzyme gene polymorphism on neurohormonal responses to high- versus low-dose enalapril in advanced heart failure.

    Science.gov (United States)

    Tang, W H Wilson; Vagelos, Randall H; Yee, Yin-Gail; Fowler, Michael B

    2004-11-01

    The impact of angiotensin-converting enzyme (ACE) gene polymorphism on neurohormonal dose response to ACE inhibitor therapy is unclear. ACE Insertion (I) or Deletion (D) genotype was determined in 74 patients with chronic heart failure who were randomly assigned to receive either high-dose or low-dose enalapril over a period of 6 months. Monthly pre-enalapril and post-enalapril neurohormone levels (serum ACE activity (sACE), plasma angiotensin II (A-II), plasma renin activity (PRA), and serum aldosterone (ALDO) were compared between genotype subgroups and between patients who received high- or low-dose enalapril within each genotype subgroup. At baseline, predose/postdose sACE and postdose PRA were significantly higher in the DD genotype. At 6-month follow-up, postdose sACE was reduced in a dose-dependent fashion in all three genotypes (P sACE were consistently higher in the DD genotype when compared with ID or II subgroups. Despite a dose-dependent suppression of sACE, there were no observed statistically significant differences in ALDO and A-II suppression or escape with escalating doses of enalapril within each subgroup.

  18. Late outcome of a controlled trial of enalapril treatment in progressive chronic renal failure. Hard end-points and influence of proteinuria

    DEFF Research Database (Denmark)

    Kamper, A L; Strandgaard, S; Leyssac, P P

    1995-01-01

    An earlier controlled trial showed that over an average of 26 months, enalapril slowed the progression of chronic renal failure. Following completion of the trial, the patients continued to receive antihypertensive treatment according to ordinary clinical criteria. All but four patients...... end-stage renal failure (ESRF) (P renal outcome groups. In all patients, baseline Calb and CIgG were negatively correlated with the rate of change in GFR during the controlled trial (r = -0.37, P .... In the original enalapril group, 12 of the 35 patients (34%) were alive without renal replacement therapy versus five of the 35 patients (14%) in the control group. This difference of 20% in favour of having been in the enalapril group in the original trial was significant (P = 0.05; 95% confidence limits 0...

  19. Efficacy of sacubitril/valsartan vs. enalapril at lower than target doses in heart failure with reduced ejection fraction: the PARADIGM-HF trial.

    Science.gov (United States)

    Vardeny, Orly; Claggett, Brian; Packer, Milton; Zile, Michael R; Rouleau, Jean; Swedberg, Karl; Teerlink, John R; Desai, Akshay S; Lefkowitz, Martin; Shi, Victor; McMurray, John J V; Solomon, Scott D

    2016-10-01

    In 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. In 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 outcome was estimated, stratified by dose level using time-updated Cox regression models. In the two treatment arms, participants with a dose reduction (43% of those randomized to enalapril and 42% of those randomized to sacubitril/valsartan) had similar baseline characteristics and similar baseline predictors of the need for dose reduction. In a time-updated analysis, any dose reduction was associated with a higher subsequent risk of the primary event [hazard ratio (HR) 2.5, 95% confidence interval (CI) 2.2-2.7]. However, the treatment benefit of sacubitril/valsartan over enalapril following a dose reduction was similar (HR 0.80, 95% CI 0.70-0.93, P sacubitril/valsartan relative to those on lower doses of enalapril was similar to that of patients who remained on target doses of both drugs. © 2016 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

  20. Similar clinical benefits from below-target and target dose enalapril in patients with heart failure in the SOLVD Treatment trial.

    Science.gov (United States)

    Lam, Phillip H; Dooley, Daniel J; Fonarow, Gregg C; Butler, Javed; Bhatt, Deepak L; Filippatos, Gerasimos S; Deedwania, Prakash; Forman, Daniel E; White, Michel; Fletcher, Ross D; Arundel, Cherinne; Blackman, Marc R; Adamopoulos, Chris; Kanonidis, Ioannis E; Aban, Inmaculada B; Patel, Kanan; Aronow, Wilbert S; Allman, Richard M; Anker, Stefan D; Pitt, Bertram; Ahmed, Ali

    2018-02-01

    To examine associations of below-target and target dose of enalapril, an angiotensin-converting enzyme (ACE) inhibitor, with outcomes in patients with heart failure and reduced ejection fraction (HFrEF) in the Studies of Left Ventricular Dysfunction (SOLVD) Treatment trial. Two thousand five hundred and sixty-nine patients with HFrEF (ejection fraction ≤35%) were randomized to below-target (5-10 mg/day) dose placebo (n = 1284) or enalapril (n = 1285). One month post-randomization, blind up-titration to target (20 mg/day) dose was attempted for both study drugs in 2458 patients. Among the 1444 patients who achieved dose up-titration (placebo, n = 748; enalapril, n = 696; mean dose for both groups, 20.0 mg/day), target dose enalapril (vs. target dose placebo) was associated with a 9% absolute lower risk of the combined endpoint of heart failure hospitalization or all-cause mortality [adjusted hazard ratio (HR) 0.70; 95% confidence interval (CI) 0.60-0.81; P target dose (placebo, n = 486; enalapril, n = 528; mean dose for both groups, 8.8 mg/day), below-target dose enalapril (vs. below-target dose placebo) was associated with a 12% absolute lower risk of the combined endpoint of heart failure hospitalization or all-cause mortality (adjusted HR 0.68; 95% CI 0.57-0.81; P target (vs. below-target) dose had no association with the combined endpoint of heart failure hospitalization or all-cause mortality (adjusted HR 1.04; 95% CI 0.87-1.23; P = 0.695). In patients with HFrEF, the clinical benefits of ACE inhibitors appear to be similar at both below-target and target doses. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

  1. Long-term effects of the angiotensin-converting enzyme inhibitor enalapril on chronic heart failure. Examination by {sup 123}I-MIBG imaging

    Energy Technology Data Exchange (ETDEWEB)

    Soeki, Takeshi; Tamura, Yoshiyuki; Bandou, Kanji; Tanaka, Hideji; Takeichi, Naoki; Shinohara, Hisanori; Yui, Yasuko; Fukuda, Nobuo; Sui, Osamu [Zentsuji National Hospital, Kagawa (Japan)

    1998-11-01

    To examine the long-term effects of the angiotensin-converting enzyme (ACE) inhibitor enalapril on chronic heart failure, 10 patients (7 men and 3 women, mean age: 62{+-}11 years) with chronic stable heart failure, classified as New York Heart Association (NYHA) functional class 2-3 for more than 3 months, and a left ventricular ejection fraction less than 45% were treated with 2.5-5.0 mg of enalapril once a day for 3-15 months (mean 7 months). The causes of heart failure were old myocardial infarction (n=7), hypertension (n=2), and atrial fibrillation (n=1). Radioiodinated metaiodobenzyl guanidine ({sup 123}I-MIBG) imaging, radionuclide angiography, and treadmill exercise test were performed before and after the treatment. With enalapril treatment, left ventricular ejection fraction (LVEF) increased significantly from 38.3{+-}6.9% to 47.5{+-}14.7%; sub-maximal exercise time increased significantly from 205{+-}112 to 272{+-}120 seconds; the heart to mediastinum (H/M) ratio of {sup 123}I-MIBG increased significantly (early image: 1.99{+-}0.38 versus 2.20{+-}0.50; delayed image: 1.86{+-}0.44 versus 2.09{+-}0.51); and the washout rate of {sup 123}I-MIBG decreased slightly from 29.1{+-}9.1% to 25.4{+-}7.0%. The improvement rate of LVEF was significantly correlated with the improvement rates of the H/M ratio and washout rate after treatment with enalapril. Thus, the long-term effects of enalapril can be observed in the cardiac sympathetic nervous system, and {sup 123}I-MIBG imaging appears to be useful for evaluating the therapeutic effects of enalapril on the cardiac sympathetic nervous system in patients with chronic heart failure. (author)

  2. Long-term effects of the angiotensin-converting enzyme inhibitor enalapril on chronic heart failure. Examination by 123I-MIBG imaging

    International Nuclear Information System (INIS)

    Soeki, Takeshi; Tamura, Yoshiyuki; Bandou, Kanji; Tanaka, Hideji; Takeichi, Naoki; Shinohara, Hisanori; Yui, Yasuko; Fukuda, Nobuo; Sui, Osamu

    1998-01-01

    To examine the long-term effects of the angiotensin-converting enzyme (ACE) inhibitor enalapril on chronic heart failure, 10 patients (7 men and 3 women, mean age: 62±11 years) with chronic stable heart failure, classified as New York Heart Association (NYHA) functional class 2-3 for more than 3 months, and a left ventricular ejection fraction less than 45% were treated with 2.5-5.0 mg of enalapril once a day for 3-15 months (mean 7 months). The causes of heart failure were old myocardial infarction (n=7), hypertension (n=2), and atrial fibrillation (n=1). Radioiodinated metaiodobenzyl guanidine ( 123 I-MIBG) imaging, radionuclide angiography, and treadmill exercise test were performed before and after the treatment. With enalapril treatment, left ventricular ejection fraction (LVEF) increased significantly from 38.3±6.9% to 47.5±14.7%; sub-maximal exercise time increased significantly from 205±112 to 272±120 seconds; the heart to mediastinum (H/M) ratio of 123 I-MIBG increased significantly (early image: 1.99±0.38 versus 2.20±0.50; delayed image: 1.86±0.44 versus 2.09±0.51); and the washout rate of 123 I-MIBG decreased slightly from 29.1±9.1% to 25.4±7.0%. The improvement rate of LVEF was significantly correlated with the improvement rates of the H/M ratio and washout rate after treatment with enalapril. Thus, the long-term effects of enalapril can be observed in the cardiac sympathetic nervous system, and 123 I-MIBG imaging appears to be useful for evaluating the therapeutic effects of enalapril on the cardiac sympathetic nervous system in patients with chronic heart failure. (author)

  3. The effect of renal diet in association with enalapril or benazepril on proteinuria in dogs with proteinuric chronic kidney disease

    Directory of Open Access Journals (Sweden)

    A. Zatelli

    2016-07-01

    Full Text Available Treating proteinuria in dogs reduces the progression of chronic kidney disease (CKD; renal diets and angiotensin-converting enzyme (ACE-inhibitors are cornerstones of treatment. Whether different ACE-inhibitors have distinct kidney protective effects is unknown; it is therefore hypothesized that renal diets and enalapril or benazepril have different beneficial effects in proteinuric CKD dogs. Forty-four dogs with proteinuric CKD (IRIS stages 1-4 were enrolled in the study and were fed renal diet for 30 days. Thereafter, they were randomly assigned to one of 2 groups. Dogs in group A (n=22 received enalapril (0.5 mg/kg, q12h and in group B (n=22 benazepril (0.5 mg/kg, q24h; in both groups, dogs were fed the same renal diet. After randomization, dogs were monitored for 120 days. Body weight and body condition score (BCS, serum concentrations of creatinine, blood urea nitrogen (BUN, albumin and total proteins, and urine protein-to-creatinine (UPC ratio were compared at different time-points. After 30 days of renal diet, creatinine, BUN and UPC ratio decreased significantly (p<0.0001. Compared to randomization, body weight, BCS, albumin, total proteins, creatinine and BUN did not vary during follow-up in the 44 dogs and differences between group A and B were not observed. However, the UPC ratio of group A at day 60, 90 and 150 was significantly lower than in group B and compared to randomization (p<0.05. In group B it did not vary overtime. It is concluded that the renal diet is beneficial to decrease creatinine, BUN and UPC ratio in proteinuric CKD dogs. Enalapril further ameliorates proteinuria if administered along with renal diet.

  4. The effect of renal diet in association with enalapril or benazepril on proteinuria in dogs with proteinuric chronic kidney disease.

    Science.gov (United States)

    Zatelli, A; Roura, X; D'Ippolito, P; Berlanda, M; Zini, E

    2016-01-01

    Treating proteinuria in dogs reduces the progression of chronic kidney disease (CKD); renal diets and angiotensin-converting enzyme (ACE)-inhibitors are cornerstones of treatment. Whether different ACE-inhibitors have distinct kidney protective effects is unknown; it is therefore hypothesized that renal diets and enalapril or benazepril have different beneficial effects in proteinuric CKD dogs. Forty-four dogs with proteinuric CKD (IRIS stages 1-4) were enrolled in the study and were fed renal diet for 30 days. Thereafter, they were randomly assigned to one of 2 groups. Dogs in group A (n=22) received enalapril (0.5 mg/kg, q12h) and in group B (n=22) benazepril (0.5 mg/kg, q24h); in both groups, dogs were fed the same renal diet. After randomization, dogs were monitored for 120 days. Body weight and body condition score (BCS), serum concentrations of creatinine, blood urea nitrogen (BUN), albumin and total proteins, and urine protein-to-creatinine (UPC) ratio were compared at different time-points. After 30 days of renal diet, creatinine, BUN and UPC ratio decreased significantly (p<0.0001). Compared to randomization, body weight, BCS, albumin, total proteins, creatinine and BUN did not vary during follow-up in the 44 dogs and differences between group A and B were not observed. However, the UPC ratio of group A at day 60, 90 and 150 was significantly lower than in group B and compared to randomization (p<0.05). In group B it did not vary overtime. It is concluded that the renal diet is beneficial to decrease creatinine, BUN and UPC ratio in proteinuric CKD dogs. Enalapril further ameliorates proteinuria if administered along with renal diet.

  5. Comparative clinical evaluation of Boerhavia diffusa root extract with standard Enalapril treatment in Canine chronic renal failure

    Science.gov (United States)

    Oburai, Nethaji Lokeswar; Rao, V. Vaikunta; Bonath, Ram Babu Naik

    2015-01-01

    Background: Complementing herbal drugs with conservative modern treatment could improve renal condition in canine chronic renal failure (CRF). Objective: In this study, clinical evaluation of Boerhavia diffusa root extract was carried out in CRF in dogs in comparison with standard enalapril. Materials and Methods: A total of 20 dogs of mixed breeds suffering from CRF from 1 to 2 months were divided into two groups (n = 10) and treated as follows: Group I - Enalapril at 0.5 mg/kg p.o. once daily for 90 days + amoxicillin and cloxacillin at 25 mg/kg i.m. once daily for 1-week; Group II - B. diffusa root extract at 500 mg p.o per dog daily for 90 days. Both groups were maintained on a supportive fluid therapy. The data were analyzed using paired t-test and one-way ANOVA followed by Dunnett's post-hoc test. Results: CRF caused a significant (P renal architecture, hyper-echoic cortex, medulla, and sunken kidneys. Both the treatments significantly (P < 0.05) reduced systolic and diastolic blood pressure by day 30. Serum Creatinine, urea nitrogen, phosphorus, urinary protein, ALP, and GGT showed significant (P < 0.05) reduction by day 60 in both the treatments. However, potassium levels were normalized only by B. diffusa root extract treatment by day 30. Both the treatments failed to show a significant improvement in nephrosonographic picture even after 90 days posttreatment. Conclusion: In conclusion, the efficacy of B. diffusa root extract was comparable to standard enalapril treatment of CRF in dogs. PMID:26604549

  6. Peritoneal clearances in hypertensive CAPD patients after oral administration of clonidine, enalapril, and nifedipine.

    Science.gov (United States)

    Favazza, A; Motanaro, D; Messa, P; Antonucci, F; Gropuzzo, M; Mioni, G

    1992-01-01

    The authors investigated whether the reduction of arterial pressure, induced by the oral administration of clonidine (CLO), enalapril (EN), and nifedipine (NIF), has any effect on peritoneal transport rates. The study was performed in nine hypertensive patients undergoing continuous ambulatory peritoneal dialysis (CAPD). The patients were submitted to administration of CLO, EN, and NIF, each in randomized succession for two weeks, after withdrawal of any hypotensive therapy for eight days (washout period). The nine patients underwent a four-hour dwell exchange using a 2.27 g/dL glucose two-liter bag after washout and after each hypotensive period. The following parameters were analyzed: mean arterial pressure (MAP), performed in the sitting position; net ultrafiltration; effluent/initial dialysate glucose ratio (GL D/Do); peritoneal clearance of K, BUN, creatinine (Cr), phosphate, beta-2 microglobulin (beta 2), total proteins, and the ratio between beta 2 and Cr clearance. Moreover, residual renal Cr and beta 2 clearances were analyzed. The three drugs significantly reduced MAP at a similar rate. The peritoneal transport parameters after CLO were similar to the results in the washout period. On the contrary, after EN and NIF therapy, Cr and beta 2 clearances were significantly increased, and GL D/Do decreased in comparison to the washout period. The other peritoneal transport parameters after EN and NIF were similar to the washout period. Residual renal Cr and beta 2 clearances after the three drugs were similar to those in the washout. these data suggest that after two weeks of therapy with EN and NIF, glucose, Cr, and beta 2 peritoneal transports are influenced by these hypotensive drugs irrespective of the effect on the arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. ABPM comparison of the anti-hypertensive profiles of telmisartan and enalapril in patients with mild-to-moderate essential hypertension.

    Science.gov (United States)

    Amerena, J; Pappas, S; Ouellet, J P; Williams, L; O'Shaughnessy, D

    2002-01-01

    In this multicentre, prospective, randomized, open-label, blinded-endpoint (PROBE) study, the efficacy of 12 weeks' treatment with once-daily telmisartan 40-80 mg and enalapril 10-20 mg was evaluated using ambulatory blood pressure monitoring (ABPM) in 522 patients with mild-to-moderate essential hypertension. Patients were titrated to the higher dose of study drug at week 6 if mean seated diastolic blood pressure (DBP) was > or = 90 mmHg. The primary endpoint was the change from baseline in ambulatory DBP in the last 6 h of the 24-h dosing interval after 12 weeks' treatment. Telmisartan and enalapril produced similar reductions from baseline in DBP and systolic blood pressure (SBP) over all ABPM periods evaluated (last 6 h, 24-h, daytime and night-time). Telmisartan produced a significantly greater reduction in mean seated trough DBP, measured unblinded with an automated ABPM device in the clinic, amounting to a difference of -2.02 mmHg (P ABPM device. Both treatments were well tolerated. Compared with telmisartan, enalapril was associated with a higher incidence of cough (8.9% versus 0.8%) and hypotension (3.9% versus 1.1%). Therefore, telmisartan may provide better long-term compliance and, consequently, better blood pressure control than enalapril.

  8. Effects of the angiotensin-converting enzyme inhibitor enalapril on sympathetic neuronal function and {beta}-adrenergic desensitization in heart failure after myocardial infarction in rats

    Energy Technology Data Exchange (ETDEWEB)

    Igawa, Akihiko; Nozawa, Takashi; Yoshida, Naohiro [Toyama Medical and Pharmaceutical Univ. (Japan)] [and others

    2002-11-01

    One of the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors in the treatment of heart failure may derive from sympathoinhibition and the prevention of {beta}-adrenergic desensitization. However, the roles of these properties in the overall effects of ACE inhibitor are not clear. We studied the effects of chronic enalapril treatment (20 mg/L in drinking water for 12 weeks) on left ventricular (LV) function, cardiac norepinephrine (NE), sympathetic neuronal function assessed by {sup 131}I-metaiodobenzylguanidine (MIBG), {beta}-receptors, and isometric contraction of papillary muscle in rats with myocardial infarction (MI) induced by coronary artery ligation. Decreased LV function in the MI rats was associated with reduced cardiac NE content and MIBG uptake, and severely blunted responses of non-infarcted papillary muscle to isoproterenol, forskolin, and calcium. Enalapril attenuated LV remodeling in association with a reduction of the ventricular loading condition and restored baseline developed tension of non-infarcted papillary muscle to the level of sham-operated rats. However, enalapril did not improve cardiac NE content, MIBG uptake, or inotropic responsiveness to {beta}-agonists. These results suggest that the major effect of the ACE inhibitor enalapril in the treatment of heart failure is not due to sympathoinhibition or restoration of {beta}-adrenergic pathway in this model of heart failure. (author)

  9. FREE-RADICAL OXIDATION ACTIVITY IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION WITHOUT Q WAVE TREATED WITH EPROSARTAN OR ENALAPRIL ADDITIONALLY TO THE BASIC THERAPY

    Directory of Open Access Journals (Sweden)

    O. G. Zaylobidinov

    2009-01-01

    Full Text Available Aim. To compare effects of eprosartan and enalapril on free-radical oxidation in patients with acute myocardial infarction (AMI without Q wave.Material and methods. 50 patients (aged 52,8±3,3 y.o. with AMI without Q were involved into the study. Patients were randomized on 2 groups. The first group consisted of 24 patients (51,1±2,4 y.o. which received basic therapy and enalapril (10 mg daily. The second group consisted of 26 patients (53,1±3,0 y.o. which received basic therapy and eprosartan (600 mg daily. Basic therapy included anticoagulants, antiplatelets, beta-blockers, nitrates and statins. Intensity of free-radical oxidation was evaluated by change of serum malonic dialdehyde (MDD concentration. Functional activity of serum enzymes of antioxidatic system (AOS was evaluated by rate of reaction of superoxide dismutase (SOD and catalase (CT.Results. The intensity of free-radical oxidation increased in patients with AMI without Q: high level of MDD and peroxinitrite (ONOO-. Besides activity of AOS enzymes (SOD and CT decreased. Eprosartan reduced intensity of peroxide oxidation more prominently in comparison with enalapril. Both drugs preserved low activity of SOD and CT.Conclusion. Eprosartan was significantly more effective than enalapril in reduction of serum free-radical oxidation in patients with AMI without Q wave during 10 days after hospital admission.

  10. ACHIEVEMENT OF TARGET BLOOD PRESSURE LEVEL IN PATIENTS WITH ARTERIAL HYPERTENSION OF 2-3 DEGREE WITH FIXED COMBINATION OF ENALAPRIL OR LOSARTAN WITH HYDROCHLOROTHIAZIDE

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    A. A. Kudryavtsev

    2010-01-01

    Full Text Available Aim. To compare the effects of fixed combinations of angiotensin converting enzyme inhibitor (enalapril or angiotensin II receptor antagonist (losartan with diuretic (hydrochlorothiazide, HCT on the "office" blood pressure (BP level in patients with arterial hypertension (HT of 2-3 degrees.Materials and methods. Patients (n=73; 34 men and 39 women; aged 50.5±5.8 with HT of 2-3 degrees were included in the study. Patients were randomized into 2 groups: patients of group 1 (n=34 received a fixed combination of enalapril with HCT; patients (n=39 of group 2 — a fixed combination of losartan with HCT. The study duration was 24 weeks. "Office" BP levels (Korotkov method were evaluated.Results. Combination of losartan with HCT shown more prominent effect on systolic BP (reduction from 176.1±2.77 to 122.3±1.54 mm Hg in comparison with combination enalapril with HCT (reduction from 172.4±1.62 to 129.8±3.4 mm Hg after 12 weeks of treatment (p<0.05. High frequency of target BP level achievement was observed in patients of groups 1 and 2 (83% and 86% respectively.Conclusion. The fixed combination of enalapril or lozartan with HCT has high efficacy and can be recommended as initial therapy in patients with HT of 2-3 degree.

  11. Effects of the angiotensin-converting enzyme inhibitor enalapril on sympathetic neuronal function and β-adrenergic desensitization in heart failure after myocardial infarction in rats

    International Nuclear Information System (INIS)

    Igawa, Akihiko; Nozawa, Takashi; Yoshida, Naohiro

    2002-01-01

    One of the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors in the treatment of heart failure may derive from sympathoinhibition and the prevention of β-adrenergic desensitization. However, the roles of these properties in the overall effects of ACE inhibitor are not clear. We studied the effects of chronic enalapril treatment (20 mg/L in drinking water for 12 weeks) on left ventricular (LV) function, cardiac norepinephrine (NE), sympathetic neuronal function assessed by 131 I-metaiodobenzylguanidine (MIBG), β-receptors, and isometric contraction of papillary muscle in rats with myocardial infarction (MI) induced by coronary artery ligation. Decreased LV function in the MI rats was associated with reduced cardiac NE content and MIBG uptake, and severely blunted responses of non-infarcted papillary muscle to isoproterenol, forskolin, and calcium. Enalapril attenuated LV remodeling in association with a reduction of the ventricular loading condition and restored baseline developed tension of non-infarcted papillary muscle to the level of sham-operated rats. However, enalapril did not improve cardiac NE content, MIBG uptake, or inotropic responsiveness to β-agonists. These results suggest that the major effect of the ACE inhibitor enalapril in the treatment of heart failure is not due to sympathoinhibition or restoration of β-adrenergic pathway in this model of heart failure. (author)

  12. Effect of sacubitril/valsartan versus enalapril on glycaemic control in patients with heart failure and diabetes: a post-hoc analysis from the PARADIGM-HF trial.

    Science.gov (United States)

    Seferovic, Jelena P; Claggett, Brian; Seidelmann, Sara B; Seely, Ellen W; Packer, Milton; Zile, Michael R; Rouleau, Jean L; Swedberg, Karl; Lefkowitz, Martin; Shi, Victor C; Desai, Akshay S; McMurray, John J V; Solomon, Scott D

    2017-05-01

    Diabetes is an independent risk factor for heart failure progression. Sacubitril/valsartan, a combination angiotensin receptor-neprilysin inhibitor, improves morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF), compared with the angiotensin-converting enzyme inhibitor enalapril, and improves peripheral insulin sensitivity in obese hypertensive patients. We aimed to investigate the effect of sacubitril/valsartan versus enalapril on HbA 1c and time to first-time initiation of insulin or oral antihyperglycaemic drugs in patients with diabetes and HFrEF. In a post-hoc analysis of the PARADIGM-HF trial, we included 3778 patients with known diabetes or an HbA 1c ≥6·5% at screening out of 8399 patients with HFrEF who were randomly assigned to treatment with sacubitril/valsartan or enalapril. Of these patients, most (98%) had type 2 diabetes. We assessed changes in HbA 1c , triglycerides, HDL cholesterol and BMI in a mixed effects longitudinal analysis model. Time to initiation of oral antihyperglycaemic drugs or insulin in subjects previously not treated with these agents were compared between treatment groups. There were no significant differences in HbA 1c concentrations between randomised groups at screening. During the first year of follow-up, HbA 1c concentrations decreased by 0·16% (SD 1·40) in the enalapril group and 0·26% (SD 1·25) in the sacubitril/valsartan group (between-group reduction 0·13%, 95% CI 0·05-0·22, p=0·0023). HbA 1c concentrations were persistently lower in the sacubitril/valsartan group than in the enalapril group over the 3-year follow-up (between-group reduction 0·14%, 95% CI 0·06-0·23, p=0·0055). New use of insulin was 29% lower in patients receiving sacubitril/valsartan (114 [7%] patients) compared with patients receiving enalapril (153 [10%]; hazard ratio 0·71, 95% CI 0·56-0·90, p=0·0052). Similarly, fewer patients were started on oral antihyperglycaemic therapy (0·77, 0·58-1·02

  13. Comparative effectiveness of enalapril, lisinopril, and ramipril in the treatment of patients with chronic heart failure: a propensity score-matched cohort study.

    Science.gov (United States)

    Fröhlich, Hanna; Henning, Felix; Täger, Tobias; Schellberg, Dieter; Grundtvig, Morten; Goode, Kevin; Corletto, Anna; Kazmi, Syed; Hole, Torstein; Katus, Hugo A; Atar, Dan; Cleland, John G F; Agewall, Stefan; Frankenstein, Lutz; Clark, Andrew L

    2018-04-01

    Angiotensin-converting enzyme inhibitors (ACEIs) are recommended as first-line therapy in patients with heart failure with reduced ejection fraction (HFrEF). The comparative effectiveness of different ACEIs is not known. A total of 4723 outpatients with stable HFrEF prescribed enalapril, lisinopril, or ramipril were identified from three registries in Norway, England, and Germany. In three separate matching procedures, patients were individually matched with respect to both dose equivalents and their respective propensity scores for ACEI treatment. During a follow-up of 21 939 patient-years, 360 (49.5%), 337 (52.4%), and 1119 (33.4%) patients died among those prescribed enalapril, lisinopril, and ramipril, respectively. In univariable analysis of the general sample, enalapril and lisinopril were both associated with higher mortality when compared with ramipril treatment [hazard ratio (HR) 1.46, 95% confidence interval (CI) 1.30-1.65, P < 0.001 and HR 1.38, 95% CI 1.22-1.56, P < 0.001, respectively). Patients prescribed enalapril or lisinopril had similar mortality (HR 1.06, 95% CI 0.92-1.24, P = 0.41). However, there was no significant association between ACEI choice and all-cause mortality in any of the matched samples (HR 1.07, 95% CI 0.91-1.25, P = 0.40; HR 1.12, 95% CI 0.96-1.32, P = 0.16; and HR 1.10, 95% CI 0.93-1.31, P = 0.25 for enalapril vs. ramipril, lisinopril vs. ramipril, and enalapril vs. lisinopril, respectively). Results were confirmed in subgroup analyses with respect to age, sex, left ventricular ejection fraction, New York Class Association functional class, cause of HFrEF, rhythm, and systolic blood pressure. Our results suggest that enalapril, lisinopril, and ramipril are equally effective in the treatment of patients with HFrEF when given at equivalent doses.

  14. Comparison of dynamic of autonomic control indices in cardiovascular system under the treatment by ACE inhibitor (Enalapril and beta-blocker (Metoprolol in patients with hypertension

    Directory of Open Access Journals (Sweden)

    A.R. Kiselev

    2010-03-01

    Full Text Available The objective of the present research was to compare the influence of Enalapril and Metoprolol on synchronization of 0.1 Hz-regulation of heart and blood microcirculation. 42 patients aged 49±9 years old with hypertension I, II were included in the study. 0.1 Hz-oscillations in heart rate variability (HRV and blood microcirculation were registered during the passive orthostatic sign while breathing spontaneously. The duration of each test was 10 minutes. Synchronization was estimated as a phase difference between 0.1 Hz-rhythms in heart rate and in filling of blood microcirculation. Quantitative measures of synchronization were also estimated. In addition frequency values of HRV spectrum in LF- and HF-ranges were assessed. Enalapril and Metoprolol had comparable effect on blood pressure reduction. Treatment with both Enalapril and Metoprolol in patients with significant vegetative dysfunction resulted in repair of functional interaction between 0.1 Hz-regulation of heart and blood microcirculation. Enalapril was preferred in hypertensive patients with prevalence of disorders of vegetative regulation of blood microcirculation. Metoprolol influenced positively on 0,1 Hz-rhythm synchronization in patients with predominance of heart vegetative regulation dysfunction and in patients with sympathicotonia. In patients with hypertension and initially normal level of synchronization of 0.1 Hz-mechanisms treatment with Enalapril or Metoprolol caused functional dissociation. Differentiated approach to the choice of hypertensive therapy should consider individual peculiarities of system vegetative dysfunction. The level of synchronization of 0.1 Hz-rhythms in cardiovascular system should especially be evaluated initially and during the treatment

  15. Effects of perindopril on cardiac sympathetic nerve activity in patients with congestive heart failure: comparison with enalapril

    Energy Technology Data Exchange (ETDEWEB)

    Kasama, Shu; Toyama, Takuji; Suzuki, Tadashi; Kurabayashi, Masahiko [Gunma University School of Medicine, Department of Cardiovascular Medicine, Maebashi, Gunma (Japan); Kumakura, Hisao; Takayama, Yoshiaki; Ichikawa, Shuichi [Cardiovascular Hospital of Central Japan, Department of Internal Medicine, Gunma (Japan)

    2005-08-01

    The production of aldosterone in the heart is suppressed by the angiotensin-converting enzyme (ACE) inhibitor perindopril in patients with congestive heart failure (CHF). Moreover, perindopril has been reported to have more cardioprotective effects than enalapril. Forty patients with CHF [left ventricular ejection fraction (LVEF) <45%; mean 33{+-}7%] were randomly assigned to perindopril (2 mg/day; n=20) or enalapril (5 mg/day; n=20). All patients were also treated with diuretics. The delayed heart/mediastinum count (H/M) ratio, delayed total defect score (TDS) and washout rate (WR) were determined from {sup 123}I-meta-iodobenzylguanidine (MIBG) images, and plasma brain natriuretic peptide (BNP) concentrations were measured before and 6 months after treatment. The left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV) and LVEF were also determined by echocardiography. After treatment, in patients receiving perindopril, TDS decreased from 39{+-}10 to 34{+-}9 (P<0.01), H/M ratios increased from 1.62{+-}0.27 to 1.76{+-}0.29 (P<0.01), WR decreased from 50{+-}14% to 42{+-}14% (P<0.05) and plasma BNP concentrations decreased from 226{+-}155 to 141{+-}90 pg/ml (P<0.0005). In addition, the LVEDV decreased from 180{+-}30 to 161{+-}30 ml (P<0.05) and the LVESV decreased from 122{+-}35 to 105{+-}36 ml (P<0.05). Although the LVEF tended to increase, the change was not statistically significant (from 33{+-}8% to 36{+-}12%; P=NS). On the other hand, there were no significant changes in these parameters in patients receiving enalapril. Plasma BNP concentrations, {sup 123}I-MIBG scintigraphic and echocardiographic parameters improved after 6 months of perindopril treatment. These findings indicate that perindopril treatment can ameliorate the cardiac sympathetic nerve activity and the left ventricular performance in patients with CHF. (orig.)

  16. The effects of age on the pharmacokinetics and pharmacodynamics of single oral doses of benazepril and enalapril.

    Science.gov (United States)

    Macdonald, N J; Sioufi, A; Howie, C A; Wade, J R; Elliott, H L

    1993-01-01

    1. Eighteen healthy, normotensive subjects (nine young and nine elderly) participated in a double-blind, 3-way, crossover study to compare aspects of the pharmacokinetics and pharmacodynamics of single oral doses of 10 mg benazepril, 10 mg enalapril and placebo. 2. The hypotensive effect was similar after both drugs but the absolute reductions were greater in the elderly who had higher initial levels of blood pressure. 3. The AUCs for both benazeprilat and enalaprilat were higher in the elderly but by a significantly greater amount for enalaprilat (+ 113% vs 40%; P benazepril are qualitatively similar to those with other ACE inhibitors. The clinical significance of the quantitative differences requires further investigation. PMID:9114905

  17. Combination therapy with lercanidipine and enalapril in the management of the hypertensive patient: an update of the evidence

    Directory of Open Access Journals (Sweden)

    Antza C

    2016-11-01

    Full Text Available Christina Antza,1 Stella Stabouli,2 Vasilios Kotsis1 1Hypertension Center, Third Department of Medicine, Papageorgiou Hospital, 2First Department of Pediatrics, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece Abstract: Hypertension is an important risk factor for premature death as it increases the probability of stroke, myocardial infarction, and heart failure. Antihypertensive drugs can decrease cardiovascular (CV morbidity and mortality. The majority of hypertensive patients need more than one antihypertensive agent to attain blood pressure (BP targets. Monotherapy can effectively reduce BP only in 20%–40% of patients. Multiple mechanisms including increased peripheral vascular resistance, increased cardiac work, and hypervolemia are involved in the pathogenesis of hypertension. Targeting multiple pathways may more potently reduce BP. Increasing the dose of a single agent in many cases does not provide the expected BP-lowering effect because the underlying mechanism of the BP increase is either different or already corrected with the lower dose. Moreover, drugs acting on different pathways may have synergistic effects and thus better control hypertension. It is well known that diuretics enhance the actions of renin–angiotensin aldosterone system and activate it as a feedback to the reduced circulated blood volume. The addition of a renin–angiotensin aldosterone system blocker to a diuretic may more effectively reduce BP because the system is upregulated. Reducing the maximal dose of an agent may also reduce possible side effects if they are dose dependent. The increased prevalence of peripheral edema with higher doses of calcium channel blockers (CCBs is reduced when renin–angiotensin aldosterone system blockers are added to CCBs through vein dilation. The effectiveness of the combination of enalapril with lercanidipine in reducing BP, the safety profile, and the use of the combination of angiotensin

  18. Cost-Effectiveness of Sacubitril-Valsartan Combination Therapy Compared With Enalapril for the Treatment of Heart Failure With Reduced Ejection Fraction.

    Science.gov (United States)

    King, Jordan B; Shah, Rashmee U; Bress, Adam P; Nelson, Richard E; Bellows, Brandon K

    2016-05-01

    The objective of this study was to determine the cost-effectiveness and cost per quality-adjusted life year (QALY) gained of sacubitril-valsartan relative to enalapril for treatment of heart failure with reduced ejection fraction (HFrEF). Compared with enalapril, combination angiotensin receptor-neprilysin inhibition (ARNI), as is found in sacubitril-valsartan, reduces cardiovascular death and heart failure hospitalization rates in patients with HFrEF. Using a Markov model, costs, effects, and cost-effectiveness were estimated for sacubitril-valsartan and enalapril therapies for the treatment of HFrEF. Patients were 60 years of age at model entry and were modeled over a lifetime (40 years) from a third-party payer perspective. Clinical probabilities were derived predominantly from PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure). All costs and effects were discounted at a 3% rate annually and are presented in 2015 U.S. dollars. In the base case, sacubitril-valsartan, compared with enalapril, was more costly ($60,391 vs. $21,758) and more effective (6.49 vs. 5.74 QALYs) over a lifetime. The cost-effectiveness of sacubitril-valsartan was highly dependent on duration of treatment, ranging from $249,411 per QALY at 3 years to $50,959 per QALY gained over a lifetime. 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. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  19. Effects of high doses of enalapril and benazepril on the pharmacologically activated renin-angiotensin-aldosterone system in clinically normal dogs.

    Science.gov (United States)

    Ames, Marisa K; Atkins, Clarke E; Lee, Seunggon; Lantis, Andrea C; zumBrunnen, James R

    2015-12-01

    To determine whether high doses of enalapril and benazepril would be more effective than standard doses of these drugs in suppressing the furosemide-activated renin-angiotensin-aldosterone system (RAAS). 6 healthy Beagles. 2 experiments were conducted; each lasted 10 days, separated by a 2-week washout period. In experiment 1, all dogs received furosemide (2 mg/kg, PO, q 12 h) and enalapril (1 mg/kg, PO, q 12 h) for 8 days (days 0 through 7). In experiment 2, dogs received furosemide (2 mg/kg, PO, q 12 h) and benazepril (1 mg/kg, PO, q 12 h) for 8 days. Effects on the RAAS were determined by assessing serum angiotensin-converting enzyme (ACE) activity on days -1, 3, and 7; serum aldosterone concentration on days -2, -1, 1, 3, and 7; and the urinary aldosterone-creatinine ratio (UAldo:C) in urine collected in the morning and evening of days -2, -1, 1, 3, and 7. High doses of enalapril and benazepril caused significant reductions in serum ACE activity on all days but were not more effective than standard doses used in other studies. Mean UAldo:C remained significantly higher on days 2 through 7, compared with baseline values. Serum aldosterone concentration also increased after drug administration, which mirrored changes in the UAldo:C. In this study, administration of high doses of enalapril and benazepril significantly inhibited ACE activity, yet did not prevent increases in mean urine and serum aldosterone concentrations resulting from furosemide activation of RAAS. This suggested that aldosterone breakthrough from ACE inhibition was a dose-independent effect of ACE inhibitors.

  20. Treatment of spontaneously hypertensive rats with rosiglitazone and/or enalapril restores balance between vasodilator and vasoconstrictor actions of insulin with simultaneous improvement in hypertension and insulin resistance.

    Science.gov (United States)

    Potenza, Maria A; Marasciulo, Flora L; Tarquinio, Mariela; Quon, Michael J; Montagnani, Monica

    2006-12-01

    Spontaneously hypertensive rats (SHRs) exhibit endothelial dysfunction and insulin resistance. Reciprocal relationships between endothelial dysfunction and insulin resistance may contribute to hypertension by causing imbalanced regulation of endothelial-derived vasodilators (e.g., nitric oxide) and vasoconstrictors (e.g., endothelin-1 [ET-1]). Treatment of SHRs with rosiglitazone (insulin sensitizer) and/or enalapril (ACE inhibitor) may simultaneously improve hypertension, insulin resistance, and endothelial dysfunction by rebalancing insulin-stimulated production of vasoactive mediators. When compared with WKY control rats, 12-week-old vehicle-treated SHRs were hypertensive, overweight, and insulin resistant, with elevated fasting levels of insulin and ET-1 and reduced serum adiponectin levels. In mesenteric vascular beds (MVBs) isolated from vehicle-treated SHRs and preconstricted with norepinephrine (NE) ex vivo, vasodilator responses to insulin were significantly impaired, whereas the ability of insulin to oppose vasoconstrictor actions of NE was absent (versus WKY controls). Three-week treatment of SHRs with rosiglitazone and/or enalapril significantly reduced blood pressure, insulin resistance, fasting insulin, and ET-1 levels and increased adiponectin levels to values comparable with those observed in vehicle-treated WKY controls. By restoring phosphatidylinositol 3-kinase-dependent effects, rosiglitazone and/or enalapril therapy of SHRs also significantly improved vasodilator responses to insulin in MVB preconstricted with NE ex vivo. Taken together, our data provide strong support for the existence of reciprocal relationships between endothelial dysfunction and insulin resistance that may be relevant for developing novel therapeutic strategies for the metabolic syndrome.

  1. Comparison of the effects of candesartan cilexetil and enalapril maleate on right ventricular myocardial remodeling in dogs with experimentally induced pulmonary stenosis.

    Science.gov (United States)

    Yamane, Tsuyoshi; Fujii, Yoko; Orito, Kensuke; Osamura, Kaori; Kanai, Takao; Wakao, Yoshito

    2008-12-01

    To compare the effects of candesartan cilexetil and enalapril maleate on right ventricular myocardial remodeling in dogs with experimentally induced pulmonary stenosis. 24 Beagles. 18 dogs underwent pulmonary arterial banding (PAB) to induce right ventricular pressure overload, and 6 healthy dogs underwent sham operations (thoracotomy only [sham-operated group]). Dogs that underwent PAB were allocated to receive 1 of 3 treatments (6 dogs/group): candesartan (1 mg/kg, PO, q 24 h [PABC group]), enalapril (0.5 mg/kg, PO, q 24 h [PABE group]), or no treatment (PABNT group). Administration of treatments was commenced the day prior to surgery; control dogs received no cardiac medications. Sixty days after surgery, right ventricular wall thickness was assessed echocardiographically and plasma renin activity, angiotensin-converting enzyme activity, and angiotensin I and II concentrations were assessed; all dogs were euthanatized, and collagenous fiber area, cardiomyocyte diameter, and tissue angiotensin-converting enzyme and chymase-like activities in the right ventricle were evaluated. After 60 days of treatment, right ventricular wall thickness, cardiomyocyte diameter, and collagenous fiber area in the PABNT and PABE groups were significantly increased, compared with values in the PABC and sham-operated groups. Chymase-like activity was markedly greater in the PABE group than in other groups. Results indicated that treatment with candesartan but not enalapril effectively prevented myocardial remodeling in dogs with experimentally induced subacute right ventricular pressure overload.

  2. Perinatal Na+ Overload Programs Raised Renal Proximal Na+ Transport and Enalapril-Sensitive Alterations of Ang II Signaling Pathways during Adulthood

    Science.gov (United States)

    Cabral, Edjair V.; Vieira-Filho, Leucio D.; Silva, Paulo A.; Nascimento, Williams S.; Aires, Regina S.; Oliveira, Fabiana S. T.; Luzardo, Ricardo; Vieyra, Adalberto; Paixão, Ana D. O.

    2012-01-01

    Background High Na+ intake is a reality in nowadays and is frequently accompanied by renal and cardiovascular alterations. In this study, renal mechanisms underlying perinatal Na+ overload-programmed alterations in Na+ transporters and the renin/angiotensin system (RAS) were investigated, together with effects of short-term treatment with enalapril in terms of reprogramming molecular alterations in kidney. Methodology/Principal Findings Male adult Wistar rats were obtained from dams maintained throughout pregnancy and lactation on a standard diet and drinking water (control) or 0.17 M NaCl (saline group). Enalapril (100 mg/l), an angiotensin converting enzyme inhibitor, was administered for three weeks after weaning. Ninety day old offspring from dams that drank saline presented with proximal tubules exhibiting increased (Na++K+)ATPase expression and activity. Ouabain-insensitive Na+-ATPase activity remained unchanged but its response to angiotensin II (Ang II) was lost. PKC, PKA, renal thiobarbituric acid reactive substances (TBARS), macrophage infiltration and collagen deposition markedly increased, and AT2 receptor expression decreased while AT1 expression was unaltered. Early treatment with enalapril reduced expression and activity of (Na++K+)ATPase, partially recovered the response of Na+-ATPase to Ang II, and reduced PKC and PKA activities independently of whether offspring were exposed to high perinatal Na+ or not. In addition, treatment with enalapril per se reduced AT2 receptor expression, and increased TBARS, macrophage infiltration and collagen deposition. The perinatally Na+-overloaded offspring presented high numbers of Ang II-positive cortical cells, and significantly lower circulating Ang I, indicating that programming/reprogramming impacted systemic and local RAS. Conclusions/Significance Maternal Na+ overload programmed alterations in renal Na+ transporters and in its regulation, as well as severe structural lesions in adult offspring. Enalapril

  3. Combined spectroscopies and molecular docking approach to characterizing the binding interaction of enalapril with bovine serum albumin.

    Science.gov (United States)

    Pan, Dong-Qi; Jiang, Min; Liu, Ting-Ting; Wang, Qi; Shi, Jie-Hua

    2017-06-01

    The binding interaction between bovine serum albumin (BSA) and enalapril (ENPL) at the imitated physiological conditions (pH = 7.4) was investigated using UV-vis absorption spectroscopy (UV-vis), fluorescence emission spectroscopy (FES), synchronous fluorescence spectroscopy (SFS), Fourier transform infrared spectroscopy (FT-IR), circular dichroism (CD) and molecular docking methods. It can be deduced from the experimental results from the steady-state fluorescence spectroscopic titration that the intrinsic BSA fluorescence quenching mechanism induced by ENPL is static quenching, based on the decrease in the BSA quenching constants in the presence of ENPL with increase in temperature and BSA quenching rates >10 10  L mol -1  sec -1 . This result indicates that the ENPL-BSA complex is formed through an intermolecular interaction of ENPL with BSA. The main bonding forces for interaction of BSA and ENPL are van der Waal's forces and hydrogen bonding interaction based on negative values of Gibbs free energy change (ΔG 0 ), enthalpic change (ΔH 0 ) and entropic change (ΔS 0 ). The binding of ENPL with BSA is an enthalpy-driven process due to |ΔH°| > |TΔS°| in the binding process. The results of competitive binding experiments and molecular docking confirm that ENPL binds in BSA sub-domain IIA (site I) and results in a slight change in BSA conformation, but BSA still retains its α-helical secondary structure. Copyright © 2016 John Wiley & Sons, Ltd.

  4. Analysis of the physico-chemical quality Enalapril and Simvastatin drugs manipulated in magistral pharmacies from Belo Horizonte, MG, Brazil; Analise da qualidade fisico-quimica dos medicamentos Enalapril e Sinvastatina manipulados em farmacias magistrais de Belo Horizonte, MG, Brasil

    Energy Technology Data Exchange (ETDEWEB)

    Gomes, Tatiana Cristina Bomfim

    2013-07-01

    The increasing expansion of compounding pharmacy associated with several reports on variances in the quality of compounded drugs demonstrates the need for verification of quality, safety and efficacy of these products. In this work, physical and chemical analyzes were performed to evaluate the quality of some capsules manipulated enalapril and simvastatin, acquired in five pharmacies in Belo Horizonte /Brazil. Among the analyzes are pharmacopoeial tests for appearance, identification, determination of weight, content, related compounds and uniformity of dosage units, and was also performed neutron activation analysis for the determination of inorganic impurities in drugs sampled. The results showed that 60% of the samples were unsatisfactory for pharmacopoeial tests. The contents of the capsules sampled for individual testing unit dose uniformity between 0% and 136.2%. This test is important in evaluating the quality, which influences the safety and efficacy of drug treatment, since it allows you to check if the product contains the proper dosage and necessary for successful pharmacotherapy. On the other hand, underdosing can lead to reduced or absent desired therapeutic response, and overdoses can provide an undesirable effects and even toxic. The concentration of inorganic impurities was considered to be relatively small. However, no specific limits for some chemical elements in medicine hamper a better thread. In addition, further studies must be performed to assess chronic exposure to low concentrations of inorganic impurities, since drugs can be continuously used, and other sources of exposure must also be considered in order to evaluate the risk. The problems related to the quality and safety of compounded drugs are still reality in the country and reveal a serious public health problem, especially regarding the lack of uniformity between the unit doses of medications. It is suggested that the competent authorities to sanitary products, propose changes in

  5. Effectiveness and tolerability of fixed-dose combination enalapril plus nitrendipine in hypertensive patients: results of the 3-month observational, post-marketing, multicentre, prospective CENIT study.

    Science.gov (United States)

    Sierra, Alejandro de la; Roca-Cusachs, Alejandro; Redón, Josep; Marín, Rafael; Luque, Manuel; Figuera, Mariano de la; Garcia-Garcia, Margarida; Falkon, Liliana

    2009-01-01

    Monotherapy with any class of antihypertensive drug effectively controls blood pressure (BP) in only about 50% of patients. Consequently, the majority of patients with hypertension require combined therapy with two or more medications. This study aimed to evaluate the effectiveness (systolic BP [SBP]/diastolic BP [DBP] control) and tolerability of the fixed-dose combination enalapril/nitrendipine 10 mg/20 mg administered as a single daily dose in hypertensive patients. This was a post-authorization, multicentre, prospective, observational study conducted in primary care with a 3-month follow-up. Patients throughout Spain with uncontrolled hypertension (> or =140/90 mmHg for patients without diabetes mellitus, or > or =130/85 mmHg for patients with diabetes) on monotherapy or with any combination other than enalapril + nitrendipine, or who were unable to tolerate their previous antihypertensive therapy, were recruited. Change from previous to study treatment was according to usual clinical practice. BP was measured once after 5 minutes of rest in the sitting position. Therapeutic response was defined as follows: 'controlled' meant controlled BP ( or =20 mmHg and in DBP of > or =10 mmHg. The main laboratory test parameters were documented at baseline and after 3 months. Patients aged >65 years, with diabetes, with isolated systolic hypertension (ISH; SBP > or =140 mmHg for patients without diabetes, SBP > or =130 mmHg for patients with diabetes) and who were obese (body mass index [BMI] > or =30 kg/m2) were analysed separately. Of 6537 patients included, 5010 and 6354 patients were assessed in effectiveness and tolerability analyses, respectively. In the tolerability analysis population, there were 3023 men (47.6%) and 3321 women (52.4%). The mean (+/- SD) age of the tolerability analysis group was 62.8 (+/- 10.7) years. A total of 71.1% of the patients presented at least one clinical cardiovascular risk factor other than hypertension, with the most frequent being

  6. Combination therapy with lercanidipine and enalapril reduced central blood pressure augmentation in hypertensive patients with metabolic syndrome.

    Science.gov (United States)

    Ghiadoni, Lorenzo; Bruno, Rosa Maria; Cartoni, Giulia; Stea, Francesco; Magagna, Armando; Virdis, Agostino; Grassi, Davide; Ferri, Claudio; Taddei, Stefano

    2017-05-01

    Arterial stiffness and blood pressure (BP) augmentation are independent predictors of cardiovascular events. In a randomized, open, parallel group study we compared the effect on these parameters of combination therapy with an ACE-inhibitor plus calcium channel blocker or thiazide diuretic in 76 hypertensive patients with metabolic syndrome uncontrolled by ACE-inhibitor monotherapy. After 4weeks run-in with enalapril (ENA, 20mg), patients were randomized to a combination therapy with lercanidipine (LER, 10-20mg) or hydrochlorothiazide (HCT, 12.5-25mg) for 24weeks. Aortic stiffness (carotid to femoral pulse wave velocity, PWV), central BP values and augmentation (augmentation index, AIx) were measured by applanation tonometry. The two groups showed similar office and central BP after run-in. Office (ENA/LER: from 149.1±4.9/94.5±1.5 to 131.7±8.1/82.2±5.3; ENA/HCT: from 150.3±4.7/94.7±2.1 to 133.1±7.1/82.8±5.3mmHg) and central BP (ENA/LER 127.4±17.1/85.2±12.1 to 120.5±13.5/80.0±9.5mmHg; ENA/HCT 121.6±13.4/79.3±9.5mmHg) were similarly reduced after 24weeks. PWV was comparable after run-in and not differently reduced by the two treatments (ENA/LER from 8.6±1.5 to 8.1±1.3m/s, pmetabolic syndrome not controlled by ENA alone. These results indicate a positive effect of the combination of ENA/LER on central BP augmentation, suggesting a potential additive role for cardiovascular protection. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Analysis of the physico-chemical quality Enalapril and Simvastatin drugs manipulated in magistral pharmacies from Belo Horizonte, MG, Brazil

    International Nuclear Information System (INIS)

    Gomes, Tatiana Cristina Bomfim

    2013-01-01

    The increasing expansion of compounding pharmacy associated with several reports on variances in the quality of compounded drugs demonstrates the need for verification of quality, safety and efficacy of these products. In this work, physical and chemical analyzes were performed to evaluate the quality of some capsules manipulated enalapril and simvastatin, acquired in five pharmacies in Belo Horizonte /Brazil. Among the analyzes are pharmacopoeial tests for appearance, identification, determination of weight, content, related compounds and uniformity of dosage units, and was also performed neutron activation analysis for the determination of inorganic impurities in drugs sampled. The results showed that 60% of the samples were unsatisfactory for pharmacopoeial tests. The contents of the capsules sampled for individual testing unit dose uniformity between 0% and 136.2%. This test is important in evaluating the quality, which influences the safety and efficacy of drug treatment, since it allows you to check if the product contains the proper dosage and necessary for successful pharmacotherapy. On the other hand, underdosing can lead to reduced or absent desired therapeutic response, and overdoses can provide an undesirable effects and even toxic. The concentration of inorganic impurities was considered to be relatively small. However, no specific limits for some chemical elements in medicine hamper a better thread. In addition, further studies must be performed to assess chronic exposure to low concentrations of inorganic impurities, since drugs can be continuously used, and other sources of exposure must also be considered in order to evaluate the risk. The problems related to the quality and safety of compounded drugs are still reality in the country and reveal a serious public health problem, especially regarding the lack of uniformity between the unit doses of medications. It is suggested that the competent authorities to sanitary products, propose changes in

  8. Simultaneous Determination of Acetylsalicylic Acid, Hydrochlorothiazide, Enalapril, and Atorvastatin in a Polypill-Based Quaternary Mixture by TLC.

    Science.gov (United States)

    Maślanka, Anna; Stolarczyk, Mariusz; Apola, Anna; Kwiecień, Anna; Hubicka, Urszula; Opoka, Włodzimierz

    2018-05-01

    A new chromatographic-densitometric method has been developed for the qualitative and quantitative determination of the active ingredients in a simulated mixture corresponding to the PolyIran polypill, composed of acetylsalicylic acid, hydrochlorothiazide (HCT), enalapril (ENA), and atorvastatin (ATR), whose efficacy in the treatment and prevention of cardiovascular disease has been documented in clinical trials. Chromatographic separation was performed using TLC silica gel 60 plates with fluorescent indicator F254 as the stationary phase and a mixture of n-hexane-ethyl acetate-methanol-water-acetic acid (8.4 + 8 + 3 + 0.4 + 0.2, v/v/v/v/v) as the mobile phase. Densitometric measurements were carried out at λ = 210 nm when determining ENA and at λ = 265 nm in the case of the other drugs. Peaks of examined substances were well separated in the recorded chromatograms, enabling the evaluation of the results in terms of both qualitative and quantitative analysis. The method was specific for the analyzed components and was characterized by high sensitivity. The LOD was between 0.043 and 0.331 μg/spot, and LOQ was between 0.100 and 0.942 μg/spot. Recovery was in the range of 97.02-101.34%. The linearity range was broad and ranged from 0.600 to 6.000 μg/spot for acetylsalicylic acid, from 0.058 to 1.102 μg/spot for HCT, from 0.505 to 6.560 μg/spot for ENA, and from 0.100 to 1.000 μg/spot for ATR. The method was characterized by good precision, with RSD values that ranged from 0.10 to 2.26%.

  9. Efecto coadyuvante del extracto liofilizado de Passiflora edulis (maracuyá en la reducción de la presión arterial en pacientes tratados con enalapril

    Directory of Open Access Journals (Sweden)

    Juan Rojas

    2009-06-01

    Full Text Available Objetivos: Determinar el efecto coadyuvante antihipertensivo y la seguridad del jugo del fruto de maracuyá en pacientes hipertensos en tratamiento con enalapril. Diseño: Ensayo clínico prospectivo piloto, de fase II, aleatorizado, a doble ciego, de grupos paralelos, controlado, de búsqueda de dosis y evaluación del producto. Institución: Instituto de Investigaciones Clínicas, Facultad de Medicina, UNMSM; Hospital Nacional Dos de Mayo en Lima; Hospital Belén de Trujillo y Centros de Salud de Moche y Laredo, en la ciudad de Trujillo. Participantes: Pacientes hipertensos. Intervenciones: Los pacientes fueron asignados aleatoriamente a 4 grupos. Todos recibieron enalapril 10 mg/día y, además, el primer grupo recibió placebo y los demás 2, 3 y 4 cápsulas de 500 mg de liofilizado de jugo de maracuyá/día, respectivamente. Principales medidas de resultados: Disminución de la presión arterial. Resultados: Los grupos que recibieron enalapril más maracuyá tuvieron una mejor reducción de la presión sanguínea en comparación con el grupo que recibió enalapril más placebo. El grupo tratado con enalapril más 4 cápsulas de jugo liofilizado de maracuyá/día produjo al final del experimento una reducción de la presión sistólica de 6,73 mmHg y de la presión diastólica de 5,33 mmHg (p<0,05, en comparación con el grupo enalapril más placebo. No se observó efectos adversos por el tratamiento. Conclusiones: El jugo del fruto de P. edulis fue coadyuvante efectivo del enalapril en la disminución de la presión arterial en pacientes con hipertensión estadio 1, y demostró ser seguro.

  10. Lercanidipine, enalapril and their combination in the treatment of elderly hypertensive patients: placebo-controlled, randomized, crossover study with four ABPM.

    Science.gov (United States)

    Puig, J G; Calvo, C; Luurila, O; Luurila, H; Sulosaari, S; Strandberg, A; Ghezzi, C

    2007-12-01

    This double-blind, placebo-controlled, four-way balanced design crossover study included hypertensive patients aged 60-85 years with mean office-measured sitting systolic blood pressure (SBP) 160-179 mm Hg and daytime SBP > or =135 mm Hg. After a 2-week run-in period, during which previous medications were discontinued, each patient received the following four treatments in randomized order for 4 weeks each: lercanidipine 10 mg (L), enalapril 20 mg (E), lercanidipine 10 mg plus enalapril 20 mg (L/E) and placebo (P). At the end of each treatment period, office trough blood pressure (BP) was measured and a 24-h Ambulatory Blood Pressure Monitoring (ABPM) was performed. Seventy-five patients (mean age 66 years, office BP 168/92 mm Hg, daytime SBP 151 mm Hg) were randomized and 62 completed the study with four valid post-baseline ABPMs. The administration of P, L, E and L/E was associated with a mean 24-h SBP of 144, 137, 133 and 127 mm Hg, respectively. All active treatments significantly reduced the mean 24-h SBP in comparison with placebo, but L/E was significantly more effective than L and E alone. Similarly, office SBP was significantly more reduced with L/E (-16.9 mm Hg) than with L (-5.0 mm Hg) or E (-5.9 mm Hg). A BP <140/90 mm Hg was recorded in 18% of patients with L, 19% with E and 45% with L/E. Two patients on P and two on L/E were withdrawn from the study due to adverse events. In conclusion, combination therapy with L/E has additive antihypertensive effects on both ambulatory and office BP in elderly patients and is well tolerated.

  11. CHARACTERIZATION OF ENALAPRIL AND RANITIDINE CHLORINATION BY-PRODUCTS BY LIQUID CHROMATOGRAPHY/HIGH-RESOLUTION MASS SPECTROMETRY AND THEIR TOXICITY EVALUATION

    Directory of Open Access Journals (Sweden)

    Frederico Jehár Oliveira Quintão

    Full Text Available Due to its low cost, its capability for disinfection and oxidation, chlorination using gaseous chlorine or hypochlorite salts, has also been commonly applied in water treatment plants for oxidation and disinfection purposes. Little is known about the identity and toxicity of by-products resulting from the chlorination of pharmaceutical micropollutants, such as enalapril (ENA and ranitidine (RAN. ENA and RAN chlorination by-products were characterized in this study by high-performance liquid chromatography coupled to high-resolution mass spectrometry (HPLC/HRMS and their toxicity were assessed by MTT assay. Chlorination experiments with ENA and RAN solutions (10 mg L-1 indicate degradation efficiencies of 100% for both compounds after only 5 min of exposure to chlorine at concentration of 9.53 mg Cl2 L-1. On the other hand mineralization rates were lower than 3%, thereby indicating there was accumulation of degradation by-products in all experiments. Mass spectrometric analysis revealed, at all times of reaction after the addition of hypochlorite, the presence of 1-(2-((4-(chlorophenyl-1-ethoxy-1-oxobutan-2-ylaminopropanoylpyrrolidine-2-carboxylic acid (enalapril by-product and N-chloro-N-(2-(((chloro-5-((dimethylaminomethylfuran-2-ylmethylsulfinylethyl-N-methyl-2-nitroethene 1,1-diamine (ranitidine by-product. Despite the formation of oxidized chlorinated by-products in all chlorination assays, the treated solutions were nontoxic to HepG2 cells by the MTT assay. It has been observed that chlorination (10 mg L-1, 5 min of ENA and RAN solutions exhibited high degradation efficiencies of the target compounds and low mineralization rates. Based on the mass spectrometry data, the routes for ENA and RAN successive oxidation by chlorine has been proposed.

  12. Influence of Enalapril on the progression of chronic renal failure in diabetic nephropathy and nephropathies of and other aethiology: A two-year study

    Directory of Open Access Journals (Sweden)

    Trbojević Jasna

    2002-01-01

    Full Text Available Chronic renal failure (CRF is almost always associated with high arterial blood pressure. Adequate control of hypertension slows down the progression of the disease, Inhibitors of angiotenzin-converting enzyme (ACE inhibitors have proved to be very efficacious in decreasing high blood pressure. The aim of this study was to assess the influence of ACE inhibitor enalapril on the progression of CRF in patients with diabetic nephropathy and nephropathies of other origin. During 1998 and 1999 thirty patients (20 males and 10 females, aged 525+1.3 have been followed-up at the Department of Nephrology, Clinical Centre of Serbia. On regular monthly controls serum creatinine, urea, calcium and protein levels, creatinine clearance, and blood pressure, were measured. All patients were suggested a low protein diet. Progression of the disease was expressed by the slope of the regression line showing reciprocal serum creatinine values. Proteinaemia was significantly higher in diabetic patients after 12 months (p<0.35 but in the next 12 months the difference between groups disappeared. The same patients had significantly lower serum urea (p<0.05 after 24 months and creatinine values (p<0.05 dur ing the whole study. Other variables changed in the same manner and with similar progression in both groups. The direction of slope lines suggested recovery of kidney function in both examined groups. However, a smaller slope in patients with diabetic nephropathy together with other results showed that enalapril had better influence on slowing down the progression of CRF in this group of patients.

  13. Enalapril and Hydrochlorothiazide

    Science.gov (United States)

    ... or pharmacist if you are taking valsartan and sacubitril (Entresto) or if you have stopped taking it ... hydrochlorothiazide, if you are also taking valsartan and sacubitril. Also, tell your doctor if you have diabetes ...

  14. Incidence, Predictors, and Outcomes Associated With Hypotensive Episodes Among Heart Failure Patients Receiving Sacubitril/Valsartan or Enalapril: The PARADIGM-HF Trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure).

    Science.gov (United States)

    Vardeny, Orly; Claggett, Brian; Kachadourian, Jessica; Pearson, Scott M; Desai, Akshay S; Packer, Milton; Rouleau, Jean; Zile, Michael R; Swedberg, Karl; Lefkowitz, Martin; Shi, Victor; McMurray, John J V; Solomon, Scott D

    2018-04-01

    In PARADIGM-HF (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure), heart failure treatment with sacubitril/valsartan reduced the primary composite outcome of cardiovascular death or heart failure hospitalization compared with enalapril but resulted in more symptomatic hypotension. Concern on hypotension may be limiting use of sacubitril/valsartan in appropriate patients. We characterized patients in PARADIGM-HF by whether they reported hypotension during study run-in periods (enalapril, followed by sacubitril/valsartan) and after randomization and assessed whether hypotension modified the efficacy of sacubitril/valsartan. Of the 10 513 patients entering the enalapril run-in, 136 (1.3%) experienced hypotension and 93 (68%) were unable to continue to the next phase; of 9419 patients entering the sacubitril/valsartan run-in period, 228 (2.4%) patients experienced hypotension and 51% were unable to successfully complete the run-in. After randomization, 388 (9.2%) participants had 501 hypotensive events with enalapril, and 588 (14.0%) participants had 803 hypotensive events with sacubitril/valsartan ( P sacubitril/valsartan compared with enalapril as those without hypotensive events ( P interaction>0.90). Hypotension was more common with sacubitril/valsartan relative to enalapril in PARADIGM-HF but did not differentially affect permanent discontinuations. Patients with hypotension during run-in derived similar benefit from sacubitril/valsartan compared with enalapril as those who did not experience hypotension. © 2018 American Heart Association, Inc.

  15. Comparing LCZ696 with enalapril according to baseline risk using the MAGGIC and EMPHASIS-HF risk scores: an analysis of mortality and morbidity in PARADIGM-HF.

    Science.gov (United States)

    Simpson, Joanne; Jhund, Pardeep S; Silva Cardoso, Jose; Martinez, Felipe; Mosterd, Arend; Ramires, Felix; Rizkala, Adel R; Senni, Michele; Squire, Iain; Gong, Jianjian; Lefkowitz, Martin P; Shi, Victor C; Desai, Akshay S; Rouleau, Jean L; Swedberg, Karl; Zile, Michael R; McMurray, John J V; Packer, Milton; Solomon, Scott D

    2015-11-10

    Although most patients in the PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial had mild symptoms, there is a poor correlation between reported functional limitation and prognosis in heart failure. The aim of this study was to examine the spectrum of risk in PARADIGM-HF and the effect of LCZ696 across that spectrum. This study analyzed rates of the primary composite outcome of cardiovascular death or heart failure hospitalization, its components, and all-cause mortality using the MAGGIC (Meta-Analysis Global Group in Chronic Heart Failure) and EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) risk scores to categorize patients. The authors determined whether risk, on the basis of these scores, modified the treatment effect of LCZ696. The complete MAGGIC risk score was available for 8,375 of the 8,399 patients in PARADIGM-HF. The median MAGGIC score was 20 (IQR: 16 to 24). An increase of 1 point was associated with a 6% increased risk for the primary endpoint (p PARADIGM-HF patients had mild symptoms, many were at high risk for adverse outcomes and obtained a large absolute benefit from LCZ696, compared with enalapril, over a relatively short treatment period. LCZ696's benefit was consistent across the spectrum of risk. (PARADIGM-HF trial [Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure]; NCT01035255). Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  16. Combinação de anlodipino e enalaprila em pacientes hipertensos com doença coronariana Combinación de amlodipino y enalapril en pacientes hipertensos con enfermedad coronaria Combination of amlodipine and enalapril in hypertensive patients with coronary disease

    Directory of Open Access Journals (Sweden)

    Marcos Rienzo

    2009-03-01

    Full Text Available FUNDAMENTO: Pacientes (pts com doença coronariana (DAC estável podem se beneficiar de menor pressão arterial (PA, conforme estudos recentes. OBJETIVO: Avaliar a eficácia e a tolerabilidade da combinação fixa anlodipino + enalaprila, comparada a anlodipino na normalização da PA diastólica (PAD ( 90 e 110 mmHg durante o wash-out de quatro semanas, em uso só de atenolol. Após wash-out randomizamos para combinação (A ou anlodipino (B e seguimos de quatro em quatro semanas até 98 dias. As doses (mg iniciais foram, respectivamente: A- 2,5/10 e B- 2,5, sendo incrementadas se PAD> 85mmHg, nas visitas. Estatística com χ2, Fischer e análise de variância, para pFUNDAMENTO: Pacientes (pts con enfermedad coronaria (EAC estable pueden beneficiarse con una menor presión arterial (PA, de acuerdo con estudios recientes. OBJETIVO: Evaluar la eficacia y la tolerancia de la combinación fija amlodipino + enalapril, comparada a el amlodipino en la normalización de la PA diastólica (PAD (90 y 110 mmHg durante el wash-out de cuatro semanas, en uso sólo de atenolol. Después del wash-out randomizamos para combinación (A o amlopidino (B y seguimos de cuatro en cuatro semanas hasta 98 días. Las dosis (mg iniciales fueron, respectivamente: A- 2,5/10 y B- 2,5, siendo incrementadas si PAD> 85mmHg, en las visitas. Estadística con χ2, Fischer y análisis de varianza, para pBACKGROUND: Patients (pts with stable coronary artery disease (CAD can benefit from a decrease in the blood pressure (BP, according to recent studies. OBJECTIVE: To evaluate the efficacy and tolerability of the fixed combination: amlodipine + enalapril, when compared to amlodipine in the normalization of the diastolic arterial pressure (DAP (90 and 110 mmHg during the four-week wash-out with atenolol treatment alone, were excluded. After the wash-out, pts were randomly distributed for the use of the combination (A or amlodipine (B and were followed every four weeks up to 98 days

  17. Sample Preparation and Extraction in Small Sample Volumes Suitable for Pediatric Clinical Studies: Challenges, Advances, and Experiences of a Bioanalytical HPLC-MS/MS Method Validation Using Enalapril and Enalaprilat

    Science.gov (United States)

    Burckhardt, Bjoern B.; Laeer, Stephanie

    2015-01-01

    In USA and Europe, medicines agencies force the development of child-appropriate medications and intend to increase the availability of information on the pediatric use. This asks for bioanalytical methods which are able to deal with small sample volumes as the trial-related blood lost is very restricted in children. Broadly used HPLC-MS/MS, being able to cope with small volumes, is susceptible to matrix effects. The latter restrains the precise drug quantification through, for example, causing signal suppression. Sophisticated sample preparation and purification utilizing solid-phase extraction was applied to reduce and control matrix effects. A scale-up from vacuum manifold to positive pressure manifold was conducted to meet the demands of high-throughput within a clinical setting. Faced challenges, advances, and experiences in solid-phase extraction are exemplarily presented on the basis of the bioanalytical method development and validation of low-volume samples (50 μL serum). Enalapril, enalaprilat, and benazepril served as sample drugs. The applied sample preparation and extraction successfully reduced the absolute and relative matrix effect to comply with international guidelines. Recoveries ranged from 77 to 104% for enalapril and from 93 to 118% for enalaprilat. The bioanalytical method comprising sample extraction by solid-phase extraction was fully validated according to FDA and EMA bioanalytical guidelines and was used in a Phase I study in 24 volunteers. PMID:25873972

  18. Design for the sacubitril/valsartan (LCZ696) compared with enalapril study of pediatric patients with heart failure due to systemic left ventricle systolic dysfunction (PANORAMA-HF study).

    Science.gov (United States)

    Shaddy, Robert; Canter, Charles; Halnon, Nancy; Kochilas, Lazaros; Rossano, Joseph; Bonnet, Damien; Bush, Christopher; Zhao, Ziqiang; Kantor, Paul; Burch, Michael; Chen, Fabian

    2017-11-01

    Sacubitril/valsartan (LCZ696) is an angiotensin receptor neprilysin inhibitor approved for the treatment of adult heart failure (HF); however, the benefit of sacubitril/valsartan in pediatric HF patients is unknown. This global multi-center study will use an adaptive, seamless two-part design. Part 1 will assess the pharmacokinetics/pharmacodynamics of single ascending doses of sacubitril/valsartan in pediatric (1 month to sacubitril/valsartan or enalapril. A novel global rank primary endpoint derived by ranking patients (worst-to-best outcome) based on clinical events such as death, initiation of mechanical life support, listing for urgent heart transplant, worsening HF, measures of functional capacity (NYHA/Ross scores), and patient-reported HF symptoms will be used to assess efficacy. The PANORAMA-HF study, which will be the largest prospective pediatric HF trial conducted to date and the first to use a global rank primary endpoint, will determine whether sacubitril/valsartan is superior to enalapril for treatment of pediatric HF patients with reduced systemic left ventricular systolic function. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Sample Preparation and Extraction in Small Sample Volumes Suitable for Pediatric Clinical Studies: Challenges, Advances, and Experiences of a Bioanalytical HPLC-MS/MS Method Validation Using Enalapril and Enalaprilat

    Directory of Open Access Journals (Sweden)

    Bjoern B. Burckhardt

    2015-01-01

    Full Text Available In USA and Europe, medicines agencies force the development of child-appropriate medications and intend to increase the availability of information on the pediatric use. This asks for bioanalytical methods which are able to deal with small sample volumes as the trial-related blood lost is very restricted in children. Broadly used HPLC-MS/MS, being able to cope with small volumes, is susceptible to matrix effects. The latter restrains the precise drug quantification through, for example, causing signal suppression. Sophisticated sample preparation and purification utilizing solid-phase extraction was applied to reduce and control matrix effects. A scale-up from vacuum manifold to positive pressure manifold was conducted to meet the demands of high-throughput within a clinical setting. Faced challenges, advances, and experiences in solid-phase extraction are exemplarily presented on the basis of the bioanalytical method development and validation of low-volume samples (50 μL serum. Enalapril, enalaprilat, and benazepril served as sample drugs. The applied sample preparation and extraction successfully reduced the absolute and relative matrix effect to comply with international guidelines. Recoveries ranged from 77 to 104% for enalapril and from 93 to 118% for enalaprilat. The bioanalytical method comprising sample extraction by solid-phase extraction was fully validated according to FDA and EMA bioanalytical guidelines and was used in a Phase I study in 24 volunteers.

  20. Rationale and design of the comParIson Of sacubitril/valsartaN versus Enalapril on Effect on nt-pRo-bnp in patients stabilized from an acute Heart Failure episode (PIONEER-HF) trial.

    Science.gov (United States)

    Velazquez, Eric J; Morrow, David A; DeVore, Adam D; Ambrosy, Andrew P; Duffy, Carol I; McCague, Kevin; Hernandez, Adrian F; Rocha, Ricardo A; Braunwald, Eugene

    2018-04-01

    The objective is to assess the safety, tolerability, and efficacy of sacubitril/valsartan compared with enalapril in patients with heart failure (HF) with a reduced ejection fraction (EF) stabilized during hospitalization for acute decompensated HF. Sacubitril/valsartan, a first-in-class angiotensin receptor-neprilysin inhibitor, improves survival among ambulatory HF patients with a reduced EF. However, there is very limited experience with the in-hospital initiation of sacubitril/valsartan in patients who have been stabilized following hospitalization for acute decompensated HF. PIONEER-HF is a 12-week, prospective, multicenter, double-blind, randomized controlled trial enrolling a planned 882 patients at more than 100 participating sites in the United States. Medically stable patients >18 years of age with an EF 1600 pg/mL or b-type natriuretic peptide >400 pg/mL are eligible for participation no earlier than 24 hours and up to 10 days from initial presentation while still hospitalized. Patients are randomly assigned 1:1 to in-hospital initiation of sacubitril/valsartan titrated to 97/103 mg by mouth twice daily versus enalapril titrated to 10 mg by mouth twice daily for 8 weeks. All patients receive open-label treatment with sacubitril/valsartan for the remaining 4 weeks of the study. The primary efficacy end point is the time-averaged proportional change in amino terminal-pro b-type natriuretic peptide from baseline through weeks 4 and 8. Secondary and exploratory end points include serum and urinary biomarkers as well as clinical outcomes. Safety end points include the incidence of angioedema, hypotension, renal insufficiency, and hyperkalemia. The PIONEER-HF trial will inform clinical practice by providing evidence on the safety, tolerability, and efficacy of in-hospital initiation of sacubitril/valsartan among patients who have been stabilized following an admission for acute decompensated HF with a reduced EF. Copyright © 2018 Elsevier Inc. All rights

  1. Synergistic therapy of enalapril and Cordyceps sinensis in the ...

    African Journals Online (AJOL)

    Yomi

    2012-04-19

    Apr 19, 2012 ... After treatment for six months, SCr and CCr were improved while 24 h. Upro and urinary TGF-ß1 decreased in group A , and SCr improved and 24 h Upro decreased in group C. Patients of group A obtained the highest degree of improvement, and more patients obtained renal improvement and stability than ...

  2. comparison of losartan and enalapril effects on renal function

    African Journals Online (AJOL)

    2014-04-01

    Apr 1, 2014 ... Results: There was a higher risk of doubling of serum creatinine with losartan ( ... In Europe, Japan and the United ... glomerulonephritis and systemic hypertension are ... (an ARB) are commonly used at the renal and diabetic ... ARBs block the angiotensin type 1 receptor (AT1). .... Use of alcohol; n (%). Yes.

  3. Initial effect of enalapril on kidney function in patients with moderate to severe chronic nephropathy

    DEFF Research Database (Denmark)

    Kamper, A L; Thomsen, H S; Nielsen, S L

    1990-01-01

    in their renal function. Thirty-one patients were studied, 26 on chronic antihypertensive treatment with drugs other than ACE inhibitors and 5 untreated normotensive. 51Cr-EDTA plasma clearance and renal technetium-99m dimercaptosuccinic acid (99mTc-DMSA) scintigraphy were made before and 24 h after start...

  4. Feasibility of combined treatment with enalapril and candesartan in advanced chronic kidney disease

    DEFF Research Database (Denmark)

    Frimodt-Møller, Marie; Høj Nielsen, Arne; Strandgaard, Svend

    2010-01-01

    BACKGROUND: Dual blockade of the renin-angiotensin system (RAS) has been claimed to have a specific renal protective effect in chronic kidney disease (CKD). The present short-term study reports on the feasibility of dual blockade in a consecutive group of patients with CKD stage 3-5. METHODS: Forty...

  5. Comparative pharmacokinetics and pharmacodynamics of lisinopril and enalapril, alone and in combination with propranolol

    DEFF Research Database (Denmark)

    Bendtsen, F; Henriksen, Jens Henrik Sahl

    1989-01-01

    ) were 64 +/- 16 ng/ml and 7.5 +/- 1.5 h, respectively. The area under the serum curve (AUC) was 916 +/- 239 h. ng/ml. The Cmax of enalaprilat (89 +/- 34 ng/ml) was greater than that of lisinopril whilst Tmax was shorter (4.3 +/- 1.7 h) and AUC smaller (718 +/- 17 h.ng/ml) (P less than 0.01). Renal...... clearance of drug 48 h post-dosing showed that enalaprilat (164 +/- 38 ml/min) was cleared from plasma significantly more rapidly than lisinopril (82 +/- 16 ml/min) (P less than 0.001). Mean supine blood pressure decreased significantly with all treatments, as did heart rate. No significant changes were...

  6. Losartan versus enalapril on cerebral edema and proteinuria in stroke-prone hypertensive rats

    NARCIS (Netherlands)

    Blezer, E.L.A.; Nicolaij, K.; Koomans, H.A.; Joles, Jaap

    2001-01-01

    Stroke-prone spontaneously hypertensive rats (SHRSP), subjected to high NaCl, show severe hypertension, organ damage, and early death. Preventive treatment with angiotensin II type 1 (AT1) receptor antagonists is known to be effective. Previously, we found that angiotensin converting enzyme (ACE)

  7. Neurohormonal and circulatory effects of short-term treatment with enalapril and quinapril in dogs with asymptomatic mitral regurgitation

    DEFF Research Database (Denmark)

    Moesgaard, Sophia Gry; Pedersen, Lotte Gam; Teerlink, Tom

    2005-01-01

    metabolites nitrate and nitrite in plasma (NOx)). Activation of angiotensin-converting enzyme (ACE) in heart failure might lead to reduced endothelial NO release. Accordingly, ACE inhibition has been shown to improve endothelial function in humans, most likely by increasing the availability of NO...

  8. Ketorolac

    Science.gov (United States)

    ... taking angiotensin-converting enzyme (ACE) inhibitors such as benazepril (Lotensin, in Lotrel), captopril, enalapril (Vasotec, in Vaseretic), ... antidepressants; angiotensin-converting enzyme (ACE) inhibitors such as benazepril (Lotensin, in Lotrel), captopril, enalapril (Vasotec, in Vaseretic), ...

  9. An Economic Evaluation of Sacubitril/Valsartan for Heart Failure Patients in the Netherlands

    NARCIS (Netherlands)

    van der Pol, Simon; Degener, Fabian; Postma, Maarten J.; Vemer, Pepijn

    Background: In September 2014, the PARADIGM-HF trial showed the heart failure drug combination sacubitril/valsartan to be superior to enalapril for patients with a reduced ejection fraction. Objectives: To determine the incremental cost-effectiveness of sacubitril/valsartan compared with enalapril

  10. Direct renin inhibition in addition to or as an alternative to angiotensin converting enzyme inhibition in patients with chronic systolic heart failure: rationale and design of the Aliskiren Trial to Minimize OutcomeS in Patients with HEart failuRE (ATMOSPHERE) study

    DEFF Research Database (Denmark)

    Krum, Henry; Massie, Barry; Abraham, William T

    2011-01-01

    AIMS: The renin-angiotensin-aldosterone system (RAAS) represents a key therapeutic target in heart failure (HF) management. However, conventional agents that block this system induce a reflex increase in plasma renin activity (PRA), which may lead to RAAS 'escape'. Direct renin inhibitors (DRIs......S for Patients with HEart failuRE (ATMOSPHERE) study is to evaluate the effect of both aliskiren and enalapril monotherapy and aliskiren/enalapril combination therapy on cardiovascular death and HF hospitalization in patients with chronic systolic HF, NYHA functional class II-IV symptoms, and elevated plasma...... levels of BNP. Methods Patients tolerant to at least 10 mg or equivalent of enalapril will undergo an open-label run-in period where they receive enalapril then aliskiren. Approximately 7000 patients tolerating this run-in period will then be randomized 1:1:1 to aliskiren monotherapy, enalapril...

  11. Direct renin inhibition in addition to or as an alternative to angiotensin converting enzyme inhibition in patients with chronic systolic heart failure: rationale and design of the Aliskiren Trial to Minimize OutcomeS in Patients with HEart failuRE (ATMOSPHERE) study

    DEFF Research Database (Denmark)

    Krum, Henry; Massie, Barry; Abraham, William T

    2011-01-01

    S for Patients with HEart failuRE (ATMOSPHERE) study is to evaluate the effect of both aliskiren and enalapril monotherapy and aliskiren/enalapril combination therapy on cardiovascular death and HF hospitalization in patients with chronic systolic HF, NYHA functional class II-IV symptoms, and elevated plasma......-inferior to enalapril monotherapy on this endpoint. Perspective The ATMOSPHERE study will definitively determine the role of a DRI strategy additional to or as an alternative to conventional RAAS blockade in patients with chronic systolic HF....

  12. High serum enalaprilat in chronic renal failure

    DEFF Research Database (Denmark)

    Elung-Jensen, T; Heisterberg, J; Kamper, A L

    2001-01-01

    renal failure. METHODS: Fifty nine out-patients with plasma creatinine >150 micromol/L and chronic antihypertensive treatment with enalapril were investigated, in a cross-sectional design. RESULTS: Median glomerular filtration rate (GFR) was 23(range 6-60) ml/minute/1.73 m2. The daily dose of enalapril......-68) ml/minute and correlated linearly with GFR (r=0.86, p=0.003). Intra-subject day-to-day variation in trough concentrations was 19.7%. CONCLUSION: Patients with chronic renal failure given small or moderately high doses of enalapril may thus have markedly elevated levels of serum enalaprilat. Whether...

  13. Irreversibel nyreinsufficiens under behandling med angiotensin I konverterende enzymhaemmer ved bilateral nyrearteriestenose

    DEFF Research Database (Denmark)

    Kamper, A L

    1989-01-01

    A case of irreversible renal failure during treatment with enalapril in bilateral renal artery stenosis is described. In the use of converting enzyme inhibitors, caution and monitoring of renal function during treatment is advised....

  14. Diabetic encephalopathy: a cerebrovascular disorder?

    NARCIS (Netherlands)

    Manschot, S.M.

    2006-01-01

    Animal study: The aim was to investigate the role of vascular disturbances in the development of experimental diabetic encephalopathy. We describe the effects of treatment with the Angiotensin Converting Enzyme(ACE)-inhibitor enalapril (treatment aimed at the

  15. Medications and Supplements (Other Than Steroids)

    Science.gov (United States)

    ... people taking this drug. Cardiac Medications Aniotensin-Converting Enzyme (ACE) Inhibitors (i.e. Lisinopril, Captopril, Enalapril) These ... Care About PPMD ❯ Mission & Impact Staff & Board News History Finance & Operations Partners Media Contact us Get Involved ❯ ...

  16. Drugs for the paediatric heart

    African Journals Online (AJOL)

    Head, Paediatric Cardiology Service of the Western Cape, Department of Paediatrics and Child Health, ... His interests also include the care of complex patients ... The pharmacy only has enalapril available – can you substitute this drug for the ...

  17. [The application of combined physiotherapeutic methods for the complex treatment of patients with dyscirculatory encephalopathy].

    Science.gov (United States)

    Shiman, A G; Klocheva, E G; Kaiumov, S F; Shoferova, S D; Zhukova, M V

    2012-01-01

    This article reports the results of applying basic pharmacotherapy (enalapril, cytoflavin) and its combination with physical factors (transcranial electrostimulation, combined application oftranscranial electrostimulation and low-frequency magnetic therapy) in the complex treatment of patients with stage I-II dyscirculatory encephalopathy. The study has demonstrated that the combined treatment with cytoflavin, enalapril, transcranial electrostimulation and low-frequency magnetic therapy produced the most pronounced therapeutic effect (82.5%), as confirmed by positive dynamics of clinical and functional parameters.

  18. Eritrocitosis post trasplante renal y su tratamiento farmacológico: inhibidores de la enzima convertidora de angiotensina versus bloqueadores de los receptores de angiotensina en un caso

    OpenAIRE

    Duclos H,Jaime

    2000-01-01

    A 35 years old male is presented. Eight months after receiving a renal allograft his hypertension worsened and his packed red cell volume raised to 53.7%. Enalapril was started and a 500 ml phlebotomy was performed. In three occasions packed red cell volumes decreased excessively and enalapril was discontinued. Finally, the drug was replaced with losartan, normalizing blood pressure values and stabilizing packed red cell volumes. This case illustrates the different reductions in packed red ce...

  19. Inhibition of angiotensin-converting enzyme increases oestradiol production in ewes submitted to oestrous synchronization protocol.

    Science.gov (United States)

    Costa, A s; Junior, A S; Viana, G E N; Muratori, M C S; Reis, A M; Costa, A P R

    2014-10-01

    This study aimed at evaluating the effects of angiotensin-converting enzyme inhibitor (enalapril) and angiotensin II antagonist (valsartan) on the oestradiol and progesterone production in ewes submitted to oestrous synchronization protocol. The animals were weighed and randomly divided into three groups (n = 7). A pre-experiment conducted to verify the effectiveness and toxicity of enalapril (0.5 mg/kg LW) and valsartan (2.2 mg/kg LW) showed that, in the doses used, these drugs were effective in reducing blood pressure without producing toxic effects. In the experiment, all animals were subjected to oestrous synchronization protocol during 12 days. On D10, D11 and D12, animals received saline, enalapril or valsartan (same doses of the pre-experiment), according to the group randomly divided. The hormonal analysis showed an increase in oestradiol on the last day of the protocol (D12) in animals that received enalapril (p progesterone in any of the treatments. It is concluded that valsartan and enalapril are safe and effective subcutaneously for use in sheep and that the angiotensin-converting enzyme (ACE) inhibition with enalapril leads to an increase in oestradiol production near ovulation without changing the concentration of progesterone. This shows that ACE inhibition may be a useful tool in reproductive biotechnologies involving induction and synchronization of oestrus and ovulation in sheep. © 2014 Blackwell Verlag GmbH.

  20. The effects of anti-hypertensives and type 2 diabetes on salivary flow and total antioxidant capacity.

    Science.gov (United States)

    Djukić, L J; Roganović, J; Brajović, M D; Bokonjić, D; Stojić, D

    2015-07-01

    The present cross-sectional study aimed to determine the effect of first-line anti-hypertensive drugs (enalapril, metoprolol, and combinations of enalapril with metoprolol and/or hydrochlorothiazide) on salivary gland function and salivary total antioxidant capacity (TAC) in hypertensive patients with/without diabetes mellitus (DM) type 2. Salivary gland function was measured as xerostomia (interview) and unstimulated whole saliva flow rate (UWSFR) in 447 subjects (387 hypertensive and 60 healthy). Salivary TAC was evaluated by spectrophotometric assay. Enalapril is not xerogenic, while metoprolol and drug combinations are. In the presence of DM type 2, all drugs, except metoprolol, had pronounced xerogenic effect. Binary logistic regression analysis found enalapril to be significantly associated with decreased risk of xerogenic effect development, while DM type 2 with increased risk. In the presence of enalapril in hypertensive patients with/without DM type 2 salivary TAC was similar to that in healthy subjects, while for metoprolol was reduced. Enalapril is not xerogenic but is antioxidant, which moderately reduces the risk of xerogenic effect development even in the presence of DM type 2. However, metoprolol and drug combinations exhibit xerogenic effect. In DM type 2, xerogenic effect of all drugs was pronounced except of metoprolol. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. [Changes of twenty-four-hour profile blood pressure and its correction of patients with arterial hypertension on the background of combined antihypertensive therapy application].

    Science.gov (United States)

    Solomennchuk, T M; Slaba, N A; Prots'ko, V V; Bedzaĭ, A O

    2014-01-01

    The aim of this research was the study of efficiency and endurance antihypertensive therapy on the basis of fixed combination of enalapril and hydrochlorothiazide (HCTZ) and enalapril and HCTZ in combination with amlodipine according to the twenty-four-hour (? day-and-night) monitoring of blood pressure (? 24H BPM) of patients with arterial hypertension (AH) 2-3 severity. The study included 33 patients with 2-3 grade of hypertension (average age--54,40 ± 3.45 years). All patients performed ? 24H BPM before treatment and after 12 weeks of therapy. The combination of enalapril and HCTZ allowed to achieve target levels of blood pressure in 79% of patients, amlodipine additional purpose--in 86% of patients. We found that this therapy has a corrective effect on daily blood pressure profile, significantly reducing the load pressure and blood pressure variability. During treatment with the combination of enalapril and HCTZ combination of enalapril, HCTZ with amlodipine optimal daily profile of blood pressure after 12 weeks of reaching respectively 63.1% and 71.4% of patients. The treatment with combination of enalapril and HCTZ and adding of amlodipine is characterized by good endurance and high adherence to treatment.

  2. The effects of sacubitril/valsartan on coronary outcomes in PARADIGM-HF.

    Science.gov (United States)

    Mogensen, Ulrik M; Køber, Lars; Kristensen, Søren L; Jhund, Pardeep S; Gong, Jianjian; Lefkowitz, Martin P; Rizkala, Adel R; Rouleau, Jean L; Shi, Victor C; Swedberg, Karl; Zile, Michael R; Solomon, Scott D; Packer, Milton; McMurray, John J V

    2017-06-01

    Angiotensin converting enzyme inhibitors (ACE-I), are beneficial both in heart failure with reduced ejection fraction (HF-REF) and after myocardial infarction (MI). We examined the effects of the angiotensin-receptor neprilysin inhibitor sacubitril/valsartan, compared with the ACE-I enalapril, on coronary outcomes in PARADIGM-HF. We examined the effect of sacubitril/valsartan compared with enalapril on the following outcomes: i) the primary composite endpoint of cardiovascular (CV) death or HF hospitalization, ii) a pre-defined broader composite including, in addition, MI, stroke, and resuscitated sudden death, and iii) a post hoc coronary composite of CV-death, non-fatal MI, angina hospitalization or coronary revascularization. At baseline, of 8399 patients, 3634 (43.3%) had a prior MI and 4796 (57.1%) had a history of any coronary artery disease. Among all patients, compared with enalapril, sacubitril/valsartan reduced the risk of the primary outcome (HR 0.80 [0.73-0.87], Psacubitril/valsartan group, compared with the enalapril group, only CV death was reduced significantly. Compared with enalapril, sacubitril/valsartan reduced the risk of both the primary endpoint and a coronary composite outcome in PARADIGM-HF. Additional studies on the effect of sacubitril/valsartan on atherothrombotic outcomes in high-risk patients are merited. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. The effects of sacubitril/valsartan on coronary outcomes in PARADIGM-HF

    DEFF Research Database (Denmark)

    Mogensen, Ulrik M.; Køber, Lars; Kristensen, Søren L.

    2017-01-01

    Background Angiotensin converting enzyme inhibitors (ACE-I), are beneficial both in heart failure with reduced ejection fraction (HF-REF) and after myocardial infarction (MI). We examined the effects of the angiotensin-receptor neprilysin inhibitor sacubitril/valsartan, compared with the ACE......-I enalapril, on coronary outcomes in PARADIGM-HF. Methods and results We examined the effect of sacubitril/valsartan compared with enalapril on the following outcomes: i) the primary composite endpoint of cardiovascular (CV) death or HF hospitalization, ii) a pre-defined broader composite including...... patients, compared with enalapril, sacubitril/valsartan reduced the risk of the primary outcome (HR 0.80 [0.73–0.87], P 

  4. Renin-angiotensin system blockers protect pancreatic islets against diet-induced obesity and insulin resistance in mice.

    Directory of Open Access Journals (Sweden)

    Eliete Dalla Corte Frantz

    Full Text Available BACKGROUND: The associations between obesity, hypertension and diabetes are well established, and the renin-angiotensin system (RAS may provide a link among them. The effect of RAS inhibition on type 2 diabetes is still unclear; however, RAS seems to play an important role in the regulation of the pancreas and glucose intolerance of mice fed high-fat (HF diet. METHODS: C57BL/6 mice fed a HF diet (8 weeks were treated with aliskiren (50 mg/kg/day, enalapril (30 mg/kg/day or losartan (10 mg/kg/day for 6 weeks, and the protective effects were extensively compared among groups by morphometry, stereological tools, immunostaining, Western blotting and hormonal analysis. RESULTS: All RAS inhibitors significantly attenuated the increased blood pressure in mice fed a HF diet. Treatment with enalapril, but not aliskiren or losartan, significantly attenuated body mass (BM gain, glucose intolerance and insulin resistance, improved the alpha and beta cell mass and prevented the reduction of plasma adiponectin. Furthermore, enalapril treatment improved the protein expression of the pancreatic islet Pdx1, GLUT2, ACE2 and Mas receptors. Losartan treatment showed the greatest AT2R expression. CONCLUSION: Our findings indicate that ACE inhibition with enalapril attenuated several of the deleterious effects of the HF diet. In summary, enalapril appears to be responsible for the normalization of islet morphology and function, of alpha and beta cell mass and of Pdx1 and GLUT2 expression. These protective effects of enalapril were attributed, primarily, to the reduction in body mass gain and food intake and the enhancement of the ACE2/Ang (1-7 /Mas receptor axis and adiponectin levels.

  5. The chronic blockade of angiotensin I-converting enzyme eliminates the sex differences of serum cytokine levels of spontaneously hypertensive rats

    Energy Technology Data Exchange (ETDEWEB)

    Dalpiaz, P.L.M.; Lamas, A.Z.; Caliman, I.F. [Departamento de Ciências Fisiológicas, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Medeiros, A.R.S. [Ciências Biológicas e da Saúde, Instituto Federal do Espírito Santo, Vitória, ES (Brazil); Abreu, G.R.; Moysés, M.R. [Departamento de Ciências Fisiológicas, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Andrade, T.U. [Departamento de Farmácia, Centro Universitário de Vila Velha, Vila Velha, ES (Brazil); Alves, M.F.; Carmona, A.K. [Departamento de Biofísica, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Bissoli, N.S. [Departamento de Ciências Fisiológicas, Universidade Federal do Espírito Santo, Vitória, ES (Brazil)

    2013-02-01

    Sex hormones modulate the action of both cytokines and the renin-angiotensin system. However, the effects of angiotensin I-converting enzyme (ACE) on the proinflammatory and anti-inflammatory cytokine levels in male and female spontaneously hypertensive rats (SHR) are unclear. We determined the relationship between ACE activity, cytokine levels and sex differences in SHR. Female (F) and male (M) SHR were divided into 4 experimental groups each (n = 7): sham + vehicle (SV), sham + enalapril (10 mg/kg body weight by gavage), castrated + vehicle, and castrated + enalapril. Treatment began 21 days after castration and continued for 30 days. Serum cytokine levels (ELISA) and ACE activity (fluorimetry) were measured. Male rats exhibited a higher serum ACE activity than female rats. Castration reduced serum ACE in males but did not affect it in females. Enalapril reduced serum ACE in all groups. IL-10 (FSV = 16.4 ± 1.1 pg/mL; MSV = 12.8 ± 1.2 pg/mL), TNF-α (FSV = 16.6 ± 1.2 pg/mL; MSV = 12.8 ± 1 pg/mL) and IL-6 (FSV = 10.3 ± 0.2 pg/mL; MSV = 7.2 ± 0.2 pg/mL) levels were higher in females than in males. Ovariectomy reduced all cytokine levels and orchiectomy reduced IL-6 but increased IL-10 concentrations in males. Castration eliminated the differences in all inflammatory cytokine levels (IL-6 and TNF-α) between males and females. Enalapril increased IL-10 in all groups and reduced IL-6 in SV rats. In conclusion, serum ACE inhibition by enalapril eliminated the sexual dimorphisms of cytokine levels in SV animals, which suggests that enalapril exerts systemic anti-inflammatory and anti-hypertensive effects.

  6. Combination of ACE inhibitor with nicorandil provides further protection in chronic kidney disease.

    Science.gov (United States)

    Shiraishi, Takeshi; Tamura, Yoshifuru; Taniguchi, Kei; Higaki, Masato; Ueda, Shuko; Shima, Tomoko; Nagura, Michito; Nakagawa, Takahiko; Johnson, Richard J; Uchida, Shunya

    2014-12-15

    An inhibition in the renin-angiotensin system (RAS) is one of the most widely used therapies to treat chronic kidney disease. However, its effect is occasionally not sufficient and additional treatments may be required. Recently, we reported that nicorandil exhibited renoprotective effects in a mouse model of diabetic nephropathy. Here we examined if nicorandil can provide an additive protection on enalapril in chronic kidney disease. Single treatment with either enalapril or nicorandil significantly ameliorated glomerular and tubulointerstitial injury in the rat remnant kidney while the combination of these two compounds provided additive effects. In addition, an increase in oxidative stress in remnant kidney was also blocked by either enalapril or nicorandil while the combination of the drugs was more potent. A mechanism was likely due for nicorandil to preventing manganase superoxide dismutase (MnSOD) and sirtuin (Sirt)3 from being reduced in injured kidneys. A study with cultured podocytes indicated that the antioxidative effect could be mediated through sulfonylurea receptor (SUR) in the mitochondrial KATP channel since blocking SUR with glibenclamide reduced MnSOD and Sirt3 expression in podocytes. In conclusion, nicorandil may synergize with enalapril to provide superior protection in chronic kidney disease. Copyright © 2014 the American Physiological Society.

  7. Systolic blood pressure, cardiovascular outcomes and efficacy and safety of sacubitril/valsartan (LCZ696) in patients with chronic heart failure and reduced ejection fraction: results from PARADIGM-HF.

    Science.gov (United States)

    Böhm, Michael; Young, Robin; Jhund, Pardeep S; Solomon, Scott D; Gong, Jianjian; Lefkowitz, Martin P; Rizkala, Adel R; Rouleau, Jean L; Shi, Victor C; Swedberg, Karl; Zile, Michael R; Packer, Milton; McMurray, John J V

    2017-04-14

    Compared to heart failure patients with higher systolic blood pressure (SBP), those with lower SBP have a worse prognosis. To make matters worse, the latter patients often do not receive treatment with life-saving therapies that might lower blood pressure further. We examined the association between SBP and outcomes in the Prospective Comparison of angiotensin receptor-neprilysin inhibitor (ARNI) with an angiotensin-converting enzyme (ACE) inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure trial (PARADIGM-HF), as well as the effect of sacubitril/valsartan, compared with enalapril, according to baseline SBP. We analysed the effect of treatment on SBP and on the primary composite outcome (cardiovascular death or heart failure hospitalization), its components and all-cause death. We examined baseline SBP as a categorical (sacubitril/valsartan over enalapril was consistent across all baseline SBP categories for all outcomes. For example, the sacubitril/valsartan versus enalapril hazard ratio for the primary endpoint was 0.88 (95%CI 0.74-1.06) in patients with a baseline SBP sacubitril/valsartan and had the same relative benefit over enalapril as patients with higher baseline SBP. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For Permissions, please email: journals.permissions@oup.com.

  8. Effect of Dual Blockade of Renin-Angiotensin Aldosterone System ...

    African Journals Online (AJOL)

    Purpose: To investigate the dual effect of angiotensin blockade by irbesartan and enalapril on proteinuria in diabetic patients with azotemia. Methods: Patients with diabetes of > 5 years duration, proteinuria at a nephrotic level and serum creatinine > 1.5 mg/dL were enrolled in the study. Forty-five enrolled patients were ...

  9. A comparative study of neuroprotective effect of angiotensin converting enzyme inhibitors against scopolamine-induced memory impairments in rats

    Directory of Open Access Journals (Sweden)

    Talha Jawaid

    2015-01-01

    Full Text Available The comparative study of neuroprotective effect of angiotensin converting enzyme inhibitors against scopolamine-induced neuroinflammation in albino Wistar rats was studied. Male albino rats were administered with scopolamine to induce memory impairment. The standard nootropic agent, piracetam (200 mg/kg b.w., [i.p.], perindopril (0.1 mg/kg b.w., [i.p.], enalapril (0.1 mg/kg b.w., [i.p.], and ramipril (0.1 mg/kg b.w., [i.p.] were administered in different group of animals for 5 days. On 5 th day, scopolamine (1 mg/kg b.w., i.p. was administered after 60 min of the last dose of test drug. Memory function was evaluated in Morris water maze (MWM test and pole climbing test (PCT. Biochemical estimations like glutathione (GSH, malondialdehyde (MDA, and acetylcholinesterase activity in the brain were estimated after completion of behavior study. All three test groups shows improvement in learning and memory in comparison to control group. Perindopril treated group showed a more effective significant decrease in escape latency time and transfer latency time compared to enalapril and ramipril treated group on day 4 in MWM test and PCT, respectively. Perindopril shows a significant reduction in MDA level and acetylcholinesterase activity and a significant rise in GSH level compared to enalapril and ramipril. The finding of this study indicates that Perindopril is more effective in memory retention compared to enalapril and ramipril.

  10. Author Details

    African Journals Online (AJOL)

    Ippolito, P.D.. Vol 6, No 2 (2016) - Articles The effect of renal diet in association with enalapril or benazepril on proteinuria in dogs with proteinuric chronic kidney disease. Abstract PDF. ISSN: 2218-6050. AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about ...

  11. Nigella sativa provides protection against metabolic syndrome ...

    African Journals Online (AJOL)

    After final diagnosis and considering inclusion and exclusion criteria, one hundred and fifty nine patients were enrolled in this study. Patients were divided into two groups. In Group I (standard group), patients were advised to take simvastatin 10 mg once a day, metformin 500 mg twice a day, Enalapril 10 mg once a day, ...

  12. THE MECHANISM AND DIAGNOSTIC-VALUE OF ANGIOTENSIN-I CONVERTING ENZYME-INHIBITION RENOGRAPHY

    NARCIS (Netherlands)

    DEZEEUW, D; JONKER, GJ; HOVINGA, TKK; BEEKHUIS, H; PIERS, DA; HUISMAN, RM; DEJONG, PE

    1991-01-01

    The effect of angiotensin converting enzyme (ACE) inhibition on the sensitivity of radionuclide renography in the diagnosis of a unilateral renal artery stenosis was tested both in a conscious dog model and in the human situation. ACE inhibition (10 mg enalaprilic acid, intravenously) markedly

  13. Early pharmacological inhibition of angiotensin-I converting enzyme activity induces obesity in adulthood

    Directory of Open Access Journals (Sweden)

    Kely ede Picoli Souza

    2015-04-01

    Full Text Available We have investigated early programming of body mass in order to understand the multifactorial etiology of obesity. Considering that the renin-angiotensin system is expressed and functional in the white adipose tissue (WAT and modulates its development, we reasoned whether early transitory inhibition of angiotensin-I converting enzyme activity after birth could modify late body mass development. Therefore, newborn Wistar rats were treated with enalapril (10 mg/kg of body mass or saline, starting at the first day of life until the age of 16 days. Between days 90th and 180th, a group of these animals received high fat diet (HFD. Molecular, biochemical, histological and physiological data were collected. Enalapril treated animals presented hyperphagia, overweight and increased serum level of triglycerides, total cholesterol and leptin, in adult life. Body composition analyses revealed higher fat mass with increased adipocyte size in these animals. Molecular analyses revealed that enalapril treatment increases neuropeptide Y (NPY and cocaine- and amphetamine-regulated transcript (CART gene expression in hypothalamus, fatty acid synthase (FAS and hormone-sensitive lipase (HSL gene expression in retroperitoneal WAT and decreases peroxixome proliferators-activated receptor (PPAR γ, PPARα, uncoupling protein (UCP 2 and UCP3 gene expression in WAT. The results of the current study indicate that enalapril administration during early postnatal development increases body mass, adiposity and serum lipids in adulthood associated with enhanced food intake and decreased metabolic activity in WAT, predisposing to obesity in adulthood.

  14. MTHFR C677T and MTR A2756G polymorphisms and the homocysteine lowering efficacy of different doses of folic acid in hypertensive Chinese adults

    Directory of Open Access Journals (Sweden)

    Qin Xianhui

    2012-01-01

    Full Text Available Abstract Background This study aimed to investigate if the homocysteine-lowering efficacy of two commonly used physiological doses (0.4 mg/d and 0.8 mg/d of folic acid (FA can be modified by individual methylenetetrahydrofolate reductase (MTHFR C677T and/or methionine synthase (MTR A2756G polymorphisms in hypertensive Chinese adults. Methods A total of 480 subjects with mild or moderate essential hypertension were randomly assigned to three treatment groups: 1 enalapril only (10 mg, control group; 2 enalapril-FA tablet [10:0.4 mg (10 mg enalapril combined with 0.4 mg of FA, low FA group]; and 3 enalapril-FA tablet (10:0.8 mg, high FA group, once daily for 8 weeks. Results After 4 or 8 weeks of treatment, homocysteine concentrations were reduced across all genotypes and FA dosage groups, except in subjects with MTR 2756AG /GG genotype in the low FA group at week 4. However, compared to subjects with MTHFR 677CC genotype, homocysteine concentrations remained higher in subjects with CT or TT genotype in the low FA group (P P P = 0.005, but not in the low FA group (CC 9.9% vs. TT 11.2%, P = 0.989. Conclusions This study demonstrated that MTHFR C677T polymorphism can not only affect homocysteine concentration at baseline and post-FA treatment, but also can modify therapeutic responses to various dosages of FA supplementation.

  15. Influence of Sacubitril/Valsartan (LCZ696) on 30-Day Readmission After Heart Failure Hospitalization.

    Science.gov (United States)

    Desai, Akshay S; Claggett, Brian L; Packer, Milton; Zile, Michael R; Rouleau, Jean L; Swedberg, Karl; Shi, Victor; Lefkowitz, Martin; Starling, Randall; Teerlink, John; McMurray, John J V; Solomon, Scott D

    2016-07-19

    Patients with heart failure (HF) are at high risk for hospital readmission in the first 30 days following HF hospitalization. This study sought to determine if treatment with sacubitril/valsartan (LCZ696) reduces rates of hospital readmission at 30-days following HF hospitalization compared with enalapril. We assessed the risk of 30-day readmission for any cause following investigator-reported hospitalizations for HF in the PARADIGM-HF trial, which randomized 8,399 participants with HF and reduced ejection fraction to treatment with LCZ696 or enalapril. Accounting for multiple hospitalizations per patient, there were 2,383 investigator-reported HF hospitalizations, of which 1,076 (45.2%) occurred in subjects assigned to LCZ696 and 1,307 (54.8%) occurred in subjects assigned to enalapril. Rates of readmission for any cause at 30 days were 17.8% in LCZ696-assigned subjects and 21.0% in enalapril-assigned subjects (odds ratio: 0.74; 95% confidence interval: 0.56 to 0.97; p = 0.031). Rates of readmission for HF at 30-days were also lower in subjects assigned to LCZ696 (9.7% vs. 13.4%; odds ratio: 0.62; 95% confidence interval: 0.45 to 0.87; p = 0.006). The reduction in both all-cause and HF readmissions with LCZ696 was maintained when the time window from discharge was extended to 60 days and in sensitivity analyses restricted to adjudicated HF hospitalizations. Compared with enalapril, treatment with LCZ696 reduces 30-day readmissions for any cause following discharge from HF hospitalization. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  16. PHARMACOECONOMIC ANALYSIS OF ANTIHYPERTENSIVE DRUG COMBINATIONS USE

    Directory of Open Access Journals (Sweden)

    E. I. Tarlovskaya

    2015-09-01

    Full Text Available Aim. To pursue pharmacoeconomic analysis of two drug combinations of ACE inhibitor (enalapril and diuretic.Material and methods. Patients with arterial hypertension degree 2 and diabetes mellitus type 2 without ischemic heart disease (n=56 were included into the study. Blood pressure (BP dynamics and cost/effectiveness ratio were evaluated.Results. In group A (fixed combination of original enalapril/hydrochlorothiazide 61% of patients achieved target BP level with initial dose, and the rest 39% of patients – with double dose. In group B (non-fixed combination of generic enalapril/indapamide 60% of patients achieved the target BP with initial dose of drugs, 33% - with double dose of ACE inhibitor, and 7% - with additional amlodipine administration. In patients of group A systolic BP (SBP reduction was 45.82±1.23 mm Hg by the 12th week vs. 40.0±0.81 mm Hg in patients of group B; diastolic BP (DBP reduction was 22.47±1.05 mm Hg and 18.76±0.70 mm Hg, respectively, by the 12th week of treatment. In the first month of treatment costs of target BP achievement was 298.62 rubles per patient in group A, and 299.50 rubles – in group B; by the 12th week of treatment – 629.45 and 631.22 rubles, respectively. Costs of SBP and DBP reduction by 1 mm Hg during 12 weeks of therapy were 13 and 27 rubles per patient, respectively, in group A, and 16 and 34 rubles per patient, respectively, in group B.Conclusion. The original fixed combination (enalapril+hydrochlorothiazide proved to be more clinically effective and more cost effective in the treatment of hypertensive patients in comparison with the non-fixed combination of generic drugs (enalapril+indapamide.

  17. Losartan Treatment Protects Retinal Ganglion Cells and Alters Scleral Remodeling in Experimental Glaucoma.

    Directory of Open Access Journals (Sweden)

    Harry A Quigley

    Full Text Available To determine if oral losartan treatment decreases the retinal ganglion cell (RGC death caused by experimental intraocular pressure (IOP elevation in mice.We produced IOP increase in CD1 mice and performed unilateral optic nerve crush. Mice received oral losartan, spironolactone, enalapril, or no drug to test effects of inhibiting angiotensin receptors. IOP was monitored by Tonolab, and blood pressure was monitored by tail cuff device. RGC loss was measured in masked axon counts and RGC bodies by β-tubulin labeling. Scleral changes that could modulate RGC injury were measured including axial length, scleral thickness, and retinal layer thicknesses, pressure-strain behavior in inflation testing, and study of angiotensin receptors and pathways by reverse transcription polymerase chain reaction, Western blot, and immunohistochemistry.Losartan treatment prevented significant RGC loss (median loss = 2.5%, p = 0.13, while median loss with water, spironolactone, and enalapril treatments were 26%, 28% and 43%; p < 0.0001. The lower RGC loss with losartan was significantly less than the loss with spironolactone or enalapril (regression model p = 0.001; drug treatment group term p = 0.01. Both losartan and enalapril significantly lowered blood pressure (p< 0.001, but losartan was protective, while enalapril led to worse than water-treated RGC loss. RGC loss after crush injury was unaffected by losartan treatment (difference from control p = 0.9. Survival of RGC in cell culture was not prolonged by sartan treatment. Axonal transport blockade after 3 day IOP elevations was less in losartan-treated than in control glaucoma eyes (p = 0.007. Losartan inhibited effects of glaucoma, including reduction in extracellular signal-related kinase activity and modification of glaucoma-related changes in scleral thickness and creep under controlled IOP.The neuroprotective effect of losartan in mouse glaucoma is associated with adaptive changes in the sclera expressed at

  18. Plasma lipid oxidation predicts atherosclerotic status better than cholesterol in diabetic apolipoprotein E deficient mice

    DEFF Research Database (Denmark)

    Petersen, Karen Ekkelund; Lykkesfeldt, Jens; Raun, Kirsten

    2017-01-01

    Increased levels of oxidative stress have been suggested to play a detrimental role in the development of diabetes-related vascular complications. Here, we investigated whether the concentration of malondialdehyde, a marker of lipid oxidation correlated to the degree of aortic plaque lesions...... in a proatherogenic diabetic mouse model. Three groups of apolipoprotein E knockout mice were studied for 20 weeks, a control, a streptozotocin-induced diabetic, and a diabetic enalapril-treated group. Enalapril was hypothesized to lower oxidative stress level and thus the plaque burden. Both diabetic groups were...... significantly different from the control group as they had higher blood glucose, HbA1c, total cholesterol, low-density lipoprotein, very low-density lipoprotein, together with a lower high-density lipoprotein concentration and body weight. Animals in the diabetic group had significantly higher plaque area...

  19. REDUCTION OF CUMULATIVE CARDIOVASCULAR RISK IN PATIENTS WITH ARTERIAL HYPERTENSION: THE ROLE OF ANGIOTENSIN CONVERTING ENZYME INHIBITORS ACCORDING TO THE NEW EUROPEAN RECOMMENDATIONS

    Directory of Open Access Journals (Sweden)

    M. N. Mamedov

    2015-12-01

    Full Text Available Conception of total cardio-vascular risk plays important role in defining tactics of arterial hypertension therapy according to the new European recommendations. Choice of antihypertensive therapy is based on meta-analysis of large clinical studies with hard end points. It is recommended to use five classes of antihypertensive drugs in mono- and combined therapy. Angiotensin converting enzyme (ACE inhibitors keep important place in the therapy of arterial hypertension accompanying with risk factors and associated diseases. Enalapril is one of the widely used ACE inhibitors, its efficiency was proved in prospective clinical studies. In high risk patients monotherapy with Enam (enalapril, Dr. Reddy’s decreases blood pressure and leads to positive metabolic changes. This results in significant risk reduction of cardio-vascular complications.

  20. REDUCTION OF CUMULATIVE CARDIOVASCULAR RISK IN PATIENTS WITH ARTERIAL HYPERTENSION: THE ROLE OF ANGIOTENSIN CONVERTING ENZYME INHIBITORS ACCORDING TO THE NEW EUROPEAN RECOMMENDATIONS

    Directory of Open Access Journals (Sweden)

    M. N. Mamedov

    2007-01-01

    Full Text Available Conception of total cardio-vascular risk plays important role in defining tactics of arterial hypertension therapy according to the new European recommendations. Choice of antihypertensive therapy is based on meta-analysis of large clinical studies with hard end points. It is recommended to use five classes of antihypertensive drugs in mono- and combined therapy. Angiotensin converting enzyme (ACE inhibitors keep important place in the therapy of arterial hypertension accompanying with risk factors and associated diseases. Enalapril is one of the widely used ACE inhibitors, its efficiency was proved in prospective clinical studies. In high risk patients monotherapy with Enam (enalapril, Dr. Reddy’s decreases blood pressure and leads to positive metabolic changes. This results in significant risk reduction of cardio-vascular complications.

  1. Dementia-related adverse events in PARADIGM-HF and other trials in heart failure with reduced ejection fraction

    DEFF Research Database (Denmark)

    Cannon, Jane A.; Shen, Li; Jhund, Pardeep S.

    2017-01-01

    Aims: Inhibition of neprilysin, an enzyme degrading natriuretic and other vasoactive peptides, is beneficial in heart failure with reduced ejection fraction (HFrEF), as shown in PARADIGM-HF which compared the angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril/valsartan with enalapril....... As neprilysin is also one of many enzymes clearing amyloid-β peptides from the brain, there is a theoretical concern about the long-term effects of sacubitril/valsartan on cognition. Therefore, we have examined dementia-related adverse effects (AEs) in PARADIGM-HF and placed these findings in the context...... of other recently conducted HFrEF trials. Methods and results: In PARADIGM-HF, patients with symptomatic HFrEF were randomized to sacubitril/valsartan 97/103 mg b.i.d. or enalapril 10 mg b.i.d. in a 1:1 ratio. We systematically searched AE reports, coded using the Medical Dictionary for Regulatory...

  2. PROBLEM OF GENERIC REPLACEMENT: ADVANTAGES AND DISADVANTAGES

    Directory of Open Access Journals (Sweden)

    S. N. Tolpygina

    2009-01-01

    Full Text Available The main differences between original and generic drugs as well as registration criteria for generics are described. Possible reasons of discrepancy in bioequivalence and therapeutic equivalence of original and generic drugs are reviewed. The examples of such a discrepancy as a result of comparative clinical trails (enalapril maleate are discussed. Approaches to planning of comparative trails on drug therapeutic equivalence are presented. 

  3. An evaluation of the effect of atorvastatin on memory and psychomotor functions in hypertensive patients

    Directory of Open Access Journals (Sweden)

    S Prajapati

    2011-01-01

    Full Text Available Background : The effect of statins on memory and psychomotor function has been controversial and needs further evaluation. Aims : To evaluate the effect of atorvastatin on memory and psychomotor functions in hypertensive patients treated with enalapril or amlodipine. Settings and Design : Prospective, comparative, non-randomized, before-after, open-label clinical study conducted at a tertiary care hospital in Western India. Materials and Methods : Memory was evaluated with PGI (Post Graduate Institute, Chandigarh Memory Scale, while psychomotor functions were evaluated with Digit Letter Substitution test, Six Letter Cancellation test, and Finger Tapping test at baseline, 1 week, 1 month, and 3 months of starting atorvastatin in 74 hypertensive patients who were prescribed either enalapril or amlodipine with or without atorvastatin 10 mg/day. Scores obtained in patients receiving enalapril or amlodipine were compared with those receiving these drugs along with atorvastatin. Memory and psychomotor functions of 12 healthy volunteers were also evaluated and compared with those of the patients at respective time periods. Statistical Analysis : Student′s t test, Wilcoxon Signed Rank test, and Mann Whitney U test were used to compare the pre- and post-treatment scores of memory and psychomotor functions in various groups. Statistical significance was considered at P<0.05. Results : A statistically significant improvement in scores of memory and psychomotor functions was observed in both healthy volunteers (P=0.009 and P=0.016 and hypertensive patients (P=0.008 and P=0.031 throughout the study period. Memory and psychomotor function in hypertensive patients remained significantly inferior to those of healthy volunteers (P=0.01 and P=0.018. There was no significant difference in the scores of memory and psychomotor functions between patients receiving atorvastatin and those not receiving this drug. Conclusion : Atorvastatin, at 10 mg/day dose, does not

  4. An Economic Evaluation of Sacubitril/Valsartan for Heart Failure Patients in the Netherlands.

    Science.gov (United States)

    van der Pol, Simon; Degener, Fabian; Postma, Maarten J; Vemer, Pepijn

    2017-03-01

    In September 2014, the PARADIGM-HF trial showed the heart failure drug combination sacubitril/valsartan to be superior to enalapril for patients with a reduced ejection fraction. To determine the incremental cost-effectiveness of sacubitril/valsartan compared with enalapril in the Netherlands using the clinical data from the PARADIGM-HF trial. To compare sacubitril/valsartan and enalapril in a cost-effectiveness study, a Markov model was developed using the effectiveness data from the PARADIGM-HF trial. A health care payer's perspective was applied in the economic evaluation. The developed model was used to evaluate the cost-effectiveness for sacubitril/valsartan at different per diem prices. The base-case analysis showed that sacubitril/valsartan can be cost-effective at maximum daily costs of €5.50 and €14.14 considering willingness-to-pay thresholds of €20,000 and €50,000 per quality-adjusted life-year (QALY), respectively. Sensitivity analysis demonstrated the robustness of the model, identifying only the price of sacubitril/valsartan and the mortality within the sacubitril/valsartan group as significant drivers of the cost-effectiveness ratio. Sacubitril/valsartan was cost-effective at a willingness-to-pay threshold of €20,000 per QALY (€50,000 per QALY) in more than 80% of the replications with certainty at the price point of €3 (€10). Sacubitril/valsartan can be considered a cost-effective treatment at a daily price of €5.25. Unless priced lower than enalapril (sacubitril/valsartan is very unlikely to be cost-saving/dominant. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  5. Sacubitril/valsartan: An important piece in the therapeutic puzzle of heart failure.

    Science.gov (United States)

    Marques da Silva, Pedro; Aguiar, Carlos

    2017-09-01

    Sacubitril/valsartan (LCZ696), a supramolecular sodium salt complex of the neprilysin inhibitor prodrug sacubitril and the angiotensin receptor blocker (ARB) valsartan, was recently approved in the EU and the USA for the treatment of chronic heart failure (HF) with reduced ejection fraction (HFrEF) (NYHA class II-IV). Inhibition of chronically activated neurohormonal pathways (the renin-angiotensin-aldosterone system [RAAS] and sympathetic nervous system [SNS]) is central to the treatment of chronic HFrEF. Furthermore, enhancement of the natriuretic peptide (NP) system, with favorable cardiovascular (CV) and renal effects in HF, is a desirable therapeutic goal to complement RAAS and SNS blockade. Sacubitril/valsartan represents a novel pharmacological approach that acts by enhancing the NP system via inhibition of neprilysin (an enzyme that degrades NPs) and by suppressing the RAAS via AT1 receptor blockade, thereby producing more effective neurohormonal modulation than can be achieved with RAAS inhibition alone. In the large, randomized, double-blind PARADIGM-HF trial, replacement of an angiotensin-converting enzyme inhibitor (ACEI) (enalapril) with sacubitril/valsartan resulted in a significant improvement in morbidity and mortality in patients with HFrEF. Sacubitril/valsartan was superior to enalapril in reducing the risk of CV death or HF hospitalization (composite primary endpoint) and all-cause death, and in limiting progression of HF. Sacubitril/valsartan was generally well tolerated, with a comparable safety profile to enalapril; symptomatic hypotension was more common with sacubitril/valsartan, whereas renal dysfunction, hyperkalemia and cough were less common compared with enalapril. In summary, sacubitril/valsartan is a superior alternative to ACEIs/ARBs in the treatment of HFrEF, a recommendation that is reflected in many HF guidelines. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. Croton schiedeanus Schltd prevents experimental hypertension in rats induced by nitric oxide deficit

    Directory of Open Access Journals (Sweden)

    María Teresa Páez

    2013-12-01

    Full Text Available Croton schiedeanus Schltd (N.V.: "almizclillo" is a plant used in traditional medicine as an antihypertensive in Colombia. It contains flavonoid, diterpenoid and fenilbutanoid metabolites that have vasodilatation effects linked to the NO/cGMP pathway. This work aimed to assess the capacity of a 96% EtOH extract to prevent the hypertension induced by nitric oxide (NO deficiency in rats. The NO synthase inhibitor L-NAME (10 mg/kg/d, i.p was administered during five weeks to three groups of rats (6-7 animals: C. Schiedeanus (200 mg/kg/d, p.o, enalapril (reference, 10 mg/kg/d, p.o and vehicle (control: olive oil 1 ml/kg/d, p.o. In addition, the blank group received only vehicle. The arterial blood pressure (BP and heart rate (HR were measured daily for six weeks. After sacrificing the animals, the aortic rings were isolated, contraction was triggered with phenylephrine (PE 10-6 M and relaxant responses were achieved with cumulative concentrations of acetylcholine (ACh, 10-10 - 10-4 M. L-NAME increased the systolic arterial pressure in the control group, attaining mean values of 131 mm Hg at week 5, whereas the C. schiedeanus, enalapril and blank groups maintained blood pressure under 100 mm Hg. The capacity of PE to contract aortic rings was greater in the C. schiedeanus, enalapril and blank groups than in the control group (2157, 2005, 1910 and 1646 mg, respectively. The pEC50 values for ACh were as follows: C. Schiedeanus (6.89 >enalapril (6.39 > blank (5.68 > control (5.09. These results give support to C. Schiedeanus as a natural antihypertensive source.

  7. Contribution of captopril thiol group to the prevention of spontaneous hypertension

    Czech Academy of Sciences Publication Activity Database

    Pecháňová, Olga

    2007-01-01

    Roč. 56, Suppl.2 (2007), S41-S48 ISSN 0862-8408 Grant - others:VEGA(SK) 2/6148/26; VEGA(SK) 1/3429/06; APPV(SK) 0586-06 Institutional research plan: CEZ:AV0Z50110509 Keywords : captopril and enalapril * thiols * spontaneous hypertension Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.505, year: 2007

  8. Herbal and dietary supplements related to diarrhea and acute kidney injury: a case report.

    Science.gov (United States)

    Wanitsriphinyo, Suphamat; Tangkiatkumjai, Mayuree

    2017-03-01

    Background There is very little evidence relating to the association of herbal medicine with diarrhea and the development of acute kidney injury (AKI). This study reports a case of diarrhea-induced AKI, possibly related to an individual ingesting copious amounts of homemade mixed fruit and herb puree. Case presentation A 45-year-old Thai man with diabetes had diarrhea for 2 days, as a result of taking high amounts of a puree made up of eight mixed fruits and herbs over a 3-day period. He developed dehydration and stage 2 AKI, with a doubling of his serum creatinine. He had been receiving enalapril, as a prescribed medication, over one year. After he stopped taking both the puree and enalapril, and received fluid replacement therapy, within a week his serum creatinine had gradually decreased. The combination of puree, enalapril and AKI may also have induced hyperkalemia in this patient. Furthermore, the patient developed hyperphosphatemia due to his worsening kidney function, exacerbated by regularly taking some dietary supplements containing high levels of phosphate. His serum levels of potassium and phosphate returned to normal within a week, once the patient stopped both the puree and all dietary supplements, and had begun receiving treatment for hyperkalemia. Results The mixed fruit and herb puree taken by this man may have led to his diarrhea due to its effect; particularly if the patient was taking a high concentration of such a drink. Both the puree and enalapril are likely to attenuate the progression of kidney function. The causal relationship between the puree and AKI was probable (5 scores) assessed by the modified Naranjo algorithm. This is the first case report, as far as the authors are aware, relating the drinking of a mixed fruit and herbal puree to diarrhea and AKI in a patient with diabetes. Conclusions This case can alert health care providers to the possibility that herbal medicine could induce diarrhea and develop acute kidney injury.

  9. Relationship between myocardial flow reserve by oxygen-15 water positron emission tomography in the subacute phase of myocardial infarction and left ventricular remodeling in the chronic phase

    International Nuclear Information System (INIS)

    Ohara, Minako; Yukiiri, Kazushi; Masugata, Hisashi

    2008-01-01

    The purposes of this study were to examine the effects of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) on myocardial flow reserve in patients with acute myocardial infarction (AMI) in the subacute phase using oxygen-15 positron emission tomography (PET) and to elucidate the relationship between the myocardial flow reserve and remodeling in the chronic phase. Sixty patients who had been treated with coronary angioplasty within 12 h after the onset of AMI were enrolled. Patients were divided into an enalapril (ACEI) group and a candesartan (ARB) group. The myocardial flow reserve was measured by oxygen-15 water PET in the subacute phase from the 20th to the 30th day after the onset of AMI. Left ventriculography was performed to measure the left ventricular ejection fraction in the chronic phase about 6 months after the onset. Ten patients (33%) in the enalapril group and 4 patients (13%) in the candesartan group stopped taking their respective medications within a few days of starting, because of side effects such as cough or hypotension. Thus, the prevalence of medication intolerance was higher in the enalapril group. The myocardial flow reserve in the subacute phase and the left ventricular ejection fraction in the chronic phase were lower in the enalapril group (2.08±0.30 and 42±6%) than in the candesartan group (2.25±0.20 and 49±5%) (p<0.05). The myocardial flow reserve significantly correlated with the left ventricular ejection fraction in all patients (r=0.45, p<0.01). The myocardial flow reserve assessed by PET in the subacute phase after AMI was found to be related to left ventricular remodeling in the chronic phase. (author)

  10. Sacubitril/Valsartan: A Review in Chronic Heart Failure with Reduced Ejection Fraction.

    Science.gov (United States)

    McCormack, Paul L

    2016-03-01

    Sacubitril/valsartan (Entresto™; LCZ696) is an orally administered supramolecular sodium salt complex of the neprilysin inhibitor prodrug sacubitril and the angiotensin receptor blocker (ARB) valsartan, which was recently approved in the US and the EU for the treatment of chronic heart failure (NYHA class II-IV) with reduced ejection fraction (HFrEF). In the large, randomized, double-blind, PARADIGM-HF trial, sacubitril/valsartan reduced the incidence of death from cardiovascular causes or first hospitalization for worsening heart failure (composite primary endpoint) significantly more than the angiotensin converting enzyme (ACE) inhibitor enalapril. Sacubitril/valsartan was also superior to enalapril in reducing death from any cause and in limiting the progression of heart failure. Sacubitril/valsartan was generally well tolerated, with no increase in life-threatening adverse events. Symptomatic hypotension was significantly more common with sacubitril/valsartan than with enalapril; the incidence of angio-oedema was low. Therefore, sacubitril/valsartan is a more effective replacement for an ACE inhibitor or an ARB in the treatment of HFrEF, and is likely to influence the basic approach to treatment.

  11. Association of insertion/deletion polymorphism of angiotensin-converting enzyme gene among Malay male hypertensive subjects in response to ACE inhibitors.

    Science.gov (United States)

    Heidari, Farzad; Vasudevan, Ramachandran; Mohd Ali, Siti Zubaidah; Ismail, Patimah; Etemad, Ali; Pishva, Seyyed Reza; Othman, Fauziah; Abu Bakar, Suhaili

    2015-12-01

    Several studies show that the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene has been associated with hypertension in various populations. The present study sought to determine the association of the I/D gene polymorphism among Malay male essential hypertensive subjects in response to ACE inhibitors (enalapril and lisinopril). A total of 72 patients with newly diagnosed hypertension and 72 healthy subjects were recruited in this study. Blood pressure was recorded from 0 to 24 weeks of treatment with enalapril or lisinopril. Genotyping of the I/D polymorphism was carried out using a standard PCR method. Statistically significant association of the D allele of the ACE gene was observed between the case and control subjects (p ACE gene. Patients carrying the DD genotype had higher blood pressure-lowering response when treated with ACE inhibitors enalapril or lisinopril than those carrying ID and II genotypes, suggesting that the D allele may be a possible genetic marker for essential hypertension among Malay male subjects. © The Author(s) 2014.

  12. Concurrent determination of Metformin and some ACE inhibitors: Its application to Pharmacokinetics

    Directory of Open Access Journals (Sweden)

    Farhan Ahmed Siddiqui

    2017-05-01

    Full Text Available This study illustrates development and validation of a simple high performance liquid chromatographic method for the simultaneous determination of metformin hydrochloride and angiotensin-converting enzyme inhibitors (captopril, lisinopril, and enalapril in bulk dosage form and their application in pharmacokinetic studies. The quality resolute chromatogram was obtained by using a Purospher® Star RP-18 endcapped (250 × 4.6 mm id column as stationary phase while acetonitrile-water 50:50 (v/v as mobile phase, adjusted to pH 3.0 with phosphoric acid. Effluent was monitored at a flow rate of 1 mL min−1 at room temperature (25 °C, detector was set at 218 nm. The method was validated according to ICH guidelines. The linearity was studied over the concentration range of 10–10,000 ng mL−1 for metformin and 30–10,000 ng mL−1 for captopril, lisinopril, and enalapril, demonstrating good linearity with minimum r = 0.9964, respectively. The developed method was successfully applied to pharmacokinetic studies of metformin, lisinopril, captopril and enalapril.

  13. COMPARATIVE EFFICACY OF LONG-TERM ANTIHYPERTENSIVE MONOTHERAPY IN PATIENTS WITH ARTERIAL HYPERTENSION AT THE WORK PLACE

    Directory of Open Access Journals (Sweden)

    О. N. Antropova

    2008-01-01

    Full Text Available Aim. To compare effects of 12-month monotherapy with nebivolol, enalapril and indapamide on blood pressure (BP, left ventricular hypertrophy and quality of life in the locomotive engineers and their assistants with stress-associated hypertension at the work place (HTwp.Material and methods. 96 locomotive engineers (20- 53 y.o and their assistants with HTwp were observed. The patients were randomized to receive nebivolol (1 group, enalapril (2 group or indapamide (3 group. 24-hour BP monitoring, echocardiography and quality of life interview with SF–36 questionnaire were performed at the start and after 12 months of the treatment.Results. Long-term therapy lead to achievement of target BP level, improved quality of life and reduced in left ventricular hypertrophy in patients with HTwp. Nebivolol reduced systolic “BP load” more significantly than indapamide did, exerted favorable influence on circadian BP rhythm and reduced heart rate. Monotherapy with nebivolol showed benefits in effect on quality of life.Conclusion. Nebivolol has some advantages in comparison with indapamide and enalapril in antihypertensive therapy of patients with stress-associated HT.

  14. Effects of Sacubitril/Valsartan on Physical and Social Activity Limitations in Patients With Heart Failure: A Secondary Analysis of the PARADIGM-HF Trial.

    Science.gov (United States)

    Chandra, Alvin; Lewis, Eldrin F; Claggett, Brian L; Desai, Akshay S; Packer, Milton; Zile, Michael R; Swedberg, Karl; Rouleau, Jean L; Shi, Victor C; Lefkowitz, Martin P; Katova, Tzvetana; McMurray, John J V; Solomon, Scott D

    2018-04-04

    Health-related quality of life (HRQL) of patients with heart failure is markedly reduced compared with that in patients with other chronic diseases, demonstrating substantial limitations in physical and social activities. In the Prospective Comparison of ARNI With an ACE-Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial, sacubitril/valsartan improved overall HRQL compared with enalapril, as determined by the Kansas City Cardiomyopathy Questionnaire (KCCQ). To examine the effects of sacubitril/valsartan on physical and social activities. The PARADIGM-HF trial was a randomized, double-blind, active treatment-controlled clinical trial performed from December 8, 2009, to March 31, 2014, in 8399 patients with New York Heart Association class II to IV disease and a left ventricular ejection fraction of 40% or less at 1043 centers in 38 countries. Data analysis was performed from August 1, 2017, to December 25, 2017. Sacubitril/valsartan, 200 mg twice daily, or enalapril, 10 mg twice daily. Patients completed HRQL assessments using the KCCQ at randomization, 4-month, 8-month, and annual visits. The effect of sacubitril/valsartan on components of the physical and social limitation sections of the KCCQ at 8 months and longitudinally and related biomarkers and clinical outcomes were studied. At baseline, 7618 of 8399 patients (90.7%) (mean [SD] age, 64 [11] years; 5987 [78.6%] male and 1631 [21.4%] female) completed the initial KCCQ assessment. Patients reported the greatest limitations at baseline in jogging and sexual relationships. Patients receiving sacubitril/valsartan had significantly better adjusted change scores in most physical and social activities at 8 months and during 36 months compared with those receiving enalapril. The largest improvement over enalapril was in household chores (adjusted change score difference, 2.35; 95% CI, 1.19-3.50; P sacubitril/valsartan significantly improved nearly all KCCQ physical

  15. Effect of Smoking and Folate Levels on the Efficacy of Folic Acid Therapy in Prevention of Stroke in Hypertensive Men.

    Science.gov (United States)

    Zhou, Ziyi; Li, Jianping; Yu, Yaren; Li, Youbao; Zhang, Yan; Liu, Lishun; Song, Yun; Zhao, Min; Wang, Yu; Tang, Genfu; He, Mingli; Xu, Xiping; Cai, Yefeng; Dong, Qiang; Yin, Delu; Huang, Xiao; Cheng, Xiaoshu; Wang, Binyan; Hou, Fan Fan; Wang, Xiaobin; Qin, Xianhui; Huo, Yong

    2018-01-01

    We aimed to examine whether the efficacy of folic acid therapy in the primary prevention of stroke is jointly affected by smoking status and baseline folate levels in a male population in a post hoc analysis of the CSPPT (China Stroke Primary Prevention Trial). Eligible participants of the CSPPT were randomly assigned to a double-blind daily treatment of a combined enalapril 10-mg and folic acid 0.8-mg tablet or an enalapril 10-mg tablet alone. In total, 8384 male participants of the CSPPT were included in the current analyses. The primary outcome was first stroke. The median treatment duration was 4.5 years. In the enalapril-alone group, the first stroke risk varied by baseline folate levels and smoking status (never versus ever). Specifically, there was an inverse association between folate levels and first stroke in never smokers ( P for linear trend=0.043). However, no such association was found in ever smokers. A test for interaction between baseline folate levels and smoking status on first stroke was significant ( P =0.045). In the total sample, folic acid therapy significantly reduced the risk of first stroke in never smokers with folate deficiency (hazard risk, 0.36; 95% confidence interval, 0.16-0.83) and in ever smokers with normal folate levels (hazard risk, 0.69; 95% confidence interval, 0.48-0.99). Baseline folate levels and smoking status can interactively affect the risk of first stroke. Our data suggest that compared with never smokers, ever smokers may require a higher dosage of folic acid to achieve a greater beneficial effect on stroke. Our findings need to be confirmed by future randomized trials. URL: https://www.clinicaltrials.gov. Unique identifier: NCT00794885. © 2017 American Heart Association, Inc.

  16. Arbutus unedo prevents cardiovascular and morphological alterations in L-NAME-induced hypertensive rats Part I: cardiovascular and renal hemodynamic effects of Arbutus unedo in L-NAME-induced hypertensive rats.

    Science.gov (United States)

    Afkir, Saida; Nguelefack, Telesphore Benoit; Aziz, Mohamed; Zoheir, Johar; Cuisinaud, Guy; Bnouham, Mohamed; Mekhfi, Hassane; Legssyer, Abdelkhaleq; Lahlou, Saad; Ziyyat, Abderrahim

    2008-03-05

    Hypertension induced by nitric oxide synthase inhibition is associated with functional abnormalities of the heart and kidney. The aim of the present study was to investigate whether chronic treatment with Arbutus unedo leaf (AuL) or root (AuR) aqueous extracts can prevent these alterations. Six groups of rats were used: control group received tap water; N(G)-nitro-l-arginine methyl-ester (L-NAME) group treated with L-NAME at 40 mg/kg/day; AuL and AuR groups received simultaneously L-NAME (40 mg/kg/day) and Au leaves or roots extract at the same concentration 250 mg/kg/day; l-arginine and enalapril groups received simultaneously L-NAME (40 mg/kg/day) and l-arginine at 50mg/kg/day or enalapril at 15 mg/kg/day. Treatment of rats during 4 weeks with L-NAME caused an increase of the systolic blood pressure (SBP) accompanied by a ventricular hypertrophy, an impairment of endothelium-dependent vasorelaxation, an increase of the cardiac baroreflex sensitivity and a decrease of water, sodium and potassium excretion. The co-administration of AuL or AuR extracts with L-NAME reduces the development of increased SBP, ameliorates the vascular reactivity as well as the baroreflex sensitivity and normalizes the renal function. AuR reduces the ventricular hypertrophy but AuL do not. Enalapril associated with L-NAME reverses the majority of alterations induced by L-NAME while l-arginine only lightly ameliorates the vascular reactivity. These results show that chronic treatment with Arbutus extract regress the development of hypertension and ameliorate cardiovascular and renal functions in NO deficient hypertension.

  17. Efficacy and safety of LCZ696 (sacubitril-valsartan) according to age: insights from PARADIGM-HF

    Science.gov (United States)

    Jhund, Pardeep S.; Fu, Michael; Bayram, Edmundo; Chen, Chen-Huan; Negrusz-Kawecka, Marta; Rosenthal, Arvo; Desai, Akshay S.; Lefkowitz, Martin P.; Rizkala, Adel R.; Rouleau, Jean L.; Shi, Victor C.; Solomon, Scott D.; Swedberg, Karl; Zile, Michael R.; McMurray, John J.V.; Packer, Milton

    2015-01-01

    Background The age at which heart failure develops varies widely between countries and drug tolerance and outcomes also vary by age. We have examined the efficacy and safety of LCZ696 according to age in the Prospective comparison of angiotensin receptor neprilysin inhibitor with angiotensin converting enzyme inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure trial (PARADIGM-HF). Methods In PARADIGM-HF, 8399 patients aged 18–96 years and in New York Heart Association functional class II–IV with an LVEF ≤40% were randomized to either enalapril or LCZ696. We examined the pre-specified efficacy and safety outcomes according to age category (years): <55 (n = 1624), 55–64 (n = 2655), 65–74 (n = 2557), and ≥75 (n = 1563). Findings The rate (per 100 patient-years) of the primary outcome of cardiovascular (CV) death or heart failure hospitalization (HFH) increased from 13.4 to 14.8 across the age categories. The LCZ696:enalapril hazard ratio (HR) was <1.0 in all categories (P for interaction between age category and treatment = 0.94) with an overall HR of 0.80 (0.73, 0.87), P < 0.001. The findings for HFH were similar for CV and all-cause mortality and the age category by treatment interactions were not significant. The pre-specified safety outcomes of hypotension, renal impairment and hyperkalaemia increased in both treatment groups with age, although the differences between treatment (more hypotension but less renal impairment and hyperkalaemia with LCZ696) were consistent across age categories. Interpretation LCZ696 was more beneficial than enalapril across the spectrum of age in PARADIGM-HF with a favourable benefit–risk profile in all age groups. PMID:26231885

  18. Sacubitril/Valsartan (LCZ696) in Heart Failure.

    Science.gov (United States)

    Khder, Yasser; Shi, Victor; McMurray, John J V; Lefkowitz, Martin P

    2017-01-01

    It has been known since the 1990s that long-term morbidity and mortality is improved in patients with heart failure with reduced ejection fraction (HFrEF) by treatments that target the renin-angiotensin-aldosterone system (RAAS). It has also long been thought that enhancement of the activity of natriuretic peptides (NPs) could potentially benefit patients with HFrEF, but multiple attempts to realize this benefit had failed over the years - until 2014, when a large, phase III, randomized, controlled clinical trial (PARADIGM-HF) was completed comparing sacubitril/valsartan with enalapril, a well-established treatment for HFrEF. Sacubitril/valsartan (formerly known as LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor (ARNI) that simultaneously suppresses RAAS activation through blockade of angiotensin II type 1 receptors and enhances vasoactive peptides including NPs through inhibition of neprilysin, the enzyme responsible for their degradation. In PARADIGM-HF, patients with HFrEF treated with sacubitril/valsartan had 20% less risk for cardiovascular death or hospitalization for heart failure (the primary endpoint), 20% less risk for cardiovascular death, 21% less risk for first hospitalization for heart failure, and 16% less risk for death from any cause, compared with enalapril (all p sacubitril/valsartan group had higher proportions of patients with hypotension and nonserious angioedema but lower proportions with renal impairment, hyperkalemia, and cough, compared with the enalapril group. The use of sacubitril/valsartan has been endorsed by the latest heart failure treatment guidelines in Europe and the USA. This chapter reviews the discoveries, scientific reasoning, and clinical evidence that led to the development of sacubitril/valsartan, the first novel therapy in a new drug class to improve survival in HFrEF in the last 15 years.

  19. Cost-effectiveness of sacubitril/valsartan in chronic heart-failure patients with reduced ejection fraction.

    Science.gov (United States)

    Ademi, Zanfina; Pfeil, Alena M; Hancock, Elizabeth; Trueman, David; Haroun, Rola Haroun; Deschaseaux, Celine; Schwenkglenks, Matthias

    2017-11-29

    We aimed to assess the cost effectiveness of sacubitril/valsartan compared to angiotensin-converting enzyme inhibitors (ACEIs) for the treatment of individuals with chronic heart failure and reduced-ejection fraction (HFrEF) from the perspective of the Swiss health care system. The cost-effectiveness analysis was implemented as a lifelong regression-based cohort model. We compared sacubitril/valsartan with enalapril in chronic heart failure patients with HFrEF and New York-Heart Association Functional Classification II-IV symptoms. Regression models based on the randomised clinical phase III PARADIGM-HF trials were used to predict events (all-cause mortality, hospitalisations, adverse events and quality of life) for each treatment strategy modelled over the lifetime horizon, with adjustments for patient characteristics. Unit costs were obtained from Swiss public sources for the year 2014, and costs and effects were discounted by 3%. The main outcome of interest was the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life years (QALYs) gained. Deterministic sensitivity analysis (DSA) and scenario and probabilistic sensitivity analysis (PSA) were performed. In the base-case analysis, the sacubitril/valsartan strategy showed a decrease in the number of hospitalisations (6.0% per year absolute reduction) and lifetime hospital costs by 8.0% (discounted) when compared with enalapril. Sacubitril/valsartan was predicted to improve overall and quality-adjusted survival by 0.50 years and 0.42 QALYs, respectively. Additional net-total costs were CHF 10 926. This led to an ICER of CHF 25 684. In PSA, the probability of sacubitril/valsartan being cost-effective at thresholds of CHF 50 000 was 99.0%. The treatment of HFrEF patients with sacubitril/valsartan versus enalapril is cost effective, if a willingness-to-pay threshold of CHF 50 000 per QALY gained ratio is assumed.

  20. 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.

    Science.gov (United States)

    Solomon, Scott D; Claggett, Brian; Desai, Akshay S; Packer, Milton; Zile, Michael; Swedberg, Karl; Rouleau, Jean L; Shi, Victor C; Starling, Randall C; Kozan, Ömer; Dukat, Andrej; Lefkowitz, Martin P; McMurray, John J V

    2016-03-01

    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. Eight thousand three hundred ninety-nine patients with New York Heart Association class II to IV HF with reduced EF [left ventricular EF (LVEF) ≤40%] were randomized to sacubitril/valsartan 97/103 mg twice daily versus enalapril 10 mg twice daily and followed for a median of 27 months. The primary study end point was cardiovascular death or HF hospitalization. LVEF was assessed at the sites and recorded on case report forms. We related LVEF to study outcomes and assessed the effectiveness of sacubitril/valsartan across the LVEF spectrum. The mean LVEF in PARADIGM-HF, reported by sites, was 29.5 (interquartile range, 25-34). The risk of all outcomes increased with decreasing LVEF. Each 5-point reduction in LVEF was associated with a 9% increased risk of cardiovascular death or HF hospitalization (hazard ratio, 1.09; 95% confidence interval, 1.05-1.13; PSacubitril/valsartan was effective across the LVEF spectrum, with no evidence of heterogeneity, when modeled either in tertiles (P interaction=0.87) or continuously (P interaction=0.95). In patients with HF and reduced EF enrolled in PARADIGM-HF, LVEF was a significant and independent predictor of all outcomes. Sacubitril/valsartan was effective at reducing cardiovascular death and HF hospitalization throughout the LVEF spectrum. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255. © 2016 American Heart Association, Inc.

  1. ANTIHYPERTENSIVE THERAPY AND CLIMACTERIC DISORDERS IN POSTMENOPAUSAL WOMEN

    Directory of Open Access Journals (Sweden)

    A. A. Kirichenko

    2008-01-01

    Full Text Available Aim. To study efficacy and tolerability of antihypertensive therapy with enalapril (Berlipril®, Berlin-Chemie AG/Menarini Group and diltiazem (Altiazem® PP, Berlin-Chemie AG/Menarini Group in postmenopausal women with arterial hypertension (HT and climacteric disorders.Material and methods. 60 postmenopausal women (aged 56,8±3,9 y.o. with HT of 1-3 degrees were included into the study. They were split in two groups. Patients of the first group (30 people received enalapril (Berlipril® 20 mg/daily, patients of the second group (30 people – diltiazem (Altiazem® PP 180-360 mg/daily. Observation period was 6 months. Ambulatory blood pressure monitoring (ABPM was performed before treatment and after 3 weeks, 1, 3 and 6 months of therapy. Climacteric syndrome severity and urodynamic disorders was estimated as well as psychic status according to score of depression and anxiety.Results. Office and ambulance blood pressure decreased after 6 months of therapy in all patients of both groups. A number of complaints on headache and giddiness reduced significantly. Severity of climacteric syndrome also decreased. Enalapril (Berlipril® monotherapy and especially combined therapy with hydrochlorothiazide led to aggravation of urodinamic disorders. On the contrary both monotherapy with diltiazem (Altiazem® PP or its combination with hydrochlorothiazide had positive effect on urodinamics. Both therapies reduced depression and anxiety levels significantly.Conclusion. All spectrum of pharmacology effects should be taken into account during antihypertensive therapy of patients with climacteric disorders.

  2. Mitigation of radiation-induced lung fibrosis by angiotensin converting enzyme inhibitors

    International Nuclear Information System (INIS)

    Kma, Lakhan; Gao, Feng; Jacobs, Elizabeth R.; Medhora, Meetha; Fish, Brian L.; Moulder, John E.

    2014-01-01

    The aim of this study was to test the mitigating potential of angiotensin converting enzyme inhibitors (ACEi) against radiation-induced pulmonary fibrosis, which could result from accidental exposure or radiological terrorism. Rats (WAG/RijCmcr) were exposed to a single dose of 13 Gy of X-irradiation to the whole thorax, at the dose rate of 1.43 Gy/min. Three structurally-different ACEi's, captopril (145-207 mg/m 2 /day), enalapril (19-28 mg/m 2 /day) and fosinopril (19-28 mg/m 2 /day) were administered in drinking water beginning 1 week after whole thoracic irradiation. Rats that survived acute pneumonitis (6-12 weeks) were accessed monthly after irradiation for the effects on lung structure and function. Endpoints included breathing rate, wet:dry weight ratio, collagen content and histolopathological studies. Treatment with captopril or enalapril, but not fosinopril, beginning 1 week after 13 Gy X-irradiation improved survival of rats. Mortality of 30-35% was observed with administration of captopril or enalapril compared to 70% for 13 Gy alone. All three ACEi's attenuated radiation-induced lung fibrosis at 7 months after irradiation based on histological indices and measurement of lung collagen. After whole-thoracic irradiation, ACEi's mitigate radiation induced pulmonary fibrosis based on histological and biochemical endpoints. These treatments were effective even when administration was not started until one week after irradiation. Our findings support the therapeutic potential of ACEi's against chronic radiation induced lung injury. (author)

  3. State of a large vessels and microcirculation - a new target for antihypertensive therapy in patients with hypertension and type 2 diabetes

    Directory of Open Access Journals (Sweden)

    M. E. Statsenko

    2016-01-01

    Full Text Available Aim. To evaluate the effect of 12 weeks of complex therapy with the fixed combination of enalapril and indapamide on indicators of vascular stiffness of large arteries and parameters of skin microcirculation (MC in patients with arterial hypertension (HT and diabetes mellitus (DM type 2.Material and methods. 30 patients with HT stage II-III in combination with DM type 2 aged 40-70 years were included into the study. The fixed combination of enalapril and indapamide in addition to lipid-lowering and hypoglycemic therapy was prescribed to all patients. Elastic properties of large arteries were assessed by analyzing the pulse wave velocity (PWV and the calculation of the index of aortic stiffness (IAS. Skin MC and level of glycated hemoglobin (HbA1c were also determined.Results. After the 12-week treatment all patients reached the target values of blood pressure (BP. Office systolic and diastolic BP levels decreased by 18.8 and 13.1% (p<0.05 for both, respectively. The treatment did not have a negative effect on glucose metabolism – HbA1C concentration decreased by 2.7%. PWV in the vessels of elastic and muscular types decreased by 10.8 and 10.1% (p<0.05 for both, respectively, and IAS decreased by 27.4% (p<0.05. Significant growth in factor myogenic regulation of MC and reduction in bypass indicator by 21.8% were found.Conclusion. Combined therapy with the inclusion of a fixed combination of enalapril and indapamide for 12 weeks had a high antihypertensive efficacy and good tolerability in patients with HT and DM type 2. Treatment significantly reduced the vascular stiffness of large arteries and improved the MC indices in these patients.

  4. Angiotensin Converting Enzyme Inhibitor Has a Protective Effect on Decompression Sickness in Rats

    Directory of Open Access Journals (Sweden)

    Aleksandra Mazur

    2018-03-01

    Full Text Available Introduction: Commercial divers, high altitude pilots, and astronauts are exposed to some inherent risk of decompression sickness (DCS, though the mechanisms that trigger are still unclear. It has been previously showed that diving may induce increased levels of serum angiotensin converting enzyme. The renin angiotensin aldosterone system (RAAS is one of the most important regulators of blood pressure and fluid volume. The purpose of the present study was to control the influence of angiotensin II on the appearance of DCS.Methods: Sprague Dawley rats have been pre-treated with inhibitor of angiotensin II receptor type 1 (losartan; 10 mg/kg, angiotensin-converting enzyme (ACE inhibitor (enalapril; 10 mg/kg, and calcium-entry blocker (nifedipine; 20 mg/kg. The experimental groups were treated for 4 weeks before exposure to hyperbaric pressure while controls were not treated. Seventy-five rats were subjected to a simulated dive at 1000 kPa absolute pressure for 45 min before starting decompression. Clinical assessment took place over a period of 60 min after surfacing. Blood samples were collected for measurements of TBARS, interleukin 6 (IL-6, angiotensin II (ANG II and ACE.Results: The diving protocol induced 60% DCS in non-treated animals. This ratio was significantly decreased after treatment with enalapril, but not other vasoactive drugs. Enalapril did not change ANG II or ACE concentration, while losartant decreased post dive level of ACE but not ANG II. None of the treatment modified the effect of diving on TBARS and IL-6 values.Conclusion: Results suggests that the rennin angiotensin system is involved in a process of triggering DCS but this has to be further investigated. However, a vasorelaxation mediated process, which potentially could increase the load of inert gas during hyperbaric exposure, and antioxidant properties were excluded by our results.

  5. Treatment of Bartter syndrome. Unsolved issue.

    Science.gov (United States)

    Nascimento, Carla Lessa Pena; Garcia, Cecilia Lopes; Schvartsman, Benita Galassi Soares; Vaisbich, Maria Helena

    2014-01-01

    To describe the results of a long-term follow-up of Bartter syndrome patients treated with different drugs. Patients were diagnosed according to clinical and laboratory data. Treatment protocol was potassium supplementation, sodium, spironolactone, and non-steroidal anti-inflammatory drug. Patients who developed proteinuria were converted to angiotensin conversion enzyme inhibitor. The variables evaluated for each drug were Z-score for weight and stature, proteinuria, creatinine clearance, gastrointestinal complaints, amount of potassium supplementation, serum potassium and bicarbonate levels, and findings of upper digestive endoscopy. 20 patients were included. Follow-up was 10.1 ± 5.2 years. 17 patients received indomethacin for 5.9 ± 5.3 years; 19 received celecoxib, median of 35 months; and five received enalapril, median of 23 months. During indomethacin, a statistically significant increase was observed in the Z-score for stature and weight, without a change in the creatinine clearance. Seven of 17 patients had gastrointestinal symptoms, and upper digestive endoscopy evidenced gastritis in three patients and gastric ulcer in four patients. During celecoxib use, a significant increase was detected in the Z-score for stature and weight and a reduction of hyperfiltration; seven patients presented gastrointestinal symptoms, and upper digestive endoscopy evidenced mild gastritis in three. During enalapril use, no significant changes were observed in the Z-score for stature, weight and creatinine clearance. The conversion to enalapril resulted in a significant reduction in proteinuria. The authors suggest starting the treatment with celecoxib, and replacing by ACEi if necessary, monitoring the renal function. The safety and efficacy of celecoxib need to be assessed in larger controlled studies. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  6. Phytochemical and in vitro and in vivo biological investigation on the antihypertensive activity of mango leaves (Mangifera indica L.).

    Science.gov (United States)

    Ronchi, Silas Nascimento; Brasil, Girlandia Alexandre; do Nascimento, Andrews Marques; de Lima, Ewelyne Miranda; Scherer, Rodrigo; Costa, Helber B; Romão, Wanderson; Boëchat, Giovanna Assis Pereira; Lenz, Dominik; Fronza, Marcio; Bissoli, Nazaré Souza; Endringer, Denise Coutinho; de Andrade, Tadeu Uggere

    2015-10-01

    The aim of this study was to investigate the antihypertensive effect of leaves Mangifera indica L. using in vitro and in vivo assays. The ethanol extract of leaves of M. indica was fractionated to dichloromethanic, n-butyl alcohol and aqueous fractions. The chemical composition of ethanolic extract and dichloromethanic fraction were evaluated by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Antioxidant activity was evaluated in the DPPH scavenging activity assay. Angiotensin-converting enzyme (ACE) inhibitory activity was investigated using in vitro and in vivo assays. The chronic antihypertensive assay was performed in spontaneously hypertensive rats (SHRs) and Wistar rats treated with enalapril (10 mg/kg), dichloromethanic fraction (100 mg/kg; twice a day) or vehicle control for 30 days. The baroreflex sensitivity was evaluated through the use of sodium nitroprusside and phenylephrine. Cardiac hypertrophy was evaluated by morphometric analysis. The dichloromethanic fraction exhibited the highest flavonoid, total phenolic content and high antioxidant activity. Dichloromethanic fraction elicited ACE inhibitory activity in vitro (99 ± 8%) similar to captopril. LC-MS/MS analysis revealed the presence of ferulic acid (48.3 ± 0.04 µg/g) caffeic acid (159.8 ± 0.02 µg/g), gallic acid (142.5 ± 0.03 µg/g), apigenin (11.0 ± 0.01 µg/g) and quercetin (203.3 ± 0.05 µg/g). The chronic antihypertensive effects elicited by dichloromethanic fraction were similar to those of enalapril, and the baroreflex sensitivity was normalized in SHR. Plasma ACE activity and cardiac hypertrophy were comparable with animals treated with enalapril. Dichloromethanic fraction of M. indica presented an antihypertensive effect, most likely by ACE inhibition, with benefits in baroreflex sensitivity and cardiac hypertrophy. Altogether, the results of the present study suggest that the dichloromethanic fraction of M. indica leaves may have potential as a promoting

  7. Clopidogrel bioactivation and risk of bleeding in patients cotreated with angiotensin-converting enzyme inhibitors after myocardial infarction

    DEFF Research Database (Denmark)

    Kristensen, K E; Zhu, H-J; Wang, X

    2014-01-01

    in vitro and linked the results with a pharmacoepidemiological study. In vitro, ACEIs inhibited CES1-mediated hydrolysis of a model substrate, and trandolapril and enalapril increased formation of clopidogrel active metabolite. In 70,934 patients with myocardial infarction, hazard ratios for clinically...... significant bleeding in ACEI-treated patients cotreated with or without clopidogrel were 1.10 (95% confidence interval (CI): 0.97-1.25, P = 0.124) and 0.90 (95% CI: 0.81-0.99, P = 0.025), respectively, as compared with patients who did not receive ACEIs. This difference was statistically significant (P = 0...

  8. Angiotensin II-AT1–receptor signaling is necessary for cyclooxygenase-2–dependent postnatal nephron generation

    DEFF Research Database (Denmark)

    Frölich, Stefanie; Slattery, Patrick; Thomas, Dominique

    2017-01-01

    was achievable. Plasma renin concentration in mouse pups showed a birth peak and a second peak around day P8 during the first 10 days post birth. Administration of the angiotensin II receptor AT1 antagonist telmisartan from day P1 to P3 did not result in cortical damage. However, telmisartan treatment from day P...... development. Inhibition of the renin angiotensin system by aliskiren and enalapril caused similar glomerular defects as telmisartan. Administration of the AT1 receptor agonist L162313 to COX-2-/- pups improved kidney growth, ameliorated renal defects, but had no beneficial effect on reduced cortical mass. L...

  9. Does renin-angiotensin system blockade have a role in preventing diabetic retinopathy? A clinical review

    DEFF Research Database (Denmark)

    Sjølie, A K; Dodson, P; Hobbs, F R R

    2011-01-01

    Diabetes management has increasingly focused on the prevention of macrovascular disease, in particular for type 2 diabetes. Diabetic retinopathy, one of the main microvascular complications of diabetes, is also an important public health problem. Much of the care invested in retinopathy relates...... the primary trial end-points were not met, there was a clear trend to less severe retinopathy with RAS blockade. A smaller trial, RASS, reported reduced retinopathy progression in type 1 diabetes from RAS blockade with both the ARB losartan and the angiotensin converting enzyme (ACE) inhibitor enalapril...

  10. Importância do metabolismo no planejamento de fármacos The importance of metabolism in drug design

    Directory of Open Access Journals (Sweden)

    Dárcio Gomes Pereira

    2007-02-01

    Full Text Available It is widely recognized that pharmacokinetic optimization needs to be addressed early in drug discovery to reduce the high failure rate in bringing drugs to market. Poor absorption, too short duration of action due to high elimination rate, or the presence of active metabolites are examples of properties that can potentially lead to unsuccessful clinical programmes. Here I describe a brief overview of advantages and molecular strategies for improving metabolic and pharmacokinetic properties applied to the discovery of fluconazol, beta-blockers, ritonavir and ezetimibe and to the development of the prodrugs enalapril and bambuterol.

  11. MTHFR Gene and Serum Folate Interaction on Serum Homocysteine Lowering: Prospect for Precision Folic Acid Treatment.

    Science.gov (United States)

    Huang, Xiao; Qin, Xianhui; Yang, Wenbin; Liu, Lishun; Jiang, Chongfei; Zhang, Xianglin; Jiang, Shanqun; Bao, Huihui; Su, Hai; Li, Ping; He, Mingli; Song, Yun; Zhao, Min; Yin, Delu; Wang, Yu; Zhang, Yan; Li, Jianping; Yang, Renqang; Wu, Yanqing; Hong, Kui; Wu, Qinhua; Chen, Yundai; Sun, Ningling; Li, Xiaoying; Tang, Genfu; Wang, Binyan; Cai, Yefeng; Hou, Fan Fan; Huo, Yong; Wang, Hong; Wang, Xiaobin; Cheng, Xiaoshu

    2018-03-01

    This post hoc analysis of the CSPPT (China Stroke Primary Prevention Trial) assessed the individual variation in total homocysteine (tHcy)-lowering response after an average 4.5 years of 0.8 mg daily folic acid therapy in Chinese hypertensive adults and evaluated effect modification by methylenetetrahydrofolate reductase ( MTHFR ) C677T genotypes and serum folate levels. This analysis included 16 413 participants from the CSPPT, who were randomly assigned to 2 double-blind treatment groups: either 10-mg enalapril+0.8-mg folic acid or 10-mg enalapril, daily and had individual measurements of serum folate and tHcy levels at baseline and exit visits and MTHFR C677T genotypes. Mean baseline tHcy levels were comparable between the 2 treatment groups (14.5±8.5 versus 14.4±8.1 μmol/L; P =0.561). After 4.5 years of treatment, mean tHcy levels were reduced to 12.7±6.1 μmol/L in the enalapril+folic acid group, but almost stayed the same in the enalapril group (14.4±7.9 μmol/L, group difference: 1.61 μmol/L; 11% reduction). More importantly, tHcy lowering varied by MTHFR genotypes and serum folate levels. Compared with CC and CT genotypes, participants with the TT genotype had a more prominent L-shaped curve between tHcy and serum folate levels and required higher folate levels (at least 15 ng/mL) to eliminate the differences in tHcy by genotypes. Compared with CC or CT, tHcy in the TT group manifested a heightened L-shaped curve from low to high folate levels, but this difference in tHcy by genotype was eliminated when plasma folate levels reach ≈15 ng/mL or higher. Our data raised the prospect to tailor folic acid therapy according to individual MTHFR C677T genotype and folate status. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00794885. © 2018 American Heart Association, Inc.

  12. Valvular dysplasia and congestive heart failure in a juvenile African penguin (Spheniscus demersus).

    Science.gov (United States)

    McNaughton, Allyson; Frasca, Salvatore; Mishra, Neha; Tuttle, Allison D

    2014-12-01

    Abstract: An aquarium-housed, 6-mo-old African penguin (Spheniscus demersus) presented with acute respiratory distress. Auscultation revealed a grade II-III systolic murmur in the absence of adventitial sounds, and an enlarged heart without pulmonary edema was seen radiographically. Echocardiographic evaluation revealed atrioventricular (AV) valvular dysplasia and ventricular enlargement. The penguin was treated with enalapril, furosemide, and pimobendan but died within 3 wk of detection of the murmur. Congenital dysplasia of the right AV valve with right atrial and ventricular dilation and ventricular hypertrophy were diagnosed on postmortem examination.

  13. Spontaneous remission of post-transplant recurrent focal and segmental glomerulosclerosis

    Directory of Open Access Journals (Sweden)

    Bassam Saeed

    2011-01-01

    Full Text Available A 12-year-old girl with a history of steroid and cyclosporine (CsA resistant nephrotic syndrome owing to focal and segmental glomerulosclerosis (FSGS has progressed to end-stage renal disease (ESRD for which she underwent hemodialysis for 18 months before she successfully received a fully matched kidney transplant from her sister at the age of nine years. The post transplantation (Tx period was marked by an early and massive proteinuria indicating recurrent FSGS for which she received 12 sessions of plasmapheresis (PP; unfortunately, she did not appear to have any response to the PP therapy; thereafter, a conservative management comprising essentially enalapril and losartan has been initiated and was also not successful during the first four months, however, a very gradual response has been noticed to occur after five months of conservative therapy and ultimately, the patient attained complete remission after 21 months of treatment. Amazingly, 15 months after discontinuation of enalapril and losartan, she remained in a complete and sustained remission with a good renal allograft function. To the best of our knowledge, this is the first case ever reported in the literature of a "spontaneous" remission of post transplant recurrent FSGS.

  14. Gingival bleeding, a possible "serious" adverse drug reaction: An observational study in the French PharmacoVigilance Database.

    Science.gov (United States)

    Bondon-Guitton, Emmanuelle; Mourgues, Thibaut; Rousseau, Vanessa; Cousty, Sarah; Cottin, Judith; Drablier, Guillaume; Micallef, Joëlle; Montastruc, Jean-Louis

    2017-09-01

    Antithrombotic drugs are known to increase the risk of gingival bleeding because they affect coagulation. However, other drugs could also be involved in gingival bleeding. We performed a pharmacoepidemiological study to identify the drugs most frequently "suspected" in the occurrence of gingival bleeding. We selected reports of "gingival bleeding" from 1 January 1985 to 30 September 2014 in the French PharmacoVigilance Database. Among 523,808 reports of adverse drug reactions, we identified 454 reports of gingival bleeding (0.09%). Most of them were "serious" (58.4%) and occurred in females (54.6%). The frequency of gingival bleeding increased with age. The most frequently "suspected" drugs were antithrombotics (67.8%), particularly fluindione. Other drugs frequently involved were furosemide followed by paracetamol, amiodarone, amoxicillin, paroxetine, ketoprofen, zolpidem, enalapril and ramipril. Thirty-nine reports involved a drug-drug interaction with antithrombotics, mainly with anti-infectives. Gingival bleeding can be an adverse drug reaction, often "serious" and rarely fatal. Patients older than 50 years and women are particularly at risk. Among drugs known to increase the risk of gingival bleeding, the most frequently involved were fluindione, furosemide, paracetamol, amiodarone, amoxicillin, paroxetine or ketoprofen. We also identified signal for drugs not usually known to be involved in bleeding, like zolpidem, enalapril or ramipril. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Sacubitril/valsartan reduces serum uric acid concentration, an independent predictor of adverse outcomes in PARADIGM-HF

    DEFF Research Database (Denmark)

    Mogensen, Ulrik M.; Køber, Lars; Jhund, Pardeep S.

    2017-01-01

    Aims: Elevated serum uric acid concentration (SUA) has been associated with an increased risk of cardiovascular disease, but this may be due to unmeasured confounders. We examined the association between SUA and outcomes as well as the effect of sacubitril/valsartan on SUA in patients with heart...... (adjusted hazard ratios) Q5 vs. Q1=1.28 [95% confidence intervals (1.09-1.50), P=0.003], cardiovascular death [1.44 (1.11-1.77), P=0.001], HF hospitalization [1.37 (1.11-1.70), P=0.004], and all-cause mortality [1.36 (1.13-1.64), P=0.001]. Compared with enalapril, sacubitril/valsartan reduced SUA by 0.24 (0.......17-0.32) mg/dL over 12months (PSacubitril/valsartan improved outcomes, irrespective of SUA concentration. Conclusion: Serum uric acid concentration was an independent predictor of worse outcomes after multivariable adjustment in patients with HFrEF. Compared with enalapril, sacubitril...

  16. Risk Related to Pre–Diabetes Mellitus and Diabetes Mellitus in Heart Failure With Reduced Ejection Fraction

    Science.gov (United States)

    Kristensen, Søren L.; Preiss, David; Jhund, Pardeep S.; Squire, Iain; Cardoso, José Silva; Merkely, Bela; Martinez, Felipe; Starling, Randall C.; Desai, Akshay S.; Lefkowitz, Martin P.; Rizkala, Adel R.; Rouleau, Jean L.; Shi, Victor C.; Solomon, Scott D.; Swedberg, Karl; Zile, Michael R.; Packer, Milton

    2016-01-01

    Background— The prevalence of pre–diabetes mellitus and its consequences in patients with heart failure and reduced ejection fraction are not known. We investigated these in the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial. Methods and Results— We examined clinical outcomes in 8399 patients with heart failure and reduced ejection fraction according to history of diabetes mellitus and glycemic status (baseline hemoglobin A1c [HbA1c]: 6.5%) and known diabetes mellitus compared with those with HbA1csacubitril/valsartan) compared with enalapril was consistent across the range of HbA1c in the trial. Conclusions— In patients with heart failure and reduced ejection fraction, dysglycemia is common and pre–diabetes mellitus is associated with a higher risk of adverse cardiovascular outcomes (compared with patients with no diabetes mellitus and HbA1c <6.0%). LCZ696 was beneficial compared with enalapril, irrespective of glycemic status. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255. PMID:26754626

  17. The safety of sacubitril-valsartan for the treatment of chronic heart failure.

    Science.gov (United States)

    Tyler, Jeffrey M; Teerlink, John R

    2017-02-01

    Sacubitril-valsartan is a combination drug that contains the neprilysin inhibitor sacubitril and angiotensin II receptor blocker valsartan. In 2015, the US Food and Drug Administration approved sacubitril-valsartan for treatment of heart failure patients with reduced ejection fraction and New York Heart Association class II-IV symptoms following a large, Phase III clinical trial (PARADIGM-HF) that demonstrated a 20% reduction in the combined primary end-point of death from cardiovascular cause or hospitalization for heart failure compared to enalapril. Areas covered: This review discusses the clinical efficacy and safety of angiotensin receptor neprilysin inhibitor sacubitril-valsartan in heart failure with reduced ejection fraction. Expert opinion: Based on the PARADIGM-HF trial, sacubitril-valsartan offers compelling reductions in meaningful clinical endpoints, independent of age or severity of disease. The rate of adverse events was comparable between the enalapril and sacubitril-valsartan groups, although the absolute rates are likely underestimated due to the entry criteria and run-in period. Future trials and post-market surveillance are critical to better understand the risk of angioedema in high risk populations, particularly African-Americans, as well as long-term theoretical risks including the potential for increased cerebral amyloid plaque deposition with possible development of neurocognitive disease. Current trials are underway to evaluate potential benefit in patients with heart failure with preserved ejection fraction.

  18. Angioedema Spotlight: A Closer Examination of Sacubitril/Valsartan Safety Results.

    Science.gov (United States)

    Owens, Ryan E; Oliphant, Carrie S

    2017-01-01

    Incorporation of neprilysin inhibition into heart failure pharmacotherapy regimens has recently been recommended by U.S. guidelines, based on results from the PARADIGM-HF trial comparing sacubitril/valsartan to enalapril. While most of the discussion has focused on efficacy, a closer examination of the safety results, particularly the incidence of angioedema during the run-in and double-blind periods, is also warranted. Although no major safety concerns were identified, an angioedema risk comparable to enalapril was found, primarily in the black population. Therefore, despite combination with an angiotensin receptor blocker, which historically has a lower incidence of angioedema, the addition of neprilysin inhibition yields an angioedema risk profile comparable to angiotensin converting enzyme (ACE) inhibitors. Clinicians should recognize this safety risk when prescribing sacubitril/valsartan and remain vigilant in counseling patients regarding the signs and symptoms of angioedema. As recommended by the guidelines, avoiding sacubitril/valsartan use concurrently or within 36 hours of the last dose of an ACE inhibitor or in patients with a history of angioedema is also crucial to minimize angioedema risk and prevent patient harm. © Copyright 2017 by the American Board of Family Medicine.

  19. Influence of mianserin on the activity of some hypotensive drugs in spontaneously hypertensive rats.

    Science.gov (United States)

    Górska, Dorota; Andrzejczak, Dariusz

    2003-01-01

    Mianserin might be an alternative drug in patients with depression accompanied by hypertension because of its effectiveness and lack of side effects in the circulatory system. However, a few studies reported in literature show influence of the drug on blood pressure. We investigate interactions between mianserin and commonly used hypotensive drugs (propranolol, enalapril and prazosin) in spontaneously hypertensive rats (SHR). The experiments were performed in two experimental designs: a single administration of both mianserin and a hypotensive drug, and repeated administration of mianserin with a single administration of a hypotensive drug. Arterial blood pressure was measured by bloodless method with manometer made by LETICA. A single administration of mianserin caused a statistically significant decrease in systolic, diastolic and mean blood pressure in the 60th minute of observation and intensified hypotensive effect of prazosin. However, long-term administration of mianserin in SHR rats had no significant influence on arterial blood pressure. Chronic and single administration of mianserin with propranolol or enalapril did not influence the circulatory system. A long-term administration of mianserin intensified the hypotensive effect of prazosin. This interaction might suggest possibility of dangerous complications in the treatment of humans with this drug combination.

  20. Interaction of mianserin and some hypotensive drugs in Wistar rats.

    Science.gov (United States)

    Górska, Dorota; Andrzejczak, Dariusz

    2004-01-01

    Mianserin is thought to exert little effect on the cardiovascular system. In fact its safety in comparison with tricyclic drugs is high. Various experiments gave varying results as for the influence of the drug on arterial blood pressure in people and animals. Therefore, a study was undertaken in Wistar rats to evaluate interactions of mianserin administered intraperitoneally as a single dose, and for 21 days with 3 hypotensive drugs showing different mechanism of action (propranolol, enalapril, prazosine). The systolic, diastolic and mean blood pressure was measured with a LETICA apparatus. The results of the study revealed that administration of mianserin in normotensive rats leads to a short-term decrease in blood pressure and significantly enhanced the hypotensive effect of prazosine. Repeated doses of mianserin lead to a temporary increase in blood pressure after 2 weeks of administration. Single and repeated administration of mianserin did not change the hypotensive effect of propranolol and enalapril. Three-week therapy with mianserin significantly enhanced the hypotensive effect of prazosine.

  1. Losartan Treatment Protects Retinal Ganglion Cells and Alters Scleral Remodeling in Experimental Glaucoma

    Science.gov (United States)

    Pitha, Ian F.; Nguyen, Cathy; Steinhart, Matthew R.; Nguyen, Thao D.; Pease, Mary Ellen; Oglesby, Ericka N.; Berlinicke, Cynthia A.; Mitchell, Katherine L.; Kim, Jessica; Jefferys, Joan J.

    2015-01-01

    Purpose To determine if oral losartan treatment decreases the retinal ganglion cell (RGC) death caused by experimental intraocular pressure (IOP) elevation in mice. Methods We produced IOP increase in CD1 mice and performed unilateral optic nerve crush. Mice received oral losartan, spironolactone, enalapril, or no drug to test effects of inhibiting angiotensin receptors. IOP was monitored by Tonolab, and blood pressure was monitored by tail cuff device. RGC loss was measured in masked axon counts and RGC bodies by β-tubulin labeling. Scleral changes that could modulate RGC injury were measured including axial length, scleral thickness, and retinal layer thicknesses, pressure-strain behavior in inflation testing, and study of angiotensin receptors and pathways by reverse transcription polymerase chain reaction, Western blot, and immunohistochemistry. Results Losartan treatment prevented significant RGC loss (median loss = 2.5%, p = 0.13), while median loss with water, spironolactone, and enalapril treatments were 26%, 28% and 43%; p glaucoma eyes (p = 0.007). Losartan inhibited effects of glaucoma, including reduction in extracellular signal-related kinase activity and modification of glaucoma-related changes in scleral thickness and creep under controlled IOP. Conclusions The neuroprotective effect of losartan in mouse glaucoma is associated with adaptive changes in the sclera expressed at the optic nerve head. PMID:26505191

  2. Aldosterone downregulates delayed rectifier potassium currents through an angiotensin type 1 receptor-dependent mechanism.

    Science.gov (United States)

    Lv, Yankun; Wang, Yanjun; Zhu, Xiaoran; Zhang, Hua

    2018-01-01

    We have previously shown that aldosterone downregulates delayed rectifier potassium currents (I Ks ) via activation of the mineralocorticoid receptor (MR) in adult guinea pig cardiomyocytes. Here, we investigate whether angiotensin II/angiotensin type 1 receptor (AngII/AT1R) and intracellular calcium also play a role in these effects. Ventricular cardiomyocytes were isolated from adult guinea pigs and incubated with aldosterone (1 μmol·L -1 ) either alone or in combination with enalapril (1 μmol·L -1 ), losartan (1 μmol·L -1 ), nimodipine (1 μmol·L -1 ), or BAPTA-AM (2.5 μmol·L -1 ) for 24 h. We used the conventional whole cell patch-clamp technique to record the I Ks component. In addition, we evaluated expression of the I Ks subunits KCNQ1 and KCNE1 using Western blotting. Our results showed that both enalapril and losartan, but not nimodipine or BAPTA-AM, completely reversed the aldosterone-induced inhibition of I Ks and its effects on KCNQ1/KCNE1 protein levels. Furthermore, we found that AngII/AT1R mediates the inhibitory effects of aldosterone on I Ks . Finally, the downregulation of I Ks induced by aldosterone did not occur secondarily to a change in intracellular calcium concentrations. Taken together, our findings demonstrate that crosstalk between MR and AT1R underlies the effects of aldosterone, and provide new insights into the mechanism underlying potassium channels.

  3. Nocturnal antihypertensive treatment in patients with type 1 diabetes with autonomic neuropathy and non-dipping

    DEFF Research Database (Denmark)

    Hjortkjær, Henrik Øder; Jensen, Tonny; Kofoed, Klaus F

    2016-01-01

    to test if bedtime dosing (BD) versus morning dosing (MD) of the ACE inhibitor enalapril would affect the 24-hour BP profile in patients with type 1 diabetes (T1D), CAN and non-dipping. SETTING: Secondary healthcare unit in Copenhagen, Denmark. PARTICIPANTS: 24 normoalbuminuric patients with T1D with CAN...... and non-dipping were included, consisting of mixed gender and Caucasian origin. Mean±SD age, glycosylated haemoglobin and diabetes duration were 60±7 years, 7.9±0.7% (62±7 mmol/mol) and 36±11 years. INTERVENTIONS: In this randomised, placebo-controlled, double-blind cross-over study, the patients were......OBJECTIVES: Cardiovascular autonomic neuropathy (CAN) and abnormal circadian blood pressure (BP) rhythm are independent cardiovascular risk factors in patients with diabetes and associations between CAN, non-dipping of nocturnal BP and coronary artery disease have been demonstrated. We aimed...

  4. Use of different types of angiotensin converting enzyme inhibitors and mortality in systolic heart failure

    DEFF Research Database (Denmark)

    Svanström, Henrik; Pasternak, Björn; Melbye, Mads

    2015-01-01

    BACKGROUND: Angiotensin converting enzyme-inhibitors (ACEIs) are the first-line treatment for patients with heart failure (HF) with reduced ejection fraction (EF). The benefit of ACEIs in HF is regarded as a class effect and different types of agents are used interchangeably. However, evidence......-2012, were identified using the Danish HF Registry. New users of enalapril (n=1807), perindopril (n=1064), ramipril (n=3270), or trandolapril (n=1150), who started treatment within 60days of first-time hospital diagnosis of HF, were selected for inclusion. Subgroup analyses were conducted by sex, age, NYHA...... with ramipril. No significant differences were observed in subgroup analyses. CONCLUSIONS: These findings suggest equal effect of different types of ACEIs on mortality in systolic HF....

  5. Effect of angiotensin-converting enzyme gene polymorphism at the results of losartan use in the patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    T. Yu. Poniatowskaya

    2015-03-01

    Odessa National Medical University   Summary The article presented is an original investigation where the effects of losartan in patients with hypertension and type 2 diabetes mellitus (T2DM have been evaluated. The effect of therapy has been estimated with the help of gene ACE allelic variant. The dependence of enalapril antihypertensive action and nephroprotective action of ACE polymorphism has been revealed. The results obtained show a different effect on ACE allele variants of lipid metabolism in patients with hypertension and T2DM and complications in the form of hypertriglyceridemia in the patients with DD-genotype.   Key words: type 2 diabetes mellitus, hypertension, I / D polymorphism of the gene ACE, pharmacogenetics, losartan.

  6. Variability in response to albuminuria-lowering drugs

    DEFF Research Database (Denmark)

    Petrykiv, Sergei I; de Zeeuw, Dick; Persson, Frederik

    2017-01-01

    AIMS: Albuminuria-lowering drugs have shown different effect size in different individuals. Since urine albumin levels are known to vary considerably from day-to-day, we questioned whether the between-individual variability in albuminuria response after therapy initiation reflects a random...... variability or a true response variation to treatment. In addition, we questioned whether the response variability is drug dependent. METHODS: To determine whether the response to treatment is random or a true drug response, we correlated in six clinical trials the change in albuminuria during placebo...... or active treatment (on-treatment) with the change in albuminuria during wash-out (off-treatment). If these responses correlate during active treatment, it suggests that at least part of the response variability can be attributed to drug response variability. We tested this for enalapril, losartan...

  7. Targeting renin-angiotensin system in malignant hypertension in atypical hemolytic uremic syndrome

    Directory of Open Access Journals (Sweden)

    V Raghunathan

    2017-01-01

    Full Text Available Hypertension is common in hemolytic uremic syndrome (HUS and often difficult to control. Local renin-angiotensin activation is believed to be an important part of thrombotic microangiopathy, leading to a vicious cycle of progressive renal injury and intractable hypertension. This has been demonstrated in vitro via enhanced tissue factor expression on glomerular endothelial cells which is enhanced by angiotensin II. We report two pediatric cases of atypical HUS with severe refractory malignant hypertension, in which we targeted the renin-angiotensin system by using intravenous (IV enalaprilat, oral aliskiren, and oral enalapril with quick and dramatic response of blood pressure. Both drugs, aliskiren and IV enalaprilat, were effective in controlling hypertension refractory to multiple antihypertensive medications. These appear to be promising alternatives in the treatment of severe atypical HUS-induced hypertension and hypertensive emergency.

  8. [Sacubitril / Valsartan in patients with diabetes and heart failure].

    Science.gov (United States)

    Brandenburg, Vincent Matthias; Rocca, Hans-Peter Brunner-La; Marx, Nikolaus

    2016-10-01

    Sacubitril / Valsartan proofed to be an effective treatment compared to enalapril in reducing heart failure hospitalisations and mortality in patients with severe "Heart failure with reduced ejection fraction" (HFREF). Recent European cardiology guidelines attributed a class IB recommendation for Sacubitril / Valsartan in HFREF patients who remain symptomatic despite optimal treatment with ACE-I, a beta-blocker, and a mineralocorticoid receptor antagonist. There is a significant overlap between diabetic and HFREF patients and thus, efficacy assessment of Sacubitril / Valsartan is a clinically meaningful issue in the large subgroup of HFREF patients with diabetes. We discuss the present evidence why local authorities speculated about a potential interaction between the two diseases decreasing the efficacy of sacubitril/valsartan in terms of reducing relevant end-points in this cohort. Overall, Sacubitril / Valsartan is obviously a treatment option in diabetics with HFREF. However, diabetic cardiomyopathy needs to be recognised as a specific disease condition. © Georg Thieme Verlag KG Stuttgart · New York.

  9. Sacubitril/Valsartan: From Clinical Trials to Real-world Experience.

    Science.gov (United States)

    Joly, Joanna M; Desai, Akshay S

    2018-04-23

    Compared to enalapril, use of angiotensin-receptor blocker and neprilysin inhibitor sacubitril/valsartan to treat patients with heart failure and reduced ejection fraction (HFrEF) is associated with substantial reductions in both cardiovascular mortality and heart failure progression. The purpose of this review is to discuss the real-world experience of sacubitril/valsartan. In the years following the publication of the landmark PARADIGM-HF trial in 2014 and its subsequent FDA approval, a growing evidence base supports the safety and efficacy of sacubitril/valsartan in a broad spectrum of patients with HFrEF. Updated clinical practice guidelines have embraced the use of sacubitril/valsartan in preference to ACE inhibitors or ARBs in selected patients. In this review, we highlight the clinical trials that led to these key updates to clinical guidelines, offer practical strategies for patient selection and utilization in clinical practice, and identify important areas of uncertainty that require future research.

  10. SUSPECTED HYPERVITAMINOSIS D IN RED-RUMPED AGOUTI ( DASYPROCTA LEPORINA) RECEIVING A COMMERCIAL RODENT DIET.

    Science.gov (United States)

    Anderson, Kadie M; Lewandowski, Albert; Dennis, Patricia M

    2018-03-01

    An 8 yr, intact male red-rumped agouti ( Dasyprocta leporina) was evaluated for weight loss. Examination revealed poor body condition, hypercalcemia, elevated serum 25-hydroxyvitamin D, metastatic calcification of soft tissues, and hyperechoic kidneys. The diet, formulated for laboratory rodents, contained elevated levels of vitamin D 3 . Histopathology from a female conspecific that died 5 mo prior identified dystrophic mineralization and nephrosclerosis, suggestive of a vitamin D 3 toxicity. The male agouti responded well to a dietary reduction in vitamin D 3 and calcium. Six months into therapy, progressive renal failure was identified and was further managed with enalapril, phosphorus binders, and dietary manipulation. Suspected vitamin D 3 toxicity has been reported in pacas ( Cuniculus paca) and agouti and has been linked to exposure to New World primate diets. In this brief communication, an agouti developed suspected hypervitaminosis D after receiving a commercial rodent diet commonly fed to this species in captivity.

  11. Análisis del consumo de inhibidores de la enzima convertidora de angioténsina en el territorio oeste de La Habana, 2005-2009 Analysis of the consumption of angiotensin-converting enzyme inhibitors in the west side of Havana, 2005-2009

    Directory of Open Access Journals (Sweden)

    José Ramón Cabrera Cepero

    2011-12-01

    Full Text Available La planificación de los recursos es un problema trascendental en los países en desarrollo y también en Cuba, por lo que hacer el mejor uso de los presupuestos limitados y de las escasas divisas, es de vital importancia. Planificar las cantidades de medicamentos necesarias, para lograr garantizar una disponibilidad adecuada de estos en todos los niveles de asistencia, es una tarea en la cual intervienen un sinnúmero de factores. El objetivo de este trabajo fue demostrar en qué medida la introducción del enalapril tabletas influyó en el consumo del captopril tabletas, mediante el análisis de los patrones de consumo de los medicamentos inhibidores de la enzima convertidora de angiotensina en el territorio oeste de La Habana entre marzo de 2005 y diciembre de 2009. Para ello se realizó un estudio de utilización de medicamentos de consumo, de tipo descriptivo, observacional y retrospectivo. Se calcularon las DHD (dosis por mil habitantes día. Los resultados de este trabajo demuestran cómo en este grupo hay un desplazamiento del consumo hacia el enalapril. Este es un comportamiento lógico por la comodidad de la administración y la menor incidencia de efectos adversos. Sin embargo, el captopril se mantiene en valores entre 20 y 30 DHD x 1 000 habitantes ya que hay un grupo de pacientes que continúan con este tratamiento y es de elección en la crisis hipertensiva.The planning of resources is a pressing problem in the developing nations including Cuba, hence using restricted budgets and dwindling foreign currencies in the best possible way is a must. Planning the amount of required drugs to assure their adequate supply at all medical assistance levels is a vital task in which a number of factors are involved. This paper was aimed at showing to what extent the introduction of enalapril pills into the market influenced the consumption of captopril tablets, through the analysis of the consumption patterns of angiotensin-converting enzyme

  12. Terapia com inibidor da ECA com dosagens relativamente altas e risco de agravamento renal na insuficiência cardíaca crônica ACE-inhibitor therapy at relatively high doses and risk of renal worsening in chronic heart failure

    Directory of Open Access Journals (Sweden)

    Renato De Vecchis

    2011-12-01

    Full Text Available FUNDAMENTO: O efeito renoprotetor dos inibidores da ECA vem sendo questionado no caso de diminuição do volume circulante efetivo, como na insuficiência cardíaca crônica direita ou biventricular. Objetivo: Detectar os preditores clínicos de agravamento renal na população de pacientes com ICC, caracterizado por dois tipos de regime de dosagem de inibidores da ECA. MÉTODOS: De acordo com um desenho de coorte retrospectiva, seguimos dois grupos de pacientes com ICC - tanto direita quanto biventricular -, todos na classe III da NYHA, tratados com inibidores da ECA (enalapril ou lisinopril, e com fração de ejeção do ventrículo esquerdo (FEVE 10 mg por dia de enalapril ou lisinopril. A disfunção renal agravada (ARD foi definida pelo aumento de Cr > 30% com relação ao segmento basal. O modelo de risco proporcional de Cox foi utilizado para identificar os preditores da ARD entre as seguintes variáveis: os inibidores da ECA com "alta" dosagem, idade, FEVE basal, histórico de repetidas terapias intensivas com diuréticos de alça por via intravenosa (diurético intravenoso, diabete, Cr basal, histórico de hipertensão, pressão arterial sistólica BACKGROUND: Renoprotective effect of ACE-inhibitors has been questioned in case of decreased effective circulating volume, like in right or biventricular chronic heart failure. OBJECTIVE: To detect clinical predictors of renal worsening in CHF patient population characterized by two types of ACE-inhibitor dosing regimens. METHODS: According to a retrospective cohort design, we followed 2 groups of patients with CHF - whether right or biventricular -, all in III NYHA class treated with ACE-inhibitors (enalapril or lisinopril, and with left ventricular ejection fraction (LVEF 10 mg per day of enalapril or lisinopril. Worsened renal failure (ARD was defined by Cr increase >30% from baseline. Cox proportional hazards model was used to identify the predictors of ARD among the following variables

  13. Dilated cardiomyopathy in cats - A case report

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    K. Jeyaraja

    2013-08-01

    Full Text Available Two cats were brought to Madras Veterinary College Teaching Hospital with the history and clinical signs suggestive of congestive heart failure ie, coughing, exercise intolerance, dyspnea, abdominal distension etc. There was history of feeding the cat with home made diet in one case and in other with commercial dog food. Based on electrocardiographic, radiographic and echocardiographic findings, the diagnosis of dilated cardiomyopathy was done in both the cases. The cases were managed with enalapril maleate, furosemide, dietary taurine supplementation and other supportive therapy. Among these two cases, one cat died on 2nd day of treatment and the other showed recovery after 8 days of treatment. [Vet World 2013; 6(4.000: 226-227

  14. [Arteriosclerosis obliterans. Treatment with angiotensin-converting enzyme inhibitors].

    Science.gov (United States)

    Orea, A; Valdés, R; Niebla, L; Rivas, R; Camacho, B

    1990-01-01

    We compare the effects of two of the main angiotensin convertase enzyme inhibitors, captopril and enalapril, aiming to evaluate their effects in the arterial circulation performance, micro-circulation, and changes in regional blood flow, assuming their property of lowering the angiotensin II blood levels, a very strong peripheral vasoconstrictor. We studied 22 patients: all of them with hypertension and/or skin ulcerations, dropping out those who had venous. They were evaluated periodically, clinically and with photoelectric plethysmography of lower extremities. To interpret the traces we designed an ideogram which gathered the plethysmographic behavior before and after the treatment. Nearly 80% showed considerable improvement in pain, functional capacity and plethysmographic traces patterns. healing of the ulcerations was achieved in all case. We propose some hypothesis to explain the good effect that we have observed.

  15. Possible pharmacological interactions in hypertensive and/or diabetic elderly in family health units at Blumenau (SC

    Directory of Open Access Journals (Sweden)

    Vicente Codagnone Neto

    2010-12-01

    Full Text Available The aim of this study was to examine the possible adverse drug-drug interactions in the elderly population (>60 years diagnosed either with diabetes, arterial hypertension or both, at a Family Health Unit (FHU clinic in Blumenau, state of Santa Catarina, Brazil. For this purpose 318 subjects were interviewed using a pretested form with social and demographic aspects regarding their disease and its complications. All drugs used by this population were grouped, and the drug-drug interactions were detected by using the "Drug Interaction Checker" software, and classified for frequency and severity. The average age of patients was 70.6 years, with a higher number of female patients (216; 67.9%. Most subjects were being treated for both diseases (149; 46.86%. Out of a total of 1,541 medications prescribed, the most prevalent were: hydrochlorothiazide (131; 8.4% and enalapril maleate (130; 8.4%. A total of 295 possible drug-drug interactions were detected in 152 patients (1.9 interactions per subject, 275 (93.2% moderate and 20 (6.8% severe or highly severe. The possible interaction prevalence was 0.93 (0.55 to 1.40 depending on health unit. The most frequent possible interaction was that between acetylsalicylic acid and enalapril maleate (37; 12.5%. Patients had an average consumption of 6.6 drugs and 9.8% of subjects reported physical discomfort when using medicines. Elderly patients use many medications that could cause adverse reactions and possible drug-drug interactions, where this issue warrants closer attention of prescribers and health providers.Buscou-se identificar possíveis interações medicamentosas em pessoas idosas com diabetes melito (DM e/ou hipertensão arterial sistêmica (HAS sendo atendidas em unidades de Saúde da Família, em Blumenau (SC. Entrevistaram-se 318 pessoas com 60 e mais anos, portadoras de DM e/ou HAS, mediante questionário estruturado pré-testado, com variáveis sócio-demográficas da doença e do tratamento. As

  16. Angiotensin-converting enzyme inhibition improves cardiac fatty acid metabolism in patients with congestive heart failure.

    Science.gov (United States)

    Yamauchi, S; Takeishi, Y; Minamihaba, O; Arimoto, T; Hirono, O; Takahashi, H; Miyamoto, T; Nitobe, J; Nozaki, N; Tachibana, H; Watanabe, T; Fukui, A; Kubota, I

    2003-08-01

    This study aimed to examine whether angiotensin-converting enzyme (ACE) inhibition improved cardiac fatty acid metabolism in patients with congestive heart failure (CHF). Myocardial 123I-beta-methyl-iodophenylpentadecanoic acid (123I-BMIPP) imaging was performed in 25 patients with CHF and in 10 control subjects. Myocardial 123I-BMIPP images were obtained 30 min and 4 h after tracer injection. The heart-to-mediastinum (H/M) ratio of 123I-BMIPP uptake and the washout rate of 123I-BMIPP from the myocardium were calculated. Patients were given enalapril for 6 months, and 123I-BMIPP imaging was repeated. H/M ratios on early and delayed images were lower in CHF patients than in normal controls (Pacid metabolism by ACE inhibition may represent a new mechanism for the beneficial effect of this therapy in heart failure.

  17. Medication usage in Majuro, Marshall Islands.

    Science.gov (United States)

    Harding, Andrew

    2005-03-01

    To conduct a drug utilisation study to determine the top 50 drugs by prescription count, top 50 drugs by cost to government and the top 30 drugs by consumption for Majuro Atoll, Marshall Islands for the year 2003. Data was collected from the Majuro Hospital computer dispensing system. All outpatient prescriptions dispensed in the year 2003 were included. The defined daily dose (DDD) methodology was employed. Drug consumption was presented as DDD/1000 population/day. The top 5 drugs by consumption in Majuro for 2003 were glibenclamide (glyburide), enalapril, ferrous sulphate, amoxycillin and ascorbic acid. Values for the DDD/1000 population/day were on average lower than many other countries. This is the first local study of medication usage in the Marshall Islands. It provided some useful baseline data.

  18. Toxic epidermal necrolysis associated with deflazacort therapy with nephrotic syndrome

    Directory of Open Access Journals (Sweden)

    Eun Chae Lee

    2014-12-01

    Full Text Available Toxic epidermal necrolysis (TEN is a drug-related fatal disease. Extensive necrosis of the epidermis can lead to serious complications. This report describes two cases of TEN, associated with deflazacort (DFZ, in two boys, aged 4 years and 14 years, with nephrotic syndrome (NS. The 14-year-old male teenager received DFZ following NS relapse. After 17 days, pruritic papules appeared on the lower extremities. Another case involved a 4-year-old boy receiving DFZ and enalapril. After a 41-day DFZ treatment period, erythematous papules appeared on the palms and soles. Within 3 days, both boys developed widespread skin lesions (>50% and were admitted to the intensive care unit for resuscitative and supportive treatment. The patients showed improvement after intravenous immunoglobulin-G therapy. Owing to the rapid, fatal course of TEN, clinicians need to be aware of the adverse effects of this drug when treating cases of NS.

  19. The influence of angiotensin-converting enzyme inhibition on renal tubular function in progressive chronic nephropathy

    DEFF Research Database (Denmark)

    Kamper, A L; Holstein-Rathlou, N H; Leyssac, P P

    1996-01-01

    The influence of angiotensin-converting enzyme (ACE) inhibition on renal tubular function in progressive chronic nephropathy was investigated in 69 patients by the lithium clearance (C(Li)) method. Studies were done repeatedly for up to 2 years during a controlled trial on the effect of enalapril...... on progression of renal failure. The pattern of proteinuria was followed over the first 9 months. At baseline, the glomerular filtration rate (GFR) was 5 to 68 mL/min. Absolute proximal tubular reabsorption rate of fluid (APR), estimated as the difference between GFR and C(Li), was 1 to 54 mL/min. Calculated...... in either treatment regimen was associated with a long-term slower progression of renal failure. Over 9 months, the 24-hour fractional clearance of albumin decreased in the ACE inhibitor group (P

  20. Immunoglobulin A nephropathy in association with generalized inflammatory peeling skin syndrome.

    Science.gov (United States)

    Srinivasaraghavan, Rangan; Krishnamurthy, Sriram; Chandar, Rumesh; Mahadevan, Subramanian; Chandrashekar, Laxmisha; Rajesh, Nachiappa Ganesh

    2015-01-01

    We describe an 8-year-old girl born to second-degree consanguineous parents with complaints of recurrent episodes of hematuria for 6 months. She had generalized peeling of the skin since birth and recurrent purulent cutaneous infections. The clinical presentation and histopathology of the skin biopsy specimen were consistent with the inflammatory variant of peeling skin syndrome (PSS). She also had a single ventricle with pulmonary stenosis, for which a bidirectional Glenn shunt had been placed. The renal biopsy specimen showed immunoglobulin A (IgA) nephropathy. She responded well to enalapril and steroids, with a decrease in proteinuria. IgA nephropathy has not been previously reported in PSS. Complications such as IgA nephropathy in children with PSS would help to further delineate the diverse clinical presentations and the clinical course of this rare dermatosis. We discuss the mechanisms that could explain this hitherto unreported association. © 2014 Wiley Periodicals, Inc.

  1. TO STUDY THE EFFECT OF ANGIOTENSIN RECEPTOR BLOCKERS ON DIABETIC RETINOPATHY

    Directory of Open Access Journals (Sweden)

    Chakravarthy K

    2017-05-01

    Full Text Available BACKGROUND Diabetic Retinopathy (DR is the most common microvascular complication of Diabetes Mellitus (DM and is the leading cause of blindness in working age adults of patients with type 1 and 2 DM. Large observational and randomised studies shown that optimal blood glucose and blood pressure control halt or regress the disease and limit the risk of progression to the proliferative stage and visual loss. Recently, evidence has also emerged that Renin-Angiotensin System (RAS inhibitors may electively prevent or delay progression of retinopathy by acting on local RAS. Thus, metabolic and blood pressure control by RAS inhibition is to prevent or limit the onset of retinopathy and its progression towards visual-threatening stages. The aim of the study is to categorise and analyse grading of DR who are on currently ACE and ARBs unchanged for at least 2 years. MATERIALS AND METHODS 178 patients with type 1 and 2 DM of both genders on ARBs and ACEI unchanged for at least 2 years are divided into two groups as follows- 1. ARB group, which includesa 28 patients on losartan (50 mg. b 32 patients on losartan (50 mg + hydrochlorothiazide (12.5 mg. c 28 patients on telmisartan (40 mg. d 32 patients on telmisartan (40 mg + hydrochlorothiazide (12.5 mg. 2. ACE inhibitor group includesa 30 patients on enalapril (5 mg. b 28 patients on ramipril (2.5 mg + hydrochlorothiazide (12.5 mg. Retinopathy grading assessed by indirect ophthalmoscope and comparison of retinopathy grading between ARBs and ACEI groups have done. Two-tailed Chi-square test, GraphPad Prism Software used for statistical calculations. RESULTS Losartan and telmisartan (ARB group showed significant protection from diabetic retinopathy than enalapril and ramipril (ACEI group (p<0.05. CONCLUSION ARBs help in preventing the progression of DR and vision loss in those belonging to mild and moderate nonproliferative diabetic retinopathy patients.

  2. Baseline characteristics and treatment of patients in prospective comparison of ARNI with ACEI to determine impact on global mortality and morbidity in heart failure trial (PARADIGM-HF).

    Science.gov (United States)

    McMurray, John J V; Packer, Milton; Desai, Akshay S; Gong, Jianjian; Lefkowitz, Martin; Rizkala, Adel R; Rouleau, Jean L; Shi, Victor C; Solomon, Scott D; Swedberg, Karl; Zile, Michael R

    2014-07-01

    To describe the baseline characteristics and treatment of the patients randomized in the PARADIGM-HF (Prospective comparison of ARNi with ACEi to Determine Impact on Global Mortality and morbidity in Heart Failure) trial, testing the hypothesis that the strategy of simultaneously blocking the renin-angiotensin-aldosterone system and augmenting natriuretic peptides with LCZ696 200 mg b.i.d. is superior to enalapril 10 mg b.i.d. in reducing mortality and morbidity in patients with heart failure and reduced ejection fraction. Key demographic, clinical and laboratory findings, along with baseline treatment, are reported and compared with those of patients in the treatment arm of the Studies Of Left Ventricular Dysfunction (SOLVD-T) and more contemporary drug and device trials in heart failure and reduced ejection fraction. The mean age of the 8442 patients in PARADIGM-HF is 64 (SD 11) years and 78% are male, which is similar to SOLVD-T and more recent trials. Despite extensive background therapy with beta-blockers (93% patients) and mineralocorticoid receptor antagonists (60%), patients in PARADIGM-HF have persisting symptoms and signs, reduced health related quality of life, a low LVEF (mean 29 ± SD 6%) and elevated N-terminal-proB type-natriuretic peptide levels (median 1608 inter-quartile range 886-3221 pg/mL). PARADIGM-HF will determine whether LCZ696 is more beneficial than enalapril when added to other disease-modifying therapies and if further augmentation of endogenous natriuretic peptides will reduce morbidity and mortality in heart failure and reduced ejection fraction. © 2014 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

  3. Cost-effectiveness of sacubitril/valsartan in the treatment of heart failure with reduced ejection fraction.

    Science.gov (United States)

    McMurray, John J V; Trueman, David; Hancock, Elizabeth; Cowie, Martin R; Briggs, Andrew; Taylor, Matthew; Mumby-Croft, Juliet; Woodcock, Fionn; Lacey, Michael; Haroun, Rola; Deschaseaux, Celine

    2018-06-01

    Chronic heart failure with reduced ejection fraction (HF-REF) represents a major public health issue and is associated with considerable morbidity and mortality. We evaluated the cost-effectiveness of sacubitril/valsartan (formerly LCZ696) compared with an ACE inhibitor (ACEI) (enalapril) in the treatment of HF-REF from the perspective of healthcare providers in the UK, Denmark and Colombia. A cost-utility analysis was performed based on data from a multinational, Phase III randomised controlled trial. A decision-analytic model was developed based on a series of regression models, which extrapolated health-related quality of life, hospitalisation rates and survival over a lifetime horizon. The primary outcome was the incremental cost-effectiveness ratio (ICER). In the UK, the cost per quality-adjusted life-year (QALY) gained for sacubitril/valsartan (using cardiovascular mortality) was £17 100 (€20 400) versus enalapril. In Denmark, the ICER for sacubitril/valsartan was Kr 174 000 (€22 600). In Colombia, the ICER was COP$39.5 million (€11 200) per QALY gained. Deterministic sensitivity analysis showed that results were most sensitive to the extrapolation of mortality, duration of treatment effect and time horizon, but were robust to other structural changes, with most scenarios associated with ICERs below the willingness-to-pay threshold for all three country settings. Probabilistic sensitivity analysis suggested the probability that sacubitril/valsartan was cost-effective at conventional willingness-to-pay thresholds was 68%-94% in the UK, 84% in Denmark and 95% in Colombia. Our analysis suggests that, in all three countries, sacubitril/valsartan is likely to be cost-effective compared with an ACEI (the current standard of care) in patients with HF-REF. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  4. Profile of sacubitril/valsartan in the treatment of heart failure: patient selection and perspectives.

    Science.gov (United States)

    Yandrapalli, Srikanth; Andries, Gabriela; Biswas, Medha; Khera, Sahil

    2017-01-01

    With an estimated prevalence of 5.8 million in the USA and over 23 million people worldwide, heart failure (HF) is growing in epidemic proportions. Despite the use of guideline-directed medical therapies such as angiotensin-converting enzyme inhibitors, beta-adrenergic blockers, angiotensin receptor blockers, and mineralocorticoid receptor antagonists for chronic systolic HF for almost two decades, HF remains a leading cause of morbidity, mortality, and health care expenditures. The Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor with Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial provided compelling evidence for the cardiovascular and mortality benefit of sacubitril/valsartan when compared to enalapril in patients with heart failure and reduced ejection fraction (HFrEF). Sacubitril/valsartan performed better than enalapril across various HFrEF patient characteristics and showed substantial benefit in patients with other common comorbidities. Following the trial, the US Food and Drug Administration approved this drug for the treatment of HF. Various international HF consensus guidelines endorse sacubitril/valsartan as a class I recommendation for the management of symptomatic HFrEF. Although this high-quality clinical study is the largest and the most globally represented trial in HFrEF patients, concerns have been raised regarding the generalizability of the trial results in real-world HF population. The gaps in US Food and Drug Administration labeling and guideline recommendations might lead to this medication being used in a larger population than it was studied in. In this review, we will discuss the current role of sacubitril/valsartan in the management of HF, concerns related to PARADIGM-HF and answers, shortcomings of this novel drug, effects on patient characteristics, real-world eligibility, and the role of ongoing and further investigations to clarify

  5. Análisis del consumo de inhibidores de la enzima convertidora de angioténsina en el territorio oeste de La Habana, 2005-2009

    Directory of Open Access Journals (Sweden)

    José Ramón Cabrera Cepero

    2011-12-01

    Full Text Available La planificación de los recursos es un problema trascendental en los países en desarrollo y también en Cuba, por lo que hacer el mejor uso de los presupuestos limitados y de las escasas divisas, es de vital importancia. Planificar las cantidades de medicamentos necesarias, para lograr garantizar una disponibilidad adecuada de estos en todos los niveles de asistencia, es una tarea en la cual intervienen un sinnúmero de factores. El objetivo de este trabajo fue demostrar en qué medida la introducción del enalapril tabletas influyó en el consumo del captopril tabletas, mediante el análisis de los patrones de consumo de los medicamentos inhibidores de la enzima convertidora de angiotensina en el territorio oeste de La Habana entre marzo de 2005 y diciembre de 2009. Para ello se realizó un estudio de utilización de medicamentos de consumo, de tipo descriptivo, observacional y retrospectivo. Se calcularon las DHD (dosis por mil habitantes día. Los resultados de este trabajo demuestran cómo en este grupo hay un desplazamiento del consumo hacia el enalapril. Este es un comportamiento lógico por la comodidad de la administración y la menor incidencia de efectos adversos. Sin embargo, el captopril se mantiene en valores entre 20 y 30 DHD x 1 000 habitantes ya que hay un grupo de pacientes que continúan con este tratamiento y es de elección en la crisis hipertensiva.

  6. Crisis de esclerodermia renal normotensiva

    Directory of Open Access Journals (Sweden)

    M. Villaverde

    2003-01-01

    Full Text Available Paciente de sexo masculino de 60 años con esclerosis sistémica que evolucionó con crisis de esclerodermia renal normotensiva. Tenía compromiso poliarticular, esofágico, pulmonar y cutáneo. Antes de internarse en nuestro hospital recibió tratamiento con altas dosis de corticoides, lo que probablemente precipitó el daño renal que presentó en su evolución, caracterizado por falla renal, anemia hemolítica microangiopática sin elevación de la presión arterial. La ausencia de hipertensión se observa sólo en el 10% de los casos de esclerodermia renal. Recibió tratamiento con enalapril y hemodiálisis. Evolucionó en forma desfavorable, sin respuesta a la terapeútica y falleció a los siete días de internado.A 60 year old male patient having systemic scleroderma and normotensive scleroderma renal crisis was admitted in our hospital. He presented polyarticular, esophagic, lung and skin compromise. Before admission he had been treated with high doses of corticosteroids. We believe corticosteroids led to the worsening of renal damage with renal failure, microangiopathic hemolytic anemia without high blood pressure. The 10% of these cases have normal blood pressure. The patient was treated with enalapril and hemodyalisis. There was no favourable response to this treatment and he died seven days after admission.

  7. Angiotensin converting enzyme inhibitors mitigate collagen synthesis induced by a single dose of radiation to the whole thorax

    International Nuclear Information System (INIS)

    Kma, L.; Gao, F.; Fish, B.L.; Moulder, J.E.; Jacobs, E.R.; Medhora, M.

    2012-01-01

    Our long-term goal is to use angiotensin converting enzyme (ACE) inhibitors to mitigate the increase in lung collagen synthesis that is induced by irradiation to the lung, which could result from accidental exposure or radiological terrorism. Rats (WAG/RijCmcr) were given a single dose of 13 Gy (dose rate of 1.43 Gy/min) of X-irradiation to the thorax. Three structurally-different ACE inhibitors, captopril, enalapril and fosinopril were provided in drinking water beginning 1 week after irradiation. Rats that survived acute pneumonitis (at 6-12 weeks) were evaluated monthly for synthesis of lung collagen. Other endpoints included breathing rate, wet to dry lung weight ratio, and analysis of lung structure. Treatment with captopril (145-207 mg/m 2 /day) or enalapril (19-28 mg/m 2 /day), but not fosinopril (19-28 mg/m 2 /day), decreased morbidity from acute pneumonitis. Lung collagen in the surviving irradiated rats was increased over that of controls by 7 months after irradiation. This increase in collagen synthesis was not observed in rats treated with any of the three ACE inhibitors. Analysis of the lung morphology at 7 months supports the efficacy of ACE inhibitors against radiation-induced fibrosis. The effectiveness of fosinopril against fibrosis, but not against acute pneumonitis, suggests that pulmonary fibrosis may not be a simple consequence of injury during acute pneumonitis. In summary, three structurally-different ACE inhibitors mitigate the increase in collagen synthesis 7 months following irradiation of the whole thorax and do so, even when therapy is started one week after irradiation. (author)

  8. Cost Effectiveness of the Angiotensin Receptor Neprilysin Inhibitor Sacubitril/Valsartan for Patients with Chronic Heart Failure and Reduced Ejection Fraction in the Netherlands: A Country Adaptation Analysis Under the Former and Current Dutch Pharmacoeconomic Guidelines.

    Science.gov (United States)

    Ramos, Isaac Corro; Versteegh, Matthijs M; de Boer, Rudolf A; Koenders, Jolanda M A; Linssen, Gerard C M; Meeder, Joan G; Rutten-van Mölken, Maureen P M H

    2017-12-01

    To describe the adaptation of a global health economic model to determine whether treatment with the angiotensin receptor neprilysin inhibitor LCZ696 is cost effective compared with the angiotensin-converting enzyme inhibitor enalapril in adult patients with chronic heart failure with reduced left ventricular ejection fraction in the Netherlands; and to explore the effect of performing the cost-effectiveness analyses according to the new pharmacoeconomic Dutch guidelines (updated during the submission process of LCZ696), which require a value-of-information analysis and the inclusion of indirect medical costs of life-years gained. We adapted a UK model to reflect the societal perspective in the Netherlands by including travel expenses, productivity loss, informal care costs, and indirect medical costs during the life-years gained and performed a preliminary value-of-information analysis. The incremental cost-effectiveness ratio obtained was €17,600 per quality-adjusted life-year (QALY) gained. This was robust to changes in most structural assumptions and across different subgroups of patients. Probability sensitivity analysis results showed that the probability that LCZ696 is cost-effective at a €50,000 per QALY threshold is 99.8%, with a population expected value of perfect information of €297,128. On including indirect medical costs of life-years gained, the incremental cost-effectiveness ratio was €26,491 per QALY gained, and LCZ696 was 99.46% cost effective at €50,000 per QALY, with a population expected value of perfect information of €2,849,647. LCZ696 is cost effective compared with enalapril under the former and current Dutch guidelines. However, the (monetary) consequences of making a wrong decision were considerably different in both scenarios. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  9. Efficacy and safety of sacubitril/valsartan (LCZ696) in Japanese patients with chronic heart failure and reduced ejection fraction: Rationale for and design of the randomized, double-blind PARALLEL-HF study.

    Science.gov (United States)

    Tsutsui, Hiroyuki; Momomura, Shinichi; Saito, Yoshihiko; Ito, Hiroshi; Yamamoto, Kazuhiro; Ohishi, Tomomi; Okino, Naoko; Guo, Weinong

    2017-09-01

    The prognosis of heart failure patients with reduced ejection fraction (HFrEF) in Japan remains poor, although there is growing evidence for increasing use of evidence-based pharmacotherapies in Japanese real-world HF registries. Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor shown to reduce mortality and morbidity in the recently completed largest outcome trial in patients with HFrEF (PARADIGM-HF trial). The prospectively designed phase III PARALLEL-HF (Prospective comparison of ARNI with ACE inhibitor to determine the noveL beneficiaL trEatment vaLue in Japanese Heart Failure patients) study aims to assess the clinical efficacy and safety of LCZ696 in Japanese HFrEF patients, and show similar improvements in clinical outcomes as the PARADIGM-HF study enabling the registration of LCZ696 in Japan. This is a multicenter, randomized, double-blind, parallel-group, active controlled study of 220 Japanese HFrEF patients. Eligibility criteria include a diagnosis of chronic HF (New York Heart Association Class II-IV) and reduced ejection fraction (left ventricular ejection fraction ≤35%) and increased plasma concentrations of natriuretic peptides [N-terminal pro B-type natriuretic peptide (NT-proBNP) ≥600pg/mL, or NT-proBNP ≥400pg/mL for those who had a hospitalization for HF within the last 12 months] at the screening visit. The study consists of three phases: (i) screening, (ii) single-blind active LCZ696 run-in, and (iii) double-blind randomized treatment. Patients tolerating LCZ696 50mg bid during the treatment run-in are randomized (1:1) to receive LCZ696 100mg bid or enalapril 5mg bid for 4 weeks followed by up-titration to target doses of LCZ696 200mg bid or enalapril 10mg bid in a double-blind manner. The primary outcome is the composite of cardiovascular death or HF hospitalization and the study is an event-driven trial. The design of the PARALLEL-HF study is aligned with the PARADIGM-HF study and aims to assess

  10. Profile of sacubitril/valsartan in the treatment of heart failure: patient selection and perspectives

    Directory of Open Access Journals (Sweden)

    Yandrapalli S

    2017-10-01

    Full Text Available Srikanth Yandrapalli,1 Gabriela Andries,1 Medha Biswas,2 Sahil Khera2,3 1Department of Internal Medicine, New York Medical College at Westchester Medical Center, Valhalla, NY, USA; 2Division of Cardiology, New York Medical College at Westchester Medical Center, Valhalla, NY, USA; 3Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Abstract: With an estimated prevalence of 5.8 million in the USA and over 23 million people worldwide, heart failure (HF is growing in epidemic proportions. Despite the use of guideline-directed medical therapies such as angiotensin-converting enzyme inhibitors, beta-adrenergic blockers, angiotensin receptor blockers, and mineralocorticoid receptor antagonists for chronic systolic HF for almost two decades, HF remains a leading cause of morbidity, mortality, and health care expenditures. The Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor with Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF trial provided compelling evidence for the cardiovascular and mortality benefit of sacubitril/valsartan when compared to enalapril in patients with heart failure and reduced ejection fraction (HFrEF. Sacubitril/valsartan performed better than enalapril across various HFrEF patient characteristics and showed substantial benefit in patients with other common comorbidities. Following the trial, the US Food and Drug Administration approved this drug for the treatment of HF. Various international HF consensus guidelines endorse sacubitril/valsartan as a class I recommendation for the management of symptomatic HFrEF. Although this high-quality clinical study is the largest and the most globally represented trial in HFrEF patients, concerns have been raised regarding the generalizability of the trial results in real-world HF population. The gaps in US Food and Drug Administration labeling and

  11. Induction of albuminuria in mice: synergistic effect of two monoclonal antibodies directed to different domains of aminopeptidase A.

    Science.gov (United States)

    Mentzel, S; van Son, J P; Dijkman, H B; Wetzels, J F; Assmann, K J

    1999-04-01

    Aminopeptidase A is an enzyme that is present on podocytes and is involved in the degradation of angiotensin II. In previous studies in mice, we administered single monoclonal antibodies directed against aminopeptidase A. We observed that only monoclonal antibodies that inhibited aminopeptidase A enzyme activity caused albuminuria. In this study, the effects of the combined injections of two monoclonal anti-aminopeptidase A antibodies (mAbs) were studied, using a combination of anti-aminopeptidase A mAbs that were directed against two different domains involved in the aminopeptidase A enzyme activity (ASD-3 or ASD-37) and an anti-aminopeptidase A mAb not related to the enzyme active site (ASD-41). An injection of the combinations ASD-3/37 (total 4 mg, 1:1 ratio) and ASD-37/41 (total 4 mg, 1:1 ratio) in doses that do not cause albuminuria when given alone (4 mg) induced massive albuminuria at day 1 after injection. The combination ASD-3/41 had no effect. This albuminuria was not dependent on systemic immune mediators of inflammation and could not merely be related to a blockade of aminopeptidase A enzyme activity. However, a correlation was observed between the induction of albuminuria and the aggregation of the mAbs injected and aminopeptidase A on the podocytes. An injection of the combinations ASD-3/37 or ASD-37/41 did not cause an increase in systemic blood pressure. The treatment with a combination of enalapril and losartan lowered blood pressure (53 +/- 10 vs. 90 +/- 3 mm Hg in untreated mice) and reduced the acute albuminuria by 55% (11,145 +/- 864 vs. 24,517 +/- 2448 micrograms albumin/18 hr in untreated mice). However, similar effects were observed using triple therapy. Therefore, the reduction of albuminuria by the combined treatment of enalapril/losartan seems to be the consequence of the reduction in the systemic blood pressure. These findings argue against a specific role for angiotensin II in this model. The combined injection of two mAbs directed

  12. Evaluation by N-terminal prohormone of brain natriuretic peptide concentrations and ross scoring of the efficacy of digoxin in the treatment of heart failure secondary to congenital heart disease with left-to-right shunts.

    Science.gov (United States)

    Elkiran, Ozlem; Sandikkaya, Ayse; Kocak, Gulendam; Karakurt, Cemsit; Taskapan, Cagatay; Yologlu, Saim

    2013-10-01

    This study aimed to evaluate the effectiveness of digoxin in children with heart failure secondary to left-to-right shunt lesions and normal left ventricular systolic function. The study registered 37 such patients (ages 10 days to 24 months, groups 1 and 2) and used 20 healthy children as a control group (group 3). Left ventricular systolic function, as assessed by conventional echocardiography, was normal in all the subjects. Congestive heart failure was diagnosed by clinical evaluation and modified Ross scoring. Plasma N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentrations and complete blood counts were assessed in all the children. Group 1 was treated with digoxin, enalapril, and furosemide and group 2 with enalapril and furosemide. Approximately 1 month after starting treatment, the patients were reevaluated by physical and echocardiographic examinations, modified Ross scoring, plasma NT-proBNP concentrations, and complete blood counts. The pre- and posttreatment Ross scores of group 1 (p = 0.377) and group 2 (p = 0.616) did not differ significantly. The NT-proBNP values in both groups decreased after treatment (p = 0.0001). The pre- and posttreatment NT-proBNP values did not differ significantly in group 1 (p = 0.094)) and group 2 (p = 0.372). The pretreatment NT-proBNP values in groups 1 and 2 (p = 0.0001) were significantly higher than in the control group (p = 0.003). A smaller difference was observed between posttreatment NT-proBNP values in group 1 and the control group (p = 0.045). We found no significant difference between the posttreatment NT-proBNP values of group 2 and those of the control group (p = 0.271). The study showed that both treatments currently used to treat heart failure secondary to congenital heart disease with left-to-right shunts and preserved left ventricular systolic function are effective and do not differ significantly. Thus, digoxin does not provide any extra benefit in the treatment of such patients.

  13. Effects of angiotensin (1-7 on nephrosis of the mice with metabolic syndrome induced by high-salt and high-fat diet

    Directory of Open Access Journals (Sweden)

    Nan ZHU

    2013-11-01

    Full Text Available Objective  To establish a metabolic syndrome model of C57BL/6 mice by high-salt and high-fat diet, and investigate the effects of angiotensin converting enzyme 2 (ACE 2 and angiotensin (1-7 on renal damage in mice. Methods Fifty-six male C57BL/6 mice were randomly divided into 7 groups (8 each, and fed with normal diet (0.3% NaCl, 10% fat, high-salt diet (8% NaCl, 10% fat, high-fat diet (0.3% NaCl, 60% fat, high-salt and high-fat diet (8% NaCl, 60% fat, high-salt and high-fat diet with enalapril 20mg/(kg•d, with valsartan 50mg/(kg•d, and with valsartan 50mg/(kg•d plus Mas receptor antagonist (A-779 150ng/(kg•d, respectively for 16 weeks. Basal metabolic index including blood pressure, body weight, blood glucose and urinary albumin excretion rate (UAER were tested. After intraperitoneal anesthesia with chloral hydrate, the blood was collected from the carotid artery. Serum angiotensin Ⅱ and angiotensin (1-7 levels were detected by ELISA; Western blotting was performed to evaluate the expression of ACE 2 protein and collagen Ⅲ in renal tissue; renal pathological changes were observed by HE and Masson staining. Results The blood pressure, ratio of visceral fat weight/body weight, blood lipid, blood glucose and UAER increased significantly in the C57BL/6 mice fed with high-salt and high-fat diet for 16 weeks, and the renal fibrosis change was obvious, serum angiotensin Ⅱ level increased, expressions of ACE 2 and angiotensin (1-7 decreased significantly in the renal tissue. In different intervention groups, valsartan obviously alleviated the abnormal metabolism, ameliorated renal injury, promoted the expression of ACE2 and angiotensin (1-7 in the kidney and serum. However, no significant change was observed in the groups with intervention of enalapril or valsartan+A-779 compared with non-intervention group. Conclusions High-salt and high-fat diet can be used to successfully establish the model of metabolic syndrome in C57BL/6

  14. Combination Therapy for the Cardiovascular Effects of Perinatal Lead Exposure in Young and Adult Rats

    International Nuclear Information System (INIS)

    Gaspar, Andréia Fresneda; Cordellini, Sandra

    2014-01-01

    Combination therapy can play a significant role in the amelioration of several toxic effects of lead (Pb) and recovery from associated cardiovascular changes. To investigate the effects of combination therapy on the cardiovascular effects of perinatal lead exposure in young and adult rats Female Wistar rats received drinking water with or without 500 ppm of Pb during pregnancy and lactation. Twenty-two- and 70-day-old rat offspring who were or were not exposed to Pb in the perinatal period received meso-dimercaptosuccinic acid (DMSA), L-arginine, or enalapril and a combination of these compounds for 30 additional days. Noradrenaline response curves were plotted for intact and denuded aortas from 23-, 52-, 70-, and 100-day-old rats stratified by perinatal Pb exposure (exposed/unexposed) and treatment received (treated/untreated). Systolic blood pressure was evaluated and shown to be higher in the 23-, 52-, 70-, and 100-day age groups with Pb exposure than in the corresponding control age groups: 117.8 ± 3.9*, 135.2 ± 1.3*, 139.6 ± 1.6*, and 131.7 ± 2.8*, respectively and 107.1 ± 1.8, 118.8 ± 2.1, 126.1 ± 1.1, and 120.5 ± 2.2, respectively (p < 0.05). Increased reactivity to noradrenaline was observed in intact, but not denuded, aortas from 52-, 70-, and 100-day-old exposed rats, and the maximum responses (g of tension) in the respective Pb-exposed and control age groups were as follows: 3.43 ± 0.16*, 4.32 ± 0.18*, and 4.21 ± 0.23*, respectively and 2.38 ± 0.33, 3.37 ± 0.13, and 3.22 ± 0.21, respectively (p < 0.05). All treatments reversed the changes in vascular reactivity to noradrenaline in rats perinatally exposed to Pb. The combination therapy resulted in an earlier restoration of blood pressure in Pb-exposed rats compared with the monotherapies, except for enalapril therapy in young rats. These findings represent a new approach to the development of therapeutic protocols for the treatment of Pb-induced hypertension

  15. Potentiation of the actions of bradykinin by angiotensin I-converting enzyme inhibitors. The role of expressed human bradykinin B2 receptors and angiotensin I-converting enzyme in CHO cells.

    Science.gov (United States)

    Minshall, R D; Tan, F; Nakamura, F; Rabito, S F; Becker, R P; Marcic, B; Erdös, E G

    1997-11-01

    Part of the beneficial effects of angiotensin I-converting enzyme (ACE) inhibitors are due to augmenting the actions of bradykinin (BK). We studied this effect of enalaprilat on the binding of [3H]BK to Chinese hamster ovary (CHO) cells stably transfected to express the human BK B2 receptor alone (CHO-3B) or in combination with ACE (CHO-15AB). In CHO-15AB cells, enalaprilat (1 mumol/L) increased the total number of low-affinity [3H]BK binding sites on the cells at 37 degrees C, but not at 4 degrees C, from 18.4 +/- 4.3 to 40.3 +/- 11.9 fmol/10(6) cells (P potentiated the release of [3H]arachidonic acid and the liberation of inositol 1,4,5-trisphosphate (IP3) induced by BK and [Hyp3-Tyr(Me)8]BK. Moreover, enalaprilat (1 mumol/L) completely and immediately restored the response of the B2 receptor, desensitized by the agonist (1 mumol/L [Hyp3-Tyr(Me)8]BK); this effect was blocked by the antagonist, HOE 140. Finally, enalaprilat, but not the prodrug enalapril, decreased internalization of the receptor from 70 +/- 9% to 45 +/- 9% (P desensitization, and decrease internalization, thereby potentiating BK beyond blocking its hydrolysis.

  16. Continuous manufacturing and analytical characterization of fixed-dose, multilayer orodispersible films.

    Science.gov (United States)

    Thabet, Yasmin; Lunter, Dominique; Breitkreutz, Joerg

    2018-05-30

    Various drug therapies require more than one active pharmaceutical ingredient (API) for an effective treatment. There are many advantages, e.g. to improve the compliance or pharmacodynamic response in comparison to a monotherapy or to increase the therapy safety. Until now, there are only a few products available for the paediatric population due to the lack of age appropriate dosage forms or studies proving the efficacy and safety of these products. This study aims to develop orodispersible films (ODFs) in a continuous solvent casting process as child appropriate dosage form containing both enalapril maleate (EM) and hydrochlorothiazide (HCT) separated in different film layers. Furthermore, they should be characterised and the API migration analysed by confocal Raman microscopy (CRM). ODFs were successfully produced in a continuous manufacturing process in form of double- and triple-layer formulations based on hydroxypropylcellulose (HPC) or a combination of HPC and polyvinyl alcohol (PVA). CRM revealed that both APIs migrate within the film layers shortly after manufacturing. PVA inhibits the migration inside the double-layer film, but is not able to prevent the API migration as an interlayer inside a triple-layer ODF. With increasing film layers, the content of residual solvents and the disintegration time increases (mono-layer films: processing two incompatible APIs. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. A Case of Refractory Heart Failure in Becker Muscular Dystrophy Improved With Corticosteroid Therapy.

    Science.gov (United States)

    Nakamura, Makiko; Sunagawa, Osahiko; Hokama, Ryo; Tsuchiya, Hiroyuki; Miyara, Takafumi; Taba, Yoji; Touma, Takashi

    2016-09-28

    The patient was a 26 year-old man who was referred to our hospital in June 2011 because of severe heart failure. At age 24 years, he was found to have Becker muscular dystrophy. He received enalapril for cardiac dysfunction; however, he had worsening heart failure and was thus referred to our hospital. Echocardiography showed enlargement of the left ventricle, with a diastolic dimension of 77 mm and ejection fraction of 19%. His condition improved temporarily after an infusion of dobutamine and milrinone. He was then administered amiodarone for ventricular tachycardia; however, he subsequently developed hemoptysis. Amiodarone was discontinued and corticosteroid pulse therapy was administered followed by oral prednisolone (PSL). His creatinine phosphokinase (CPK) level and cardiomegaly improved after the corticosteroid therapy. The PSL dose was reduced gradually, bisoprolol was introduced, and the catecholamine infusion was tapered. A cardiac resynchronization device was implanted; however, the patient's condition gradually worsened, which necessitated dobutamine infusion for heart failure. We readministered 30 mg PSL, which decreased the CPK level and improved the cardiomegaly. The dobutamine infusion was discontinued, and the patient was discharged. He was given 7.5 mg PSL as an outpatient, and he returned to normal life without exacerbation of the heart failure. There are similar reports showing that corticosteroids are effective for skeletal muscle improvement in Duchenne muscular dystrophy; however, their effectiveness for heart failure has been rarely reported. We experienced a case of Becker muscular dystrophy in which corticosteroid therapy was effective for refractory heart failure.

  18. Splanchnic blood flow and hepatic glucose production in exercising humans

    DEFF Research Database (Denmark)

    Bergeron, R; Kjaer, M; Simonsen, L

    2001-01-01

    The study examined the implication of the renin-angiotensin system (RAS) in regulation of splanchnic blood flow and glucose production in exercising humans. Subjects cycled for 40 min at 50% maximal O(2) consumption (VO(2 max)) followed by 30 min at 70% VO(2 max) either with [angiotensin-converti......The study examined the implication of the renin-angiotensin system (RAS) in regulation of splanchnic blood flow and glucose production in exercising humans. Subjects cycled for 40 min at 50% maximal O(2) consumption (VO(2 max)) followed by 30 min at 70% VO(2 max) either with [angiotensin......-converting enzyme (ACE) blockade] or without (control) administration of the ACE inhibitor enalapril (10 mg iv). Splanchnic blood flow was estimated by indocyanine green, and splanchnic substrate exchange was determined by the arteriohepatic venous difference. Exercise led to an approximately 20-fold increase (P ...-blockade group vs. the control group, hormones, metabolites, VO(2), and RER followed the same pattern of changes in ACE-blockade and control groups during exercise. Splanchnic blood flow (at rest: 1.67 +/- 0.12, ACE blockade; 1.59 +/- 0.18 l/min, control) decreased during moderate exercise (0.78 +/- 0.07, ACE...

  19. Potential Expanded Indications for Neprilysin Inhibitors

    Science.gov (United States)

    Riddell, Elizabeth; Vader, Justin M.

    2017-01-01

    Purpose of review The goal of this article is to review potential expanded indications for neprilysin inhibitors. This article reviews the rationale and design for ongoing and future trials of sacubitril/valsartan in cardiovascular and non-cardiovascular disease. Recent findings Randomized trial data are lacking for use of sacubitril/valsartan in acute heart failure and advanced heart failure. Mechanistic data from animal studies suggest a role for neprilysin inhibition in the treatment of post-myocardial infarction systolic dysfunction and heart failure with preserved ejection fraction. Beyond the cardiovascular system, renal and neurological function may be impacted by neprilysin inhibition. Forthcoming randomized trials will address the clinical impact of sacubitril/valsartan on these conditions. Summary Neprolysin inhibition with sacubitril/valsartan offers a new therapeutic strategy with a broad range of potential therapeutic actions. In PARADIGM-HF, the combination of neprolysin and RAAS inhibition was proven to be superior to enalapril for patients with stable NYHA class II–III heart failure and reduced left ventricular ejection fraction. Preliminary data suggests it may also have a role in other cardiovascular and non-cardiovascular disease. Several ongoing and planned studies will determine the extent of its benefit for these other indications. PMID:28281174

  20. Sacubitril/valsartan and short-term changes in the 6-minute walk test: A pilot study.

    Science.gov (United States)

    Beltrán, Paola; Palau, Patricia; Domínguez, Eloy; Faraudo, Mercedes; Núñez, Eduardo; Guri, Olga; Mollar, Anna; Sanchis, Juan; Bayés-Genís, Antoni; Núñez, Julio

    2018-02-01

    Impaired exercise capacity is the most disabling symptom in patients with heart failure with reduced ejection fraction (HFrEF). Despite sacubitril/valsartan showing reduced long-term morbidity and mortality over enalapril in HFrEF, its effects on short-term functional capacity remain uncertain. We sought to evaluate the effects of sacubitril/valsartan on a 30-day six-minute walk test in eligible patients with HFrEF. From November 1, 2016 to February 1, 2017, a total of 58 stable symptomatic patients with HFrEF were eligible for sacubitril/valsartan and underwent 6-MWT before and 30days after initiation of sacubitril/valsartan therapy. A mixed-effects model for repeated-measures was used to analyze the changes. Mean age was 70±11years. 72.4% males, 46.6% with ischemic heart disease, and 51.7% on NYHA functional class III were included. The mean (SD) values of baseline LVEF and 6MWT were 30±7%, and 300±89m, respectively. The median (IQR) of NT-proBNP at baseline was 2701pg/ml (1087-4200). Compared with baseline, the 6-MWT distance increased significantly at 30days by 13.9% (+∆=41.8m (33.4-50.2); psacubitril/valsartan was associated with an improvement in exercise tolerance in symptomatic patients with HFrEF. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  1. Spotlight on valsartan-sacubitril fixed-dose combination for heart failure: the evidence to date.

    Science.gov (United States)

    Vilela-Martin, José Fernando

    2016-01-01

    Heart failure is a global problem with elevated prevalence, and it is associated with substantial cardiovascular morbidity and mortality. Treating heart-failure patients has been a very challenging task. This review highlights the main pharmacological developments in the field of heart failure with reduced ejection fraction, giving emphasis to a drug that has a dual-acting inhibition of the neprilysin and renin-angiotensin-aldosterone system. Neprilysin is an enzyme that participates in the breakdown of biologically active natriuretic peptides and several other vasoactive compounds. The inhibition of neprilysin has been a therapeutic target for several drugs tested in cardiovascular disease, mainly for heart failure and/or hypertension. However, side effects and a lack of efficacy led to discontinuation of their development. LCZ696 is a first-in-class neprilysin- and angiotensin-receptor inhibitor that has been developed for use in heart failure. This drug is composed of two molecular moieties in a single crystalline complex: a neprilysin-inhibitor prodrug (sacubitril) and the angiotensin-receptor blocker (valsartan). The PARADIGM-HF trial demonstrated that this drug was superior to an angiotensin-converting enzyme inhibitor (enalapril) in reducing mortality in patients with heart failure with reduced ejection fraction. The ability to block the angiotensin receptor and augment the endogenous natriuretic peptide system provides a distinctive mechanism of action in cardiovascular disease.

  2. Practical considerations on the introduction of sacubitril/valsartan in clinical practice: Current evidence and early experience.

    Science.gov (United States)

    Farmakis, Dimitrios; Bistola, Vassiliki; Karavidas, Apostolos; Parissis, John

    2016-11-15

    The combination of neprilysin inhibitor sacubitril with the angiotensin II receptor 1 blocker valsartan is the first agent from the angiotensin receptor neprilysin inhibitors (ARNI) class authorized for clinical use in heart failure (HF) patients with reduced ejection fraction (HFrEF). Sacubitril/valsartan resulted in 20% reduction in the incidence rate of death or HF hospitalization compared to enalapril in symptomatic HFrEF patients in the seminal PARADIGM-HF trial. As a result, the recently updated European and American HF guidelines granted this agent a class IB indication for the treatment of ambulatory/chronic symptomatic HFrEF patients. However, translating the positive results of trials into true clinical benefit is often challenging. This is particularly true in the case of sacubitril/valsartan, as HF is a heterogeneous syndrome including many severely ill patients who are prone to decompensation, while this new agent comes to replace a cornerstone of current evidence-based HF therapy. In the present paper, we address a number of practical issues regarding the introduction of sacubitril/valsartan and propose an algorithm based on available evidence and early clinical experience. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Sacubitril/valsartan in heart failure: latest evidence and place in therapy

    Science.gov (United States)

    Kaplinsky, Edgardo

    2016-01-01

    Despite significant therapeutic advances, patients with chronic heart failure (HF) remain at high risk for HF progression and death. Sacubitril/valsartan (previously known as LCZ696) is a first-in-class medicine that contains a neprilysin (NEP) inhibitor (sacubitril) and an angiotensin II (Ang-II) receptor blocker (valsartan). NEP is an endopeptidase that metabolizes different vasoactive peptides including natriuretic peptides, bradykinin and Ang-II. In consequence, its inhibition increases mainly the levels of both, natriuretic peptides (promoting diuresis, natriuresis and vasodilatation) and Ang-II whose effects are blocked by the angiotensin receptor blocker, valsartan (reducing vasoconstriction and aldosterone release). Results from the 8442 patient PARADIGM-HF study showed in patients with New York Heart Association (NYHA) class II–IV and reduced ejection fraction treated with LCZ696 (versus enalapril), the following benefits: reduction of the risk of death from cardiovascular causes by 20%; reduction of HF hospitalizations by 21%; reduction of the risk of all-cause mortality by 16%. Overall there was a 20% risk reduction on the primary endpoint, composite measure of cardiovascular (CV) death or time to first HF hospitalization. PARADIGM-HF was stopped early after a median follow up of 27 months. Post hoc analyses of PARADIGM-HF as well as the place in therapy of sacubitril/valsartan, including future directions, are included in the present review. PMID:27803793

  4. Effects of Sacubitril/Valsartan in the PARADIGM-HF Trial (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) According to Background Therapy.

    Science.gov (United States)

    Okumura, Naoki; Jhund, Pardeep S; Gong, Jianjian; Lefkowitz, Martin P; Rizkala, Adel R; Rouleau, Jean L; Shi, Victor C; Swedberg, Karl; Zile, Michael R; Solomon, Scott D; Packer, Milton; McMurray, John J V

    2016-09-01

    In the PARADIGM-HF trial (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure), the angiotensin receptor neprilysin inhibitor sacubitril/valsartan was more effective than the angiotensin-converting enzyme inhibitorenalapril in patients with heart failure and reduced ejection fraction. We examined whether this benefit was consistent irrespective of background therapy. We examined the effect of study treatment in the following subgroups: diuretics (yes/no), digitalis glycoside (yes/no), mineralocorticoid receptor antagonist (yes/no),and defibrillating device (implanted defibrillating device, yes/no). We also examined the effect of study drug according to β-blocker dose (≥50% and sacubitril/valsartan versus enalapril hazard ratio for the primary composite end point was 0.80 (95% confidence interval,0.73-0.87;Psacubitril/valsartan was consistent across all subgroups examined. The hazard ratio for primary end point ranged from 0.74 to 0.85 and for cardiovascular death rangedfrom 0.75 to 0.89, with no treatment-by-subgroup interaction. The benefit of sacubitril/valsartan, over an angiotensin-converting enzyme inhibitor, was consistent regardless of background therapy and irrespective of previouscoronary revascularization or β-blocker dose. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255. © 2016 American Heart Association, Inc.

  5. Benefits and Harms of Sacubitril in Adults With Heart Failure and Reduced Left Ventricular Ejection Fraction.

    Science.gov (United States)

    Aronow, Wilbert S; Shamliyan, Tatyana A

    2017-10-01

    The quality of evidence regarding patient-centered outcomes in adults with heart failure (HF) after sacubitril combined with valsartan has not been systematically appraised. We searched 4 databases in February 2017 and graded the quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation working group approach. We reviewed 1 meta-analysis and multiple publications of 2 randomized controlled trials (RCT) and 1 unpublished RCT. In adults with HF and reduced ejection fraction, low-quality evidence from 1 RCT of 8,432 patients suggests that sacubitril combined with valsartan reduces all-cause (number needed to treat [NNT] to prevent 1 event [NNTp] = 35) and cardiovascular mortality (NNTp = 32), hospitalization (NNTp = 11), emergency visits (NNTp = 69), and serious adverse effects, leading to treatment discontinuation (NNTp = 63) and improves quality of life when compared with enalapril. In adults with HF and preserved ejection fraction, very low-quality evidence from 1 RCT of 301 patients suggests that there are no differences in mortality, morbidity, or adverse effects between sacubitril combined with valsartan and valsartan alone. In conclusion, in adults with HF and reduced ejection fraction, to reduce cardiovascular mortality and hospitalizations and improve quality of life, clinicians may recommend sacubitril combined with valsartan over angiotensin-converting enzyme inhibitors. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Spotlight on valsartan–sacubitril fixed-dose combination for heart failure: the evidence to date

    Science.gov (United States)

    Vilela-Martin, José Fernando

    2016-01-01

    Heart failure is a global problem with elevated prevalence, and it is associated with substantial cardiovascular morbidity and mortality. Treating heart-failure patients has been a very challenging task. This review highlights the main pharmacological developments in the field of heart failure with reduced ejection fraction, giving emphasis to a drug that has a dual-acting inhibition of the neprilysin and renin–angiotensin–aldosterone system. Neprilysin is an enzyme that participates in the breakdown of biologically active natriuretic peptides and several other vasoactive compounds. The inhibition of neprilysin has been a therapeutic target for several drugs tested in cardiovascular disease, mainly for heart failure and/or hypertension. However, side effects and a lack of efficacy led to discontinuation of their development. LCZ696 is a first-in-class neprilysin- and angiotensin-receptor inhibitor that has been developed for use in heart failure. This drug is composed of two molecular moieties in a single crystalline complex: a neprilysin-inhibitor prodrug (sacubitril) and the angiotensin-receptor blocker (valsartan). The PARADIGM-HF trial demonstrated that this drug was superior to an angiotensin-converting enzyme inhibitor (enalapril) in reducing mortality in patients with heart failure with reduced ejection fraction. The ability to block the angiotensin receptor and augment the endogenous natriuretic peptide system provides a distinctive mechanism of action in cardiovascular disease. PMID:27274196

  7. Changing the treatment of heart failure with reduced ejection fraction: clinical use of sacubitril-valsartan combination

    Science.gov (United States)

    Kaplinsky, Edgardo

    2016-01-01

    Despite significant therapeutic advances, patients with chronic heart failure (HF) remain at high risk of morbidity and mortality. Sacubitril valsartan (previously known as LCZ696) is a new oral agent approved for the treatment of symptomatic chronic heart failure in adults with reduced ejection fraction. It is described as the first in class angiotensin receptor neprilysin inhibitor (ARNI) since it incorporates the neprilysin inhibitor, sacubitril and the angiotensin II receptor antagonist, valsartan. Neprilysin is an endopeptidase that breaks down several vasoactive peptides including natriuretic peptides (NPs), bradykinin, endothelin and angiotensin II (Ang-II). Therefore, a natural consequence of its inhibition is an increase of plasmatic levels of both, NPs and Ang-II (with opposite biological actions). So, a combined inhibition of these both systems (Sacubitril / valsartan) may enhance the benefits of NPs effects in HF (natriuresis, diuresis, etc) while Ang-II receptor is inhibited (reducing vasoconstriction and aldosterone release). In a large clinical trial (PARADIGM-HF with 8442 patients), this new agent was found to significantly reduce cardiovascular and all cause mortality as well as hospitalizations due to HF (compared to enalapril). This manuscript reviews clinical evidence for sacubitril valsartan, dosing and cautions, future directions and its considered place in the therapy of HF with reduced ejection fraction. PMID:28133468

  8. Effect of Age on Hypertension: Analysis of Over 4,800 Referred Hypertensive Patients

    Directory of Open Access Journals (Sweden)

    Anderson Gunnar

    1999-01-01

    Full Text Available We evaluate in this study the factors associated with the effect of age on blood pressure in more than 4800 patients. Their physicians referred them to evaluate for secondary causes for their hypertension. Factors studied included history and physical examination, serum sodium, potassium and creatinine, a stimulated plasma renin and catecholamine. We also studied the blood pressure response to infusion of either saralasin (an angiotensin II analogue or enalapril (an angiotensin converting enzyme inhibitor, and plasma aldosterone and cortisol after infusion of saline. We measured serum thyroxin and thyroid stimulating hormone concentrations on 1061 consecutive patients in this series. The results of our study show that increased age is associated with a significant increase in the prevalence of hypertension and especially of systolic hypertension after age 60 years. Increased obesity between age 30-50 years is associated with significant increases in diastolic blood pressure and this trend is also seen in African-Americans who are heavier than whites. Increased age is associated with an increased prevalence of secondary forms of hypertension including atherosclerotic renovascular hypertension, renal insufficiency and primary hypothyroidism.

  9. Roselle is cardioprotective in diet-induced obesity rat model with myocardial infarction.

    Science.gov (United States)

    Si, Lislivia Yiang-Nee; Ali, Siti Aishah Mohd; Latip, Jalifah; Fauzi, Norsyahida Mohd; Budin, Siti Balkis; Zainalabidin, Satirah

    2017-12-15

    Obesity increase the risks of hypertension and myocardial infarction (MI) mediated by oxidative stress. This study was undertaken to investigate the actions of roselle aqueous extract (R) on cardiotoxicity in obese (OB) rats and thereon OB rats subjected to MI. Male Sprague-Dawley rats were fed with either normal diet or high-fat diet for 8weeks. Firstly, OB rats were divided into (1) OB and (2) OB+R (100mg/kg, p.o, 28days). Then, OB rats were subjected to MI (ISO, 85mg/kg, s.c, 2days) and divided into three groups: (1) OB+MI, (2) OB+MI+R and (3) OB+MI+enalapril for another 4weeks. Roselle ameliorated OB and OB+MI's cardiac systolic dysfunction and reduced cardiac hypertrophy and fibrosis. The increased oxidative markers and decreased antioxidant enzymes in OB and OB+MI groups were all attenuated by roselle. These observations indicate the protective effect of roselle on cardiac dysfunction in OB and OB+MI rats, which suggest its potential to be developed as a nutraceutical product for obese and obese patients with MI in the future. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Isolated unilateral absence of the right pulmonary artery in two cats visualized by computed tomography angiography

    Directory of Open Access Journals (Sweden)

    Tyler JM Jordan

    2016-10-01

    Full Text Available Case series summary Two cats were evaluated for progressive exercise intolerance, dyspnea and unilateral infiltrate of the left lung. Computed tomography angiography (CTA revealed absence of the right pulmonary artery in both cats with systemic arterial collateral vessels perfusing the right segmental pulmonary arteries. In one case, the collateral vessels arose from the esophageal artery, while in the other case they derived off the right costocervical trunk. One cat was diagnosed with pulmonary hypertension and was euthanized owing to progressive respiratory distress despite medical management with sildenafil, pimobendan, clopidogrel and furosemide. The other cat, without echocardiographic evidence of pulmonary hypertension, was successfully managed with furosemide and enalapril for more than 4 years. Relevance and novel information CTA allowed visualization of a rare congenital heart malformation, unilateral absence of the right pulmonary artery, in two cats and accurately characterized the source of collateral blood supply to the affected lung. Severe pulmonary hypertension may be a negative prognostic factor in cats with this condition as medical therapy in the cat without evidence of pulmonary hypertension resolved clinical signs, while the cat with severe pulmonary hypertension died from the disease.

  11. Theoretical repeatability assessment without repetitive measurements in gradient high-performance liquid chromatography.

    Science.gov (United States)

    Kotani, Akira; Tsutsumi, Risa; Shoji, Asaki; Hayashi, Yuzuru; Kusu, Fumiyo; Yamamoto, Kazuhiro; Hakamata, Hideki

    2016-07-08

    This paper puts forward a time and material-saving method for evaluating the repeatability of area measurements in gradient HPLC with UV detection (HPLC-UV), based on the function of mutual information (FUMI) theory which can theoretically provide the measurement standard deviation (SD) and detection limits through the stochastic properties of baseline noise with no recourse to repetitive measurements of real samples. The chromatographic determination of terbinafine hydrochloride and enalapril maleate is taken as an example. The best choice of the number of noise data points, inevitable for the theoretical evaluation, is shown to be 512 data points (10.24s at 50 point/s sampling rate of an A/D converter). Coupled with the relative SD (RSD) of sample injection variability in the instrument used, the theoretical evaluation is proved to give identical values of area measurement RSDs to those estimated by the usual repetitive method (n=6) over a wide concentration range of the analytes within the 95% confidence intervals of the latter RSD. The FUMI theory is not a statistical one, but the "statistical" reliability of its SD estimates (n=1) is observed to be as high as that attained by thirty-one measurements of the same samples (n=31). Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Sex differences in the enhanced responsiveness to acute angiotensin II in growth-restricted rats: role of fasudil, a Rho kinase inhibitor.

    Science.gov (United States)

    Ojeda, Norma B; Royals, Thomas P; Alexander, Barbara T

    2013-04-01

    This study tested the hypothesis that Rho kinase contributes to the enhanced pressor response to acute angiotensin II in intact male growth-restricted and gonadectomized female growth-restricted rats. Mean arterial pressure (MAP) and renal function were determined in conscious animals pretreated with enalapril (250 mg/l in drinking water) for 1 wk to block the endogenous renin-angiotensin system and normalize blood pressure (baseline). Blood pressure and renal hemodynamics did not differ at baseline. Acute Ang II (100 ng·kg(-1)·min(-1)) induced a greater increase in MAP and renal vascular resistance and enhanced reduction in glomerular filtration rate in intact male growth-restricted rats compared with intact male controls (P back to baseline in male growth-restricted rats, and yet glomerular filtration rate remained significantly reduced (P < 0.05). Thus, these data suggest a role for enhanced renal sensitivity to acute Ang II in the developmental programming of hypertension in male growth-restricted rats. However, inhibition of Rho kinase had no effect on the basal or enhanced increase in blood pressure induced by acute Ang II in the gonadectomized female growth-restricted rat. Therefore, these studies suggest that Rho kinase inhibition exerts a sex-specific effect on blood pressure sensitivity to acute Ang II in growth-restricted rats.

  13. A Zebrafish Heart Failure Model for Assessing Therapeutic Agents.

    Science.gov (United States)

    Zhu, Xiao-Yu; Wu, Si-Qi; Guo, Sheng-Ya; Yang, Hua; Xia, Bo; Li, Ping; Li, Chun-Qi

    2018-03-20

    Heart failure is a leading cause of death and the development of effective and safe therapeutic agents for heart failure has been proven challenging. In this study, taking advantage of larval zebrafish, we developed a zebrafish heart failure model for drug screening and efficacy assessment. Zebrafish at 2 dpf (days postfertilization) were treated with verapamil at a concentration of 200 μM for 30 min, which were determined as optimum conditions for model development. Tested drugs were administered into zebrafish either by direct soaking or circulation microinjection. After treatment, zebrafish were randomly selected and subjected to either visual observation and image acquisition or record videos under a Zebralab Blood Flow System. The therapeutic effects of drugs on zebrafish heart failure were quantified by calculating the efficiency of heart dilatation, venous congestion, cardiac output, and blood flow dynamics. All 8 human heart failure therapeutic drugs (LCZ696, digoxin, irbesartan, metoprolol, qiliqiangxin capsule, enalapril, shenmai injection, and hydrochlorothiazide) showed significant preventive and therapeutic effects on zebrafish heart failure (p failure model developed and validated in this study could be used for in vivo heart failure studies and for rapid screening and efficacy assessment of preventive and therapeutic drugs.

  14. Right Heart Failure in an African Penguin ( Spheniscus demersus ).

    Science.gov (United States)

    Cusack, Lara; Field, Cara; McDermott, Alexa; Pogue, Brandon; Clauss, Tonya; Bossart, Gregory; Camus, Alvin

    2016-09-01

    A 19-year-old male African penguin ( Spheniscus demersus ) was presented with coelomic distention after a 6-week history of lethargy and decreased appetite. Results of radiographs showed loss of coelomic detail, and ultrasound and computed tomography results revealed coelomic fluid and dilated hepatic veins. Echocardiography revealed moderate right atrial enlargement. Findings were consistent with right-sided cardiac disease. Treatment with furosemide initially reduced ascites, but the clinical condition worsened weeks later and enalapril, pimobendan, and sildenafil were added to the medical therapy. At 12 weeks after presentation, results of an echocardiogram revealed persistent right atrioventricular valve regurgitation, moderate ascites, and dilation of hepatic veins. Clinical signs of right heart failure were managed through adjustments in medical therapy and coelomic fluid aspiration, but the bird died 18 weeks after initial presentation. Gross and microscopic findings were consistent with valvular insufficiency and right-sided heart failure. To our knowledge, this case is the first documented report of cardiac disease in an African penguin.

  15. Evaluation of ACE inhibitors lipophilicity using in silico and chromatographically obtained hydrophobicity parameters

    Directory of Open Access Journals (Sweden)

    Odović Jadranka V.

    2013-01-01

    Full Text Available The aim of this study was to compare different calculation methods to determine lipophilicity, expressed as logP value, of seven ACE inhibitors (enalapril, quinapril, fosinopril, lisinopril, cilazapril, ramipril, and benazapril with significantly different structure. Experimentally determined n-octanol/water partition coefficients, logPO/W values, were obtained from relevant literature. The correlations between all collected logP values were studied and the best agreements between calculated logP and experimentally determined logPO/W values, were observed for KOWWINlogP or MilogP values (r = 0.999 or r = 0.974, respectively. The correlations between all collected logP values and chromatographically (reversed-phase thin-layer chromatography obtained hydrophobicity parameters, RM0 and C0, were established. The good correlations (r > 0.90 were obtained in the majority of relationships. The KOWWINlogP was established as the most suitable hydrophobicity parameter of investigated group of ACE inhibitors with r = 0.981 for correlation with RM0 and r = 0.977 for correlation with C0 parameters (water-methanol mobile phase. Using multiple linear regressions, it was established that application of two selected logP, calculated by different mathematical approaches, led to very good correlation due to the benefits of both calculation methods. The good relationships indicate that the computed logP, with careful selection of method calculation, can be useful in ACE inhibitors lipophilicity evaluation, as high-throughput screening technique.

  16. pH-metric solubility. 3. Dissolution titration template method for solubility determination.

    Science.gov (United States)

    Avdeef, A; Berger, C M

    2001-12-01

    The main objective of this study was to develop an effective potentiometric saturation titration protocol for determining the aqueous intrinsic solubility and the solubility-pH profile of ionizable molecules, with the specific aim of overcoming incomplete dissolution conditions, while attempting to shorten the data collection time. A modern theory of dissolution kinetics (an extension of the Noyes-Whitney approach) was applied to acid-base titration experiments. A thermodynamic method was developed, based on a three-component model, to calculate interfacial, diffusion-layer, and bulk-water reactant concentrations in saturated solutions of ionizable compounds perturbed by additions of acid/base titrant, leading to partial dissolution of the solid material. Ten commercial drugs (cimetidine, diltiazem hydrochloride, enalapril maleate, metoprolol tartrate, nadolol, propoxyphene hydrochloride, quinine hydrochloride, terfenadine, trovafloxacin mesylate, and benzoic acid) were chosen to illustrate the new titration methodology. It was shown that the new method is about 10 times faster in determining equilibrium solubility constants, compared to the traditional saturation shake-flask methods.

  17. A case of mitochondrial cardiomyopathy with restrictive transmitral filling pattern

    Directory of Open Access Journals (Sweden)

    Otsui K

    2012-04-01

    Full Text Available Kazunori Otsui, Nobutaka Inoue, Anna Tamagawa, Kazuo OnishiDepartment of Cardiovascular Medicine, Kobe Rosai Hospital, Kobe, JapanAbstract: A 61-year-old diabetic woman with a mitochondrial A3243G mutation was hospitalized for evaluation of breathlessness, general fatigue, and leg edema. Chest radiography revealed cardiomegaly with massive pleural effusion. Serum lactate, pyruvate, and brain natriuretic peptide concentrations were elevated. Transthoracic echocardiography revealed a restrictive pattern of transmitral flow, although systolic function of the left ventricle was only mildly impaired. Based on these findings and her clinical course, the patient was diagnosed with right-sided heart failure caused by mitochondrial cardiomyopathy associated with a restrictive transmitral filling pattern. Treatment with furosemide, enalapril, and eplerenone was effective, and improvement in her symptoms was associated with amelioration of transthoracic echocardiographic findings and a reduction in serum brain natriuretic peptide levels. Previous reports have indicated heterogeneity in the clinical features of mitochondrial cardiomyopathy in patients carrying the A3243G mutation; the present case highlights the substantial variability in the clinical features of this disease.Keywords: mitochondrial disease, A3243G mutation, diastolic dysfunction, transmitral flow

  18. Hydronephrosis alters cardiac ACE2 and Mas receptor expression in mice.

    Science.gov (United States)

    Zhang, Yanling; Ma, Lulu; Wu, Junyan; Chen, Tingting

    2015-06-01

    Hydronephrosis is characterized by substantial loss of tubules and affects renin secretion in the kidney. However, whether alterations of angiotensin-converting enzyme (ACE), ACE2 and Mas receptor in the heart are observed in hydronephrosis is unknown. Thus, we assessed these components in hydronephrotic mice treated with AT1 receptor blockade and ACE inhibitor. Hydronephrosis was induced by left ureteral ligation in Balb/C mice except sham-operated animals. The levels of cardiac ACE, ACE2 and Mas receptor were measured after treatment of losartan or enalapril. Hydronephrosis led to an increase of ACE level and a decrease of ACE2 and Mas receptor in the heart. Losartan decreased cardiac ACE level, but ACE2 and Mas receptor levels significantly increased in hydronephrotic mice (p Hydronephrosis increased cardiac ACE and suppressed ACE2 and Mas receptor levels. AT1 blockade caused sustained activation of cardiac ACE2 and Mas receptor, but ACE inhibitor had the limitation of such activation of Mas receptor in hydronephrotic animals. © The Author(s) 2015.

  19. Incumplimiento y depresión

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    García Delgado MA.

    2009-06-01

    Full Text Available Tensión arterial elevada desde hace varios años, tiene prescrito enalapril 20 mg (1-1-0 desde que se le detectó el problema. Actualmente está bien controlado. _ Depresión desde hace 1 año. Ha estado tratado por un psiquiatra de la seguridad social que le tenía prescrito paroxetina 20 mg (1-0-0. Con esta medicación el paciente sentía que iba mejorando poco a poco. Cuando fue de nuevo a consulta, le recibió otro psiquiatra, que le cambió el tratamiento, indicándole la retirada de paroxetina y el inicio de mirtazapina 20 mg (1-0-0 y clorazepato dipotásico 5 mg (1-1-1. Este último fármaco hasta que se sienta claramente mejor. _ Alteración del sueño desde hace 2 años. Tiene prescrito lorazepam 1 mg (0-0-1. Le ayuda bastante a dormir.

  20. The Evaluation of Angiotensin-Converting Enzyme Inhibitors in Renal Elimination with Selected Molecular Descriptors

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    Trbojevic Jovana

    2017-06-01

    Full Text Available Angiotensin-converting enzyme (ACE inhibitors modulate the function of the renin-angiotensin-aldosterone system, and they are commonly prescribed antihypertensive drugs especially in patients with renal failure. In this study, the relationships between several molecular properties of eight ACE inhibitors (enalapril, quinapril, fosinopril, ramipril, benazepril, perindopril, moexipril, trandolapril and their renal elimination data, from relevant literature, were investigated. The ’molecular descriptors of the ACE inhibitors, which included aqueous solubility data (logS; an electronic descriptor, polar surface area (PSA;, a constitutional parameter, molecular mass (Mr; and a geometric descriptor, volume value (Vol, as well as lipophilicity descriptors (logP values, were calculated using different software packages. Simple linear regression analysis showed the best correlation between renal elimination data and lipophilicity descriptor AClogP values (R2 = 0.5742. In the next stage of the study, multiple linear regression was applied to assess a higher correlation between the ACE inhibitors’ renal elimination data and lipophilicity, AClogP, with one additional descriptor as an independent variable. Good correlations were established between renal elimination data from the literature and the AClogP lipophilicity descriptor using the constitutional parameter (molecular mass (R2 = 0.7425 or the geometric descriptor (volume value (R2 = 0.7224 as an independent variable. The application of computed molecular descriptors in evaluating drug elimination is of great importance in drug research.

  1. CORRELATION BETWEEN ANGIOTENSIN-CONVERTING ENZYME INHIBITORS LIPOPHILICITY AND PROTEIN BINDING DATA

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    Jasna Trbojević-Stanković

    2012-01-01

    Full Text Available Angiotensin-converting enzyme (ACE inhibitors represent a significant group of drugs primarily used in the treatment of hypertension and congestive heart failure. In this research, seven ACE inhibitors (enalapril, quinapril, fosinopril, lisinopril, cilazapril, ramipril, benazepril were studied to evaluate the relationship between their protein binding and calculated (logP values or ultra-high performance liquid chromatographytandem mass spectrometry (UHPLC-MS and reversed-phase thin-layer chromatography (RP-TLC lipophilicity data (ϕ0, CHI or C0 parameters, respectively. Their protein binding data varied from negligible (lisinopril to 99% (fosinopril, while calculated logPKOWWINvalues ranged from -0.94 (lisinopril to 6.61 (fosinopril. The good correlations were established between protein binding values and logPKOWWIN data (R2=0.7520 as well as between protein binding and chromatographic hydrophobicity data, ϕ0, CHI or C0parameters (R2 were 0.6160, 0.6242 and 0.6547, respectively. The possible application of hydrophobicity data in drugs protein binding evaluation can be of great importance in drug bioavailability.

  2. Angiotensin converting enzyme immobilized on magnetic beads as a tool for ligand fishing.

    Science.gov (United States)

    de Almeida, Fernando G; Vanzolini, Kenia L; Cass, Quezia B

    2017-01-05

    Angiotensin converting enzyme (ACE) presents an important role in blood pressure regulation, since that converts angiotensin I to the vasoconstrictor angiotensin II. Some commercially available ACE inhibitors are captopril, lisinopril and enalapril; due to their side effects, naturally occurring inhibitors have been prospected. In order to endorse this research field we have developed a new tool for ACE ligand screening. To this end, ACE was extracted from bovine lung, purified and chemically immobilized in modified ferrite magnetic beads (ACE-MBs). The ACE-MBs have shown a Michaelian kinetic behavior towards hippuryl-histidyl-leucine. Moreover, as proof of concept, the ACE-MBs was inhibited by lisinopril with a half maximal inhibitory concentration (IC 50 ) of 10nM. At the fishing assay, ACE-MBs were able not only to fish out the reference inhibitor, but also one peptide from a pool of tryptic digested BSA. In conclusion, ACE-MBs emerge as new straightforward tool for ACE kinetics determination, inhibition and binder screening. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Shenqiwan Ameliorates Renal Fibrosis in Rats by Inhibiting TGF-β1/Smads Signaling Pathway

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    Hongshu Chen

    2017-01-01

    Full Text Available Epithelial-mesenchymal transition (EMT refers to the transition of epithelial cells into mesenchymal cells. Emerging evidence suggests that EMT is a key point in renal interstitial fibrosis (RIF. Traditional Chinese Medicine Shenqiwan (SQW is widely used in clinical treatment of chronic kidney disease, but the underlying mechanism remains unclear. The purpose of this study is to investigate the effect of SQW on renal fibrosis and its association with TGF-β1/Smads signaling pathway. A rat model of adenine (150 mg/kg was established and intragastrically treated with various concentrations of SQW at dose of 1.5 g/kg, 3 g/kg, and 6 g/kg. Control group and model group were given the same volume of saline. Meanwhile, the positive control group was treated with Enalapril (4 mg/kg. Animals were sacrificed on 21st day after administration. The results showed that SQW could significantly relieve renal pathological damage caused by adenine, increase gene and protein expression of E-cadherin, and decrease the expression of Vimentin in kidney samples. In addition, SQW efficiently inhibited the mRNA and protein expression of p-Smad2/3 by upregulating Smad7. These results suggest that SQW could slow down the progression of renal fibrosis, possibly by inhibiting TGF-β1/Smads signaling pathway.

  4. Oral carcinogenesis is not achieved in different carcinogen-treated PAI-1 transgenic and wild-type mouse models.

    Science.gov (United States)

    Avgoustidis, Dimitris; Nisyrios, Themistoklis; Nkenke, Emeka; Lijnen, Roger; Ragos, Vassilis; Perrea, Despina; Donta, Ismini; Vaena, Apostolia; Yapijakis, Christos; Vairaktaris, Eleftherios

    2012-01-01

    In an effort to assess the role of plasminogen activator inhibitor-1 (PAI-1) in oral squamous cancer development and progression, two different carcinogen treatment protocols were conducted. Protocol I included mice from a PAI-1 transgenic (Tg) breed (n=56) and their wild-type (WT) counterparts (n=56), divided into one control group and two main experimental groups, treated with 7,12-dimethylbenz[a]anthracene (DMBA) for 8 and 16 weeks, respectively. Protocol II included the same number and types of animals and groups, which were similarly treated with 4-Nitroquinoline 1-oxide (4-NQO) in drinking water. Two drugs that affect plasma PAI-1 levels, enalapril and pravastatin, were administered to certain subgroups of animals in both protocols. None of the animals developed macroscopically-visible oral cancer lesions. Eleven animals under Protocol I and 52 animals under Protocol II died. Skin lesions were noted only in DMBA-treated animals (n=9). Almost all animals administered with 4-NQO developed alopecia and lost weight, while two of them developed stomach tumours, and one female mouse developed a large ovarian cyst. Transgenic mice may respond differently when used in well-established carcinogen models and oral carcinogenesis is hard to achieve in these rodents.

  5. Advances in simultaneous DSC-FTIR microspectroscopy for rapid solid-state chemical stability studies: some dipeptide drugs as examples.

    Science.gov (United States)

    Lin, Shan-Yang; Wang, Shun-Li

    2012-04-01

    The solid-state chemistry of drugs has seen growing importance in the pharmaceutical industry for the development of useful API (active pharmaceutical ingredients) of drugs and stable dosage forms. The stability of drugs in various solid dosage forms is an important issue because solid dosage forms are the most common pharmaceutical formulation in clinical use. In solid-state stability studies of drugs, an ideal accelerated method must not only be selected by different complicated methods, but must also detect the formation of degraded product. In this review article, an analytical technique combining differential scanning calorimetry and Fourier-transform infrared (DSC-FTIR) microspectroscopy simulates the accelerated stability test, and simultaneously detects the decomposed products in real time. The pharmaceutical dipeptides aspartame hemihydrate, lisinopril dihydrate, and enalapril maleate either with or without Eudragit E were used as testing examples. This one-step simultaneous DSC-FTIR technique for real-time detection of diketopiperazine (DKP) directly evidenced the dehydration process and DKP formation as an impurity common in pharmaceutical dipeptides. DKP formation in various dipeptides determined by different analytical methods had been collected and compiled. Although many analytical methods have been applied, the combined DSC-FTIR technique is an easy and fast analytical method which not only can simulate the accelerated drug stability testing but also at the same time enable to explore phase transformation as well as degradation due to thermal-related reactions. This technique offers quick and proper interpretations. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. Multi-residue analysis method for analysis of pharmaceuticals using liquid chromatography-time of flight/mass spectrometry (LC-TOF/MS) in water sample

    Science.gov (United States)

    Al-Qaim, Fouad Fadhil; Abdullah, Md Pauzi; Othman, Mohamed Rozali

    2013-11-01

    In this work, a developed method using solid - phase extraction (SPE) followed by liquid chromatography - time of flight mass spectrometry (LC-ESI-TOF/MS) was developed and validated for quantification and confirmation of eleven pharmaceuticals with different therapeutic classes in water samples, Malaysia. These compounds are caffeine (CAF), prazosin (PRZ), enalapril (ENL), carbamazepine (CBZ), nifedipine (NFD), levonorgestrel (LNG), simvastatin (SMV), hydrochlorothiazide (HYD), gliclazide (GLIC), diclofenac-Na (DIC-Na) and mefenamic acid (MEF). LC was performed on a Dionex Ultimate 3000/LC 09115047 (USA) system. Chromatography was performed on a Thermo Scientific C18 (250 mm × 2.1 mm, i.d.: 5μm) column. Several parameters were optimised such as; mobile phase, gradient elution, collision energy and solvent elution for extraction of compounds from water. The recoveries obtained ranged from 30-148 % in river water. Five pharmaceutical compounds were detected in the surface water samples: caffeine, prazosin, enalpril, diclofenac-Na and mefenamic acid. The developed method is precise and accepted recoveries were got. In addition, this method is suitable to identify and quantify trace concentrations of pharmaceuticals in surface water.

  7. [Drug-induced oral ulcerations].

    Science.gov (United States)

    Madinier, I; Berry, N; Chichmanian, R M

    2000-06-01

    Different side effects of drugs have been described in the oral cavity, including oral ulcerations. Direct contact between drugs and oral mucosa may induce chemical burn or local hypersensitivity. Less frequently, these drug-induced oral ulcerations are part of a complex reaction with cutaneous or systemic manifestations. Sometimes, one or more oral ulcerations appear as the main side-effect of a drug, or exceptionally as solitary lesions. Solitary oral ulcerations usually appear after few weeks of treatment. In most of cases, these lesions resist to conventional treatments, with a rapid healing following the suppression of the responsible drug. This diagnosis is usually difficult, particularly with patients receiving multiple drug therapy. Besides, special attention must be paid to new drugs. Oral ulcerations following symptoms of burning mouth, metallic taste, dysgueusia or agueusia are strongly suggestive of a pharmacological origin. Most of the molecules able to induce solitary oral ulcerations are commonly prescribed in a) rheumatology: NSAI (diclofenac, flurbiprofen, indomethacin, naproxen), long-term rheumatoid arthritis therapy (azathioprine, methotrexate, penicillamine, gold compounds, tiopronin); b) cardiology: angiotensin-converting-enzyme inhibitors (captopril, enalapril), angiotensin 2-receptor antagonist (losartan), anti-angorous (nicorandil), c) psychiatry: antidepressants (fluoxetine, lithium), d) AIDS therapy (foscarnet, zalcitabine).

  8. Effect of ipsilateral ureteric obstruction on contralateral kidney and role of renin angiotensin system blockade on renal recovery in experimentally induced unilateral ureteric obstruction

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    Shasanka S Panda

    2013-01-01

    Full Text Available Aims: To study, the effects of ipsilateral ureteric obstruction on contralateral kidney and the role of renin angiotensin system (RAS blockade on renal recovery in experimentally induced unilateral ureteric obstruction. Materials and Methods: Unilateral upper ureteric obstruction was created in 96 adult Wistar rats that were reversed after pre-determined intervals. Losartan and Enalapril were given to different subgroups of rats following relief of obstruction. Results: The severity of dilatation on the contralateral kidney varied with duration of ipsilateral obstruction longer the duration more severe the dilatation. There is direct correlation between renal parenchymal damage, pelvi-ureteric junction (PUJ fibrosis, inflammation and severity of pelvi-calyceal system dilatation of contralateral kidney with duration of ipsilateral PUJ obstruction. Conclusions: Considerable injury is also inflicted to the contralateral normal kidney while ipsilateral kidney remains obstructed. Use of RAS blocking drugs has been found to significantly improve renal recovery on the contralateral kidney. It can, thus, be postulated that contralateral renal parenchymal injury was mediated through activation of RAS.

  9. Uso de antihipertensivos en Cantabria (1995-2002: el desfase con las evidencias Use of antihypertensive agents in Cantabria, Spain [1995-2002]: discrepancy with the published evidence

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    Luis Vara

    2004-10-01

    Full Text Available Objetivo: Conocer el patrón de prescripción de los fármacos antihipertensivos en Cantabria y su variación según las nuevas evidencias publicadas entre 1995 y 2002. Método: Se realiza una revisión de la base de datos del Sistema Informático de Gestión de Farmacia, del Servicio Cántabro de Salud, acerca del consumo y coste de los medicamentos que tienen como indicación el tratamiento de la hipertensión arterial. El consumo se expresa en dosis diarias definidas por 1.000 habitantes y día (DHD. Resultados: En 1995, el consumo de antihipertensivos se situó en 130,2 DHD y fue de 235 DHD en 2002. La contribución de los diuréticos al consumo total disminuyó del 34,3% en 1995 al 25,8% en 2002, y la de los bloqueadores beta del 6,5% en 1995 al 5,9% en 2002. El grupo más utilizado en todos los años fue el de los inhibidores de la enzima de conversión de la angiotensina, que representó el 36,8% en 2002. Los antagonistas de los receptores de la angiotensina experimentaron el mayor incremento y originaron el 13,2% de las prescripciones en 2002, que supuso el 26% del gasto en antihipertensivos. Excepto enalapril, no varió la tendencia de uso de ninguno de los fármacos utilizados en los principales estudios publicados en este período o incluso disminuyó. Conclusiones: Se comprueba un notable incremento de la prescripción de antihipertensivos con un cambio en su patrón de consumo. Este diferente patrón no cambia en armonía con la publicación de los grandes ensayos clínicos y podría tener importantes implicaciones económicas.Objective: To ascertain the pattern of prescription of antihypertensive drugs in Cantabria and its variation from published evidence between 1995 and 2002. Method: We reviewed the database of the pharmaceutical data processing system of the Cantabrian Health Service on the consumption and cost of the drugs indicated in the treatment of hypertension. Consumption data is expressed in defined daily doses per

  10. Investigation of interaction studies of cefpirome with ACE-inhibitors in various buffers

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    Nawaz, Muhammad; Arayne, Muhammad Saeed; Sultana, Najma; Abbas, Hira Fatima

    2015-02-01

    This work describes a RP-HPLC method for the determination and interaction studies of cefpirome with ACE-inhibitors (captopril, enalapril and lisinopril) in various buffers. The separation and interaction of cefpirome with ACE-inhibitors was achieved on a Purospher Star, C18 (5 μm, 250 × 4.6 mm) column. Mobile phase consisted of methanol: water (80:20, v/v, pH 3.3); however, for the separation of lisinopril, it was modified to methanol-water (40:60, v/v, pH 3.3) and pumped at a flow rate of 1 mL min-1. In all cases, UV detection was performed at 225 nm. Interactions were carried out in physiological pH i.e., pH 1 (simulated gastric juice), 4 (simulated full stomach), 7.4 (blood pH) and 9 (simulated GI), drug contents were analyzed by reverse phase high performance liquid chromatography. Method was found linear in the concentration range of 1.0-50.0 μg mL-1 with correlation coefficient (r2) of 0.999. Precision (RSD%) was less than 2.0%, indicating good precision of the method and accuracy was 98.0-100.0%. Furthermore, cefpirome-ACE-inhibitors' complexes were also synthesized and results were elucidated on the basis of FT-IR, and 1H NMR. The interaction results show that these interactions are pH dependent and for the co-administration of cefpirome and ACE-inhibitors, a proper interval should be given.

  11. Hydrogen Sulfide Releasing 2-Mercaptoacrylic Acid-Based Derivative Possesses Cytoprotective Activity in a Small Intestine of Rats with Medication-Induced Enteropathy

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    Yulia Sklyarova

    2017-10-01

    Full Text Available Small intestinal injury is known to be one of the most commonly appearing pathologies, resulting in the use of medications such as: nonsteroidal anti-inflammatory drugs (NSAIDs, antitumor drugs and angiotensin-converting enzyme (ACE inhibitors. The principal objective of this study is to evaluate the action of a novel mercaptoacrylic acid derivative able to release H2S on parameters of NO-synthase system and oxidative stress. Inducing enteropathy, three types of medications were used: indomethacin, an NSAID (35 mg/kg; methotrexate, an antitumor drug (10 mg/kg; and enalapril, an ACE inhibitor (2 mg/kg/day. 2-[(4-chlorophenyl-carbamoyl-methyl]-3-(3,5-di-tert-butyl-4-hydroxyphenyl-acrylic acid (2C3DHTA was introduced based on the background of medication-induced enteropathy (10 mg/kg/day. The survey showed that malondialdehyde (MDA concentration, myeloperoxidase (MPO activity, superoxide dismutase (SOD, catalase, and NO-synthases (NOS were determined in the small intestinal mucosa. The increase in inducible NO-synthase (iNOS activity was due to indomethacin and methotrexate administration. Constitutive NO-synthase (cNOS activity was decreased by an ACE-inhibitor. The cytoprotective effect was demonstrated by 2C3DHTA, which returned iNOS activity to its control level and increased cNOS activity. The enterotoxic action of studied medication was accompanied by the development of oxidative stress manifested, activity of MPO was increased. MPO activity and manifestations of oxidative stress were decreased by 2C3DHTA. Effects of 2C3DHTA can be explained by the action of H2S, released from this compound in the gastrointestinal (GI system.

  12. Intrauterine growth restriction programs an accelerated age-related increase in cardiovascular risk in male offspring

    Science.gov (United States)

    Dasinger, John Henry; Intapad, Suttira; Backstrom, Miles A.; Carter, Anthony J.

    2016-01-01

    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 offspring at 18 mo of age relative to control counterparts at 12 mo; however, blood pressure was not increased in growth-restricted at 18 mo relative to growth-restricted counterparts at 12 mo. Serum testosterone levels were not elevated in growth-restricted offspring relative to control at 12 mo of age. Thus, male growth-restricted offspring no longer exhibited a positive association between blood pressure and testosterone at 12 mo of age. Unlike hypertension in male growth-restricted offspring at 4 mo of age, inhibition of the renin-angiotensin system with enalapril (250 mg/l for 2 wk) did not abolish the difference in blood pressure in growth-restricted offspring relative to control counterparts at 12 mo of age. Therefore, these data suggest that intrauterine growth restriction programs an accelerated age-related increase in blood pressure in growth-restricted offspring. Furthermore, this study suggests that the etiology of increased blood pressure in male growth-restricted offspring at 12 mo of age differs from that at 4 mo of age. PMID:27147668

  13. Low mercury concentration produces vasoconstriction, decreases nitric oxide bioavailability and increases oxidative stress in rat conductance artery.

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    Núbia Belem Lemos

    Full Text Available Mercury is an environmental pollutant that reduces nitric oxide (NO bioavailability and increases oxidative stress, having a close link with cardiovascular diseases, as carotid atherosclerosis, myocardial infarction, coronary heart disease and hypertension. One of the main sites affected by oxidative stress, which develops atherosclerosis, is the aorta. Under acute exposure to low mercury concentrations reactive oxygen species (ROS production were only reported for resistance vessels but if low concentrations of mercury also affect conductance arteries it is still unclear. We investigated the acute effects of 6 nM HgCl(2 on endothelial function of aortic rings measuring the reactivity to phenylephrine in rings incubated, or not, with HgCl(2 for 45 min, the protein expression for cyclooxygenase 2 (COX-2 and the AT1 receptor. HgCl(2 increased Rmax and pD2 to phenylephrine without changing the vasorelaxation induced by acetylcholine and sodium nitroprusside. Endothelial damage abolished the increased reactivity to phenylephrine. The increase of Rmax and pD2 produced by L-NAME was smaller in the presence of HgCl(2. Enalapril, losartan, indomethacin, furegrelate, the selective COX-2 inhibitor NS 398, superoxide dismutase and the NADPH oxidase inhibitor apocynin reverted HgCl(2 effects on the reactivity to phenylephrine, COX-2 protein expression was increased, and AT1 expression reduced. At low concentration, below the reference values, HgCl(2 increased vasoconstrictor activity by reducing NO bioavailability due to increased ROS production by NADPH oxidase activity. Results suggest that this is due to local release of angiotensin II and prostanoid vasoconstrictors. Results also suggest that acute low concentration mercury exposure, occurring time to time could induce vascular injury due to endothelial oxidative stress and contributing to increase peripheral resistance, being a high risk factor for public health.

  14. Efecto antihipertensivo del extracto de Piper aduncum ‘matico’ sobre la hipertensión inducida por L-NAME en ratones

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    Jorge Arroyo

    2012-10-01

    Full Text Available Introducción: El Piper aduncum es una planta conocida como matico. Se le atribuye efectos antihipertensivo, antiinflamatorio, cicatrizante. Objetivos: Determinar el efecto antihipertensivo del extracto de Piper aduncum ‘matico’, sobre la hipertensión inducida por L-NAME, en ratones. Diseño: Experimental. Lugar: Facultades de Medicina y de Farmacia y Bioquímica, Universidad Nacional Mayor de San Marcos, Lima, Perú. Material biológico: Extracto etanólico de las hojas de Piper aduncum y ratas. Intervenciones: Se utilizó seis grupos de seis ratones Muss musculus cada uno, uno sin hipertensión (control negativo y cuatro con hipertensión inducida por L-NAME: un control positivo y tres grupos para las dosis de 50, 150 y 300 mg/kg, respectivamente. El tratamiento se realizó por vía oral, una vez por día, durante 25 días. Las mediciones de la presión arterial sistólica (PAS, presión arterial diastólica (PAD y presión arterial media (PAM fueron realizadas dos veces por semana (martes y viernes y se consideró las mediciones entre los días 19 y 23 de iniciado el tratamiento. Principales medidas de resultados: Actividad antihipertensiva. Resultados: En los días 19 y 23 se observó los mejores niveles de presión arterial en el grupo control y los experimentales, correspondiendo a las mediciones 6 y 7. La eficacia antihipertensiva para enalapril fue 24,1 a 20,6%, respectivamente, seguida por matico, entre 24,9 y 13,7% (p<0,05. Conclusiones: En las condiciones experimentales, se demostró la actividad antihipertensiva del extracto etanólico de hojas de Piper aduncum ‘matico’.

  15. Acute effect of resistance, aerobic and combined exercise circuits on blood pressure of hypertensive women

    Directory of Open Access Journals (Sweden)

    Elizabeth Carpio Rivera

    2012-11-01

    Full Text Available Carpio-Rivera, E. y Solera-Herrera, A. (2012. Acute effect of resistance, aerobic and combined exercise circuits on blood pressure of hypertensive women. Pensar en Movimiento: Revista de Ciencias del Ejercicio y la Salud, 10 (2, 1-12. The purpose of this study was to observe the acute effect of different exercises executed in circuit on the resting blood pressure of hypertensive women. Nine trained persons (aged 53.22 ± 4.67 years, hypertensive but medicated with enalapril, participated in four training treatments, each carried out on different days under a randomized repeated measures design: (1 A: aerobic training condition (steps training; (2 R: resistance training condition (machine training (3 AR: aerobic and resistance training condition (alternating aerobic and resistance training every 30 seconds (4 C: control condition (30 minutes resting. Exercise conditions were performed during 30 minutes at 70% of maximum heart rate and resting blood pressure was measured 5 minutes before and immediately after each condition. A two-way analysis of variance detected a significant interaction between conditions and measurements (p<0.05 on systolic blood pressure (sBP. Tukey Post-hoc analyses showed a significant increase of sBP following the three exercise conditions (A: +19 mmHg; R: +28 mmHg; AR: +22 mmHg, while the sBP remained unchanged during the control condition. In contrast, there was no significant effect of any type of exercise on diastolic blood pressure (dBP. In conclusion, the acute elevation in sBP following this type of resistance exercise was similar to the increase produced by aerobic exercise.

  16. Hypersensitivity myocarditis associated with ephedra use.

    Science.gov (United States)

    Zaacks, S M; Klein, L; Tan, C D; Rodriguez, E R; Leikin, J B

    1999-01-01

    Ephedrine has previously been described as a causative factor of vasculitis but myocarditis has not yet been associated with either ephedrine or its plant derivative ephedra. A 39-year-old African American male with hypertension presented to Rush Presbyterian St. Luke's Medical Center with a 1-month history of progressive dyspnea on exertion, orthopnea, and dependent edema. He was taking Ma Huang (Herbalife) 1-3 tablets twice daily for 3 months along with other vitamin supplements, pravastatin, and furosemide. Physical examination revealed a male in mild respiratory distress. The lung fields had rales at both bases without audible wheezes. Internal jugular venous pulsations were 5 cm above the sternal notch. Medical therapy with intravenous furosemide and oral enalapril was initiated upon admission. Cardiac catheterization with coronary angiography revealed normal coronary arteries, a dilated left ventricle, moderate pulmonary hypertension, and a pulmonary capillary wedge pressure of 34 mm Hg. The patient had right ventricular biopsy performed demonstrating mild myocyte hypertrophy and an infiltrate consisting predominantly of lymphocytes with eosinophils present in significantly increased numbers. Treatment for myocarditis was initiated with azothioprine 200 mg daily and prednisone 60 mg per day with a tapering course over 6 months. Anticoagulation with warfarin and diuretics was initiated and angiotensin-converting enzyme inhibition was continued. Hydralazine was added later. One month into therapy, an echocardiogram demonstrated improved left ventricular function with only mild global hypokinesis. A repeat right ventricular biopsy 2 months after the first admission showed no evidence of myocarditis. At 6 months, left ventricular ejection fraction was normal (EFN 50%) and the patient asymptomatic. Ephedra (Ma Huang) is the suspected cause of hypersensitivity myocarditis in this patient due to the temporal course of disease and its propensity to induce vasculitis.

  17. Influenza Vaccination in Patients With Chronic Heart Failure: The PARADIGM-HF Trial.

    Science.gov (United States)

    Vardeny, Orly; Claggett, Brian; Udell, Jacob A; Packer, Milton; Zile, Michael; Rouleau, Jean; Swedberg, Karl; Desai, Akshay S; Lefkowitz, Martin; Shi, Victor; McMurray, John J V; Solomon, Scott D

    2016-02-01

    This study sought to examine the prevalence and predictors of influenza vaccination among participants in the PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) study and investigate associations between receiving influenza vaccine and cardiovascular death or heart failure hospitalizations, all-cause hospitalizations, and cardiopulmonary or influenza-related hospitalizations. Influenza is associated with an increased risk for cardiovascular events in patients with heart failure. We used data from the PARADIGM-HF trial in which patients with heart failure were randomized to the angiotensin receptor neprilysin inhibitor LCZ696 (sacubitril/valsartan) or enalapril. We assessed predictors of receiving influenza vaccination, and examined the relationship between influenza vaccination and outcomes in a propensity-adjusted model. Of 8,099 study participants, 1,769 (21%) received influenza vaccination. We observed significant regional variation in vaccination rates, with highest rates in the Netherlands (77.5%), Great Britain (77.2%), and Belgium (67.5%), and lowest rates in Asia (2.6%), with intermediate rates in North America (52.8%). Top predictors of vaccination included enrolling country, white race, implanted defibrillator, older age, lower New York Heart Association functional class, lower heart rate, and a history of diabetes mellitus. Influenza vaccination was associated with a reduced risk for all-cause mortality in propensity-adjusted (hazard ratio: 0.81; 95% confidence interval: 0.67 to 0.97; p = 0.015) models. Influenza vaccination rates varied widely in patients with heart failure with reduced ejection fraction enrolled in the PARADIGM-HF trial, and vaccination was associated with reduced risk for death, although whether this association was causal cannot be determined. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  18. Contraceptive Provision to Adolescent Females Prescribed Teratogenic Medications.

    Science.gov (United States)

    Stancil, Stephani L; Miller, Melissa; Briggs, Holley; Lynch, Daryl; Goggin, Kathy; Kearns, Gregory

    2016-01-01

    Rates of adult women receiving contraceptive provision when simultaneously prescribed a known teratogen are alarmingly low. The prevalence of this behavior among pediatric providers and their adolescent patients is unknown. The objective of this study was to describe pediatric provider behaviors for prescribing teratogens concurrently with counseling, referral, and/or prescribing of contraception (collectively called contraceptive provision) in the adolescent population. A retrospective review was conducted examining visits in 2008-2012 by adolescents aged 14 to 25 years in which a known teratogen (US Food and Drug Administration pregnancy risk category D or X) was prescribed. The electronic medical records were queried for demographic information, evidence of contraceptive provision, and menstrual and sexual histories. The data were analyzed using standard statistical methods. Within 4172 clinic visits, 1694 females received 4506 prescriptions for teratogenic medications. The most commonly prescribed teratogens were topiramate, methotrexate, diazepam, isotretinoin, and enalapril. The subspecialties prescribing teratogens most frequently were neurology, hematology-oncology, and dermatology. Overall, contraceptive provision was documented in 28.6% of the visits. Whites versus nonwhites and older versus younger girls were more likely to receive contraceptive provision. The presence of a federal risk mitigation system for the teratogen also increased the likelihood of contraceptive provision. Our data demonstrate female adolescents prescribed teratogens receive inadequate contraception provision, which could increase their risk for negative pregnancy outcomes. Although the presence of a federal risk mitigation system appears to improve contraceptive provision, these systems are costly and, in some instances, difficult to implement. Efforts to improve provider practices are needed. Copyright © 2016 by the American Academy of Pediatrics.

  19. Frequency of cough during therapy with ACE inhibitors in Greek hypertensives.

    Science.gov (United States)

    Efstratopoulos, A D; Meikopoulos, M; Voyaki, S

    1993-12-01

    Persistent dry cough is one of the most common side-effects during therapy with ACE inhibitors. The frequency of cough ranges widely (from 0.2% to 15%) in different series, being higher in small studies and smaller in retrospective studies with large number of patients. The aim of the present study was to evaluate the true frequency of cough induced by treatment with ACE inhibitors in Greek hypertensives and to determine various possibly correlated parameters, including sex, duration of therapy and kind and dose of ACE inhibitors. All hypertensive patients followed in our Hypertension Clinic and treated with ACE inhibitors participated in the study. A total of 228 patients, 103 males and 125 females, 24-80 years of age, were treated with ACE inhibitors for a period of 1-41 months: 121 with enalapril, 40 with captopril, 39 with lisinopril, 25 with perindopril and 3 with ramipril. During treatment with ACE inhibitors persistent dry cough occurred in 15 patients, 12 women and 3 men, giving a frequency of 6.58%. Eleven patients (4.82%) volunteered the information and three after questioning. The mean age of these 15 patients with cough was significantly higher from that of the group (n = 213) without cough (64.27 +/- 2.5 vs. 57.9 +/- 0.74 years, mean +/- SEM, P = 0.024). The 12 women with cough were significantly older than the 113 without cough (67.77 +/- 2.8 vs. 57.8 +/- 1.04 years, P = 0.032).(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Risk Related to Pre-Diabetes Mellitus and Diabetes Mellitus in Heart Failure With Reduced Ejection Fraction: Insights From Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial.

    Science.gov (United States)

    Kristensen, Søren L; Preiss, David; Jhund, Pardeep S; Squire, Iain; Cardoso, José Silva; Merkely, Bela; Martinez, Felipe; Starling, Randall C; Desai, Akshay S; Lefkowitz, Martin P; Rizkala, Adel R; Rouleau, Jean L; Shi, Victor C; Solomon, Scott D; Swedberg, Karl; Zile, Michael R; McMurray, John J V; Packer, Milton

    2016-01-01

    The prevalence of pre-diabetes mellitus and its consequences in patients with heart failure and reduced ejection fraction are not known. We investigated these in the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial. We examined clinical outcomes in 8399 patients with heart failure and reduced ejection fraction according to history of diabetes mellitus and glycemic status (baseline hemoglobin A1c [HbA1c]: diabetes mellitus], and ≥ 6.5% [≥ 48 mmol/mol; diabetes mellitus]), in Cox regression models adjusted for known predictors of poor outcome. Patients with a history of diabetes mellitus (n = 2907 [35%]) had a higher risk of the primary composite outcome of heart failure hospitalization or cardiovascular mortality compared with those without a history of diabetes mellitus: adjusted hazard ratio, 1.38; 95% confidence interval, 1.25 to 1.52; P diabetes mellitus and 2103 (25%) had pre-diabetes mellitus. The hazard ratio for patients with undiagnosed diabetes mellitus (HbA1c, > 6.5%) and known diabetes mellitus compared with those with HbA1c diabetes mellitus were also at higher risk (hazard ratio, 1.27 [1.10-1.47]; P diabetes mellitus is associated with a higher risk of adverse cardiovascular outcomes (compared with patients with no diabetes mellitus and HbA1c < 6.0%). LCZ696 was beneficial compared with enalapril, irrespective of glycemic status. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255. © 2016 The Authors.

  1. Application of Polar Organic Chemical Integrative Sampler (POCIS) to monitor emerging contaminants in tropical waters.

    Science.gov (United States)

    Bayen, Stéphane; Segovia, Elvagris; Loh, Lay Leng; Burger, David F; Eikaas, Hans S; Kelly, Barry C

    2014-06-01

    Tools specifically validated for tropical environments are needed to accurately describe the behavior of chemical contaminants in tropical ecosystems. In the present study, sampling rates (Rs) were determined for the commercial pharmaceutical-type Polar Organic Chemical Integrative Sampler (POCIS) with a 45.8cm(2) exposure surface for 35 Pharmaceutically Active Compounds (PhACs) and Endocrine Disrupting Compounds (EDCs), of which eight compounds (albuterol, atorvastatin, diltiazem, dilantin, enalapril, norfluoxetine, risperidone and warfarin) were reported for the first time. These sampling rates were measured in an outdoor laboratory calibration setup to best capture diurnal tropical temperature variations (29±3°C). The effect of stirring and salinity was investigated. For all compounds, the sampling rates were higher under stirred conditions as compared to quiescent conditions. Calibration results in the presence of 30g sodium chloride support that the effects of salinity on POCIS sampling rates are compound-specific. Comparisons between Time-Weight Average (TWA) water concentrations using POCIS and spot sample levels in the field (2 lake and 1 mangrove estuary sites) are presented. Results showed that POCIS TWA concentrations were in agreement with spot sample concentrations for these aquatic systems. Results indicate that POCIS can be used to effectively measure the TWA concentration for a range of PhACs and EDCs in tropical waters. However, based on the results from mass balance and field deployments, POCIS did not appear suitable for compounds with a low mass balance recovery during calibration (e.g. triclosan and linuron in this study). Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Dual Angiotensin Receptor and Neprilysin Inhibition with Sacubitril/Valsartan in Chronic Systolic Heart Failure: Understanding the New PARADIGM.

    Science.gov (United States)

    Lillyblad, Matthew P

    2015-11-01

    To evaluate the clinical role of sacubitril/valsartan, a novel angiotensin-neprilysin inhibitor, for the treatment of chronic heart failure with a reduced ejection fraction (HFrEF). A search of PubMed was conducted using a combination of the search terms sacubitril, valsartan, LCZ696, neprilysin inhibition, natriuretic peptide system, renin-angiotensin system, and heart failure with reduced ejection fraction. Bibliographies of all retrieved articles were reviewed for relevant literature. All references included were published between 1980 and May 2015. All studies and review articles that contained data describing the use of sacubitril/valsartan in HFrEF were reviewed. HFrEF remains a disease of high morbidity and mortality. Natriuretic peptide (NP) augmentation has emerged as a most promising neurohormonal target in HFrEF. NPs provide vasodilatory, natriuretic, diuretic, and antiproliferative actions to help support the failing heart. Neprilysin, a neutral endopeptidase, is a primary pathway for NP metabolism. Combined inhibition of the renin angiotensin aldosterone system and neprilysin augments the beneficial natriuretic peptide pathway while providing direct antagonism to increases in angiotensin II. In the landmark PARADIGM HF trial, the neprilysin inhibitor sacubitril added to valsartan significantly improved morbidity and mortality over enalapril, a standard of care in HFrEF. Application of these results to clinical practice requires careful considerations of trial design, study patient population, and clinical monitoring. Sacubitril/valsartan significantly improved morbidity and mortality in patients with chronic HFrEF but will require careful application to "real-world" populations of HFrEF. © The Author(s) 2015.

  3. Combined Angiotensin Receptor Antagonism and Neprilysin Inhibition

    Science.gov (United States)

    Hubers, Scott A.; Brown, Nancy J.

    2016-01-01

    Heart failure affects approximately 5.7 million people in the United States alone. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and aldosterone antagonists have improved mortality in patients with heart failure and reduced ejection fraction, but mortality remains high. In July 2015, the FDA 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 prodrug sacubitril in a 1:1 ratio in a sodium supramolecular complex. Sacubitril is converted by esterases to LBQ657, which inhibits neprilysin, the enzyme responsible for the degradation of the natriuretic peptides and many other vasoactive peptides. Thus, this combined angiotensin receptor antagonist and neprilysin inhibitor addresses two of the pathophysiologic mechanisms of heart failure - activation of the renin-angiotensin-aldosterone system and decreased sensitivity to natriuretic peptides. In the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM-HF) trial, valsartan/sacubitril significantly reduced mortality and hospitalization for heart failure, as well as blood pressure, compared to enalapril in patients with heart failure, reduced ejection fraction, and an elevated circulating level of brain natriuretic peptide or N-terminal pro-brain natriuretic peptide. Ongoing clinical trials are evaluating the role of valsartan/sacubitril in the treatment of heart failure with preserved ejection fraction and hypertension. We review here the mechanisms of action of valsartan/sacubitril, the pharmacologic properties of the drug, and its efficacy and safety in the treatment of heart failure and hypertension. PMID:26976916

  4. The neprilysin pathway in heart failure: a review and guide on the use of sacubitril/valsartan.

    Science.gov (United States)

    Jhund, Pardeep S; McMurray, John J V

    2016-09-01

    Inhibition of neurohumoural pathways such as the renin angiotensin aldosterone and sympathetic nervous systems is central to the understanding and treatment of heart failure (HF). Conversely, until recently, potentially beneficial augmentation of neurohumoural systems such as the natriuretic peptides has had limited therapeutic success. Administration of synthetic natriuretic peptides has not improved outcomes in acute HF but modulation of the natriuretic system through inhibition of the enzyme that degrades natriuretic (and other vasoactive) peptides, neprilysin, has proven to be successful. After initial failures with neprilysin inhibition alone or dual neprilysin-angiotensin converting enzyme (ACE) inhibition, the Prospective comparison of angiotensin receptor neprilysin inhibitor (ARNI) with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF) trial demonstrated that morbidity and mortality can be improved with the angiotensin receptor blocker neprilysin inhibitor sacubitril/valsartan (formerly LCZ696). In comparison to the ACE inhibitor enalapril, sacubitril/valsartan reduced the occurrence of the primary end point (cardiovascular death or hospitalisation for HF) by 20% with a 16% reduction in all-cause mortality. These findings suggest that sacubitril/valsartan should replace an ACE inhibitor or angiotensin receptor blocker as the foundation of treatment of symptomatic patients (NYHA II-IV) with HF and a reduced ejection fraction. This review will explore the background to neprilysin inhibition in HF, the results of the PARADIGM-HF trial and offer guidance on how to use sacubitril/valsartan in clinical practice. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  5. Cost-Effectiveness of Sacubitril-Valsartan in Patients With Heart Failure With Reduced Ejection Fraction.

    Science.gov (United States)

    Sandhu, Alexander T; Ollendorf, Daniel A; Chapman, Richard H; Pearson, Steven D; Heidenreich, Paul A

    2016-11-15

    Sacubitril-valsartan therapy reduces cardiovascular mortality compared with enalapril therapy in patients with heart failure with reduced ejection fraction. To evaluate the cost-effectiveness of sacubitril-valsartan versus angiotensin-converting enzyme inhibitor therapy in patients with chronic heart failure. Markov decision model. Clinical trials, observational analyses, reimbursement data from the Centers for Medicare & Medicaid Services, drug pricing databases, and Centers for Disease Control and Prevention life tables. Patients at an average age of 64 years, New York Heart Association (NYHA) class II to IV heart failure, and left ventricular ejection fraction of 0.40 or less. Lifetime. Societal. Treatment with sacubitril-valsartan or lisinopril. Life-years, quality-adjusted life-years (QALYs), costs, heart failure hospitalizations, and incremental cost-effectiveness ratios. The sacubitril-valsartan group experienced 0.08 fewer heart failure hospitalization, 0.69 additional life-year, 0.62 additional QALY, and $29 203 in incremental costs, equating to a cost per QALY gained of $47 053. The cost per QALY gained was $44 531 in patients with NYHA class II heart failure and $58 194 in those with class III or IV heart failure. Sacubitril-valsartan treatment was most sensitive to the duration of improved outcomes, with a cost per QALY gained of $120 623 if the duration was limited to the length of the trial (median, 27 months). No variations in other parameters caused the cost to exceed $100 000 per QALY gained. The benefit of sacubitril-valsartan is based on a single clinical trial. Treatment with sacubitril-valsartan provides reasonable value in reducing cardiovascular mortality and morbidity in patients with NYHA class II to IV heart failure. U.S. Department of Veterans Affairs and Institute for Clinical and Economic Review.

  6. Sacubitril/valsartan for heart failure with reduced left ventricular ejection fraction : A retrospective cohort study.

    Science.gov (United States)

    De Vecchis, R; Ariano, C; Di Biase, G; Noutsias, M

    2018-01-19

    The combination drug sacubitril/valsartan was reported to be superior to enalapril in reducing all-cause death, cardiovascular mortality, and heart failure (HF) hospitalizations in patients with cardiac insufficiency and reduced left ventricular ejection fraction (HFREF) with NYHA class II-IV. Our retrospective cohort study aimed to assess the effects of sacubitril/valsartan in addition to a beta-blocker and mineral receptor antagonist (MRA) in a group of HFREF patients with NYHA class II-III HF vs. conventional therapy (ACE inhibitor or angiotensin II receptor blocker added to a beta-blocker plus an MRA) administered to a control group of HFREF patients with comparable clinical features. In both groups, treatment was supplemented by a loop diuretic, usually furosemide, at variable doses. The primary outcomes were all-cause death and HF hospitalizations. Safety outcomes were symptomatic hypotension, angioedema, hyperkalemia, and worsening renal function. Mortality at 6 months was 6.8% in patients taking sacubitril/valsartan vs. 34% in those on conventional therapy (odds ratio [OR] = 0.14; 95% CI: 0.04-0.49). Moreover, there was a 4.5% rate of HF hospitalizations in the sacubitril/valsartan group vs. 59% in the control group (OR = 0.03; 95% CI: 0.01-0.14). Safety outcomes were comparable in the two groups, although hypotension (systolic blood pressure sacubitril/valsartan group vs. 5.7% in the control group (OR = 3.14; 95% CI: 0.94-10.55). Sacubitril/valsartan offered strong protection against all-cause death and HF hospitalizations at 6 months without any significant side effects. To validate this efficacious molecule, further postmarketing observational studies, focusing mainly on hypotension and angioedema are warranted.

  7. Efficacy of Sacubitril/Valsartan Relative to a Prior Decompensation: The PARADIGM-HF Trial.

    Science.gov (United States)

    Solomon, Scott D; Claggett, Brian; Packer, Milton; Desai, Akshay; Zile, Michael R; Swedberg, Karl; Rouleau, Jean; Shi, Victor; Lefkowitz, Martin; McMurray, John J V

    2016-10-01

    This study assessed whether the benefit of sacubtril/valsartan therapy varied with clinical stability. Despite the benefit of sacubitril/valsartan therapy shown in the PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial, it has been suggested that switching from an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker should be delayed until occurrence of clinical decompensation. Outcomes were compared among patients who had prior hospitalization within 3 months of screening (n = 1,611 [19%]), between 3 and 6 months (n = 1,009 [12%]), between 6 and 12 months (n = 886 [11%]), >12 months (n = 1,746 [21%]), or who had never been hospitalized (n = 3,125 [37%]). Twenty percent of patients without prior HF hospitalization experienced a primary endpoint of cardiovascular death or heart failure (HF) hospitalization during the course of the trial. Despite the increased risk associated with more recent hospitalization, the efficacy of sacubitril/valsartan therapy did not differ from that of enalapril according to the occurrence of or time from hospitalization for HF before screening, with respect to the primary endpoint or with respect to cardiovascular or all-cause mortality. 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). Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  8. Spotlight on valsartan–sacubitril fixed-dose combination for heart failure: the evidence to date

    Directory of Open Access Journals (Sweden)

    Vilela-Martin JF

    2016-05-01

    Full Text Available José Fernando Vilela-Martin Internal Medicine Department, São José do Rio Preto State Medical School (FAMERP, São José do Rio Preto, Brazil Abstract: Heart failure is a global problem with elevated prevalence, and it is associated with substantial cardiovascular morbidity and mortality. Treating heart-failure patients has been a very challenging task. This review highlights the main pharmacological developments in the field of heart failure with reduced ejection fraction, giving emphasis to a drug that has a dual-acting inhibition of the neprilysin and renin–angiotensin–aldosterone system. Neprilysin is an enzyme that participates in the breakdown of biologically active natriuretic peptides and several other vasoactive compounds. The inhibition of neprilysin has been a therapeutic target for several drugs tested in cardiovascular disease, mainly for heart failure and/or hypertension. However, side effects and a lack of efficacy led to discontinuation of their development. LCZ696 is a first-in-class neprilysin- and angiotensin-receptor inhibitor that has been developed for use in heart failure. This drug is composed of two molecular moieties in a single crystalline complex: a neprilysin-inhibitor prodrug (sacubitril and the angiotensin-receptor blocker (valsartan. The PARADIGM-HF trial demonstrated that this drug was superior to an angiotensin-converting enzyme inhibitor (enalapril in reducing mortality in patients with heart failure with reduced ejection fraction. The ability to block the angiotensin receptor and augment the endogenous natriuretic peptide system provides a distinctive mechanism of action in cardiovascular disease. Keywords: heart failure, vasopeptidase, natriuretic peptides, neprilysin, sacubitril, valsartan

  9. Sacubitril/Valsartan: The Newest Addition to the Toolbox for Guideline-Directed Medical Therapy of Heart Failure.

    Science.gov (United States)

    Rodgers, Jo E

    2017-06-01

    Sacubitril/valsartan combines a neprilysin inhibitor with an angiotensin receptor blocker. As an inhibitor of neprilysin, an enzyme that degrades biologically active natriuretic peptides, this first-in-class therapy increases levels of circulating natriuretic peptides, resulting in natriuretic, diuretic, and vasodilatory effects. In patients with chronic New York Heart Association class II-IV heart failure with reduced ejection fraction, the PARADIGM-HF trial demonstrated that sacubitril/valsartan significantly reduced the primary endpoint of cardiovascular mortality and heart failure hospitalization, compared with enalapril. The rate of all-cause mortality was also significantly reduced. Subsequently, the American College of Cardiology/American Heart Association/Heart Failure Society of America recently updated guideline recommendations for Stage C patients with heart failure with reduced ejection fraction to recommend angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or sacubitril/valsartan in conjunction with other evidence-based therapies to reduce morbidity and mortality. Several analyses have suggested the cost-effectiveness of this new therapy. To ensure tolerability, initiating the lower dosage form of sacubitril/valsartan is warranted in patients with severe renal impairment, moderate hepatic impairment, and low blood pressure, and close monitoring is warranted in such patients. A 36-hour washout period is recommended when switching patients from an angiotensin-converting enzyme inhibitor to sacubitril/valsartan. Similarly, sacubitril/valsartan is contraindicated in patients receiving concomitant angiotensin-converting enzyme inhibitor or angiotensin receptor blocker and those with a history of angioedema. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. What proportion of patients with chronic heart failure are eligible for sacubitril-valsartan?

    Science.gov (United States)

    Pellicori, Pierpaolo; Urbinati, Alessia; Shah, Parin; MacNamara, Alexandra; Kazmi, Syed; Dierckx, Riet; Zhang, Jufen; Cleland, John G F; Clark, Andrew L

    2017-06-01

    The PARADIGM-HF trial showed that sacubitril-valsartan, an ARB-neprilysin inhibitor, is more effective than enalapril for some patients with heart failure (HF). It is uncertain what proportion of patients with HF would be eligible for sacubitril-valsartan in clinical practice. Between 2001 and 2014, 6131 patients consecutively referred to a community HF clinic with suspected HF were assessed. The criteria required to enter the randomized phase of PARADIGM-HF, including symptoms, NT-proBNP, and current treatment with or without target doses of ACE inhibitors or ARBs, were applied to identify the proportion of patients eligible for sacubitril-valsartan. Recognizing the diversity of clinical opinion and guideline recommendations concerning this issue, entry criteria were applied singly and in combination. Of 1396 patients with reduced left ventricular ejection fraction (≤40%, HFrEF) and contemporary measurement of NT-proBNP, 379 were on target doses of an ACE inhibitor or ARB at their initial visit and, of these, 172 (45%) fulfilled the key entry criteria for the PARADIGM-HF trial. Lack of symptoms (32%) and NT-proBNP <600 ng/L (49%) were common reasons for failure to fulfil criteria. A further 122 patients became eligible during follow-up (n = 294, 21%). However, if background medication and doses were ignored, then 701 (50%) were eligible initially and a further 137 became eligible during follow-up. Of patients with HFrEF referred to a clinic such as ours, only 21% fulfilled the PARADIGM-HF randomization criteria, on which the ESC Guidelines are based; this proportion rises to 60% if background medication is ignored. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

  11. Antidepressant-like effect of losartan involves TRKB transactivation from angiotensin receptor type 2 (AGTR2) and recruitment of FYN.

    Science.gov (United States)

    Diniz, Cassiano R A F; Casarotto, Plinio C; Fred, Senem M; Biojone, Caroline; Castrén, Eero; Joca, Sâmia R L

    2018-06-01

    The renin-angiotensin system (RAS) is associated with peripheral fluid homeostasis and cardiovascular function, but recent evidence also suggests a functional role in the brain. RAS regulates physiological and behavioral parameters related to the stress response, including depressive symptoms. Apparently, RAS can modulate levels of brain-derived neurotrophic factor (BDNF) and TRKB, which are important in the neurobiology of depression and antidepressant action. However, the interaction between the BDNF/TRKB system and RAS in depression has not been investigated before. Accordingly, in the forced swimming test, we observed an antidepressant-like effect of systemic losartan but not with captopril or enalapril treatment. Moreover, infusion of losartan into the ventral hippocampus (vHC) and prelimbic prefrontal cortex (PL) mimicked the consequences of systemically injected losartan, whereas K252a (a blocker of TRK) infused into these brain areas impaired such effect. PD123319, an antagonist of AT2 receptor (AGTR2), also prevented the systemic losartan effect when infused into PL but not into vHC. Cultured cortical cells of rat embryos revealed that angiotensin II (ANG2), possibly through AGTR2, increased the surface levels of TRKB and its coupling to FYN, a SRC family kinase. Higher Agtr2 levels in cortical cells were reduced after stimulation with glutamate, and only under this condition an interaction between losartan and ANG2 was achieved. TRKB/AGTR2 heterodimers were also observed, in MG87 cells GFP-tagged AGTR2 co-immunoprecipitated with TRKB. Therefore, the antidepressant-like effect of losartan is proposed to occur through a shift of ANG2 towards AGTR2, followed by coupling of TRK/FYN and putative TRKB transactivation. Thus, the blockade of AGTR1 has therapeutic potential as a novel antidepressant therapy. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  12. Diuretics for Hypertension: A Review and Update.

    Science.gov (United States)

    Roush, George C; Sica, Domenic A

    2016-10-01

    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 resistant hypertension. HCTZ is 4.2-6.2 systolic mm Hg less potent than CTDN, angiotensin-converting enzyme inhibitors, beta blockers, and calcium channel blockers by 24-hour measurements and 5.1mm Hg systolic less potent than INDAP by office measurements. For reducing cardiovascular events (CVEs), HCTZ is less effective than enalapril and amlodipine in randomized trials, and, in network analysis of trials, it is less effective than CTDN and HCTZ-amiloride. Combined with thiazide-type diuretics, potassium-sparing agents decrease ventricular ectopy and reduce the risk for sudden cardiac death relative to thiazide-type diuretics used alone. A recent synthesis of 44 trials has shown that the relative potencies in milligrams among spironolactone (SPIR), amiloride, and eplerenone (EPLER) are approximately from 25 to 10 to 100, respectively, which may be important when SPIR is poorly tolerated. SPIR reduces proteinuria beyond that provided by other renin angiotensin aldosterone inhibitors. EPLER also reduces proteinuria and has beneficial effects on endothelial function. While guidelines often do not differentiate among specific diuretics, this review demonstrates that these distinctions are important for managing hypertension. © American Journal of Hypertension, Ltd 2016. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. THE ANALYSIS OF DIFFERENCES IN DOCTORS PREFERENCES IN THE PRESCRIPTIONS OF ANTIHYPERTENSIVE DRUGS IN FOUR REGIONS OF THE FAR EASTERN FEDERAL DISTRICT

    Directory of Open Access Journals (Sweden)

    M. S. Soboleva

    2018-01-01

    Full Text Available Aim. To study regional features and preferences of specialists in the choice of drug therapy of arterial hypertension in four subjects of the Far Eastern Federal District.Material and methods. Statistical data, demographic indicators, state and municipal drug procurements in Chukotka Autonomous Okrug, the Sakha Republic (Yakutia, the Magadan Region, and Kamchatka Krai were analyzed. The studied period was 2012-2016. Dynamics of the use (procurements of five main therapeutic classes of antihypertensive drugs was studied.Results. Among β-blockers the leaders were metoprolol (from 2% to 30.8% and bisoprolol (from 2.4% to 20.3%, in group of angiotensin converting enzyme inhibitors – enalapril (from 3.6% to 27%, lisinopril (from 4.4% to 23.9% and perindopril (from 0.9% to 7.8%, among calcium channel blockers – amlodipine (from 5.6% to 11.3%, in group of diuretics – indapamide (from 2.5% to 13% and spironolactone (from 3% to 12.5%, and in group of angiotensin II antagonists – losartan (from 0.4% to 15.6%. Angiotensin converting enzyme inhibitors were the most used therapeutic class of antihypertensive drugs in Chukotka Autonomous Okrug, the Magadan region and Kamchatka Krai. At the same time, β-blockers accounted for more than a half of state and municipal procurements in the Sakha Republic (Yakutia.Conclusion. It is necessary to study regional aspects and approaches to therapy to assess the extent and specificity of the implementation of research results, standards and recommendations in real clinical practice.

  14. Evaluation of contributing factors of post transplant erythrocytosis in renal transplant patients

    International Nuclear Information System (INIS)

    Ahmed, S.; Ahmed, E.; Naqvi, R.; Qureshi, S.

    2012-01-01

    Objective: To evaluate the prevalence and contributing factors causing post transplant erythrocytosis in renal transplant patients. Methods: This retrospective study was conducted on live related renal transplant patients at SIUT. The records of all transplant recipients transplanted between April 2008 and December 2008 and who had at least 24 months follow up were studied. Patients in whom haematocrit exceeded 51% and those who received treatment for it were classified into post transplant erythrocytosis group. Results: Out of 200 renal transplant patients who had functioning graft at the time of analysis, 40 (20%) developed post transplant erythrocytosis (HCT >51%) after a mean interval of 9.5+- 2.5 months. Patients with erythrocytosis were mostly males (95% in PTE group vs 73.75% in non PTE group) ,had a shorter period on dialysis before undergoing renal transplantation (9.28 months in PTE group vs 14.56 months in non PTE group) and had relatively better graft function at the onset of erythrocytosis as judged by serum creatinine (S. Creatinine of 1.06+-0.29 mg/dl in PTE group vs 1.37 +- 0.51 mg/dl in non PTE group). No thrombotic complications were observed. All patients with erythrocytosis were treated with enalapril (ACE inhibitors) and 28 out of 40 required phlebotomy in addition to ACE inhibitors. The mean HCT at the time of last follow up in treated patients was 48.61+-1.85%. Conclusion: Post transplant erythrocytosis generally occurs in male patients with good graft function, thrombotic complications are of rare occurrence and response to ACE inhibitors is good. (author)

  15. Do cardiologists at a university hospital adopt the guidelines for the treatment of heart failure?

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    Barretto Antonio Carlos Pereira

    2001-01-01

    Full Text Available OBJECTIVE: To verify whether the guidelines for the treatment of heart failure have been adopted at a university hospital. The guidelines recommend the following: use of angiotensin-converting enzyme inhibitors for all patients with systolic ventricular dysfunction, use of digitalis and diuretics for symptomatic patients, use of beta-blockers for patients in functional classes II or III, use of spironolactone for patients in functional classes III or IV. METHODS: We analyzed the prescriptions of 199 patients. All these patients had ejection fraction (EF <=0.50, their ages ranged from 25 to 86 years, and 142 were males. Cardiomyopathy was the most frequent diagnosis: 67 (33.6% patients had dilated cardiomyopathy, 65 (32.6% had ischemic cardiomyopathy. RESULTS: Angiotensin-converting enzyme inhibitors were prescribed for 93% of the patients. 71.8% also had a prescription for digitalis, 86.9% for diuretics, 27.6% for spironolactone, 12% for beta-blockers, 37.2% for acetylsalicylic acid, 6.5% for calcium channel antagonists, and 12.5% for anticoagulants. In regard to vasodilators, 71% of the patients were using captopril (85.2mg/day, 20% enalapril (21.4mg/day, 3% hydralazine and nitrates. In 71.8% of the cases, the dosages prescribed were in accordance with those recommended in the large studies. CONCLUSION: Most patients were prescribed the same doses as those recommended in the large studies. Brazilian patients tolerate well the doses recommended in the studies, and that not using these doses may be a consequence of the physician's fear of prescribing them and not of the patient's intolerance.

  16. Oxidative stress/reactive metabolite gene expression signature in rat liver detects idiosyncratic hepatotoxicants

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    Leone, Angelique; Nie, Alex; Brandon Parker, J.; Sawant, Sharmilee; Piechta, Leigh-Anne; Kelley, Michael F., E-mail: mkelley2@its.jnj.com; Mark Kao, L.; Jim Proctor, S.; Verheyen, Geert; Johnson, Mark D.; Lord, Peter G.; McMillian, Michael K.

    2014-03-15

    Previously we reported a gene expression signature in rat liver for detecting a specific type of oxidative stress (OS) related to reactive metabolites (RM). High doses of the drugs disulfiram, ethinyl estradiol and nimesulide were used with another dozen paradigm OS/RM compounds, and three other drugs flutamide, phenacetin and sulindac were identified by this signature. In a second study, antiepileptic drugs were compared for covalent binding and their effects on OS/RM; felbamate, carbamazepine, and phenobarbital produced robust OS/RM gene expression. In the present study, liver RNA samples from drug-treated rats from more recent experiments were examined for statistical fit to the OS/RM signature. Of all 97 drugs examined, in addition to the nine drugs noted above, 19 more were identified as OS/RM-producing compounds—chlorpromazine, clozapine, cyproterone acetate, dantrolene, dipyridamole, glibenclamide, isoniazid, ketoconazole, methapyrilene, naltrexone, nifedipine, sulfamethoxazole, tamoxifen, coumarin, ritonavir, amitriptyline, valproic acid, enalapril, and chloramphenicol. Importantly, all of the OS/RM drugs listed above have been linked to idiosyncratic hepatotoxicity, excepting chloramphenicol, which does not have a package label for hepatotoxicity, but does have a black box warning for idiosyncratic bone marrow suppression. Most of these drugs are not acutely toxic in the rat. The OS/RM signature should be useful to avoid idiosyncratic hepatotoxicity of drug candidates. - Highlights: • 28 of 97 drugs gave a positive OS/RM gene expression signature in rat liver. • The specificity of the signature for human idiosyncratic hepatotoxicants was 98%. • The sensitivity of the signature for human idiosyncratic hepatotoxicants was 75%. • The signature can help eliminate hepatotoxicants from drug development.

  17. Response to angiotensin-converting enzyme inhibition is selectively blunted by high sodium in angiotensin-converting enzyme DD genotype: evidence for gene-environment interaction in healthy volunteers.

    Science.gov (United States)

    Lely, A Titia; Heerspink, Hiddo J Lambers; Zuurman, Mike; Visser, Folkert W; Kocks, Menno J A; Boomsma, Frans; Navis, Gerjan

    2010-12-01

    Renin-angiotensin-aldosterone system blockade is a cornerstone in cardiovascular protection. Angiotensin-converting enzyme (ACE)-DD genotype has been associated with resistance to angiotensin-converting enzyme inhibition (ACEi), but data are conflicting. As sodium intake modifies the effect of ACEi as well as the genotype-phenotype relationship, we hypothesize gene-environment interaction between sodium-status, the response to ACEi, and ACE genotype. Thirty-five male volunteers (26 ± 9 years; II n = 6, ID n = 18, DD n = 11) were studied during placebo and ACEi (double blind, enalapril 20 mg/day) on low [7 days 50 mmol Na/day (low salt)] and high [7 days 200 mmol Na/day (high salt)] sodium, with a washout of 6 weeks in-between. After each period mean arterial pressure (MAP) was measured before and during graded infusion of angiotensin II (Ang II). During high salt, ACEi reduced MAP in II and ID, but not in DD [II: 88 (78-94) versus 76 (72-88); ID: 87 (84-91) versus 83 (79-87); both P DD: 86 (82-96) versus 88 (80-90); ns, P DD: 84 (80-91) versus 81 (75-85); all P DD, with an 18% rise in MAP during the highest dose versus 22 and 31% in ID and II (P DD genotype during high salt, accompanied by blunted sensitivity to Ang II. Low salt corrects both abnormalities. Further analysis of this gene-environment interaction in patients may contribute to strategies for improvement of individual treatment efficacy.

  18. Lipodistrofia parcial familiar tipo 1: ¿Un síndrome subdiagnosticado o raro?

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    Jimena Soutelo

    2015-02-01

    Full Text Available La lipodistrofia parcial familiar de tipo1 (LPF 1 es un síndrome caracterizado por la pérdida parcial de grasa subcutánea en extremidades con distribución incrementada de la misma en rostro, cuello y tronco. Es una identidad familiar aunque hay casos espontáneos. Hasta ahora no se conoce mutación responsable. Se debe realizar diagnóstico diferencial con el síndrome de Cushing. Es un síndrome poco frecuente y en oportunidades se llega al diagnóstico cuando los pacientes presentan complicaciones cardiovasculares o afectación pancreática como consecuencia de una grave alteración metabólica. Se presenta el caso de una paciente de 45 años con diabetes mellitus desde los 20 años de edad, mal control glucémico (HbA1c: 11.7% e hipertrigliceridemia (TG: 3000 mg/dl, índice de masa corporal (IMC: 38, extremidades adelgazadas, pérdida de grasa subcutánea en glúteos, sobreelevación de pliegue por encima de los mismos, venas prominentes en miembros inferiores, cara de luna llena y marcada acantosis nigricans, hipertensión (TA: 150/100 mm Hg y medidas de pliegues subcutáneos disminuidos. El dosaje de leptina fue 16.8 mg/ml. El estudio genético para gen LMNA fue negativo. Se instauraron medidas de cambio de estilo de vida, tratamiento con fenofibrato, insulina premezcla 50/50 y enalapril, obteniéndose una franca mejoría clínica, de la HbA1c (7.8% y de los TG (243 mg/dl.

  19. Cardiovascular and Metabolic Consequences of Testosterone Supplements in Young and Old Male Spontaneously Hypertensive Rats: Implications for Testosterone Supplements in Men.

    Science.gov (United States)

    Dalmasso, Carolina; Patil, Chetan N; Yanes Cardozo, Licy L; Romero, Damian G; Maranon, Rodrigo O

    2017-10-17

    The safety of testosterone supplements in men remains unclear. In the present study, we tested the hypothesis that in young and old male spontaneously hypertensive rats (SHR), long-term testosterone supplements increase blood pressure and that the mechanism is mediated in part by activation of the renin-angiotensin system. In untreated males, serum testosterone exhibited a sustained decrease after 5 months of age, reaching a nadir by 18 to 22 months of age. The reductions in serum testosterone were accompanied by an increase in body weight until very old age (18 months). Testosterone supplements were given for 6 weeks to young (12 weeks-YMSHR) and old (21-22 months-OMSHR) male SHR that increased serum testosterone by 2-fold in young males and by 4-fold in old males. Testosterone supplements decreased body weight, fat mass, lean mass, and plasma leptin, and increased plasma estradiol in YMSHR but had no effect in OMSHR. Mean arterial pressure (MAP) was significantly higher in OMSHR than in YMSHR and testosterone supplements decreased MAP in OMSHR, but significantly increased MAP in YMSHR. Enalapril, the angiotensin-converting enzyme inhibitor, reduced MAP in both control and testosterone-supplemented YMSHR, but had a greater effect on MAP in testosterone-treated rats, suggesting the mechanism responsible for the increase in MAP in YMSHR is mediated at least in part by activation of the renin-angiotensin system. Taken together with previous studies, these data suggest that testosterone supplements may have differential effects on men depending on age, cardiovascular and metabolic status, and dose and whether given long-term or short-term. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  20. How well can blood pressure be controlled? Progress report on the Systolic Hypertension in Europe Follow-Up Study (Syst-Eur 2

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    Sarti Cinzia

    2001-10-01

    Full Text Available Abstract Background The randomised, double-blind, placebo-controlled Systolic Hypertension in Europe trial (Syst-Eur 1 proved that blood pressure (BP lowering therapy starting with nitrendipine reduces the risk of cardiovascular complications in elderly patients with isolated systolic hypertension. In an attempt to confirm the safety of long-term antihypertensive therapy based on a dihydropyridine, the Syst-Eur patients remained in open follow-up after the end of Syst-Eur 1. This paper presents the second progress report of this follow-up study (Syst-Eur 2. It describes BP control and adherence to study medications. Methods After the end of Syst-Eur 1 all patients, treated either actively or with placebo, were invited either to continue or to start antihypertensive treatment with the same drugs as previously used in the active treatment arm. In order to reach the target BP (sitting SBP Results Of the 3787 eligible patients, 3516 (93% entered Syst-Eur 2. At the last available visit, 72% of the patients were taking nitrendipine. SBP/DBP at entry in Syst-Eur 2 averaged 160/83 mmHg in the former placebo group and 151/80 mmHg in the former active-treatment group. At the last follow-up visit SBP/DBP in the patients previously randomised to placebo or active treatment had decreased by 16/5 mmHg and 7/5 mmHg, respectively. The target BP was reached by 74% of the patients. Conclusion Substantial reductions in systolic BP may be achieved in older patients with isolated systolic hypertension with a treatment strategy starting with the dihydropyridine calcium-channel blocker, nitrendipine, with the possible addition of enalapril and/or hydrochlorothiazide.

  1. Thyroxine-induced cardiac hypertrophy: influence of adrenergic nervous system versus renin-angiotensin system on myocyte remodeling.

    Science.gov (United States)

    Hu, L W; Benvenuti, L A; Liberti, E A; Carneiro-Ramos, M S; Barreto-Chaves, M L M

    2003-12-01

    The present study assessed the possible involvement of the renin-angiotensin system (RAS) and the sympathetic nervous system (SNS) in thyroxine (T4)-induced cardiac hypertrophy. Hemodynamic parameters, heart weight (HW), ratio of HW to body weight (HW/BW), and myocyte width were evaluated in absence of thyroid hormone (hypothyroidism) and after T4 administration. Male Wistar rats were used. Some were subjected to thyroidectomies, whereas hyperthyroidism was induced in others via daily intraperitoneal injection of T4 (25 or 100 microg x 100 g BW(-1) x day(-1)) for 7 days. In some cases, T4 administration was combined with the angiotensin I-converting enzyme inhibitor enalapril (Ena), with the angiotensin type 1 (AT1) receptor blocker losartan (Los) or with the beta-adrenergic blocker propanolol (Prop). Hemodynamics and morphology were then evaluated. Systolic blood pressure (SBP) was not altered by administration of either T4 alone or T4 in combination with the specific inhibitors. However, SBP decreased significantly in hypothyroid rats. An increased heart rate was seen after administration of either T4 alone or T4 in combination with either Los or Ena. Although the higher dose of T4 significantly increased HW, HW/BW increased in both T4-treated groups. Ena and Prop inhibited the increase in HW or HW/BW in hyperthyroid rats. Morphologically, both T4 dose levels significantly increased myocyte width, an occurrence prevented by RAS or SNS blockers. There was a good correlation between changes in HW/BW and myocyte width. These results indicate that T4-induced cardiac hypertrophy is associated with both the SNS and the RAS.

  2. Perception of teratogenic and foetotoxic risk by health professionals: a survey in Midi-Pyrenees area.

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    Damase-Michel C

    2008-03-01

    Full Text Available Counselling or prescribing drugs during pregnancy requires health professionals to assess risk/benefit ratio for women and their baby. A misperception of the risk may lead to inappropriate decisions for pregnancy outcomes. The aim of the present study was to assess teratogenic and/or foetotoxic risk perception of common medications by general practitioners (GPs and community pharmacists (CPs from the Midi-Pyrenees area.Methods: 103 GPs and 104 CPs were interviewed. For 21 given drugs, a visual-analogue scale was used to evaluate the risk to give birth to a malformed infant if the mother had taken the drug during first trimester of pregnancy. For 9 drugs, health professionals had to say if they thought there was a potential foetotoxic and/or neonatal risk when drugs were administered during late pregnancy.Results: 97% and 91% of GPs and CPs respectively thought that isotretinoin and thalidomide are teratogenic and more than 80% thought that amoxicillin and acetaminophen are safe in early pregnancy. However, 19% of the GPs and 33% of CPs answered there were no teratogenic risk for valproate. Around 11% of both GPs and CPs said that warfarin was safe during pregnancy. For 22% of GPs and for 13% and 27% of CPs respectively, ibuprofen and enalapril were safe on late pregnancy. For each drug, mean value of perceived teratogenic risk by health professionals was higher than values that can be found in scientific references. Concerning isotretinoin, thalidomide and metoclopramide, perceived teratogenic risk was higher for CPs.Conclusion: These data show that the potential teratogenic and foetotoxic risk of several commonly used drugs is unknown by health professionals. Conversely, GPs and CPs who think that a risk exists, overestimate it. This misperception can lead to inappropriate decisions for pregnancy outcomes.

  3. Partial podocyte replenishment in experimental FSGS derives from nonpodocyte sources.

    Science.gov (United States)

    Kaverina, Natalya V; Eng, Diana G; Schneider, Remington R S; Pippin, Jeffrey W; Shankland, Stuart J

    2016-06-01

    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 staining, which is consistent with podocyte depletion. Staining for p57, synaptopodin, podocin, and DAPI increased at FSGS day 28 and was augmented by the ACE inhibitor enalapril, which is consistent with a partial replenishment of podocytes. In contrast, ZsGreen fluorescence did not return and remained significantly low at day 28, indicating replenishment was from a nonpodocyte origin. Despite administration of bromodeoxyuridine (BrdU) thrice weekly throughout the course of disease, BrdU staining was not detected in podocytes, which is consistent with an absence of proliferation. Although ZsGreen reporting was reduced in the tuft at FSGS day 28, labeled podocytes were detected along the Bowman's capsule in a subset of glomeruli, which is consistent with migration from the tuft. Moreover, more than half of the migrated podocytes coexpressed the parietal epithelial cell (PEC) proteins claudin-1, SSeCKS, and PAX8. These results show that although podocytes can be partially replenished following abrupt depletion, a process augmented by ACE inhibition, the source or sources are nonpodocyte in origin and are independent of proliferation. Furthermore, a subset of podocytes migrate to the Bowman's capsule and begin to coexpress PEC markers. Copyright © 2016 the American Physiological Society.

  4. Adverse drug reaction reports for cardiometabolic drugs from sub-Saharan Africa: a study in VigiBase.

    Science.gov (United States)

    Berhe, Derbew Fikadu; Juhlin, Kristina; Star, Kristina; Beyene, Kidanemariam G M; Dheda, Mukesh; Haaijer-Ruskamp, Flora M; Taxis, Katja; Mol, Peter G M

    2015-06-01

    Identifying key features in individual case safety reports (ICSR) of suspected adverse drug reactions (ADRs) with cardiometabolic drugs from sub-Saharan Africa (SSA) compared with reports from the rest of the world (RoW). Reports on suspected ADRs of cardiometabolic drugs (ATC: A10[antidiabetic], B01[antithrombotics] and C[cardiovascular]) were extracted from WHO Global database, VigiBase(®) (1992-2013). We used vigiPoint, a logarithmic odds ratios (log2 OR)-based method to study disproportional reporting between SSA and RoW. Case-defining features were considered relevant if the lower limit of the 99% CI > 0.5. In SSA, 3773 (9%) of reported ADRs were for cardiometabolic drugs, in RoW for 18%. Of these, 79% originated from South Africa and 81% were received after 2007. Most reports were for drugs acting on the renin-angiotensin system (36% SSA & 14% RoW). Compared with RoW, reports were more often sent for patients 18-44 years old (log2 OR 0.95 [99 CI 0.80; 1.09]) or with non-fatal outcome (log2 OR 1.16 [99 CI 1.10; 1.22]). Eight ADRs (cough, angioedema, lip swelling, face oedema, swollen tongue, throat irritation, drug ineffective and blood glucose abnormal) and seven drugs (enalapril, rosuvastatin, perindopril, vildagliptin, insulin glulisine, nifedipine and insulin lispro) were disproportionally more reported in SSA than in the RoW. 'In recent years, the number of adverse drug reactions (ADRs) reported in Sub-Saharan Africa (SSA) has sharply increased. The data showed the well-known population-based differential ADR profile of ACE inhibitors in the SSA population.' © 2015 John Wiley & Sons Ltd.

  5. Effect of long-term treatment with urocortin on the activity of somatic angiotensin-converting enzyme in spontaneously hypertensive rats.

    Science.gov (United States)

    Yang, Cui; Liu, Xiuxia; Li, Shengnan

    2010-02-01

    Our previous acute study on urocortin (Ucn) demonstrated that Ucn altered serum and tissue angiotensin-converting enzyme (ACE) activity in rats. Therefore, the present investigation was designed to explore the effect of long-term treatment with Ucn on somatic ACE (sACE) and other components of the renin-angiotensin system (RAS). After 8 weeks of intravenous administration of Ucn in spontaneously hypertensive rats (SHR), serum and tissue sACE, angiotensin II (Ang II), nitric oxide (NO), Ang-(1-7), and tissue chymase activities were evaluated. RT-PCR analysis was performed to determine the quantity of tissue sACE mRNA. Serum sACE activity was reduced by Ucn, although tissue sACE activity and tissue sACE mRNA were elevated. Chymase activity was observed to be enhanced by Ucn, whereas the ACE inhibitor enalapril failed to influence chymase. Serum and tissue Ang II activity was reduced, but NO and Ang-(1-7) production was increased in a concentration-dependent manner after Ucn treatment. Meanwhile, a significant decrease of the systolic blood pressure (SBP) was observed after the long-term Ucn administration, and there was a significant positive correlation (r2 = 0.6993) between serum ACE activity and SBP. Pretreatment with the corticotropin-releasing factor (CRF) blocker astressin and the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway blocker PD98059 abolished these effects of Ucn. Our findings further support the hypothesis that the changes of sACE activity and the production of other RAS components may play roles in the vasodilatory property of Ucn via the activation of the ERK1/2 pathway.

  6. Dual renin-angiotensin system blockade plus oral methylprednisone for the treatment of proteinuria in IgA nephropathy Doble bloqueo del sistema renina-angiotensina más metilprednisona oral para el tratamiento de la proteinuria en la nefropatía por IgA

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    Hernán Trimarchi

    2007-10-01

    Full Text Available Renin-angiotensin system inhibition is a widely accepted approach to initially deal with proteinuria in IgA nephropathy, while the role of immunosuppressants remains controversial in many instances. A prospective, uncontrolled, open-label trial was undertaken in patients with biopsy-proven IgA nephropathy with proteinuria > 0.5 g/day and normal renal function to assess the efficacy of a combination treatment of angiotensin converting enzyme inhibitors plus angiotensin receptor blockers enalapril valsartan coupled with methylprednisone to decrease proteinuria to levels below 0.5 g/day. Twenty patients were included: Age 37.45 ± 13.26 years (50% male; 7 patients (35% were hypertensive; proteinuria 2.2 ± 1.86 g/day; serum creatinine 1.07 ± 0.29 mg/dl; mean follow-up 60.10 ± 31.47 months. IgA nephropathy was subclassified according to Haas criteria. Twelve patients (60% were class II; seven (35% were class III and one (5% class V. All patients received dual reninangiotensin system blockade as tolerated. Oral methylprednisone was started at 0.5 mg/kg/day for the initial 8 weeks and subsequently tapered bi-weekly until the maintenance dose of 4 mg was reached. Oral steroids were discontinued after 24 weeks (6 months of therapy but renin-angiotensin inhibition remained unchanged. At 10 weeks of therapy proteinuria decreased to 0.15 ± 0.07 g/day (P El doble bloqueo del sistema renina-angiotensina con inhibidores de la enzima convertidora de angiotensina junto a bloqueadores del receptor tipo I de angiotensina II es aceptado como tratamiento en la proteinuria de la nefropatía por IgA, ya que el rol de los inmunosupresores continúa siendo controvertido. Estudio prospectivo, no controlado, abierto para pacientes con nefropatía por IgA con proteinurias >0.5 g/día y creatininas séricas <1.4 mg/dl, para evaluar la eficacia de tratamiento de enalapril más valsartán asociado a metilprednisona vía oral para disminuir las proteinurias a <0.5 g

  7. The renal blood flow reserve in healthy humans and patients with atherosclerotic renovascular disease measured by positron emission tomography using [15O]H2O.

    Science.gov (United States)

    Päivärinta, Johanna; Koivuviita, Niina; Oikonen, Vesa; Iida, Hidehiro; Liukko, Kaisa; Manner, Ilkka; Löyttyniemi, Eliisa; Nuutila, Pirjo; Metsärinne, Kaj

    2018-06-11

    Microvascular function plays an important role in ARVD (atherosclerotic renovascular disease). RFR (renal flow reserve), the capacity of renal vasculature to dilate, is known to reflect renal microvascular function. In this pilot study, we assessed PET (positron emission tomography)-based RFR values of healthy persons and renal artery stenosis patients. Seventeen patients with ARVD and eight healthy subjects were included in the study. Intravenous enalapril 1 mg was used as a vasodilatant, and the maximum response (blood pressure and RFR) to it was measured at 40 min. Renal perfusion was measured by means of oxygen-15-labeled water PET. RFR was calculated as a difference of stress flow and basal flow and was expressed as percent [(stress blood flow - basal blood flow)/basal blood flow] × 100%. RFR of the healthy was 22%. RFR of the stenosed kidneys of bilateral stenosis patients (27%) was higher than that of the stenosed kidneys of unilateral stenosis patients (15%). RFR of the contralateral kidneys of unilateral stenosis patients was 21%. There was no difference of statistical significance between RFR values of ARVD subgroups or between ARVD subgroups and the healthy. In the stenosed kidneys of unilateral ARVD patients, stenosis grade of the renal artery correlated negatively with basal (p = 0.04) and stress flow (p = 0.02). Dispersion of RFR values was high. This study is the first to report [ 15 O]H 2 O PET-based RFR values of healthy subjects and ARVD patients in humans. The difference between RFR values of ARVD patients and the healthy did not reach statistical significance perhaps because of high dispersion of RFR values. [ 15 O]H 2 O PET is a valuable non-invasive and quantitative method to evaluate renal blood flow though high dispersion makes imaging challenging. Larger studies are needed to get more information about [ 15 O]H 2 O PET method in evaluation of renal blood flow.

  8. Prevention of airway hyperresponsiveness induced by left ventricular dysfunction in rats

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    Petak Ferenc

    2012-12-01

    Full Text Available Abstract Background The effectiveness of strategies for treatment of the altered static lung volume and against the development of bronchial hyperreactivity (BHR following a left ventricular dysfunction (LVD induced by myocardial ischaemia was investigated in a rat model of sustained postcapillary pulmonary hypertension. Methods Airway resistance (Raw was identified from the respiratory system input impedance (Zrs in four groups of rats. End-expiratory lung volume (EELV was determined plethysmographically, and Zrs was measured under baseline conditions and following iv infusions of 2, 6 or 18 μg/kg/min methacholine. Sham surgery was performed in the rats in Group C, while the left interventricular coronary artery was ligated and Zrs and its changes following identical methacholine challenges were reassessed in the same rats 8 weeks later, during which no treatment was applied (Group I, or the animals were treated daily with a combination of an angiotensin enzyme converter inhibitor and a diuretic (enalapril and furosemide, Group IE, or a calcium channel blocker (diltiazem, Group ID. The equivalent dose of methacholine causing a 100% increase in Raw (ED50 was determined in each group. Diastolic pulmonary arterial pressure (PapD was assessed by introducing a catheter into the pulmonary artery. Results The sustained presence of a LVD increased PapD in all groups of rats, with variable but significant elevations in Groups I (p = 0.004, ID (p = 0.013 and IE (p = 0.006. A LVD for 8 weeks induced no changes in baseline Raw but elevated the EELV independently of the treatments. In Group I, BHR consistently developed following the LVD, with a significant decrease in ED50 from 10.0 ± 2.5 to 6.9 ± 2.5 μg/kg/min (p = 0.006. The BHR was completely abolished in both Groups ID and IE, with no changes in ED50 (9.5 ± 3.6 vs. 10.7 ± 4.7, p = 0.33 and 10.6 ± 2.1 vs. 9.8 ± 3.5 μg/kg/min p = 0.56, respectively

  9. Occurrence and modeling of pharmaceuticals on a sewage-impacted Mediterranean river and their dynamics under different hydrological conditions

    Energy Technology Data Exchange (ETDEWEB)

    Osorio, Victoria [IDAEA-CSIC, Jordi Girona 18-26, Barcelona (Spain); Marce, Rafael [Catalan Institute for Water Research (ICRA), Scientific and Technological Park of the University of Girona, Emili Grahit 101, Girona (Spain); Perez, Sandra [IDAEA-CSIC, Jordi Girona 18-26, Barcelona (Spain); Ginebreda, Antoni, E-mail: agmqam@idaea.csic.es [IDAEA-CSIC, Jordi Girona 18-26, Barcelona (Spain); Cortina, Jose Luis [Cetaqua, Water Technology Centre, UPC North Campus, Paseo de los Tilos, 3, Barcelona (Spain); Barcelo, Damia [IDAEA-CSIC, Jordi Girona 18-26, Barcelona (Spain); Catalan Institute for Water Research (ICRA), Scientific and Technological Park of the University of Girona, Emili Grahit 101, Girona (Spain)

    2012-12-01

    The occurrence of 73 representative pharmacologically active compounds (PhACs) was assessed in a sewage-impacted section of the Llobregat River (NE Catalonia, Spain). This Mediterranean river is characterized by flow rate fluctuations strongly influenced by seasonal rainfall. River flow variations increase the potential environmental risk posed by organic micro-pollutants as their concentrations may increase substantially under low flow conditions. Little is known about the transport behavior of emerging contaminants in surface waters once they are discharged from waste water treatment plants (WWTP) into rivers. This research aimed to study the presence and fate of emerging contaminants under different hydrological conditions by sampling two different sites along the river in different seasons. The highest levels of pharmaceuticals were determined during cold and dry periods. The impact of the flow changes on the concentration of the pharmaceuticals in the river was assessed with the relative sensitive coefficients. Due to expected dilution effects, the response of pharmaceuticals to river flow was negative. Only in a few cases, positive relationships between drug concentrations and flow were detected, suggesting an important role of other hydrological phenomena like sediment re-suspension as well as the source of pollutants. To evaluate the role of other factors influencing PhAC concentrations, a plug-flow model was applied to obtain disappearance constants 'k' for a set of selected compounds. Erythromycin presented k values of - 0.15 h{sup -1} in both sites being the compound more efficiently removed from the water column. The k values for ibuprofen, furosemide, enrofloxacin, enalapril, acetaminophen, diclofenac and Ketoprofen were between - 0.04 and - 0.10 h{sup -1} showing less disappearance than erythromycin in the water column. However, other compounds presented k values < 0.06, which suggested conservative behavior of these compounds in the water

  10. Occurrence and modeling of pharmaceuticals on a sewage-impacted Mediterranean river and their dynamics under different hydrological conditions

    International Nuclear Information System (INIS)

    Osorio, Victoria; Marcé, Rafael; Pérez, Sandra; Ginebreda, Antoni; Cortina, Jose Luís; Barceló, Damià

    2012-01-01

    The occurrence of 73 representative pharmacologically active compounds (PhACs) was assessed in a sewage-impacted section of the Llobregat River (NE Catalonia, Spain). This Mediterranean river is characterized by flow rate fluctuations strongly influenced by seasonal rainfall. River flow variations increase the potential environmental risk posed by organic micro-pollutants as their concentrations may increase substantially under low flow conditions. Little is known about the transport behavior of emerging contaminants in surface waters once they are discharged from waste water treatment plants (WWTP) into rivers. This research aimed to study the presence and fate of emerging contaminants under different hydrological conditions by sampling two different sites along the river in different seasons. The highest levels of pharmaceuticals were determined during cold and dry periods. The impact of the flow changes on the concentration of the pharmaceuticals in the river was assessed with the relative sensitive coefficients. Due to expected dilution effects, the response of pharmaceuticals to river flow was negative. Only in a few cases, positive relationships between drug concentrations and flow were detected, suggesting an important role of other hydrological phenomena like sediment re-suspension as well as the source of pollutants. To evaluate the role of other factors influencing PhAC concentrations, a plug-flow model was applied to obtain disappearance constants “k” for a set of selected compounds. Erythromycin presented k values of − 0.15 h −1 in both sites being the compound more efficiently removed from the water column. The k values for ibuprofen, furosemide, enrofloxacin, enalapril, acetaminophen, diclofenac and Ketoprofen were between − 0.04 and − 0.10 h −1 showing less disappearance than erythromycin in the water column. However, other compounds presented k values < 0.06, which suggested conservative behavior of these compounds in the water column

  11. Síndrome urémico hemolítico. Tratamiento de la glomerulopatía secundaria Hemolytic uremic syndrome. Treatment of secondary glomerulopathy

    Directory of Open Access Journals (Sweden)

    María G. Caletti

    2005-12-01

    Full Text Available La insuficiencia renal crónica es la complicación más grave del síndrome urémico hemolítico (SUH. En el año 1996 se publicó la secuencia histológica de su evolución en pacientes con períodos oligoanúricos prolongados. En los últimos años se han propuesto diferentes esquemas terapéuticos para enlentecer la evolución a la insuficiencia renal crónica terminal en distintas nefropatías, diabéticas y no diabéticas, cuya expresión puede comenzar aun en la adolescencia. En este trabajo se comenta la respuesta a dos esquemas terapéuticos de dos grupos de pacientes con SUH que presentaron proteinuria con o sin hipertensión arterial e insuficiencia renal. Se enfatiza la indicación de la dieta hiposódica y controlada en proteínas en el mismo momento del alta del paciente y la incorporación de un inhibidor de la enzima de conversión de angiotensina II, iECA, (enalapril al comienzo de la aparición de la proteinuria.Chronic renal failure (CRF is the most severe complication of hemolytic uremic syndrome (HUS. In 1996, the histological sequence of changes in patients with long lasting oligoanuric periods was clarified. In the last years different therapeutic schemes have been proposed in order to slacken the development of terminal CRF in different renal conditions secondary to diabetes and other diseases. Some of these cases can suffer the onset of renal failure at adolescence. In this review, response to two treatment schemes in different patients with HUS and proteinuria with or without hypertension or renal failure is commented. Early indication of poor sodium diet and strict control of protein intake at the very moment of hospital discharge is strongly recommended, as well as angiotensin II conversion inhibiting enzymes (iACE at the appearance of proteinuria.

  12. Plasma bradykinin and early diabetic nephropathy lesions in type 1 diabetes mellitus.

    Directory of Open Access Journals (Sweden)

    Kevin M Wheelock

    Full Text Available To examine the association of bradykinin and related peptides with the development of diabetic nephropathy lesions in 243 participants with type 1 diabetes (T1D from the Renin-Angiotensin System Study who, at baseline, were normoalbuminuric, normotensive and had normal or increased glomerular filtration rate (GFR.Plasma concentrations of bradykinin and related peptides were measured at baseline by quantitative mass spectrometry. All participants were randomly assigned at baseline to receive placebo, enalapril or losartan during the 5 years between kidney biopsies. Kidney morphometric data were available from kidney biopsies at baseline and after 5 years. Relationships of peptides with changes in morphometric variables were assessed using multiple linear regression after adjustment for age, sex, diabetes duration, HbA1c, mean arterial pressure, treatment assignment and, for longitudinal analyses, baseline structure.Baseline median albumin excretion rate of study participants was 5.0 μg/min, and mean GFR was 128 mL/min/1.73 m2. After multivariable adjustment, higher plasma concentration of bradykinin (1-8 was associated with greater glomerular volume (partial r = 0.191, P = 0.019 and total filtration surface area (partial r = 0.211, P = 0.010, and higher bradykinin (1-7 and hyp3-bradykinin (1-7 were associated with lower cortical interstitial fractional volume (partial r = -0.189, P = 0.011; partial r = -0.164, P = 0.027 respectively. In longitudinal analyses, higher bradykinin was associated with preservation of surface density of the peripheral glomerular basement membrane (partial r = 0.162, P = 0.013, and for participants randomized to losartan, higher hyp3-bradykinin (1-8 was associated with more limited increase in cortical interstitial fractional volume (partial r = -0.291, P = 0.033.Higher plasma bradykinin and related peptide concentrations measured before clinical onset of diabetic nephropathy in persons with T1D were associated with

  13. Study population and treatment titration in the International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT).

    Science.gov (United States)

    Brown, M J; Castaigne, A; de Leeuw, P W; Mancia, G; Rosenthal, T; Ruilope, L M

    1998-12-01

    To ascertain the baseline characteristics of the high-risk hypertensive patients entering the International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT). To determine the success of single and combination therapy in achieving target blood pressures in such a population. INSIGHT is a double-blind, prospective outcome trial comparing the efficacy of the calcium channel blocker, nifedipine GITS, and the thiazide, co-amilozide, in preventing myocardial infarction and stroke. We recruited 2996 men and 3454 women, aged 55-80 years, with blood pressure during placebo run-in >150/95 mmHg or isolated systolic blood pressure >160 mmHg from nine countries. Treatment allocation to nifedipine GITS 30 mg daily or co-amilozide (hydrochlorothiazide 25 mg/amiloride 5 mg) once daily was performed by minimization rather than randomization to balance additional risk factors. This was followed by four optional increases in treatment: dose-doubling of the primary drug, addition of atenolol 25/50 mg or enalapril 5/10 mg, and then any other hypotensive drug excluding calcium blockers or diuretics. Target blood pressure was 140/90 mmHg or a fall > or = 20/10 mmHg. Blood pressure at randomization was 172+/-15 / 99+/-9 mmHg. Thirteen per cent of the patients were previously untreated. The proportions of each additional risk factors were: smoking > 10/day, 29%; cholesterol > 6.43 mmol/l, 52%; family history of premature myocardial infarction or stroke, 21%; diabetes mellitus 20%; left ventricular hypertrophy, 10%; previous myocardial infarction, other presentations of coronary heart disease, and peripheral vascular disease, each 6%; proteinuria, 3%. Fifty-five per cent of patients had one additional risk factor, whereas 33%, 9% and 3% had two, three or more additional risk factors, respectively. The blood pressure (and falls in blood pressure) at the end of titration and at 1 year after minimization was 139+/-12 / 82+/-7 mmHg (33+/-15 / 17+/-9) in the 5226

  14. A Comparative Effectiveness Meta-Analysis of Drugs for the Prophylaxis of Migraine Headache.

    Directory of Open Access Journals (Sweden)

    Jeffrey L Jackson

    Full Text Available To compare the effectiveness and side effects of migraine prophylactic medications.We performed a network meta-analysis. Data were extracted independently in duplicate and quality was assessed using both the JADAD and Cochrane Risk of Bias instruments. Data were pooled and network meta-analysis performed using random effects models.PUBMED, EMBASE, Cochrane Trial Registry, bibliography of retrieved articles through 18 May 2014.We included randomized controlled trials of adults with migraine headaches of at least 4 weeks in duration.Placebo controlled trials included alpha blockers (n = 9, angiotensin converting enzyme inhibitors (n = 3, angiotensin receptor blockers (n = 3, anticonvulsants (n = 32, beta-blockers (n = 39, calcium channel blockers (n = 12, flunarizine (n = 7, serotonin reuptake inhibitors (n = 6, serotonin norepinephrine reuptake inhibitors (n = 1 serotonin agonists (n = 9 and tricyclic antidepressants (n = 11. In addition there were 53 trials comparing different drugs. Drugs with at least 3 trials that were more effective than placebo for episodic migraines included amitriptyline (SMD: -1.2, 95% CI: -1.7 to -0.82, -flunarizine (-1.1 headaches/month (ha/month, 95% CI: -1.6 to -0.67, fluoxetine (SMD: -0.57, 95% CI: -0.97 to -0.17, metoprolol (-0.94 ha/month, 95% CI: -1.4 to -0.46, pizotifen (-0.43 ha/month, 95% CI: -0.6 to -0.21, propranolol (-1.3 ha/month, 95% CI: -2.0 to -0.62, topiramate (-1.1 ha/month, 95% CI: -1.9 to -0.73 and valproate (-1.5 ha/month, 95% CI: -2.1 to -0.8. Several effective drugs with less than 3 trials included: 3 ace inhibitors (enalapril, lisinopril, captopril, two angiotensin receptor blockers (candesartan, telmisartan, two anticonvulsants (lamotrigine, levetiracetam, and several beta-blockers (atenolol, bisoprolol, timolol. Network meta-analysis found amitriptyline to be better than several other medications including candesartan, fluoxetine, propranolol, topiramate and valproate and no different than

  15. Angiotensin I-Converting-Enzyme-Inhibitory and Antibacterial Peptides from Lactobacillus helveticus PR4 Proteinase-Hydrolyzed Caseins of Milk from Six Species

    Science.gov (United States)

    Minervini, F.; Algaron, F.; Rizzello, C. G.; Fox, P. F.; Monnet, V.; Gobbetti, M.

    2003-01-01

    Sodium caseinates prepared from bovine, sheep, goat, pig, buffalo or human milk were hydrolyzed by a partially purified proteinase of Lactobacillus helveticus PR4. Peptides in each hydrolysate were fractionated by reversed-phase fast-protein liquid chromatography. The fractions which showed the highest angiotensin I-converting-enzyme (ACE)-inhibitory or antibacterial activity were sequenced by mass spectrum and Edman degradation analyses. Various ACE-inhibitory peptides were found in the hydrolysates: the bovine αS1-casein (αS1-CN) 24-47 fragment (f24-47), f169-193, and β-CN f58-76; ovine αS1-CN f1-6 and αS2-CN f182-185 and f186-188; caprine β-CN f58-65 and αS2-CN f182-187; buffalo β-CN f58-66; and a mixture of three tripeptides originating from human β-CN. A mixture of peptides with a C-terminal sequence, Pro-Gly-Pro, was found in the most active fraction of the pig sodium caseinate hydrolysate. The highest ACE-inhibitory activity of some peptides corresponded to the concentration of the ACE inhibitor (S)-N-(1-[ethoxycarbonyl]-3-phenylpropyl)-ala-pro maleate (enalapril) of 49.253 μg/ml (100 μmol/liter). Several of the above sequences had features in common with other ACE-inhibitory peptides reported in the literature. The 50% inhibitory concentration (IC50) of some of the crude peptide fractions was very low (16 to 100 μg/ml). Some identified peptides were chemically synthesized, and the ACE-inhibitory activity and IC50s were confirmed. An antibacterial peptide corresponding to β-CN f184-210 was identified in human sodium caseinate hydrolysate. It showed a very large spectrum of inhibition against gram-positive and -negative bacteria, including species of potential clinical interest, such as Enterococcus faecium, Bacillus megaterium, Escherichia coli, Listeria innocua, Salmonella spp., Yersinia enterocolitica, and Staphylococcus aureus. The MIC for E. coli F19 was ca. 50 μg/ml. Once generated, the bioactive peptides were resistant to further

  16. CARDIORENAL RELATIONS AND QUALITY OF LIFE IN ELDERLY PATIENTS WITH CHRONIC HEART FAILURE IN LONG TERM THERAPY WITH CARVEDILOL AND BISOPROLOL

    Directory of Open Access Journals (Sweden)

    M. A. Statsenko

    2005-01-01

    Full Text Available Aim. To compare effects of long term therapy with сarvedilol and bisoprolol on heart and renal functions, heart rate variability (HRV and quality of life in elderly patients with chronic heart failure (CHF.Material and methods. We examined 40 patients aged 60-75 years on the 15-30 day after myocardial infarction complicated with CHF. All the patients taking basic therapy with enalapril, aspirin, simvastatin and diuretics were randomized to either bisoprolol (n=20 or сarvedilol (n=20 therapy group. The average daily doses were 5,7+0,8 mg for and 32,6+3,4 mg for carvedilol. The duration of the observation period was 12 months. Cardiac morphofunctional parameters, HRV, renal function and quality of life were determined at baseline, after 12 weeks and at the end of the study.Results. Complex therapy of CHF including both beta-blockers resulted in clinical improvement, increase in myocardial contractility. However, carvedilol group showed more pronounced increase in ejection fraction in comparison with bisoprolol group, 8,97% and 5,14%, respectively. Local contractility index decreased significantly only in carvedilol group by 29,9% (p<0,05. Carvedilol demonstrated more significant nephroprotective effects: glomerular filtration rate increased by 32,2%, renal functional reserve restored in 70% of patients. Tubular reabsorbtion, sodium clearance and excretion also increased in carvedilol group. After 12 month of treatment microalbuminuria reduced in both groups of patients, but more significant in carvedilol group. Carvedilol provided more strong blocking effect on sympathetic part of autonomic nervous system according to HRV data.Conclusion. In elderly patients with CHF long term therapy with both carvedilol and bisoprolol provided with improvement in clinical conditions and renal function, increased in HRV and was well tolerated. However, carvedilol compared with bisoprolol showed more significant beneficial effects on cardiac morphofunctional

  17. Development and validation of methodology SPE-LC-MS/MS for pharmaceuticals and illicit drug determination in the waters of Guarapiranga Dam, Sao Paulo, SP, Brazil; Desenvolvimento e validacao de metodologia SPE-LC-MS/MS para a determinacao de farmacos e droga de abuso nas aguas da represa Guarapiranga, Sao Paulo, SP, Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Shihomatsu, Helena Miho

    2015-07-01

    This study presents the development of the methodology of solid phase extraction and liquid chromatography - tandem mass spectrometry, SPE-LC-MS/MS, for the determination of 21 (twenty one) pharmaceuticals belonging to different therapeutic groups, 1 (one) illicit drug and its major metabolite, in surface water samples. The chromatographic separation was optimized by studying the performance of different stationary and mobile phases. Quantitation of selected compounds was performed by electrospray ionization (ESI) and the mass spectrometer operating in a multiple reaction monitoring (MRM) mode. The validation of the proposed methodology was performed using the parameters of selectivity, matrix effect, dynamic range, linearity, limit of detection (LOD), limit of quantification (LOQ), precision, accuracy, recovery and robustness. The validation of methodology allowed to apply the methodology in the evaluation of the distribution of the 23 (twenty one) selected compounds, in Guarapiranga Dam waters, an of the major producer system of drinking water of the Metropolitan Region of Sao Paulo (MRSP). The presence of these pollutants in aquatic environments is from the direct release of urban sewage from the homes of your surroundings, as a result of poor sanitation system. The waters of Guarapiranga dam were evaluated in 14 (fourteen) locations strategically chosen and sampled in 3 (three) campaigns of sample collection (August 2011, September 2012 and April 2013). In these samples were quantified acetaminophen (9.6 - 254 ng L{sup -1}), atenolol (8.5 - 177 ng L{sup -1}), benzoylecgonine (7.9 - 139 ng L{sup -1}), caffeine (27 - 27386 ng L{sup -1}) carbamazepine (12 - 358 ng L{sup -1}), chlorthalidone (9.4 - 35 ng L{sup -1}), cocaine (12.8 - 2560 ng L{sup -1}), diclofenac (8 - 36 ng L{sup -1}), enalapril (20 ng L{sup -1}), losartan (6.7 - 114 ng L{sup -1}) and valsartan (9.7 - 47 ng L{sup -1}). The sample siting GU103-12 (23°41'88.5”S 46°44'67.3”W) was the

  18. Editorial

    Directory of Open Access Journals (Sweden)

    Rodolfo Souza Cardoso

    2012-06-01

    Full Text Available A Revista Ciências em Saúde da FMIt procura se diferenciar da maioria das publicações cientificas especializadas, pela abordagem de vários assuntos, relacionados a área da saúde, dentro de um contexto multidisciplinar. Nossa revista têm publicado artigos bem redigidos, de boa qualidade e que têm despertado o interesse de vários profissionais da área da saúde. Para o presente número, apresentamos cinco (05 artigos originais, um (01 artigo de revisão, um (01 relato de caso e duas abordagens em seção especial. Na seção especial chamamos a atenção para o tema “O Sagrado e a Ritualidade Diante da Morte”, de João Batista Alves de Oliveira. Em outro, o Professor Alcino Lázaro da Silva nos traz uma reflexão sobre a “Saúde no Brasil”. Os artigos científicos abordam temas variados, como o perfil nutricional de crianças internadas em um hospital, o grau de inserção e satisfação de egressos de um curso de Medicina no mercado de trabalho, fatores de risco para mortalidade por doenças cardiovasculares em uma cidade do Sul de Minas Gerais e também a doação de órgãos. Em um trabalho experimental, os autores avaliam os efeitos da suplementação de L-Arginina, associada ao maleato de enalapril na pressão arterial média de ratos hipertensos. No relato de caso é mostrado um tumor raro do intestino delgado, de diagnóstico difícil. A revisão sobre síndrome metabólica e infertilidade masculina, mostra a importância da correlação entre esses dois temas, de grande interesse na prevenção e na manutenção de saúde. Os editores da Revista Ciências em Saúde agradecem a todos que contribuíram para que essa edição se transformasse em realidade.

  19. A Comparative Effectiveness Meta-Analysis of Drugs for the Prophylaxis of Migraine Headache

    Science.gov (United States)

    2015-01-01

    Objective To compare the effectiveness and side effects of migraine prophylactic medications. Design We performed a network meta-analysis. Data were extracted independently in duplicate and quality was assessed using both the JADAD and Cochrane Risk of Bias instruments. Data were pooled and network meta-analysis performed using random effects models. Data Sources PUBMED, EMBASE, Cochrane Trial Registry, bibliography of retrieved articles through 18 May 2014. Eligibility Criteria for Selecting Studies We included randomized controlled trials of adults with migraine headaches of at least 4 weeks in duration. Results Placebo controlled trials included alpha blockers (n = 9), angiotensin converting enzyme inhibitors (n = 3), angiotensin receptor blockers (n = 3), anticonvulsants (n = 32), beta-blockers (n = 39), calcium channel blockers (n = 12), flunarizine (n = 7), serotonin reuptake inhibitors (n = 6), serotonin norepinephrine reuptake inhibitors (n = 1) serotonin agonists (n = 9) and tricyclic antidepressants (n = 11). In addition there were 53 trials comparing different drugs. Drugs with at least 3 trials that were more effective than placebo for episodic migraines included amitriptyline (SMD: -1.2, 95% CI: -1.7 to -0.82), -flunarizine (-1.1 headaches/month (ha/month), 95% CI: -1.6 to -0.67), fluoxetine (SMD: -0.57, 95% CI: -0.97 to -0.17), metoprolol (-0.94 ha/month, 95% CI: -1.4 to -0.46), pizotifen (-0.43 ha/month, 95% CI: -0.6 to -0.21), propranolol (-1.3 ha/month, 95% CI: -2.0 to -0.62), topiramate (-1.1 ha/month, 95% CI: -1.9 to -0.73) and valproate (-1.5 ha/month, 95% CI: -2.1 to -0.8). Several effective drugs with less than 3 trials included: 3 ace inhibitors (enalapril, lisinopril, captopril), two angiotensin receptor blockers (candesartan, telmisartan), two anticonvulsants (lamotrigine, levetiracetam), and several beta-blockers (atenolol, bisoprolol, timolol). Network meta-analysis found amitriptyline to be better than several other medications including

  20. Estudio de las fracciones lipídicas de colesterol y triglicéridos en pacientes de dos consultorios médicos de la familia

    Directory of Open Access Journals (Sweden)

    José Luis Cusidó Carralero

    2014-11-01

    Full Text Available La segunda causa de muerte en la provincia de Las Tunas son las enfermedades del corazón, estas se asocian a múltiples factores de riesgo, como, por ejemplo, los niveles elevados de colesterol y triglicéridos. La alta frecuencia de valores patológicos de colesterol y triglicéridos en pacientes de los Consultorios Médicos de la Familia (CMF 19-01 y 20-01 en el Policlínico Docente “Manuel Fajardo Rivero” motivó a la realización de este trabajo, que tiene como objetivo evaluar el comportamiento de las fracciones lipídicas de colesterol y triglicéridos en pacientes de estos CMF, durante el período comprendido entre enero y junio de 2014. Las variables analizadas fueron: rango de valores de colesterol y triglicéridos, edad, sexo, antecedentes patológicos personales, diagnóstico clínico y tratamiento médico. Se incluyeron los pacientes mayores de 20 años de ambos consultorios, los diabéticos, hipertensos, cardiópatas; se excluyeron de la investigación las gestantes, enfermos hospitalizados o con ingreso domiciliario. Se obtuvo como resultado que casi la mitad de los pacientes presentó valores elevados en las fracciones lipídicas de colesterol y triglicéridos, las edades más afectadas fueron los adultos de 41 a 60 años, con predominio del sexo masculino. En la revisión de historias clínicas se tabularon como principales antecedentes patológicos personales que más de la mitad de los pacientes con alteraciones lipídicas son fumadores y un cuarto de ellos consumen alcohol. En el diagnóstico clínico y tratamiento médico registrado en la historia clínica de los pacientes afectados se constató que dos tercios de ellos son hipertensos y utilizan el captopril, enalapril y atenolol y casi un tercio son diabéticos, que se medican con los hipoglucemiantes, insulina y glibenclamida

  1. Development and validation of methodology SPE-LC-MS/MS for pharmaceuticals and illicit drug determination in the waters of Guarapiranga Dam, Sao Paulo, SP, Brazil

    International Nuclear Information System (INIS)

    Shihomatsu, Helena Miho

    2015-01-01

    This study presents the development of the methodology of solid phase extraction and liquid chromatography - tandem mass spectrometry, SPE-LC-MS/MS, for the determination of 21 (twenty one) pharmaceuticals belonging to different therapeutic groups, 1 (one) illicit drug and its major metabolite, in surface water samples. The chromatographic separation was optimized by studying the performance of different stationary and mobile phases. Quantitation of selected compounds was performed by electrospray ionization (ESI) and the mass spectrometer operating in a multiple reaction monitoring (MRM) mode. The validation of the proposed methodology was performed using the parameters of selectivity, matrix effect, dynamic range, linearity, limit of detection (LOD), limit of quantification (LOQ), precision, accuracy, recovery and robustness. The validation of methodology allowed to apply the methodology in the evaluation of the distribution of the 23 (twenty one) selected compounds, in Guarapiranga Dam waters, an of the major producer system of drinking water of the Metropolitan Region of Sao Paulo (MRSP). The presence of these pollutants in aquatic environments is from the direct release of urban sewage from the homes of your surroundings, as a result of poor sanitation system. The waters of Guarapiranga dam were evaluated in 14 (fourteen) locations strategically chosen and sampled in 3 (three) campaigns of sample collection (August 2011, September 2012 and April 2013). In these samples were quantified acetaminophen (9.6 - 254 ng L -1 ), atenolol (8.5 - 177 ng L -1 ), benzoylecgonine (7.9 - 139 ng L -1 ), caffeine (27 - 27386 ng L -1 ) carbamazepine (12 - 358 ng L -1 ), chlorthalidone (9.4 - 35 ng L -1 ), cocaine (12.8 - 2560 ng L -1 ), diclofenac (8 - 36 ng L -1 ), enalapril (20 ng L -1 ), losartan (6.7 - 114 ng L -1 ) and valsartan (9.7 - 47 ng L -1 ). The sample siting GU103-12 (23°41'88.5”S 46°44'67.3”W) was the region with the highest values in the level of

  2. The prevention, detection and management of cancer treatment-induced cardiotoxicity: a meta-review

    International Nuclear Information System (INIS)

    Conway, Aaron; McCarthy, Alexandra L; Lawrence, Petra; Clark, Robyn A

    2015-01-01

    The benefits associated with some cancer treatments do not come without risk. A serious side effect of some common cancer treatments is cardiotoxicity. Increased recognition of the public health implications of cancer treatment-induced cardiotoxicity has resulted in a proliferation of systematic reviews in this field to guide practice. Quality appraisal of these reviews is likely to limit the influence of biased conclusions from systematic reviews that have used poor methodology related to clinical decision-making. The aim of this meta-review is to appraise and synthesise evidence from only high quality systematic reviews focused on the prevention, detection or management of cancer treatment-induced cardiotoxicity. Using Cochrane methodology, we searched databases, citations and hand-searched bibliographies. Two reviewers independently appraised reviews and extracted findings. A total of 18 high quality systematic reviews were subsequently analysed, 67 % (n = 12) of these comprised meta-analyses. One systematic review concluded that there is insufficient evidence regarding the utility of cardiac biomarkers for the detection of cardiotoxicity. The following strategies might reduce the risk of cardiotoxicity: 1) The concomitant administration of dexrazoxane with anthracylines; 2) The avoidance of anthracyclines where possible; 3) The continuous administration of anthracyclines (>6 h) rather than bolus dosing; and 4) The administration of anthracycline derivatives such as epirubicin or liposomal-encapsulated doxorubicin instead of doxorubicin. In terms of management, one review focused on medical interventions for treating anthracycline-induced cardiotoxicity during or after treatment of childhood cancer. Neither intervention (enalapril and phosphocreatine) was associated with statistically significant improvement in ejection fraction or mortality. This review highlights the lack of high level evidence to guide clinical decision-making with respect to the detection

  3. Effect of Combination Treatment for Hypothyroidism on Renal Function in Patients with Hypothyroidism

    Directory of Open Access Journals (Sweden)

    O.M. Didushko

    2016-02-01

    = –0.337. Conclusions. In patients with uncompensated hypothyroidism, we have detected renal dysfunction, which was characterized by a decrease in GFR, albuminuria appearance. During combined treatment with the inclusion of angiotensin-converting enzyme inhibitor (enalapril and atorvastatin, we have noted pathogenetically grounded effect on markers of functional kidney injury.

  4. Cost–Utility of Angiotensin-Converting Enzyme Inhibitor-Based Treatment Compared With Thiazide Diuretic-Based Treatment for Hypertension in Elderly Australians Considering Diabetes as Comorbidity

    Science.gov (United States)

    Chowdhury, Enayet K.; Ademi, Zanfina; Moss, John R.; Wing, Lindon M.H.; Reid, Christopher M.

    2015-01-01

    Abstract The objective of this study was to examine the cost-effectiveness of angiotensin-converting enzyme inhibitor (ACEI)-based treatment compared with thiazide diuretic-based treatment for hypertension in elderly Australians considering diabetes as an outcome along with cardiovascular outcomes from the Australian government's perspective. We used a cost–utility analysis to estimate the incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained. Data on cardiovascular events and new onset of diabetes were used from the Second Australian National Blood Pressure Study, a randomized clinical trial comparing diuretic-based (hydrochlorothiazide) versus ACEI-based (enalapril) treatment in 6083 elderly (age ≥65 years) hypertensive patients over a median 4.1-year period. For this economic analysis, the total study population was stratified into 2 groups. Group A was restricted to participants diabetes free at baseline (n = 5642); group B was restricted to participants with preexisting diabetes mellitus (type 1 or type 2) at baseline (n = 441). Data on utility scores for different events were used from available published literatures; whereas, treatment and adverse event management costs were calculated from direct health care costs available from Australian government reimbursement data. Costs and QALYs were discounted at 5% per annum. One-way and probabilistic sensitivity analyses were performed to assess the uncertainty around utilities and cost data. After a treatment period of 5 years, for group A, the ICER was Australian dollars (AUD) 27,698 (€ 18,004; AUD 1–€ 0.65) per QALY gained comparing ACEI-based treatment with diuretic-based treatment (sensitive to the utility value for new-onset diabetes). In group B, ACEI-based treatment was a dominant strategy (both more effective and cost-saving). On probabilistic sensitivity analysis, the ICERs per QALY gained were always below AUD 50,000 for group B; whereas for group A

  5. Nemaline myopathy and heart failure: role of ivabradine; a case report.

    Science.gov (United States)

    Sarullo, Filippo M; Vitale, Giuseppe; Di Franco, Antonino; Sarullo, Silvia; Salerno, Ylenia; Vassallo, Laura; Baviera, Emanuela Petrona; Marazia, Stefania; Mandalà, Giorgio; Lanza, Gaetano A

    2015-01-19

    Nemaline myopathy (NM) is a rare congenital myopathy characterized by muscle weakness, hypotonia and the presence in muscle fibers of inclusions known as nemaline bodies and a wide spectrum of clinical phenotypes, ranging from severe forms with neonatal onset to asymptomatic forms. The adult-onset form is heterogeneous in terms of clinical presentation and disease progression. Cardiac involvement occurs in the minority of cases and little is known about medical management in this subgroup of NM patients. We report a rare case of heart failure (HF) in a patient with adult-onset NM in whom ivabradine proved to be able to dramatically improve the clinical picture. We report a case of a 37-year-old man with adult-onset NM, presenting with weakness and hypotonia of the proximal limb muscles and shoulder girdle, severely limiting daily activities. He developed progressive HF over a period of 6 months while attending a rehabilitation program, with reduced left ventricular ejection fraction (LVEF = 20%), manifested by dyspnea and signs of systemic congestion. The patient was started HF therapy with enalapril, carvedilol, spironolactone and loop diuretics. Target HF doses of these drugs (including carvedilol) were not reached because of symptomatic hypotension causing a high resting heart rate (HR) ≥70 beats per minute (bpm). Further deterioration of the clinical picture occurred with several life-threatening arrhythmic episodes requiring external defibrillation. An implantable cardioverter defibrillator (ICD) was then implanted. Persistent high resting HR was successfully treated with ivabradine with HR lowering from 90 bpm to 55 bpm at 1 month follow up, LVEF rising to 50% at 3 month follow up and to 54% at 2,5 year follow up. To date no more hospitalizations for heart failure occurred. A single hospitalization due to aspiration pneumonia required insertion of a tracheostomy tube to protect airways from further aspiration. At present, the patient is attending

  6. Access to and use of high blood pressure medications in Brazil.

    Science.gov (United States)

    Mengue, Sotero Serrate; Bertoldi, Andréa Dâmaso; Ramos, Luiz Roberto; Farias, Mareni Rocha; Oliveira, Maria Auxiliadora; Tavares, Noemia Urruth Leão; Arrais, Paulo Sergio Dourado; Luiza, Vera Lucia; Pizzol, Tatiane da Silva Dal

    2016-12-01

    To analyze the access to and use of medicines for high blood pressure among the Brazilian population according to social and demographic conditions. Analysis of data from Pesquisa Nacional Sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos (PNAUM - National Survey on Access, Use and Promotion of Rational Use of Medicines), a nationwide cross-sectional, population-based study, with probability sampling, carried out between September 2013 and February 2014 in urban households in the five Brazilian regions. The study evaluated the access and use of medicines to treat people with high blood pressure. The independent variables were gender, age, socioeconomic status and Brazilian region. The study also described the most commonly used drugs and the percentage of people treated with one, two, three or more drugs. Point estimations and confidence intervals were calculated considering the sample weights and sample complex plan. Prevalence of high blood pressure was 23.7% (95%CI 22.8-24.6). Regarding people with this condition, 93.8% (95%CI 92.8-94.8) had indication for drug therapy and, of those, 94.6% (95%CI 93.5-95.5) were using the medication at the time of interview. Full access to medicines was 97.9% (95%CI 97.3-98.4); partial access, 1.9% (95%CI 1.4-2.4); and no access, 0.2% (95%CI 0.1-0.4). The medication used to treat high blood pressure, 56.0% (95%CI 52.6-59.2) were obtained from SUS (Brazilian Unified Health System), 16.0% (95%CI 14.3-17.9) from Popular Pharmacy Program, 25.7% (95%CI 23.4-28.2) were paid for by the patients themselves and 2.3% (95%CI 1.8-2.9) were obtained from other locations. The five most commonly used drugs were, in descending order, hydrochlorothiazide, losartan, captopril, enalapril and atenolol. Of the total number of patients on treatment, 36.1% (95%CI 34.1-37.1) were using two medicines and 13.5% (95%CI 12.3-14.9) used three or more. Access to medicines for the treatment of high blood pressure may be considered high

  7. Perfil do tratamento da insuficiência cardíaca na era dos betabloqueadores Heart failure treatment profile at the beta blockers era

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    Christiano Pereira Silva

    2007-04-01

    Full Text Available OBJETIVOS: A inibição dos sistemas renina-angiotensina-aldosterona (SRAA e sistema nervoso autônomo simpático aumentou a perspectiva de sobrevida desses pacientes, além de permitir substancial melhora na qualidade de vida. O objetivo deste trabalho foi avaliar a realidade do tratamento aplicado e seu impacto sobre a doença em pacientes acompanhados em um ambulatório especializado em insuficiência cardíaca(IC. MÉTODOS: Foram estudados 96 pacientes acompanhados no ambulatório de Insuficiência Cardíaca e Transplante do Instituto do Coração, do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP. Os dados foram coletados durante a consulta ambulatorial a partir de prontuário médico e exame clínico. A escolha dos pacientes foi aleatória. RESULTADOS: A maior parte dos pacientes encontrava-se em classe funcional II (42,3% e em estágio C de evolução (94,9%. A prescrição médica para os pacientes foi bastante próxima do preconizado pelas diretrizes. Aproximadamente 95% recebem inibidores do SRAA (inibidor de ECA - enalapril e captopril - ou antagonista dos receptores de angiotensina-losartan, enquanto 85% dos pacientes recebem, além desses, agentes betabloqueadores (carvedilol. A dose média prescrita também se aproxima das utilizadas nos grandes estudos, e atinge mais de 60% da dose máxima de cada medicação. Os dados hemodinâmicos encontrados mostram pacientes estáveis, apesar da intensidade da disfunção e do remodelamento ventricular destes. CONCLUSÃO: Pacientes portadores de IC acompanhados por equipe médica especializada têm prescrição médica mais próxima do preconizado. Esses pacientes, embora com características marcadas de gravidade da doença, conseguem estabilidade hemodinâmica e clínica com a otimização terapêutica adequada.OBJECTIVES: The inhibition of the rennin-angiotensin-aldosterone system (RAAS and sympathetic autonomous nervous system has increased the

  8. A propósito de un caso: ¿Sirven los genéricos para moderar el gasto en hipertensión? Apropos of a case: do generic drugs help control expenditure on hypertension?

    Directory of Open Access Journals (Sweden)

    Antonio J. García

    2004-04-01

    Full Text Available Objetivo: Se analiza desde la perspectiva del pagador (Sistema Nacional de Salud [SNS] la influencia que tienen los genéricos en el gasto en medicamentos en la hipertensión arterial, examinándose el subgrupo terapéutico de mayor consumo y utilización, los inhibidores de la enzima de conversión de la angiotensina (IECA y antagonistas de los receptores de la angiotensina II (ARA II. Métodos: Partiendo de los datos de facturación al SNS de todas las oficinas de farmacia del Área de Salud de Málaga, se explora el consumo (envases y gasto de los fármacos IECA, IECA + especialidades farmacéuticas genéricas (EFG y ARA II, desde 1999 hasta 2002, así como el precio medio (ponderando según ventas y el porcentaje de desviación de prescripción de un grupo a otro. Resultados: El incremento en envases del subgrupo C09 fue del 20,79%, muy superior para los ARA II (136% y los IECA + EFG (177%. El gasto total creció en más del 42%. Se redujo el gusto en IECA en casi el 7%, a pesar del incremento en gasto de los IECA + EFG, mientras que los ARA II lo aumentaron en más del 154%. El precio medio ponderado según las ventas de este subgrupo terapéutico se incrementó en cerca del 18%. Se produjo un descenso en el precio medio ponderado de los principios activos donde había EFG (captopril y enalapril además de otros (trandolapril, pero entre los ARA II destaca el aumento en el precio medio ponderado según las ventas de irbesartán (9% y valsartán (16%. Conclusiones: Los genéricos usados han originado una disminución en el gasto de IECA y del precio medio ponderado del subgrupo. Pero a pesar del incesante aumento en el consumo de las especialidades farmacéuticas genéricas, no se ha producido el efecto ahorrador pretendido con este tipo de medicamentos por el Ministerio de Sanidad y Consumo. Se apunta como posible causa la desviación de las prescripciones hacia los medicamentos no afectados de sustitución por parte de la oficina de

  9. Adherence to EBM guidelines in clinical practice.

    Science.gov (United States)

    Khafizianova, R Kh; Burykin, I M

    2015-01-01

    of patients is smoking cessation and normalization of body weight. Nicotine replacement therapy and prescriptions of drugs for weight loss is one of the strategies to achieve goals. According to our study, drugs for smoking cessation and overweight were not prescribed at all. In terms of evidence-based medicine, the use of beta-blockers and ACE inhibitors for a long time by all patients is an important element of secondary prevention.The frequency of prescribing of beta-blockers was 86.1% and 91.1 %% in 2006 and 2009 respectively. The frequency of prescribing of subgroup C09 "Agents acting on the renin-angiotensin system (RAAS)" was 67.7% and 44.4% in 2006 and 2009 respectively. Beta-blockers had the highest frequency of use, while the subgroup RAAS drugs were second to them.We found that the following recommendations of clinical guidelines, based on the principles of evidence-based medicine, were not followed. We found low rates of ACE inhibitors prescribing. The structure of prescribed ACE inhibitors varied in 2006 and 2009. In 2006, 58.4% of all prescriptions were for enalapril. In 2009 enalapril use decreased to 30%, while prescribing of lisinopril increased from 0 in 2006 to 13.3%. Among angiotensin II antagonists (C09C) only losartan was used in 3.1% and 1.1% of cases in 2006 and 2009, respectively. Fixed drug combinations were not used at all.The proportion of patients who had hypertension was 73.9% and 61.9 %% in 2006 and 2009, respectively. The rate of Antihypertensive use (C02), namely Guanfacine and Moxonidine was less than 2% in both 2006 and 2009.In accordance with evidence-based principles the strategy for prevention of recurrent myocardial infarction with prescription of lipid-lowering drugs was used. Lipid-lowering drugs were prescribed to 13.8% of patients in 2006 and to 82.2% of patients in 2009. Doctors used atorvastatin and simvastatin only from the list of drugs of this group. We found that in clinical practice physicians used drugs, not

  10. Azelnidipine plus olmesartan versus amlodipine plus olmesartan on arterial stiffness and cardiac function in hypertensive patients: a randomized trial

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    Takami T

    2013-04-01

    Full Text Available CorrigendumTakami T, Saito Y. Drug Design, Development and Therapy. 2013;7:175–183. On page 177, line 26, heading "Measurement of LVMI and LF diastolic function" should have been "Measurement of LVMI and LV diastolic function". Line 32, "Devereux et al18" should read "Devereux et al19". Line 40, "(E/e’ ratio were measured as previously described.19" should read "(E/e’ ratio were measured as previously described.20". On page 181, line 15, "baPWV with LVMI.20" should read "baPWV with LVMI.21". Line 23, "baPWV and LVMI, E/A ratio.20" should read "baPWV and LVMI, E/A ratio.21,22". Line 28 "diastolic dysfunction.21" should read "diastolic dysfunction.23". Line 38 "is high.22" should read "is high.24". Line 39, "in clinical treatment.23" should read "in clinical treatment.25". Line 57, "A recent cohort study24" should read "A recent cohort study21".On page 182, line 1, "diastolic heart failure.25" should read "diastolic heart failure.26". Line 3, "untreated hypertensive patients.26" should read "untreated hypertensive patients.27". Line 6, "linear regression analysis.27" should read "linear regression analysis.21".On page 183, the references 18 to 27 should be updated as shown below:18. Takami T. Evaluation of arterial stiffness in morning hypertension under high-dose valsartan compared to valsartan plus low-dose diuretic. Hypertens Res. 2009;32:1086–1090.19. Devereux RB, Palmieri V, Sharpe N, et al. Effects of once-daily angiotensin-converting enzyme inhibition and calcium channel blockade-based antihypertensive treatment regimens on left ventricular hypertrophy and diastolic filling in hypertension: the prospective randomized enalapril study evaluating regression of ventricular enlargement (PRESERVE trial. Circulation. 2001;104:1248–1254.20. Ito H, Ishii K, Kihara H, et al. Adding thiazide to a renin-angiotensin blocker improves left ventricular relaxation and improves heart failure in patients with hypertension. Hypertens Res. 2012;35:93

  11. [The best of valvular heart disease in 2006].

    Science.gov (United States)

    de Gevigney, G

    2007-01-01

    In the field of valvular diseases, the year 2006 has been above all marked by the publication of new joint AHA/ACC guidelines. Besides, other publications included severe aortic stenosis, drug therapy in chronic aortic regurgitation, the indications for surgery in asymptomatic mitral regurgitation, as well as valve surgery in the elderly and mismatch severity after aortic valve replacement. In a series of 66 cases of aortic stenosis with poor LV function undergoing stress echocardiography, it has been shown that whether the absence of contractile reserve identifies a high-risk subgroup for aortic valve replacement (33% vs. 6%), this exam does not predict the functional prognosis and the post-operative LV function improvement. Hence, the absence of contractile reserve should not contra-indicate aortic valve replacement surgery, even though the prognosis is severe, since the natural prognosis is extremely severe. The question of aortic valve replacement in case of mild stenosis with the indication of CABG remains difficult. Taking into account the important mortality of redo surgery, a study was in favor of a systematic aortic valve replacement associated to CABG in patients 30 mmHg, a LVH and aortic valve calcifications. Old patients (>80 years) with severe aortic stenosis have a very severe natural prognosis, authorizing wide indications for aortic valve replacement, in the absence of important comorbidities. The use of vasodilators in severe chronic aortic regurgitation remains debated. In a randomized study comparing Nifedipine 40 mg vs. Enalapril 20 mm vs. placebo, it has been shown that the use of a vasodilator does not modify the time of valvular surgery at all. After a mean follow-up of 7 years, the rates of aortic valve replacement were identical in the 3 groups, and there wa no difference regarding the preoperative regurgitation volume, LV dimensions and mass, and LVEF. The timing for huge chronic and asymptomatic mitral regurgitation remains debated, even

  12. Metabolismo de fármacos y lesión hepática

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    Elso Manuel Cruz Cruz

    2015-03-01

    el menor porcentaje. Los fármacos que ocasionan lesión hepática de forma intrínseca pueden actuar directamente sobre el hepatocito, o a través de algún compuesto tóxico generado durante su metabolismo; ejemplos de ello son el paracetamol, ácido acetilsalicílico y muchos de sus derivados. Por otra parte, la hepatotoxicidad idiosincrática es aquella que ocurre de forma impredecible y no depende de la dosis del fármaco, ésta tiene mayor incidencia. Ejemplos de medicamentos que provocan esta hepatotoxicidad son: ácido valproico, alopurinol, amiodarona, bupropión, captopril, carbamazepina, ciclofosfamida, ciproheptadina, clindamicina, clotrimazol, diclofenaco, enalapril, estatinas, fenitoína, fenobarbital, fluoxetina, flutamida, glibenclamida, ibuprofeno, isoniazida, ketoconazol, lisinopril, losartán, metotrexate, nefazodona, nevirapina, nitrofurantoína, paroxetina, pirazinamida, quinolonas, rifampicina, risperidona, ritonavir, sertralina, sulfonamidas, tetraciclina, trazodona, troglitazona, verapamil, entre muchos otros. (1, 3 Se proponen diferentes mecanismos causantes de lesión hepatocelular: la alteración de la homeostasis del calcio intracelular, que conduce al desarreglo de las fibrillas de actina existentes en la superficie del hepatocito, modificando la membrana celular, con posterior rotura y lisis; interrupción de los filamentos cerca de los canalículos, con la rotura de éstos y reducción en la excreción biliar, fenómeno que también puede estar asociado a la interrupción del transporte de bilis por las bombas proteicas; reacciones que involucran al sistema del citocromo P-450, al generar reacciones de alta energía que producen enlaces covalentes fármaco-enzima, creando complejos proteicos no funcionales que migran hacia la superficie de la célula y son inmunogénicos, convirtiéndose en blanco de las células T citolíticas y de las citosinas; algunos fármacos inhiben la función mitocondrial por efecto en la beta-oxidación de los