Interação medicamentosa de venlafaxina com captopril Drug interaction of velanfaxine with captopril

Directory of Open Access Journals (Sweden)

Douglas D Sucar

2000-09-01

Full Text Available O autor descreve um caso de interação medicamentosa, em uma senhora de 53 anos de idade, com diagnóstico de depressão e de hipertensão arterial. Com níveis pressóricos estáveis, em conseqüência de um regime dietético e de uso do captopril -anti-hipertensivo inibidor da enzima de conversão da angiotensina -, passou a apresentar constantes descompensações do seu quadro clínico, com elevações da tensão arterial (TA, logo após a introdução da venlafaxina no seu esquema terapêutico. Esse medicamento é um potente antidepressivo de última geração, que atua no sistema nervoso central (SNC, inibindo a recaptação de serotonina e noradrenalina. Demonstra a interação pelo monitoramento da TA e aplicação do instrumento de Naranjo. Descreve as condições clínicas gerais da paciente e sua evolução, e discute os mecanismos prováveis que conduziram a interação pela hipótese que envolve o aumento de noradrenalina nos terminais sinápticos, o sistema renina-angiotensina e a bradicinina, concluindo que a venlafaxina agiu como antagonista, de modo indireto, sobre os efeitos hipotensores do captopril.This is a case report of drug interaction in a 53 year-old woman diagnosed with depression and arterial hypertension. As a result of a low-salt diet and the use of the captopril (an antihypertensive that inhibites the angiotensine conversion enzyme, her pressoric levels had been stable till venlafaxine was introduced in her therapeutic regime. By then she started to show an unstableclinical condition, with elevations of her arterial blood pressure (ABP. Venlafaxine is a potent last generation antidepressant drug, acting in the central nervous system (CNS by inhibiting the reuptake of serotonine and noradrenaline. The drug interaction is demonstrated by monitoring the ABP and using the Naranjo's tool.The patient's general clinical conditions and herprogress are presented, and the hypothetical mechanisms to the interaction, such as

Captopril as a replacement for multiple therapy in hypertension: a controlled study.

Science.gov (United States)

Yodfat, Y; Fidel, J; Bloom, D S

1985-11-01

A controlled study was conducted in hypertensive patients to investigate whether captopril can be substituted for the various other antihypertensive drugs (not including diuretics) to reduce side effects and improve the quality of life. Captopril in a twice daily dose of 25-50 mg, was substituted and titrated in 54 patients. Fifty-two patients, matched by age and sex, comprised the control group, and were treated with a variety of agents. During a follow-up of 9 months, 44 of the patients receiving captopril (81%) achieved the goal of supine blood pressure less than 90 mmHg. Captopril was discontinued in two patients due to side effects. Mild proteinuria was observed in two patients. A significant reduction in scores or rates of side effects (numbness, blurred vision, insomnia, vivid dreams, cold extremities, sleepiness, sexual dysfunction and fatigue) and improvement in quality of life (general feeling, mood and concentration) was observed in the study group compared with the control group. Captopril alone in a twice daily dose of 25-50 mg, or in co-treatment with thiazide, provided sustained blood pressure control with minimal side effects and improvement in quality of life compared with the treatment of hypertension with beta-blockers, vasodilators or methyldopa.

Treatment effects of captopril on non-proliferative diabetic retinopathy

Institute of Scientific and Technical Information of China (English)

WANG Ning; ZHENG Zhi; JIN Hui-yi; XU Xun

2012-01-01

Background Diabetic retinopathy (DR) is one of the most common complications of diabetes.Angiotensin-converting enzyme inhibitor is thought to play an important role in preventing and treating retinal diseases in animal models of DR.The aim of the present study was to investigate the role of angiotensin-converting enzyme inhibitor (ACEI,captopril) in the treatment of patients with non-proliferative DR.Methods Three hundred and seventeen type 2 diabetic patients (88.05％ of participants) without or with mild to moderate non-proliferative retinopathy were randomly divided into captopril group (n=202) and placebo group (n=115).All subjects received 24-month follow-up.General clinical examinations,including blood pressure and glycated hemoglobin,as well as comprehensive standardized ophthalmic examinations were performed.Color fundus photography and optical coherence tomography (OCT) were used to grade diabetic retinopathy and detect macular edema respectively.Results The levels of blood pressure and glycated hemoglobin in the two groups of patients remained within the normal range during the entire follow-up and no significant difference was found between the initial and last visits,suggesting that ACEI drugs play a protective role on the DR patients independent of its anti-blood pressure role.DR classification showed that 169 eyes (83.66％) remained unchanged and the DR grade of 33 eyes (16.34％) increased in captopril group,while 84 eyes (73.04％) remained unchanged and the grade of 31 eyes (26.96％) increased in placebo group (P=0.024).Captopril treatment improved macular edema in 55.45％ eyes,which was significantly higher than the 37.39％ improvement in placebo group (P=0.002).No significant difference was found in the visual acuity between the two groups (P=0.271).Conclusion Captopril can improve or delay the development of DR and macular edema,which can be used in the early treatment of DR patients with type 2 diabetic mellitus.

Captopril to Mitigate Chronic Renal Failure After Hematopoietic Stem Cell Transplantation: A Randomized Controlled Trial

International Nuclear Information System (INIS)

Cohen, Eric P.; Irving, Amy A. B.A.; Drobyski, William R.; Klein, John P.; Passweg, Jakob; Talano, Julie-An M.; Juckett, Mark B.; Moulder, John E.

2008-01-01

Purpose: To test whether the angiotensin-converting enzyme inhibitor captopril was effective in mitigating chronic renal failure after hematopoietic stem cell transplantation (HSCT). Methods and Materials: A total of 55 subjects undergoing total body irradiation (TBI)-HSCT were enrolled in this randomized controlled trial. Captopril or identical placebo was started at engraftment and continued as tolerated until 1 year after HSCT. Results: The baseline serum creatinine and calculated glomerular filtration rate (GFR) did not differ between groups. The 1-year serum creatinine level was lower and the GFR higher in the captopril compared with the placebo group (p = 0.07 for GFR). Patient survival was higher in the captopril compared with the placebo group, but this was also not statistically significant (p = 0.09). In study subjects who received the study drug for more than 2 months, the 1-year calculated GFRs were 92 mL/min and 80 mL/min, for the captopril and placebo groups, respectively (p = 0.1). There was no adverse effect on hematologic outcome. Conclusions: There is a trend in favor of captopril in mitigation of chronic renal failure after radiation-based HSCT

Captopril 99mTc-DTPA Renal Scintigraphy in Diagnosis of Renovascular Hypertension

International Nuclear Information System (INIS)

Yang, In Hyung; Lee, Dong Soo; Kim, Sung Chul

1992-01-01

To evaluate the sensitivity and specificity of captopril renal scan for renovascular hypertension, we employed the captopril renal scan in conjunction with renal angiography in 81 patients, 159 kidneys, who were referred to evaluate the cause of hypertension. We defined the renovascular hypertension by the criteria of demonstration of renal artery stenosis by angiography, and improvement or cure of hypertension by revascularization. Visual and quantitative evaluation of 99m Tc-DTPA renal scan was performed pre and post captopril administration. The prevalence rate of renovascular hypertension was 40% in comparing with renal angiography, and 70% in confirmed cases. The causes of renovascular hypertension in 81 patients were Takayasu's arteritis, fibromuscular dysplasia, atherosclerosis, essential hypertension, chronic pyelonephritis etc. The sensitivity and specificity of captopril renal scan in comparing with renal angiography were 80%, 86.5%, respectively and also 84.2%, 72.6% in confirmed cases of renovascular hypertension, respectively. The causes of false negative cases were nonfunctioning kidney due to complete obstruction or long duration of disease in basal scan, segmental branch artery stenosis, unknown causes, and suspicious true negative cases without confirmation. The false positive cases were abdominal aortic stenosis or aneurysm, dehydration, unknown causes, and suspicious true positive cases. We conclude that captopril renal scintigraphy is highly sensitive, reasonably specific diagnostic method and comparable to other techniques very favorably.

Exercise performance during captopril and atenolol treatment in hypertensive patients.

OpenAIRE

Van Baak, M A; Koene, F M; Verstappen, F T; Tan, E S

1991-01-01

1. Maximal aerobic exercise capacity, submaximal endurance exercise performance, and exercise haemodynamics have been studied in sixteen patients with mild to moderate essential hypertension during treatment with captopril and atenolol. 2. Administration of atenolol (1 x 100 mg day-1) or captopril (1 x 100 mg day-1) for 6 weeks resulted in similar supine and erect systolic and diastolic blood pressures. Heart rate was significantly lower during atenolol treatment. 3. Exercise heart rate and s...

Parafac and PLS Applied to Determination of Captopril in Pharmaceutical Preparation and Biological Fluids by Ultraviolet Spectrophotometry

International Nuclear Information System (INIS)

Niazi, A.; Ghasemi, N.

2007-01-01

A new ultraviolet spectrophotometric method has been developed for the direct qualitative determination of captopril in pharmaceutical preparation and biological fluids such as human plasma and urine samples. The method was accomplished based on parallel factor analysis (PARAFAC) and partial least squares (PLS). The study was carried out in the pH range from 2.0 to 12.8 and with a concentration from 0.70 to 61.50 μg ml -1 of captopril. Multivariate calibration models PLS at various pH and PARAFAC were elaborated from ultraviolet spectra deconvolution and captopril determination. The best models for this system were obtained with PARAFAC and PLS at pH = 2.04 (PLS-PH2). The applications of the method for the determination of real samples were evaluated by analysis of captopril in pharmaceutical preparations and biological (human plasma and urine) fluids with satisfactory results. The accuracy of the method, evaluated through the root mean square error of prediction (RMSEP), was 0.58 for captopril with PARAFAC and 0.67 for captopril with PLS-PH2 model. Acidity constant of captopril at 25 0 C and ionic strength of 0.1 M have also been determined spectrophotometrically. The obtained pK a values of captopril are 3.90 ± 0.05 and 10.03 ± 0.08 for pK a1 and pK a2 , respectively

Renal scintigraphy with captopril for the investigation of arterial hypertension. Captopril-Nierenfunktionsszintigraphie (C-NFSZ) bei der Abklaerung der arteriellen Hypertonie

Energy Technology Data Exchange (ETDEWEB)

Nitzsche, E; Strauss, E; Moser, E [Freiburg Univ. (Germany, F.R.). Abt. Klinische Nuklearmedizin; Grosser, G [Freiburg Univ. (Germany, F.R.). Abt. Roentgendiagnostik Sankt Marienkrankenhaus, Frankfurt am Main (Germany, F.R.). Radiologische Abt.; Rump, C; Keller, E [Freiburg Univ. (Germany, F.R.). Abt. Nephrologie; Meyer, E [Freiburg Univ. (Germany, F.R.). Abt. Roentgendiagnostik

1991-03-01

Renal artery stenosis (RAS) is a rare cause of hypertension. Radiological tests can disclose the morphological changes, but not their functional effect on renal function and perfusion. Normalization of the blood pressure can be achieved by intervention (operation, percutaneous transluminal renal angiography; PTRA), in cases of prolonged RAS-induced hypertension long-term preservation of the organ function is most important. The purpose of this study was the validation of captopril renography as a screening test for hypertension secondary to RAS prior to PTRA. Captopril renography with {sup 99m}Tc-MAG 3 has a high sensitivity (94%) and acceptable specificity (88%) for the screening of hypertensive patients. The positive predictive value is 74% and the negative predictive value 98%, compared with the 'gold standard' of angiography. (orig.).

Determination of captopril in biological samples by high-performance liquid chromatography with ThioGlo 3 derivatization.

Science.gov (United States)

Aykin, N; Neal, R; Yusof, M; Ercal, N

2001-11-01

Captopril, a well-known angiotensin converting enzyme (ACE) inhibitor, is widely used for treatment of arterial hypertension. Recent studies suggest that it may also act as a scavenger of free radicals because of its thiol group. Therefore, the present study describes a rapid, sensitive and relatively simple method for the detection of captopril in biological tissues with reverse-phase HPLC. Captopril was first derivatized with ThioGlo 3 [3H-Naphto[2,1-b]pyran,9-acetoxy-2-(4-(2,5-dihydro-2,5-dioxo-1H-pyrrol-1-yl)phenyl-3-oxo-)]. It was then detected by fluorescence-HPLC using an Astec C(18) column as the stationary phase and a water:acetonitrile:acetic acid:phosphoric acid mixture (50:50; 1 mL/L acids) as the mobile phase (excitation wavelength, 365 nm; emission wavelength, 445 nm). The calibration curve for captopril was linear over a range of 10-2500 nM and the coefficient of variation acquired for the within- and between-run precision for captopril was 0.5 and 3.8%, respectively. The detection limit of captopril with this method was found to be 200 fmol/20 microL injection volume. Its relative recovery from biological samples was determined to the range from 93.3 to 105.3%. Based on these results, we believe that our method is advantageous for captopril determination. Copyright 2001 John Wiley & Sons, Ltd.

Captopril improves tumor nanomedicine delivery by increasing tumor blood perfusion and enlarging endothelial gaps in tumor blood vessels.

Science.gov (United States)

Zhang, Bo; Jiang, Ting; Tuo, Yanyan; Jin, Kai; Luo, Zimiao; Shi, Wei; Mei, Heng; Hu, Yu; Pang, Zhiqing; Jiang, Xinguo

2017-12-01

Poor tumor perfusion and unfavorable vessel permeability compromise nanomedicine drug delivery to tumors. Captopril dilates blood vessels, reducing blood pressure clinically and bradykinin, as the downstream signaling moiety of captopril, is capable of dilating blood vessels and effectively increasing vessel permeability. The hypothesis behind this study was that captopril can dilate tumor blood vessels, improving tumor perfusion and simultaneously enlarge the endothelial gaps of tumor vessels, therefore enhancing nanomedicine drug delivery for tumor therapy. Using the U87 tumor xenograft with abundant blood vessels as the tumor model, tumor perfusion experiments were carried out using laser Doppler imaging and lectin-labeling experiments. A single treatment of captopril at a dose of 100 mg/kg significantly increased the percentage of functional vessels in tumor tissues and improved tumor blood perfusion. Scanning electron microscopy of tumor vessels also indicated that the endothelial gaps of tumor vessels were enlarged after captopril treatment. Immunofluorescence-staining of tumor slices demonstrated that captopril significantly increased bradykinin expression, possibly explaining tumor perfusion improvements and endothelial gap enlargement. Additionally, imaging in vivo, imaging ex vivo and nanoparticle distribution in tumor slices indicated that after a single treatment with captopril, the accumulation of 115-nm nanoparticles in tumors had increased 2.81-fold with a more homogeneous distribution pattern in comparison to non-captopril treated controls. Finally, pharmacodynamics experiments demonstrated that captopril combined with paclitaxel-loaded nanoparticles resulted in the greatest tumor shrinkage and the most extensive necrosis in tumor tissues among all treatment groups. Taken together, the data from the present study suggest a novel strategy for improving tumor perfusion and enlarging blood vessel permeability simultaneously in order to improve

Effects of captopril on cerebral blood flow in normotensive and hypertensive rats

International Nuclear Information System (INIS)

Barry, D.I.; Paulson, O.B.; Jarden, J.O.; Juhler, M.; Graham, D.I.; Strandgaard, S.

1984-01-01

Cerebrovascular effects of the angiotensin converting enzyme inhibitor captopril were examined in normotensive and hypertensive rats. Cerebral blood flow was measured with the intracarotid 133 xenon injection method in halothane-anesthetized animals. The blood-brain barrier permeability of captopril (determined with an integral-uptake method) was negligible, the permeability-surface area product in most brain regions being 1 X 10(-5) cm3/g per second, that is, three to four times lower than that of sodium ion. When administered into the cerebral ventricles to bypass the blood-brain barrier, captopril had no effect on cerebral blood flow: furthermore, cerebral blood flow autoregulation (studied by raising and lowering blood pressure) was identical to that in controls. In contrast, when given intravenously, captopril had a marked effect on cerebral blood flow autoregulation--both the lower and upper limits of autoregulation being shifted to a lower pressure (by about 20 to 30 and 50 to 60 mm Hg, respectively), and the autoregulatory range was shortened by about 40 mm Hg. This effect may be ascribed to inhibition of converting enzyme in the cerebral blood vessels rather than within the brain

APPLICATION OF UV-SPECTROPHOTOMETRY FOR THE QUANTITATIVE DETERMINATION OF CAPTOPRIL IN DRUG

Directory of Open Access Journals (Sweden)

Yu. V. Monaykina

2015-04-01

Full Text Available Introduction. In this paper the simple, rapid and sensitive assay method for the quantitative determination of captopril in two new pharmaceutical formulations (suppositories and nasal gel is proposed. Analysis was performed directly by using zero-order UV spectrophotometry. It is known from the special literature that the chromatographic techniques used for captopril assay require the expensive equipment and are rather time consuming. Therefore UV spectrophotometry is preferable due to its accuracy, sensitivity and simplicity. The aim of this study was to develop and validate a new, simple, rapid, precise and accurate UV spectrophotometric method for the quantitative determination of captopril in suppositories and nasal gel. Materials and methods. The objects of the study were the new drug formulations of captopril, namely 0,05 suppositories and 2,5% nasal gel developed by the scientists of The Chair of Technology of Drugs ofZaporozhye State Medical University. Distilled water was used as the solvent, working standard sample of captopril was used as a reference standard. Analytical equipment: spectrophotometer Specord 200, electronic balance ABT-120-5DM, measuring glassware of class A. Assay procedure: An accurately weighed sample of gel (0,4000 –0,8000 g or one suppository was dissolved in distilled water and filtered into a volumetric flask (50,00 ml for gel and 250,0 ml for suppository . Then the solution was brought to the mark with the same solvent and stirred. 1,00 ml of the resulting solution was transferred into a 25,00 ml volumetric flask and brought to the mark with distilled water. Absorbance was measured at a wavelength of 203 nm on the blank of a solvent. The parallel measurement with 1,00 ml of 0,03% captopril standard solution was carried out. The content of active substance was calculated according to standard formulas. Results. The suggested procedure was successfully applied for the analysis of two new pharmaceutical

Comparison of aspirin renogram and captopril renogram in the diagnosis of renovascular hypertension

International Nuclear Information System (INIS)

Dabiri Oskoie, S.; Argani, H.

2002-01-01

Renal artery stenosis is the most common cause of secondary hypertension. Preliminary data indicate that aspirin renography with hippurate may be more sensitive for detection renal artery stenosis. In this study 20 patients with known or suspected renal artery stenosis underwent aspirin renography (20 mg/kg orally 1 hour before injection of radiotracer) and captopril renography (50 mg orally) with 99 Tc-DTPA. Renal angiography was performed in all patients. Of the 20 patients enrolled, 11 had unilateral renal artery stenosis on angiography. Captopril renography was positive in 10 patients (915 sensitivity and 90% specificity). Aspirin renogram showed 9 patients with renal artery stenosis correctly (81.85 sensitivity and 100% specificity). Our data suggest that aspirin renography with 99 Tc-DTPA has comparable sensitivity with captopril in detection of unilateral renal artery stenosis

Comparative assessment of captopril and aspirin administration during dynamic renal scintigraphy in diagnosing renovascular hypertension

International Nuclear Information System (INIS)

Kostadinova, I.; Simeonova, A.

1997-01-01

The shortcoming of the captopril test used as a noninvasing screening method in diagnosing renovascular hypertension (RVH) is that in the course of study, ACE-inhibitors (angiotensin-converting enzymes) and diuretics should be discontinued from the therapeutic scheme of patients. The authors compare it to the alternative one with aspirin. The study covers eight patients with angiographic evidence of RVH with significant unilateral stenosis of the renal artery. The obtained results are evaluated on the ground of quantitative (T max , T 1/2 , divided renal function and retention index), as well as qualitative criteria (visual assay). As shown by the results the functional effect of captopril is rather markedly expressed in 6 patients, and the effect of aspirin - in 2. It is concluded that captopril test is more accurate in demonstrating RVH, but in patients with firm clinical evidence of a significant angiotensin II-dependent RVH and negative captopril test, it is advisable to apply aspirin test with a view to differentiate renovascular from essential hypertension

[Dependence of the pharmacokinetics of captopril on the type of adaptation reactions in the organism].

Science.gov (United States)

Udut, V V; Khazanov, V A; Gurto, R V; Borodulina, E V; Postnikova, Iu E

2007-01-01

The dependence of the pharmacokinetic profiles (PhP) of captopril in the phase of adaptation reactions in the organism has been studied within the framework of randomized, comparative, double cross research of bioeqivalency of captopril (Aspharma Co, Anzhero-Sudzhensk) and capoten (Bristol Myers Squibb Co.; official Russian producer, Akrikhin KhimFarmKombinat). It is established that the maximum bioaccessibility and high concentration of captopril in the blood plasma is determined on the background of physiologically optimum reactions of training and in the zone of quiet activation. These characteristics decrease during the reactions of general adaptation syndrome according to the type of increased activation and reactivation.

Kinetics of cardiac and vascular remodeling by spontaneously hypertensive rats after discontinuation of long-term captopril treatment

Directory of Open Access Journals (Sweden)

W.A. Rocha

2010-04-01

Full Text Available Angiotensin-converting enzyme inhibitors reduce blood pressure and attenuate cardiac and vascular remodeling in hypertension. However, the kinetics of remodeling after discontinuation of the long-term use of these drugs are unknown. Our objective was to investigate the temporal changes occurring in blood pressure and vascular structure of spontaneously hypertensive rats (SHR. Captopril treatment was started in the pre-hypertensive state. Rats (4 weeks were assigned to three groups: SHR-Cap (N = 51 treated with captopril (1 g/L in drinking water from the 4th to the 14th week; SHR-C (N = 48 untreated SHR; Wistar (N = 47 control rats. Subgroups of animals were studied at 2, 4, and 8 weeks after discontinuation of captopril. Direct blood pressure was recorded in freely moving animals after femoral artery catheterism. The animals were then killed to determine left ventricular hypertrophy (LVH and the aorta fixed at the same pressure measured in vivo. Captopril prevented hypertension (105 ± 3 vs 136 ± 5 mmHg, LVH (2.17 ± 0.05 vs 2.97 ± 0.14 mg/g body weight and the increase in cross-sectional area to luminal area ratio of the aorta (0.21 ± 0.01 vs 0.26 ± 0.02 μm² (SHR-Cap vs SHR-C. However, these parameters increased progressively after discontinuation of captopril (22nd week: 141 ± 2 mmHg, 2.50 ± 0.06 mg/g, 0.27 ± 0.02 μm². Prevention of the development of hypertension in SHR by using captopril during the prehypertensive period prevents the development of cardiac and vascular remodeling. Recovery of these processes follows the kinetic of hypertension development after discontinuation of captopril.

Negative captopril renography on patients with renin mediated hypertension due to page kidney and reninoma

International Nuclear Information System (INIS)

Yung, B.C.K.; Wong, K.W.; Fan, W.C.; Chan, J.C.S.; Lo, S.S.S.

1999-01-01

Through a mechanism similar to renal artery stenosis, patients with reninoma and page kidney also suffered from renin mediated hypertension. Captopril renograms performed on our patients with the latter two conditions, however, did not yield diagnostic findings. Therefore, equivocal or negative captopril renography cannot serve to rule out conditions with elevated renin other than renal artery stenosis

Validation of a liquid chromatographic method for determination of related substances in a candidate certified reference material of captopril

Directory of Open Access Journals (Sweden)

Raquel Nogueira

2011-06-01

Full Text Available This paper describes the validation of a reversed-phase high performance liquid chromatography method (RP-HPLC with diode array detection (DAD for determination of related substances (impurities from organic synthesis and degradation products of captopril according to the Brazilian Pharmacopeia IV. The aim of this study was to guarantee the method accuracy for quantification of related substances, an essential requisite to determine, using the mass balance approach, the captopril content in the first Brazilian certified reference material (CRM of an active pharmaceutical ingredient (API, developed by Inmetro. The captopril instability in solution is discussed and the captopril content determined by mass balance is compared to the results from titration and differential scanning calorimetry (DSC.Este artigo descreve a validação de método de cromatografia líquida de alta eficiência em fase reversa (CLAE-RP com detector de fotodiodos (DAD para determinação de substâncias relacionadas (impurezas orgânicas de síntese e produtos de degradação de captopril segundo Farmacopéia Brasileira IV ed. Este estudo teve como objetivo garantir que o método é capaz de quantificar com exatidão o teor de substâncias relacionadas, um requisito essencial para que o teor de captopril seja determinado por balanço de massa no primeiro material de referência certificado (MRC de fármacos brasileiro, o qual foi desenvolvido pelo Inmetro. A instabilidade do captopril em solução é discutida em detalhes e o teor de captopril determinado por balanço de massa é comparado com aqueles obtidos por titulação e por calorimetria exploratória diferencial (DSC.

Renal scintigraphy with captopril for the investigation of arterial hypertension

International Nuclear Information System (INIS)

Nitzsche, E.; Strauss, E.; Moser, E.; Grosser, G.; Sankt Marienkrankenhaus, Frankfurt am Main; Rump, C.; Keller, E.; Meyer, E.

1991-01-01

Renal artery stenosis (RAS) is a rare cause of hypertension. Radiological tests can disclose the morphological changes, but not their functional effect on renal function and perfusion. Normalization of the blood pressure can be achieved by intervention (operation, percutaneous transluminal renal angiography; PTRA), in cases of prolonged RAS-induced hypertension long-term preservation of the organ function is most important. The purpose of this study was the validation of captopril renography as a screening test for hypertension secondary to RAS prior to PTRA. Captopril renography with 99m Tc-MAG 3 has a high sensitivity (94%) and acceptable specificity (88%) for the screening of hypertensive patients. The positive predictive value is 74% and the negative predictive value 98%, compared with the 'gold standard' of angiography. (orig.) [de

A chemiluminescence reagent free method for the determination of captopril in medicine and urine samples by using trivalent silver

Directory of Open Access Journals (Sweden)

Zhaofu Fu

2017-08-01

Full Text Available A novel flow-injection chemiluminescence (FI-CL method free of CL reagent was developed for the determination of captopril based on its enhancing effect on the CL derived from diperiodatoargentate(III-sulfuric acid system. Compared with the conventional CL system, the CL system based on trivalent silver was characterized of good selectivity for the absence of CL reagent. The CL mechanism was discussed through CL spectra and UV–vis absorption spectra. The conditions of the FI-CL system were investigated and optimized. Under the optimal conditions, the relative CL intensity was linear with the captopril concentration in the range of 0.3–15.0 μg/mL. The detection limit for captopril was 0.05 μg/mL, and the relative standard deviation (n=11 was 2.0% for 5.0 μg/mL captopril. The proposed method was applied to the analysis of captopril in tablet and human urine with the recoveries of 83.1%–112.5%, and the relative standard deviations of 0.5%–4.4%. The results obtained by the proposed method agreed well with those obtained from HPLC method. The proposed method is fast, convenient, and cost-effective for the determination of captopril in medicine and biological samples.

Estudo termoanalítico de comprimidos revestidos contendo captopril através de termogravimetria (TG e calorimetria exploratória diferencial (DSC Thermal analysis study of captopril coated tablets by thermogravimetry (TG and differential scanning calorimetry (DSC

Directory of Open Access Journals (Sweden)

Giovana Carolina Bazzo

2005-09-01

Full Text Available No presente trabalho foram desenvolvidos comprimidos de captopril revestidos com hidroxipropilmetilcelulose (HPMC, Opadry®, polivinilpirrolidona (PVP, Eudragit® E e goma laca. Foi realizado estudo termoanalítico do fármaco e das formulações através de termogravimetria (TG e calorimetria exploratória diferencial (DSC. Através da análise das curvas DSC verificou-se que não houve a ocorrência de interação entre o fármaco e os excipientes lactose, celulose microcristalina, croscarmelose sódica, Aerosil® e talco, utilizados na formulação do comprimido. Através desta técnica detectou-se a possibilidade de interação entre captopril e estearato de magnésio. De acordo com os resultados obtidos através de DSC não foram observadas alterações na cristalinidade do fármaco decorrentes dos processos de compressão e revestimento. A termogravimetria foi utilizada para o estudo da cinética de degradação do captopril e dos comprimidos. Os parâmetros cinéticos foram determinados através do método de Ozawa. Os resultados demonstraram que não houve alteração da estabilidade térmica do captopril na forma de comprimido. A formulação revestida com HPMC foi a que apresentou maior estabilidade térmica, quando comparada às demais formulações de revestimento.In the present study, captopril coated tablets with hydroxypropylmethylcellulose (HPMC, Opadry®, polyvinylpirrolidone (PVP, Eudragit® and shellac were produced. Differential scanning calorimetry (DSC and thermogravimetry (TG were used to evaluate the thermal properties of the drug and the formulations. On the basis of DSC results, captopril was found to be compatible with lactose, microcrystalline cellulose, sodium croscarmellose, Aerosil® and talc. Some possibility of interaction between drug-excipient was observed with magnesium stearate. However, additional techniques to confirm the results obtained are needed. There was no influence of mechanical treatment (tableting

Reusable fluorescent sensor for captopril based on energy transfer from photoluminescent graphene oxide self-assembly multilayers to silver nanoparticles.

Science.gov (United States)

Sun, Xiangying; Liu, Bin; Li, Shuchun; Li, Fang

2016-05-15

In this work we designed a self-assembly multilayers, in which photoluminescent graphene oxide was employed as a fluorescence probe. This multilayers film can effectively recognize captopril by resonance energy transfer from graphite oxide to silver nanoparticles. A new interfacial sensing method for captopril with high signal to noise ratio was established, by means of that multilayers was quenched by silver nanoparticles and subsequently recovered by adding captopril. The linear relation between intensity and captopril concentration was good, and the detection limit was found to be 0.1578 μM. Also, this novel detection platform demonstrated intriguing reusable properties, and the sensor could be repeated more than ten times without obviously losing its sensing performance. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of captopril on renal blood flow in renal artery stenosis assessed by positron tomography with rubidium-82

International Nuclear Information System (INIS)

Tamaki, N.; Alpert, N.M.; Rabito, C.A.; Barlai-Kovach, M.; Correia, J.A.; Strauss, H.W.

1988-01-01

The sequence and magnitude of acute changes in renal blood flow following administration of captopril were determined in a canine model of acute unilateral renal artery stenosis using rubidium-82 and positron emission tomography. Data were recorded in each of nine dogs under three conditions: 1) during a baseline control interval, 2) during renal artery stenosis, and 3) during stenosis with intravenous injection of captopril (1.2 mg/kg). Mean arterial blood pressure was 108 +/- 12 mm Hg at control, increased significantly to 125 +/- 13 mm Hg (p less than 0.01) during stenosis, and decreased to 98 +/- 13 mm/Hg (p less than 0.01) after captopril infusion. Mean renal blood flow was calculated using a steady state single compartment model from the images produced by positron emission tomography. The estimated flow to the affected kidney was 3.37 +/- 1.48 ml/min/g at control, 0.86 +/- 0.62 ml/min/g during stenosis (p less than 0.01), and 0.64 +/- 0.57 ml/min/g after captopril administration (p = NS compared with precaptopril value). The estimated flow to the contralateral kidney was minimally reduced from a baseline of 3.84 +/- 0.95 to 3.24 +/- 1.13 ml/min/g (p = NS) during stenosis and increased after captopril infusion (4.08 +/- 0.94 ml/min/g; p = 0.01). These data suggest that repetitive imaging with positron emission tomography can be used to delineate acute changes in renal perfusion following captopril administration

Prediction of response to revascularization in patients with renal artery stenosis by Tc-99m-ethylene dicysteine captopril scintigraphy

Energy Technology Data Exchange (ETDEWEB)

Ugur, O.; Ergun, E.L.; Peksoy, I.; Cekirge, S. [Hacettepe Univ., Ankara (Turkey). Medical School; Serdengecti, M.; Karacalioglu, O.

1999-04-01

The aim of the present study was to assess the predictive value of captopril scintigraphy with the new renal agent {sup 99m}Tc-ethylene dicysteine ({sup 99m}Tc-EC) for post-interventional improvement in blood pressure. Twelve patients who had persistently high blood pressure with previous demonstration of various degrees of renal artery lesion on angiography were included into the study. Baseline and captopril scintigraphies were performed on the same day at 4 hour intervals after the injection of 74 and 296 MBq of {sup 99m}Tc-EC, respectively. All patients had percutaneous transluminal angioplasty (PTA), and improvement in blood pressure was evaluated 3-6 months after the intervention. {sup 99m}Tc-EC captopril scintigraphy successfully predicted a positive or negative outcome in 11 of 12 patients. In one patient with captopril induced renal function deterioration, scintigraphy failed to predict post-interventional response. Our preliminary findings showed that {sup 99m}Tc-EC captopril scintigraphy can be used to determine patients who will benefit from revascularization. (author)

Captopril 25 mg tablets stability assessment in different primary packing materials

Directory of Open Access Journals (Sweden)

Flávia Costa Mendes Paiva

2017-11-01

Full Text Available Introduction: Packaging is used to provide protection and information, from the production to the administration of a formulation. It is essential to define the primary packaging, for keeping the therapeutic efficacy of drugs, safety of users and for protecting drugs from instability. Objectives: The main objective of this study was to assess the stability of captopril 25 mg tablets in different primary packaging materials. Method: The characterization (IR, DSC and physical tests of the packaging materials used for captopril was carried out prior to the manufacture of tablets. Tablets were also characterized by physical-chemical analysis, comparative dissolution profile and stability studies. Results: The characterization of packaging materials was crucial for understanding the behavior of captopril when packed in each material. Materials with significant barrier, as blisters PVC/PVdC 90 g.m-² and hard aluminum and PVC/PE/PVdC and hard aluminum showed satisfactory results in a second stage, S2. On the contrary, lower barrier materials as blisters PVC/PVdC 40 g.m-² and hard aluminum did not present dissolution analysis S2. Conclusions: The aluminum strip presented the best results. And the batch in glass bottle, although packaged in excellent material, was disapproved in accelerated stability.

Effect of antihypertensive agents - captopril and nifedipine - on the functional properties of rat heart mitochondria

Directory of Open Access Journals (Sweden)

Ivana Kancirová

2016-06-01

Full Text Available Objective(s: Investigation of acute effect on cellular bioenergetics provides the opportunity to characterize the possible adverse effects of drugs more comprehensively. This study aimed to investigate the changes in biochemical and biophysical properties of heart mitochondria induced by captopril and nifedipine antihypertensive treatment. Materials and Methods: Male, 12-week-old Wistar rats in two experimental models (in vivo and in vitro were used. In four groups, the effects of escalating doses of captopril, nifedipine and combination of captopril + nifedipine added to the incubation medium (in vitro or administered per os to rat (in vivo on mitochondrial ATP synthase activity and membrane fluidity were monitored. Results: In the in vitro model we observed a significant inhibitory effect of treatment on the ATP synthase activity (P

A STUDY OF THE ANTIOXIDANT EFFECTS OF IRANIAN CAPTOPRIL ON PATIENTS WITH HYPERTENSION AND HEART FAILURE

Directory of Open Access Journals (Sweden)

Sedighe Asgari

2010-12-01

Full Text Available Abstract INTRODUCTION: Myocardial ischemia, cerebral ischemia and myocardial infarction are the most important complications of hypertension and atherosclerotic disease in developing countries. Angiotensin converting enzyme (ACE inhibitors are among the drugs used to treat hypertension and heart failure. Captopril is an ACE-inhibitor which also has antioxidant properties. This study was conducted to assess the antioxidant effects of Iranian Captopril on malondialdehyde (MDA, conjugated dienes (CD and serum antioxidant capacity before and after treatment. methods: This interventional prospective single-blind study was conducted on 34 mildly hypertensive individuals and 34 patients with stage I and II heart failure. MDA, CD and serum antioxidant capacity were measured in all samples. The patients were then given 50 mg Captopril tablets 2-3 times daily. The measurements were repeated 1.5 months later. results: Comparison of mean MDA, CD and serum antioxidant capacity in hypertensive patients and patients with heart failure before and after drug administration revealed no significant difference in any of the parameters studied. Discussion: Existing evidence is suggestive of the strong antioxidative properties of Captopril in vitro, although these effects have not been borne out by some studies. In the present study, comparison of MDA, CD and serum antioxidants before and after the period of treatment with Iranian Captopril did not reveal any statistically significant difference.Keywords • Antioxidant • ACE inhibitor • High blood pressure • Heart failure • Clinical trial

Weak interactions in clobazam-lactose mixtures examined by differential scanning calorimetry: Comparison with the captopril-lactose system

Energy Technology Data Exchange (ETDEWEB)

Toscani, S. [Departement de Chimie - UMR 6226, Faculte des Sciences, Universite de Rennes 1, Batiment 10B, 263 avenue du General Leclerc, F-35042 Rennes Cedex (France); Cornevin, L. [Universite de Rennes 1, Faculte de Pharmacie, 2 Avenue Leon Bernard, F-35043 Rennes Cedex (France); Burgot, G., E-mail: Gwenola.burgot@univ-rennes1.fr [Universite de Rennes 1, Faculte de Pharmacie, Laboratoire de Chimie Analytique, EA 1274 ' Mouvement, sports, sante' , 2 Avenue Leon Bernard, F-35043 Rennes Cedex (France); CHGR Rennes, Pole Medico-Technique Pharmacie, F-35703 Rennes Cedex (France)

2012-09-10

Highlights: Black-Right-Pointing-Pointer Thermodynamic and kinetic parameters of weak interactions in binary systems by DSC. Black-Right-Pointing-Pointer Energy-barrier decrease for lactose dehydration induced by clobazam. Black-Right-Pointing-Pointer Recrystallisation of metastable liquid clobazam induced by anhydrous alpha lactose. Black-Right-Pointing-Pointer Decrease of lactose dehydration temperature in binary mixtures with captopril. Black-Right-Pointing-Pointer Increase of lactose dehydration enthalpy in binary mixtures with captopril. - Abstract: The thermal behaviour of binary mixtures of two drugs (clobazam and captopril, respectively) and a pharmaceutical excipient (lactose monohydrate) was measured with differential scanning calorimetry to determine thermodynamic and kinetic parameters (dehydration and melting enthalpies and dehydration and glass-transition activation energies) which might be affected by intermolecular interactions. A kinetic study showed that lactose dehydration is not a single-step conversion and that clobazam contributed to reduce the energy barrier for the bulk dehydration of the excipient. On the other hand, the physical interactions between metastable liquid clobazam and crystalline anhydrous {alpha}-lactose obtained from monohydrate dehydration gave rise to the recrystallisation of clobazam. In the captopril-lactose system, the liquid captopril influenced the lactose dehydration: a sharp increase of the dehydration enthalpy and a concurrent reduction of the dehydration temperature were observed. Finally, it turned out that solid-phase transitions were enhanced by the contact with a liquid phase.

Antioxidant effects of captopril against lead acetate-induced hepatic and splenic tissue toxicity in Swiss albino mice

Directory of Open Access Journals (Sweden)

Badr A. Aldahmash

2016-11-01

Full Text Available Considering that lead caused a lot of health problems in the world, the present study was carried out to investigate the protective effect of captopril as antioxidants to reduce liver and spleen toxicity induced by lead. Animals were divided into 3 groups, the 1st group served as control group, the 2nd group received 20 mg/kg of lead acetate and the 3rd group received 50 mg/kg of captopril one hour prior to lead administration for 5 days. Results showed that lead intake caused severe alterations in the liver and spleen manifested by hepatocytes degeneration, leukocytic infiltration, fibrosis in liver and moderate to severe liver pathological score. Spleen showed ill-defined architecture, presence of large macrophages and lymphoid necrosis. Administration of captopril reduced hepatotoxicity, liver fibrosis and decrease in pathological scoring system. Moreover, reduced toxicity in spleen is represented by reduction in necrotic areas, more or less healthy lymphoid follicles and decreasing in pathological scoring system. Keywords: Captopril, Mice, Liver, Spleen

Inhibition of the dapE-Encoded N-Succinyl-L,L-diaminopimelic Acid Desuccinylase from Neisseria meningitidis by L-Captopril.

Science.gov (United States)

Starus, Anna; Nocek, Boguslaw; Bennett, Brian; Larrabee, James A; Shaw, Daniel L; Sae-Lee, Wisath; Russo, Marie T; Gillner, Danuta M; Makowska-Grzyska, Magdalena; Joachimiak, Andrzej; Holz, Richard C

2015-08-11

Binding of the competitive inhibitor L-captopril to the dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase from Neisseria meningitidis (NmDapE) was examined by kinetic, spectroscopic, and crystallographic methods. L-Captopril, an angiotensin-converting enzyme (ACE) inhibitor, was previously shown to be a potent inhibitor of the DapE from Haemophilus influenzae (HiDapE) with an IC50 of 3.3 μM and a measured Ki of 1.8 μM and displayed a dose-responsive antibiotic activity toward Escherichia coli. L-Captopril is also a competitive inhibitor of NmDapE with a Ki of 2.8 μM. To examine the nature of the interaction of L-captopril with the dinuclear active site of DapE, we have obtained electron paramagnetic resonance (EPR) and magnetic circular dichroism (MCD) data for the enzymatically hyperactive Co(II)-substituted forms of both HiDapE and NmDapE. EPR and MCD data indicate that the two Co(II) ions in DapE are antiferromagnetically coupled, yielding an S = 0 ground state, and suggest a thiolate bridge between the two metal ions. Verification of a thiolate-bridged dinuclear complex was obtained by determining the three-dimensional X-ray crystal structure of NmDapE in complex with L-captopril at 1.8 Å resolution. Combination of these data provides new insights into binding of L-captopril to the active site of DapE enzymes as well as important inhibitor-active site residue interaction's. Such information is critical for the design of new, potent inhibitors of DapE enzymes.

Captopril increases the intensity of monocyte infection by Trypanosoma cruzi and induces human T helper type 17 cells.

Science.gov (United States)

Coelho dos Santos, J S; Menezes, C A S; Villani, F N A; Magalhães, L M D; Scharfstein, J; Gollob, K J; Dutra, W O

2010-12-01

The anti-hypertensive drug captopril is used commonly to reduce blood pressure of patients with severe forms of Chagas disease, a cardiomyopathy caused by chronic infection with the intracellular protozoan Trypanosoma cruzi. Captopril acts by inhibiting angiotensin-converting enzyme (ACE), the vasopressor metallopeptidase that generates angiotensin II and promotes the degradation of bradykinin (BK). Recent studies in mice models of Chagas disease indicated that captopril can potentiate the T helper type 1 (Th1)-directing natural adjuvant property of BK. Equipped with kinin-releasing cysteine proteases, T. cruzi trypomastigotes were shown previously to invade non-professional phagocytic cells, such as human endothelial cells and murine cardiomyocytes, through the signalling of G protein-coupled bradykinin receptors (B(2) KR). Monocytes are also parasitized by T. cruzi and these cells are known to be important for the host immune response during infection. Here we showed that captopril increases the intensity of T. cruzi infection of human monocytes in vitro. The increased parasitism was accompanied by up-regulated expression of ACE in human monocytes. While T. cruzi infection increased the expression of interleukin (IL)-10 by monocytes significantly, compared to uninfected cells, T. cruzi infection in association with captopril down-modulated IL-10 expression by the monocytes. Surprisingly, studies with peripheral blood mononuclear cells revealed that addition of the ACE inhibitor in association with T. cruzi increased expression of IL-17 by CD4(+) T cells in a B(2) KR-dependent manner. Collectively, our results suggest that captopril might interfere with host-parasite equilibrium by enhancing infection of monocytes, decreasing the expression of the modulatory cytokine IL-10, while guiding development of the proinflammatory Th17 subset. © 2010 The Authors. Clinical and Experimental Immunology © 2010 British Society for Immunology.

Permanganate-bromide-silver nanoparticles as a new chemiluminescence system and its application to captopril determination.

Science.gov (United States)

Amjadi, Mohammad; Manzoori, Jamshid L; Hassanzadeh, Javad; Sorouraddin, Mohammad H

2013-10-15

A novel chemiluminescence (CL) system based on the oxidation of bromide by permanganate in sulfuric acid medium is introduced. The enhancing effect of silver nanoparticles (NPs), synthesized by chemical reduction method, on this reaction was studied. It was demonstrated that spherical silver nanoparticles with average size of 18 nm had a most remarkable catalytic effect on this reaction. CL emission wavelengths and UV-vis spectra were used to characterize the system and propose a possible mechanism. Furthermore, it was found that captopril inhibits the action of NPs and decreases the intensity of CL. Based on this phenomenon, a new CL method was developed for the determination of captopril in the 3.0 × 10(-10) to 1.0 × 10(-7) mol L(-1) concentration range with a detection limit (3s) of 0.12 nmol L(-1). The method was successfully applied to the determination of captopril in pharmaceutical formulations, human urine and serum samples. Copyright © 2013 Elsevier B.V. All rights reserved.

Determination of effect of aspirin and captopril on cat glomerular ...

African Journals Online (AJOL)

Four days later, renovascular hypertension was induced through renal-artery stenosis by clipping half of the left renalarteries. Renal scintigraphy was conducted after four days. After confirming the presence of hypertension, the cats were divided into two groups of 10 animals each (aspirin and captopril groups, respectively).

The effect of valsartan, captopril, or both on atherosclerotic events after acute myocardial infarction: an analysis of the Valsartan in Acute Myocardial Infarction Trial (VALIANT)

DEFF Research Database (Denmark)

McMurray, John; Solomon, Scott; Pieper, Karen

2006-01-01

failure, most treated with an ACE inhibitor). One of the main active controlled trials was confounded by a blood pressure difference between treatments. METHODS: We compared the effects of captopril, valsartan, and their combination on atherosclerotic events in 14,703 patients randomized in the Valsartan...... in Acute Myocardial Infarction Trial (VALIANT). RESULTS: The number of individuals adjudicated as having a fatal or non-fatal MI in the captopril group was 559 (total investigator reported events 798), 587 (796) in the valsartan group, and 554 (756) in the combination group; valsartan versus captopril, p...... = 0.651 (0.965); combination versus captopril, p = 0.187 (0.350). Overall, all atherosclerotic events examined occurred at a similar frequency in the captopril and valsartan groups. CONCLUSIONS: Angiotensin receptor blockers appear to be as effective as ACE inhibitors in reducing atherosclerotic...

ACE-2/Ang1-7/Mas cascade mediates ACE inhibitor, captopril, protective effects in estrogen-deficient osteoporotic rats.

Science.gov (United States)

Abuohashish, Hatem M; Ahmed, Mohammed M; Sabry, Dina; Khattab, Mahmoud M; Al-Rejaie, Salim S

2017-08-01

The local role of the renin angiotensin system (RAS) was documented recently beside its conventional systemic functions. Studies showed that the effector angiotensin II (AngII) alters bone health, while inhibition of the angiotensin converting enzyme (ACE-1) preserved these effects. The newly identified Ang1-7 exerts numerous beneficial effects opposing the AngII. Thus, the current study examines the role of Ang1-7 in mediating the osteo-preservative effects of ACEI (captopril) through the G-protein coupled Mas receptor using an ovariectomized (OVX) rat model of osteoporosis. 8 weeks after the surgical procedures, captopril was administered orally (40mgkg -1 d -1 ), while the specific Mas receptor blocker (A-779) was delivered at infusion rate of 400ngkg -1 min -1 for 6 weeks. Bone metabolic markers were measured in serum and urine. Minerals concentrations were quantified in serum, urine and femoral bones by inductive coupled plasma mass spectroscopy (ICP-MS). Trabecular and cortical morphometry was analyzed in the right distal femurs using micro-CT. Finally, the expressions of RAS peptides, enzymes and receptors along with the receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) were determined femurs heads. OVX animals markedly showed altered bone metabolism and mineralization along with disturbed bone micro-structure. Captopril significantly restored the metabolic bone bio-markers and corrected Ca 2+ and P values in urine and bones of estrogen deficient rats. Moreover, the trabecular and cortical morphometric features were repaired by captopril in OVX groups. Captopril also improved the expressions of ACE-2, Ang1-7, Mas and OPG, while abolished OVX-induced up-regulation of ACE-1, AngII, Ang type 1 receptor (AT1R) and RANKL. Inhibition of Ang1-7 cascade by A-779 significantly eradicated captopril protective effects on bone metabolism, mineralization and micro-structure. A-779 also restored OVX effects on RANKL expression and ACE-1/AngII/AT1R

Diagnostic criteria of 99mTc-diethylenetriaminepentaacetic acid captopril renal scan for the diagnosis of renovascular hypertension by unilateral renal artery stenosis

International Nuclear Information System (INIS)

Choi, Seung Jin; Hong, Il Ki; Chang, Jae Won; Park, Su Kil; Moon, Dae Hyuk

2004-01-01

We compared captopril renal scintigraphic criteria for the diagnosis of renovascular hypertension by unilateral renal artery stenosis. The study group consisted of 24 patients (m/f = 16/8, age: 39±18 years) with unilateral renal artery stenosis who underwent renal artery revascularization and captopril renal scintigraphy with 99m Tc-diethylenetriaminepentaacetic acid between May 1995 and April 2004. The blood pressure response was classified as cure/improvement or failure. We evaluated captopril-induced changes in relative function (BCfun) and renogram grade (0 to 5: 0 = normal, and 5 = renal failure pattern without measurable uptake) (CBren) and the difference of renograms between the normal and stenotic kidney on captopril scan (CNren). Eight of 24 patients were cured and 11 improved and 5 patients were classified as failed revascularization. Significant predictors of a cure or improvement of blood pressure were younger age, stenosis by fibromuscular dysplasia or arteritis, BCfun, CBren and CNren. Areas under the receiver operating characteristic curve of age, BCfun, CBren and CNren were not significantly different. Positive and negative predictive values of predictors were 100% and 42% (age ≤ 38); 92% and 50% (BCfun≥ 1 %); 92% and 75% (CBren≥ 1), and 90% and 60% (CNren≥ 1), respectively. Captopril induced changes in renal function and renogram can reliably predict hypertension response to revascularization. Renogram pattern on captopril scan can diagnose renovascular hypertension without baseline data in patients with unilateral renal artery stenosis

Flow-injection spectrophotometric determination of captopril in pharmaceutical formulations using a new solid-phase reactor containing AgSCN immobilized in a polyurethane resin

Directory of Open Access Journals (Sweden)

Fernando Campanhã Vicentini

2012-06-01

Full Text Available A simple flow-injection analysis procedure was developed for determining captopril in pharmaceutical formulations employing a novel solid-phase reactor containing silver thiocyanate immobilized in a castor oil derivative polyurethane resin. The method was based on silver mercaptide formation between the captopril and Ag(I in the solid-phase reactor. During such a reaction, the SCN- anion was released and reacted with Fe3+, which generated the FeSCN2+ complex that was continuously monitored at 480 nm. The analytical curve was linear in the captopril concentration range from 3.0 × 10-4 mol L-1 to 1.1 × 10-3 mol L-1 with a detection limit of 8.0 × 10-5 mol L-1. Recoveries between 97.5% and 103% and a relative standard deviation of 2% for a solution containing 6.0 × 10-4 mol L-1 captopril (n = 12 were obtained. The sample throughput was 40 h-1 and the results obtained for captopril in pharmaceutical formulations using this procedure and those obtained using a pharmacopoeia procedure were in agreement at a 95% confidence level.Um procedimento simples de análise por injeção em fluxo foi desenvolvido para a determinação de captopril em formulações farmacêuticas empregando um novo reator em fase sólida contendo tiocianato de prata imobilizado em resina poliuretana obtida a partir de óleo de mamona. O método foi baseado na formação de um mercapto composto de prata, no reator em fase sólida, obtido entre o captopril e Ag (I imobilizada. Durante a reação, íons SCN- eram liberados e reagiam com Fe3+, gerando o complexo FeSCN2+, que foi continuamente monitorado em 480 nm. A curva analítica foi linear no intervalo de concentração de captopril entre 3,0 × 10-4 a 1,1 × 10-3 mol L-1 com um limite de detecção de 8,0 × 10-5 mol L-1. Recuperações entre 97,5-103% e desvio padrão relativo de 2% para uma solução contendo 6,0 × 10-4 mol L-1 de captopril (n = 12 foram obtidos. A frequência de amostragem foi de 40 h-1 e os resultados

Renal scintigraphy by captopril in hypertension with hypokalemia

International Nuclear Information System (INIS)

Grandet, P.J.

1997-01-01

A study on 30 files of hypertensive patients with an associated hypokalemia was achieved from January 1996 to May 1997. The technique was that of a basic examination effected by MAG 3 (80 MBq), followed by oral intake of 25 to 50 mg of Captopril; one hour after, a new examination was done by MAG 3, with 130 MBq. The classical aspect of isotopic nephro-gram (IN) was not constantly found in case of renal artery stenosis. The reduction of the peak of the level approached might be the only sign, even without any delay of this summit; the lowering of the peak after Captopril of at least 50% should be taken into account. Thus, on the basis of these arguments, we have found 5 stenoses of renal artery. Twenty patients considered as normal have had not arteriography and are relatively well-equilibrated by medical treatment. Among the false negatives, one is explained by a renal insufficiency given an IE of bad quality, while the other is a dysplasia of renal arteries. The 3 false positives presented a discrete difference between the two examinations by MAG 3. Consequently, we considered that the discrete signs should not be retained. The slowing down of transit time, the net lowering of the peak or its delay (classically, 11 min) are good arguments

Preparation and Characterization of Cerium (III Doped Captopril Nanoparticles and Study of their Photoluminescence Properties

Directory of Open Access Journals (Sweden)

Ghamami Shahriar

2016-01-01

Full Text Available In this research Ce3+ doped Captopril nanoparticles (Ce3+ doped CAP-NP were prepared by a cold welding process and have been studied. Captopril may be applied in the treatment of hypertension and some types of congestive heart failure and for preventing kidney failure due to high blood pressure and diabetes. CAP-NP was synthesized by a cold welding process. The cerium nitrate was added at a ratio of 10% and the optical properties have been studied by photoluminescence (PL. The synthesized compounds were characterized by Fourier transform infrared spectroscopy. The size of CAP-NP was calculated by X-ray diffraction (XRD. The size of CAP-NP was in the range of 50 nm. Morphology of surface of synthesized nanoparticles was studied by scanning electron microscopy (SEM. Finally the luminescence properties of undoped and doped CAP-NP were compared. PL spectra from undoped CAP-NP show a strong pack in the range of 546 nm after doped cerium ion into the captopril appeared two bands at 680 and 357 nm, which is ascribed to the well-known 5d–4f emission band of the cerium.

Captopril renal scan - a noninvasive screening test for renovascular hypertension

International Nuclear Information System (INIS)

Akhter, M.S.

2001-01-01

Captopril renal scan is simple, noninvasive and cost-effective test for the initial diagnosis with the sensitivity of 98%. Renal scan with Tc-99m DTPA was performed on the suspected patient one hour after oral intake of 25 mg of captopril. Relative renal function, renogram curves and GFR for both the kidneys were calculated by computer software. Right kidney was small in size, showed relative renal function of 12% and the GFR was 9.64 ml/min. The left organ revealed relative function of 88% and the GFR was 72.12 ml/min. There was marked difference in renogram peaks. On baseline study, the right kidney showed marked improvement of renogram curve peak and the renal function improved to 23% while the GFR showed rise to 19 ml/min. In comparison with baseline findings, the right kidney, in response to ACE inhibitor showed deterioration of renogram peak, 47.8% deterioration of relative renal function and 49.2% fall in GFR. Major criteria for renovascular cause was fulfilled and the patient was labeled for having high probability for renal artery stenosis. Renal angiography, later on confirmed the diagnosis. (author)

Effect of concentration and pH on the surface-enhanced Raman scattering of captopril on nano-colloidal silver surface

Science.gov (United States)

Gao, Junxiang; Gu, Huaimin; Liu, Fangfang; Dong, Xiao; Xie, Min; Hu, Yongjun

2011-07-01

In this report, Raman and surface-enhanced Raman scattering (SERS) spectra of captopril are studied in detail. Herein, the Raman bands are assigned by the density functional theory (DFT) calculations and potential energy distributions (PED) based on internal coordinates of the molecule, which are found to be in good agree with the experimental values. Furthermore, the concentration and pH dependence of the SERS intensity of the molecule is discussed. By analyzing the intensities variation of SERS bands of the different concentrations of captopril solution, it can be concluded that the molecules orientation adsorbed on the silver nanoparticles surface change with the change of the concentrations. The variation of SERS spectra of captopril with the change of pH suggests that the interaction among the adsorbates with Ag cluster depend on the protonated state of the adsorbate and the aggregation of silver nanoparticles.

Novel Neurovascular Protective Agents: Effects of INV-155, INV-157, INV-159, and INV-161 versus Lipoic Acid and Captopril in a Rat Stroke Model

Directory of Open Access Journals (Sweden)

Barry J. Connell

2012-01-01

Full Text Available Background. Lipoic acid (LA, which has significant antioxidant properties, may also function as a potent neuroprotectant. The synthetic compounds INV-155, INV-157, INV-159, and INV-161 are physiochemical combinations of lipoic acid and captopril. We sought to determine if these compounds have neuroprotective potential following middle cerebral artery occlusion (MCAO in rats. Methods. Male Sprague-Dawley rats were injected intravenously with captopril (1–50 mg/kg 30 minutes prior to MCAO. Blood pressure, heart rate, baroreceptor reflex sensitivity, and infarct size were measured. In addition, dose response effect on infarct size and cardiovascular parameters was determined using INV-155, INV-157, INV-159, and INV-161 and compared to captopril and LA. Results. Pretreatment with captopril and LA at all doses tested was neuroprotective. The compounds INV-159 (0.5–10 mg/kg and INV-161 (1–10 mg/kg produced a significant,dose-dependent decrease in infarct size. In contrast, INV-155 and INV-157 had no effect on infarct size. Conclusions. Combined pretreatment with captopril potentiated the neuroprotective benefit observed following LA alone. Both INV-159 and INV-161 were also neuroprotective. These results suggest that patients taking combinations of captopril and LA, either as combination therapy or in the form of INV-159 or INV-161, may also benefit from significant protection against cerebral infarction.

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

Effect of Captopril on Aqueous Levels of Angiotensin II and Its Correlation with Macular Edema in Diabetic Patients

Directory of Open Access Journals (Sweden)

Morteza Shahshahan

2008-12-01

Full Text Available

PURPOSE: To determine whether angiotensin II (AT II levels in aqueous humor are related to diabetes mellitus and to evaluate the effect of captopril on this level. We also evaluated the correlation between severity of macular edema and captopril use. METHODS: In a case-control study, aqueous humor samples were obtained at the onset of cataract surgery from 58 eyes of 58 patients, of whom 37 were diabetic. From these latter subjects, 16 had taken captopril (captopril group for at least six months and 21 had not taken any angiotensin converting enzyme inhibitor (non-captopril group. AT II level was assessed by radioimmunoassay. Severity of macular edema was evaluated by clinical examination after surgery. RESULTS: The aqueous level of AT II was significantly higher in diabetic patients (31.0±7.3 pg/ml compared to non-diabetics (6.28±2.8 pg/ml (Mann Whitney U test, P < 0.0001. In diabetic patients, aqueous concentration of AT II in the captopril group (16.3±6.5 mg/ml was significantly lower than the non-captopril group (75.73±9.36 mg/ml (Mann Whitney U test, P < 0.0003. The severity of macular edema was significantly less in the captopril group compared to the non-captopril group: 68.75% of the captopril group vs 33.3% of the non-captopril group had no macular edema (P < 0.005. CONCLUSION: These findings suggest that the

Synergistic Antihypertensive Effect of Carthamus tinctorius L. Extract and Captopril in l-NAME-Induced Hypertensive Rats via Restoration of eNOS and AT1R Expression

Directory of Open Access Journals (Sweden)

Putcharawipa Maneesai

2016-02-01

Full Text Available This study examined the effect of Carthamus tinctorius (CT extract plus captopril treatment on blood pressure, vascular function, nitric oxide (NO bioavailability, oxidative stress and renin-angiotensin system (RAS in Nω-Nitro-l-arginine methyl ester (l-NAME-induced hypertension. Rats were treated with l-NAME (40 mg/kg/day for five weeks and given CT extract (75 or 150 or 300 or 500 mg/kg/day: captopril (5 mg/kg/day or CT extract (300 mg/kg/day plus captopril (5 mg/kg/day for two consecutive weeks. CT extract reduced blood pressure dose-dependently, and the most effective dose was 300 mg/kg/day. l-NAME-induced hypertensive rats showed abnormalities including high blood pressure, high vascular resistance, impairment of acetylcholine-induced vasorelaxation in isolated aortic rings and mesenteric vascular beds, increased vascular superoxide production and plasma malondialdehyde levels, downregulation of eNOS, low level of plasma nitric oxide metabolites, upregulation of angiotensin II type 1 receptor and increased plasma angiotensin II. These abnormalities were alleviated by treatment with either CT extract or captopril. Combination treatment of CT extract and captopril normalized all the abnormalities found in hypertensive rats except endothelial dysfunction. These data indicate that there are synergistic antihypertensive effects of CT extract and captopril. These effects are likely mediated by their anti-oxidative properties and their inhibition of RAS.

Amplified nanostructure electrochemical sensor for simultaneous determination of captopril, acetaminophen, tyrosine and hydrochlorothiazide

Energy Technology Data Exchange (ETDEWEB)

Karimi-Maleh, Hassan, E-mail: h.karimi.maleh@gmail.com [Department of Chemistry, Graduate University of Advanced Technology, Kerman (Iran, Islamic Republic of); Ganjali, Mohammad R.; Norouzi, Parviz; Bananezhad, Asma [Center of Excellence in Electrochemistry, Faculty of Chemistry, University of Tehran, Tehran (Iran, Islamic Republic of)

2017-04-01

A novel nanomaterial-based voltammetric sensor has been developed for use a highly sensitive tool for the simultaneous determination of captopril (CA), acetaminophen (AC), tyrosine (TY) and hydrochlorothiazide (HCTZ). The device is based on the application of NiO/CNTs and (2-(3,4-dihydroxyphenethyl)isoindoline-1,3-dione) (DPID) to modify carbon paste electrodes. The NiO/CNTs nanocomposite was synthesized through a direct chemical precipitation approach and was characterized with X-ray powder diffraction (XRD), and scanning electron microscopy (SEM). The NiO/CNTs/DPID/CPEs were found to facilitate the analysis of CA, AC, TY and HCTZ in the concentration ranges of 0.07–200.0, 0.8–550.0, 5.0–750.0 and 10.0–600.0 μM with the respective detection limits of 9.0 nM, 0.3 μM, 1.0 μM and 5.0 μM. The developed NiO/CNTs/DPID/CPEs were used for the determination of the mentioned analytes in pharmaceutical and biological real samples. - Graphical abstract: In this study a novel sensor based on NiO/CNTs and (2-(3,4-dihydroxyphenethyl)isoindoline-1,3-dione) (DPID) modified carbon paste electrode fabricated for simultaneous determination of captopril, acetaminophen, tyrosine and hydrochlorothiazide for the first time. - Highlights: • Fabrication of NiO/CNTs and new catechol derivative modified carbon paste electrode • Good ability of proposed sensor for biological and pharmaceutical analysis • Simultaneous determination captopril, acetaminophen, tyrosine and hydrochlorothiazide.

Novel Antihypertensive Prodrug from Grape Seed Proanthocyanidin Extract via Acid-Mediated Depolymerization in the Presence of Captopril: Synthesis, Process Optimization, and Metabolism in Rats.

Science.gov (United States)

Cui, Can; Shi, Ailong; Bai, Shuang; Yan, Pengyu; Li, Qing; Bi, Kaishun

2018-04-11

Grape seed extract contains a high content of proanthocyanidins that can be depolymerized into C-4-substituted (epi)catechin derivatives in the presence of nucleophiles. However, the biological and medicinal values of depolymerization products have been rarely investigated. Recently, we developed a novel depolymerization product (-)-epicatechin-4β- S-captopril methyl ester (ECC) derived from the reaction of grape seed proanthocyanidin extract with captopril in the presence of acidified methanol. A central composite design was employed to select the most appropriate depolymerization temperature and time to obtain the target product ECC with a high yield. A total of 16 metabolites of ECC in rat urine, feces, and plasma were identified using liquid chromatography quadrupole time-of-flight tandem mass spectrometry. The in vivo results suggested that ECC could release captopril methyl ester and epicatechin, followed by the generation of further metabolites captopril and epicatechin sulfate conjugates. Therefore, ECC may be used as a potential prodrug with synergistic or additive hypotensive effects.

Inhibition of the dapE-Encoded N-Succinyl-L,L-diaminopimelic Acid Desuccinylase from Neisseria meningitidis by L-Captopril

OpenAIRE

Starus, Anna; Nocek, Boguslaw; Bennett, Brian; Larrabee, James A.; Shaw, Daniel L.; Sae-Lee, Wisath; Russo, Marie T.; Gillner, Danuta M.; Makowska-Grzyska, Magdalena; Joachimiak, Andrzej; Holz, Richard C.

2015-01-01

Binding of the competitive inhibitor L-captopril to the dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase from Neisseria meningitidis (NmDapE) was examined by kinetic, spectroscopic, and crystallographic methods. L-Captopril, an angiotensin-converting enzyme (ACE) inhibitor, was previously shown to be a potent inhibitor of the DapE from Haemophilus influenzae (HiDapE) with an IC50 of 3.3 μM and a measured Ki of 1.8 μM and displayed a dose-responsive antibiotic activity toward Esch...

Glomerular filtration rate measured by 51Cr-EDTA clearance: evaluation of captopril-induced changes in hypertensive patients with and without renal artery stenosis

International Nuclear Information System (INIS)

Chaves, Anna Alice Rolim; Buchpiguel, Carlos Alberto; Praxedes, Jose Nery; Bortolotto, Luiz Aparecido; Sapienza, Marcelo Tatit

2010-01-01

Introduction: renal artery stenosis can lead to renovascular hypertension; however, the detection of stenosis alone does not guarantee the presence of renovascular hypertension. Renovascular hypertension depends on activation of the renin-angiotensin system, which can be detected by functional tests such as captopril renal scintigraphy. A method that allows direct measurement of the baseline and post-captopril glomerular filtration rate using chromium-51 labeled ethylenediamine tetraacetic acid ( 51 Cr-EDTA) could add valuable information to the investigation of hypertensive patients with renal artery stenosis. The purposes of this study were to create a protocol to measure the baseline and post-captopril glomerular filtration rate using 51 Cr-EDTA, and to verify whether changes in the glomerular filtration rate permit differentiation between hypertensive patients with and without renal artery stenosis. Methods: this prospective study included 41 consecutive patients with poorly controlled severe hypertension. All patients had undergone a radiological investigation of renal artery stenosis within the month prior to their inclusion. The patients were divided into two groups: patients with (n=21) and without renal artery stenosis, (n=20). In vitro glomerular filtration rate analysis ( 51 Cr-EDTA) and 99m Tc-DMSA scintigraphy were performed before and after captopril administration in all patients. Results: the mean baseline glomerular filtration rate was 48.6±21.8 ml/kg/1.73 m 2 in the group with renal artery stenosis, which was significantly lower than the GFR of 65.1±28.7 ml/kg/1.73m 2 in the group without renal artery stenosis (p=0.04). Captopril induced a significant reduction of the glomerular filtration rate in the group with renal artery stenosis (to 32.6±14.8 ml/kg/1.73m 2 , p=0.001) and an insignificant change in the group without RAS (to 62.2±23.6 ml/kg/1.73m 2 , p=0.68). Scintigraphy with technetium-99m dimercapto-succinic acid (DMSA) did not show

Glomerular filtration rate measured by {sup 51}Cr-EDTA clearance: evaluation of captopril-induced changes in hypertensive patients with and without renal artery stenosis

Energy Technology Data Exchange (ETDEWEB)

Chaves, Anna Alice Rolim; Buchpiguel, Carlos Alberto; Praxedes, Jose Nery; Bortolotto, Luiz Aparecido; Sapienza, Marcelo Tatit, E-mail: annaalice100@yahoo.com.b [Universidade de Sao Paulo (USP), SP (Brazil). Faculdade de Medicina. Dept. de Neurologia

2010-07-01

Introduction: renal artery stenosis can lead to renovascular hypertension; however, the detection of stenosis alone does not guarantee the presence of renovascular hypertension. Renovascular hypertension depends on activation of the renin-angiotensin system, which can be detected by functional tests such as captopril renal scintigraphy. A method that allows direct measurement of the baseline and post-captopril glomerular filtration rate using chromium-51 labeled ethylenediamine tetraacetic acid ({sup 51}Cr-EDTA) could add valuable information to the investigation of hypertensive patients with renal artery stenosis. The purposes of this study were to create a protocol to measure the baseline and post-captopril glomerular filtration rate using {sup 51}Cr-EDTA, and to verify whether changes in the glomerular filtration rate permit differentiation between hypertensive patients with and without renal artery stenosis. Methods: this prospective study included 41 consecutive patients with poorly controlled severe hypertension. All patients had undergone a radiological investigation of renal artery stenosis within the month prior to their inclusion. The patients were divided into two groups: patients with (n=21) and without renal artery stenosis, (n=20). In vitro glomerular filtration rate analysis ({sup 51}Cr-EDTA) and {sup 99m}Tc-DMSA scintigraphy were performed before and after captopril administration in all patients. Results: the mean baseline glomerular filtration rate was 48.6+-21.8 ml/kg/1.73 m{sup 2} in the group with renal artery stenosis, which was significantly lower than the GFR of 65.1+-28.7 ml/kg/1.73m{sup 2} in the group without renal artery stenosis (p=0.04). Captopril induced a significant reduction of the glomerular filtration rate in the group with renal artery stenosis (to 32.6+-14.8 ml/kg/1.73m{sup 2}, p=0.001) and an insignificant change in the group without RAS (to 62.2+-23.6 ml/kg/1.73m{sup 2}, p=0.68). Scintigraphy with technetium-99m dimercapto

[Effects of captopril on hemodynamics, gas exchange and exercise capacity in patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease].

Science.gov (United States)

Paitl, C E; Nery, L E; Romaldini, H; Herrmann, J L; Portugal, O P; dos Santos, M L; Martinez Filho, E E

1989-02-01

Captopril, a potent inhibitor of angiotensin converting enzyme, was tested in patients with COPD (means forced expired volume in the first second--FEV1 = 0.73 l) and pulmonary hypertension (PAP = 41.3 mmHg). In the first phase of the experiment, patients underwent and incremental exercise test to the limit of tolerance. These were double blind, randomized, cross-over studies, where the patients received oral placebo (Pl) or captopril (Cp) 25 mg, on different days. In a second phase, the patients were submitted to hemodynamic and gasometric studies in the supine position, before placebo, the 60 min after and immediately after exercise (cycling-like leg movements). After 30 min of rest the same protocol was repeated with oral administration of 25 mg of captopril. In the metabolic evaluation (cycloergometry) captopril increased significantly exercise tolerance (means VO2-uptake at maximal exercise: CP = 0.81 vs Pl = 0.73 1/min), associated with a slower heart rate and higher O2-pulse at maximal exercise. In the hemodynamic study, when the effects of Cp and Pl were compared, the mean values of pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) were similar at rest, but significantly lower during exercise, after captopril (means PAP Cp = 41.3 vs Pl = 51.2 mmHg; XPVR Cp = 278 vs Pl = 392 dyn. sec. cm5). There were similar systemic hemodynamic effects after Cp, but these were more intense in the pulmonary circulation (lower PVR/SVR ratio post-Cp in relation to post-Pl, during exercise). The cardiac index, systemic O2 transport and arterial and mixed venous blood gases were similar at rest and during exercise, with Pl or Cp.(ABSTRACT TRUNCATED AT 250 WORDS)

Value of renal scintigraphy with captopril test in the exploration of renovascular hypertension: Case report

International Nuclear Information System (INIS)

Ghfir, I.; Berehou, F.Z.; Ben Rais, N.

2007-01-01

Introduction Dynamic renal scintigraphy with 99m Tc-DTPA and captopril test is a non-invasive functional method for the diagnosis of renovascular hypertension. It allows differentiating between hypertension induced by renal arterial stenosis from primary arterial hypertension with an incidental stenosis. Case report A 14-year-old girl, without previous medical history, developed a severe arterial hypertension with cephalalgia and ears buzzing. Auscultation revealed a murmur in the left lumbar pit. Renal angiography objectified a stenosis of the infra renal aorta due to a circumferential parietal thickening associated to renal arteries stenosis more marked in the left side. Dynamic renal scintigraphy after administration of captopril highlighted a marked collapse of the rate of tracer uptake exceeding 40% on the left side with an increase in the time of collecting on the right side testifying a frankly positive test prevailing on the left. A transluminal angioplasty of the left renal artery and a revascularization surgery on the right side were carried out. The evolution was marked by an improvement of blood pressure figures. Discussion Dynamic renal scintigraphy using 99m Tc-DTPA with captopril test constitutes a non-invasive process with a low dosimetry for the patients. Its principal goal is to affirm the role of renovascular stenosis in the origin of arterial hypertension and to determine which hypertensive patients with renal arterial stenosis can be treated successfully by surgical or endoscopic revascularization of the kidney. (authors)

A case study presentation: The MAG3 captopril renal scan, which side are you on ?

International Nuclear Information System (INIS)

Richards, A.

1998-01-01

Full text: A 68-year-old woman with widespread vascular disease presented to the Nuclear Medicine Department with severe hypertension, (a blood pressure of 200/160 supine), a known small right kidney, and a large abdominal aortic aneurysm. A baseline renal scan was performed with IV administration of 300 MBq of 99m Tc-labelled MAG3. A normal left kidney was demonstrated, with a Grade 0 renogram pattern. The right kidney was non visualised and non functioning. The patient was then administered orally with 25 mg of A.C.E. inhibitor captopril and her blood pressure fell by greater than 100 mm Hg. A second MAG3 Renal Scan was performed. The finding conflicted with results of a Renal Artery Angiogram and Renal Artery Doppler Ultrasound, both demonstrating a normal left renal artery. A repeat MAG3 Renal scan with captopril challenge was performed. Differential diagnosis included: 1.Left sided microvascular disease; 2. A functioning though very ischaemic right kidney that was producing renin, suggested by contrast opacification of the right renal cortex on CT; or 3. A false negative renal artery angiogram, with non-visualisation of an arterial stenosis caused by thrombus or compression of the left renal artery by the abdominal aortic aneurysm. Subsequent Renal Vein Renin Sampling measured left renal vein renin activity at 4.50,μg/L/h, (compared with 4.80μg/L/h in the IVC). Right renal vein renin activity was 13.20μg/L/h. This lateralization of renin secretion to the right side with suppression of left sided secretion suggested that the renovascular hypertension was caused by the right kidney. This was a very unusual result, as the MAG3 captopril renal scan had incorrectly and strongly suggested a left sided origin to the renovascular hypertension. In addition, the right kidney not seen to accumulate MAG3 was in fact functioning sufficiently to produce renin. It is hypothesized that the left kidney had adjusted to allow normal function only at very high circulating

Renal scintigraphy following angiotensin-converting enzyme inhibition in the diagnosis of renovascular hypertension (captopril scintigraphy)

International Nuclear Information System (INIS)

Sfakianakis, G.N.; Sfakianakis, E.; Bourgoignie, J.

1988-01-01

There is definitely a niche for an accurate test for the diagnosis of RVH; more important, there is a need for a predictive test to help select patients suitable for revascularization procedures as opposed to medical treatment. All current tests have less than optimal results. Captopril scintigraphy warrants evaluation. It is important, however, to approach the test with a full understanding of its theoretical potentials on the basis of current clinical experience. Several options, techniques, and combinations are possible, given the availability of more than one radiopharmaceutical. The purpose of this chapter is to: (a) briefly review RVH and its pathophysiology, with emphasis on the need to establish the diagnosis, lateralize the abnormality, and decide about the mode of treatment; (b) review the current knowledge about converting-enzyme inhibitors; (c) analyze the handling of the different radiopharmaceuticals by the RVH-related kidney with and without pharmacologic intervention; and (d) compare and critically examine proposed protocols for captopril scintigraphy

Hemodynamic and radionuclide effects of acute captopril therapy for heart failure: changes in left and right ventricular volumes and function at rest and during exercise

International Nuclear Information System (INIS)

Massie, B.; Kramer, B.L.; Topic, N.; Henderson, S.G.

1982-01-01

Although the resting hemodynamic effects of captopril in congestive heart failure are known, little information is available about the hemodynamic response to captopril during exercise or about changes in noninvasive measurements of the size and function of both ventricles. In this study, 14 stable New York Heart Association class III patients were given 25 mg of oral captopril. Rest and exercise hemodynamic measurements and blood pool scintigrams were performed simultaneously before and 90 minutes after captopril. The radionuclide studies were analyzed for left and right ventricular end-diastolic volumes, end-systolic volumes, ejection fractions and pulmonary blood volume. The primary beneficial responses at rest were decreases in left and right ventricular end-diastolic volumes from 388 +/- 81 to 350 +/- 77 ml and from 52 +/- 26 to 43 +/- 20 volume units, respectively, and in their corresponding filling pressures, from 24 +/- 10 to 17 +/- 9 mm Hg and 10 +/- 5 to 6 +/- 5 mm Hg. Although stroke volume did not increase significantly, both left and right ventricular ejection fractions increased slightly, from 19 +/- 6% to 22+/- 5% and from 25 +/- 9% to 29 +/- 11%, respectively. During exercise, similar changes were noted in both hemodynamic and radionuclide indexes. This, in patients with moderate symptomatic limitation from chronic heart failure, captopril predominantly reduces ventricular volume and filling pressure, with a less significant effect on cardiac output. These effects persist during exercise, when systemic vascular resistance is already very low. Radionuclide techniques are valuable in assessing the drug effect in these subjects, particularly when ventricular volumes are also measured

Value of renal scintigraphy with captopril test in the exploration of renovascular hypertension: Case report; Apport de la scintigraphie renale avec test au captopril dans l'exploration de l'hypertension arterielle renovasculaire: a propos d'un cas

Energy Technology Data Exchange (ETDEWEB)

Ghfir, I.; Berehou, F.Z.; Ben Rais, N. [Centre Hospitalier Universitaire de Rabat, Hopital Ibn-Sina, Service de Medecine Nucleaire (Morocco)

2007-08-15

Introduction Dynamic renal scintigraphy with {sup 99m}Tc-DTPA and captopril test is a non-invasive functional method for the diagnosis of renovascular hypertension. It allows differentiating between hypertension induced by renal arterial stenosis from primary arterial hypertension with an incidental stenosis. Case report A 14-year-old girl, without previous medical history, developed a severe arterial hypertension with cephalalgia and ears buzzing. Auscultation revealed a murmur in the left lumbar pit. Renal angiography objectified a stenosis of the infra renal aorta due to a circumferential parietal thickening associated to renal arteries stenosis more marked in the left side. Dynamic renal scintigraphy after administration of captopril highlighted a marked collapse of the rate of tracer uptake exceeding 40% on the left side with an increase in the time of collecting on the right side testifying a frankly positive test prevailing on the left. A transluminal angioplasty of the left renal artery and a revascularization surgery on the right side were carried out. The evolution was marked by an improvement of blood pressure figures. Discussion Dynamic renal scintigraphy using {sup 99m}Tc-DTPA with captopril test constitutes a non-invasive process with a low dosimetry for the patients. Its principal goal is to affirm the role of renovascular stenosis in the origin of arterial hypertension and to determine which hypertensive patients with renal arterial stenosis can be treated successfully by surgical or endoscopic revascularization of the kidney. (authors)

Targeting of captopril to the kidney reduces renal angiotensin-converting enzyme activity without affecting systemic blood pressure

NARCIS (Netherlands)

Kok, RJ; Haverdings, Rene; Grijpstra, F; Koiter, J.; Moolenaar, F; De Zeeuw, D; Meijer, DKF

We have synthesized a prodrug of the angiotensin-converting enzyme (ACE) inhibitor captopril by coupling this drug covalently to the low molecular weight protein (LMWP) lysozyme. Such drug-LMWP conjugates can be used for renal drug delivery, since LMWPs accumulate specifically in the proximal

Comparative study on the ACE inhibitors Quinapril and Captopril for the (Angiotensin converting enzyme) treatment of the decompensated cardiac insufficiency in dog

International Nuclear Information System (INIS)

Morisse, B.; Kersten, U.

1994-01-01

In a randomized study of 52 dogs the efficacy and safety of captopril and quinapril in the treatment of canine heart failure is studied. The drugs were found to be comparably effective. The recommended dosage schedule for the short acting captopril is three times daily 0.5 mg/kg body weight. Quinapril belongs to a newer generation of ACE inhibitors with a longer half life than captopril and the treatment was started with a single dose of 0.5 mg/kg body weight. This dosage schedule was sufficient for the successful therapy of most of the dogs with heart failure phase II (12 of 13), but in 4 of 7 dogs with heart failure phase III and in all of the patients with phase IV the single dose had to be increased and/or the dosing interval of quinapril had to be shortened, because they still showed complaints due to heart failure. We recommend to adjust the dosage schedule of quinapril individually to the severity of heart failure. Therapy should be started once daily with an application of 0,5 mg/kg body weight and the dog should be controlled about one week later. If there are still symptoms of decompensated heart failure, the dosage may be increased gradually until a maximum dosage of 0.5 mg/kg three times daily. Especially for patients with severe heart failure we recommend at least when treatment is started a concomitant diuretic therapy. Echocardiographic evaluation of cardiac function shows if there is an indication for positive inotropic support witha digitalis glycoside. Quinapril, a novel inhibitor of the angiotensin-converting enzyme can ease the management of canine heart failure, because at least in dogs with mild to moderate heart failure dosing interval is longer compared with captopril. Moreover, quinapril is available as 5 mg tablets whereas the smallest captopril tablets contain 12.5 mg agent. It has to be mentioned that expenses for a treatment with ACE inhibitors are significantly higher than for a therapy with digitalis, so frequently above all the

[The experimental study of captopril and valsartan on the preventing and treatment of diabetic retinopathy in diabetic mice].

Science.gov (United States)

Xie, Xi-Wei; Zhao, Ping

2004-11-01

To evaluate the action of Angiotensin II (AngII) on the occurrence and development of diabetic retinopathy and the effect of captopril and valsartan on preventing and treating diabetic retinopathy. Male C57BL/KsJ db/+ mice were obtained at 3 weeks of age and maintained on diets enriched animal fat for 4 weeks. After exposure to high-fat diet for 4 weeks, mice were injected intraperitoneally with streptozotocin (STZ) 100 mg/kg body weight. After 2 weeks, nonfasting plasma glucose concentration was measured by nipping the distal part of the tail. Mice whose plasma glucose concentrations were higher than 11.1 mmol/L were selected for the study as model groups. Starting from day 2, captopril 12.5 mg/kg or valsartan 40 mg/kg was given to treatment group via the oral route After treatment for 4, 8, 12 weeks, respectively, eyeballs of mice from each group were enucleated, embedded in paraffin to make tissue sections for immunohistochemistry analysis. The instrument for computer image-analysis was used to analyze the expression of AngII and VEGF in ganglion cell layer. The analyzed indices were mean gray scale value and area density value. With increased duration of diabetes, the mean gray scale values of AngII and VEGF decreased significantly. At the same time, area density values of AngII and VEGF increased significantly. The area density values of VEGF in captopril treated-group was significantly lower than that in valsartan-treated group for the same duration. Moreover, the area density values of VEGF at 4 weeks was significantly lower than that at 8 weeks or 12 weeks. The area density value in captopril treated-group had a significant negative correlation with diabetes duration. AngII had significant positive correlation with VEGF. AngII possibly participated directly and/or indirectly in the occurrence and development of diabetic retinopathy via the upregulation the expression of VEGF. Early treatment with angiotensin-converting enzyme inhibitors (ACEi) and

Antihypertensive mechanisms of chronic captopril (CPT) or N-Acetylcysteine (NAC) treatment in L-NAME hypertensive rats

Czech Academy of Sciences Publication Activity Database

Dobešová, Zdenka; Zicha, Josef; Pecháňová, Olga; Kuneš, Jaroslav

2005-01-01

Roč. 46, č. 4 (2005), s. 912-913 ISSN 0194-911X. [Annual Meeting of the European Council for Cardiovascular Research (ECCR) /10./. 14.10.2005-16.10.2005, La Colle sur Loup] R&D Projects: GA MZd(CZ) NR7786 Keywords : antihypertensive mechanism * captopril * N-Acetylcysteine * L-NAME hypertension Subject RIV: ED - Physiology

Placebo-controlled comparison of captopril, metoprolol, and hydrochlorothiazide therapy in non-insulin-dependent diabetic patients with primary hypertension

DEFF Research Database (Denmark)

Gall, M A; Rossing, P; Skøtt, P

1992-01-01

The antihypertensive effect of captopril, metoprolol, and hydrochlorothiazide was compared in 23 non-insulin-dependent (NIDDM) diabetic patients less than or equal to 75 years of age, with borderline to moderate primary hypertension. In a double blind, placebo-controlled cross-over trial...

Separation methods for captopril in pharmaceuticals and biological fluids.

Science.gov (United States)

Mansour, Fotouh R; Danielson, Neil D

2012-06-01

Captopril (CAP) is an orally active angiotensin-converting enzyme (ACE) inhibitor and has been widely used for management of hypertension and congestive heart failure. CAP lacks an aromatic chromophore required for facile direct UV detection and also has two chiral centers. These factors can render the determination of CAP in complex matrices challenging. This review covers more than 20 years of analytical research on this drug, focusing mainly on pharmaceutical and biological applications. The primary separation techniques discussed are gas chromatography, liquid chromatography, and capillary electrophoresis. The structures of the CAP derivatizing agents as well as a table summarizing various HPLC methods are provided. A discussion of key recent chromatographic and electrophoretic methods for other ACE inhibitors is also present. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Captopril and Valsartan May Improve Cogniti ve Function Through Potentiation of the Brain Antioxidant Defense System and Attenuation of Oxidative/Nitrosative Damage in STZ - Induced Dementia in Rat

Directory of Open Access Journals (Sweden)

Yasaman Arjmand Abbassi

2016-12-01

Full Text Available Purpose: Previous findings have shown the crucial roles of brain renin-angiotensin system (RAS in pathogenesis of Alzheimer’s disease (AD. Since RAS inhibitors may have beneficial effects on dementia and cognitive function in elderly people, the aim of present study was to examine the neuroprotective actions of captopril and valsartan on memory function and neuronal damage in experimental model of AD. Methods: Adult forty male Wistar rats (220-280g were randomly divided into 5 groups; Control, Vehicle, Alzheimer and treatment groups. AD was induced by the injections of streptozotocin (3mg/kg, bilateral intracerebroventricular at days 1&3. Treated rats received orally captopril (50mg/kg/day and valsartan (30mg/kg/day. Memory function and histological assessments were done at termination of experiment. Finally, superoxide dismutase (SOD and catalase (CAT activities as well as malondialdehyde (MDA and NOx contents were determined. Results: There was a significant increase in the mean value of latency in Alzheimer group (66%. Captopril and valsartan considerably decreased this value in both treatment groups (45% and 72%, respectively. In Alzheimer group the activities of brain’s SOD and CAT reduced (40% and 47%, respectively in accompany with an increase in MDA and NOx contents (49% and 50%, respectively. Captopril and valsartan significantly increased the activities of brain’s SOD and CAT concomitant reduction in MDA and NOx contents. Also, histopathological damages noticeably decreased in both treatment groups. Conclusion: Our findings indicate that RAS inhibition by using captopril and valsartan potentiates the antioxidant defense system of brain and reduces oxidative/nitrosative stress in accompany with neuronal damage during AD.

Comparing the impact of melatonin and captopril on early effects of radiation on the heart tissue by studying glutathione, malondialdehyde, and lactate dehydrogenase enzyme activity in rats

International Nuclear Information System (INIS)

Shirazi, Alireza; Tabatabaie, Farnaz; Ghazi-Khansari, Mahmoud; Mirzaei, Hamidreza

2015-01-01

Prevention of secondary malignancy while the patient is receiving radiotherapy for the management of primary cancer has been an enormous challenge for biological and medical safety. The aim of the study is to compare protective effects of melatonin and captopril on early effects of radiation on the heart tissue of rats. Forty-eight adult male Wistar rats weighing 180-220 g were used. The rats were divided into six groups and the rats were exposed to 8 Gy whole body dose from Cobalt-60 sources. Thirty minutes prior to irradiation, six animals received melatonin (100 mg/kg body weight), and six animals received captopril (50 mg/kg body weight). All groups were sacrificed 10 days post-irradiation, and hearts were collected. Malondialdehyde (MDA), lactate dehydrogenase (LDH), and glutathione (GSH) were measured to evaluate cellular oxidative stress-induced injury. The biochemical data are presented as mean ± standard error of the mean, and the difference between the groups was analyzed using a two-way variance analysis. Treatment with captopril resulted in a significant increase in LDH and MDA, although the level of GSH was decreased (P < 0.01). MDA and LDH levels were decreased after melatonin treatment while GSH level was increased (P < 0.001). Melatonin has protective effects following radiation, while treatment with captopril post-irradiation seems to be radiosensitizing and does not have protective effects against radiation exposure. (author)

Prediction of renovascualar hypertension by captopril-stimulated renal vein renin ratios

International Nuclear Information System (INIS)

Roubidoux, M.A.; Dunnick, N.R.; Svetkey, L.; Newmann, G.E.; Cohan, R.H.; Kadir, S.; Klotman, P.

1989-01-01

The authors have prospectively studied 114 patients with suspected renovascular hypertension to determine whether captopril-stimulated, selective, renal vein renin ratios could be used to predict renovascular hypertension. As judged by the response to correction of renal artery lesions, 14 patients had renovascular hypertension, and renal vein renin ratios were significant in eight (sensitivity 57%). Overall, the positive predictive value of renal vein renin ratios was 33%, and the negative predictive value was 89%. The authors concluded that, in patients with renal artery stenosis, renal vein renin ratios predict neither the need for conventional arteriography nor potential benefit from the correction of vascular insufficiency

Cost Minimization Analysis of Antihypertensive Therapy with Captopril-Hydrochlorothiazide and Amlodipine-Hydrochlorothiazide in One of Hospitals in Bandung

Directory of Open Access Journals (Sweden)

Andini Faramitha

2017-09-01

Full Text Available The successful therapy of stage 2 hypertension can be supported by the administration of antihypertensive. Existence of various antihypertensive alternative, making pharmacoeconomics study is needed in order to have an effective and efficient therapy. Purpose of this study is to find the antihypertensive group therapy which is more efficient in cost (cost minimization which used in the treatment of stage 2 hypertension in patients at one hospital in Bandung from 2011 until 2013. This study is an observational reserach with retrospective data collection. Data retrieval is done by taking the medical records of hospitalized patients who received therapy of stage 2 hypertension antihypertensive, captopril-hydrochlorothiazide or amlodipin-hydrochlorothiazide. Components that are collected include the cost of antihypertensive, supportive therapy costs, the cost of action, administrative expenses and cost of hospitalization. The result of the study cost minimization analysis showed that the total cost of treatment with the antihypertensive captopril-hydrochlorothiazide is lower compared to amlodipin- hydrochlorothiazide, with the difference amounting to Rp126,798.

Clonidine versus captopril for treatment of postpartum very high blood pressure: study protocol for a randomized controlled trial (CLONCAP).

Science.gov (United States)

Noronha-Neto, Carlos; Katz, Leila; Coutinho, Isabela C; Maia, Sabina B; Souza, Alex Sandro Rolland; Amorim, Melania Maria Ramos

2013-07-30

The behavior of arterial blood pressure in postpartum of women with hypertension and pregnancy and the best treatment for very high blood pressure in this period still need evidence. The Cochrane systematic review assessing prevention and treatment of postpartum hypertension found only two trials (120 patients) comparing hydralazine with nifedipine and labetalol for the treatment of severe hypertension and did not find enough evidence to know how best to treat women with hypertension after birth. Although studies have demonstrated the effectiveness of treatment with captopril, side effects were reported. Because of these findings, new classes of antihypertensive drugs began to be administered as an alternative therapy. Data on the role of clonidine in this particular group of patients, its effects in the short and long term are still scarce in the literature. To determine the effectiveness of clonidine, compared to captopril, for the treatment of postpartum very high blood pressure in women with hypertension in pregnancy. The study is a triple blind randomized controlled trial including postpartum women with diagnosis of hypertension in pregnancy presenting very high blood pressure, and exclusion criteria will be presence of heart disease, smoking, use of illicit drugs, any contraindication to the use of captopril or clonidine and inability to receive oral medications.Eligible patients will be invited to participate and those who agree will be included in the study and receive captopril or clonidine according to a random list of numbers. The subjects will receive the study medication every 20 minutes until blood pressure is over 170 mmHg of systolic blood pressure and 110 mmHg diastolic blood pressure. A maximum of six pills a day for very high blood pressure will be administered. In case of persistent high blood pressure levels, other antihypertensive agents will be used.During the study the women will be subject to strict control of blood pressure and urine

SYNTHESIS AND IN VITRO CHARACTERIZATION OF HYDROXYPROPYL METHYLCELLULOSE-GRAFT-POLY (ACRYLIC ACID/2-ACRYLAMIDO-2-METHYL-1-PROPANESULFONIC ACID) POLYMERIC NETWORK FOR CONTROLLED RELEASE OF CAPTOPRIL.

Science.gov (United States)

Furqan Muhammad, Iqbal; Mahmood, Ahmad; Aysha, Rashid

2016-01-01

A super-absorbent hydrogel was developed by crosslinking of 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS) and acrylic acid with hydroxypropyl methylcellulose (HPMC) for controlled release drug delivery of captopril, a well known antihypertensive drug. Acrylic acid and AMPS were polymerized and crosslinked with HPMC by free radical polymerization, a widely used chemical crosslinking method. N,N'-methylenebisacrylamide (MBA) and potassium persulfate (KPS) were added as cross-linker and initiator, respectively. The hydrogel formulation was loaded with captopril (as model drug). The concentration of captopril was monitored at 205 nm using UV spectrophotometer. Equilibrium swelling ratio was determined at pH 2, 4.5 and 7.4 to evaluate the pH responsiveness of the formed hydrogel. The super-absorbent hydrogels were evaluated by FTIR, SEM, XRD, and thermal analysis (DSC and TGA). The formation of new copolymeric network was determined by FTIR, XRD, TGA and DSC analysis. The hydrogel formulations with acrylic acid and AMPS ratio of 4: 1 and lower amounts of crosslinker had shown maximum swelling. Moreover, higher release rate of captopril was observed at pH 7.4 than at pH 2, because of more swelling capacity of copolymer with increasing pH of the aqueous medium. The present research work confirms the development of a stable hydrogel comprising of HPMC with acrylic acid and AMPS. The prepared hydrogels exhibited pH sensitive behav-ior. This superabsorbent composite prepared could be a successful drug carrier for treating hypertension.

Influence of chronic captopril treatment on norepinephrine-induced vasoconstriction in SHR and WKY : In vivo study

Czech Academy of Sciences Publication Activity Database

Pintérová, Mária; Kuneš, Jaroslav; Dobešová, Zdenka; Zicha, Josef

2008-01-01

Roč. 26, Suppl.1 (2008), S174-S174 ISSN 0263-6352. [Scientific Meeting International Society of Hypertension /22./ , Scientific Meeting European Society of Hypertension /18./. 14.06.2008-19.06.2008, Berlin] Institutional research plan: CEZ:AV0Z50110509 Keywords : cpo1 * captopril teratment * norepinephrine-induced vasoconstriction * SHR and WKY Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

The effect of Valsartan and Captopril for the improvement of left ventricular systolic function after acute anterior myocardial infarction

International Nuclear Information System (INIS)

Liu Jun; Fu Xianghua; Xue Ling; Wu Weili; Li Shiqiang

2010-01-01

Objective: To compare the therapeutic effect of angiotensin II antagonist (Valsartan) and angiotension-converting enzyme inhibitor (Captopril) for the improvement of left ventricular systolic function (LVSF) after acute myocardial infarction (AMI) at anterior wall. Methods: A total of 75 patients with initial AMI at anterior wall were enlisted in the study. Patients were divided randomly into three groups: control group (n = 15), Captopril treated (n =30), and Valsartan treated (n =30). At 1 week and 28 weeks post AMI, the LVSF and left ventricular regional ejection fraction (LrEF) were measured by equilibrium radionuclide angiography (ERNA). The t-test was used to compare the dada. Results: (1) At 28 weeks, left ventricular ejection fraction (LVEF) and left ventricular peak ejection rate (LPER) in Valsartan treated group were significantly increased as compared with those of control: (59.4±8.6) % vs (44.9±8.4)%, t = 3.87, P 2 , LrEF 4 , LrEF 5 , LrEF-6: (71.6±18.8)% vs (57.0±11.4)%, t=2.11, P<0.05;(78.1±16.8)% vs (68.9±21.0)%, t =2.06, P<0.05; (70.5±16.9)% vs (59.9±23.4)%, t=1.99, P<0.05; and (58.1±9.0) % vs (46.0±18.9) %, t = 2.43, P<0.05, respectively. Conclusions: Valsartan and Captopril are effective for the improvement of LVEF after AMI at anterior wall. The effects of the two drugs are similar. (authors)

Selectivity of Inhibition of N-Succinyl-l,l-Diaminopimelic Acid Desuccinylase in Bacteria: The product of dapE-gene Is Not the Target of l-Captopril Antimicrobial Activity.

Science.gov (United States)

Uda, Narasimha Rao; Creus, Marc

2011-01-01

The emergence of bacterial strains that are resistant to virtually all currently available antibiotics underscores the importance of developing new antimicrobial compounds. N-succinyl-l,l-diaminopimelic acid desuccinylase (DapE) is a metallohydrolase involved in the meso-diaminopimelate (mDAP)/lysine biosynthetic pathway necessary for lysine biosynthesis and for building the peptidoglycan cell wall. Because DapE is essential for Gram-negative and some Gram-positive bacteria, DapE has been proposed as a good target for antibiotic development. Recently, l-captopril has been suggested as a lead compound for inhibition of DapE, although its selectivity for this enzyme target in bacteria remains unclear (Gillner et al. (2009)). Here, we tested the selectivity of l-captopril against DapE in bacteria. Since DapE knockout strains of gram-negative bacteria are viable upon chemical supplementation with mDAP, we reasoned that the antimicrobial activity of compounds targeting DapE should be abolished in mDAP-containing media. Although l-captopril had modest antimicrobial activity in Escherichia coli and in Salmonella enterica, to our surprise, inhibition of bacterial growth was independent both of mDAP supplementation and DapE over-expression. We conclude that DapE is not the main target of l-captopril inhibition in these bacteria. The methods implemented here will be useful for screening DapE-selective antimicrobial compounds directly in bacterial cultures.

Pharmacogenetic Analysis of Captopril Effects on Blood Pressure: Possible Role of the Ednrb (Endothelin Receptor Type B) Candidate Gene

Czech Academy of Sciences Publication Activity Database

Zicha, Josef; Dobešová, Zdenka; Zídek, Václav; Šilhavý, Jan; Šimáková, Miroslava; Mlejnek, Petr; Vaněčková, Ivana; Kuneš, Jaroslav; Pravenec, Michal

2014-01-01

Roč. 63, č. 2 (2014), s. 263-265 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) LH11049 Institutional support: RVO:67985823 Keywords : captopril * blood pressure * QTL * Ednrb gene * spontaneously hypertensive rat Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.293, year: 2014

Regulation of the instantaneous inward rectifier and the delayed outward rectifier potassium channels by Captopril and Angiotensin II via the Phosphoinositide-3 kinase pathway in volume-overload-induced hypertrophied cardiac myocytes.

Science.gov (United States)

Alvin, Zikiar V; Laurence, Graham G; Coleman, Bernell R; Zhao, Aiqiu; Hajj-Moussa, Majd; Haddad, Georges E

2011-07-01

Early development of cardiac hypertrophy may be beneficial but sustained hypertrophic activation leads to myocardial dysfunction. Regulation of the repolarizing currents can be modulated by the activation of humoral factors, such as angiotensin II (ANG II) through protein kinases. The aim of this work is to assess the regulation of IK and IK1 by ANG II through the PI3-K pathway in hypertrophied ventricular myocytes. Cardiac eccentric hypertrophy was induced through volume-overload in adult male rats by aorto-caval shunt (3 weeks). After one week half of the rats were given captopril (2 weeks; 0.5 g/l/day) and the other half served as control. The voltage-clamp and western blot techniques were used to measure the delayed outward rectifier potassium current (IK) and the instantaneous inward rectifier potassium current (IK1) and Akt activity, respectively. Hypertrophied cardiomyocytes showed reduction in IK and IK1. Treatment with captopril alleviated this difference seen between sham and shunt cardiomyocytes. Acute administration of ANG II (10-6M) to cardiocytes treated with captopril reduced IK and IK1 in shunts, but not in sham. Captopril treatment reversed ANG II effects on IK and IK1 in a PI3-K-independent manner. However in the absence of angiotensin converting enzyme inhibition, ANG II increased both IK and IK1 in a PI3-K-dependent manner in hypertrophied cardiomyocytes. Thus, captopril treatment reveals a negative effect of ANG II on IK and IK1, which is PI3-K independent, whereas in the absence of angiotensin converting enzyme inhibition IK and IK1 regulation is dependent upon PI3-K.

Influence of chronic renal failure on captopril pharmacokinetics and clinical and biological effects in hypertensive patients.

OpenAIRE

Giudicelli, J F; Chaignon, M; Richer, C; Giroux, B; Guedon, J

1984-01-01

The pharmacokinetic parameters of unchanged plasma captopril and the kinetics of the drug effects on plasma converting enzyme activity (PCEA), plasma renin activity (PRA), plasma aldosterone (PA) and mean blood pressure (MBP) were studied over 24 h after oral administration in three groups of hypertensive patients: with normal renal function (group 1, plasma creatinine less than 110 mumol/l, n = 10), with moderate chronic renal failure (group 2, 135 less than plasma creatinine less than 450 m...

The critical role of NIR spectroscopy and statistical process control (SPC) strategy towards captopril tablets (25 mg) manufacturing process understanding: a case study.

Science.gov (United States)

Curtivo, Cátia Panizzon Dal; Funghi, Nathália Bitencourt; Tavares, Guilherme Diniz; Barbosa, Sávio Fujita; Löbenberg, Raimar; Bou-Chacra, Nádia Araci

2015-05-01

In this work, near-infrared spectroscopy (NIRS) method was used to evaluate the uniformity of dosage units of three captopril 25 mg tablets commercial batches. The performance of the calibration method was assessed by determination of Q value (0.9986), standard error of estimation (C-set SEE = 1.956), standard error of prediction (V-set SEP = 2.076) as well as the consistency (106.1%). These results indicated the adequacy of the selected model. The method validation revealed the agreement of the reference high pressure liquid chromatography (HPLC) and NIRS methods. The process evaluation using the NIRS method showed that the variability was due to common causes and delivered predictable results consistently. Cp and Cpk values were, respectively, 2.05 and 1.80. These results revealed a non-centered process in relation to the average target (100% w/w), in the specified range (85-115%). The probability of failure was 21:100 million tablets of captopril. The NIRS in combination with the method of multivariate calibration, partial least squares (PLS) regression, allowed the development of methodology for the uniformity of dosage units evaluation of captopril tablets 25 mg. The statistical process control strategy associated with NIRS method as PAT played a critical role in understanding of the sources and degree of variation and its impact on the process. This approach led towards a better process understanding and provided the sound scientific basis for its continuous improvement.

The angiotensin converting enzyme inhibitor, captopril, prevents the hyperactivity and impulsivity of neurokinin-1 receptor gene 'knockout' mice: sex differences and implications for the treatment of attention deficit hyperactivity disorder.

Science.gov (United States)

Porter, Ashley J; Pillidge, Katharine; Grabowska, Ewelina M; Stanford, S Clare

2015-04-01

Mice lacking functional neurokinin-1 receptors (NK1R-/-) display behavioural abnormalities resembling attention deficit hyperactivity disorder (ADHD): locomotor hyperactivity, impulsivity and inattentiveness. The preferred ligand for NK1R, substance P, is metabolised by angiotensin converting enzyme (ACE), which forms part of the brain renin angiotensin system (BRAS). In view of evidence that the BRAS modulates locomotor activity and cognitive performance, we tested the effects of drugs that target the BRAS on these behaviours in NK1R-/- and wildtype mice. We first tested the effects of the ACE inhibitor, captopril, on locomotor activity. Because there are well-established sex differences in both ADHD and ACE activity, we compared the effects of captopril in both male and female mice. Locomotor hyperactivity was evident in male NK1R-/- mice, only, and this was abolished by treatment with captopril. By contrast, male wildtypes and females of both genotypes were unaffected by ACE inhibition. We then investigated the effects of angiotensin AT1 (losartan) and AT2 (PD 123319) receptor antagonists on the locomotor activity of male NK1R-/- and wildtype mice. Both antagonists increased the locomotor activity of NK1R-/- mice, but neither affected the wildtypes. Finally, we tested the effects of captopril on the performance of male NK1R-/- and wildtype mice in the 5-choice serial reaction-time task (5-CSRTT) and found that ACE inhibition prevented the impulsivity of NK1R-/- mice. These results indicate that certain behaviours, disrupted in ADHD, are influenced by an interaction between the BRAS and NK1R, and suggest that ACE inhibitors could provide a novel treatment for this disorder. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Utilization of oxidation reactions for the spectrophotometric determination of captopril using brominating agents

Science.gov (United States)

El-Didamony, Akram M.; Erfan, Eman A. H.

2010-03-01

Three simple, accurate and sensitive methods (A-C) for the spectrophotometric assay of captopril (CPL) in bulk drug, in dosage forms and in the presence of its oxidative degradates have been described. The methods are based on the bromination of captopril with a solution of excess brominating mixture in hydrochloric acid medium. After bromination, the excess brominating mixture is followed by the estimation of surplus bromine by three different reaction schemes. In the first method (A), the determination of the residual bromine is based on its ability to bleach the indigo carmine dye and measuring the absorbance at 610 nm. Method B, involves treating the unreacted bromine with a measured excess of iron(II) and the remaining iron(II) is complexed with 1,10-phenanthroline and the increase in absorbance is measured at 510 nm. In method (C), the surplus bromine is treated with excess of iron(II) and the resulting iron(III) is complexed with thiocyanate and the absorbance is measured at 478 nm. In all the methods, the amount of bromine reacted corresponds to the drug content. The different experimental parameters affecting the development and stability of the color are carefully studied and optimized. Beer's law is valid within a concentration range of 0.4-6.0, 0.4-2.8 and 1.2-4.8 μg mL -1 for methods A, B and C, respectively. The calculated apparent molar absorptivity was found to be 5.16 × 10 4, 9.95 × 10 4 and 1.74 × 10 5 L mol -1 cm -1, for methods A, B and C, respectively. Sandell's sensitivity, correlation coefficients, detection and quantification limits are also reported. No interference was observed from common additives found in pharmaceutical preparations. The proposed methods are successfully applied to the determination of CPL in the tablet formulations with mean recoveries of 99.94-100.11% and the results were statistically compared with those of a reference method by applying Student's t- and F-test.

Análise da prescrição de captopril em pacientes hospitalizados Analysis of the prescription of captopril to hospitalized patients

Directory of Open Access Journals (Sweden)

Márcio Galvão Oliveira

2008-12-01

Full Text Available Uma das complicações mais comuns da hipertensão arterial sistêmica é a crise hipertensiva¹ que se caracteriza por uma elevação sintomática da pressão arterial (PA, com ou sem envolvimento de órgãos-alvo, que pode conduzir a um risco imediato ou potencial de vida2-4. A crise hipertensiva pode se manifestar como emergência ou urgência hipertensiva. Na emergência, há a rápida deterioração de órgãos-alvo e risco imediato de vida, situação que não ocorre na urgência hipertensiva2-4. Além disso, as situações em que o paciente apresenta PA elevada diante de algum evento emocional, doloroso ou desconfortável, sem evidências de lesões de órgãos-alvo ou risco imediato de vida, caracterizam a pseudocrise hipertensiva, condição em que não é necessário o uso da terapia anti-hipertensiva de emergência1-3,5. Apesar disso, tem se tornado comum a prática de prescrever anti-hipertensivos precedendo situações em que se identifica algum risco de elevação abrupta da PA, independentemente de sintomas. O presente estudo tem como objetivo avaliar a freqüência de prescrição do captopril precedendo elevação da PA em pacientes internados em um hospital universitário. Pretende também mapear os locais (enfermarias clínicas ou cirúrgicas onde essa conduta foi mais freqüente.One of the most common complications of Systemic Arterial Hypertension is the hypertensive crisis¹ characterized by a symptomatic elevation of blood pressure (BP with or without involvement of target organs, which may lead to immediate or potential risk to life2-4. The hypertensive crisis may manifest itself as hypertensive emergency or urgency. In the emergency there is fast deterioration of target organs and immediate risk to life, a situation that does not occur in hypertensive urgency2-4. On the other hand, situations in which the patient presents elevated BP due to an emotionally charged, painful or uncomfortable event, with no evidence of

The expression of neuronal nitric oxide synthase (NNOS) in brainstem and cerebellum of spontaneously hypertensive rats (SHR): The effect of chronic captopril treatment

Czech Academy of Sciences Publication Activity Database

Hojná, Silvie; Dobešová, Zdenka; Zicha, Josef; Kuneš, Jaroslav

2005-01-01

Roč. 46, č. 4 (2005), s. 895-895 ISSN 0194-911X. [Annual Meeting of the European Council for Cardiovascular Research (ECCR) /10./. 14.10.2005-16.10.2005, La Colle sur Loup] R&D Projects: GA ČR(CZ) GA305/03/0769 Keywords : nitric oxide synthase * brain * captopril * hypertension Subject RIV: ED - Physiology

The angiotensin converting enzyme (ACE) inhibitor, captopril disrupts the motility activation of sperm from the silkworm, Bombyx mori.

Science.gov (United States)

Nagaoka, Sumiharu; Kawasaki, Saori; Kawasaki, Hideki; Kamei, Kaeko

2017-11-01

Angiotensin I-converting enzyme (also known as peptidyl dicarboxypeptidase A, ACE, and EC 3.4.15.1), which is found in a wide range of organisms, cleaves C-terminal dipeptides from relatively short oligopeptides. Mammalian ACE plays an important role in the regulation of blood pressure. However, the precise physiological functions of insect ACE homologs have not been understood. As part of our effort to elucidate new physiological roles of insect ACE, we herein report a soluble ACE protein in male reproductive secretions from the silkmoth, Bombyx mori. Seminal vesicle sperm are quiescent in vitro, but vigorous motility is activated by treatment with either a glandula (g.) prostatica homogenate or trypsin in vitro. When seminal vesicle sperm were pre-incubated with captopril, a strong and specific inhibitor of mammalian ACE, and then stimulated to initiate motility by the addition of the g. prostatica homogenate or trypsin, the overall level of acquired motility was reduced in an inhibitor-concentration-dependent manner. In the course of this project, we detected ACE-related carboxypeptidase activity that was inhibited by captopril in both the vesicular (v.) seminalis of the noncopulative male reproductive tract and in the spermatophore that forms in the female bursa copulatrix at the time of mating, just as in an earlier report on the tomato moth, Lacanobia oleracea, which belongs to a different lepidopteran species (Ekbote et al., 2003a). Two distinct genes encoding ACE-like proteins were identified by analysis of B. mori cDNA, and were named BmAcer and BmAcer2, respectively [the former was previously reported by Quan et al. (2001) and the latter was first isolated in this paper]. RT-qPCR and Western blot analyses indicated that the BmAcer2 was predominantly produced in v. seminalis and transferred to the spermatophore during copulation, while the BmAcer was not detected in the adult male reproductive organs. A recombinant protein of BmAcer2 (devoid of a signal

Arterial morphology responds differently to Captopril then N-acetylcysteine in a monocrotaline rat model of pulmonary hypertension

Science.gov (United States)

Molthen, Robert; Wu, Qingping; Baumgardt, Shelley; Kohlhepp, Laura; Shingrani, Rahul; Krenz, Gary

2010-03-01

Pulmonary hypertension (PH) is an incurable condition inevitably resulting in death because of increased right heart workload and eventual failure. PH causes pulmonary vascular remodeling, including muscularization of the arteries, and a reduction in the typically large vascular compliance of the pulmonary circulation. We used a rat model of monocrotaline (MCT) induced PH to evaluated and compared Captopril (an angiotensin converting enzyme inhibitor with antioxidant capacity) and N-acetylcysteine (NAC, a mucolytic with a large antioxidant capacity) as possible treatments. Twenty-eight days after MCT injection, the rats were sacrificed and heart, blood, and lungs were studied to measure indices such as right ventricular hypertrophy (RVH), hematocrit, pulmonary vascular resistance (PVR), vessel morphology and biomechanics. We implemented microfocal X-ray computed tomography to image the pulmonary arterial tree at intravascular pressures of 30, 21, 12, and 6 mmHg and then used automated vessel detection and measurement algorithms to perform morphological analysis and estimate the distensibility of the arterial tree. The vessel detection and measurement algorithms quickly and effectively mapped and measured the vascular trees at each intravascular pressure. Monocrotaline treatment, and the ensuing PH, resulted in a significantly decreased arterial distensibility, increased PVR, and tended to decrease the length of the main pulmonary trunk. In rats with PH induced by monocrotaline, Captopril treatment significantly increased arterial distensibility and decrease PVR. NAC treatment did not result in an improvement, it did not significantly increase distensibility and resulted in further increase in PVR. Interestingly, NAC tended to increase peripheral vascular density. The results suggest that arterial distensibility may be more important than distal collateral pathways in maintaining PVR at normally low values.

Avaliação do uso do captopril na fibrose peritoneal induzida em ratos pelo uso de solução de glicose a 4,25%

Directory of Open Access Journals (Sweden)

Adriana Fátima Menegat Schuinski

2013-12-01

Full Text Available INTRODUÇÃO: A Insuficiência Renal Crônica (IRC tem incidência alarmante neste século. A diálise peritoneal, uma das modalidades de terapia renal pode ter complicações, e entre estas a fibrose peritoneal, que ocorre com o decorrer dos anos nestes pacientes. Sua forma mais grave é a chamada peritonite esclerosante encapsulante, levando à mudança de terapia dialítica. OBJETIVO: Estudar a influência do uso do captopril na fibrose peritoneal induzida em ratos pelo uso de solução de glicose a 4,25 %. MÉTODOS: Estudo prospectivo controlado, em ratos Wistar não urêmicos. Foram estudados 20 animais. Os animais foram submetidos diariamente à punção abdominal, sendo infundida solução de diálise peritoneal com glicose a 4,25% na dose de 10 ml/100 g de peso. Os animais foram divididos em 2 grupos: experimental e controle. O grupo experimental recebeu captopril na dose de 30 mg/kg/dia por gavagem. O grupo controle não recebeu nenhuma droga. Foram acompanhados por 21 e 49 dias. Ao final do período foram submetidos à procedimento cirúrgico para retirada de peritônio parietal e visceral. As amostras obtidas foram analisadas histologicamente, usando-se coloração Hematoxilina - Eosina e Sirius Red, para avaliação do grau de fibrose. RESULTADOS: A análise mostrou que a intensidade da fibrose, a espessura do peritônio e o número de células não atingiram diferença estatisticamente significante entre os grupos experimental e controle. CONCLUSÃO: O estudo mostrou que o uso do captopril não foi capaz de alterar a intensidade da fibrose peritoneal induzida pelo uso de solução de diálise em ratos.

Sensitive kinetic spectrophotometric determination of captopril and ethamsylate in pharmaceutical preparations and biological fluids.

Science.gov (United States)

El-Shabrawy, Y; El-Enany, N; Salem, K

2004-10-01

A highly sensitive kinetic spectrophotometric method was developed for the determination of captopril (CPL) and ethamsylate (ESL) in pharmaceutical preparations and biological fluids. The method is based on a catalytic acceleration of the reaction between sodium azide and iodine in an aqueous solution. Concentration range of 0.1-1.5 microg ml(-1) for CPL and 0.3-3 microg ml(-1) for ESL was determined by measuring the decrease in the absorbance of iodine at 348 nm by a fixed time method. The decrease in absorbance after 5 min was markedly correlated to the concentration. The relative standard deviations obtained were 1.30 and 1.87 for CPL and ESL, respectively, in pure forms. Correlation coefficients were 0.9997 and 0.9999 for CPL and ESL, respectively. The detection limits were determined as (S/N = 3) were 20 ng ml(-1) for CPL and 50 ng ml(-1) for ESL. The proposed procedure was successively applied for the determination of both drugs in pharmaceutical preparations and in biological fluids.

Nanostructural drug-inorganic clay composites: Structure, thermal property and in vitro release of captopril-intercalated Mg-Al-layered double hydroxides

International Nuclear Information System (INIS)

Zhang Hui; Zou Kang; Guo Shaohuan; Duan Xue

2006-01-01

A nanostructural drug-inorganic clay composite involving a pharmaceutically active compound captopril (Cpl) intercalated Mg-Al-layered double hydroxides (Cpl-LDHs) with Mg/Al molar ratio of 2.06 has been assembled by coprecipitation method. Powder X-ray diffraction (XRD), Fourier transform infrared spectra (FT-IR) and Raman spectra analysis indicate a successful intercalation of Cpl between the layers with a vertical orientation of Cpl disulphide-containing S-S linkage. SEM photo indicates that as-synthesized Cpl-LDHs possess compact and non-porous structure with approximately and linked elliptical shape particles of ca. 50 nm. TG-DTA analyses suggest that the thermal stability of intercalated organic species is largely enhanced due to host-guest interaction involving the hydrogen bond compared to pure form before intercalation. The in vitro release studies show that both the release rate and release percentages markedly decrease with increasing pH from 4.60 to 7.45 due to possible change of release mechanism during the release process. The kinetic simulation for the release data, and XRD and FT-IR analyses for samples recovered from release media indicate that the dissolution mechanism is mainly responsible for the release behaviour of Cpl-LDHs at pH 4.60, while the ion-exchange one is responsible for that at pH 7.45. - Graphical abstract: Based on XRD, FT-IR and Raman spectra analyses, it is suggested that captopril (Cpl) exists as its disulphide metabolites in the interlayer of Mg-Al-LDHs via hydrogen bonding between guest carboxylate function and hydroxyl group of the host layers. A schematic supramolecular structure of Cpl intercalates involving a vertical orientation of Cpl disulphide-containing S-S bond between the layers with carboxylate anions pointing to both hydroxide layers is presented

Colorimetric microdetermination of captopril in pure form and in pharmaceutical formulations

Science.gov (United States)

Shama, Sayed Ahmed; El-Sayed Amin, Alla; Omara, Hany

2006-11-01

A simple, rapid, accurate, precise and sensitive colorimetric method for the determination of captopril (CAP) in bulk sample and in dosage forms is described. The method is based on oxidation of the drug by potassium permanganate in acidic medium and determination of the unreacted oxidant by measuring the decrease in absorbance for five different dyes; methylene blue (MB); acid blue 74 (AB), acid red 73 (AR), amaranth dye (AM) and acid orange 7 (AO) at a suitable λmax (660, 610, 510, 520, and 485 nm), respectively. Regression analysis of Beer's plots showed good correlation in the concentration ranges (0.4 12.5, 0.3 10, 0.5 11, 0.4 8.3 and 0.5 9.3 μg ml-1), respectively. The apparent molar absorbtivity, Sandell sensitivity, detection and quantitation limits were calculated. For more accurate results, Ringbom optimum concentration ranges were 0.5 12, 0.5 9.6, 0.6 10.5, 0.5 8.0 and 0.7 9.0 μg ml-1, respectively. The validity of the proposed method was tested by analyzing in pure and dosage forms containing CAP whether alone or in combination with hydrochlorothiazide. Statistical analysis of the results reflects that the proposed procedures are precise, accurate and easily applicable for the determination of CAP in pure form and in pharmaceutical preparations. Also, the stability constant was determined and the free energy change was calculated potentiometrically.

Estabilidad física y química de preparaciones líquidas extemporáneas elaboradas a partir de tabletas de captopril

OpenAIRE

Olaya, Maria del Pilar; Muñoz, Ilvar José; Ponce D´León, Luisa Fernanda; Barbosa, Helber; Bautista, Sandra Elizabeth

2008-01-01

Se estudió la estabilidad de preparaciones líquidas extemporáneas para administración peroral, elaboradas  a partir de tabletas de captopril de dos marcas comerciales del mercado nacional colombiano, codificadas como A y B, utilizando solventes de uso común en hospitales. Vehículo 1: agua destilada + vitamina C 10 %  (98 % : 2 %), Vehículo 2: dextrosa 10 % en agua destilada + vitamina C 10 % (98 % : 2 %). Las muestras fueron almacenadas a 5 ºC, 25 ºC y 40 ºC. La cuantificación del fármaco se ...

Quantification of captopril in urine through surface-assisted laser desorption/ionization mass spectrometry using 4-mercaptobenzoic acid-capped gold nanoparticles as an internal standard.

Science.gov (United States)

Chen, Wen-Tsen; Chiang, Cheng-Kang; Lin, Yang-Wei; Chang, Huan-Tsung

2010-05-01

We have developed a new internal standard method for the determination of the concentration of captopril (CAP) through surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS) using gold nanoparticles (Au NPs). This approach provided linearity for CAP over the concentration range 2.5-25 microM (R(2) = 0.987), with a limit of detection (signal-to-noise ratio = 3) of 1.0 microM. The spot-to-spot variations in the concentration of CAP through SALDI-MS analyses performed in the absence and presence of the internal standard were 26% and 9%, respectively (15 measurements). This approach provides simplicity, accuracy, precision, and great reproducibility to the determination of the levels of CAP in human urine samples. Copyright 2010 American Society for Mass Spectrometry. Published by Elsevier Inc. All rights reserved.

The use of response surface methodology in the evaluation of captopril microparticles manufactured using an oil in oil solvent evaporation technique.

Science.gov (United States)

Khamanga, Sandile Maswazi; Walker, Roderick B

2012-01-01

Captopril (CPT) microparticles were manufactured by solvent evaporation using acetone (dispersion phase) and liquid paraffin (manufacturing phase) with Eudragit® and Methocel® as coat materials. Design of experiments and response surface methodology (RSM) approaches were used to optimize the process. The microparticles were characterized based on the percent of drug released and yield, microcapsule size, entrapment efficiency and Hausner ratio. Differential scanning calorimetry (DSC), Infrared (IR) spectroscopy, scanning electron microscopy (SEM) and in vitro dissolution studies were conducted. The microcapsules were spherical, free-flowing and IR and DSC thermograms revealed that CPT was stable. The percent drug released was investigated with respect to Eudragit® RS and Methocel® K100M, Methocel® K15M concentrations and homogenizing speed. The optimal conditions for microencapsulation were 1.12 g Eudragit® RS, 0.67 g Methocel® K100M and 0.39 g Methocel® K15M at a homogenizing speed of 1643 rpm and 89% CPT was released. The value of RSM-mediated microencapsulation of CPT was elucidated.

Efeito antioxidante do captopril e a influência da via de sinalização de PKC na produção de EROS induzida por Bradicinina no modelo experimental de diabetes mellitus tipo 1

OpenAIRE

Araújo, Glaucy Rodrigues de

2011-01-01

O diabetes é uma doença que acomete milhões de pessoas em todo o mundo e tem sido alvo de muitos estudos. As complicações no diabetes, como a cardiomiopatia e o estresse oxidativo aumentado são importantes focos de estudo e são responsáveis em grande parte pelo aumento na morbidade e mortalidade associado à doença. Drogas anti-hipertensivas, principalmente aquelas que bloqueiam o sistema renina-angiotensina, como o captopril, são utilizadas com freqüência para o tratamento de diabetes, contri...

The use of experimental design for the development of a capillary zone electrophoresis method for the quantitation of captopril.

Science.gov (United States)

Mukozhiwa, S Y; Khamanga, S M M; Walker, R B

2017-09-01

A capillary zone electrophoresis (CZE) method for the quantitation of captopril (CPT) using UV detection was developed. Influence of electrolyte concentration and system variables on electrophoretic separation was evaluated and a central composite design (CCD) was used to optimize the method. Variables investigated were pH, molarity, applied voltage and capillary length. The influence of sodium metabisulphite on the stability of test solutions was also investigated. The use of sodium metabisulphite prevented degradation of CPT over 24 hours. A fused uncoated silica capillary of 67.5cm total and 57.5 cm effective length was used for analysis. The applied voltage and capillary length affected the migration time of CPT significantly. A 20 mM phosphate buffer adjusted to pH 7.0 was used as running buffer and an applied voltage of 23.90 kV was suitable to effect a separation. The optimized electrophoretic conditions produced sharp, well-resolved peaks for CPT and sodium metabisulphite. Linear regression analysis of the response for CPT standards revealed the method was linear (R2 = 0.9995) over the range 5-70 μg/mL. The limits of quantitation and detection were 5 and 1.5 μg/mL. A simple, rapid and reliable CZE method has been developed and successfully applied to the analysis of commercially available CPT products.

The effect of captopriland amlodipine on C-reactive protein concentrations in type 2 diabetic hypertensive patients

International Nuclear Information System (INIS)

Mahmood, I.H.

2008-01-01

To compare the effects of the ACE inhibitor captopril with the calcium channel blocker amlodipine on serum CRP concentrations in hypertensive type 2 diabetic patients. This is a case control study conducted in Al-Wafa Diabetic Center in Mosul. Serum CRP concentrations were measured in two groups of hypertensive type 2 diabetic patients before and after drug administration (group 1 on captopril therapy, group two on amlodipine therapy). A significant reduction of serum CRP level was demonstrated after treatment with captopril but not with amlodipine. Mean CRP concentration of the control group was statistically lower than those of captopril and amlodipine groups. The present study showed that hypertensive type 2 diabetic patients are associated with increased level of CRP and therapy with captopril but not amlodipine significantly reduced CRP, suggesting a possible anti-inflammatory action of captopril in addition to its BP lowering effects thus captopril may be regarded as the drug of choice in the treatment of BP in diabetic hypertensive patients. (author)

ACE inhibition is superior to angiotensin receptor blockade for renography in renal artery stenosis

International Nuclear Information System (INIS)

Karanikas, Georgios; Becherer, Alexander; Wiesner, Karoline; Dudczak, Robert; Kletter, Kurt

2002-01-01

Angiotensin converting enzyme (ACE) inhibitors as well as angiotensin II receptor antagonists are able to prevent the vasoconstrictive effect of angiotensin II on the efferent renal vessels, which is believed to play an important role in renovascular hypertension. This effect is assumed to be essential for the demonstration of renovascular hypertension by captopril renography. In this study, renographic changes induced by captopril and the AT1 receptor antagonist valsartan were compared in patients with a high probability for renovascular hypertension. Twenty-five patients with 33 stenosed renal arteries (grade of stenosis >50%) and hypertension were studied. Captopril, valsartan and baseline renography were performed within 48 h using technetium-99m mercaptoacetyltriglycine. Blood pressure was monitored, plasma renin concentration before and after intervention was determined and urinary flow was estimated from the urinary output of the hydrated patients. Alterations in renographic curves after intervention were evaluated according to the Santa Fe consensus on ACE inhibitor renography. Captopril renography was positive, indicating renovascular hypertension, in 25 of the 33 stenosed vessels, whereas valsartan renography was positive in only ten. Blood pressure during captopril and valsartan renography was not different; reduction in blood pressure was the same after valsartan and captopril. Plasma renin concentration was comparable for valsartan and captopril studies, showing suppressed values after intervention in as many as 12 of the 25 patients. Urinary flow after valsartan was higher than after captopril (P<0.05). However, this difference could not explain the markedly higher sensitivity of captopril compared with valsartan in demonstrating renal artery stenosis. In 14 of the 25 patients, blood pressure response to revascularisation was monitored, showing a much better predictive value for captopril renography. It is concluded that captopril renography is much

ACE inhibition is superior to angiotensin receptor blockade for renography in renal artery stenosis

Energy Technology Data Exchange (ETDEWEB)

Karanikas, Georgios; Becherer, Alexander; Wiesner, Karoline; Dudczak, Robert; Kletter, Kurt [Department of Nuclear Medicine, University of Vienna (Austria)

2002-03-01

Angiotensin converting enzyme (ACE) inhibitors as well as angiotensin II receptor antagonists are able to prevent the vasoconstrictive effect of angiotensin II on the efferent renal vessels, which is believed to play an important role in renovascular hypertension. This effect is assumed to be essential for the demonstration of renovascular hypertension by captopril renography. In this study, renographic changes induced by captopril and the AT1 receptor antagonist valsartan were compared in patients with a high probability for renovascular hypertension. Twenty-five patients with 33 stenosed renal arteries (grade of stenosis >50%) and hypertension were studied. Captopril, valsartan and baseline renography were performed within 48 h using technetium-99m mercaptoacetyltriglycine. Blood pressure was monitored, plasma renin concentration before and after intervention was determined and urinary flow was estimated from the urinary output of the hydrated patients. Alterations in renographic curves after intervention were evaluated according to the Santa Fe consensus on ACE inhibitor renography. Captopril renography was positive, indicating renovascular hypertension, in 25 of the 33 stenosed vessels, whereas valsartan renography was positive in only ten. Blood pressure during captopril and valsartan renography was not different; reduction in blood pressure was the same after valsartan and captopril. Plasma renin concentration was comparable for valsartan and captopril studies, showing suppressed values after intervention in as many as 12 of the 25 patients. Urinary flow after valsartan was higher than after captopril (P<0.05). However, this difference could not explain the markedly higher sensitivity of captopril compared with valsartan in demonstrating renal artery stenosis. In 14 of the 25 patients, blood pressure response to revascularisation was monitored, showing a much better predictive value for captopril renography. It is concluded that captopril renography is much

CUSP9* treatment protocol for recurrent glioblastoma: aprepitant, artesunate, auranofin, captopril, celecoxib, disulfiram, itraconazole, ritonavir, sertraline augmenting continuous low dose temozolomide.

Science.gov (United States)

Kast, Richard E; Karpel-Massler, Georg; Halatsch, Marc-Eric

2014-09-30

CUSP9 treatment protocol for recurrent glioblastoma was published one year ago. We now present a slight modification, designated CUSP9*. CUSP9* drugs--aprepitant, artesunate, auranofin, captopril, celecoxib, disulfiram, itraconazole, sertraline, ritonavir, are all widely approved by regulatory authorities, marketed for non-cancer indications. Each drug inhibits one or more important growth-enhancing pathways used by glioblastoma. By blocking survival paths, the aim is to render temozolomide, the current standard cytotoxic drug used in primary glioblastoma treatment, more effective. Although esthetically unpleasing to use so many drugs at once, the closely similar drugs of the original CUSP9 used together have been well-tolerated when given on a compassionate-use basis in the cases that have come to our attention so far. We expect similarly good tolerability for CUSP9*. The combined action of this suite of drugs blocks signaling at, or the activity of, AKT phosphorylation, aldehyde dehydrogenase, angiotensin converting enzyme, carbonic anhydrase -2,- 9, -12, cyclooxygenase-1 and -2, cathepsin B, Hedgehog, interleukin-6, 5-lipoxygenase, matrix metalloproteinase -2 and -9, mammalian target of rapamycin, neurokinin-1, p-gp efflux pump, thioredoxin reductase, tissue factor, 20 kDa translationally controlled tumor protein, and vascular endothelial growth factor. We believe that given the current prognosis after a glioblastoma has recurred, a trial of CUSP9* is warranted.

Ontogenetic role of angiontensin-converting enzyme in rats: thirst and sodium appetite evaluation.

Science.gov (United States)

Mecawi, André S; Araujo, Iracema G; Rocha, Fábio F; Coimbra, Terezila M; Antunes-Rodrigues, José; Reis, Luís C

2010-01-12

We investigated the influence of captopril (an angiotensin converting enzyme inhibitor) treatment during pregnancy and lactation period on hydromineral balance of the male adult offspring, particularly, concerning thirst and sodium appetite. We did not observe significant alterations in basal hydromineral (water intake, 0.3M NaCl intake, volume and sodium urinary concentration) or cardiovascular parameters in adult male rats perinatally treated with captopril compared to controls. However, male offspring rats that perinatally exposed to captopril showed a significant attenuation in water intake induced by osmotic stimulation, extracellular dehydration and beta-adrenergic stimulation. Moreover, captopril treatment during perinatal period decreased the salt appetite induced by sodium depletion. This treatment also attenuated thirst and sodium appetite aroused during inhibition of peripheral angiotensin II generation raised by low concentration of captopril in the adult offspring. Interestingly, perinatal exposure to captopril did not alter water or salt intake induced by i.c.v. administration of angiotensin I or angiotensin II. These results showed that chronic inhibition of angiotensin converting enzyme during pregnancy and lactation modifies the regulation of induced thirst and sodium appetite in adulthood.

Angiotensin converting enzyme in the brain, testis, epididymis, pituitary gland and adrenal gland

International Nuclear Information System (INIS)

Strittmatter, S.M.

1986-01-01

[ 3 H]Captopril binds to angiotensin converting enzyme (ACE) in rat tissue homogenates. The pharmacology, regional distribution and copurification of [ 3 H]captopril binding with enzymatic activity demonstrate the selectivity of [ 3 H]captopril labeling of ACE. [ 3 H]Captopril binding to purified ACE reveals differences in cationic dependence and anionic regulation between substrate catalysis and inhibitor recognition. [ 3 H]Captopril association with ACE is entropically driven. The selectivity of [ 3 H]captopril binding permits autoradiographic localization of the ACE in the brain, male reproductive system, pituitary gland and adrenal gland. In the brain, ACE is visualized in a striatonigral neuronal pathway which develops between 1 and 7 d after birth. In the male reproductive system, [ 3 H]captopril associated silver grains are found over spermatid heads and in the lumen of seminiferous tubules in stages I-VIII and XII-XIV. In the pituitary gland, ACE is localized to the posterior lobe and patches of the anterior lobe. The adrenal medulla contains moderate ACE levels while low levels are found in the adrenal cortex. Adrenal medullary ACE is increased after hypophysectomy and after reserpine treatment. The general of ligand binding techniques for the study of enzymes is demonstrated by the specific labeling of another enzyme, enkephaline convertase, in crude tissue homogenates by the inhibitor [ 3 H]GEMSA

Effects of angiotensin converting enzyme inhibitor and angiotensin II antagonist receptor on neointima hyperplasia after vascular balloon injury

International Nuclear Information System (INIS)

Wang Yeling; Zhao Lihua

2004-01-01

Objective: To study the effects of angiotensin converting enzyme inhibitor (captopril) and angiotensin II antagonist receptor (valsartan) on neointima hyperplasia after vascular balloon injury. Methods: Thirty-six rabbit models were randomly divided into three groups: injuried group, captopril group and valsartan group. Captopril (2 mg·kg -1 ·d -1 po) and valsartan (10 mg·kg -1 ·d -1 po) were given to twelve rabbits respectively from 1 day before the right carotidarteries were injuried by 2.0 mm ballon cathether to 14 days after injury in captopil group and valsartan group. The medicine was not administered in the injuried group. The tissue plasminogen activator (tPA), plaminogen activor inhibitor-1 (PAI-1) antigen level and plasma endothelin (ET) levels were measured before injury, and 7, 14 days after vascular injury. The pathomorphoiogical examination were carried out 14 days after angioplasty. Results: The levels of plasma PAI-1 and ET in captopril group and valsartan group were significantly lower than those in the injuried group (P<0.05). The intimal thickness and extent of lumen stenosis in captopril and valsartan groups were significantly lower than those in the injuried group (P<0.05). Conclusion: Captopril and valsartan can inhibit neointima hyperplasia after vascular ballon injury. (authors)

Hypertension and Cardiovascular Remodelling in Rats Exposed to Continuous Light: Protection by ACE-Inhibition and Melatonin

Directory of Open Access Journals (Sweden)

Fedor Simko

2014-01-01

Full Text Available Exposure of rats to continuous light attenuates melatonin production and results in hypertension development. This study investigated whether hypertension induced by continuous light (24 hours/day exposure induces heart and aorta remodelling and if these alterations are prevented by melatonin or angiotensin converting enzyme inhibitor captopril. Four groups of 3-month-old male Wistar rats (10 per group were treated as follows for six weeks: untreated controls, exposed to continuous light, light-exposed, and treated with either captopril (100 mg/kg/day or melatonin (10 mg/kg/day. Exposure to continuous light led to hypertension, left ventricular (LV hypertrophy and fibrosis, and enhancement of the oxidative load in the LV and aorta. Increase in systolic blood pressure by continuous light exposure was prevented completely by captopril and partially by melatonin. Both captopril and melatonin reduced the wall thickness and cross-sectional area of the aorta and reduced the level of oxidative stress. However, only captopril reduced LV hypertrophy development and only melatonin reduced LV hydroxyproline concentration in insoluble and total collagen in rats exposed to continuous light. In conclusion, captopril prevented LV hypertrophy development in the continuous light-induced hypertension model, while only melatonin significantly reduced fibrosis. This antifibrotic action of melatonin may be protective in hypertensive heart disease.

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), ...

Mitigation of Late Renal and Pulmonary Injury After Hematopoietic Stem Cell Transplantation

Energy Technology Data Exchange (ETDEWEB)

Cohen, Eric P., E-mail: Eric.Cohen2@va.gov [Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Bedi, Manpreet; Irving, Amy A. [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Jacobs, Elizabeth; Tomic, Rade [Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Klein, John [Department of Biostatistics, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Lawton, Colleen A.; Moulder, John E. [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States)

2012-05-01

Purpose: To update the results of a clinical trial that assessed whether the angiotensin-converting enzyme inhibitor captopril was effective in mitigating chronic renal failure and pulmonary-related mortality in subjects undergoing total body irradiation (TBI) in preparation for hematopoietic stem cell transplantation (HSCT). Methods and Materials: Updated records of the 55 subjects who were enrolled in this randomized controlled trial were analyzed. Twenty-eight patients received captopril, and 27 patients received placebo. Definitions of TBI-HSCT-related chronic renal failure (and relapse) were the same as those in the 2007 analysis. Pulmonary-related mortality was based on clinical or autopsy findings of pulmonary failure or infection as the primary cause of death. Follow-up data for overall and pulmonary-related mortality were supplemented by use of the National Death Index. Results: The risk of TBI-HSCT-related chronic renal failure was lower in the captopril group (11% at 4 years) than in the placebo group (17% at 4 years), but this was not statistically significant (p > 0.2). Analysis of mortality was greatly extended by use of the National Death Index, and no patients were lost to follow-up for reasons other than death prior to 67 months. Patient survival was higher in the captopril group than in the placebo group, but this was not statistically significant (p > 0.2). The improvement in survival was influenced more by a decrease in pulmonary mortality (11% risk at 4 years in the captopril group vs. 26% in the placebo group, p = 0.15) than by a decrease in chronic renal failure. There was no adverse effect on relapse risk (p = 0.4). Conclusions: Captopril therapy produces no detectable adverse effects when given after TBI. Captopril therapy reduces overall and pulmonary-related mortality after radiation-based HSCT, and there is a trend toward mitigation of chronic renal failure.

Antihypertensive and cardioprotective effects of the dipeptide isoleucine-tryptophan and whey protein hydrolysate.

Science.gov (United States)

Martin, M; Kopaliani, I; Jannasch, A; Mund, C; Todorov, V; Henle, T; Deussen, A

2015-12-01

Angiotensin-converting enzyme inhibitors are treatment of choice in hypertensive patients. Clinically used inhibitors exhibit a structural similarity to naturally occurring peptides. This study evaluated antihypertensive and cardioprotective effects of ACE-inhibiting peptides derived from food proteins in spontaneously hypertensive rats. Isoleucine-tryptophan (in vitro IC50 for ACE = 0.7 μm), a whey protein hydrolysate containing an augmented fraction of isoleucine-tryptophan, or captopril was given to spontaneously hypertensive rats (n = 60) over 14 weeks. Two further groups, receiving either no supplement (Placebo) or intact whey protein, served as controls. Systolic blood pressure age-dependently increased in the Placebo group, whereas the blood pressure rise was effectively blunted by isoleucine-tryptophan, whey protein hydrolysate and captopril (-42 ± 3, -38 ± 5, -55 ± 4 mm Hg vs. Placebo). At study end, myocardial mass was lower in isoleucine-tryptophan and captopril groups but only partially in the hydrolysate group. Coronary flow reserve (1 μm adenosine) was improved in isoleucine-tryptophan and captopril groups. Plasma ACE activity was significantly decreased in isoleucine-tryptophan, hydrolysate and captopril groups, but in aortic tissue only after isoleucine-tryptophan or captopril treatment. This was associated with lowered expression and activity of matrix metalloproteinase-2. Following isoleucine-tryptophan and captopril treatments, gene expression of renin was significantly increased indicating an active feedback within renin-angiotensin system. Whey protein hydrolysate and isoleucine-tryptophan powerfully inhibit plasma ACE resulting in antihypertensive effects. Moreover, isoleucine-tryptophan blunts tissue ACE activity, reduces matrix metalloproteinase-2 activity and improves coronary flow reserve. Thus, whey protein hydrolysate and particularly isoleucine-tryptophan may serve as innovative food additives with the goal of attenuating

Mitigation of Late Renal and Pulmonary Injury After Hematopoietic Stem Cell Transplantation

International Nuclear Information System (INIS)

Cohen, Eric P.; Bedi, Manpreet; Irving, Amy A.; Jacobs, Elizabeth; Tomic, Rade; Klein, John; Lawton, Colleen A.; Moulder, John E.

2012-01-01

Purpose: To update the results of a clinical trial that assessed whether the angiotensin-converting enzyme inhibitor captopril was effective in mitigating chronic renal failure and pulmonary-related mortality in subjects undergoing total body irradiation (TBI) in preparation for hematopoietic stem cell transplantation (HSCT). Methods and Materials: Updated records of the 55 subjects who were enrolled in this randomized controlled trial were analyzed. Twenty-eight patients received captopril, and 27 patients received placebo. Definitions of TBI-HSCT-related chronic renal failure (and relapse) were the same as those in the 2007 analysis. Pulmonary-related mortality was based on clinical or autopsy findings of pulmonary failure or infection as the primary cause of death. Follow-up data for overall and pulmonary-related mortality were supplemented by use of the National Death Index. Results: The risk of TBI-HSCT-related chronic renal failure was lower in the captopril group (11% at 4 years) than in the placebo group (17% at 4 years), but this was not statistically significant (p > 0.2). Analysis of mortality was greatly extended by use of the National Death Index, and no patients were lost to follow-up for reasons other than death prior to 67 months. Patient survival was higher in the captopril group than in the placebo group, but this was not statistically significant (p > 0.2). The improvement in survival was influenced more by a decrease in pulmonary mortality (11% risk at 4 years in the captopril group vs. 26% in the placebo group, p = 0.15) than by a decrease in chronic renal failure. There was no adverse effect on relapse risk (p = 0.4). Conclusions: Captopril therapy produces no detectable adverse effects when given after TBI. Captopril therapy reduces overall and pulmonary-related mortality after radiation-based HSCT, and there is a trend toward mitigation of chronic renal failure.

The use of experimental design in the development of an HPLC-ECD method for the analysis of captopril.

Science.gov (United States)

Khamanga, Sandile M; Walker, Roderick B

2011-01-15

An accurate, sensitive and specific high performance liquid chromatography-electrochemical detection (HPLC-ECD) method that was developed and validated for captopril (CPT) is presented. Separation was achieved using a Phenomenex(®) Luna 5 μm (C(18)) column and a mobile phase comprised of phosphate buffer (adjusted to pH 3.0): acetonitrile in a ratio of 70:30 (v/v). Detection was accomplished using a full scan multi channel ESA Coulometric detector in the "oxidative-screen" mode with the upstream electrode (E(1)) set at +600 mV and the downstream (analytical) electrode (E(2)) set at +950 mV, while the potential of the guard cell was maintained at +1050 mV. The detector gain was set at 300. Experimental design using central composite design (CCD) was used to facilitate method development. Mobile phase pH, molarity and concentration of acetonitrile (ACN) were considered the critical factors to be studied to establish the retention time of CPT and cyclizine (CYC) that was used as the internal standard. Twenty experiments including centre points were undertaken and a quadratic model was derived for the retention time for CPT using the experimental data. The method was validated for linearity, accuracy, precision, limits of quantitation and detection, as per the ICH guidelines. The system was found to produce sharp and well-resolved peaks for CPT and CYC with retention times of 3.08 and 7.56 min, respectively. Linear regression analysis for the calibration curve showed a good linear relationship with a regression coefficient of 0.978 in the concentration range of 2-70 μg/mL. The linear regression equation was y=0.0131x+0.0275. The limits of detection (LOQ) and quantitation (LOD) were found to be 2.27 and 0.6 μg/mL, respectively. The method was used to analyze CPT in tablets. The wide range for linearity, accuracy, sensitivity, short retention time and composition of the mobile phase indicated that this method is better for the quantification of CPT than the

Renovascular hypertension due to insufficient collateral flow in segmental artery occulusion

International Nuclear Information System (INIS)

Park, Y. H.; Lee, S. Y.; Kim, S. H.; Sohn, H. S.; Chung, S. K.

2001-01-01

We report a case in which a 33-year-old woman with renovascular hypertension due to insufficient collateral flow in segmental renal artery occlusion demonstrated abnormality on captopril renal scintigram. Baseline renal scintigram with DTPA showed normal perfusion and excretion in left kidney and captopril renal scintigram with DTPA showed a focal area of decreased perfusion and delayed clearance in lower half of left kidney, suggesting segmental renal artery stenosis. Selective left renal arteriography showed complete obstruction in proximal portion of anterior segmental artery with multiple small collateral vessels from posterior segmental artery and capsular artery and delayed opacification in lower half of left kidney. These findings are suggestive of segmental hypoperfusion due to insufficient collateral blood flow resulting to positive captopril response. Patient's blood pressure have been controlled well with ACE (angiotensin converting enzyme) inhibitor and calcium channel blocker for 2 year. Follow-up baseline renal scintigram with MAG3 showed normal perfusion and excretion in left kidney and captopril renal scintigram with MAG3 showed a focal area of decreased perfusion and delayed clearance in lower lateral portion of left kidney, which was smaller size than that of previous renal scintigram. And captopril renal scintigram with DMSA demonstrated a small area of decreased DMSA uptake on this lesion compared to baseline DMSA scintigram

L-arginine fails to prevent ventricular remodeling and heart failure in the spontaneously hypertensive rat.

Science.gov (United States)

Brooks, Wesley W; Conrad, Chester H; Robinson, Kathleen G; Colucci, Wilson S; Bing, Oscar H L

2009-02-01

The effects of long-term oral administration of L-arginine, a substrate for nitric oxide (NO) production, on left ventricular (LV) remodeling, myocardial function and the prevention of heart failure (HF) was compared to the angiotensin-converting enzyme (ACE) inhibitor captopril in a rat model of hypertensive HF (aged spontaneously hypertensive rat (SHR)). SHRs and age-matched normotensive Wistar-Kyoto (WKY) rats were assigned to either no treatment, treatment with L-arginine (7.5 g/l in drinking water) or captopril (1 g/l in drinking water) beginning at 14 months of age, a time when SHRs exhibit stable compensated hypertrophy with no hemodynamic impairment; animals were studied at 23 months of age or at the time of HF. In untreated SHR, relative to WKY, there was significant LV hypertrophy, myocardial fibrosis, and isolated LV muscle performance and response to isoproterenol (ISO) were depressed; and, 7 of 10 SHRs developed HF. Captopril administration to six SHRs attenuated hypertrophy and prevented impaired inotropic responsiveness to ISO, contractile dysfunction, fibrosis, increased passive stiffness, and HF. In contrast, L-arginine administration to SHR increased LV hypertrophy and myocardial fibrosis while cardiac performance was depressed; and 7 of 9 SHRs developed HF. In WKY, L-arginine treatment but not captopril resulted in increased LV weight and the contractile response to ISO was blunted. Neither L-arginine nor captopril treatment of WKY changed fibrosis and HF did not occur. These data demonstrate that in contrast to captopril, long-term treatment with L-arginine exacerbates age-related cardiac hypertrophy, fibrosis, and did not prevent contractile dysfunction or the development of HF in aging SHR.

Evaluation of the effect of Spathodea campanulata flower bud ...

African Journals Online (AJOL)

Lenses were incubated in artificial aqueous humor (Normal control) with simultaneous incubation in 30 mM galactose (Untreated cataract). Co-incubation with captopril (Captopril treated cataract); 0.1 mg/ml of the exudate (Exudate treated cataract - Low dose) and 0.2 mg/ml of exudate (Exudate treated cataract- High dose) ...

Design and Development of a Proniosomal Transdermal Drug ...

African Journals Online (AJOL)

Purpose: The aim of the study was to develop a proniosomal carrier system for captopril for the treatment of hypertension that is capable of efficiently delivering entrapped drug over an extended period of time. Method: The potential of proniosomes as a transdermal drug delivery system for captopril was investigated by ...

Efeito de drogas utilizadas no tratamento de hipertensão arterial sistêmica sobre a pressão intra-ocular: estudo experimental no cão

Directory of Open Access Journals (Sweden)

Hashimoto Mitsuo

2002-01-01

Full Text Available Objetivo: Estudar os efeitos de duas drogas utilizadas no tratamento de hipertensão arterial sistêmica (captopril e propranolol sobre a pressão intra-ocular (PIO e pressão de perfusão (PP em cães anestesiados. Métodos: Foram estudados 24 cães, divididos em 3 grupos de 8. No primeiro grupo (GI, foi administrado captopril (um inibidor da enzima conversora de angiotensina na dose de 1,5 mg/kg por via endovenosa. No segundo grupo (GII, foi administrado propranolol (um beta-bloqueador na dose de 1,5 mg/kg por via endovenosa. O terceiro grupo (GIII foi o grupo controle. A PIO e a pressão arterial média (PAm foram medidas por manometria. A pressão de perfusão (PP foi calculada pela diferença entre a PAm e a PIO. A freqüência cardíaca (FC foi monitorada com oxímetro de pulso. Os parâmetros foram estudados em 6 momentos (0, 10, 30, 60, 90 e 120 minutos. Resultados: Houve redução estatisticamente significativa da PIO (p<0,05 nos grupos em que foram administrados captopril e propranolol, sem diferença entre as drogas. Com captopril, houve redução da PAm e da PP aos 10 e 30 minutos. Com propranolol, não houve redução da PAm ou da PP. Conclusão: Houve redução da PIO com uso do captopril e também do propranolol. Entretanto, a redução acentuada da PAm e da PP causadas pelo captopril, podem ser indesejáveis para a irrigação do nervo óptico.

Lupus induced by medicaments

International Nuclear Information System (INIS)

Canas D, Carlos Alberto; Perafan B, Pablo Eduardo

2001-01-01

We describe a 55 years old female patient who consulted by fever syndrome, artralgias and the presence of high tittles positives antinuclear antibodies. She had arterial hypertension in treatment with captopril. We suspected the clinical diagnoses of drug-induced lupus; the withdraw of captopril was associated with the remission of the clinical and laboratory manifestations

Angiotensin-(1-7) augments endothelium-dependent relaxations of porcine coronary arteries to bradykinin by inhibiting angiotensin-converting enzyme 1.

Science.gov (United States)

Raffai, Gábor; Khang, Gilson; Vanhoutte, Paul M

2014-05-01

Angiotensin-converting enzyme 2 (ACE2) converts angiotensin II to angiotensin-(1-7) that activates Mas receptors, inhibits ACE1, and modulates bradykinin receptor sensitivity. This in vitro study compared the direct and indirect effects of angiotensin-(1-7), the ACE1 inhibitor captopril, and diminazene aceturate (DIZE) an alleged ACE2 activator in rings of porcine coronary arteries, by measuring changes of isometric tension. Angiotensin-(1-7), captopril, and DIZE did not cause significant changes in tension before or after desensitization of bradykinin receptors in preparations contracted with U46619. Bradykinin caused concentration-dependent and endothelium-dependent relaxations that were not affected by DIZE but were potentiated to a similar extent by angiotensin-(1-7) and captopril, given alone or in combination. Bradykinin responses potentiated by angiotensin-(1-7) and captopril were not affected by the BK1 antagonist SSR240612 and remained augmented in the presence of either N-nitro-L-arginine methyl ester hydrochloride plus indomethacin or TRAM-34 plus UCL-1684. ACE2 was identified in the coronary endothelium by immunofluorescence, but its basal activity was not influenced by DIZE. These results suggest that in coronary arteries, angiotensin-(1-7) and captopril both improves NO bioavailability and enhances endothelium-dependent hyperpolarization to bradykinin solely by ACE1 inhibition. Endothelial ACE2 activity cannot be increased by DIZE to produce local adequate amounts of angiotensin-(1-7) to influence vascular tone.

Captopril 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 ...

1,4-Anthraquinone: A new useful pre-column reagent for the determination of N-acetylcysteine and captopril in pharmaceuticals by high performance liquid chromatography.

Science.gov (United States)

Gatti, Rita; Morigi, Rita

2017-09-05

1,4-Anthraquinone (ANQ) is proposed as a novel pre-column reagent for high performance liquid chromatography (HPLC) determination of N-acetylcysteine (NAC) and captopril (CAP) in pharmaceutical formulations. The derivatization reactions were carried out at room temperature: NAC at pH 8 for 1min, while CAP at pH 7.5 for 20min. Both reactions reached completeness at a reagent to thiol molar ratio of about 2.5. The synthesised derivatives were characterized by 1 H NMR and IR. The chromatographic separations were performed on a C 18 Phenomenex Synergi Fusion 4μm (250mm×4.6mm I.D.) stainless steel column with detection at λ=300nm. The mobile phase consisted of methanol/triethylammonium (TEA) phosphate buffer (pH 3; 0.05mol/L) 75:25 (v/v) at a flow-rate of 0.4mL/min for NAC and 88:12 (v/v), at a flow-rate of 0.6mL/min for CAP. The validation parameters (linearity, sensitivity, accuracy, precision, specificity and stability) were highly satisfactory. Linear response was observed (determination coefficient ≥0.9996). Detection limits were about 8 and 18ng/mL for NAC and CAP, respectively. Intra-day precision (relative standard deviation, R.S.D.) was ≤1.58%, for thiol to internal standard (IS) peak area ratio and ≤0.33%, for thiol and IS retention times (t R ), without significant differences between intra- and inter-day data. Thiol recovery studies were satisfactory (99.50%) with R.S.D. ≤0.56%. The results highlight the high sensitivity of the method and the remarkable reactivity and selectivity of the reagent towards the thiol function. The developed method is suitable for the quality control of both thiols in commercial products. The method can be applied in any analytical laboratory not requiring a sophisticated instrumentation. Copyright © 2017 Elsevier B.V. All rights reserved.

Targeting the Renin–Angiotensin System Combined With an Antioxidant Is Highly Effective in Mitigating Radiation-Induced Lung Damage

Energy Technology Data Exchange (ETDEWEB)

Mahmood, Javed [Ontario Cancer Institute and the Campbell Family Institute for Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Radiation Medicine Program, STTARR Innovation Centre, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Jelveh, Salomeh [Radiation Medicine Program, STTARR Innovation Centre, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Zaidi, Asif [Ontario Cancer Institute and the Campbell Family Institute for Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Doctrow, Susan R. [Pulmonary Center, Department of Medicine, Boston University, Boston, Massachusetts (United States); Medhora, Meetha [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Hill, Richard P., E-mail: hill@uhnres.utoronto.ca [Ontario Cancer Institute and the Campbell Family Institute for Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Departments of Medical Biophysics and Radiation Oncology, University of Toronto, Toronto, Ontario (Canada)

2014-07-15

Purpose: To investigate the outcome of suppression of the renin angiotensin system using captopril combined with an antioxidant (Eukarion [EUK]-207) for mitigation of radiation-induced lung damage in rats. Methods and Materials: The thoracic cavity of female Sprague-Dawley rats was irradiated with a single dose of 11 Gy. Treatment with captopril at a dose of 40 mg/kg/d in drinking water and EUK-207 given by subcutaneous injection (8 mg/kg daily) was started 1 week after irradiation (PI) and continuing until 14 weeks PI. Breathing rate was monitored until the rats were killed at 32 weeks PI, when lung fibrosis was assessed by lung hydroxyproline content. Lung levels of the cytokine transforming growth factor-β1 and macrophage activation were analyzed by immunohistochemistry. Oxidative DNA damage was assessed by 8-hydroxy-2-deoxyguanosine levels, and lipid peroxidation was measured by a T-BARS assay. Results: The increase in breathing rate in the irradiated rats was significantly reduced by the drug treatments. The drug treatment also significantly decreased the hydroxyproline content, 8-hydroxy-2-deoxyguanosine and malondialdehyde levels, and levels of activated macrophages and the cytokine transforming growth factor-β1 at 32 weeks. Almost complete mitigation of these radiation effects was observed by combining captopril and EUK-207. Conclusion: Captopril and EUK-207 can provide mitigation of radiation-induced lung damage out to at least 32 weeks PI after treatment given 1-14 weeks PI. Overall the combination of captopril and EUK-207 was more effective than the individual drugs used alone.

Changes in the renin angiotensin system during the development of colorectal cancer liver metastases

International Nuclear Information System (INIS)

Neo, Jaclyn H; Ager, Eleanor I; Angus, Peter W; Zhu, Jin; Herath, Chandana B; Christophi, Christopher

2010-01-01

Blockade of the renin angiotensin system (RAS) via angiotensin I converting enzyme (ACE) inhibition reduces growth of colorectal cancer (CRC) liver metastases in a mouse model. In this work we defined the expression of the various components of the RAS in both tumor and liver during the progression of this disease. Immunohistochemistry and quantitative RT-PCR was used to examine RAS expression in a mouse CRC liver metastases model. CRC metastases and liver tissue was assessed separately at key stages of CRC liver metastases development in untreated (control) mice and in mice treated with the ACE inhibitor captopril (750 mg/kg/day). Non-tumor induced (sham) mice indicated the effect of tumors on normal liver RAS. The statistical significance of multiple comparisons was determined using one-way analysis of variance followed by Bonferroni adjustment with SAS/STAT software. Reduced volume of CRC liver metastases with captopril treatment was evident. Local RAS of CRC metastases differed from the surrounding liver, with lower angiotensin II type 1 receptor (AT1R) expression but increased ANG-(1-7) receptor (MasR) compared to the liver. The AT1R localised to cancer and stromal infiltrating cells, while other RAS receptors were detected in cancer cells only. Tumor induction led to an initial increase in AT1R and ACE expression while captopril treatment significantly increased ACE expression in the final stages of tumor growth. Conversely, captopril treatment decreased expression of AT1R and angiotensinogen. These results demonstrate significant changes in RAS expression in the tumor-bearing captopril treated liver and in CRC metastases. The data suggests the existence of a tumor-specific RAS that can be independently targeted by RAS blockade

Weak interactions in clobazam–lactose mixtures examined by differential scanning calorimetry: Comparison with the captopril–lactose system

International Nuclear Information System (INIS)

Toscani, S.; Cornevin, L.; Burgot, G.

2012-01-01

Highlights: ► Thermodynamic and kinetic parameters of weak interactions in binary systems by DSC. ► Energy-barrier decrease for lactose dehydration induced by clobazam. ► Recrystallisation of metastable liquid clobazam induced by anhydrous alpha lactose. ► Decrease of lactose dehydration temperature in binary mixtures with captopril. ► Increase of lactose dehydration enthalpy in binary mixtures with captopril. - Abstract: The thermal behaviour of binary mixtures of two drugs (clobazam and captopril, respectively) and a pharmaceutical excipient (lactose monohydrate) was measured with differential scanning calorimetry to determine thermodynamic and kinetic parameters (dehydration and melting enthalpies and dehydration and glass-transition activation energies) which might be affected by intermolecular interactions. A kinetic study showed that lactose dehydration is not a single-step conversion and that clobazam contributed to reduce the energy barrier for the bulk dehydration of the excipient. On the other hand, the physical interactions between metastable liquid clobazam and crystalline anhydrous α-lactose obtained from monohydrate dehydration gave rise to the recrystallisation of clobazam. In the captopril–lactose system, the liquid captopril influenced the lactose dehydration: a sharp increase of the dehydration enthalpy and a concurrent reduction of the dehydration temperature were observed. Finally, it turned out that solid-phase transitions were enhanced by the contact with a liquid phase.

Ativação da enzima conversora de angiotensina no coração após infarto do miocárdio e suas repercussões no remodelamento ventricular

Directory of Open Access Journals (Sweden)

Mill José Geraldo

1997-01-01

Full Text Available OBJETIVO: Determinar as alterações de atividade da enzima conversora de angiotensina (ECA no coração com infarto do miocárdio (IM e comparar os efeitos do captopril e losartan em parâmetros morfológicos e funcionais de ratos com IM. MÉTODOS: O IM foi produzido em ratos Wistar por ligadura de ramos da artéria coronária esquerda. Os controles (Con foram submetidos a uma cirurgia fictícia. Animais com IM e Con foram tratados com captopril (30mg/kg/dia ou losartan (15mg/kg/dia e estudados 30 dias após, determinando-se a atividade da ECA nos ventrículos direito (VD e esquerdo (VE, as alterações hemodinâmicas e as concentrações de hidroxiprolina (OH-Pro e proteína total no VD e VE. RESULTADOS: A atividade da ECA aumentou no VD (+25% e VE (+70% após IM. A maior atividade foi observada na cicatriz fibrótica, onde atingiu cerca de 4,5 vezes a do músculo do VE que sobreviveu ao IM (420±68 vs 94±8nmoles/g/min; P<0,01. O IM determinou aumento da pressão diastólica final e hipertrofia do VD e VE. Captopril e losartan foram igualmente eficazes em atenuar a hipertrofia e o aumento da pré-carga. O captopril também atenuou o aumento de OH-Pro no VD e VE após IM. O IM reduziu a concentração de proteína principalmente no músculo de VE, efeito esse acentuado pelo captopril. CONCLUSÃO: A grande atividade da ECA na cicatriz deve produzir altas concentrações de angiotensina II (AII no sangue que drena da cicatriz. Os efeitos dos inibidores da ECA seriam decorrentes, principalmente, da redução de geração local de AII, e não de aumento de cininas, uma vez que captopril e losartan exerceram efeitos similares no remodelamento pós-infarto.

Reduction of regurgitation in aortic insufficiency by inhibition of the renin/angiotensin conversion enzyme

Energy Technology Data Exchange (ETDEWEB)

Reske, S.N.; Heck, I.; Mattern, H.

1984-10-01

The effect of captopril-mediated afterload reduction on regurgitation was investigated in 10 patients with aortic insufficiency. Regurgitation was quantitated by the regurgitation fraction and the relation of regurgitant volume to end-diastolic volume, which were derived from gated radionuclide ventriculography. 19 patients with coronary artery disease and no evidence of valvular heart disease served as controls. In patients with coronary artery disease no significant reguration was found. In patients with aortic regurgitation the blood concentration of angiotensin I increased whereas that of angiotensin II decreased significantly after captopril-medication; thus, the conversion of angiotensin I to II was reduced to about 50% of the control value. Whereas blood pressure and heart rate did not change significantly, the regurgitation fraction and the normalized regurgitant volume were significantly reduced. The ejection fraction remained essentially unchanged. These findings suggest a favorable influence of captopril-induced afterload reduction on hemodynamics in aortic regurgitation.

Relationship between insulin resistance and plasma endothelin in hypertension patients

International Nuclear Information System (INIS)

Duan Yongqiang; Wang Zuobing; Yu Hui; Cao Wei; Wang Jing; Li Xiaoqin

2011-01-01

To explore the relationship between plasma endothelin and hypertension insulin resistance, and the improvement of insulin resistance in hypertension patients treated with captopril and l-amlodipine, 25 patients with primary hypertension and impaired glucose tolerance were selected and treated by captopril and l-amlodipine. Systolic pressure, diastolic pressure, fasting blood glucose, insulin and insulin antibody were measured before and after treatment and compared with healthy controls. The results showed that the plasma ET-1 level in hypertension group was significantly higher than that of healthy controls (P<0.01), and he plasma ET-1 level was positively correlated with FPG, FINS, Anti-INS, HOMA-IR. The systolic pressure, diastolic pressure, fasting blood glucose, insulin, insulin antibody and insulin resistance index in hypertension patients were decreased significantly after treatment (P<0.05). There is a good correlation between endothelin and insulin resistance index in hypertension patients. Captopril and l-amlodipine had obvious improvement effect on insulin resistance in hypertension patients. (authors)

A bradykinin-potentiating peptide (BPP-10c) from Bothrops jararaca induces changes in seminiferous tubules

Science.gov (United States)

2013-01-01

Background The testis-specific isoform of angiotensin-converting enzyme (tACE) is exclusively expressed in germ cells during spermatogenesis. Although the exact role of tACE in male fertility is unknown, it clearly plays a critical function in spermatogenesis. The dipeptidase domain of tACE is identical to the C-terminal catalytic domain of somatic ACE (sACE). Bradykinin potentiating peptides (BPPs) from snake venoms are the first natural sACE inhibitors described and their structure–activity relationship studies were the basis for the development of antihypertensive drugs such as captopril. In recent years, it has been showed that a number of BPPs – including BPP-10c – are able to distinguish between the N- and C-active sites of sACE, what is not applicable to captopril. Considering the similarity between tACE and sACE (and since BPPs are able to distinguish between the two active sites of sACE), the effects of the BPP-10c and captopril on the structure and function of the seminiferous epithelium were characterized in the present study. BPP-10c and captopril were administered in male Swiss mice by intraperitoneal injection (4.7 μmol/kg for 15 days) and histological sections of testes were analyzed. Classification of seminiferous tubules and stage analysis were carried out for quantitative evaluation of germ cells of the seminiferous epithelium. The blood-testis barrier (BTB) permeability and distribution of claudin-1 in the seminiferous epithelium were analyzed by hypertonic fixative method and immunohistochemical analyses of testes, respectively. Results The morphology of seminiferous tubules from animals treated with BPP-10c showed an intense disruption of the epithelium, presence of atypical multinucleated cells in the lumen and degenerated germ cells in the adluminal compartment. BPP-10c led to an increase in the number of round spermatids and total support capacity of Sertoli cell in stages I, V, VII/VIII of the seminiferous epithelium cycle, without

A bradykinin-potentiating peptide (BPP-10c) from Bothrops jararaca induces changes in seminiferous tubules.

Science.gov (United States)

Gilio, Joyce M; Portaro, Fernanda Cv; Borella, Maria I; Lameu, Claudiana; Camargo, Antonio Cm; Alberto-Silva, Carlos

2013-11-06

The testis-specific isoform of angiotensin-converting enzyme (tACE) is exclusively expressed in germ cells during spermatogenesis. Although the exact role of tACE in male fertility is unknown, it clearly plays a critical function in spermatogenesis. The dipeptidase domain of tACE is identical to the C-terminal catalytic domain of somatic ACE (sACE). Bradykinin potentiating peptides (BPPs) from snake venoms are the first natural sACE inhibitors described and their structure-activity relationship studies were the basis for the development of antihypertensive drugs such as captopril. In recent years, it has been showed that a number of BPPs - including BPP-10c - are able to distinguish between the N- and C-active sites of sACE, what is not applicable to captopril. Considering the similarity between tACE and sACE (and since BPPs are able to distinguish between the two active sites of sACE), the effects of the BPP-10c and captopril on the structure and function of the seminiferous epithelium were characterized in the present study. BPP-10c and captopril were administered in male Swiss mice by intraperitoneal injection (4.7 μmol/kg for 15 days) and histological sections of testes were analyzed. Classification of seminiferous tubules and stage analysis were carried out for quantitative evaluation of germ cells of the seminiferous epithelium. The blood-testis barrier (BTB) permeability and distribution of claudin-1 in the seminiferous epithelium were analyzed by hypertonic fixative method and immunohistochemical analyses of testes, respectively. The morphology of seminiferous tubules from animals treated with BPP-10c showed an intense disruption of the epithelium, presence of atypical multinucleated cells in the lumen and degenerated germ cells in the adluminal compartment. BPP-10c led to an increase in the number of round spermatids and total support capacity of Sertoli cell in stages I, V, VII/VIII of the seminiferous epithelium cycle, without affecting BTB permeability

Tissue distribution in mice of BPP 10c, a potent proline-rich anti-hypertensive peptide of Bothrops jararaca.

Science.gov (United States)

Silva, Carlos A; Portaro, Fernanda C V; Fernandes, Beatriz L; Ianzer, Danielle A; Guerreiro, Juliano R; Gomes, Claudiana L; Konno, Katsuhiro; Serrano, Solange M T; Nascimento, Nanci; Camargo, Antonio C M

2008-03-15

The snake venom proline-rich peptide BPP 10c is an active somatic angiotensin-converting enzyme (sACE) inhibitors. Recently we demonstrated that the anti-hypertensive effect of BPP 10c is not related to the inhibition of sACE alone, thus suggesting that this enzyme is not its only target for blood pressure reduction. In the present work, a biodistribution study in Swiss mice of [(125)I]-BPP 10c in the absence or in the presence of a saturating concentration of captopril, a selective active-site inhibitor of sACE, demonstrated that: (1) [(125)I]-BPP 10c was present in several organs and the renal absorption was significantly high; (2) [(125)I]-BPP 10c showed a clear preference for the kidney, maintaining a high concentration in this organ in the presence of captopril for at least 3h; (3) The residual amount of [(125)I]-BPP 10c in the kidney of animals simultaneously treated with captopril suggest that the peptide can interact with other targets different from sACE in this organ. We also showed that Cy3-labeled BPP 10c was internalized by human embryonic kidney cells (HEK-293T). Taken together, these results suggest that sACE inhibition by captopril affects the tissue distribution of [(125)I]-BPP 10c and that the anti-hypertensive effects of BPP 10c are not only dependent on sACE inhibition.

Renal dynamic scintigraphy with captropil in systemic arterial hypertension diagnosis

International Nuclear Information System (INIS)

Cervo, Marco Antonio Cadorna; Amarante Junior, Jose Luiz de Medeiros; Souza, Ricardo Alberto Manhaes; Evangelista, Maria Gardenia

1995-01-01

Forty one patients, 15 male and 16 female presenting systemic arterial hypertension were submitted to Basal RDC and after being simulated by Captopril; the radiotracer used was 99 mTc-DTPA (dietileno triamino pentacetic acid-99 Tc-technetium). From the 41 patients studied, 13 had the GFR (Glomerular filtration rate) Captopril when compared to Basal RDC radioactive, 11 of them were confirmed as having vascular renal disease by Renal Artiography and two of them were false (one case renal litiase and the other chronic pyelonephritis). Two more false negative cases have occurred in the RDC and three patients refused to be submitted to a Renal Arteriography. In the cases which the Total Glomerular Filtration Rate was reduced, there was an agreement of 89,5% between the RDC and the Renal Arteriography. No alterations have been observed in the Renal Arteriography on the remaining 23 patients and in the RDC after Captopril there was normal increase in the Glomerular Filtration Rate when compared to the Basal RDC. The method has showed sensitivity of 84% and specificity of 92%. We can conclude that the RDC with Captopril test is not an invasive method, it has good sensitivity and specificity and it can be indicated as a beginning test to select patients when you intend to detect vascular renal disease; nevertheless the RDC will never be used as a final test of vascular lesion. (author)

Inhibitors of bacterial N-succinyl-L,L-diaminopimelic acid desuccinylase (DapE) and demonstration of in vitro antimicrobial activity.

Science.gov (United States)

Gillner, Danuta; Armoush, Nicola; Holz, Richard C; Becker, Daniel P

2009-11-15

The dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase (DapE) is a critical bacterial enzyme for the construction of the bacterial cell wall. A screen biased toward compounds containing zinc-binding groups (ZBG's) including thiols, carboxylic acids, boronic acids, phosphonates and hydroxamates has delivered a number of micromolar inhibitors of DapE from Haemophilus influenzae, including the low micromolar inhibitor L-captopril (IC(50)=3.3 microM, K(i)=1.8 microM). In vitro antimicrobial activity was demonstrated for L-captopril against Escherichia coli.

Protective Effects of Water Extract of Morus Nigra L. on 6-Hydroxydopamine Induced Parkinson’s Disease in Male Rats

Directory of Open Access Journals (Sweden)

Seyed Ali Ziai

2018-01-01

Full Text Available Background: Parkinson’s disease (PD is a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Although the etiology of PD is unknown, but major biochemical processes such as oxidative stress is largely described. Angiotensin II activates NADPH depending oxidases and produce superoxides formation. Morus nigra L. extract is an Angiotensin Converting Enzyme (ACE inhibitor and tested for anti-Parkinsonism effects by biochemical and behavioral evaluations.Materials and Methods: In total 48 Male Wistar rats weighting 200-250 g were divided into 4 groups: (1 Sham (normal saline was injected in the left SNC, (2 Neurotoxin (injection of 6-hydroxydopamine into left SNC, (3 Morus nigra L. aqueous extract and (4 captopril. Morus nigra (10 mg/kg and captopril (5 mg/kg were daily-injected i.p. from 6 days before neurotoxin injection, until one day after 6-hydroxydopamine injection. Muscle stiffness and apomorphine test were assessed in 6 rats of any groups after two weeks. Protein oxidation, lipid peroxidation and ACE activity were assessed in brains of 6 rats of each group after 24 hours.Results: Rotation test with apomorphine, Rigidity with Murprogo’s test, and lipid peroxidation in sham, captopril and Morus nigra groups were significantly lower than neurotoxin group. Protein oxidation in Morus nigra group was significantly lower than neurotoxin group. Brain ACE activity in neurotoxin, captopril and Morus nigra groups were inhibited.Conclusion: Morus nigra L. extract had protective effects on neuronal oxidation and death and improved signs of PD possibly by ACE inhibition.

Combinational chelation therapy abrogates lead-induced neurodegeneration in rats

International Nuclear Information System (INIS)

Pachauri, Vidhu; Saxena, Geetu; Mehta, Ashish; Mishra, Deepshikha; Flora, Swaran J.S.

2009-01-01

Lead, a ubiquitous and potent neurotoxicant causes oxidative stress which leads to numerous neurobehavioral and physiological alterations. The ability of lead to bind sulfhydryl groups or compete with calcium could be one of the reasons for its debilitating effects. In the present study, we addressed: i) if chelation therapy could circumvent the altered oxidative stress and prevent neuronal apoptosis in chronic lead-intoxicated rats, ii) whether chelation therapy could reverse biochemical and behavioral changes, and iii) if mono or combinational therapy with captopril (an antioxidant) and thiol chelating agents (DMSA/MiADMSA) is more effective than individual thiol chelator in lead-exposed rats. Results indicated that lead caused a significant increase in reactive oxygen species, nitric oxide, and intracellular free calcium levels along with altered behavioral abnormalities in locomotor activity, exploratory behavior, learning, and memory that were supported by changes in neurotransmitter levels. A fall in membrane potential, release of cytochrome c, and DNA damage indicated mitochondrial-dependent apoptosis. Most of these alterations showed significant recovery following combined therapy with captopril with MiADMSA and to a smaller extend with captopril + DMSA over monotherapy with these chelators. It could be concluded from our present results that co-administration of a potent antioxidant (like captopril) might be a better treatment protocol than monotherapy to counter lead-induced oxidative stress. The major highlight of the work is an interesting experimental evidence of the efficacy of combinational therapy using an antioxidant with a thiol chelator in reversing neurological dystrophy caused due to chronic lead exposure in rats.

Hypertrophic response to hemodynamic overload: role of load vs. renin-angiotensin system activation

Science.gov (United States)

Koide, M.; Carabello, B. A.; Conrad, C. C.; Buckley, J. M.; DeFreyte, G.; Barnes, M.; Tomanek, R. J.; Wei, C. C.; Dell'Italia, L. J.; Cooper, G. 4th;

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.

Sol-gel encapsulation for controlled drug release and biosensing

Science.gov (United States)

Fang, Jonathan

The main focus of this dissertation is to investigate the use of sol-gel encapsulation of biomolecules for controlled drug release and biosensing. Controlled drug release has advantages over conventional therapies in that it maintains a constant, therapeutic drug level in the body for prolonged periods of time. The anti-hypertensive drug Captopril was encapsulated in sol-gel materials of various forms, such as silica xerogels and nanoparticles. The primary objective was to show that sol-gel silica materials are promising drug carriers for controlled release by releasing Captopril at a release rate that is within a therapeutic range. We were able to demonstrate desired release for over a week from Captopril-doped silica xerogels and overall release from Captopril-doped silica nanoparticles. As an aside, the antibiotic Vancomycin was also encapsulated in these porous silica nanoparticles and desired release was obtained for several days in-vitro. The second part of the dissertation focuses on immobilizing antibodies and proteins in sol-gel to detect various analytes, such as hormones and amino acids. Sol-gel competitive immunoassays on antibody-doped silica xerogels were used for hormone detection. Calibration for insulin and C-peptide in standard solutions was obtained in the nM range. In addition, NASA-Ames is also interested in developing a reagentless biosensor using bacterial periplasmic binding proteins (bPBPs) to detect specific biomarkers, such as amino acids and phosphate. These bPBPs were doubly labeled with two different fluorophores and encapsulated in silica xerogels. Ligand-binding experiments were performed on the bPBPs in solution and in sol-gel. Ligand-binding was monitored by fluorescence resonance energy transfer (FRET) between the two fluorophores on the bPBP. Titration data show that one bPBP has retained its ligand-binding properties in sol-gel.

Evidence for modulation of pericryptal sheath myofibroblasts in rat descending colon by Transforming Growth Factor β and Angiotensin II.

Directory of Open Access Journals (Sweden)

Pedley Kevin C

2002-02-01

Full Text Available Abstract Background Absorption of water and Na+ in descending colonic crypts is dependent on the barrier function of the surrounding myofibroblastic pericryptal sheath. Here the effects of high and low Na+ diets and exposure to whole body ionising radiation on the growth and activation of the descending colonic pericryptal myofibroblasts are evaluated. In addition the effect of a post-irradiation treatment with the angiotensin converting enzyme inhibitor Captopril was investigated. Methods The levels of Angiotensin II type 1 receptor (AT1, ACE, collagen type IV, transforming growth factor-β type 1 receptor (TGF-βR1, OB cadherin and α-smooth muscle actin in both descending colon and caecum were evaluated, using immunocytochemistry and confocal microscopy, in rats fed on high and low Na+ diets (LS. These parameters were also determined during 3 months post-irradiation with 8Gy from a 60Co source in the presence and absence of the angiotensin converting enzyme inhibitor, Captopril. Results Increases in AT1 receptor (135.6% ± 18.3, P Conclusions These results demonstrate an activation of descending colonic myofibroblasts to trophic stimuli, or irradiation, which can be attenuated by Captopril, indicative of local trophic control by angiotensin II and TGF-β release.

The contributions of adrenal hormones, hemodynamic factors, and the endotoxin-related stress reaction to stable prostaglandin analog-induced peripheral lymphopenia and neutrophilia.

Science.gov (United States)

Ulich, T R; Keys, M; Ni, R X; del Castillo, J; Dakay, E B

1988-01-01

Stable prostaglandin analogs are known to induce lymphopenia and neutrophilia in a dose-dependent fashion after subcutaneous injection in rats. The purpose of the present investigation is to determine whether the prostaglandin-induced changes in circulating leukocytes might be secondary to hypotension with the ensuing release of adrenal hormones. The adrenal medullary catecholamine epinephrine was found to induce neutrophilia in both intact and adrenalectomized rats, and the glucocorticosteroid analog dexamethasone induced a profound lymphopenia in rats as reported by previous investigators. A stable analog of PGF2 alpha (15-S-15-methyl PGF2 alpha; M-PGF2 alpha) at the dose of 1 mg/kg induced marked systemic hypotension 1 h after injection, with lymphopenia and neutrophilia 6 h after injection. The non-prostanoid hypotensive agent captopril, at a dose of 63 mg/kg, induced a hypotension of similar magnitude and kinetics to that induced by prostaglandin. Captopril also induced lymphopenia and neutrophilia at 6 h, although the neutrophilia was of lesser magnitude than that induced by prostaglandins. The prostaglandin-induced lymphopenia was found to be mediated, at least in part, by the hypotension-induced release of adrenal hormones, as evidenced by the abrogation of lymphopenia in prostaglandin-treated adrenalectomized rats. Captopril-treated adrenalectomized rats, however, did develop a significant lymphopenia, suggesting that hypotension can result in lymphopenia even in adrenalectomized rats. The M-PGF2 alpha-induced neutrophilia in adrenalectomized rats, by comparison to captopril-induced neutrophilia in adrenalectomized rats, was greater than the neutrophilia expected as the result of hypotension alone. Indeed, the M-PGF2 alpha-induced neutrophilia in adrenalectomized rats was greater than the captopril-induced neutrophilia in sham-adrenalectomized rats. Thus, a portion of the neutrophilia induced by M-PGF2 alpha in intact rats may be mediated through adrenal

application of new ferrocene derivative for electrocatalytic

African Journals Online (AJOL)

B. S. Chandravanshi

application of electrochemical impedance spectroscopy, differential pulse voltammetry ... The poor selectivity, slow kinetic of electrooxidation and very weak ..... cysteine and glutathione that have similar structure affect on the signal of captopril.

Smooth muscle LDL receptor-related protein-1 deletion induces aortic insufficiency and promotes vascular cardiomyopathy in mice.

Directory of Open Access Journals (Sweden)

Joshua E Basford

Full Text Available Valvular disease is common in patients with Marfan syndrome and can lead to cardiomyopathy. However, some patients develop cardiomyopathy in the absence of hemodynamically significant valve dysfunction, suggesting alternative mechanisms of disease progression. Disruption of LDL receptor-related protein-1 (Lrp1 in smooth muscle cells has been shown to cause vascular pathologies similar to Marfan syndrome, with activation of smooth muscle cells, vascular dysfunction and aortic aneurysms. This study used echocardiography and blood pressure monitoring in mouse models to determine whether inactivation of Lrp1 in vascular smooth muscle leads to cardiomyopathy, and if so, whether the mechanism is a consequence of valvular disease. Hemodynamic changes during treatment with captopril were also assessed. Dilation of aortic roots was observed in young Lrp1-knockout mice and progressed as they aged, whereas no significant aortic dilation was detected in wild type littermates. Diastolic blood pressure was lower and pulse pressure higher in Lrp1-knockout mice, which was normalized by treatment with captopril. Aortic dilation was followed by development of aortic insufficiency and subsequent dilated cardiomyopathy due to valvular disease. Thus, smooth muscle cell Lrp1 deficiency results in aortic dilation and insufficiency that causes secondary cardiomyopathy that can be improved by captopril. These findings provide novel insights into mechanisms of cardiomyopathy associated with vascular activation and offer a new model of valvular cardiomyopathy.

Hypotensive and Angiotensin-Converting Enzyme Inhibitory Activities of Eisenia fetida Extract in Spontaneously Hypertensive Rats

Directory of Open Access Journals (Sweden)

Shumei Mao

2015-01-01

Full Text Available Objectives. This study aimed to investigate the antihypertensive effects of an Eisenia fetida extract (EFE and its possible mechanisms in spontaneously hypertensive rats (SHR rats. Methods. Sixteen-week-old SHR rats and Wistar-Kyoto rats (WKY rats were used in this study. Rats were, respectively, given EFE (EFE group, captopril (captopril group, or phosphate-buffered saline (PBS (normal control group and SHR group for 4 weeks. ACE inhibitory activity of EFE in vitro was determined. The systolic blood pressure (SBP and diastolic blood pressure (DBP were measured using a Rat Tail-Cuff Blood Pressure System. Levels of angiotensin II (Ang II, aldosterone (Ald, and 6-keto-prostaglandin F1 alpha (6-keto-PGF1α in plasma were determined by radioimmunoassay, and serum nitric oxide (NO concentration was measured by Griess reagent systems. Results. EFE had marked ACE inhibitory activity in vitro (IC50 = 2.5 mg/mL. After the 4-week drug management, SHR rats in EFE group and in captopril group had lower SBP and DBP, lower levels of Ang II and Ald, and higher levels of 6-keto-PGF1α and NO than the SHR rats in SHR group. Conclusion. These results indicate that EFE has hypotensive effects in SHR rats and its effects might be associated with its ACE inhibitory activity.

Frequency, Levels and Predictors of Potential Drug-Drug ...

African Journals Online (AJOL)

major or moderate interactions included rifampin + pyrazinamide (14 cases), phenobarbital + diazepam (14), dexamethasone + rifampin (8), amikacin + furosemide (7), furosemide + captopril (7), dexamethasone + phenobarbital (6), phenobarbital + divalproex sodium (6), isoniazid + rifampin (5) amikacin + ibuprofen (5), ...

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 ❯ ...

Renovascular Hypertension: Clinical Features, Differential Diagnoses and Basic Principles of Treatment

Directory of Open Access Journals (Sweden)

Petrovic Dejan

2016-09-01

Full Text Available Renovascular hypertension is caused by renal artery stenosis. Its prevalence in populations of hypertensive patients is 1-8%, and in populations of patients with resistant hypertension, it is up to 20%. The two main causes of stenosis are atherosclerosis and fibromuscular dysplasia of the renal artery. The main clinical consequences of renal artery stenosis include renovascular hypertension, ischemic nephropathy and “flash” acute pulmonary oedema. Unilateral stenosis of the renal artery causes angiotensin II-dependent hypertension, and bilateral stenosis of the renal arteries produces volume-dependent hypertension. Renovascular aetiology of hypertension should be questioned in patients with resistant hypertension, hypertension with a murmur identified upon auscultation of the renal arteries, and a noticeable side-to-side difference in kidney size. Non-invasive diagnostic tests include the determination of concentrations of peripheral vein plasma renin activity, the captopril test, captopril scintigraphy, colour Doppler ultrasonography, computed tomography angiography, and nuclear resonance angiography. Renovasography represents the gold standard for the diagnosis of renovascular hypertension. The indications for revascularization of the renal artery include haemodynamically significant renal artery stenosis (with a systolic pressure gradient at the site of stenosis of - ΔP ≥ 20 mmHg, along with the ratio of the pressure in the distal part of the renal artery (Pd and aortic pressure (Pa less than 0.9 (Pd/Pa 0.8, chronic kidney disease (GFR <30 ml/min/1.73 m2 and negative captopril scintigraphy (lack of lateralization.

Impact of angiotensin and endothelin converting enzymes and related bradykinin on renal functions in L-NAME hypertensive rats

Science.gov (United States)

Omar, Ali Zainal; Maulood, Ismail M.

2017-09-01

The renin-angiotensin system (RAS), one of the most important hormonal systems, controls the kidney functions by regulating fluid volume, and electrolyte balance. The current study included the effects of kinin-kallikrein system (KKS) and its interaction with both angiotensin converting enzyme (ACE) and endothelin converting enzyme (ECE) on some of kidney function test parameters. In the present experiment, rats were divided into six groups, the first group was infused with normal saline, the second group was L-NG-Nitroarginine methyl ester (L-NAME) treated rats, third group was bradykinin (BK), forth group was captopril (ACEi), fifth group was phosphoramidon (ECEi), sixth group was a combination of BK with phosphoramidon. L-NAME was intravenously infused for one hour to develop systematic hypertension in male rats. After one hour of infusion, the results showed that L-NAME significantly increased serum creatinine. While, it decreased glomerular filtration rate (GFR), and K+ excretion rate. Moreover, BK increased packed cell volume PCV%, serum creatinine and K+ ion concentration. While, it reduced GFR, serum Ca+2 ion concentration, K+ and Na+ excretion rates. On the other hand, captopril infusion showed its effect by reduction in GFR, serum Ca+2 ion and electrolyte excretion rates. Phosphoramidon an ECEi dramatically reduced serum Ca+2 ion, but it increased pH, GFR and Ca+2 excretion rate. The results suggested that BK and Captopril each alone severely reduces GFR value. Interestingly, inhibition of ET-1 production via phosphoramidon could markedly elevate GFR values.

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)

Soft-Template-Synthesized Mesoporous Carbon for Oral Drug Delivery

Energy Technology Data Exchange (ETDEWEB)

Saha, Dipendu [ORNL; Warren, Kaitlyn E [ORNL; Naskar, Amit K [ORNL

2014-01-01

Template-synthesized mesoporous carbons were successfully used in in vitro investigations of controlled delivery of three model drugs, captopril, furosemide, and ranitidine hydrochloride. Captopril and furosemide exhibited desorption kinetics over 30 40 h, and ranitidine HCl had a complete release time of 5 10 h. As evident from the slow release kinetics, we contend that our mesoporous carbon is an improved drug-delivery medium compared to state-of-the-art porous silica-based substrates. The mesoporous carbons, synthesized from phloroglucinol and lignin, a synthetic and a sustainable precursor, respectively, exhibit BET surface area of 200 400 m2 g-1 and pore volume of 0.2 0.6 cm3 g-1. The phloroglucinol-based carbon has narrower pore widths and higher pore volume than the lignin-derived counterpart and maintains a longer release time. Numerical modeling of the release kinetics data reveals that the diffusivities of all the drugs from lignin-based carbon media are of equivalent magnitude (10-22 to 10-24 m2 s-1). However, a tailored reduction of pore width in the sorbent reduces the diffusivity of smaller drug molecules (captopril) by an order of magnitude. Thus, engineered pore morphology in our synthesized carbon sorbent, along with its potential to tailor the chemistry of its interaction with sorbet, can be exploited for optimal delivery system of a preferred drug within its therapeutic level and below the level of toxicity.

Angiotensin-converting enzyme inhibitors of Bothrops jararaca snake venom affect the structure of mice seminiferous epithelium.

Science.gov (United States)

Alberto-Silva, Carlos; Gilio, Joyce M; Portaro, Fernanda C V; Querobino, Samyr M; Camargo, Antonio C M

2015-01-01

Considering the similarity between the testis-specific isoform of angiotensin-converting enzyme and the C-terminal catalytic domain of somatic ACE as well as the structural and functional variability of its natural inhibitors, known as bradykinin-potentiating peptides (BPPs), the effects of different synthetic peptides, BPP-10c (captopril were evaluated in the seminiferous epithelium of male mice. The adult animals received either one of the synthetic peptides or captopril (120 nmol/dose per testis) via injection into the testicular parenchyma. After seven days, the mice were sacrificed, and the testes were collected for histopathological evaluation. BPP-10c and BPP-AP showed an intense disruption of the epithelium, presence of atypical multinucleated cells in the lumen and high degree of seminiferous tubule degeneration, especially in BPP-AP-treated animals. In addition, both synthetic peptides led to a significant reduction in the number of spermatocytes and round spermatids in stages I, V and VII/VIII of the seminiferous cycle, thickness of the seminiferous epithelium and diameter of the seminiferous tubule lumen. Interestingly, no morphological or morphometric alterations were observed in animals treated with captopril or BPP-11e. The major finding of the present study was that the demonstrated effects of BPP-10c and BPP-AP on the seminiferous epithelium are dependent on their primary structure and cannot be extrapolated to other BPPs.

Reversible diminished renal sup(99m)Tc-DMSA uptake during converting-enzyme inhibition in a patient with renal artery stenosis

Energy Technology Data Exchange (ETDEWEB)

Kremer Hovinga, T K; Beukhof, J R; Donker, A J.M.; Luyk, W H.J. van; Piers, D A

1984-03-01

A patient is described who had accelerated hypertension and unilateral renal artery stenosis, and who developed further deterioration in renal function during treatment with captopril, an angiotension-I (AI) converting-enzyme inhibitor. sup(99m)Tc-DMSA uptake was greatly diminished in the stenotic kidney, although renal blood flow and handling of /sup 131/I hippurate was preserved. Uptake of sup(99m)Tc-DMSA in the affected kidney returned after substitution of captopril by the vasodilator minoxidil, while a comparable degree of blood pressure control was maintained. This, caution must be taken when interpreting results of sup(99m)Tc-DMSA scintigraphy in patients with proven or suspected renal artery stenosis treated with an AI converting-enzyme inhibiting drug. Moreover, our finding points to the importance of glomerular filtration in the renal handling of /sup 99/Tc-DMSA.

Reversible diminished renal sup(99m)Tc-DMSA uptake during converting-enzyme inhibition in a patient with renal artery stenosis

International Nuclear Information System (INIS)

Kremer Hovinga, T.K.; Beukhof, J.R.; Donker, A.J.M.; Luyk, W.H.J. van; Piers, D.A.

1984-01-01

A patient is described who had accelerated hypertension and unilateral renal artery stenosis, and who developed further deterioration in renal function during treatment with captopril, an angiotension-I (AI) converting-enzyme inhibitor. sup(99m)Tc-DMSA uptake was greatly diminished in the stenotic kidney, although renal blood flow and handling of 131 I hippurate was preserved. Uptake of sup(99m)Tc-DMSA in the affected kidney returned after substitution of captopril by the vasodilator minoxidil, while a comparable degree of blood pressure control was maintained. This, caution must be taken when interpreting results of sup(99m)Tc-DMSA scintigraphy in patients with proven or suspected renal artery stenosis treated with an AI converting-enzyme inhibiting drug. Moreover, our finding points to the importance of glomerular filtration in the renal handling of 99 Tc-DMSA. (orig.)

CONVERTING ENZYME-INHIBITORS AND THE ROLE OF THE SULFHYDRYL-GROUP IN THE POTENTIATION OF EXOGENOUS AND ENDOGENOUS NITROVASODILATORS

NARCIS (Netherlands)

VANGILST, WH; DEGRAEFF, PA; DELEEUW, MJ; WESSELING, H

In this study, the effect of bradykinin on coronary flow in the isolated rat heart was significantly potentiated when cysteine or the sulfhydryl-containing converting enzyme inhibitors captopril and zofenoprilat were administered simultaneously. In contrast, the effect of concomitant administration

Geographic variation in the treatment of acute myocardial infarction in the VALsartan In Acute myocardial iNfarcTion (VALIANT) trial

DEFF Research Database (Denmark)

Reed, Shelby D; McMurray, John J V; Velazquez, Eric J

2006-01-01

BACKGROUND: The VALIANT trial compared the efficacy and safety of captopril, valsartan, and their combination in patients with left ventricular systolic dysfunction, heart failure, or both after acute myocardial infarction (MI). By examining this international trial population of high-risk patients...

Is Dysguesia Going to be a Rare or a Common Side‑effect of ...

African Journals Online (AJOL)

amlodipine are peripheral edema (8.3%), fatigue (4.5%), dizziness, palpitations, myalgia, stomachache, headache, dyspepsia, nausea, blood disorders, gynecomastia, .... Coulter DM. Eye pain with nifedipine and disturbance of taste with captopril: A mutually controlled study showing a method of postmarketing surveillance.

Comparison of renal function and cardiovascular risk following acute myocardial infarction in patients with and without diabetes mellitus

DEFF Research Database (Denmark)

Anavekar, Nagesh S; Solomon, Scott D; McMurray, John J V

2008-01-01

. The valiant trial identified 14,527 patients with acute myocardial infarction complicated by either clinical or radiologic signs of heart failure and/or left ventricular dysfunction for whom baseline creatinine was measured. Patients were randomly assigned to receive captopril, valsartan, or both. Glomerular...

VALsartan In Acute myocardial iNfarcTion (VALIANT) trial: baseline characteristics in context

DEFF Research Database (Denmark)

Velazquez, Eric J; Pfeffer, Marc A; McMurray, John V

2003-01-01

BACKGROUND: The VALsartan In Acute myocardial iNfarcTion (VALIANT) trial compared outcomes with: (1) angiotensin-converting enzyme inhibition (ACEI) with the reference agent captopril; (2) angiotensin-receptor blockade (ARB) with valsartan; or (3) both in patients with heart failure (HF) and...

Effects of aspirin on angiotensin-converting enzyme inhibition and left ventricular dilation one year after acute myocardial infarction

NARCIS (Netherlands)

Oosterga, M; Anthonio, RL; de Kam, PJ; Kingma, JH; Crijns, HJGM; van Gilst, WH

1998-01-01

There are conflicting reports on the interaction of aspirin with angiotensin-converting enzyme inhibitors in heart failure and systemic hypertension. A past hoc analysis of the Captopril and Thrombolysis Study (CATS) study was conducted. At randomization, 94 patients (31.5%) took aspirin. In

Blockade of Rennin-Angiotensin system blunts the fibrotic response in experimental acute pyelonephritis

Directory of Open Access Journals (Sweden)

Singal A

2005-01-01

Full Text Available Aim: To study the impact of Renin-Angiotensin system blockade in experimental acute pyelonephritis, induced by a novel surgical approach via dorsal lumbotomy incision. Materials and Methods : 45 Adult female WISTAR rats aged 8-12 weeks, underwent direct inoculation of 0.1 ml of E.coli suspension into the parenchyma of the surgically exposed kidney. 3 groups of rats were studied: Group A - treated with antibiotics only; Group B- Captopril and antibiotics and Group C- Losartan and antibiotics. Changes of acute inflammation, parenchymal destruction and scarring were compared between the groups on histopathological sections. Kruskal-Wallis test was used for statistical analysis. Results : Changes consistent with acute pyelonephritis were seen in all the kidneys. Mean% scar area in Group A, Group B and Group C was 37.08±1.79, 24.40±1.88 and 24.68±1.32% respectively at end of six weeks. Mean tubular density in Group A, B and C was 17.26±1.92, 47.18±3.00 and 47.00±5.08-tubules/lac mm2 respectively. The differences between the control and the treated animals were significant, though the results did not differ between the losartan and captopril treated rats. Conclusions : Dorsal lumbotomy approach to the kidney provides a good exposure of the kidney. Induction of acute pyelonephritis by direct inoculation of bacteria into renal cortex produced a consistent scar at 6 weeks. Blockade of renin angiotensin system by either captopril or losartan decreased the renal scar area by almost 1/3 at 6 weeks.

Amiodarone use after acute myocardial infarction complicated by heart failure and/or left ventricular dysfunction may be associated with excess mortality

DEFF Research Database (Denmark)

Thomas, Kevin L; Al-Khatib, Sana M; Lokhnygina, Yuliya

2008-01-01

, a randomized comparison of valsartan, captopril, or both in patients with acute myocardial infarction with HF and/or left ventricular systolic dysfunction. We compared baseline characteristics of 825 patients treated with amiodarone at randomization with 13,875 patients not treated with amiodarone. Using Cox...

Udvikling af sklerodermisk krise hos patient med uerkendt sklerodermi

DEFF Research Database (Denmark)

Madsen, Kristine Lindhard; Hansen, Alastair; Halberg, Poul

2014-01-01

Less than 10% of the patients with systemic scleroderma develop renal crisis, i.e. acute renal failure and severe hypertension in most cases. Kidney biopsy shows hypertensive arteriolar changes. This complication was lethal until treatment with captopril was introduced in 1976. Since that time...

APPLICATION OF NEW FERROCENE DERIVATIVE FOR ...

African Journals Online (AJOL)

B. S. Chandravanshi

coefficient (α) and rate constant for chemical reaction between captopril and redox sites in the modified electrode were 0.31 ... electrochemical behavior of carbon nanotube paste electrode modified azodianiline ferrocenyl in ... electrode cell assembly (Ag/AgCl electrode as reference electrode, a platinum wire as counter.

Author Details

African Journals Online (AJOL)

Hasanpour, F. Vol 29, No 1 (2015) - Articles Application of new ferrocene derivative for electrocatalytic determination of captopril using multiwall carbon nanotube modified carbon paste electrode. Abstract PDF. ISSN: 1726-801X. AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians ...

Vasorelaxing and antihypertensive activities of synthesized peptides derived from computer-aided simulation of pepsin hydrolysis of yam dioscorin.

Science.gov (United States)

Lin, Yin-Shiou; Lu, Yeh-Lin; Wang, Guei-Jane; Liang, Hong-Jen; Hou, Wen-Chi

2014-12-01

We reported that yam dioscorin and its peptic hydrolysates exhibited ACE inhibition and antihypertensive effects on SHRs, however, the active peptides are not really isolated until now. Using ACE inhibitory screenings, two penta-peptides, KTCGY and KRIHF, were selected for ex vivo and in vivo experiments. KTCGY, KRIHF, and captopril were shown to have similar vasodilating effects against phenylephrine (PE)-induced tensions in rat endothelium-dependent thoracic aortic rings, however, KTCGYKTCGY (two-repeated KTCGY) and TCGYTCGY (two-repeated TCGY) were showed endothelium-independent vasodilating effects against PE-induced tensions. KTCGY, KRIHF (10 or 20 mg/kg), and captopril (10 mg/kg) were used to evaluate antihypertensive activity during 24-h after a single oral administration to spontaneously hypertensive rats (SHRs). The KTCGY and KRIHF showed significantly different and reduced the systolic blood pressure of SHRs compared to the blank. These results suggest that KTCGY and KRIHF may contribute important roles in yam dioscorin for regulating blood pressure in vivo.

[Effect of losartan on human platelet activation by thromboxane A2].

Science.gov (United States)

Guerra, J I; Montón, M; Rodríguez-Feo, J A; Farré, J; Jiménez, A M; Núñez, A; Gómez, J; Rico, L; Marcos, P; Castilla, C; Sánchez De Miguel, L; Casado, S; López-Farré, A

2000-04-01

Previous studies have demonstrated that losartan, an AT-1 receptor antagonist of angiotensin II (Ang II) could block the receptor of thromboxane A2 (TXA2) in the vascular wall. The aim of the present study was to assess the effect of losartan on human platelet activation. Platelets were obtained from 15 healthy men between the age 26 and 40. Platelet activation was measured by changes in the light transmission of platelet-rich plasma stimulated by a synthetic TXA2 analogue, U46619 (5 x 10(-6) mol/l). The U46619-stimulated platelet aggregation was significantly inhibited by losartan in a dose-response manner. Only a high dose of EXP 3174 (5 10-5 mol/l), the in vivo active metabolite of losartan, was able to attenuate U46619-induced platelet activation. Captopril, an angiotensin I-converting inhibitor failed to modify U46619-induced platelet aggregation. Despite the platelets expressing AT-1 type receptors, of Ang II exogenous Ang II did not modify platelet aggregation induced by U46619. The binding of U46619 to platelets was competitively inhibited by losartan in dose-dependent manner. However, only a high dose of EXP 3174 reduced the binding of U46619. Captopril failed to modify the binding of U46619 to platelets. Losartan decreased platelet aggregation by a TXA2-dependent mechanism. EXP 3174 showed a lesser potency than losartan to reduce TXA2-platelet activation. Captopril and exogenous angiotensin II had no effect on human platelet activation. These results suggest that losartan reduced TXA2-dependent platelet activation independently of the blockade of AT-1 receptors.

Role of the renin-angiotensin system, renal sympathetic nerve system, and oxidative stress in chronic foot shock-induced hypertension in rats.

Science.gov (United States)

Dong, Tao; Chen, Jing-Wei; Tian, Li-Li; Wang, Lin-Hui; Jiang, Ren-Di; Zhang, Zhe; Xu, Jian-Bing; Zhao, Xiao-Dong; Zhu, Wei; Wang, Guo-Qing; Sun, Wan-Ping; Zhang, Guo-Xing

2015-01-01

The renin-angiotensin system (RAS) and renal sympathetic nerve system (RSNS) are involved in the development of hypertension. The present study is designed to explore the possible roles of the RAS and the RSNS in foot shock-induced hypertension. Male Sprague-Dawley rats were divided into six groups: control, foot shock, RSNS denervation, denervation plus foot shock, Captopril (angiotensin I converting enzyme inhibitor, ACE inhibitor) plus foot shock, and Tempol (superoxide dismutase mimetic) plus foot shock. Rats received foot shock for 14 days. We measured the quantity of thiobarbituric acid reactive substances (TBARS), corticosterone, renin, and angiotensin II (Ang II) in plasma, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and renal noradrenaline content. RAS component mRNA and protein levels were quantified in the cerebral cortex and hypothalamus. The two week foot shock treatment significantly increased systolic blood pressure, which was accompanied by an increase in angiotensinogen, renin, ACE1, and AT1a mRNA and protein expression in the cerebral cortex and hypothalamus, an increase of the plasma concentrations of renin, Ang II, corticosterone, and TBARS, as well as a decrease in plasma SOD and GSH-Px activities. Systolic blood pressure increase was suppressed by denervation of the RSNS or treatment with Captopril or Tempol. Interestingly, denervation or Tempol treatment both decreased main RAS components not only in the circulatory system, but also in the central nervous system. In addition, decreased antioxidant levels and increased TBARS and corticosterone levels were also partially restored by denervation or treatment with Tempol or Captopril. RAS, RSNS and oxidative stress reciprocally potentiate to play important roles in the development of foot shock-induced hypertension.

Effects of the bradykinin antagonist B4310 on smooth muscles and blood pressure in the rat, and its enzymatic degradation.

Science.gov (United States)

Griesbacher, T.; Lembeck, F.; Saria, A.

1989-01-01

1. Six competitive bradykinin (Bk) antagonists were tested for their agonistic properties on the rat uterus. Five of these peptides showed agonistic effects only at concentrations at least two orders of magnitude higher than those of bradykinin. 2. The antagonistic potency of Lys-Lys-3-Hyp-5,8-Thi-7-DPhe-Bk (B4310) in the rat uterus (pA2 = 7.24) and in the rat duodenum (pA2 = 7.31) was very similar to that determined in an earlier study for the antagonism of the bradykinin-induced stimulation of the trigeminal nerve in the rabbit iris sphincter muscle preparation (pA2 = 7.59). 3. The fall in mean arterial blood pressure induced by i.a. injections of bradykinin was greatly reduced during an i.a. infusion of B4310, but not 10 min thereafter, which indicates a rapid inactivation of B4310 in vivo. Bacitracin possibly interferes with the enzymatic cleavage of B4310 but seems to have no effect on the degradation of bradykinin. 4. An i.a. infusion of captopril greatly enhanced the potency of bradykinin in inducing a fall in arterial blood pressure, confirming the important role of angiotensin converting enzyme in the cleavage of bradykinin. However, the design of this experiment did not allow conclusions about the effect of captopril on the degradation of B4310. 5. B4310 incubated with rat lung tissue disappeared from the incubation medium within a few minutes, i.e. as fast as bradykinin, which explains its short duration of action in vivo. Captopril partially inhibited the cleavage of both bradykinin and B4310.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2655805

Efecto hipotensor del extracto de ajo (Allium sativum macerado por 18 semanas en un modelo experimental in vivo

Directory of Open Access Journals (Sweden)

David Chaupis-Meza

Full Text Available Objetivos. Determinar si el extracto de ajo (Allium sativum macerado por 18 semanas tiene igual o mejor efecto hipotensor que el captopril en ratas. Materiales y métodos. Se realizó un estudio experimental in vivo con ratas machos Holtzman, clasificados en cinco grupos: 100, 500 y 1000 mg/kg de extracto de ajo, Captopril de 100 mg/kg y un grupo vehículo. El L-NAME (N- -nitro L-arginina-metil-éster administrado vía intraperitoneal 50 mg/kg desde el inicio del experimento, elevó la presión arterial desde el tercer día. El análisis estadístico consistió en las pruebas T de Student para medias pareadas, ANOVA y comparación múltiple de Scheffe. Resultados. El ajo macerado extraído por un proceso hidroalcohólico durante 18 semanas provocó una disminución de la presión arterial en animales de experimentación. El análisis de los tratamientos sobre la presión arterial media (PAM, obtuvieron diferencias significativas desde el tercer día. La comparación sobre la PAM final versus PAM basal (medias no diferentes y el efecto hipotensor (% fueron: ajo-100 (p=0,008, 59,8%; ajo-500 (p=0,021, 80,6%; ajo-1000 (p=0,034, 88,5%, Captopril (p=0,437, 99,9% y vehículo (p=0,001, 0%. Conclusiones. El ajo macerado a un periodo de 18 semanas resultó eficaz para producir un efecto hipotensor en ratas, inducidas a hipertensión arterial por L-NAME

Moderate additive effects of endothelin receptor A blockade in Ren-2 transgenic rats subjected to various types of RAS blockade

Czech Academy of Sciences Publication Activity Database

Vaněčková, Ivana; Řezáčová, Lenka; Kuneš, Jaroslav; Zicha, Josef

2016-01-01

Roč. 159, Aug 15 (2016), s. 127-154 ISSN 0024-3205 R&D Projects: GA MZd(CZ) NV15-25396A Institutional support: RVO:67985823 Keywords : aliskiren * captopril * atrasentan * hypertension * losartan * ren-2 transgenic rats Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 2.936, year: 2016

Ameliorative effect of Draba nemorosa extract on chronic heart ...

African Journals Online (AJOL)

Purpose: To evaluate the effect of Draba nemorosa extract (DNE) on oxidative stress and hemodynamics in rats with chronic congestive heart failure (CHF). Methods: Adriamycin was used to establish CHF in Sprague Dawley (SD) rat model. Six groups of SD rats were used in this study: control group, CHF group, captopril ...

Effect of losartan on human platelet activation.

Science.gov (United States)

Guerra-Cuesta, J I; Montón, M; Rodríguez-Feo, J A; Jiménez, A M; González-Fernández, F; Rico, L A; García, R; Gómez, J; Farré, J; Casado, S; López-Farré, A

1999-03-01

Previous studies have demonstrated that losartan can block the thromboxane A2 receptor on the vascular wall. The aim of the present study was to assess the effect of losartan on human platelet activation. Platelets were obtained from 15 healthy men, aged 26-40 years. Platelet activation was measured by changes in the light transmission of platelet-rich plasma stimulated by the thromboxane A2 analog U46619 (5 x 10(-6) mol/l) or ADP (10(-5) mol/l). U46619-stimulated platelet aggregation was significantly inhibited by losartan in a dose-dependent manner. Only a high dose of EXP 3174 (5 x 10(-5) mol/l), the in vivo active metabolite of losartan, was able to attenuate U46619-induced platelet activation. Captopril, an angiotensin I converting inhibitor, failed to modify U46619-induced platelet aggregation. Furthermore, the binding of [3H]-U46619 to platelets was competitively inhibited by losartan, whereas only a high dose of EXP 3174 reduced the binding of [3H]-U46619. Captopril failed to modify the binding of [3H]-U46619 to platelets. Losartan also reduced the platelet activation induced by ADP (10(-5) mol/l), a platelet agonist partially dependent on thromboxane A2. In addition, when thromboxane A2 generation was blocked by aspirin, ADP-induced platelet aggregation was inhibited to a similar degree to the inhibition induced by losartan. Exogenous angiotensin II did not elicit any modification of either U46619- or ADP-stimulated platelet aggregation. Losartan decreased platelet aggregation by a thromboxane A2-dependent mechanism. EXP 3174 was less potent than losartan in reducing thromboxane A2-dependent platelet activation. Captopril and exogenous angiotensin II had no effect on human platelet activation. These results suggest that losartan reduced thromboxane A2-dependent platelet activation independently of its effect on angiotensin II.

Flax lignan concentrate attenuate hypertension and abnormal left ventricular contractility via modulation of endogenous biomarkers in two-kidney-one-clip (2K1C hypertensive rats

Directory of Open Access Journals (Sweden)

Sameer Hanmantrao Sawant

Full Text Available ABSTRACT The present investigation was designed to study the effect of flax lignan concentrate obtained from Linum usitatissimum L., Linaceae, in two-kidney, one clip (2K1C hypertension model in Wistar rats. 2K1C Goldblatt model rats were divided randomly into six groups: sham, 2K1C control, captopril (30 mg/kg, flax lignan concentrate (200, 400 and 800 mg/kg. Flax lignan concentrate and captopril were administered daily for eight consecutive weeks. Sham-operated, and 2K1C control rats received the vehicle. Treatment with flax lignan concentrate (400 and 800 mg/kg significantly and dose-dependently restored the hemodynamic parameters systolic blood pressure, diastolic blood pressure, mean arterial blood pressure and left ventricular functions. The flax lignan concentrate significantly restored the elevated hepatic, renal and cardiac marker enzymes in the serum. It also restored the organs weights (kidney and heart, serum electrolyte level and histological abnormalities. Furthermore, flax lignan concentrate significantly elevated the level of biochemical markers that is enzymatic antioxidants superoxide dismutase, glutathione and decreased malondialdehyde in the heart and kidney tissues. Meanwhile, we found that plasma nitric oxide and plasma nitric oxide synthase contents were significantly increased in the flax lignan concentrate-treated group, and plasma endothelin-1 and renal angiotensin-II levels were significantly lower than 2K1C hypertensive group. In conclusion, the antihypertensive and antioxidant effect of flax lignan concentrate were dose-dependent and at the highest dose (i.e. 800 mg/kg similar to those of captopril (30 mg/kg. It is suggested that flax lignan concentrate reduced blood pressure by reduction of renal angiotensin-II level, inhibition of plasma endothelin-1 production, induction of the nitric oxide, nitric oxide synthase and in vivo antioxidant defense system.

Tropical Journal of Pharmaceutical Research - Vol 6, No 2 (2007)

African Journals Online (AJOL)

Design and Development of a Proniosomal Transdermal Drug Delivery System for Captopril · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. A Gupta, S K Prajapati, M Balamurugan, M Singh, D Bhatia, 687-693. http://dx.doi.org/10.4314/tjpr.v6i2.14647 ...

The renogram in renovascular hypertension

International Nuclear Information System (INIS)

Geyskes, G.G.

1987-01-01

This thesis comprises five reports on studies with renograms, radionuclide investigations of individual renal function in patients suspected of renovascular hypertension. The main question was to determine whether the renogram could trace functional changes in a kidney with a stenosed artery, before and after percutaneous transluminal angioplasty (PTA) treatment. In a given patient these functional changes could provide information on the significance of the artery stenosis as a cause of that patients' hypertension, and to some extent predict the blood pressure response after PTA treatment. An important issue in these studies is the registration of the renal effects created by captopril on the renogram. This drug with its specific inhibition of the conversion of angiotensine I to angiotensine II, amplifies the impairment of the glomerular filtration rate (GFR) in a kidney behind a stenosis. Captopril-induced deterioration of the GFR can be shown by renography, especially when it occurs in only one of two kidneys and for that reason does escape detection by overall renal function studies. 157 refs.; 16 figs.; 12 tabs

Cardiovascular-Active Venom Toxins: An Overview.

Science.gov (United States)

Rebello Horta, Carolina Campolina; Chatzaki, Maria; Rezende, Bruno Almeida; Magalhães, Bárbara de Freitas; Duarte, Clara Guerra; Felicori, Liza Figueiredo; Ribeiro Oliveira-Mendes, Bárbara Bruna; do Carmo, Anderson Oliveira; Chávez-Olórtegui, Carlos; Kalapothakis, Evanguedes

2016-01-01

Animal venoms are a mixture of bioactive compounds produced as weapons and used primarily to immobilize and kill preys. As a result of the high potency and specificity for various physiological targets, many toxins from animal venoms have emerged as possible drugs for the medication of diverse disorders, including cardiovascular diseases. Captopril, which inhibits the angiotensin-converting enzyme (ACE), was the first successful venom-based drug and a notable example of rational drug design. Since captopril was developed, many studies have discovered novel bradykinin-potentiating peptides (BPPs) with actions on the cardiovascular system. Natriuretic peptides (NPs) have also been found in animal venoms and used as template to design new drugs with applications in cardiovascular diseases. Among the anti-arrhythmic peptides, GsMTx-4 was discovered to be a toxin that selectively inhibits the stretch-activated cation channels (SACs), which are involved in atrial fibrillation. The present review describes the main components isolated from animal venoms that act on the cardiovascular system and presents a brief summary of venomous animals and their venom apparatuses.

Chronic and acute effects of different antihypertensive drugs on femoral artery relaxations of L-NAME hypertensive rats

Czech Academy of Sciences Publication Activity Database

Sládková, M.; Kojšová, S.; Jendeková, L.; Pecháňová, Olga

2007-01-01

Roč. 56, Suppl.2 (2007), S85-S91 ISSN 0862-8408 Grant - others:VEGA(SK) 2/6148/26; VEGA(SK) 1/3429/06; -(SK) APVV-0586-06 Institutional research plan: CEZ:AV0Z50110509 Keywords : L-NAME induced hypertension * indapamide * hydrochlorothiazide * captopril Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.505, year: 2007

28. Critical pulmonary valve stenosis: Medical management beyond balloon dilation

Directory of Open Access Journals (Sweden)

Muhammad Arif Khan

2015-10-01

Conclusion: Phentolamine and/or Captopril have a therapeutic role in neonates with critical PVS who remain oxygen dependent after balloon dilation. Both medicationslead to vasodilatation of pulmonary and systemic vascularity. They facilitate inflowto the right ventricle. Right to left shunt across a PFO or/ ASD minimizesand saturation improves leading to a significantreduction in length of hospitalization.

Reacciones adversas a medicamentos como causa de abandono del tratamiento farmacológico en hipertensos Adverse reactions to drugs as leaving drug therapy cause in hypertensive persons

Directory of Open Access Journals (Sweden)

Ana Julia García Milián

2009-03-01

Full Text Available INTRODUCCIÓN: los fallos al seguir las prescripciones médicas exacerban los problemas de salud y la progresión de las enfermedades, e imposibilitan estimar los efectos y el valor de un determinado tratamiento. OBJETIVO: caracterizar las causas que generan la no adherencia al tratamiento farmacológico en hipertensos. MÉTODOS: estudio observacional descriptivo de corte transversal, constituido por 241 hipertensos inscriptos por algún fármaco antihipertensivo en farmacias comunitarias seleccionadas de Guantánamo, Las Tunas, Camagüey, Cienfuegos, Villa Clara, Granma, Santiago de Cuba y Ciego de Ávila. El método de recogida de la información fue la encuesta. RESULTADOS: los antihipertensivos más consumidos fueron el captopril, la hidroclorotiacida y el atenolol, y fue el primero, con el 31,9 %, el medicamento que tuvo un mayor porcentaje de incumplidores y productor de evento adverso. El cumplimiento fue mayor en los pacientes menores de 30 años. Dentro de los motivos las reacciones adversas ocuparon el 2do. lugar, con el 16,9 %. Las reacciones que causaron abandono terapéutico fueron la tos, las reacciones cutáneas y el decaimiento. CONCLUSIONES: las reacciones adversas se ubican dentro de las causas más frecuentes de abandono de tratamiento antihipertensivo, y fueron el captopril y la hidroclorotiacida los que con mayor frecuencia la provocaron. Las reacciones adversas referidas, en su mayoría, son consideradas como leves.INTRODUCTION: failures to follow medical prescriptions increase health problems and diseases progression, and make it impossible for to estimate effects and value of a specific treatment. AIM: to characterize causes generating the non-adherence to pharmacologic treatment in hypertensive patients. METHODS: cross-sectional descriptive and observational study including 241 hypertensive patients registered by some anti-hypertensive drug in selected community drugstore In Guantánamo, Las Tunas, Camaguey, Villa Clara

Physiological factors affecting renal radiation tolerance: a guide to the treatment of late effects

International Nuclear Information System (INIS)

Robbins, M.E.C.; Hopewell, J.W.

1986-01-01

The results presented provide preliminary information concerning the ability of vasoactive compounds to modify the reduction in renal haemodynamics following renal irradiation. The two compounds are widely used in the clinical treatment of hypertension. The radiation-induced changes in glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) observed in bilaterally irradiated pigs which received 150 mg indoramin daily were similar to those seen in pigs which received radiation alone: if anything the former exhibited greater decline in renal function. Two of the three Captopril-treated animals appeared to show a reduced impairment of renal function compared with irradiated controls. It is not known why the remaining pig did not show a similar response. However, plasma renin levels in this pig, measured 10 weeks after irradiation, were markedly higher than in the other two animals, i.e. 10.7 compared with 2.3 and 4.5 pmol -1 ml -1 , possibly reflecting greater renal damage. The total renal weight at postmortem of this pig was considerably reduced (approx. 50%), whereas the renal weights of the remaining Captopril-treated pigs were similar to those of age-related controls. (UK)

Characterization of dipeptidylcarboxypeptidase of Leishmania donovani: a molecular model for structure based design of antileishmanials

Science.gov (United States)

Baig, Mirza Saqib; Kumar, Ashutosh; Siddiqi, Mohammad Imran; Goyal, Neena

2010-01-01

Leishmania donovani dipeptidylcarboxypeptidsae (LdDCP), an angiotensin converting enzyme (ACE) related metallopeptidase has been identified and characterized as a putative drug target for antileishmanial chemotherapy. The kinetic parameters for LdDCP with substrate, Hip-His-Leu were determined as, Km, 4 mM and Vmax, 1.173 μmole/ml/min. Inhibition studies revealed that known ACE inhibitors (captopril and bradykinin potentiating peptide; BPP1) were weak inhibitors for LdDCP as compared to human testicular ACE (htACE) with Ki values of 35.8 nM and 3.9 μM, respectively. Three dimensional model of LdDCP was generated based on crystal structure of Escherichia coli DCP (EcDCP) by means of comparative modeling and assessed using PROSAII, PROCHECK and WHATIF. Captopril docking with htACE, LdDCP and EcDCP and analysis of molecular electrostatic potentials (MEP) suggested that the active site domain of three enzymes has several minor but potentially important structural differences. These differences could be exploited for designing selective inhibitor of LdDCP thereby antileishmanial compounds either by denovo drug design or virtual screening of small molecule databases.

INFLUENCE OF COMBINED ANTIHYPERTENSIVE AND ANTIDEPRESSANT THERAPY ON LEFT VENTRICULAR REMODELING IN PATIENTS WITH ARTERIAL HYPERTENSION, ANXIETY AND DEPRESSION

Directory of Open Access Journals (Sweden)

Y. A. Vasyuk

2008-01-01

Full Text Available Aim. To assess influence of combined antihypertensive (captopril or metoprolol and antidepressant (thianeptin or sertralin therapy on clinical status, blood pressure (BP and myocardial function in patients with arterial hypertension (HT and affective disorders (AD.Material and methods. 106 patients with HT were involved in the study. 64 patients (60,4% had concomitant AD. All patients were divided into 3 groups. 46 patients with HT and AD were included in the 1-st group. They received metoprolol or captopril in combination with tianeptine or sertaline. The 2-nd group included 18 patients with HT and AD who received only antihypertensive therapy. The 3-rd group consisted of 42 patients with HT without AD. They also received only antihypertensive therapy.Results. After 6 month therapy patients of the 1-st and the 3-rd groups had more significant clinical improvement and BP reduction (according to 24- hour BP monitoring as well as more farourable structural and functional changes of left ventricular in comparison with patients of the 2-nd group.Conclusion. In patients with HT and concomitant AD combined antihypertensive and antidepressant therapy result in favourable clinical changes, effectively reduce BP, improve left ventricular structure and function.

Community pharmacists’ attitudes and knowledge on dispensing drugs.

Directory of Open Access Journals (Sweden)

Baldon JP

2006-03-01

Full Text Available The present study aimed to assess knowledge and attitudes of the pharmacists on dispensing drugs to pregnant women. Methods: Cross-sectional study in 150 community pharmacies randomly selected in Curitiba (Brazil. A closed end questionnaire with 25 questions were used, including dispensing scenarios containing risk types A, B, D or X and questions on pharmacist interaction with pregnant women, physicians, and information sources availability. Results: Pharmacists performed appropriately in 53% of the encounters. Lower success were associated to prednison and captopril (24.8% in both, end cases producing more doubts were captopril (31.7% and simvastatin (30.7%. Most of the pharmacists state have advised drugs to pregnant women or contact to the physician to discuss about a prescription related with this issue. A Majority (64.4% did not feel able to understand FDA risk classification and did not have trustable information sources in pharmacy. Conclusions: Pharmacists dispensing drugs in Curitiba are not able to interpret information on the use of drugs in pregnant women, and they don have reliable information sources on the use of dugs in pregnancy. However, they advice and counsel drugs to pregnant women and discuss with physicians therapeutic strategies.

Transplante cardíaco em Campo Grande - MS. Redução significativa de lesão coronária pós transplante: relato de caso

Directory of Open Access Journals (Sweden)

Marcos Vinícius R. P. CALDAS

1997-04-01

Full Text Available No Serviço de Cirurgia Cardíaca da Santa Casa de Campo Grande/MS - foi realizado, em 23 de setembro de 1994, um transplante cardíaco ortotópico no paciente C.A.D., 27 anos, portador de miocardiopatia dilatada idiopática, o qual transcorreu sem anormalidades. O paciente recebeu alta da UTI com 7 dias e alta hospitalar no 40º dia de pós-operatório, recebendo ciclosporina, azatioprina e prednisona para manutenção do enxerto, captopril, furosemida e aspirina. Apresentou no 1º ano de seguimento 2 episódios de rejeição, leve e moderada, sendo modificada a posologia dos imunossupressores. Em setembro de 1995, nos exames de seguimento, foi detectada, na coronariografia, lesão obstrutiva de 50% em artéria coronária direita. Decidiu-se modificar a terapêutica do paciente, iniciando diltiazen substituindo o captopril, e associando-se complexo vitamínico (betacaroteno, C e E mais selênio, na tentativa de evitar progressão da lesão obstrutiva. Foi também realizada orientação dietética por nutricionista. Após 12 meses com a nova terapêutica, a coronariografia mostrou redução significativa da lesão obstrutiva em artéria coronária direita. Durante todo o período de seguimento o paciente apresentou níveis normais no lipidograma. Hoje o paciente encontra-se no terceiro ano de seguimento, assintomático e tendo suas atividades habituais sem intercorrências.The Cardiac Surgery Service of Campo Grande, Santa Casa/MS performed on September 23 rd, 1994 an orthotopic cardiac transplantation in a 27 year-old man with idiopathic dilated cardiomyopathy, which elapsed without abnormalities. The patient left the ICU in 7 days and was discharged at 40 th postoperative day, receiving cyclosporine, azathioprine and prednisone for graft support; captopril, furosemide and aspirin. Presented at one year follow-up, 2 rejection episodes, mil and moderate, when the immunesupressivet herapy dose was modified. On September 1995, at follow up, an

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

Vasorelaxing and antihypertensive activities of synthesized peptides derived from computer-aided simulation of pepsin hydrolysis of yam dioscorin

OpenAIRE

Lin, Yin-Shiou; Lu, Yeh-Lin; Wang, Guei-Jane; Liang, Hong-Jen; Hou, Wen-Chi

2014-01-01

Background We reported that yam dioscorin and its peptic hydrolysates exhibited ACE inhibition and antihypertensive effects on SHRs, however, the active peptides are not really isolated until now. Using ACE inhibitory screenings, two penta-peptides, KTCGY and KRIHF, were selected for ex vivo and in vivo experiments. Results KTCGY, KRIHF, and captopril were shown to have similar vasodilating effects against phenylephrine (PE)-induced tensions in rat endothelium-dependent thoracic aortic rings,...

Management of patients with severe hypertension in emergency department, Maharaj Nakorn Chiang Mai hospital.

Science.gov (United States)

Sruamsiri, Kamphee; Chenthanakij, Boriboon; Wittayachamnankul, Borwon

2014-09-01

Management of patients with severe hypertension without progressive target organ damage remains controversial. Some guidelines mentioned oral anti-hypertensive medication as a treatment to reduce blood pressure in the emergency department, while others recommended against such treatment. To review the management ofpatients with severe hypertension without progressive target organ damage in the emergency department, Maharaj Nakorn Chiang Mai hospital. In a retrospective descriptive analysis study, medical records ofadult patients diagnosed with severe hypertension without progressive target organ damage between January 2011 and December 2012 were reviewed. Patient demographics, data on management including investigation sent and treatment given were collected. Statistical analysis was done by using descriptive statistics and Kruskal-Wallis one-way analysis of variance test. One hundred fifty one medical records were reviewed. Four oral anti-hypertensive medication were used to reduce blood pressure, Amlodipine, Captopril, Hydralazine, and Nifedipine. There were no significant diference between each medication in terms of their effect on bloodpressure reduction (p = 0.513). No side effect or other complications from the use of oral anti-hypertensive medication were recorded The choice of medication used for the treatment of hypertensive urgency ranged from Amlodipine, Captopril, Hydralazine, and Nifedipine, which varied in dosage. However their efficacies were the same when compared with each other and none produced any notable side effects.

Zinc-selective inhibition of the promiscuous bacterial amide-hydrolase DapE: implications of metal heterogeneity for evolution and antibiotic drug design.

Science.gov (United States)

Uda, Narasimha Rao; Upert, Grégory; Angelici, Gaetano; Nicolet, Stefan; Schmidt, Tobias; Schwede, Torsten; Creus, Marc

2014-01-01

The development of resistance to virtually all current antibiotics makes the discovery of new antimicrobial compounds with novel protein targets an urgent challenge. The dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase (DapE) is an essential metallo-enzyme for growth and proliferation in many bacteria, acting in the desuccinylation of N-succinyl-L,L-diaminopimelic acid (SDAP) in a late stage of the anabolic pathway towards both lysine and a crucial building block of the peptidoglycan cell wall. L-Captopril, which has been shown to exhibit very promising inhibitory activity in vitro against DapE and has attractive drug-like properties, nevertheless does not target DapE in bacteria effectively. Here we show that L-captopril targets only the Zn(2+)-metallo-isoform of the enzyme, whereas the Mn(2+)-enzyme, which is also a physiologically relevant isoform in bacteria, is not inhibited. Our finding provides a rationale for the failure of this promising lead-compound to exhibit any significant antibiotic activity in bacteria and underlines the importance of addressing metallo-isoform heterogeneity in future drug design. Moreover, to our knowledge, this is the first example of metallo-isoform heterogeneity in vivo that provides an evolutionary advantage to bacteria upon drug-challenge.

S-nitrosocaptopril nanoparticles as nitric oxide-liberating and transnitrosylating anti-infective technology.

Science.gov (United States)

Mordorski, Breanne; Pelgrift, Robert; Adler, Brandon; Krausz, Aimee; da Costa Neto, Alexandre Batista; Liang, Hongying; Gunther, Leslie; Clendaniel, Alicea; Harper, Stacey; Friedman, Joel M; Nosanchuk, Joshua D; Nacharaju, Parimala; Friedman, Adam J

2015-02-01

Nitric oxide (NO), an essential agent of the innate immune system, exhibits multi-mechanistic antimicrobial activity. Previously, NO-releasing nanoparticles (NO-np) demonstrated increased antimicrobial activity when combined with glutathione (GSH) due to formation of S-nitrosoglutathione (GSNO), a transnitrosylating agent. To capitalize on this finding, we incorporated the thiol-containing ACE-inhibitor, captopril, with NO-np to form SNO-CAP-np, nanoparticles that both release NO and form S-nitrosocaptopril. In the presence of GSH, SNO-CAP-np demonstrated increased transnitrosylation activity compared to NO-np, as exhibited by increased GSNO formation. Escherichia coli and methicillin-resistant Staphylococcus aureus were highly susceptible to SNO-CAP-np in a dose-dependent fashion, with E. coli being most susceptible, and SNO-CAP-np were nontoxic in zebrafish embryos at translatable concentrations. Given SNO-CAP-np's increased transnitrosylation activity and increased E. coli susceptibility compared to NO-np, transnitrosylation rather than free NO is likely responsible for overcoming E. coli's resistance mechanisms and ultimately killing the pathogen. This team of authors incorporated the thiol-containing ACE-inhibitor, captopril, into a nitric oxide releasing nanoparticle system, generating nanoparticles that both release NO and form S-nitrosocaptopril, with pronounced toxic effects on MRSA and E. coli in the presented model system. Copyright © 2015 Elsevier Inc. All rights reserved.

The effect of hypertension on adult hippocampal neurogenesis in young adult spontaneously hypertensive rats and Dahl rats

Czech Academy of Sciences Publication Activity Database

Pištíková, Adéla; Brožka, Hana; Bencze, Michal; Radostová, Dominika; Valeš, Karel; Stuchlík, Aleš

2017-01-01

Roč. 66, č. 5 (2017), s. 881-887 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GBP304/12/G069 Grant - others:Rada Programu interní podpory projektů mezinárodní spolupráce AV ČR(CZ) M200111204 Institutional support: RVO:67985823 Keywords : adult neurogenesis * Captopril * hypertension * Dahl rats * SHR * young animals Subject RIV: FH - Neurology OBOR OECD: Neurosciences (including psychophysiology Impact factor: 1.461, year: 2016

Cicatrização de feridas: estudo comparativo em ratos hipertensos não tratados e tratados com inibidor da enzima conversora da angiotensina

Directory of Open Access Journals (Sweden)

Maria de Lourdes Pessole Biondo-Simões

Full Text Available OBJETIVO: Reconhecer a interferência do captopril na cicatrização de feridas cutâneas de ratos hipertensos. MÉTODOS: Distribuíram-se 111 ratos em quatro grupos: controle normotenso (N=30; controle hipertenso (N=30, os quais receberam 1 ml/dia de solução de cloreto de sódio a 0.9% por via oral; grupo experimento (N=31, hipertensos que receberam 7,5mg/kg/dia de captopril e um grupo aferição (N=20, 10 hipertensos e 10 normotensos, nos quais aferiu-se a pressão na aorta abdominal, no último dia de experimento. Após 15 dias de medicação, fez-se uma incisão da pele e da tela subcutânea, na região médio-dorsal dos grupos I, II e III, seguida de síntese. Ressecaram-se as cicatrizes de 10 animais de cada grupo, no 4.º, 7.º e 14.º dias após a operação, que divididas em duas partes foram enviadas para a tensiometria e para análise histológica. RESULTADOS: A pressão arterial média de 83,18 ± 7,51 mmHg nos normotensos e 151,36 ± 10,51 mmHg nos hipertensos. As cicatrizes dos hipertensos tratados e não tratados eram menos resistentes que as dos normotensos, nos tempos iniciais (p<0,05 e que ao 14.º dia as resistências se igualaram. Não houve diferença entre o grupo tratado e o não tratado. A densidade de colágeno total foi maior nos normotensos em todos os tempos (p<0,05 e não houve diferença entre hipertensos tratados e não tratados. A epitelização, a reação inflamatória e a formação do tecido de granulação foi semelhante nos três grupos. CONCLUSÕES: O captopril, em ratos, não modifica a cicatrização, ficando as diferenças relacionadas à hipertensão.

Determination of effect of aspirin and captopril on cat glomerular ...

African Journals Online (AJOL)

Index Medicus, JournalSeek, Journal Citation Reports/Science Edition, Directory of Open Access Journals. (DOAJ), African Journal Online, Bioline International, Open-J-Gate and Pharmacy Abstracts. INTRODUCTION. Scintigraphy has been proposed as a practical method in nuclear medicine. In addition, it is one.

SINERGISMO FARMACODINÁMICO. A PROPÓSITO DE UN CASO INTERVENIDO QUIRÚRGICAMENTE DE URGENCIA BAJO ANESTESIA GENERAL.

Directory of Open Access Journals (Sweden)

Yesid Pallares Villarreal

2004-01-01

Full Text Available Presentamos una paciente femenina geriatrica con antecedentes de hipertensiòn arterial y trastornos psiquiatricos intervenida quirurgicamente de urgencia por un cuadro doloroso abdominal, con una interaccion farmacodinamica por sinergismo del doxepin y captopril potenciada por los efectos de la anestesia general. La hipotensiòn arterial fue la forma clínica de presentación. La paciente se recibió hipotensa por la administración preoperatoria de doxepin tratamiento de base y de captopril tratamiento impuesto por crisis hipertensiva antes de su llegada al hospital. Después de la inducción de la anestesia general desarrolla hipotensión arterial que sólo responde a la administración de noradrenalina. En un inicio se interpreta como un shock séptico en fase hipodinámica por el cuadro doloroso abdominal y la vasoplejia pero descartadas otras causas se concluye como hipotensión arterial de origen farmacológico con relación a la ingestión de antidepresivos triciclicos e inhibidores de la enzima convertora de angiotensina I en angiotensina II por su acción sobre el sistema nervioso simpático por potenciada por los agentes anestésicos. La paciente fue dada de alta del hospital satisfactoriamente a los 7 dias de operada.

3D printing of tablets containing multiple drugs with defined release profiles.

Science.gov (United States)

Khaled, Shaban A; Burley, Jonathan C; Alexander, Morgan R; Yang, Jing; Roberts, Clive J

2015-10-30

We have employed three-dimensional (3D) extrusion-based printing as a medicine manufacturing technique for the production of multi-active tablets with well-defined and separate controlled release profiles for three different drugs. This 'polypill' made by a 3D additive manufacture technique demonstrates that complex medication regimes can be combined in a single tablet and that it is viable to formulate and 'dial up' this single tablet for the particular needs of an individual. The tablets used to illustrate this concept incorporate an osmotic pump with the drug captopril and sustained release compartments with the drugs nifedipine and glipizide. This combination of medicines could potentially be used to treat diabetics suffering from hypertension. The room temperature extrusion process used to print the formulations used excipients commonly employed in the pharmaceutical industry. Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR) and X-ray powder diffraction (XRPD) were used to assess drug-excipient interaction. The printed formulations were evaluated for drug release using USP dissolution testing. We found that the captopril portion showed the intended zero order drug release of an osmotic pump and noted that the nifedipine and glipizide portions showed either first order release or Korsmeyer-Peppas release kinetics dependent upon the active/excipient ratio used. Copyright © 2015. Published by Elsevier B.V.

Metabolism of enkephalin in stomach wall of rats

Energy Technology Data Exchange (ETDEWEB)

Bunnett, N.W.; Walsh, J.H.; Debas, H.T. (Univ. of California, San Francisco (USA))

1990-01-01

Peptidases degrade neuropeptides and thereby limit the duration and extent of their influence. This investigation examined the importance of peptidases in the degradation of the neuropeptide enkephalin in the stomach wall of the rat. Metabolism of (Leu5)- and (D-Ala2)(Leu5)enkephalin by gastric membranes was examined in vitro. Degradation of (Tyr1-3H)(Leu5)enkephalin was studied in the gastric submucosa of anesthetized and conscious rats in vivo by using a catheter to deliver peptide to tissues and implanted dialysis fibers to collect the metabolites. Specific inhibitors were used to assess the contribution of particular enzymes. (Leu5)- and (Tyr1-3H)(Leu5)enkephalin were metabolized by membranes and in the stomach wall by hydrolysis of the Tyr1-Gly2 bond. Degradation was inhibited by the aminopeptidase inhibitor amastatin (10(-5) M in vitro, 10 nmol in vivo). Inhibitors of endopeptidase-24.11 (phosphoramidon) and angiotensin-converting enzyme (captopril) did not inhibit degradation. Metabolism of the aminopeptidase-resistant analogue (D-Ala2)(Leu5)enkephalin by membranes was unaffected by amastatin and weakly inhibited by phosphoramidon affected by amastatin and weakly inhibited by phosphoramidon and captopril. A carboxypeptidase removed the COOH-terminal leucine residue and made a substantial contribution to degradation of both peptides by gastric membranes.

Caso clínico de la Unidad de Medicina Interna Hipertensión arterial de origen renovascular

Directory of Open Access Journals (Sweden)

Análida E. Pinilla Roa

1993-10-01

Full Text Available Hombre de 28 años, natural y procedente de Bogotá, consulto por cefalea progresiva fronta-occipital de treinta horas de evolución, acompañada de vomito en dos oportunidades y de trastorno de la conciencia, con relajación del esfínter vesical. La esposa informo episodio similar un mes ames, cuando fue hospitalizado, encontrándose HTA y hemorragia subaracnoidea. Salió contratamiento triconjugado (captopril, nifedipina, propanolol, el cual suspendió ocho días antes del ingreso.

A prevenção da hipertensão arterial determina a redução da lesão renal no diabetes experimental

OpenAIRE

Maria Valeria Pavan

2002-01-01

Resumo: O objetivo deste estudo foi avaliar o efeito da prevenção da hipertensão arterial com drogas que bloqueiam o sistema renina-angiotensina ou terapia convencional na nefropatia diabética de um modelo de hipertensão genética e diabetes mellitus. Ratos espontaneamente hipertensos (SHR), com 4 semanas de idade, com diabetes induzido por estreptozotocina, foram randomizados para não receberem tratamento anti-hipertensivo, ou serem tratados com captopril, ou losartan, ou terapia tríplice (hi...

Estudo da atividade inibitória enzimática da quercetina sobre a resposta vasodepressora induzida pela bradicinina

Directory of Open Access Journals (Sweden)

Luciane Pereira Nascimento Häckl

Full Text Available Em estudos recentes tem sido sugerido que os flavonóides, compostos de origem vegetal sendo encontrados em vários produtos alimentares, possuem uma ação inibitória de vários sistemas enzimáticos. A inibição da enzima conversora da angiotensina (ECA tem sido utilizada no tratamento da hipertensão. O mecanismo de ação dos inibidores da ECA implica na formação da Angiotensina II e na degradação da bradicinina. O propósito do presente estudo foi de analisar a ação da quercetina na atividade da ECA através da avaliação do efeito da angiotensina I (AI e da bradicinina (BK na pressão arterial de ratos anestesiados. Foram utilizados neste estudo ratos Wistar machos adultos. Estes animais foram anestesiados com uretana e foi introduzida na traquéia uma cânula de polietileno (PE 240 para facilitar a respiração. Também foi isolada e canulada (PE 50 a veia jugular para administração das substâncias em estudo. Para registro da pressão arterial foi introduzida na artéria carótida comum esquerda uma cânula de polietileno (PE 50 acoplada a um transdutor de pressão. A administração de BK (10 nmol/kg, i.v. induziu um efeito hipotensor, enquanto que a administração de AI (0,1 nmol/kg induziu uma resposta hipertensora. Pré-tratamento com captopril v.o. (100 nmol/kg 45 min antes e i.v. (10 nmol/kg 5 min antes aumentou significativamente a resposta à BK; embora captopril reduziu, também significativamente, o efeito da AI. O tratamento com quercetina via oral (30 mg/kg 45 min antes e via intravenosa (5 mg/kg 5 min antes aumentou significativamente o efeito da BK. O efeito da AI foi significativamente reduzido por ambos os tratamentos. Estes resultados sugerem que a quercetina potenciou o efeito hipotensor da bradicinina e reduziu o efeito hipertensor da angiotensina I através de ação inibitória sobre a enzima conversora da angiotensina, portanto apresentando um mecanismo de ação semelhante ao captopril.

Analysis of captopril in surface waters by differential pulse voltammetry method

International Nuclear Information System (INIS)

Baranowska, I.; Markowski, P.; Wilk, K.

2009-01-01

One of the important problems concerning waters ecosystems is the presence of pharmaceuticals remains in different kinds of surface waters. These compounds cause huge changes in waters environment. They cause genetic changes in water organisms, are not also neutral for people in case of penetrating into drinking water. (Author)

Mitigation of radiation nephropathy after internal α-particle irradiation of kidneys

International Nuclear Information System (INIS)

Jaggi, Jaspreet Singh; Seshan, Surya V.; McDevitt, Michael R.; Sgouros, George; Hyjek, Elizabeth; Scheinberg, David A.

2006-01-01

Purpose: Internal irradiation of kidneys as a consequence of radioimmunotherapy, radiation accidents, or nuclear terrorism can result in radiation nephropathy. We attempted to modify pharmacologically, the functional and morphologic changes in mouse kidneys after injection with the actinium ( 225 Ac) nanogenerator, an in vivo generator of α- and β-particle emitting elements. Methods and Materials: The animals were injected with 0.35 μCi of the 225 Ac nanogenerator, which delivers a dose of 27.6 Gy to the kidneys. Then, they were randomized to receive captopril (angiotensin-converting enzyme inhibitor), L-158,809 (angiotensin II receptor-1 blocker), spironolactone (aldosterone receptor antagonist), or a placebo. Results: Forty weeks after the 225 Ac injection, the placebo-control mice showed a significant increase in blood urea nitrogen (BUN) (87.6 ± 6.9 mg/dL), dilated Bowman spaces, and tubulolysis with basement membrane thickening. Captopril treatment accentuated the functional (BUN 119.0 ± 4.0 mg/dL; p <0.01 vs. placebo controls) and histopathologic damage. In contrast, L-158,809 offered moderate protection (BUN 66.6 ± 3.9 mg/dL; p = 0.02 vs. placebo controls). Spironolactone treatment, however, significantly prevented the development of histopathologic and functional changes (BUN 31.2 ± 2.5 mg/dL; p <0.001 vs. placebo controls). Conclusions: Low-dose spironolactone and, to a lesser extent, angiotensin receptor-1 blockade can offer renal protection in a mouse model of internal α-particle irradiation

Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction

DEFF Research Database (Denmark)

Anavekar, Nagesh S; McMurray, John J V; Velazquez, Eric J

2004-01-01

BACKGROUND: The presence of coexisting conditions has a substantial effect on the outcome of acute myocardial infarction. Renal failure is associated with one of the highest risks, but the influence of milder degrees of renal impairment is less well defined. METHODS: As part of the Valsartan...... captopril, valsartan, or both. The glomerular filtration rate (GFR) was estimated by means of the four-component Modification of Diet in Renal Disease equation, and the patients were grouped according to their estimated GFR. We used a 70-candidate variable model to adjust and compare overall mortality...

Role of the renin-angiotensin system in regulation and autoregulation of renal blood flow

DEFF Research Database (Denmark)

Sørensen, Charlotte Mehlin; Leyssac, Paul Peter; Skøtt, Ole

2000-01-01

The role for ANG II in renal blood flow (RBF) autoregulation is unsettled. The present study was designed to test the effect of clamping plasma ANG II concentrations ([ANG II]) by simultaneous infusion of the angiotensin-converting enzyme inhibitor captopril and ANG II on RBF autoregulation...... in halothane-anesthetized Sprague-Dawley rats. Autoregulation was defined as the RBF response to acute changes in renal perfusion pressure (RPP). Regulation was defined as changes in RBF during long-lasting changes in RPP. The results showed that a prolonged reduction of RPP reset the lower limit...

Vliv chronického podávání captoprilu na vasokonstrikci vyvolanou noradrenalinem (NA) u SHR a WKY : In vivo studie

Czech Academy of Sciences Publication Activity Database

Pintérová, Mária; Kuneš, Jaroslav; Dobešová, Zdenka; Zicha, Josef

2008-01-01

Roč. 50, č. 9 (2008), K168-K168 ISSN 0010-8650. [Konference ČSH /25./, Konference prac. skupiny preventivní kardiologie ČKS /17./, Konference prac. skupiny srdeční selhání ČKS /13./. 02.10.2008-04.10.2008, Český Krumlov] R&D Projects: GA MŠk(CZ) 1M0510; GA ČR(CZ) GA305/08/0139 Institutional research plan: CEZ:AV0Z50110509 Keywords : cpo1 * captopril * norepinephrine-induced vasoconstriction * SHR and WKY rat Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

Recent advances and future projections in clinical radionuclide imaging

International Nuclear Information System (INIS)

Peters, A.M.

1990-01-01

This outline review of recent advances in radionuclide imaging draws attention to developments in nuclear medicine of the urinary tract such as Captopril renography and the introduction of MAG-3, the technetium-99m labelled mimic of hippuran, the use of radionuclides for infection diagnosis, advances in lung perfusion scanning, new radiopharmaceuticals for cardiac imaging, and developments in radiopharmaceuticals for imaging tumours, including gallium-67, thallium-201, and the development of radiolabelled monoclonal antibodies. Attention is drawn to the wider use of nuclear medicine in child care. (author)

Efecto vasodilatador mediado por óxido nítrico del extracto hidroalcohólico de Zea mays L. (maíz morado en anillos aórticos de rata Vasodilator effect mediated by nitric oxide of the Zea mays L (andean purple corn hydroalcoholic extract in aortic rings of rat

Directory of Open Access Journals (Sweden)

Oscar Moreno-Loaiza

2010-12-01

Full Text Available Objetivo. Evaluar la respuesta vasodilatadora e inhibidora de la vasoconstricción del extracto hidroalcohólico de Zea mays L. (maíz morado y determinar si esta respuesta es mediada por óxido nítrico (NO. Materiales y métodos. Se obtuvo un extracto de las corontas de maíz morado maceradas durante ocho días en etanol al 70%, y posterior concentración del producto. Se trabajó con anillos aórticos de rata en cámara de órganos aislados, bañada con solución Krebs-Hensleit (K-H y se registró la actividad vasomotora con un transductor de tensión isométrica. Se produjo una contracción basal con KCl 120 mM sobre la cual determinó el efecto vasodilatador de tres dosis del extracto: 0,1; 0,5 y 1,0 mg/mL. Se utilizó L-NG-Nitroarginina metil ester (L-NAME para comprobar que la vasodilatación depende de la óxido nítrico sinteasa (NOs. Luego se comparó la inhibición de la contracción vascular tras la incubación durante 30 minutos, con extracto de maíz morado y captopril 10-5 M. Resultados. Se observó una reducción de la contracción máxima (100% a 85,25 ± 2,60%, 77,76 ± 3,23% y 73,3 ± 4,87%, para las dosis de 0,1; 0,5 y 1,0 mg/mL, respectivamente. La vasodilatación fue inhibida por la incubación previa con L-NAME. El extracto de maíz morado no inhibió la contracción vascular, a diferencia del captopril (reducción a 75,27 ± 8,61%. Conclusión. El extracto hidroalcohólico de Zea mays L produce vasodilatación dependiente de la síntesis de NO.Objective: To evaluate the vasodilator response of the hydroalcoholic extract of Zea mays L. (Andean purple corn and to determine if this response is mediated by nitric oxide (NO. Material and methods: We obtained an extract by maceration for eight days of Andean purple corn cobs in 70% ethanol and subsequent concentration of the product. Thoracic aortic rings were evaluated in an isolated organ chamber, bathed with Krebs-Hensleit solution (KH, and vasomotor activity was recorded

Adaptation of pharmaceutical excipients to FDM 3D printing for the fabrication of patient-tailored immediate release tablets.

Science.gov (United States)

Sadia, Muzna; Sośnicka, Agata; Arafat, Basel; Isreb, Abdullah; Ahmed, Waqar; Kelarakis, Antonios; Alhnan, Mohamed A

2016-11-20

This work aims to employ fused deposition modelling 3D printing to fabricate immediate release pharmaceutical tablets with several model drugs. It investigates the addition of non-melting filler to methacrylic matrix to facilitate FDM 3D printing and explore the impact of (i) the nature of filler, (ii) compatibility with the gears of the 3D printer and iii) polymer: filler ratio on the 3D printing process. Amongst the investigated fillers in this work, directly compressible lactose, spray-dried lactose and microcrystalline cellulose showed a level of degradation at 135°C whilst talc and TCP allowed consistent flow of the filament and a successful 3D printing of the tablet. A specially developed universal filament based on pharmaceutically approved methacrylic polymer (Eudragit EPO) and thermally stable filler, TCP (tribasic calcium phosphate) was optimised. Four model drugs with different physicochemical properties were included into ready-to-use mechanically stable tablets with immediate release properties. Following the two thermal processes (hot melt extrusion (HME) and fused deposition modelling (FDM) 3D printing), drug contents were 94.22%, 88.53%, 96.51% and 93.04% for 5-ASA, captopril, theophylline and prednisolone respectively. XRPD indicated that a fraction of 5-ASA, theophylline and prednisolone remained crystalline whilst captopril was in amorphous form. By combining the advantages of thermally stable pharmaceutically approved polymers and fillers, this unique approach provides a low cost production method for on demand manufacturing of individualised dosage forms. Copyright © 2016 Elsevier B.V. All rights reserved.

Perinatal DDT Exposure Induces Hypertension and Cardiac Hypertrophy in Adult Mice.

Science.gov (United States)

La Merrill, Michele A; Sethi, Sunjay; Benard, Ludovic; Moshier, Erin; Haraldsson, Borje; Buettner, Christoph

2016-11-01

Dichlorodiphenyltrichloroethane (DDT) was used extensively to control malaria, typhus, body lice, and bubonic plague worldwide, until countries began restricting its use in the 1970s. However, the use of DDT to control vector-borne diseases continues in developing countries. Prenatal DDT exposure is associated with elevated blood pressure in humans. We hypothesized that perinatal DDT exposure causes hypertension in adult mice. DDT was administered to C57BL/6J dams from gestational day 11.5 to postnatal day 5. Blood pressure (BP) and myocardial wall thickness were measured in male and female adult offspring. Adult mice were treated with an angiotensin converting enzyme (ACE) inhibitor, captopril, to evaluate sensitivity to amelioration of DDT-associated hypertension by ACE inhibition. We further assessed the influence of DDT exposure on the expression of mRNAs that regulate BP through renal ion transport. Adult mice perinatally exposed to DDT exhibited chronically increased systolic BP, increased myocardial wall thickness, and elevated expression of mRNAs of several renal ion transporters. Captopril completely reversed hypertension in mice perinatally exposed to DDT. These data demonstrate that perinatal exposure to DDT causes hypertension and cardiac hypertrophy in adult offspring. A key mechanism underpinning this hypertension is an overactivated renin angiotensin system because ACE inhibition reverses the hypertension induced by perinatal DDT exposure. Citation: La Merrill M, Sethi S, Benard L, Moshier E, Haraldsson B, Buettner C. 2016. Perinatal DDT exposure induces hypertension and cardiac hypertrophy in adult mice. Environ Health Perspect 124:1722-1727; http://dx.doi.org/10.1289/EHP164.

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)

New trends in radioisotope renal function studies: Improved diagnostic potential by pharmacological intervention and by quantitative analysis

International Nuclear Information System (INIS)

Kletter, K.

1988-01-01

Tc99m mercaptoacetyltriglycine (Tc99m MAG3) was tested as replacement for I123 orthoiodohippuric acid (I123 oIH) both in the form of a HPLC purified substance and as an impure kit preparation. The influence of angiotensin converting enzyme (ACE) inhibitors (captopril) leads to characteristic changes in the renograms of patients with Goldblatt hypertension. Quantitative criteria for the evidence of haemodynamically significant renal artery stenosis were derived from investigations without and with captopril (25 mg) (I123 oIH and Tc99m DTPA) in 21 patients with essential hypertension. Diuresis renography is used for the assessment of urinary outflow obstruction. Up till now mainly qualitative criteria have been used for the evaluation of the washout curves. The introduction of the quantitative parameter of peak elimination rate for washout curve analysis yielded a significantly better concordance between diuresis renography and the invasive Whitaker test. The parameter of peak elimination (E max ) is mathematically clearly defined and is closely related to the peak urinary flow after frusemide. The dependence of the diuresis renogram on renal function and the degree of hydronephrosis was investigated in 80 ureterorenal units. Diuresis renography was tested and found to be a useful method for the assessment of hydronephrosis in newborn children. Follow up investigations of 7 children during the first weeks and months post partum revealed valuable diagnostic results in all cases. There was no sign that the diagnostic potential of diuresis renography was in any way restricted by as yet incompletely developed renal function during the first months of life. (Author, shortened by Quittner)

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.

Hypotensive effect of aqueous extract of jamu antiatherosclerosis in male rats

Science.gov (United States)

Tristantini, Dewi; Amelinda, Kelly

2018-02-01

For many years, Averrhoa carambola L leaves, Mimusops elengi Linn leaves and Curcuma xanthorrhiza Roxb are used empirically in Indonesian traditional medicine to treat hypertension. This study was conducted to investigate the hypotensive effect of Averrhoa carambola L leaves, Mimusops elengi Linn leaves, and Curcuma xanthorrhiza Roxb extract (Jamu Antiatherosclerosis) in hypertensive induced rats. The effect of aqueous extract of jamu antiatherosclerosis on diastolic and systolic blood pressure was determined in sodium chloride induced rats. Twenty-four male rats weighted 160-200 g were randomly divided into 6 groups of 4 rats. The groups are consisting of normal control (without treatment), positive control (induced and given captopril 1.35 mg / 200 g body weight of rats), negative control (induced and standard feed), dosage controls (induced and given the extract of jamu antiatherosclerosis) each group with 3 different doses. The composition is dose I (13.2 mg / 200 g body weight of rats), dose II (26.4 mg / 200 g body weight of rats ml) and dose III (52.8 mg / 200 g body weight of rats). Blood pressure were measured via non-invasive blood pressure. The blood pressure was decreased in all dose. However, dose III has the highest blood pressure reducing effect that is 29.42 mmHg or 25.14% for diastolic blood pressure and 34.58 mmHg or 22.03% for systolic blood pressure. This performance equals to 91.15% and 93.56% of captopril activity in decreasing diastolic and systolic blood pressure. The aqueous extract has blood pressure lowering property that can be used as antihypertension herbal medicine.

Antioxidant and ACE Inhibitory Bioactive Peptides Purified from Egg Yolk Proteins

Directory of Open Access Journals (Sweden)

Marwa Yousr

2015-12-01

Full Text Available Protein by-products from the extraction of lecithin from egg yolk can be converted into value-added products, such as bioactive hydrolysates and peptides that have potential health enhancing antioxidant, and antihypertensive properties. In this study, the antioxidant and angiotensin converting enzyme (ACE inhibitory activities of peptides isolated and purified from egg yolk protein were investigated. Defatted egg yolk was hydrolyzed using pepsin and pancreatin and sequentially fractionated by ultrafiltration, followed by gel filtration to produce egg yolk gel filtration fractions (EYGF. Of these, two fractions, EYGF-23 and EYGF-33, effectively inhibited the peroxides and thiobarbituric acid reactive substance (TBARS in an oxidizing linoleic acid model system. The antioxidant mechanism involved superoxide anion and hydroxyl radicals scavenging and ferrous chelation. The presence of hydrophobic amino acids such as tyrosine (Y and tryptophan (W, in sequences identified by LC-MS as WYGPD (EYGF-23 and KLSDW (EYGF-33, contributed to the antioxidant activity and were not significantly different from the synthetic BHA antioxidant. A third fraction (EYGF-56 was also purified from egg yolk protein by gel filtration and exhibited high ACE inhibitory activity (69% and IC50 value (3.35 mg/mL. The SDNRNQGY peptide (10 mg/mL had ACE inhibitory activity, which was not significantly different from that of the positive control captopril (0.5 mg/mL. In addition, YPSPV in (EYGF-33 (10 mg/mL had higher ACE inhibitory activity compared with captopril. These findings indicated a substantial potential for producing valuable peptides with antioxidant and ACE inhibitory activity from egg yolk.

Antioxidant and ACE Inhibitory Bioactive Peptides Purified from Egg Yolk Proteins.

Science.gov (United States)

Yousr, Marwa; Howell, Nazlin

2015-12-07

Protein by-products from the extraction of lecithin from egg yolk can be converted into value-added products, such as bioactive hydrolysates and peptides that have potential health enhancing antioxidant, and antihypertensive properties. In this study, the antioxidant and angiotensin converting enzyme (ACE) inhibitory activities of peptides isolated and purified from egg yolk protein were investigated. Defatted egg yolk was hydrolyzed using pepsin and pancreatin and sequentially fractionated by ultrafiltration, followed by gel filtration to produce egg yolk gel filtration fractions (EYGF). Of these, two fractions, EYGF-23 and EYGF-33, effectively inhibited the peroxides and thiobarbituric acid reactive substance (TBARS) in an oxidizing linoleic acid model system. The antioxidant mechanism involved superoxide anion and hydroxyl radicals scavenging and ferrous chelation. The presence of hydrophobic amino acids such as tyrosine (Y) and tryptophan (W), in sequences identified by LC-MS as WYGPD (EYGF-23) and KLSDW (EYGF-33), contributed to the antioxidant activity and were not significantly different from the synthetic BHA antioxidant. A third fraction (EYGF-56) was also purified from egg yolk protein by gel filtration and exhibited high ACE inhibitory activity (69%) and IC50 value (3.35 mg/mL). The SDNRNQGY peptide (10 mg/mL) had ACE inhibitory activity, which was not significantly different from that of the positive control captopril (0.5 mg/mL). In addition, YPSPV in (EYGF-33) (10 mg/mL) had higher ACE inhibitory activity compared with captopril. These findings indicated a substantial potential for producing valuable peptides with antioxidant and ACE inhibitory activity from egg yolk.

Blood Pressure Lowering and Safety Improvements With Liver Angiotensinogen Inhibition in Models of Hypertension and Kidney Injury.

Science.gov (United States)

Mullick, Adam E; Yeh, Steve T; Graham, Mark J; Engelhardt, Jeffery A; Prakash, Thazha P; Crooke, Rosanne M

2017-09-01

Uncontrolled hypertension is an important contributor to cardiovascular disease. Despite the armamentarium of antihypertensive treatments, there remains a need for novel agents effective in individuals who cannot reach acceptable blood pressure levels. Inhibitors targeting the renin-angiotensin-aldosterone system (RAAS) are widely used but may not optimally inhibit RAAS and demonstrate an acceptable safety profile. Experiments were conducted to characterize a series of AGT (angiotensinogen) antisense oligonucleotides (ASOs) and compare their efficacy and tolerability to traditional RAAS blockade. AGT ASOs which target multiple systemic sites of AGT versus an N-acetylgalactosamine-conjugated AGT ASO that targets the liver were compared with captopril and losartan. Spontaneously hypertensive rats fed an 8% NaCl diet, a model of malignant hypertension resistant to standard RAAS inhibitors, demonstrated robust and durable blood pressure reductions with AGT ASO treatments, which was not observed with standard RAAS blockade. Studies in rat models of acute kidney injury produced by salt deprivation revealed kidney injury with ASO treatment that reduced kidney-expressed AGT, but not in animals treated with the N-acetylgalactosamine AGT ASO despite comparable plasma AGT reductions. Administration of either captopril or losartan also produced acute kidney injury during salt deprivation. Thus, intrarenal RAAS derived from kidney AGT, and inhibited by the standard of care, contributes to the maintenance of renal function during severe RAAS challenge. Such improvements in efficacy and tolerability by a liver-selective AGT inhibitor could be desirable in individuals not at their blood pressure goal with existing RAAS blockade. © 2017 American Heart Association, Inc.

Long-term outcomes of left bundle branch block in high-risk survivors of acute myocardial infarction: the VALIANT experience

DEFF Research Database (Denmark)

Stephenson, Kent; Skali, Hicham; McMurray, John J V

2006-01-01

was to determine if new LBBB is an independent predictor of long-term fatal and nonfatal outcomes in high-risk survivors of MI by reviewing data from the VALsartan In Acute myocardial iNfarcTion (VALIANT) trial. METHODS: In VALIANT, 14,703 patients with LV systolic dysfunction and/or HF were randomized...... to valsartan, captopril, or both a mean of 5 days after MI. Baseline ECG data were available from 14,259 patients. We assessed the predictive value of new LBBB for death and major cardiovascular outcomes after 3 years, adjusting for multiple baseline covariates including LV ejection fraction. RESULTS...

Renin-angiotensin system (RAS) blockade attenuates growth and metastatic potential of renal cell carcinoma in mice.

Science.gov (United States)

Araújo, Wedson F; Naves, Marcelo A; Ravanini, Juliana N; Schor, Nestor; Teixeira, Vicente P C

2015-09-01

Renal cell carcinoma (RCC) is the most frequent type of cancer among renal neoplasms in adults and responds poorly to radiotherapy and chemotherapy. There is evidence that blockade of the renin-angiotensin system (RAS) might have antineoplastic effects. The aim of this study was to investigate the effects of RAS blockade on RCC in a murine model. Murine renal cancer cells (Renca) were injected (1 × 10(5)) into the subcapsular space of the left kidney of BALB/c mice (8 wk of age). The animals were divided into 4 groups: a control group (no treatment), angiotensin-receptor blockers group (losartan 100mg/kg/d), angiotensin-converting enzyme inhibitor group (captopril 10mg/kg/d), and angiotensin-receptor blockers +angiotensin-converting enzyme inhibitor group (losartan 100mg/kg/d +captopril 10mg/kg/d). The animals received the drugs by gavage for 21 days after inoculation, beginning 2 days before tumor induction, and were then euthanized. After killing the animals, the kidneys and lungs were removed, weighed, and processed for histopathological and immunohistochemical analyses. Angiogenesis and vascular microvessels were assessed with the antibodies anti-vascular endothelial growth factor and anti-CD34. Angiotensin II-inoculated animals developed renal tumors. Treated animals presented smaller tumors, regardless of the therapeutic regimen, and far fewer lung metastases in both quantity and dimension compared with the controls. The expression of vascular endothelial growth factor and CD34 were significantly decreased in renal tumors of treated animals compared with the controls. Our findings suggest that blockade of RAS decreases tumor proliferation and metastatic capacity of RCC in this experimental model. Copyright © 2015 Elsevier Inc. All rights reserved.

Probiotic-fermented purple sweet potato yogurt activates compensatory IGF‑IR/PI3K/Akt survival pathways and attenuates cardiac apoptosis in the hearts of spontaneously hypertensive rats.

Science.gov (United States)

Lin, Pei-Pei; Hsieh, You-Miin; Kuo, Wei-Wen; Lin, Yueh-Min; Yeh, Yu-Lan; Lin, Chien-Chung; Tsai, Fuu-Jen; Tsai, Chang-Hai; Huang, Chih-Yang; Tsai, Cheng-Chih

2013-12-01

Apoptosis is recognized as a predictor of adverse outcomes in subjects with cardiac diseases. The aim of this study was to explore the effects of probiotic-fermented purple sweet potato yogurt (PSPY) with high γ-aminobutyric acid (GABA) content on cardiac apoptosis in spontaneously hypertensive rat (SHR) hearts. The rats were orally adminsitered with 2 different concentrations of PSPY (10 and 100%) or captopril, 15.6 mg/kg, body weight (BW)/day. The control group was administered distilled water. DAPI and TUNEL staining were used to detect the numbers of apoptotic cells. A decrease in the number of TUNEL-positive cardiac myocytes was observed in the SHR-PSPY (10 and 100%) groups. In addition, the levels of key components of the Fas receptor- and mitochondrial-dependent apoptotic pathways were determined by western blot analysis. The results revealed that the levels of the key components of the Fas receptor- and mitochondrial-dependent apoptotic pathway were significantly decreased in the SHR-captopril, and 10 and 100% PSPY groups. Additionally, the levels of phosphorylated insulin-like growth factor‑I receptor (p-IGF‑IR) were increased in SHR hearts from the SHR-control group; however, no recovery in the levels of downstream signaling components was observed. In addition, the levels of components of the compensatory IGF-IR-dependent survival pathway (p-PI3K and p-Akt) were all highly enhanced in the left ventricles in the hearts form the SHR-10 and 100% PSPY groups. Therefore, the oral administration of PSPY may attenuate cardiomyocyte apoptosis in SHR hearts by activating IGF‑IR-dependent survival signaling pathways.

Minoxidil-associated anorexia in an infant with refractory hypertension.

Science.gov (United States)

Vesoulis, Zachary A; Attarian, Stephanie J; Zeller, Brandy; Cole, Francis Sessions

2014-12-01

Minoxidil is a potent antihypertensive used as an adjunctive agent in refractory hypertension. It exerts an antihypertensive effect through two mechanisms: selective arterial vasodilation by activation of potassium channels in the vascular smooth muscle and stimulation of carotid and aortic baroreceptors, leading to downstream release of renin and norepinephrine. Although frequently cited in reviews of antihypertensive agents, limited data about the use of minoxidil in neonates are available. We describe an infant girl, born at 35 weeks of gestation, who was diagnosed with idiopathic hypertension after extensive diagnostic evaluation. Adequate blood pressure control was not achieved with captopril, amlodipine, and clonidine. Oliguria secondary to captopril and rapid-onset congestive heart failure due to persistent hypertension led to the introduction of intravenous agents labetalol and nitroprusside. Although adequate blood pressure control was achieved, attempts to transition back to oral agents were unsuccessful, prompting the use of minoxidil as an alternative agent. Although good blood pressure control was achieved, the infant's oral intake plummeted from 210 to 63 ml/kg/day. The anorexia quickly resolved after stopping minoxidil, and she was discharged home at 5 months of age receiving propranolol, amlodipine, and doxazosin. Use of the Naranjo adverse drug reaction probability scale indicated a definite relationship (score of 10) between the patient's development of anorexia and minoxidil therapy. To our knowledge, there have been no previous reports of minoxidil-associated anorexia in preterm or term infants. Clinicians should be aware that anorexia is a possible adverse effect of minoxidil in this patient population when initiating the drug in similar patients. © 2014 Pharmacotherapy Publications, Inc.

Delayed Treatment with a Small Pigment Epithelium Derived Factor (PEDF Peptide Prevents the Progression of Diabetic Renal Injury.

Directory of Open Access Journals (Sweden)

Alaa S Awad

Full Text Available Our recent publication showed that a small bioactive pigment epithelium derived factor (PEDF peptide (P78-PEDF prevents the development of diabetic nephropathy (DN. However, its effects on the progression of established DN were not clear. Therefore, the purpose of this study was to determine the effect of P78-PEDF in the progression of DN and to compare the effects of P78-PEDF and an ACE inhibitor (ACEi, a standard of care in DN. Experiments were conducted in Ins2(Akita mice treated with P78-PEDF or captopril starting at 6 wks of age for 12 wks (early treatment or starting at 12 wks of age for 6 wks (late treatment. We first established the optimal dose of the P78-PEDF peptide to ameliorate DN in Ins2(Akita mouse for a 6 wk study period and found that the peptide was effective at 0.1- 0.5 µg/g/day. We next showed that early or late treatment with P78-PEDF resulted in protection from DN as indicated by reduced albuminuria, kidney macrophage recruitment, histological changes, inflammatory cytokines and fibrotic markers (kidney TNF-α, fibronectin, VEGFA and EGFR, and restored nephrin expression compared with vehicle-treated Ins2(Akita mice. Interestingly, only early but not late treatment with captopril was as effective as P78-PEDF in reducing most DN complications, despite its lack of effect on nephrin, VEGFA and EGFR expression. These findings highlight the importance of P78-PEDF peptide as a potential therapeutic modality in both the development and progression of diabetic renal injury.

Layered double hydroxides as supports for intercalation and sustained release of antihypertensive drugs

International Nuclear Information System (INIS)

Xia Shengjie; Ni Zheming; Xu Qian; Hu Baoxiang; Hu Jun

2008-01-01

Zn/Al layered double hydroxides (LDHs) were intercalated with the anionic antihypertensive drugs Enalpril, Lisinopril, Captopril and Ramipril by using coprecipitation or ion-exchange technique. TG-MS analyses suggested that the thermal stability of Ena - , Lis - (arranged with monolayer, resulted from X-ray diffraction (XRD) and Fourier transform infrared spectra (FT-IR) analysis was enhanced much more than Cap - and Ram - (arranged with bilayer). The release studies show that the release rate of all samples markedly decreased in both pH 4.25 and 7.45. However, the release time of Ena - , Lis - were much longer compared with Cap - , Ram - in both pH 4.25 and 7.45, it is possible that the intercalated guests, arranged with monolayer in the interlayer, show lesser repulsive force and strong affinity with the LDH layers. And the release data followed both the Higuchi-square-root law and the first-order equation well. Based on the analysis of batch release, intercalated structural models as well as the TG-DTA results, we conclude that for drug-LDH, stronger the affinity between intercalated anions and the layers is, better the thermal property and the stability to the acid attack of drug-LDH, and the intercalated anions are easier apt to monolayer arrangement within the interlayer, were presented. - Graphical abstract: A series of antihypertensive drugs including Enalpril, Lisinopril, Captopril and Ramipril were intercalated into Zn/Al-NO 3 -LDHs successfully by coprecipitation or ion-exchange technique. We focus on the structure, thermal property and low/controlled release property of as-synthesized drug-LDH composite intended for the possibility of applying these LDH-antihypertensive nanohybrids in drug delivery and controlled release systems

Atrial and ventricular septal defect with pulmonary and tricuspid valvular anomalies in a dog

International Nuclear Information System (INIS)

Ishikawa, Y.; Wakao, Y.; Watanabe, T.; Minami, T.; Muto, M.; Suzuki, T.; Takahashi, M.; Une, Y.; Nomura, Y.; Ichioka, N.

1989-01-01

A 15-month-old male boxer dog weighing 22 kg was referred to Azabu University Animal Hospital for evaluation of the syncopal attack. There was no cardiac murmur, but electrocardiograms revealed an atrial fibrillation. Thoracic radiograph revealed enlargement of the right and left atrial regions. The medical treatment with digitalis and captopril was made for conversion from the atrial fibrillation to the sinus rhythm. By cardiac catheterization, atrial and ventricular septal defect with pulmonary stenosis was demonstrated. The patient died at 20 months from the first medical examination. At autopsy, there were severe enlargement of both atria, atrial defect, and pulmonary and tricuspid valvular anomalies. (author)

Atrial and ventricular septal defect with pulmonary and tricuspid valvular anomalies in a dog

Energy Technology Data Exchange (ETDEWEB)

Ishikawa, Y. [Azabu Univ., Sagamihara, Kanagawa (Japan); Wakao, Y.; Watanabe, T.; Minami, T.; Muto, M.; Suzuki, T.; Takahashi, M.; Une, Y.; Nomura, Y.; Ichioka, N.

1989-12-15

A 15-month-old male boxer dog weighing 22 kg was referred to Azabu University Animal Hospital for evaluation of the syncopal attack. There was no cardiac murmur, but electrocardiograms revealed an atrial fibrillation. Thoracic radiograph revealed enlargement of the right and left atrial regions. The medical treatment with digitalis and captopril was made for conversion from the atrial fibrillation to the sinus rhythm. By cardiac catheterization, atrial and ventricular septal defect with pulmonary stenosis was demonstrated. The patient died at 20 months from the first medical examination. At autopsy, there were severe enlargement of both atria, atrial defect, and pulmonary and tricuspid valvular anomalies. (author)

CYSTINURIA - A TEN-YEAR FOLLOW-UP OF THE PATIENTS

Directory of Open Access Journals (Sweden)

Anđelka Slavković

2001-09-01

Full Text Available In the period from 1991 to 2001 there were four patients followed up who suffered from cystinuria and cystine calcinosis. The therapy consisting of the cystine dilution in the urine by a great taking-in of liquids and the urine alkalization was combined with alphamercaptopropione glycine and captoprile that bind cystine as well as a respective diet. Alphamercaptopropione glycine leads to the reduction of the already-formed calculus and their easier treatment in the case of a possible need for extracorporeal lithotripsy (ESWEL. During the ten-year follow-up of a small series of patients there were no complications related to the medicament treatment.

Efeitos da angiotensina-I e isquemia na recuperação funcional em corações isolados Effects of angiotensin-I and ischemia on functional recovery in isolated hearts

Directory of Open Access Journals (Sweden)

Ubirajara Oliveira de Oliveira

2011-11-01

Full Text Available FUNDAMENTO: A ressuscitação de parada cardíaca pode apresentar disfunção miocárdica determinada pelo tempo da isquemia, e a inibição da enzima conversora de angiotensina (ECA pode reduzir a disfunção cardíaca durante a reperfusão. OBJETIVO: Investigar os efeitos da angiotensina-I e diferentes períodos de isquemia na recuperação funcional em corações de ratos isolados. MÉTODOS: Os corações isolados de ratos Wistar (n = 45; 250-300 g foram submetidos a diferentes períodos de isquemia global (20, 25 ou 30 min e reperfundidos (30 min com o tampão Krebs-Henseleit, ou com a adição de 400 nmol/L de angiotensina-I, ou com 400 nmol/L de angiotensina-I + 100 µmol/L de captopril durante o período de reperfusão. RESULTADOS: A derivada positiva máxima de pressão (+dP/dt max e o produto frequência-pressão foram reduzidos nos corações expostos à isquemia de 25 min (~ 73% e à isquemia de 30 min (~ 80% vs. isquemia de 20 min. A pressão diastólica final do ventrículo esquerdo (PDFVE e a pressão de perfusão (PP foram aumentadas nos corações expostos à isquemia de 25 min (5,5 e 1,08 vezes, respectivamente e à isquemia de 30 min (6 e 1,10 vezes, respectivamente vs. isquemia de 20 min. A angiotensina-I ocasionou uma diminuição no +dP/dt max e no produto frequência-pressão (~ 85-94% em todos os períodos de isquemia e um aumento na PDFVE e na PP (6,9 e 1,25 vezes, respectivamente apenas na isquemia de 20 min. O captopril foi capaz de reverter parcial ou completamente os efeitos da angiotensina-I na recuperação funcional nas isquemias de 20 e 25 min CONCLUSÃO: Os dados sugerem que a angiotensina-II participa direta ou indiretamente no dano pós-isquêmico e que a capacidade de um inibidor da ECA atenuar esse dano depende do tempo de isquemia.BACKGROUND: Cardiac arrest resuscitation can present myocardial dysfunction determined by ischemic time, and inhibition of the angiotensin-converting enzyme (ACE can reduce cardiac

A 1H nuclear magnetic resonance study of structural and organisational changes in the cell

International Nuclear Information System (INIS)

Tunnah, Susan K.

2000-01-01

Increasing importance is being placed on understanding the role of membrane lipids in many different areas of biochemistry. It is of interest to determine what interactions may occur between membrane lipids and drug species. Furthermore, an increasing body of evidence suggests that membrane lipids are involved in the pathology of numerous diseases such as rheumatoid arthritis, cancer and HIV. Clearly, the more information available on the mechanisms involved in diseases, the greater the potential for identifying a cure or even a prevention. 1 H nuclear magnetic resonance (NMR) spectroscopy was used to study the alterations in membrane lipid organisation and structure in intact, viable cultured cells. Changes in the 1 H NMR spectra and the spin-lattice relaxation measurements of the human K562 and the rat FRTL-5 cell lines were observed on the addition of the fatty acid species: triolein, evening primrose oil, arachidonic acid and ITF 1779. Results indicate that the membrane lipids are reorganised to accommodate the interpolation of these molecules. The spatial arrangement adopted by each of these species appeared to dictate its effect on the lipids. Doxorubicin and menadione, both known to cause oxidative stress, were added to K562 cells. Although both agents are known to act by different mechanisms, the NMR data and scanning electron microscopy suggested that both caused similar alterations in the membrane organisation and lipid fluidity. Protrusions were formed indicating areas of weakness in the membrane. Spin-echo NMR was employed to investigate the action of the thiol-containing compounds, penicillamine, captopril and N-acetylcysteine in erythrocytes under conditions of oxidative stress. Results indicate that while captopril acts as a free radical scavenger, penicillamine may act as either oxidant or reductant. N-acetylcysteine was observed to act as a reducing agent. (author)

A {sup 1}H nuclear magnetic resonance study of structural and organisational changes in the cell

Energy Technology Data Exchange (ETDEWEB)

Tunnah, Susan K

2000-07-01

Increasing importance is being placed on understanding the role of membrane lipids in many different areas of biochemistry. It is of interest to determine what interactions may occur between membrane lipids and drug species. Furthermore, an increasing body of evidence suggests that membrane lipids are involved in the pathology of numerous diseases such as rheumatoid arthritis, cancer and HIV. Clearly, the more information available on the mechanisms involved in diseases, the greater the potential for identifying a cure or even a prevention. {sup 1}H nuclear magnetic resonance (NMR) spectroscopy was used to study the alterations in membrane lipid organisation and structure in intact, viable cultured cells. Changes in the {sup 1}H NMR spectra and the spin-lattice relaxation measurements of the human K562 and the rat FRTL-5 cell lines were observed on the addition of the fatty acid species: triolein, evening primrose oil, arachidonic acid and ITF 1779. Results indicate that the membrane lipids are reorganised to accommodate the interpolation of these molecules. The spatial arrangement adopted by each of these species appeared to dictate its effect on the lipids. Doxorubicin and menadione, both known to cause oxidative stress, were added to K562 cells. Although both agents are known to act by different mechanisms, the NMR data and scanning electron microscopy suggested that both caused similar alterations in the membrane organisation and lipid fluidity. Protrusions were formed indicating areas of weakness in the membrane. Spin-echo NMR was employed to investigate the action of the thiol-containing compounds, penicillamine, captopril and N-acetylcysteine in erythrocytes under conditions of oxidative stress. Results indicate that while captopril acts as a free radical scavenger, penicillamine may act as either oxidant or reductant. N-acetylcysteine was observed to act as a reducing agent. (author)

Chronic excitotoxic lesion of the dorsal raphe nucleus induces sodium appetite

Directory of Open Access Journals (Sweden)

Cavalcante-Lima H.R.

2005-01-01

Full Text Available We determined if the dorsal raphe nucleus (DRN exerts tonic control of basal and stimulated sodium and water intake. Male Wistar rats weighing 300-350 g were microinjected with phosphate buffer (PB-DRN, N = 11 or 1 µg/0.2 µl, in a single dose, ibotenic acid (IBO-DRN, N = 9 to 10 through a guide cannula into the DRN and were observed for 21 days in order to measure basal sodium appetite and water intake and in the following situations: furosemide-induced sodium depletion (20 mg/kg, sc, 24 h before the experiment and a low dose of dietary captopril (1 mg/g chow. From the 6th day after ibotenic acid injection IBO-DRN rats showed an increase in sodium appetite (12.0 ± 2.3 to 22.3 ± 4.6 ml 0.3 M NaCl intake whereas PB-DRN did not exceed 2 ml (P < 0.001. Water intake was comparable in both groups. In addition to a higher dipsogenic response, sodium-depleted IBO-DRN animals displayed an increase of 0.3 M NaCl intake compared to PB-DRN (37.4 ± 3.8 vs 21.6 ± 3.9 ml 300 min after fluid offer, P < 0.001. Captopril added to chow caused an increase of 0.3 M NaCl intake during the first 2 days (IBO-DRN, 33.8 ± 4.3 and 32.5 ± 3.4 ml on day 1 and day 2, respectively, vs 20.2 ± 2.8 ml on day 0, P < 0.001. These data support the view that DRN, probably via ascending serotonergic system, tonically modulates sodium appetite under basal and sodium depletion conditions and/or after an increase in peripheral or brain angiotensin II.

Diagnosis and treatment of primary aldosteronism. An analysis of 18 cases

International Nuclear Information System (INIS)

Hiroi, Naoki; Yoshihara, Aya; Sue, Mariko

2009-01-01

Early diagnosis of primary aldosteronism (PA) is important because the worldwide prevalence of PA among unselected hypertensive patients is 5% to 15%. We examined the records of 18 patients with PA who were evaluated at Toho University Medical Center Omori Hospital. We analyzed the results of confirmatory testing and subtype differentiation among 18 patients (7 men and 11 women, mean age (mean±standard deviation (SD), 55.1±14.7 years) who had received a diagnosis of PA within the previous 2.5 years. On confirmatory testing of PA, the ratios of positive results on the furosemide-upright test, captopril-loading test, and adrenocorticotropic hormone (ACTH) stimulation test were 88.9, 69.2 and 68.8%, respectively. On subtype differentiation, among 14 patients who underwent ACTH-stimulated adrenal venous sampling (ACTH-AVS), 6 were found to have bilateral hyperaldosteronism (BHA) and 8 were found to have aldosterone-producing adrenal adenoma (APA, 1 right and 7 left adenomas). In 2 of 4 patients who did not undergo ACTH-AVS, APA with right adenoma was diagnosed by abdominal CT scan and 131 I-adosterol scintigraphy, however, determination of PA subtype was not possible in the remaining 2 patients. Patients with APA underwent adrenalectomy, and spironolactone was administered to patients with BHA. The therapeutic effectiveness of adrenalectomy and spironolactone did not differ. The furosemide-upright test should be the first choice for definitive diagnosis of PA; the captopril-loading test and ACTH stimulation test should be regarded as secondary examinations. It is necessary to use more than one confirmatory test, because these tests sometimes result in false negatives. Abdominal CT scan is not always useful for localizing adrenal tumors; therefore, we suggest a combination of CT scan, 131 I-adosterol scintigraphy, and ACTH-AVS in determining the appropriate therapy. (author)

Comportamiento de las crisis hipertensivas en el Área Intensiva Municipal de Centro Habana

Directory of Open Access Journals (Sweden)

Edrinson Alfredo Naranjo Casañas

Full Text Available Introducción: la Hipertensión Arterial continúa siendo una de las enfermedades crónicas más comunes en nuestro país y el mundo, llegando a tener un rol protagónico como factor de riesgo importante para el padecimiento o agravamiento de otras enfermedades letales. Objetivo: caracterizar el comportamiento de las crisis hipertensivas en los pacientes ingresados en el Área Intensiva del Policlínico Docente "Dr. Joaquín Albarrán". Métodos: se realizó una investigación descriptiva, de corte transversal, en el período comprendido entre diciembre de 2010 a diciembre de 2012. El universo estuvo constituido por los 767 pacientes de 15 y más años de edad, de ambos sexos, que acudieron al Servicio de Urgencia del policlínico y requirieron ingreso en la Unidad de Cuidados Intensivos. Los resultados se mostraron en tablas estadísticas de frecuencias absolutas y relativas. Resultados: predominó el ingreso en los grupos de edades de 40-49 años (23,8 %, seguido del grupo de 60 y más (22,1 %. La principal modalidad de crisis se correspondió con las Urgencias Hipertensivas, 442 (57,6 %. El medicamento de mayor uso como tratamiento de la crisis fue el Captopril en tableta con un total de 562 (93,2 %. El principal órgano diana afectado fue el corazón. Conclusiones: el mayor número de ingresos se produjo en los pacientes de 40-49 años de edad con mayoría del sexo masculino; la modalidad de crisis hipertensiva que más se presentó fue las Urgencias Hipertensivas, y el medicamento de mayor uso como tratamiento fue el Captopril en tableta.

Beneficial effects of Acer okamotoanum sap on L-NAME-induced hypertension-like symptoms in a rat model.

Science.gov (United States)

Yang, Hyun; Hwang, Inho; Koo, Tae-Hyoung; Ahn, Hyo-Jin; Kim, Sun; Park, Mi-Jin; Choi, Won-Sil; Kang, Ha-Young; Choi, In-Gyu; Choi, Kyung-Chul; Jeung, Eui-Bae

2012-02-01

The sap of Acer okamotoanum has been termed 'bone-benefit-water' in Korea owing to its mineral and sugar content. In particular, the calcium (Ca) and potassium (K) concentrations of the sap of Acer okamotoanum are 40- and 20-times higher, respectively, than commercial spring water. In the present study, we examined whether Acer okamotoanum sap improves or prevents hypertension-like symptoms in a rat model. Male Sprague-Dawley rats (8-weeks-old) were provided commercial spring water supplemented with 25, 50 or 100% Acer okamotoanum sap, 3% potassium ions (K+) or captopril, and treated daily for 2 weeks with NG-nitro-L-arginine methyl ester (L-NAME; 100 mg/kg/day) by subcutaneous injection, in order to induce hypertensive symptoms. Rats were euthanized 6 h following the final injection. To assess the effect of the sap on hypertension-like symptoms, we examined the mean blood pressure (BP), protein levels and localization of endothelial nitric oxide synthase (eNOS) in the descending aorta of the rats. BP levels were significantly lower in hypertensive rats received 25, 50 and 100% sap compared with rats who were administered only commercial spring water. Protein levels of eNOS were repressed in L-NAME-only-treated rats, but were elevated in the descending aorta of rats administered captopril, K+ water and Acer okamotoanum sap (25, 50 and 100%) up to the level of the sham group provided commercial spring water, and then injected with dimethyl sulfoxide for the same period of time. Localized eNOS protein was abundantly expressed in the perivascular descending aorta adipose tissue of the rats. Taken together, these results demonstrated that the sap of Acer okamotoanum ameliorated high BP induced by L-NAME treatment in a rat model.

Qishenyiqi protects ligation-induced left ventricular remodeling by attenuating inflammation and fibrosis via STAT3 and NF-κB signaling pathway.

Directory of Open Access Journals (Sweden)

Chun Li

Full Text Available AIM: Qi-shen-yi-qi (QSYQ, a formula used for the routine treatment of heart failure (HF in China, has been demonstrated to improve cardiac function through down-regulating the activation of the Renin-Angiotensin-Aldosterone System (RAAS. However, the mechanisms governing its therapeutic effects are largely unknown. The present study aims to demonstrate that QSYQ treatment can prevent left ventricular remodeling in heart failure by attenuating oxidative stress and inhabiting inflammation. METHODS: Sprague-Dawley (SD rats were randomly divided into 6 groups: sham group, model group (LAD coronary artery ligation, QSYQ group with high dosage, middle dosage and low dosage (LAD ligation and treated with QSYQ, and captopril group (LAD ligation and treated with captopril as the positive drug. Indicators of fibrosis (Masson, MMPs, and collagens and inflammation factors were detected 28 days after surgery. RESULTS: Results of hemodynamic alterations (dp/dt value in the model group as well as other ventricular remodeling (VR markers, such as MMP-2, MMP-9, collagen I and III elevated compared with sham group. VR was accompanied by activation of RAAS (angiotensin II and NADPHoxidase. Levels of pro-inflammatory cytokines (TNF-α, IL-6 in myocardial tissue were also up-regulated. Treatment of QSYQ improved cardiac remodeling through counter-acting the aforementioned events. The improvement of QSYQ was accompanied with a restoration of angiotensin II-NADPHoxidase-ROS-MMPs pathways. In addition, "therapeutic" QSYQ administration can reduce both TNF-α-NF-B and IL-6-STAT3 pathways, respectively, which further proves the beneficial effects of QSYQ. CONCLUSIONS: Our study demonstrated that QSYQ protected LAD ligation-induced left VR via attenuating AngII -NADPH oxidase pathway and inhabiting inflammation. These findings provide evidence as to the cardiac protective efficacy of QSYQ to HF and explain the beneficial effects of QSYQ in the clinical application for HF.

Possíveis interações medicamentosas entre os antihipertensivos e antidiabéticos em participantes do Grupo HIPERDIA de Parobé, RS (Uma análise teórica

Directory of Open Access Journals (Sweden)

Deise Margarete Duarte do Amaral

2012-01-01

Full Text Available Devido à alta incidência simultânea de hipertensão arterial sistêmica e diabetes mellitus, é comum encontrar pacientes que usam anti-hipertensivos e antidiabéticos simultaneamente. Desta forma, tornase importante identificar as possíveis interações medicamentosas no tratamento da hipertensão arterial e do diabetes e realizar manejo farmacoterapêutico adequado para evitar efeitos adversos graves ou até a morte. Este trabalho teve como objetivo identificar possíveis interações com os medicamentos antihipertensivos e antidiabéticos em participantes idosos do grupo HIPERDIA no município de Parobé/RS. Trata-se de um estudo quantitativo, observacional e transversal e foi realizado através de um questionário estruturado aplicado em 45 (39 idosos, 37 com interações medicamentosas participantes do programa HIPERDIA. Foram identificadas 144 possíveis interações medicamentosas, sendo 30% desejáveis e 70% indesejáveis. Destas indesejáveis, 85% classificadas como moderada com maior ocorrência da associação de captopril e ácido acetilsalicílico, 5% grave (interação de diurético de alça com digitálico e 10% leves. Das desejáveis, a associação de captopril e hidroclorotiazida teve maior ocorrência. Este estudo revelou um alto índice de possíveis interações medicamentosas em idosos participantes do programa HIPERDIA. A maioria das interações pode comprometer a segurança do paciente, evidenciando a relevância deste tema e a necessidade de avaliar e monitorar a terapêutica medicamentosa no idoso, no sentido de prevenir e diminuir as consequências dos efeitos decorrentes de potenciais interações medicamentosas.

Effect of γ-aminobutyric acid and nattokinase-enriched fermented beans on the blood pressure of spontaneously hypertensive and normotensive Wistar–Kyoto rats

Directory of Open Access Journals (Sweden)

Kanintra Suwanmanon

2014-12-01

Full Text Available In this study we have evaluated the changes in arterial blood pressure in spontaneously hypertensive rats (SHR caused by the short-term intake of Bacillus subtilis B060-fermented beans with significant γ-aminobutyric acid (GABA and nattokinase activity. After being weaned, 7-week-old male SHR and 7-week-old male Wistar–Kyoto (WKY rats were randomized into seven groups. Until the 8th week of life, the rats in each group were given one of the following: Group 1, high dose of GABA and nattokinase in the SHR (SHD; Group 2, medium dose of GABA and nattokinase in the SHR (SMD; Group 3, low dose of GABA and nattokinase in the SHR (SLD; Group 4, negative control in the SHR (SD; Group 5, positive control in the SHR (SM; Group 6, high dose of GABA and nattokinase in the WKY (WHD; and Group 7, negative control in the WKY (WD. Distilled water served as the negative control, and captopril (50 mg/kg, a known ACE inhibitor, served as the positive control. Systolic blood pressure and diastolic blood pressure values were measured weekly from the 8th week to the 16th week of life using the tail-cuff method. A definite decrease in systolic and diastolic blood pressure values could be observed in the rats treated with captopril and in the rats that received GABA and nattokinase. The greatest antihypertensive effect was observed when the pharmacological treatment was administered. The effect of the daily intake of fermented beans containing GABA and nattokinase may be helpful in controlling blood pressure levels in hypertensive model animals. The fermentation of beans with B. subtilis B060 may therefore constitute a successful strategy for producing a functional food with antihypertensive activity.

Effect of γ-aminobutyric acid and nattokinase-enriched fermented beans on the blood pressure of spontaneously hypertensive and normotensive Wistar-Kyoto rats.

Science.gov (United States)

Suwanmanon, Kanintra; Hsieh, Pao-Chuan

2014-12-01

In this study we have evaluated the changes in arterial blood pressure in spontaneously hypertensive rats (SHR) caused by the short-term intake of Bacillus subtilis B060-fermented beans with significant γ-aminobutyric acid (GABA) and nattokinase activity. After being weaned, 7-week-old male SHR and 7-week-old male Wistar-Kyoto (WKY) rats were randomized into seven groups. Until the 8 th week of life, the rats in each group were given one of the following: Group 1, high dose of GABA and nattokinase in the SHR (SHD); Group 2, medium dose of GABA and nattokinase in the SHR (SMD); Group 3, low dose of GABA and nattokinase in the SHR (SLD); Group 4, negative control in the SHR (SD); Group 5, positive control in the SHR (SM); Group 6, high dose of GABA and nattokinase in the WKY (WHD); and Group 7, negative control in the WKY (WD). Distilled water served as the negative control, and captopril (50 mg/kg), a known ACE inhibitor, served as the positive control. Systolic blood pressure and diastolic blood pressure values were measured weekly from the 8 th week to the 16 th week of life using the tail-cuff method. A definite decrease in systolic and diastolic blood pressure values could be observed in the rats treated with captopril and in the rats that received GABA and nattokinase. The greatest antihypertensive effect was observed when the pharmacological treatment was administered. The effect of the daily intake of fermented beans containing GABA and nattokinase may be helpful in controlling blood pressure levels in hypertensive model animals. The fermentation of beans with B. subtilis B060 may therefore constitute a successful strategy for producing a functional food with antihypertensive activity. Copyright © 2014. Published by Elsevier B.V.

Renal oxygen content is increased in healthy subjects after angiotensin-converting enzyme inhibition

Directory of Open Access Journals (Sweden)

Anna Stein

2012-07-01

Full Text Available OBJECTIVE: The association between renal hypoxia and the development of renal injury is well established. However, no adequate method currently exists to non-invasively measure functional changes in renal oxygenation in normal and injured patients. METHOD: R2* quantification was performed using renal blood oxygen level-dependent properties. Five healthy normotensive women (50±5.3 years underwent magnetic resonance imaging in a 1.5T Signa Excite HDx scanner (GE Healthcare, Waukesha, WI. A multiple fast gradient-echo sequence was used to acquire R2*/T2* images (sixteen echoes from 2.1 ms/slice to 49.6 ms/slice in a single breath hold per location. The images were post-processed to generate R2* maps for quantification. Data were recorded before and at 30 minutes after the oral administration of an angiotensin II-converting enzyme inhibitor (captopril, 25 mg. The results were compared using an ANOVA for repeated measurements (mean + standard deviation followed by the Tukey test. ClinicalTrials.gov: NCT01545479. RESULTS: A significant difference (p<0.001 in renal oxygenation (R2* was observed in the cortex and medulla before and after captopril administration: right kidney, cortex = 11.08 ± 0.56ms, medulla = 17.21 ± 1.47ms and cortex = 10.30 ± 0.44ms, medulla = 16.06 ± 1.74ms, respectively; and left kidney, cortex= 11.79 ± 1.85ms, medulla = 17.03 ± 0.88ms and cortex = 10.89 ± 0.91ms, medulla = 16.43 ± 1.49ms, respectively. CONCLUSIONS: This result suggests that the technique efficiently measured alterations in renal blood oxygenation after angiotensin II-converting enzyme inhibition and that it may provide a new strategy for identifying the early stages of renal disease and perhaps new therapeutic targets.

Hyponatremic Hypertensive Syndrome in an Obese man with Renal Ischemia

International Nuclear Information System (INIS)

Saeed, K.

2006-01-01

Renovascular hypertension occasionally manifests as an electrolyte disorder. The combination of hyponetrimia and renovascular hypertension occasionally manifests as an electrolyte disorder. The combination of hyponatremia and renovascular hypertension is known as hyponatremic-hypertensive syndrome. This syndrome was initially reported in children. Here we describe a 45 year-old Saudi man who was admitted to the hospital with generalized body weakness and inability to walk. He was confused and was noted to have severe hypertension and very low serum sodium and potassium. The patient was recently started on captopril for blood pressure control, which was discontinued because of deterioration renal function. Color Doppler renal ultrasound, and magnetic resonance angiography confirmed the diagnosis of renal artery stenosis. (author)

Effects of autogenic training and antihypertensive agents on circadian and circaseptan variation of blood pressure.

Science.gov (United States)

Watanabe, Yoshihiko; Cornélissen, Germaine; Watanabe, Misako; Watanabe, Fumihiko; Otsuka, Kuniaki; Ohkawa, Shi-ichiro; Kikuchi, Takenori; Halberg, Franz

2003-10-01

Even when the daily blood pressure mean is acceptable, too large a circadian amplitude of blood pressure largely increases cardiovascular disease risk. Autogenic training (N = 11), a non-pharmacologic intervention capable of lowering an excessive blood pressure variability, may be well-suited for MESOR-normotensive patients diagnosed with circadian-hyper-amplitude-tension (CHAT). Not all anti-hypertensive drugs affect blood pressure variability. Accordingly, long-acting carteolol (N = 11) and/or atenolol (N = 8) may be preferred to captopril retard (N = 13), nilvadipine (N = 8), or amlodipine (N = 7) for midline-estimating statistic of rhythm (MESOR)-hypertensive patients with CHAT. Prospective outcome studies are needed to assess whether the relative merits of these treatments are in keeping with their effects on blood pressure and blood pressure variability.

A new structurally atypical bradykinin-potentiating peptide isolated from Crotalus durissus cascavella venom (South American rattlesnake).

Science.gov (United States)

Lopes, Denise M; Junior, Norberto E G; Costa, Paula P C; Martins, Patrícia L; Santos, Cláudia F; Carvalho, Ellaine D F; Carvalho, Maria D F; Pimenta, Daniel C; Cardi, Bruno A; Fonteles, Manassés C; Nascimento, Nilberto R F; Carvalho, Krishnamurti M

2014-11-01

Venom glands of some snakes synthesize bradykinin-potentiating peptides (BPP's) which increase bradykinin-induced hypotensive effect and decrease angiotensin I vasopressor effect by angiotensin-converting enzyme (ACE) inhibition. The present study shows a new BPP (BPP-Cdc) isolated from Crotalus durissus cascavella venom: Pro-Asn-Leu-Pro-Asn-Tyr-Leu-Gly-Ile-Pro-Pro. Although BPP-Cdc presents the classical sequence IPP in the C-terminus, it has a completely atypical N-terminal sequence, which shows very low homology with all other BPPs isolated to date. The pharmacological effects of BPP-Cdc were compared to BBP9a from Bothrops jararaca and captopril. BPP-Cdc (1 μM) significantly increased BK-induced contractions (BK; 1 μM) on the guinea pig ileum by 267.8% and decreased angiotensin I-induced contractions (AngI; 10 nM) by 62.4% and these effects were not significantly different from those of BPP9a (1 μM) or captopril (200 nM). Experiments with 4-week hypertensive 2K-1C rats show that the vasopressor effect of AngI (10 ng) was decreased by 50 μg BPP-Cdc (69.7%), and this result was similar to that obtained with 50 μg BPP9a (69.8%). However, the action duration of BPP-Cdc (60 min) was 2 times greater than that of BPP-9a (30 min). On the other hand, the hypotensive effect of BK (250 ng) was significantly increased by 176.6% after BPP-Cdc (50 μg) administration, value 2.5 times greater than that obtained with BPP9a administered at the same doses (71.4%). In addition, the duration of the action of BPP-Cdc (120 min) was also at least 4 times greater than that of BPP-9a (30 min). Taken together, these results suggest that BPP-Cdc presents more selective action on arterial blood system than BPP9a. Besides the inhibition of ACE, it may present other mechanisms of action yet to be elucidated. Copyright © 2014 Elsevier Ltd. All rights reserved.

How to measure renal artery stenosis - a retrospective comparison of morphological measurement approaches in relation to hemodynamic significance

International Nuclear Information System (INIS)

Andersson, Malin; Jägervall, Karl; Eriksson, Per; Persson, Anders; Granerus, Göran; Wang, Chunliang; Smedby, Örjan

2015-01-01

Although it is well known that renal artery stenosis may cause renovascular hypertension, it is unclear how the degree of stenosis should best be measured in morphological images. The aim of this study was to determine which morphological measures from Computed Tomography Angiography (CTA) and Magnetic Resonance Angiography (MRA) are best in predicting whether a renal artery stenosis is hemodynamically significant or not. Forty-seven patients with hypertension and a clinical suspicion of renovascular hypertension were examined with CTA, MRA, captopril-enhanced renography (CER) and captopril test (Ctest). CTA and MRA images of the renal arteries were analyzed by two readers using interactive vessel segmentation software. The measures included minimum diameter, minimum area, diameter reduction and area reduction. In addition, two radiologists visually judged the diameter reduction without automated segmentation. The results were then compared using limits of agreement and intra-class correlation, and correlated with the results from CER combined with Ctest (which were used as standard of reference) using receiver operating characteristics (ROC) analysis. A total of 68 kidneys had all three investigations (CTA, MRA and CER + Ctest), where 11 kidneys (16.2 %) got a positive result on the CER + Ctest. The greatest area under ROC curve (AUROC) was found for the area reduction on MRA, with a value of 0.91 (95 % confidence interval 0.82–0.99), excluding accessory renal arteries. As comparison, the AUROC for the radiologists’ visual assessments on CTA and MRA were 0.90 (0.82–0.98) and 0.91 (0.83–0.99) respectively. None of the differences were statistically significant. No significant differences were found between the morphological measures in their ability to predict hemodynamically significant stenosis, but a tendency of MRA having higher AUROC than CTA. There was no significant difference between measurements made by the radiologists and measurements made with

Recommendations on procedures for renal function imaging; Anleitung zur Durchfuehrung der Nierenfunktionsszintigraphie

Energy Technology Data Exchange (ETDEWEB)

Klaeser, B.; Eberl, A.; Bubeck, B. [Klinik fuer Nuklearmedizin, Kantonsspital St. Gallen (Switzerland)

2003-09-01

Renal function diagnostics in nuclear medicine is nowadays performed primarily as scintigraphic study using {sup 99m}Tc-MAG3, in many cases accompanied by quantitative clearance measurement. The present recommendations are based on the technical protocols of the Clinic of Nuclear Medicine at the Kantonsspital St. Gallen and do not claim to be complete or the Gold Standard. The procedures described are not subject to discussion, but the authors attempt to give practical guidelines as orientation for users in their daily routine. Focal points are preparation and performance of the diuretic renography with furosemide to evaluate urinary outflow obstructions and scintigraphic studies under captopril for detection of renovascular hypertension. Further subjects are the quantitative clearance measurement according to the single-sample method and, of course, the calculation of the split clearance. All of these subjects are described mainly under practical aspects, looking in particular at frequent pitfalls or wrong interpretations, but also taking into account quality assurance and data analysis. Selected cases are presented to document the importance of renal function imaging in practice. (orig.) [German] Die nuklearmedizinische Nierenfunktionsdiagnostik wird heute vorrangig als Szintigraphie mit {sup 99m}Tc-MAG3 betrieben, haeufig mit begleitender quantitativer Clearancemessung. Die vorliegende Anleitung basiert auf den Untersuchungsprotokollen der Klinik fuer Nuklearmedizin des Kantonsspitals St. Gallen und erhebt weder Anspruch auf Vollstaendigkeit noch darauf, als Goldstandard zu gelten. Die beschriebenen Vorgehensweisen werden nicht diskutiert, sondern die Autoren versuchen, pragmatische Leitlinien zu vermitteln, an denen sich der Anwender in der taeglichen Routine orientieren kann. Schwerpunkte bilden die Vorbereitung und Durchfuehrung der so genannten Lasix-Szintigraphie zur Beurteilung der renalen Abflussverhaeltnisse und die Captopril-Szintigraphie bei der Frage

Kallikrein–Kinin System Suppresses Type I Interferon Responses: A Novel Pathway of Interferon Regulation

Directory of Open Access Journals (Sweden)

Alecia Seliga

2018-02-01

Full Text Available The Kallikrein–Kinin System (KKS, comprised of kallikreins (klks, bradykinins (BKs angiotensin-converting enzyme (ACE, and many other molecules, regulates a number of physiological processes, including inflammation, coagulation, angiogenesis, and control of blood pressure. In this report, we show that KKS regulates Type I IFN responses, thought to be important in lupus pathogenesis. We used CpG (TLR9 ligand, R848 (TLR7 ligand, or recombinant IFN-α to induce interferon-stimulated genes (ISGs and proteins, and observed that this response was markedly diminished by BKs, klk1 (tissue kallikrein, or captopril (an ACE inhibitor. BKs significantly decreased the ISGs induced by TLRs in vitro and in vivo (in normal and lupus-prone mice, and in human PBMCs, especially the induction of Irf7 gene (p < 0.05, the master regulator of Type I IFNs. ISGs induced by IFN-α were also suppressed by the KKS. MHC Class I upregulation, a classic response to Type I IFNs, was reduced by BKs in murine dendritic cells (DCs. BKs decreased phosphorylation of STAT2 molecules that mediate IFN signaling. Among the secreted pro-inflammatory cytokines/chemokines analyzed (IL-6, IL12p70, and CXCL10, the strongest suppressive effect was on CXCL10, a highly Type I IFN-dependent cytokine, upon CpG stimulation, both in normal and lupus-prone DCs. klks that break down into BKs, also suppressed CpG-induced ISGs in murine DCs. Captopril, a drug that inhibits ACE and increases BK, suppressed ISGs, both in mouse DCs and human PBMCs. The effects of BK were reversed with indomethacin (compound that inhibits production of PGE2, suggesting that BK suppression of IFN responses may be mediated via prostaglandins. These results highlight a novel regulatory mechanism in which members of the KKS control the Type I IFN response and suggest a role for modulators of IFNs in the pathogenesis of lupus and interferonopathies.

pH-Induced transformation of ligated Au25 to brighter Au23 nanoclusters.

Science.gov (United States)

Waszkielewicz, Magdalena; Olesiak-Banska, Joanna; Comby-Zerbino, Clothilde; Bertorelle, Franck; Dagany, Xavier; Bansal, Ashu K; Sajjad, Muhammad T; Samuel, Ifor D W; Sanader, Zeljka; Rozycka, Miroslawa; Wojtas, Magdalena; Matczyszyn, Katarzyna; Bonacic-Koutecky, Vlasta; Antoine, Rodolphe; Ozyhar, Andrzej; Samoc, Marek

2018-05-01

Thiolate-protected gold nanoclusters have recently attracted considerable attention due to their size-dependent luminescence characterized by a long lifetime and large Stokes shift. However, the optimization of nanocluster properties such as the luminescence quantum yield is still a challenge. We report here the transformation of Au25Capt18 (Capt labels captopril) nanoclusters occurring at low pH and yielding a product with a much increased luminescence quantum yield which we have identified as Au23Capt17. We applied a simple method of treatment with HCl to accomplish this transformation and we characterized the absorption and emission of the newly created ligated nanoclusters as well as their morphology. Based on DFT calculations we show which Au nanocluster size transformations can lead to highly luminescent species such as Au23Capt17.

Post-streptococcal glomerulonephritis

Directory of Open Access Journals (Sweden)

Odalovic A.

2014-01-01

Full Text Available Post-streptococcal glomerulonephritis (PSGN is a frequent cause of acute nephritis in children. This case study was done with the aim to point out that the infections caused by Group A streptococci, in spite of antibiotic era, are still present in the population. An 8-year old boy was admitted in our hospital with a two-day history of fewer, tonsillopharyngitis. After hospital admission, patient was treated with penicillin during the period of 10 days, antihypertensive medications (captopril, furosemide, including restricted diet of salt. After the treatment, patient became better. On demission it was found proteinuria and microhematuria PSGN is very serious disease, which leaves severe complications if the valid therapy with penicillin is not used in propriety time, during the recommended period of 10 days.

[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.

Rare Acute Pancreatitis Cases Due to Different Antihypertensive Drugs: Four Cases

Directory of Open Access Journals (Sweden)

Gökhan Celbek

2014-03-01

Full Text Available The most important reasons of acute pancreatitis (AP are benign biliary tract diseases, metabolic diseases and alcoholism. Some drugs also(sulfonamides, thiazides, lysinopril, captopril, estrogens and tetracyclines can induce AP. We herein report four cases of AP patients who were using different drugs. The first case was 73 years old male patient who has been using zofenopril for 4 weeks and the second patient was 24 years old female who was using furosemide after her pregnancy. Third one was using valsartan for one month. Fourth patient was using lysinopril for six weeks and resulted in AP. All patients had no known risk factors for pancreatitis. After cessation of the drugs, four patients recovered in a few days without any complications. AP due to zofenopril was firstly reported in our manuscript in the literature.

Sensitive method for precise measurement of endogenous angiotensins I, II and III in human plasma

International Nuclear Information System (INIS)

Kawamura, M.; Yoshida, K.; Akabane, S.

1987-01-01

We measured endogenous angiotensins (ANGs) I, IIandIII using a system of extraction by Sep-Pak column followed by high performance liquid chromatography (HPLC) combined with radioimmunoassay (RIA). An excellent separation of ANGs was obtained by HPLC. The recovery of ANGs I, IIandIII was 80-84%, when these authentic peptides were added to 6 ml of plasma. The coefficient of variation of the ANGs was 0.04-0.09 for intra-assay and 0.08-0.13 for inter-assay, thereby indicating a good reproducibility. Plasma ANGs I, IIandIII measured by this method in 5 normal volunteers were 51,4.5 and 1.2 pg/ml. In the presence of captopril, ANGs IIandIII decreased by 84% and 77%, respectively, while ANG I increased 5.1 times. This method is therefore useful to assess the precise levels of plasma ANGs

Structural Insights into TMB-1 and the Role of Residues 119 and 228 in Substrate and Inhibitor Binding.

Science.gov (United States)

Skagseth, Susann; Christopeit, Tony; Akhter, Sundus; Bayer, Annette; Samuelsen, Ørjan; Leiros, Hanna-Kirsti S

2017-08-01

Metallo-β-lactamases (MBLs) threaten the effectiveness of β-lactam antibiotics, including carbapenems, and are a concern for global public health. β-Lactam/β-lactamase inhibitor combinations active against class A and class D carbapenemases are used, but no clinically useful MBL inhibitor is currently available. Tripoli metallo-β-lactamase-1 (TMB-1) and TMB-2 are members of MBL subclass B1a, where TMB-2 is an S228P variant of TMB-1. The role of S228P was studied by comparisons of TMB-1 and TMB-2, and E119 was investigated through the construction of site-directed mutants of TMB-1, E119Q, E119S, and E119A (E119Q/S/A). All TMB variants were characterized through enzyme kinetic studies. Thermostability and crystallization analyses of TMB-1 were performed. Thiol-based inhibitors were investigated by determining the 50% inhibitory concentrations (IC 50 ) and binding using surface plasmon resonance (SPR) for analysis of TMB-1. Thermostability measurements found TMB-1 to be stabilized by high NaCl concentrations. Steady-state enzyme kinetics analyses found substitutions of E119, in particular, substitutions associated with the penicillins, to affect hydrolysis to some extent. TMB-2 with S228P showed slightly reduced catalytic efficiency compared to TMB-1. The IC 50 levels of the new thiol-based inhibitors were 0.66 μM (inhibitor 2a) and 0.62 μM (inhibitor 2b), and the equilibrium dissociation constant ( K D ) of inhibitor 2a was 1.6 μM; thus, both were more potent inhibitors than l-captopril (IC 50 = 47 μM; K D = 25 μM). The crystal structure of TMB-1 was resolved to 1.75 Å. Modeling of inhibitor 2b in the TMB-1 active site suggested that the presence of the W64 residue results in T-shaped π-π stacking and R224 cation-π interactions with the phenyl ring of the inhibitor. In sum, the results suggest that residues 119 and 228 affect the catalytic efficiency of TMB-1 and that inhibitors 2a and 2b are more potent inhibitors for TMB-1 than l-captopril. Copyright

Acute and chronic antihypertensive effects of Cinnamomum zeylanicum stem bark methanol extract in L-NAME-induced hypertensive rats

Directory of Open Access Journals (Sweden)

Nyadjeu Paulin

2013-01-01

Full Text Available Abstract Background Previous study showed that the aqueous extract of the stem bark of Cinnamomum zeylanicum possesses antihypertensive and vasodilatory properties. The present work investigates the acute and chronic antihypertensive effects of the methanol extract of Cinnamomum zeylanicum stem bark (MECZ in L-NAME-induced hypertensive rats. Methods The acute antihypertensive effects of MECZ (5, 10 and 20 mg/kg administered intravenously were evaluated in rats in which acute arterial hypertension has been induced by intravenous administration of L-NAME (20 mg/kg. For chronic antihypertensive effects, animals were treated with L-NAME (40 mg/kg/day plus the vehicle or L-NAME (40 mg/kg/day in combination with captopril (20 mg/kg/day or MECZ (300 mg/kg/day and compared with control group receiving only distilled water. All drugs were administered per os and at the end of the experiment that lasted for four consecutive weeks, blood pressure was measured by invasive method and blood samples were collected for the determination of the lipid profile. The heart and aorta were collected, weighed and used for both histological analysis and determination of NO tissue content. Results Acute intravenous administration of C. zeylanicum extract (5, 10 and 20 mg/kg to L-NAME-induced hypertensive rats provoked a long-lasting decrease in blood pressure. Mean arterial blood pressure decreased by 12.5%, 26.6% and 30.6% at the doses of 5, 10 and 20 mg/kg, respectively. In chronic administration, MECZ and captopril significantly prevented the increase in blood pressure and organs’ weights, as well as tissue histological damages and were able to reverse the depletion in NO tissue’s concentration. The MECZ also significantly lower the plasma level of triglycerides (38.1%, total cholesterol (32.1% and LDL-cholesterol (75.3% while increasing that of HDL-cholesterol (58.4% with a significant low atherogenic index (1.4 versus 5.3 for L-NAME group. Conclusion MECZ

Características da clientela atendida por crise hipertensiva na emergência de um hospital municipal de Fortaleza, Estado do Ceará - DOI: 10.4025/actascihealthsci.v32i1.5746 Characteristics of the clientele assisted for hypertensive crisis in the emergency of a municipal hospital in Fortaleza, Ceará State - DOI: 10.4025/actascihealthsci.v32i1.5746

Directory of Open Access Journals (Sweden)

Ana Célia Caetano de Souza

2009-12-01

Full Text Available Objetivou-se descrever as características da clientela com crise hipertensiva. A pesquisa, quantitativa, descritiva e documental foi realizada em um hospital municipal de Fortaleza, Estado do Ceará em 2006. Na análise de 790 fichas de atendimento, observamos que 48,2% dos pacientes que apresentavam crise hipertensiva, encontravam-se na faixa etária de 40 a 59 anos e a maioria dos indivíduos era de casados (57,5%. Os principais sintomas encontrados foram cefaleia (35,7% e dor precordial (12.3% e, em 36,8% das fichas, não houve registro de sinais e sintomas. As medicações mais prescritas foram o captopril (90,6% e furosemida (53%. Conclui-se que a crise hipertensiva acomete muitos adultos, a maioria casados e que geralmente vão à emergência para fazer avaliação clínica de algum sinal/sintoma. Ressalta-se a necessidade de se alertar os profissionais de saúde quanto à importância do registro para conhecimento e compreensão das características dessa clientela para o controle e a prevenção da crise hipertensiva.The objective was to describe the characteristics of the clientele with hypertensive crisis. The research, which was quantitative, descriptive and documentary, was conducted at a municipal hospital in Fortaleza, Ceará Estate in 2006. In the analysis of 790 patient files, we found that 48.2% of patients presenting hypertensive crisis were in the age group between 40 and 59 years old. Most of the individuals were married (57.5%. The main symptoms were headache (35.7% and chest pain (12.3%, and in 36.8% of files there was no record of signs and symptoms. The most prescribed medications were captopril (90.6% and furosemide (53%. We conclude that hypertensive crisis affects many adults, most married and who usually go to the emergency room for clinical evaluation of a sign/symptom. We emphasize the need to alert health professionals about the importance of records for knowledge and understanding of the characteristics of that

Características da clientela atendida por crise hipertensiva na emergência de um hospital municipal de Fortaleza, Estado do Ceará = Characteristics of the clientele assisted for hypertensive crisis in the emergency of a municipal hospital in Fortaleza, Ceará State

Directory of Open Access Journals (Sweden)

Ione Cavalcante Lacerda

2010-01-01

Full Text Available Objetivou-se descrever as características da clientela com crise hipertensiva. A pesquisa, quantitativa, descritiva e documental foi realizada em um hospital municipal de Fortaleza, Estado do Ceará em 2006. Na análise de 790 fichas de atendimento, observamos que 48,2% dos pacientes que apresentavam crise hipertensiva, encontravam-se na faixa etária de 40 a 59 anos e a maioria dos indivíduos era de casados (57,5%. Os principais sintomas encontrados foram cefaleia (35,7% e dor precordial (12.3% e, em 36,8% das fichas, não houve registro de sinais e sintomas. As medicações mais prescritas foram o captopril (90,6% e furosemida (53%. Conclui-se que a crise hipertensiva acomete muitos adultos, a maioria casados e que geralmente vão à emergência para fazer avaliação clínica de algum sinal/sintoma. Ressalta-se a necessidade de se alertar os profissionais de saúde quanto à importância do registro para conhecimento e compreensão das características dessa clientela para o controle e a prevenção da crise hipertensiva.The objective was to describe the characteristics of the clientele with hypertensive crisis. The research, which was quantitative, descriptive and documentary, was conducted at a municipal hospital in Fortaleza, Ceará Estate in 2006. In the analysis of 790 patient files, we found that 48.2% of patients presenting hypertensive crisis were in the age group between 40 and 59 years old. Most of the individuals were married (57.5%. The main symptoms were headache (35.7% and chest pain (12.3%, and in 36.8% of files there was no record of signs and symptoms. The most prescribed medications were captopril (90.6% and furosemide (53%. We conclude that hypertensive crisis affects many adults, most married and who usually go to the emergency room for clinical evaluation of a sign/symptom. We emphasize the need to alert health professionals about the importance of records for knowledge and understanding of the characteristics of that

Benazepril-Induced Agranulocytosis: A Case Report and Review of the Literature.

Science.gov (United States)

Hashmi, Hafiz Rizwan Talib; Jabbour, Rami; Schreiber, Zwi; Khaja, Misbahuddin

2016-06-23

Angiotensin-converting enzyme inhibitors are widely used drugs, and in appropriately selected patients, serious side effects are infrequent. Commonly seen side effects include cough, rash, hyperkalemia, renal dysfunction, and angioedema. Historically, dose-related agranulocytosis has been associated with captopril. Benazepril, a relatively more potent angiotensin-converting enzyme inhibitor, is rarely associated with agranulocytosis. Here, we report a case of drug-induced agranulocytosis due to benazepril, with complete recovery of white blood cell count upon discontinuation of the drug. All tests for other causes of agranulocytosis were unremarkable. This report highlights a serious and rare side effect associated with benazepril. Benazepril is a commonly employed anti-hypertensive medication, and we report an unusual condition associated with this medication in order to increase vigilance among caregivers. In such cases, prompt recognition and discontinuation of the causative drug can make the difference between a recovery and a fatal outcome associated with drug-induced agranulocytosis.

Toxins and drug discovery.

Science.gov (United States)

Harvey, Alan L

2014-12-15

Components from venoms have stimulated many drug discovery projects, with some notable successes. These are briefly reviewed, from captopril to ziconotide. However, there have been many more disappointments on the road from toxin discovery to approval of a new medicine. Drug discovery and development is an inherently risky business, and the main causes of failure during development programmes are outlined in order to highlight steps that might be taken to increase the chances of success with toxin-based drug discovery. These include having a clear focus on unmet therapeutic needs, concentrating on targets that are well-validated in terms of their relevance to the disease in question, making use of phenotypic screening rather than molecular-based assays, and working with development partners with the resources required for the long and expensive development process. Copyright © 2014 The Author. Published by Elsevier Ltd.. All rights reserved.

Posterior reversible encephalopathy syndrome and acute post-streptococcal glomerulonephritis mimicking breakthrough seizures

Directory of Open Access Journals (Sweden)

Kamille Abdool

2015-05-01

Full Text Available We report the case of a 14-year-old boy with a past history of primary generalized seizures, who had been seizure-free for 2 years on sodium valproate and presented with generalized tonic clonic seizures suggestive of breakthrough seizures. Examination revealed hypertension, impetiginous lesions of the lower limbs, microscopic hematuria, elevated antistreptolysin O titre and low complement levels consistent with acute post-streptococcal glomerulonephritis. Cranial magnetic resonance imaging (MRI demonstrated changes consistent with posterior reversible encephalopathy syndrome. Hypertension was controlled with intravenous nitroglycerin followed by oral captopril and amlodipine. Brain MRI changes returned normal within 2 weeks. The nephritis went in to remission within 2 months and after 8 months the patient has been seizure free again. Posterior reversible encephalopathy syndrome appeared to have neither short nor intermediate effect on seizure control in this patient. The relationship between posterior reversible encephalopathy syndrome and seizures is reviewed.

Characterization of antidiabetic and antihypertensive properties of canary seed (Phalaris canariensis L.) peptides.

Science.gov (United States)

Estrada-Salas, Patricia A; Montero-Morán, Gabriela M; Martínez-Cuevas, Pedro P; González, Carmen; Barba de la Rosa, Ana P

2014-01-15

Canary grass is used as traditional food for diabetes and hypertension treatment. The aim of this work is to characterize the biological activity of encrypted peptides released after gastrointestinal digestion of canary seed proteins. Canary peptides showed 43.5% inhibition of dipeptidyl peptidase IV (DPPIV) and 73.5% inhibition of angiotensin-converting enzyme (ACE) activity. An isolated perfused rat heart system was used to evaluate the canary seed vasoactive effect. Nitric oxide (NO), a major vasodilator agent, was evaluated in the venous effluent from isolated perfused rat heart. Canary seed peptides (1 μg/mL) were able to induce the production of NO (12.24 μM) in amounts similar to those induced by captopril (CPT) and bradykinin (BK). These results show that encrypted peptides in canary seed have inhibitory activity against DPPIV and ACE, enzymes that are targets for diabetes and hypertension treatments.

Organ distribution of quantum dots after intraperitoneal administration, with special reference to area-specific distribution in the brain

Energy Technology Data Exchange (ETDEWEB)

Kato, Shingo; Itoh, Kyoko; Yaoi, Takeshi; Tozawa, Takenori; Fushiki, Shinji [Department of Pathology and Applied Neurobiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto (Japan); Yoshikawa, Yutaka; Yasui, Hiroyuki [Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, Kyoto (Japan); Kanamura, Narisato [Department of Dental Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto (Japan); Hoshino, Akiyoshi; Manabe, Noriyoshi; Yamamoto, Kenji, E-mail: sfushiki@koto.kpu-m.ac.jp [The International Clinical Research Center, Research Institute, International Medical Center of Japan, Tokyo (Japan)

2010-08-20

Quantum dots (QDs) are well known for their potential application in biosensing, ex vivo live-cell imaging and in vivo animal targeting. The brain is a challenging organ for drug delivery, because the blood brain barrier (BBB) functions as a gatekeeper guarding the body from exogenous substances. Here, we evaluated the distribution of bioconjugated QDs, i.e., captopril-conjugated QDs (QDs-cap) following intraperitoneal injection into male ICR mice as a model system for determining the tissue localization of QDs, employing ICP-MS and confocal microscopy coupled with spectrometric analysis. We have demonstrated that intraperitoneally administered QDs-cap were delivered via systemic blood circulation into liver, spleen, kidney and brain at 6 h after injection. QDs-cap were located predominantly inside the blood vessels in the liver, kidney and brain, but a few were distributed in the parenchyma, especially noteworthy in the brain. Careful studies on acute as well as chronic toxicity of QDs in the brain are required prior to clinical application to humans.

Organ distribution of quantum dots after intraperitoneal administration, with special reference to area-specific distribution in the brain

International Nuclear Information System (INIS)

Kato, Shingo; Itoh, Kyoko; Yaoi, Takeshi; Tozawa, Takenori; Fushiki, Shinji; Yoshikawa, Yutaka; Yasui, Hiroyuki; Kanamura, Narisato; Hoshino, Akiyoshi; Manabe, Noriyoshi; Yamamoto, Kenji

2010-01-01

Quantum dots (QDs) are well known for their potential application in biosensing, ex vivo live-cell imaging and in vivo animal targeting. The brain is a challenging organ for drug delivery, because the blood brain barrier (BBB) functions as a gatekeeper guarding the body from exogenous substances. Here, we evaluated the distribution of bioconjugated QDs, i.e., captopril-conjugated QDs (QDs-cap) following intraperitoneal injection into male ICR mice as a model system for determining the tissue localization of QDs, employing ICP-MS and confocal microscopy coupled with spectrometric analysis. We have demonstrated that intraperitoneally administered QDs-cap were delivered via systemic blood circulation into liver, spleen, kidney and brain at 6 h after injection. QDs-cap were located predominantly inside the blood vessels in the liver, kidney and brain, but a few were distributed in the parenchyma, especially noteworthy in the brain. Careful studies on acute as well as chronic toxicity of QDs in the brain are required prior to clinical application to humans.

Novel angiotensin-converting enzyme (ACE) inhibitory peptides derived from boneless chicken leg meat.

Science.gov (United States)

Terashima, Masaaki; Baba, Takako; Ikemoto, Narumi; Katayama, Midori; Morimoto, Tomoko; Matsumura, Saki

2010-06-23

Four peptides that inhibit angiotensin-converting enzyme (ACE) were separated from the hydorlysate of boneless chicken leg meat digested with artificial gastric juice (pepsin). Two peptides were identified as the peptides encrypted in myosin heavy chain. The peptide P1 (MNVKHWPWMK) corresponds to the amino acid sequence from amino acids 825 to 834 of myosin heavy chain, and the peptide P4 (VTVNPYKWLP) corresponds to the amino acid sequence from amino acids 125 to 135 of myosin heavy chain. They are novel ACE inhibitory peptides derived from chicken, and IC(50) values of P1 and P4 were determined as 228 and 5.5 microM, respectively. Although these values were much larger than 0.022 microM for captopril, a typical synthetic ACE inhibitor, they are comparable to IC(50) values reported for various ACE inhibitory peptides derived from foods. Because the peptide P4 has a relatively low IC(50) value, it is a good starting substance for designing food supplements for hypertensive patients.

Somatic ACE regulates self-renewal of mouse spermatogonial stem cells via the MAPK signaling pathway.

Science.gov (United States)

Gao, Tingting; Zhao, Xin; Liu, Chenchen; Shao, Binbin; Zhang, Xi; Li, Kai; Cai, Jinyang; Wang, Su; Huang, Xiaoyan

2018-05-24

Spermatogonial stem cell (SSC) self-renewal is an indispensable part of spermatogenesis. Angiotensin I-converting enzyme (ACE) is a zinc dipeptidyl carboxypeptidase that plays a critical role in regulation of the renin-angiotensin system. Here, we used RT-PCR and Western blot analysis to confirm that somatic ACE (sACE) but not testicular ACE (tACE) is highly expressed in mouse testis before postpartum day 7 and in cultured SSCs. Our results revealed that sACE is located on the membrane of SSCs. Treating cultured SSCs with the ACE competitive inhibitor captopril was found to inhibit sACE activity, and significantly reduced the proliferation rate of SSCs. Microarray analysis identified 651 genes with significant differential expression. KEGG pathway analysis showed that these differentially expressed genes are mainly involved in the mitogen-activated protein kinase (MAPK) signaling pathway and cell cycle. sACE was found to play an important role in SSC self-renewal via the regulation of MAPK-dependent cell proliferation.

Efeitos da angiotensina-I e isquemia na recuperação funcional em corações isolados

Directory of Open Access Journals (Sweden)

Ubirajara Oliveira de Oliveira

2011-11-01

Full Text Available FUNDAMENTO: A ressuscitação de parada cardíaca pode apresentar disfunção miocárdica determinada pelo tempo da isquemia, e a inibição da enzima conversora de angiotensina (ECA pode reduzir a disfunção cardíaca durante a reperfusão. OBJETIVO: Investigar os efeitos da angiotensina-I e diferentes períodos de isquemia na recuperação funcional em corações de ratos isolados. MÉTODOS: Os corações isolados de ratos Wistar (n = 45; 250-300 g foram submetidos a diferentes períodos de isquemia global (20, 25 ou 30 min e reperfundidos (30 min com o tampão Krebs-Henseleit, ou com a adição de 400 nmol/L de angiotensina-I, ou com 400 nmol/L de angiotensina-I + 100 µmol/L de captopril durante o período de reperfusão. RESULTADOS: A derivada positiva máxima de pressão (+dP/dt max e o produto frequência-pressão foram reduzidos nos corações expostos à isquemia de 25 min (~ 73% e à isquemia de 30 min (~ 80% vs. isquemia de 20 min. A pressão diastólica final do ventrículo esquerdo (PDFVE e a pressão de perfusão (PP foram aumentadas nos corações expostos à isquemia de 25 min (5,5 e 1,08 vezes, respectivamente e à isquemia de 30 min (6 e 1,10 vezes, respectivamente vs. isquemia de 20 min. A angiotensina-I ocasionou uma diminuição no +dP/dt max e no produto frequência-pressão (~ 85-94% em todos os períodos de isquemia e um aumento na PDFVE e na PP (6,9 e 1,25 vezes, respectivamente apenas na isquemia de 20 min. O captopril foi capaz de reverter parcial ou completamente os efeitos da angiotensina-I na recuperação funcional nas isquemias de 20 e 25 min CONCLUSÃO: Os dados sugerem que a angiotensina-II participa direta ou indiretamente no dano pós-isquêmico e que a capacidade de um inibidor da ECA atenuar esse dano depende do tempo de isquemia.

COMPARATIVE ASSESSMENT OF EFFECT OF COMBINED DRUGS OF ACE INHIBITOR AND DIURETIC (“NOLIPREL FORTE” AND “CAPOZIDE” ON CARDIOVASCULAR REMODELING IN HYPERTENSIVE PATIENTS

Directory of Open Access Journals (Sweden)

T. D. Kaplanov

2015-12-01

Full Text Available Aim. To assess antihypertensive efficacy and effect on cardio-vascular remodeling of combined drugs of ACE inhibitor and diuretic, “Noliprel forte” (NF and “Capozide” (CA, in hypertensive high risk patients.Material and methods. 50 hypertensive (II grade patients (25 men and 25 women, 19-65 years old with high cardio-vascular risk took part in comparative opened randomized study. No one of patients received antihypertensive therapy before study. All patients were randomized for therapy with one of combined drug of ACE inhibitors and diuretic. 25 patients took NF (perindopril 4 mg and indapamide 1,25 mg, and 25 patients -CA (captopril 50 mg and hydrochlorothiazide 25 mg. Duration of observation period was 6 months. Before study, after 3 and 6 months of therapy ambulatory blood pressure monitoring (ABPM, echocardiography, cardiac and vessel Dopplerography, ultrasound scanning of general carotid arteries with detection of intima-media thickness (IMT, pulse wave speed (PWS were held in all patients. Blood bio-chemical analysis was done also.Results. After 3 months 2 patients in NF group and 4 ones in CA group were required to reinforce of ther-apy with additional administration of perindoprile 4 mg and captopril 50 mg respectively. As a result of 6-month of therapy in NF group systolic dlood pressure (BP decreased in 14,0% (р<0,001 and diastolic BP – на 12,9% (р<0,001. CA reduced systolic BP by 17,9% (р<0,0001 and diastolic BP – by 17,5% (р<0,001. 76% and 70% of patients in NF and CA groups, respectively, reached target BP level. Positive dynamic of daily profile of BP was observed according to ABPM data. Cerebral blood flow did not worsen despite of BP decrease. Both drugs decreased in thickness of inter-ventricular septum and left ventricular mass. Besides, NF decreased in thickness of left ventricular posterior wall. Both drugs reduced in IMT and decreased in PWS. NF therapy did not change of blood biochemical parameters. CA

COMPARATIVE ASSESSMENT OF EFFECT OF COMBINED DRUGS OF ACE INHIBITOR AND DIURETIC (“NOLIPREL FORTE” AND “CAPOZIDE” ON CARDIOVASCULAR REMODELING IN HYPERTENSIVE PATIENTS

Directory of Open Access Journals (Sweden)

T. D. Kaplanov

2005-01-01

Full Text Available Aim. To assess antihypertensive efficacy and effect on cardio-vascular remodeling of combined drugs of ACE inhibitor and diuretic, “Noliprel forte” (NF and “Capozide” (CA, in hypertensive high risk patients.Material and methods. 50 hypertensive (II grade patients (25 men and 25 women, 19-65 years old with high cardio-vascular risk took part in comparative opened randomized study. No one of patients received antihypertensive therapy before study. All patients were randomized for therapy with one of combined drug of ACE inhibitors and diuretic. 25 patients took NF (perindopril 4 mg and indapamide 1,25 mg, and 25 patients -CA (captopril 50 mg and hydrochlorothiazide 25 mg. Duration of observation period was 6 months. Before study, after 3 and 6 months of therapy ambulatory blood pressure monitoring (ABPM, echocardiography, cardiac and vessel Dopplerography, ultrasound scanning of general carotid arteries with detection of intima-media thickness (IMT, pulse wave speed (PWS were held in all patients. Blood bio-chemical analysis was done also.Results. After 3 months 2 patients in NF group and 4 ones in CA group were required to reinforce of ther-apy with additional administration of perindoprile 4 mg and captopril 50 mg respectively. As a result of 6-month of therapy in NF group systolic dlood pressure (BP decreased in 14,0% (р<0,001 and diastolic BP – на 12,9% (р<0,001. CA reduced systolic BP by 17,9% (р<0,0001 and diastolic BP – by 17,5% (р<0,001. 76% and 70% of patients in NF and CA groups, respectively, reached target BP level. Positive dynamic of daily profile of BP was observed according to ABPM data. Cerebral blood flow did not worsen despite of BP decrease. Both drugs decreased in thickness of inter-ventricular septum and left ventricular mass. Besides, NF decreased in thickness of left ventricular posterior wall. Both drugs reduced in IMT and decreased in PWS. NF therapy did not change of blood biochemical parameters. CA

99mTc-DTPA candesartan renography in the diagnosis of renovascular hypertension

International Nuclear Information System (INIS)

Alonso, O.; Moreira, E.; Galvalisi, M.E.; Alvarez, G.; Andruskevicius, P.; Guisoli, P.; Lago, G.; Beretta, M.

2002-01-01

Aim: Captopril renography (CPR) has been proved to be highly accurate in the diagnosis of patients with renovascular hypertension (RVH). However, a false-negative rate up to 20% has been described. Candesartan, a new angiotensin II AT1-receptor antagonist (ARA), has proved to be more effective to lower blood pressure in hypertensive patients than losartan, the most widely used drug of the group. The aim of this study was to evaluate the feasibility and the potential clinical value of candesartan renography (CSR) in the diagnosis of RVH and to compare on a head-to-head basis, the results of CPR and CSR. Material and Methods: A total of 39 studies were performed on 14 patients (9 female, 5 male, median age 45.5 yr, range: 35-74 yr) with moderate-to-high risk of RVH, using a three-day protocol (1: CPR, 2: CSR, 3: baseline). If the CPR and CSR studies were normal, no further studies were done. A dose of 296 MBq of 99m Tc-DTPA was i.v. injected one hour after captopril (50 mg), and three hours after candesartan (8 mg) interventions. Patients were imaged supine with a LFOV camera equipped with a LEHR collimator. Renogram curves were generated and split kidney uptake was also calculated during tracer uptake interval (2 to 3 min), using the area method. A study was considered of high probability for RVH (positive) when an unilateral change ≥2 in the renogram grade and/or a reduction in the relative kidney uptake greater than 10% was seen in the CPR/CSR study compared with the baseline acquisition. Patients underwent angiography (n=10) or colour doppler (n=4) within 2 weeks of nuclear studies. Results: Six patients were diagnosed by correlative imaging with unilateral (n=5) or bilateral (n=1) renal artery stenosis (RAS). In this group CPR was positive in 2/7 (29%) renal units whereas CSR was positive in 6/7 (86%). No evidence of significant RAS was demonstrated in the remaining group of patients (n=8) in whom CPR and CSR studies were negative for RVH. Conclusion: These

Extent of dispensing prescription-only medications without a prescription in community drug retail outlets in Addis Ababa, Ethiopia: a simulated-patient study

Directory of Open Access Journals (Sweden)

Erku DA

2016-07-01

Full Text Available Daniel Asfaw Erku,1 Abebe Basazn Mekuria,2 Abdrrahman Shemsu Surur,1 Begashaw Melaku Gebresillassie3 1Department of Pharmaceutical Chemistry, 2Department of Pharmacology, 3Department of Clinical Pharmacy, School of Pharmacy, University of Gondar, Gondar, Ethiopia Purpose: This study was aimed at assessing the extent of dispensing prescription-only medications without a prescription in community drug retail outlets (CDROs of Addis Ababa, Ethiopia.Methods: A descriptive cross-sectional observational study design was used to sample 31 pharmacies, 25 drug stores, and two rural drug vendors from August 11, 2015, to October 21, 2015, through a simple random sampling method. A simulated-patient method of visit was implemented to collect data. Requests of six tracer prescription-only medicines (amoxicillin + clavulanic acid capsule, amitriptyline, captopril, glibenclamide [also known as glyburide], omeprazole capsule, and sildenafil citrate and upper respiratory tract infection were selected as the simulated clinical scenario.Results: Amoxicillin–clavulanic acid capsule was dispensed when requested in 87.93% of the dispensaries. All of the CDROs dispensed omeprazole upon request. Sildenafil citrate (Viagra was in stock in 96.55% of the CDROs, all of which issued the requested number of tablets without asking why or for whom the drug was needed. Amitriptyline, captopril, and glibenclamide (glyburide were dispensed in 84.48%, 89.65%, and 87.93% of CDROs upon the provision of an empty container. Antibiotics were obtained from 75.86% of CDROs for presentation of upper respiratory tract infection symptoms. Among the dispensed antibiotics, the most common was amoxicillin (93.18%, followed by amoxicillin–clavulanic acid capsule (72.72%, and azithromycin (50%. Only 4.5% of the dispensaries asked about drug allergies, and 15.9% of the CDROs informed the simulated patient about the possible side effects of the drugs.Conclusion: This study revealed a very high

COMPORTAMIENTO DE LAS REACCIONES ADVERSAS A MEDICAMENTOS EN CUBA. AÑO 2007

Directory of Open Access Journals (Sweden)

Ashley Chao Cardeso

2009-01-01

Full Text Available Introducción. La farmacovigilancia es una actividad de salud pública destinada a la identificación, evaluación y prevención de los riesgos asociados a los medicamentos una vez comercializados. En Cuba existe un sistema de Farmacovigilancia con una tasa elevada de reporte de efectos adversos por medicamentos (7000 a 10 000 casos anuales. Desarrollo. Se realizó un estudio farmacovigilancia, descriptivo, transversal y retrospectivo, que utilizo la Metodología y Procedimientos de Trabajo de la Unidad Coordinadora Nacional de Farmacovigilancia, donde se analizaron todos los reportes de RAM llegados a la unidad durante el 2007 procedentes de todo el país. Resultados: Se analizaron 6928 notificaciones de reacciones adversas medicamentosas (RAM, notificándose 12963 RAM a razón de 1.9 RAM por notificación, de ellas 4251 fueron reacciones importantes (61.3% según criterios establecidos por la unidad coordinadora nacional de farmacovigilancia de Cuba. Los sistemas de órganos más afectados durante el año fueron piel y anejos (1774, 25.6% seguido del tracto gastrointestinal (1438, 20.7%. Entre los fármacos con mayor numero de reportes se encontró captopril (418/6.03%, el ibuprofeno 289 / 4.2% y ciprofloxacina 259/3.7%. Predominaron las RAM probables (68.7% y moderadas 47.1% y las más frecuentes fueron erupción cutánea, vómitos y fiebre. Entre las asociaciones fármaco - RAM muy importantes y con baja frecuencia de aparición se reportaron en total unas 2953 (35.9% en el año, de ellas el 9.1% fueron reacciones no descritas en la literatura revisada. Conclusiones: se detectaron entre una o dos reacciones adversas a medicamentos por cada notificación realizada. Dejando claro la importancia en la selección de los medicamentos y su uso racional. Los fármacos más asociados a las reacciones adversas notificadas fueron captopril, ciprofloxacina e ibuprofeno, la piel y el sistema digestivo fueron los sistemas más afectados y las reacciones

Effect of melatonin, captopril, spironolactone and simvastatin on blood pressure and left ventricular remodelling in spontaneously hypertensive rats

Czech Academy of Sciences Publication Activity Database

Šimko, F.; Pecháňová, Olga; Pelouch, Václav; Krajčírovičová, K.; Müllerová, M.; Bednárová, K.; Adamcová, M.; Paulis, L.

2009-01-01

Roč. 27, Suppl.6 (2009), S5-S10 ISSN 0263-6352 R&D Projects: GA ČR GA305/09/0336 Institutional research plan: CEZ:AV0Z50110509 Keywords : cardiac hypertrophy * fibrosis * ventricular remodeling Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 4.988, year: 2009

Reconstruction of diaminopimelic acid biosynthesis allows characterisation of Mycobacterium tuberculosis N-succinyl-L,L-diaminopimelic acid desuccinylase.

Science.gov (United States)

Usha, Veeraraghavan; Lloyd, Adrian J; Roper, David I; Dowson, Christopher G; Kozlov, Guennadi; Gehring, Kalle; Chauhan, Smita; Imam, Hasan T; Blindauer, Claudia A; Besra, Gurdyal S

2016-03-15

With the increased incidence of tuberculosis (TB) caused by Mycobacterium tuberculosis there is an urgent need for new and better anti-tubercular drugs. N-succinyl-L,L-diaminopimelic acid desuccinylase (DapE) is a key enzyme in the succinylase pathway for the biosynthesis of meso-diaminopimelic acid (meso-DAP) and L-lysine. DapE is a zinc containing metallohydrolase which hydrolyses N-succinyl L,L diaminopimelic acid (L,L-NSDAP) to L,L-diaminopimelic acid (L,L-DAP) and succinate. M. tuberculosis DapE (MtDapE) was cloned, over-expressed and purified as an N-terminal hexahistidine ((His)6) tagged fusion containing one zinc ion per DapE monomer. We redesigned the DAP synthetic pathway to generate L,L-NSDAP and other L,L-NSDAP derivatives and have characterised MtDapE with these substrates. In contrast to its other Gram negative homologues, the MtDapE was insensitive to inhibition by L-captopril which we show is consistent with novel mycobacterial alterations in the binding site of this drug.

Xenon-133 determination of muscle blood flow: Use in evaluating cardioactive drugs

International Nuclear Information System (INIS)

Wexler, J.P.; Davis, L.; Mancini, D.; Chadwick, B.; Le Jemtel, T.

1985-01-01

Cardioactive drugs may effect both the central and peripheral circulatory systems. The effects on the central and peripheral circulatory systems of chronic Captorpril therapy in 7 pts with severe congestive heart failure (CHF) were evaluated simultaneously. Skeletal muscle blood flow (SMBF) determined using 133-Xe washout and a Cd/Te detector, oxygen consumption (VO/sub 2/), and radial artery and femoral vein O/sub 2/ concentration difference (A-V) were determined at rest and peak upright bicycle exercise before (BT) and after (AT) 6-12 weeks of Captopril therapy. In CI pts there was a significant increase in VO/sub 2/ and SMBF AT vs BT. In contrast, in CNC pts there was no change in VO/sub 2/ and a significant decrease in SMBF AT vs BT. In pts with severe CHF who are CI, there is an apparent fall in peripheral vascular resistance (PVR). In contrast, in CNC pts there is an increase in PVR. This study demonstrates that SMBF determines using 133-Xe is an important method for determining the effects of cardioactive drugs

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.

Bartter Syndrome Type 3: Phenotype-Genotype Correlation and Favorable Response to Ibuprofen

Directory of Open Access Journals (Sweden)

Xuejun Yang

2018-05-01

Full Text Available Objective: To investigate the phenotype-genotype correlation in different genetic kinds of Bartter syndrome type 3 in children.Methods: Clinical and genetic data of 2 patients with different mutations in Bartter syndrome type 3 was analyzed while the prognosis was compared after a 6-year follow-up or 2-year follow-up, respectively.Results: Bartter syndrome is a kind of autosomal recessive inherited renal disorder. The manifestation and prognosis of Bartter syndrome change with mutation types, and severe mutation were often accompanied with unfavorable prognosis. Comprehensive therapy with ibuprofen, antisterone, captopril, and potassium have remarkable effect, while ibuprofen may improve growth retardation partly.Conclusion: Bartter syndrome should be considered when children have unreasonable continuous electrolyte disturbance, metabolic alkalosis and growth retardation.As a genetic disease, its clinical features depend on the mutation type. It can be ameliorated by electrolyte supplementation, prostaglandin synthetase inhibitors, angiotensin-converting enzyme inhibitors and potassium-sparing diuretic. Considering the following electrolyte disturbances, infections, growth retardation, kidney failure and even death, Bartter syndrome need lifelong treatment, early diagnosis and treatment is the most important.

Variantes alélicas de CYP2D6: *4, *6 y *10 en una muestra de residentes del estado Aragua, Venezuela

Directory of Open Access Journals (Sweden)

Carlos Flores-Angulo

Full Text Available El objetivo del estudio fue determinar la frecuencia de las variantes del gen CYP2D6: *4, *6 y *10 y predecir el fenotipo metabolizador en una muestra de 145 individuos no consanguíneos, aparentemente sanos, residentes del estado Aragua, Venezuela. Los genotipos fueron determinados mediante ensayos de reacción en cadena de la polimerasa seguidos de digestión con endonucleasas de restricción. La predicción del fenotipo metabolizador se realizó con base al sistema Activity score. Las frecuencias de CYP2D6 *4, *6 y *10 fueron de 14,5%, 0,3% y 1%, respectivamente; un porcentaje significativo de individuos fueron categorizados como metabolizador rápido heterocigoto/metabolizador intermedio (23,5% y metabolizador lento (4,1%. Esta información tiene impacto clínico potencial, porque CYP2D6 interviene en el metabolismo de fármacos de prescripción frecuente como: carvedilol, captopril, cloroquina, codeína, fluoxetina, fluvastatina, haloperidol, idarrubicina, indinavir, imatinib, loperamida, nifedipina, ondansetrón y tamoxifeno

A liver metalloendopeptidase which degrades the circulating hypotensive peptide hormones bradykinin and atrial natriuretic peptide

Directory of Open Access Journals (Sweden)

Carvalho K.M.

1999-01-01

Full Text Available A new metalloendopeptidase was purified to apparent homogeneity from a homogenate of normal human liver using successive steps of chromatography on DEAE-cellulose, hydroxyapatite and Sephacryl S-200. The purified enzyme hydrolyzed the Pro7-Phe8 bond of bradykinin and the Ser25-Tyr26 bond of atrial natriuretic peptide. No cleavage was produced in other peptide hormones such as vasopressin, oxytocin or Met- and Leu-enkephalin. This enzyme activity was inhibited by 1 mM divalent cation chelators such as EDTA, EGTA and o-phenanthroline and was insensitive to 1 µM phosphoramidon and captopril, specific inhibitors of neutral endopeptidase (EC 3.4.24.11 and angiotensin-converting enzyme (EC 3.4.15.1, respectively. With Mr 85 kDa, the enzyme exhibits optimal activity at pH 7.5. The high affinity of this endopeptidase for bradykinin (Km = 10 µM and for atrial natriuretic peptide (Km = 5 µM suggests that it may play a physiological role in the inactivation of these circulating hypotensive peptide hormones.

Efecto vasodilatador e inhibidor de vasoconstricción del extracto hidroalcohólico de hojas de Olea europaea (olivo sobre anillos aórticos de ratas

Directory of Open Access Journals (Sweden)

Job Nexar-QH

2013-10-01

Full Text Available Objetivos: Evaluar el efecto vasodilatador, la inhibición de la vasoconstricción, así como el mecanismo responsable, del extracto hidroalcohólico de hojas de Olea europaea (olivo, sobre anillos aórticos en ratas. Diseño: Experimental. Lugar: Centro de Investigación y Desarrollo Científico, Facultad de Medicina, Universidad Nacional de San Agustín, Arequipa, Perú. Material biológico: Hojas de Olea europea y anillos aórticos de Rattus norvegicus, variedad albina swiss. Intervenciones: Se obtuvo un extracto hidroalcohólico de las hojas de Olea europaea. Se usó anillos aórticos de rata en cámara de órganos aislados y se registró la actividad vasomotora con un transductor de tensión isométrica. Se produjo contracción basal máxima con CaCl2 6 mM y se determinó el efecto vasodilatador con dosis de 25, 50 y 100 mg/mL de extracto hidroalcohólico de las hojas de Olea europaea. Se usó 1H-[1,2,4] oxadiazolo [4,3 alquinoxalin-1-one] (ODQ y nifedipino para determinar el mecanismo de acción. Se comparó la inhibición de la vasoconstricción tras la incubación durante 30 minutos con extracto 100 mg/mL y con captopril 10 µM. Principales medidas de resultados: Porcentaje de vasodilatación y de vasoconstricción. Resultados: Se obtuvo una vasodilatación de 7,20 ± 1,49%, 9,84 ± 1,42% y 12,31 ± 1,16% para las dosis de 25, 50 y 100 mg/mL, respectivamente, siendo significativa con la dosis de 100 mg/mL. La vasodilatación se incrementó tras la administración de ODQ 100 mM. La vasodilatación se inhibió tras la incubación con ODQ 100 mM más nifedipino 5 µM. No se encontró diferencia significativa entre la inhibición de la vasoconstricción con captopril 10µM y extracto a 100 mg/mL. Conclusiones: El extracto hidroalcohólico de hojas de Olea europea, a una dosis de 100 mg/mL, tiene efecto vasodilatador sobre anillos aórticos de ratas, mediado por el bloqueo de canales de calcio; además, posee efecto inhibidor de la

BPP-5a produces a potent and long-lasting NO-dependent antihypertensive effect.

Science.gov (United States)

Ianzer, Danielle; Xavier, Carlos Henrique; Fraga, Fabiana Costa; Lautner, Roberto Queiroga; Guerreiro, Juliano Rodrigo; Machado, Leonor Tapias; Mendes, Elizabeth Pereira; de Camargo, Andônio Carlos Martins; Santos, Robson Augusto Souza

2011-12-01

The bradykinin potentiating peptides (BPPs) are oligopeptides found in different animal venoms. BPPs isolated from Bothrops jararaca venom were the first natural inhibitors described for somatic angiotensin I-converting enzyme (ACE). They were used in the structural modeling for captopril development, a classical ACE inhibitor widely used to treat human hypertension. We evaluated the effect of BPP-5a on cardiovascular parameters of conscious Wistar (WTs) and spontaneously hypertensive rats (SHRs). In SHR, BPP-5a showed potent cardiovascular effects, at doses ranging from 0.47 to 710 nmol/kg. The maximal changes in mean arterial pressure (MAP) and heart rate (HR) were found at the dose of 2.37 nmol/kg (Δ MAP: -38 ± 4 mmHg, p BPP-5a upon argininosuccinate synthetase and B(1), B(2), AT(1), AT(2) or Mas receptors. Ex vivo assays showed that BPP-5a induced endothelium-dependent vasorelaxation in isolated aortic rings of SHRs and WTs. Although the BPP-5a is considered an ACE inhibitor, our results indicate that its antihypertensive effect is exerted via a unique target, a nitric-oxide-dependent mechanism.

Direct and indirect assessment of skeletal muscle blood flow in chronic congestive heart failure

International Nuclear Information System (INIS)

LeJemtel, T.H.; Scortichini, D.; Katz, S.

1988-01-01

In patients with chronic congestive heart failure (CHF), skeletal muscle blood flow can be measured directly by the continuous thermodilution technique and by the xenon-133 clearance method. The continuous thermodilution technique requires retrograde catheterization of the femoral vein and, thus, cannot be repeated conveniently in patients during evaluation of pharmacologic interventions. The xenon-133 clearance, which requires only an intramuscular injection, allows repeated determination of skeletal muscle blood flow. In patients with severe CHF, a fixed capacity of the skeletal muscle vasculature to dilate appears to limit maximal exercise performance. Moreover, the changes in peak skeletal muscle blood flow noted during long-term administration of captopril, an angiotensin-converting enzyme inhibitor, appears to correlate with the changes in aerobic capacity. In patients with CHF, resting supine deep femoral vein oxygen content can be used as an indirect measurement of resting skeletal muscle blood flow. The absence of a steady state complicates the determination of peak skeletal muscle blood flow reached during graded bicycle or treadmill exercise in patients with chronic CHF. Indirect assessments of skeletal muscle blood flow and metabolism during exercise performed at submaximal work loads are currently developed in patients with chronic CHF

Aktivitas Ramuan Daun Salam, Herba Pegagan, Akar Alang-Alang dan Biji Pala pada Tikus Hipertensi yang Diinduksi Prednison dan Garam

Directory of Open Access Journals (Sweden)

Ulfatun Nisa

2017-08-01

Full Text Available The prevalence of hypertension in Indonesia was 25,8%. As much as 70% types of hypertensive patients were mild hypertension. There were some medicinal plants contain single formulation could be used for lowering blood pressure but not in a herbal formulation. This study determined the efficacy of antihypertension herbal formulation that consists of Indonesian bay leaves, Centella herbs, blady grass roots dan nutmeg seeds. This study was an experimental laboratory research with pre and post-test controlled design, used thirty Sprague-Dawley rats that were classified randomly into five groups (negative control group which didn't have treatment, positive control group which consumed captopril 0,25 mg, and three groups which consumed antihypertension herbal formulation with doses of 0,08 g; 0,16 g; and 0,32 g. The rats were induced by prednisone and NaCl 2,5 % for 21 days.  The data were analysed using ANOVA test with CI 95%. After two weeks observation, the results showed that the blood pressure in the negative control group increased,  but in the positive control and treatment groups decreased significantly (p=0,001. In conclusion, the herbal formulation could decrease rat's blood pressure.  

[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).

Animal toxins with high therapeutic potential and their use in biomedicine Toxinas de serpientes con alto potencial terapéutico y su uso en la biomedicina

Directory of Open Access Journals (Sweden)

Leidy Johana Vargas Muñoz

2009-11-01

Full Text Available

Animal venoms are complex mixtures of proteins, peptides, enzymes and trace elements such as carbohydrates and salts, which serve to immobilize preys and to begin their digestion. Some of these compounds have been isolated and characterized, or described as lethal toxins, while others have powerful actions on specific proteins, such as those involved in blood coagulation. Due to the discovery in 1971 of the peptide that gave rise to captopril and to a better understanding of the potential effects of toxins, animal venoms started to be considered as rich sources of bioactive compounds, which not only provide the necessary tools to decipher molecular details of various physiological processes, but also are a source of inspiration to design and develop a range of new therapeutic agents. This review presents the application of new therapeutic options or models to design them based on certain molecules isolated from snake venoms, with high potential in fields such as biomedicine and pharmacy.

Los venenos de animales son mezclas complejas de proteínas, péptidos, enzimas y trazas de elementos no proteicos tales como carbohidratos y sales, cuya finalidad es inmovilizar la presa y comenzar a digerirla; algunos de estos compuestos han sido aislados y caracterizados o descritos como toxinas letales, o se les han atribuido acciones potentes sobre proteínas específicas como, por ejemplo, las involucradas en la coagulación sanguínea. Debido al descubrimiento

Inhibition of angiotensin II-induced facilitation of sympathetic neurotransmission in the pithed rat: a comparison between losartan, irbesartan, telmisartan, and captopril

NARCIS (Netherlands)

Balt, J. C.; Mathy, M. J.; Pfaffendorf, M.; van Zwieten, P. A.

2001-01-01

Numerous studies have shown that angiotensin II enhances sympathetic nervous transmission. The objective of the present study was to quantify the inhibitory effect of the angiotensin II type 1 (AT1) receptor blockers losartan, irbesartan and telmisartan and the angiotensin converting enzyme (ACE)

Both dioscorin, the tuber storage protein of yam (Dioscorea alata cv. Tainong No. 1), and its peptic hydrolysates exhibited angiotensin converting enzyme inhibitory activities.

Science.gov (United States)

Hsu, Feng-Lin; Lin, Yaw-Huei; Lee, Mei-Hsien; Lin, Chien-Liang; Hou, Wen-Chi

2002-10-09

Dioscorin, the tuber storage protein of yam (Dioscorea alata cv. Tainong No. 1), was purified to homogeneity by DE-52 ion-exchange chromatography. This purified dioscorin was shown by spectrophotometric methods to inhibit angiotensin converting enzyme (ACE) in a dose-dependent manner (12.5-750 microg, respectively, 20.83-62.5% inhibitions) using N-[3-(2-furyl)acryloyl]-Phe-Gly-Gly (FAPGG) as substrates. The 50% inhibition (IC(50)) of ACE activity was 6.404 microM dioscorin (250 microg corresponding to 7.81 nmol) compared to that of 0.00781 microM (0.0095 nmol) for captopril. The commercial bovine serum albumin and casein (bovine milk) showed less ACE inhibitory activity. The use of qualitative TLC also showed dioscorin as ACE inhibitors. Dioscorin showed mixed noncompetitive inhibitions against ACE; when 31.25 microg of dioscorin (0.8 microM) was added, the apparent inhibition constant (K(i)) was 2.738 microM. Pepsin was used for dioscorin hydrolysis at 37 degrees C for different times. It was found that the ACE inhibitory activity was increased from 51.32% to about 75% during 32 h hydrolysis. The smaller peptides were increased with increasing pepsin hydrolytic times. Dioscorin and its hydrolysates might be a potential for hypertension control when people consume yam tuber.

QGQS Granule in SHR Serum Metabonomics Study Based on Tools of UPLC-Q-TOF and Renin-Angiotensin-Aldosterone System Form Protein Profilin-1

Directory of Open Access Journals (Sweden)

Ke Li

2017-01-01

Full Text Available QGQS granule is effective for the therapeutic of hypertension in clinic. The aim of this research is to observe the antihypertension effect of QGQS granule on SHR and explain the mechanism of its lowering blood pressure. 30 SHR were selected as model group, captopril group, and QGQS group, 10 WKYr were used as control group, and RBP were measured on tail artery consciously. And all the serum sample analysis was carried out on UPLC-TOF-MS system to determine endogenous metabolites and to find the metabonomics pathways. Meanwhile, ELISA kits for the determination pharmacological indexes of PRA, AngI, AngII, and ALD were used for pathway confirmatory; WB for determination of profilin-1 protein expression was conducted for Ang II pathway analysis as well. It is demonstrated that QGQS granule has an excellent therapeutic effect on antihypertension, which exerts effect mainly on metabonomics pathway by regulating glycerophospholipid, sphingolipid, and arachidonic acid metabolism, and it could inhibit the overexpression of the profilin-1 protein. We can come to a conclusion that RAAS should be responsible mainly for the metabonomics pathway of QGQS granule on antihypertension, and it plays a very important role in protein of profilin-1 inhibition.

A mouse model for Costello syndrome reveals an Ang II–mediated hypertensive condition

Science.gov (United States)

Schuhmacher, Alberto J.; Guerra, Carmen; Sauzeau, Vincent; Cañamero, Marta; Bustelo, Xosé R.; Barbacid, Mariano

2008-01-01

Germline activation of H-RAS oncogenes is the primary cause of Costello syndrome (CS), a neuro-cardio-facio-cutaneous developmental syndrome. Here we describe the generation of a mouse model of CS by introduction of an oncogenic Gly12Val mutation in the mouse H-Ras locus using homologous recombination in ES cells. Germline expression of the endogenous H-RasG12V oncogene, even in homozygosis, resulted in hyperplasia of the mammary gland. However, development of tumors in these mice was rare. H-RasG12V mutant mice closely phenocopied some of the abnormalities observed in patients with CS, including facial dysmorphia and cardiomyopathies. These mice also displayed alterations in the homeostasis of the cardiovascular system, including development of systemic hypertension, extensive vascular remodeling, and fibrosis in both the heart and the kidneys. This phenotype was age dependent and was a consequence of the abnormal upregulation of the renin–Ang II system. Treatment with captopril, an inhibitor of Ang II biosynthesis, prevented development of the hypertension condition, vascular remodeling, and heart and kidney fibrosis. In addition, it partially alleviated the observed cardiomyopathies. These mice should help in elucidating the etiology of CS symptoms, identifying additional defects, and evaluating potential therapeutic strategies. PMID:18483625

A radionuclide method for differentiating renovascular from essential hypertension

International Nuclear Information System (INIS)

Simeonova, A.; Kostadinova, I.; Milanov, S.; Delijska, B.; Nikolov, D.

1995-01-01

Renovascular hypertension occurs in nearly 5 per cent of patients with high blood pressure but nevertheless its diagnosis has important practical implication insofar as a complete cure is possible by resorting to percutaneous transluminal angioplasty or surgery. It is the purpose of this work to develop a radionuclide method for differential diagnosis of the two conditions using 99m Tc-DTPA which contributes to overall functional assessment of the kidneys, and introduces an objective indicator for estimating the extent of renal response to Captopril (C). A total of thirty patients, 25 of them with essential hypertension (EH) and 5 with renovascular hypertension (RVH), are studied. From the obtained data on transit time of kidneys, T max and their perceptual contribution to total renal function in EH patients, it becomes evident that the effect of C on the listed indicators is insignificant (p>0.05). In RVH patients, following drug intake, there is prolongation of the transit time, T max as well as reduced contribution of the kidney affected to total renal function (by over 6 per cent). In conclusion it is stressed that using the noninvasive radionuclide method and quantitative indicators proposed, it is possible to differentiate RVH from EH and renoparenchymal hypertension with a high-degree certainty. 6 refs., 1 tab., 2 figs. (author)

Inhibition of Urease by Disulfiram, an FDA-Approved Thiol Reagent Used in Humans.

Science.gov (United States)

Díaz-Sánchez, Ángel Gabriel; Alvarez-Parrilla, Emilio; Martínez-Martínez, Alejandro; Aguirre-Reyes, Luis; Orozpe-Olvera, Jesica Aline; Ramos-Soto, Miguel Armando; Núñez-Gastélum, José Alberto; Alvarado-Tenorio, Bonifacio; de la Rosa, Laura Alejandra

2016-11-26

Urease is a nickel-dependent amidohydrolase that catalyses the decomposition of urea into carbamate and ammonia, a reaction that constitutes an important source of nitrogen for bacteria, fungi and plants. It is recognized as a potential antimicrobial target with an impact on medicine, agriculture, and the environment. The list of possible urease inhibitors is continuously increasing, with a special interest in those that interact with and block the flexible active site flap. We show that disulfiram inhibits urease in Citrullus vulgaris (CVU), following a non-competitive mechanism, and may be one of this kind of inhibitors. Disulfiram is a well-known thiol reagent that has been approved by the FDA for treatment of chronic alcoholism. We also found that other thiol reactive compounds (l-captopril and Bithionol) and quercetin inhibits CVU. These inhibitors protect the enzyme against its full inactivation by the thiol-specific reagent Aldrithiol (2,2'-dipyridyl disulphide, DPS), suggesting that the three drugs bind to the same subsite. Enzyme kinetics, competing inhibition experiments, auto-fluorescence binding experiments, and docking suggest that the disulfiram reactive site is Cys592, which has been proposed as a "hinge" located in the flexible active site flap. This study presents the basis for the use of disulfiram as one potential inhibitor to control urease activity.

Clinical nuclear medicine applications in Turkey and specific renal studies

International Nuclear Information System (INIS)

Erbas, B.

2004-01-01

Full text: Nuclear cardiology, nuclear oncology, pediatric nuclear medicine and nuclear endocrinology are the main application areas of clinical nuclear medicine in Turkey. Not only imaging studies, but also therapeutic application of radiopharmaceuticals is also performed at many institutes, such as hyperthyroidism treatment with radioiodine, thyroid cancer ablation and metastases treatment with radioiodine, radio synovectomy, metastatic pain therapy, and recently radioimmunotherapy of lymphomas. Almost all radionuclides and radiopharmaceuticals are obtained commercially from European countries, except 18-FDG which is obtained from two cyclotrons in Turkey. More than 30.000 renal procedures are performed at the University hospitals in a year. Pediatric age groups is approximately % 55 of patients. 99mTc-DTPA (%44), 99mTc-DMSA (%37), 99mTc-MAG3 (%17) and 99mTc-EC (%2) are the most commonly used radiopharmaceuticals for renal imaging. More than 6.000 vials of several pharmaceuticals are used for renal cortical scintigraphy (%35), dynamic renal imaging (%34), renal scintigraphy with diuretic (%27) and captopril scintigraphy (%4). Most common indication for renal cortical scintigraphy is detection of cortical scarring (%53). In addition, using single plasma sample method or gamma-camera method renal clearance measurements with 99mTc-MAG3 99mTc-DTPA have been used at some institutions

Prediction of Clinically Relevant Safety Signals of Nephrotoxicity through Plasma Metabolite Profiling

Directory of Open Access Journals (Sweden)

W. B. Mattes

2013-01-01

Full Text Available Addressing safety concerns such as drug-induced kidney injury (DIKI early in the drug pharmaceutical development process ensures both patient safety and efficient clinical development. We describe a unique adjunct to standard safety assessment wherein the metabolite profile of treated animals is compared with the MetaMap Tox metabolomics database in order to predict the potential for a wide variety of adverse events, including DIKI. To examine this approach, a study of five compounds (phenytoin, cyclosporin A, doxorubicin, captopril, and lisinopril was initiated by the Technology Evaluation Consortium under the auspices of the Drug Safety Executive Council (DSEC. The metabolite profiles for rats treated with these compounds matched established reference patterns in the MetaMap Tox metabolomics database indicative of each compound’s well-described clinical toxicities. For example, the DIKI associated with cyclosporine A and doxorubicin was correctly predicted by metabolite profiling, while no evidence for DIKI was found for phenytoin, consistent with its clinical picture. In some cases the clinical toxicity (hepatotoxicity, not generally seen in animal studies, was detected with MetaMap Tox. Thus metabolite profiling coupled with the MetaMap Tox metabolomics database offers a unique and powerful approach for augmenting safety assessment and avoiding clinical adverse events such as DIKI.

[The introduction of generic pharmaceutical products into Galicia].

Science.gov (United States)

Verdejo González, A; López-Lázaro, L; Rodríguez Moreno, C; Piñeiro Lago, B; Pereira Martínez, M L

1999-11-30

To know the evolution of the introduction of generic drugs (GDs) in Galicia. Secondarily, to evaluate its potential impact on pharmaceutical expenditure. Descriptive study of GDs utilization. Cost-minimization analysis. Galician autonomous region, year 1998. Using data from the prescription billing registry of Social Security we have selected the active ingredients corresponding to GDs with prescriptions in Galicia in 1997. We have analyzed the data for their oral single substance preparations by quarters. Consumption in DHDs of allopurinol, atenolol, captopril, naproxen and ranitidine remained stable during 1998. The market share for their GDs in quantitative terms relative to both total consumption of the active ingredients and to their pharmaceutical equivalents, showed an overall growing trend. The maximum observed value was seen for ranitidine at last quarter. Total expenditure (in final customer prices) during 1998 on the selected active substances was higher than 1864 million pesetas. Potential savings afforded by substitution for the lowest price GD prescribed in Galicia would reach 427 million pesetas. GDs market penetration in Galicia during 1998 was limited but increasing. Its utilization may afford estimated savings of 21-28% of the cost for the selected drugs. However, the expenditure on the above drugs was just 2.7% of total pharmaceutical expenditure.

Antioxidant and Angiotensin-Converting Enzyme Inhibitory Activity of Eucalyptus camaldulensis and Litsea glaucescens Infusions Fermented with Kombucha Consortium.

Science.gov (United States)

Gamboa-Gómez, Claudia I; González-Laredo, Rubén F; Gallegos-Infante, José Alberto; Pérez, Mş Del Mar Larrosa; Moreno-Jiménez, Martha R; Flores-Rueda, Ana G; Rocha-Guzmán, Nuria E

2016-09-01

Physicochemical properties, consumer acceptance, antioxidant and angiotensin-converting enzyme (ACE) inhibitory activities of infusions and fermented beverages of Eucalyptus camaldulensis and Litsea glaucescens were compared. Among physicochemical parameters, only the pH of fermented beverages decreased compared with the unfermented infusions. No relevant changes were reported in consumer preference between infusions and fermented beverages. Phenolic profile measured by UPLC MS/MS analysis demonstrated significant concentration changes of these compounds in plant infusions and fermented beverages. Fermentation induced a decrease in the concentration required to stabilize 50% of DPPH radical ( i . e . lower IC 50 ). Additionally, it enhanced the antioxidant activity measured by the nitric oxide scavenging assay (14% of E. camaldulensis and 49% of L. glaucescens ); whereas relevant improvements in the fermented beverage were not observed in the lipid oxidation assay compared with unfermented infusions. The same behaviour was observed in the inhibitory activity of ACE; however, both infusions and fermented beverages had lower IC 50 than positive control (captopril). The present study demonstrated that fermentation has an influence on the concentration of phenolics and their potential bioactivity. E. camaldulensis and L. glaucescens can be considered as natural sources of biocompounds with antihypertensive potential used either as infusions or fermented beverages.

ACE inhibition and antioxidant activity of different part of Channa striata prepared by various cooking method

Science.gov (United States)

Chasanah, E.; Budiari, S.; Thenawijaya, M.; Palupi, N. S.

2018-03-01

Channa striata (snakehead) extract has been known possessing positive activity, one of which is the ability to inhibit Angiotensin Converting Enzyme (ACE) activity in vitro. Aims of this study were to determine the effect of cooking and parts of C. striata, i.e. meat/fillet, gonad, skin, gill against the ACE inhibition activity and antioxidant activity in vitro. Heat processing methods used were direct boiling and indirect boiling and steamed at 100 °C for 10 min. ACE inhibition activity was analyzed using hippuryl-L-histidyl-L-leucine (HHL) as substrate and antioxidant activity was analyzed using DPPH method. The result shows that the higher the concentration of the extract (5 %, 20 %, 35 % and 50 %), the higher the antioxidant activity. The highest antioxidant activity was shown by gonad followed by meat extract, skin, and gill. Cooking treatment affected antioxidant activity, being the detrimental treatment were steam and direct boiling. The egg/gonad of C. striata showed the highest capability to inhibit ACE activity followed by meat/fillet, gill and skin. In concentration of 10 mg, extract of C. striata gonad was comparable to captopril, a commercial hypertension drug. While uncooked fillet showed the highest ACE inhibition activity followed by indirect boiling, direct boiling and steaming.

Antioxidant and Angiotensin-Converting Enzyme Inhibitory Activity of Eucalyptus camaldulensis and Litsea glaucescens Infusions Fermented with Kombucha Consortium

Directory of Open Access Journals (Sweden)

Claudia I. Gamboa-Gómez

2016-01-01

Full Text Available Physicochemical properties, consumer acceptance, antioxidant and angiotensin-converting enzyme (ACE inhibitory activities of infusions and fermented beverages of Eucalyptus camaldulensis and Litsea glaucescens were compared. Among physicochemical parameters, only the pH of fermented beverages decreased compared with the unfermented infusions. No relevant changes were reported in consumer preference between infusions and fermented beverages. Phenolic profi le measured by UPLC MS/MS analysis demonstrated significant concentration changes of these compounds in plant infusions and fermented beverages. Fermentation induced a decrease in the concentration required to stabilize 50 % of DPPH radical (i.e. lower IC50. Additionally, it enhanced the antioxidant activity measured by the nitric oxide scavenging assay (14 % of E. camaldulensis and 49 % of L. glaucescens; whereas relevant improvements in the fermented beverage were not observed in the lipid oxidation assay compared with unfermented infusions. The same behaviour was observed in the inhibitory activity of ACE; however, both infusions and fermented beverages had lower IC50 than positive control (captopril. The present study demonstrated that fermentation has an influence on the concentration of phenolics and their potential bioactivity. E. camaldulensis and L. glaucescens can be considered as natural sources of biocompounds with antihypertensive potential used either as infusions or fermented beverages.

Drug hypersensitivity syndrome

Directory of Open Access Journals (Sweden)

Rashmi Kumari

2011-01-01

Full Text Available Drug hypersensitivity syndrome (DHS is an adverse drug reaction commonly associated with the aromatic antiepileptic drugs (AEDs, viz., phenytoin (PHT, carbamazepine (CBZ, phenobarbital (PB, lamotrigine, primidone, etc. It can also be caused by other drugs, such as sulfonamides, dapsone, minocycline, gold derivatives, cyclosporine, captopril, diltiazem, terbinafine, azathioprine and allopurinol. Diagnosis of DHS may be difficult because of the variety of clinical and laboratory abnormalities and manifestations and because the syndrome may mimic infectious, neoplastic or collagen vascular disorders. The risk for developing hypersensitivity within 60 days of the first or second prescription in new users of PHT or CBZ was estimated to be 2.3-4.5 per 10,000 and 1-4.1 per 10,000, respectively. The syndrome is defined by the fever, skin rash, lymphadenopathy and internal organ involvement within the first 2-8 weeks after initiation of therapy. Internal manifestations include, among others, agranulocytosis, hepatitis, nephritis and myositis. Insufficient detoxification may lead to cell death or contribute to the formation of antigen that triggers an immune reaction. Cross-reactivity among PHT, CBZ and PB is as high as 70%-80%. Management mainly includes immediate withdrawal of the culprit drug, symptomatic treatment and systemic steroids or immunoglobulins.

Stimultion by angiotensin of prostacyclin biosynthesis in rats and dogs.

Science.gov (United States)

Dusting, G J; Mullins, E M

1980-01-01

1. Stimulation of prostanoid release by angiotensins (AI and AII) in rat isolated mesenteric vasculature and in the circulation of anaesthetized dogs has been investigated by bioassay. 2. AI and AII released a PGI2-like substance into rat mesenteric effluent and arterial blood of dogs; PGE2, PGF2 alpha, or TXA2 were not detected. 3. AI stimulated PGI2 release in both systems largely as a result of its conversion to AII, since PGI2 release was much reduced after treatment with captorpril. 3. AI stimulated PGI2 release in both systems largely as a result of its conversion to AII, since PGI2 release was much reduced after treatment with captopril. 4. Intravenous AII (0.02-1.0 microgram kg-1min-1) in dogs released PGI2 mainly from the lungs since right atrial blood contained much less than arterial blood. 5. Indomethacin (1 microgram/ml) abolished AII-induced PGI2 release from the memestery preparation, but intravenous idomethacin (10 mg/kg), meclofenamate (2 mg/kg) or aspirin (100 mg/kg) did not eliminate the pulmonary source of PGI2 in dogs. These findings highlight the dangers of assuming in vivo treatment with cyclo-oxygenase inhibitors abolished biosynthesis of all prostanoids.

Clinical nuclear medicine applications in Turkey and specific renal studies

International Nuclear Information System (INIS)

Erbas, B.

2004-01-01

Nuclear cardiology, nuclear oncology, pediatric nuclear medicine and nuclear endocrinology are the main application areas of clinical nuclear medicine in Turkey. Not only imaging studies, but also therapeutic application of radiopharmaceuticals is also performed at many institutes, such as hyperthyroidism treatment with radioiodine, thyroid cancer ablation and metastases treatment with radioiodine, radio synovectomy, metastatic pain therapy, and recently radioimmunotherapy of lymphomas. Almost all radionuclides and radiopharmaceuticals are obtained commercially from European countries, except 18-FDG which is obtained from two cyclotrons in Turkey. More than 30.000 renal procedures are performed at the University hospitals in a year. Pediatric age groups is approximately % 55 of patients. 99m Tc-DTPA (%44), 99m Tc-DMSA (%37), 99m Tc-MAG3 (%17) and 99m Tc-EC (%2) are the most commonly used radiopharmaceuticals for renal imaging. More than 6.000 vials of several pharmaceuticals are used for renal cortical scintigraphy (%35), dynamic renal imaging (%34), renal scintigraphy with diuretic (%27) and captopril scintigraphy (%4). Most common indication for renal cortical scintigraphy is detection of cortical scarring (%53). In addition, using single plasma sample method or gamma-camera method renal clearance measurements with 99m Tc-MAG3 99m Tc-DTPA have been used at some institutions. (author)

Cystinuria in children in Bahrain

International Nuclear Information System (INIS)

Al-Hermi, B.; Al-Kameli, A.; Aal, Abbas A.

2002-01-01

Cystinuria is a rare autosomal recessive trait with a defect in transportof cystine and other dibasic amino acids in the kidney and intestine. Renalstone formation is the only clinical presentation of Cystinuria. We presentherewith three cases with Cystinuria. We present herewith three cases withcystinuria. Case 1 is a 13-year-old boy known to have Bernard Souliersyndrome who presented at the age of six years with staghorn stone of theleft kidney. He was treated with extracorporeal shock wave lithotripsy (ESWL)with little benefit, followed by percutaneous nephrolithotomy (PCNL). Hestill gets recurrent renal stones and is being treated with high fluidintake, low sodium diet, captopril, K-citrate and D-pencillamine. Case 2 is a10-year-old boy, brother of the first patient, who was diagnosed ascystinuria on family screening. He presented with bilateral tiny renalstones. Case 3 is a four-year-old girl who was presented at the age of 1.5years with urinary tract infection (UTI). Renal ultrasound showed lefthydronephrosis and intravenous pyelography (IVP) showed bilateral ureteralstones. She underwent cystoscopy and lithiotripsy twice; currently she is oncaptopril, K-citrate, high fluid intake and low sodium diet. We believe thisis the first report of cystinuria in children from Bahrain. (author)

HOW ADVERSE DRUG-REACTIONS CAN PLAY A ROLE IN INNOVATIVE DRUG RESEARCH - SIMILARITIES IN ADVERSE DRUG REACTION PROFILES OF CAPTOPRIL AND PENICILLAMINE

NARCIS (Netherlands)

RIKKEN, F; VOS, R

1995-01-01

We describe how adverse drug reactions (ADRs) can play an important role in pharmaceutical research and drug development. Not only do ADRs represent the risks and drawbacks associated with drugs but they can also be related to other knowledge available in pharmaceutical and medical research. We

Penggunaan Obat Antihipertensi pada Pasien Hipertensi Esensial di Poliklinik Ginjal Hipertensi RSUP DR. M. Djamil Tahun 2011

Directory of Open Access Journals (Sweden)

Heri Fitrianto

2014-01-01

Full Text Available AbstrakPenyakit hipertensi tidak dapat disembuhkan dan berkaitan erat dengan penurunan usia harapan hidup. Penderita hipertensi juga sering kali disertai oleh penyakit penyerta. Umumnya, golongan obat antihipertensi yang dikenal yaitu, diuretik, ACE Inhibitor, Angiotensin Reseptor Bloker, Canal Calcium Blocker, and Beta Blocker. Terapi yang diberikan pada penderita hipertensi tanpa penyakit penyerta dan dengan penyakit penyerta tentunya berbeda. Tujuan penelitian ini adalah mengetahui penggunaan obat antihipertensi antara pasien hipertensi esensial dengan penyakit penyerta dan yang tidak disertai dengan penyakit penyerta di poliklinik RSUD Dr. M. Djamil, Padang. Metode penelitian yang digunakan adalah deskriptif dengan mengambil data dari rekam medik. Data dari 380 pasien yang dikumpulkan selama periode Januari 2011 sampai dengan Desember 2011. Jumlah subjek ditentukan dengan teknik total sampling. Dari data penelitian didapatkan bahwa 277 pasien hipertensi tanpa penyakit penyerta dan sebanyak 103 pasien hipertensi dengan penyakit penyerta. Komposisi dari 103 pasien hipertensi dengan penyakit penyerta yaitu 63 pasien dengan diabetes melitus, 13 pasien dengan PJK, 13 pasien dengan stroke, 7 pasien dengan gagal jantung, 4 pasien dengan pasca infark miokard, 3 pasien dengan gagal ginjal kronik. Berdasarkan data penelitian didapatkan penggunaan obat antihipertensi yang sering digunakan yaitu Hidroklortiazid (35,5%, Captopril (26,2%, Valsartan (20,6%, Amlodipin (15,2%, dan obat antihipertensi lain (2,5%. Berdasarkan hasil penelitian disimpulkan bahwa hipertensi dengan penyakit penyerta terbanyak adalah diabetes melitus dan penggunaan obat terbanyak berasal dari golongan diuretik yaitu penggunaan Hidroklortiazid.Kata kunci: obat antihipertensi, hipertensi, diuretikAbstractHypertension can not be cured and is closely related to a decrease in life expectancy. Patients with hypertension are also often accompanied by complience indication. Generally

Snake Venom: From Deadly Toxins to Life-saving Therapeutics.

Science.gov (United States)

Waheed, Humera; Moin, Syed F; Choudhary, M I

2017-01-01

Snakes are fascinating creatures and have been residents of this planet well before ancient humans dwelled the earth. Venomous snakes have been a figure of fear, and cause notable mortality throughout the world. The venom constitutes families of proteins and peptides with various isoforms that make it a cocktail of diverse molecules. These biomolecules are responsible for the disturbance in fundamental physiological systems of the envenomed victim, leading to morbidity which can lead to death if left untreated. Researchers have turned these life-threatening toxins into life-saving therapeutics via technological advancements. Since the development of captopril, the first drug that was derived from bradykininpotentiating peptide of Bothrops jararaca, to the disintegrins that have potent activity against certain types of cancers, snake venom components have shown great potential for the development of lead compounds for new drugs. There is a continuous development of new drugs from snake venom for coagulopathy and hemostasis to anti-cancer agents. In this review, we have focused on different snake venom proteins / peptides derived drugs that are in clinical use or in developmental stages till to date. Also, some commonly used snake venom derived diagnostic tools along with the recent updates in this exciting field are discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The effectiveness of Hibiscus sabdariffa in the treatment of hypertension: a systematic review.

Science.gov (United States)

Wahabi, H A; Alansary, L A; Al-Sabban, A H; Glasziuo, P

2010-02-01

Hypertension is a common global health problem with significant mortality and morbidity. Hibiscus sabdariffa is a plant known in many countries and is consumed as hot and cold drinks In addition to its use in folk medicine; it has been suggested as treatment for many conditions including hypertension. The objectives of this review were to examine the evidence of effectiveness and safety of hibiscus in the treatment of hypertension. We searched several medical databases (MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and the specialized register of the Cochrane Hypertension Group and the general engine Google) to January 2009. We included randomized controlled trials that had examined Hibiscus's effectiveness and safety in the treatment of primary hypertension in adults. Two authors independently selected the trials for the review, extracted the data, and critically appraised the included studies. Four trials, with a total of 390 patients, met our inclusion criteria. Two studies compared Hibiscus sabdariffa to black tea; one study compared it to captopril and one to lisinopril. The studies found that Hibiscus had greater blood pressure reduction than tea but less than the ACE-inhibitors. However, all studies, except one, were short term and of poor quality with a Jadad scoring of Hibiscus sabdariffa for the treatment of primary hypertension in adults. Copyright 2009 Elsevier GmbH. All rights reserved.

Analysis of possible food/nutrient and drug interactions in hospitalized patients

Directory of Open Access Journals (Sweden)

Everton Moraes Lopes

2010-09-01

Full Text Available Objective: To evaluate the prescription in relation to the possible interactions between drugs and foods/nutrients in the diets of patients in the Hospital Regional Justino Luz in the municipality of Picos, Piauí, Brazil. Methods: The sample consisted of 60 medical records of patients admitted at the hospital. The records were analyzed according to the presence or absence of interactions between drugs and foods/nutrients of the prescribed diets. Results: Of the 82 drugs prescribed in all periods, there were 16 drugs (19.5% with possible interaction with food, a total of 60 interactions between nutrient/food and medicine. Thus, 18 (30%, 10 (17% and 8 (13% possible interactions were identified with captopril (cardiovascular drug with acetylsalicylic acid (anti-inflammatory and spironolactone (diuretic, respectively representing the highest numbers of interactions among the classes of investigated drugs. It was also found that the total interactions between food/nutrients and drugs, 32 (53% accounted for interactions with cardiovascular drugs, 13 (22% with anti-inflammatory drugs, 11 (18% with diuretic agents e 4 (7% with drugs that act on the digestive tract. Conclusion: There was a high number of interactions between food/nutrients and medicines emphasizing the need for prior knowledge of these interactions as a way to avoid impairment in the treatment, longer hospital stays and/or damage to the nutritional status of the patients.

Antihypertensive Effect of Radix Paeoniae Alba in Spontaneously Hypertensive Rats and Excessive Alcohol Intake and High Fat Diet Induced Hypertensive Rats

Directory of Open Access Journals (Sweden)

Chen Su-Hong

2015-01-01

Full Text Available Radix Paeoniae Alba (Baishao, RPA has long been used in traditional Chinese medicine formulation to treat hypertension by repression the hyperfunction of liver. However, whether the RPA itself has the antihypertensive effect or not is seldom studied. This study was to evaluate the protective effect of RPA on hypertensive rats. Alcohol in conjunction with a high fat diet- (ACHFD- induced hypertensive rats and spontaneously hypertensive rats (SHR was constantly received either RPA extract (25 or 75 mg/kg or captopril (15 mg/kg all along the experiments. As a result, RPA extract (75 mg/kg could significantly reduce systolic blood pressure of both ACHFD-induced hypertensive rats and SHR after 9-week or 4-week treatment. In ACHFD-induced hypertensive rats, the blood pressure was significantly increased and the lipid profiles in serum including triglyceride, total cholesterol, LDL-cholesterol, and HDL-cholesterol were significantly deteriorated. Also, hepatic damage was manifested by a significant increase in alanine transaminase (ALT and aspartate transaminase (AST in serum. The RPA extract significantly reversed these parameters, which revealed that it could alleviate the liver damage of rats. In SHR, our result suggested that the antihypertensive active of RPA extract may be related to its effect on regulating serum nitric oxide (NO and endothelin (ET levels.

Marketing research on the angiotensin-converting enzyme inhibitors antihypertensive medicines.

Science.gov (United States)

Boboia, Anamaria; Grigorescu, Marius Rareş; Turcu-Ştiolică, Adina

2017-01-01

The research aimed at investigating sales trends of angiotensin-converting enzyme inhibitors antihypertensive medicines, both in terms of quantity and value, in ten community pharmacies, for a period of three years. The research on the antihypertensive medicines consumption is important for highlighting the ever increasing impact of hypertension among the population. The methods used in this research were the following: marketing research, method of sampling, descriptive methods, retrospective analysis, method of comparison. The results showed that the drugs containing the active substances of the angiotensin converting enzyme inhibitors class had had significant increases in quantitative and value sales, bringing substantial revenues to pharmacies. From the quantitative perspective, the best-selling products were those containing Enalaprilum, while in terms of value, the best-selling medicines were those containing Perindoprilum. We evidenced that spectacular sales were also achieved for products that have Lisinoprilum, respectively Captoprilum, as active substances. The largest quantities were marketed for the Captopril Terapia® product and the highest earnings were recorded for the Prestarium® medicine. This paper approaches an interesting and topical issue, which can be helpful to professionals (pharmacists, doctors) and other categories, such as economists, statisticians, representatives of companies manufacturing medicines, as well as to hypertensive patients, as it could be used to warn population regarding the incidence of cardiovascular diseases, and, at the same time, trace sales trends in order to accomplish profitable business plans.

Analysis of Drug Effects on Primary Human Coronary Artery Endothelial Cells Activated by Serum Amyloid A

Directory of Open Access Journals (Sweden)

K. Lakota

2018-01-01

Full Text Available Background. RA patients have a higher incidence of cardiovascular diseases compared to the general population. Serum amyloid A (SAA is an acute-phase protein, upregulated in sera of RA patients. Aim. To determine the effects of medications on SAA-stimulated human coronary artery endothelial cells (HCAEC. Methods. HCAEC were preincubated for 2 h with medications from sterile ampules (dexamethasone, methotrexate, certolizumab pegol, and etanercept, dissolved in medium (captopril or DMSO (etoricoxib, rosiglitazone, meloxicam, fluvastatin, and diclofenac. Human recombinant apo-SAA was used to stimulate HCAEC at a final 1000 nM concentration for 24 hours. IL-6, IL-8, sVCAM-1, and PAI-1 were measured by ELISA. The number of viable cells was determined colorimetrically. Results. SAA-stimulated levels of released IL-6, IL-8, and sVCAM-1 from HCAEC were significantly attenuated by methotrexate, fluvastatin, and etoricoxib. Both certolizumab pegol and etanercept significantly decreased PAI-1 by an average of 43%. Rosiglitazone significantly inhibited sVCAM-1 by 58%. Conclusion. We observed marked influence of fluvastatin on lowering cytokine production in SAA-activated HCAEC. Methotrexate showed strong beneficial effects for lowering released Il-6, IL-8, and sVCAM-1. Interesting duality was observed for NSAIDs, with meloxicam exhibiting opposite-trend effects from diclofenac and etoricoxib. This represents unique insight into specific responsiveness of inflammatory-driven HCAEC relevant to atherosclerosis.

A conceptually new treatment approach for relapsed glioblastoma: Coordinated undermining of survival paths with nine repurposed drugs (CUSP9) by the International Initiative for Accelerated Improvement of Glioblastoma Care

Science.gov (United States)

Kast, Richard E.; Boockvar, John A.; Brüning, Ansgar; Cappello, Francesco; Chang, Wen-Wei; Cvek, Boris; Dou, Q. Ping; Duenas-Gonzalez, Alfonso; Efferth, Thomas; Focosi, Daniele; Ghaffari, Seyed H.; Karpel-Massler, Georg; Ketola, Kirsi; Khoshnevisan, Alireza; Keizman, Daniel; Magné, Nicolas; Marosi, Christine; McDonald, Kerrie; Muñoz, Miguel; Paranjpe, Ameya; Pourgholami, Mohammad H.; Sardi, Iacopo; Sella, Avishay; Srivenugopal, Kalkunte S.; Tuccori, Marco; Wang, Weiguang; Wirtz, Christian R.; Halatsch, Marc-Eric

2013-01-01

To improve prognosis in recurrent glioblastoma we developed a treatment protocol based on a combination of drugs not traditionally thought of as cytotoxic chemotherapy agents but that have a robust history of being well-tolerated and are already marketed and used for other non-cancer indications. Focus was on adding drugs which met these criteria: a) were pharmacologically well characterized, b) had low likelihood of adding to patient side effect burden, c) had evidence for interfering with a recognized, well-characterized growth promoting element of glioblastoma, and d) were coordinated, as an ensemble had reasonable likelihood of concerted activity against key biological features of glioblastoma growth. We found nine drugs meeting these criteria and propose adding them to continuous low dose temozolomide, a currently accepted treatment for relapsed glioblastoma, in patients with recurrent disease after primary treatment with the Stupp Protocol. The nine adjuvant drug regimen, Coordinated Undermining of Survival Paths, CUSP9, then are aprepitant, artesunate, auranofin, captopril, copper gluconate, disulfiram, ketoconazole, nelfinavir, sertraline, to be added to continuous low dose temozolomide. We discuss each drug in turn and the specific rationale for use- how each drug is expected to retard glioblastoma growth and undermine glioblastoma's compensatory mechanisms engaged during temozolomide treatment. The risks of pharmacological interactions and why we believe this drug mix will increase both quality of life and overall survival are reviewed. PMID:23594434

Severe Hypertension Secondary to Renal Artery Stenosis and Cushing's Syndrome

International Nuclear Information System (INIS)

Al-Zahrani, Ali S.; Al-Hajjaj, Alya; Al-Watban, Jehad; Kanaan, Imaduddin

2005-01-01

We present an unusual patient who simultaneously had severe renal artery stenosis RAS and Cushings syndrome. The case highlights the difficulty of reaching a specific diagnosis of Cushings syndrome and the possible interaction between Cushings syndrome and some other concurrent illnesses that this patient had. A 37-year old man presented with severe hypertension HTN and uncontrolled diabetes mellitus DM without clear physical signs of Cushings syndrome. He was found to have severe osteoporosis, proximal myopathy, several cutaneous warts, tinea versicolor, and chronic viral hepatitis. Captopril-stimulated renal scan and renal artery angiogram revealed severe RAS. Partial balloon dilatation of RAS led to improvement in HTN. Unexpectedly, urine free cortisol 24 hour was found extremely high. Serum adrenocorticotropic hormone ACTH was also elevated and high dose dexamethasone suppression tests were inconclusive. Several imaging studies failed to localize the source of ACTH. Despite normal MRI of the pituitary gland, bilateral inferior petrosal sinus sampling IPSS localized the source of ACTH secretion to the right side of the pituitary gland and right anterior hemihypophysectomy resulted in cure of Cushings disease, HTN, DM, and tinea versicolor with significant improvement in cutaneous warts, osteoporosis, and chronic hepatitis. In conclusion, RAS and Cushings syndrome may occur together. Significant hypercortisolemia can occur without clear signs of Cushings syndrome. Controlling hypercortisolemia is of paramount importance when treating chronic infections in patients with Cushing's syndrome. (author)

Case Report: A case report of acromegaly associated with primary aldosteronism [v1; ref status: indexed, http://f1000r.es/2ny

Directory of Open Access Journals (Sweden)

Joanna Matrozova

2014-02-01

Full Text Available We describe a patient with a rare combination of acromegaly and primary aldosteronism. A 37 year-old female patient was diagnosed with acromegaly on the basis of typical clinical, hormonal and image characteristics. She presented also with one of the most common co-morbidities – arterial hypertension. The patient has been regularly followed-up and after three surgical interventions, irradiation and adjuvant treatment with a dopamine agonist, acromegaly was finally controlled in 2008 (20 years after diagnosis. Arterial hypertension however, remained a therapeutic problem even after prescription of four antihypertensive drugs. She had normal biochemical parameters, except for low potassium levels 3.2 (3.5-5.6 mmol/l. This raised the suspicion of primary hyperaldosteronism, confirmed by a high aldosterone to plasma rennin activity ratio, high aldosterone level after a Captopril challenge test and visualization of a 35 mm left adrenal nodule on a CT scan. After an operation, the patient recovered from hypokalemia and antihypertensive therapy was reduced to a small dose of a Ca blocker. Co-morbid arterial hypertension is common in acromegaly, though it is rare for this to be caused by Conn’s adenoma. The association of Conn’s adenoma with acromegaly has been interpreted in two lines: as a component of multiple endocrine neoplasia type (MEN1 syndrome or as a direct mitogenic effect of hyperactivated GH-IGF1 axis.

Prediction of Wound Healing in Diabetic Foot Ulcers: an Observational Study in Tertiary Hospital in Indonesia.

Science.gov (United States)

Soewondo, Pradana; Suyono, Slamet; Sastrosuwignyo, Mpu Kanoko; Harahap, Alida R; Sutrisna, Bambang; Makmun, Lukman H

2017-01-01

to evaluate the role of clinical characteristics, functional markers of vasodilation, inflammatory response, and atherosclerosis in predicting wound healing in diabetic foot ulcer. a cohort study (February - October 2010) was conducted from 40 subjects with acute diabetic foot ulcer at clinical ward of Dr. Cipto Mangunkusumo National Central General Hospital, Jakarta, Indonesia. Each subject underwent at least two variable measurements, i.e. during inflammatory phase and proliferation phase. The studied variables were clinical characteristics, complete peripheral blood count (CBC) and differential count, levels of HbA1c, ureum, creatinine, lipid profile, fasting blood glucose (FBG), marker of endothelial dysfunction (asymmetric dimethylarginine/ADMA, endothelin-1/ET-1, and flow-mediated dilation/FMD of brachial artery), and marker of vascular calcification (osteoprotegerin/OPG). median of time achieving 50% granulation tissue in our study was 21 days. There were nine factors that contribute in the development of 50% granulation tissue, i.e. family history of diabetes mellitus (DM), previous history of wound, wound area, duration of existing wound, captopril and simvastatin medications, levels of ADMA, ET-1, and OPG. There were three out of the nine factors that significantly correlated with wound healing, i.e. wound area, OPG levels, and simvastatin medications. in acute diabetic foot ulcers, wound area and OPG levels had positive correlation with wound healing, whereas simvastatin medications had negative correlation with wound healing.

In vivo antihypertensive and antidyslipidemic effects of the crude extracts and fractions of Moringa stenopetala (Baker f. Cufod. leaves in rats.

Directory of Open Access Journals (Sweden)

Bekesho eGeleta

2016-04-01

Full Text Available Moringa stenopetala (Baker f. Cufod. is a medicinal plant that has been used in Ethiopian traditional medicine as a remedy for treatment of hypertension and diabetes. The aim of this study was to evaluate antihypertensive and antihyperlipidemic effect in fructose induced hypertensive rats.Rats were randomly divided into control and treatment groups (n=6. Treatment groups were given daily extracts (250, 500, and 1000 mg/kg orally with fructose. Whereas, positive, negative and normal control groups were received captopril (20 mg/kg/day with fructose, only fructose (66% w/v ad libitum and distilled water ad libitum for 15 days, respectively. The blood pressure was measured every 5th day using tail cuff blood pressure analyzer, and on the 16th day the blood was sampled to evaluate antihyperlipidemic effect using clinical chemistry analyzer. The study showed that aqueous and 70% ethanol extracts significantly prevented blood pressure increment in a dose dependent manner comparable to that of the standard drug. Similarly, the extracts suppressed increment in lipid profile (cholesterol, glucose and triglycerides compared with negative control. The biochemical test revealed that extracts produced a rise in liver but no effect on kidney function indicators compared with normal control.These findings revealed that both crude extracts of Moringa stenopetala (Baker f. Cufod. possess antihypertensive and antihyperlipidemic effect.

Cuantificación de glibenclamida en muestras de limpieza de equipos farmacéuticos mediante cromatografía líquida de alta resolución Quantification of glibenclamide in cleaning samples of pharmaceutical equipment through high performance liquid chromatography

Directory of Open Access Journals (Sweden)

Alen Nils Baeza Fonte

2012-03-01

Full Text Available Objetivo: proponer un procedimiento analítico selectivo para la cuantificación de glibenclamida en muestras de limpieza de equipos farmacéuticos mediante cromatografía líquida de alta resolución. Métodos: la fase móvil consistió en una mezcla equivalente de volúmenes de acetonitrilo y solución amortiguadora KH2PO4 de concentración 0,037 mol/L a pH 5,25 y flujo 1,5 mL/min, en una columna Nucleosil 100 C8. La glibenclamida se inyectó con progesterona como estándar interno y empleando detector UV a una l= 230 nm. Resultados: el método resultó lineal en el intervalo de concentraciones de 0,4-150 mg/mL, teniendo como límites de detección y cuantificación 10 y 40 ng/mL respectivamente y siendo específico al analito en presencia del placebo, sus productos de degradación y a otros ingredientes farmacéuticamente activos. Se consideraron potenciales de interferencias para el método propuesto: captopril, clortalidona, dexametasona, digoxina, 8-cloroteofilina, difenhidramina HCl, fenobarbital, haloperidol, hidroclorotiazida, ácido fumárico, ketotifeno, metoclopramida HCl, piridoxina HCl, piroxicam, prednisona y nifedipino. Se identificaron: ibuprofeno, indometacina, trifluoperazina HCl, tioridazina HCl e imipramina HCl, como interferentes del procedimiento en concentraciones cercanas a 10 mg/mL. Conclusiones: el método desarrollado es sensible, rápido y especialmente selectivo para la evaluación de residuales del principio activo glibenclamida en equipos de producción de tabletas, empleando un muestreo por hisopado, y pudiera utilizarse potencialmente cuando exista sospecha de contaminación cruzada de glibenclamida con otros fármacos de los aquí descritos.Objective: to submit a selective analytical method for quantization of glibenclamide in cleaning samples of pharmaceutical equipment using high performance liquid chromatography. Methods: the mobile phase consisted of an equal mixing of acetonitrile/phosphate buffer KH2PO4

ACESSO A MEDICAMENTOS ESSENCIAIS EM FARMÁCIAS E DROGARIAS DO MUNICÍPIO DE ARARAQUARA.

Directory of Open Access Journals (Sweden)

Cesar Rente Ferreira

2010-11-01

Full Text Available

O levantamento teve como objetivo avaliar a disponibilidade de 20 medicamentos essenciais para doenças importantes da atenção básica a saúde, pela presença e o preço nas as farmácias e drogarias do setor privado do município de Araraquara/SP. O estudo foi realizado utilizando-se dois formulários, preconizados pela OMS, um para disponibilidade e outro para os preços. Os medicamentos mais disponíveis nas farmácias e drogarias foram o propranolol (90,5%, captopril (96% e ranitidina (96%, e os menos disponíveis foram sulfato ferroso (27%, beclometasona (33,8% e ibuprofeno (41,9%. Os medicamentos que apresentaram maior variação entre os preços praticados foram propranolol (97,1%, hidroclorotiazida 96,4% e glibenclamida (95,0%, e os de menor variação foram salbutamol (30,8% e sulfametoxazol + trimetoprima (30,2%. Metade dos medicamentos avaliados (10 o menor preço era do medicamento genérico. Os indicadores de acesso por capacidade de aquisição para o tratamento das principais doenças no nível de atenção básica demonstrou que nenhum estabelecimento continha todos os medicamentos avaliados e evidenciaram grandes variações de preços, comprometendo o seu acesso aos usuários que a única forma de adquiri-los é em farmácias e drogarias. Palavras-chave: Preço de medicamento. Economia Farmacêutica. Medicamentos Genéricos.Farmacoepidemiologia. ABSTRACT A survey to determine the availability of 20 essential medicines for the diseases with highest prevalence in primary health care was conducted in the city of Araraquara. The presence and the price of these medicines in private sector pharmacies and drugstores of the city were recorded. Two forms, recommended by the WHO, were used in the survey, one for availability and the other for prices. The drugs most commonly available in pharmacies and drugstores were: propranolol (90.5%, captopril (96% and ranitidine (96%, while the least available were ferrous

Clinical study on the effect of Tongxinluo combined with trimetazidine on cardiac function in patients with acute ST-segment elevation myocardial infarction after percutaneous coronary intervention

Directory of Open Access Journals (Sweden)

Qun-Xiong Fan

2017-07-01

Full Text Available Objective: To investigate the clinical effect of Tongxinluo combined with trimetazidine on cardiac function in patients with acute ST-segment elevation myocardial infarction after percutaneous coronary intervention. Method: From March 2014 to September 2016, we selected 190 patients with ST-segment elevation myocardial infarction with percutaneous coronary intervention, according to the admission time is divided into observation group and control group, the control group was treated with conventional therapy (aspirin, isosorbide dinitrate, metoprolol tartrate, clopidogrel sulfate, captopril, atorvastatin calcium and diuretics and trimetazidine, observation group in the control group based on Tongxinluo combined treatment, each group of 95 cases, and hs-CRP, aldosterone, NT-proBNP, TNF-α, IL-6, and cardiac function (LVEDV, LVESV, LVEF, SV were compared. Result: The Hs-CRP in the observation group was significantly lower than that in the control group; The aldosterone in the observation group was significantly lower than that in the control group; The levels of NT-proBNP, TNF-α and IL-6 in the observation group were significantly lower than those in the control group; LVVEV and LVESV were significantly lower in the observation group than in the control group, LVEF and SV were significantly higher than those in the control group. Conclusion: Tongxinluo combined with trimetazidine in patients with acute STsegment elevation myocardial infarction after percutaneous coronary intervention in patients with clinical effect is better, stable plaque, effectively improve microcirculation and cardiac function, recommended a wide range of clinical application.

Marketing research on the angiotensin-converting enzyme inhibitors antihypertensive medicines

Science.gov (United States)

BOBOIA, ANAMARIA; GRIGORESCU, MARIUS RAREŞ; TURCU - ŞTIOLICĂ, ADINA

2017-01-01

Background and aims The research aimed at investigating sales trends of angiotensin-converting enzyme inhibitors antihypertensive medicines, both in terms of quantity and value, in ten community pharmacies, for a period of three years. The research on the antihypertensive medicines consumption is important for highlighting the ever increasing impact of hypertension among the population. Methods The methods used in this research were the following: marketing research, method of sampling, descriptive methods, retrospective analysis, method of comparison. Results The results showed that the drugs containing the active substances of the angiotensin converting enzyme inhibitors class had had significant increases in quantitative and value sales, bringing substantial revenues to pharmacies. From the quantitative perspective, the best-selling products were those containing Enalaprilum, while in terms of value, the best-selling medicines were those containing Perindoprilum. We evidenced that spectacular sales were also achieved for products that have Lisinoprilum, respectively Captoprilum, as active substances. The largest quantities were marketed for the Captopril Terapia® product and the highest earnings were recorded for the Prestarium® medicine. Conclusion This paper approaches an interesting and topical issue, which can be helpful to professionals (pharmacists, doctors) and other categories, such as economists, statisticians, representatives of companies manufacturing medicines, as well as to hypertensive patients, as it could be used to warn population regarding the incidence of cardiovascular diseases, and, at the same time, trace sales trends in order to accomplish profitable business plans. PMID:28246502

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

Science.gov (United States)

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.

Dutch guideline for the management of hypertensive crisis -- 2010 revision.

Science.gov (United States)

van den Born, B J H; Beutler, J J; Gaillard, C A J M; de Gooijer, A; van den Meiracker, A H; Kroon, A A

2011-05-01

Hypertensive crises are divided into hypertensive urgencies and emergencies. Together they form a heterogeneous group of acute hypertensive disorders depending on the presence or type of target organs involved. Despite better treatment options for hypertension, hypertensive crisis and its associated complications remain relatively common. In the Netherlands the number of patients starting renal replacement therapy because of 'malignant hypertension' has increased in the past two decades. In 2003, the first Dutch guideline on hypertensive crisis was released to allow a standardised evidence-based approach for patients presenting with a hypertensive crisis. In this paper we give an overview of the current management of hypertensive crisis and discuss several important changes incorporated in the 2010 revision. These changes include a modification in terminology replacing 'malignant hypertension' with 'hypertensive crisis with retinopathy and reclassification of hypertensive crisis with retinopathy under hypertensive emergencies instead of urgencies. With regard to the treatment of hypertensive emergencies, nicardipine instead of nitroprusside or labetalol is favoured for the management of perioperative hypertension, whereas labetalol has become the drug of choice for the treatment of hypertension associated with pre-eclampsia. For the treatment of hypertensive urgencies, oral administration of nifedipine retard instead of captopril is recommended as first-line therapy. In addition, a section on the management of hypertensive emergencies according to the type of target organ involved has been added. Efforts to increase the awareness and treatment of hypertension in the population at large may lower the incidence of hypertensive crisis and its complications.

Prediction of Wound Healing in Diabetic Foot Ulcers: an Observational Study in Tertiary Hospital in Indonesia

Directory of Open Access Journals (Sweden)

Pradana Soewondo

2017-04-01

Full Text Available Aim: to evaluate the role of clinical characteristics, functional markers of vasodilation, inflammatory response, and atherosclerosis in predicting wound healing in diabetic foot ulcer. Methods: a cohort study (February – October 2010 was conducted from 40 subjects with acute diabetic foot ulcer at clinical ward of Dr. Cipto Mangunkusumo National Central General Hospital, Jakarta, Indonesia. Each subject underwent at least two variable measurements, i.e. during inflammatory phase and proliferation phase. The studied variables were clinical characteristics, complete peripheral blood count (CBC and differential count, levels of HbA1c, ureum, creatinine, lipid profile, fasting blood glucose (FBG, marker of endothelial dysfunction (asymmetric dimethylarginine/ADMA, endothelin-1/ET-1, and flow-mediated dilation/FMD of brachial artery, and marker of vascular calcification (osteoprotegerin/OPG. Results: median of time achieving 50% granulation tissue in our study was 21 days. There were nine factors that contribute in the development of 50% granulation tissue, i.e. family history of diabetes mellitus (DM, previous history of wound, wound area, duration of existing wound, captopril and simvastatin medications, levels of ADMA, ET-1, and OPG. There were three out of the nine factors that significantly correlated with wound healing, i.e. wound area, OPG levels, and simvastatin medications. Conclusion: in acute diabetic foot ulcers, wound area and OPG levels had positive correlation with wound healing, whereas simvastatin medications had negative correlation with wound healing.

N-domain angiotensin-I converting enzyme is expressed in immortalized mesangial, proximal tubule and collecting duct cells.

Science.gov (United States)

Mei Wang, Pamella Huey; Andrade, Maria Claudina; Quinto, Beata Marie Redublo; Di Marco, Giovana; Mortara, Renato Arruda; Vio, Carlos P; Casarini, Dulce Elena

2015-01-01

Somatic ACE (sACE) is found in glomerulus, proximal tubule and excreted in urine. We hypothesized that N-domain ACE can also be found at these sites. ACE profile was analyzed in mesangial (IMC), proximal (LLC-PK1), distal tubule (MDCK) and collecting duct (IMCD) cells. Cell lysate and culture medium were submitted to gel filtration chromatography, which separated two peaks with ACE activity from cells and medium, except from distal tubule. The first had a high molecular weight and the second, a lower one (65 kDa; N-domain ACE). We focused on N-domain ACE purification and characterization from LLC-PK1. Total LLC-PK1 N-domain ACE purification was achieved by ion-exchange chromatography, which presented only one peak with ACE activity, denominated ACE(int2A). ACE(int2A) activity was influenced by pH, NaCl and temperature. The purified enzyme was inhibited by Captopril and hydrolyzed AngI, Ang1-7 and AcSDKP. Its ability to hydrolyze AcSDKP characterized it as an N-domain ACE. ACE(int2A) also presented high amino acid sequence homology with the N-terminal part of sACE from mouse, rat, human and rabbit. The presence of secreted and intracellular N-domain ACE and sACE in IMC, LLC-PK1 and IMCD cells confirmed our studies along the nephron. We identified, purified and characterized N-domain ACE from LLC-PK1. Copyright © 2014 Elsevier B.V. All rights reserved.

Caracterización de las reacciones adversas medicamentosas en ancianos: Cuba, 2003-2005 Characterization of the adverse reactions to drugs in the elderly: Cuba, 2003-2005

Directory of Open Access Journals (Sweden)

Raisa Rodriguez Duque

2007-12-01

Full Text Available El seguimiento de las reacciones adversas en poblaciones de riesgo como los ancianos es prioridad del sistema cubano de farmacovigilancia. Por lo que se realizó una investigación descriptiva y prospectiva, para caracterizar las notificaciones de sospechas de reacciones adversas medicamentosas en ancianos mayores de 60 años de edad, recibidas en la Unidad Coordinadora Nacional de Farmacovigilancia desde el 1ro de enero de 2003 al 31 de diciembre de 2005. Constituyeron objetivos del trabajo la identificación de los grupos farmacológicos que produjeron las reacciones adversas medicamentosas así como los fármacos más comprometidos, la clasificación de las reacciones adversas según la severidad, el mecanismo de producción, el sistema de órgano afectado y el grado de imputabilidad. De igual manera, se analizó si la presencia de factores como la polifarmacia y los antecedentes patológicos personales predisponen la aparición de la reacción adversa medicamentosa y su posible prevención. Los resultados más importantes muestran que los grupos farmacológicos con mayor representatividad resultaron los antibacterianos, los antihipertensivos y los antiinflamatorios y analgésicos no opioides; los fármacos más frecuentes fueron el captopril, la penicilina procaínica y la nifedipina; las reacciones leves ocuparon el mayor porcentaje así como las reacciones probables. Predominó el mecanismo de producción tipo A; el sistema de órgano más afectado fue la piel y anejos, y la presencia de antecedentes patológicos personales propició en gran medida la aparición de las reacciones adversas medicamentosas, lo que no ocurrió con la polifarmacia. Se pudieron haber evitado el 82,3 % del total de reacciones adversas medicamentosas estudiadasThe follow-up of adverse reactions in risk populations as the elderly is a priority of the Cuban drug surveillance system. A descriptive and prospective research was conducted to characterize the

Preços e disponibilidade de medicamentos no Programa Farmácia Popular do Brasil Precios y disponibilidad de medicamentos en el Programa Farmacia Popular de Brasil Medicine prices and availability in the Brazilian Popular Pharmacy Program

Directory of Open Access Journals (Sweden)

Cláudia Du Bocage Santos Pinto

2010-08-01

Full Text Available OBJETIVO: Analisar o desempenho do Programa Farmácia Popular do Brasil perante os setores público e privado, em relação a: disponibilidade, preço e custo, para o paciente, de medicamentos para hipertensão e diabetes. MÉTODOS: Foi utilizada a metodologia desenvolvida pela Organização Mundial da Saúde em conjunto com a Ação Internacional para Saúde, para comparação de preços e disponibilidade de medicamentos. A pesquisa foi aplicada em maio de 2007, em estabelecimentos de diferentes setores [público, privado e as modalidades própria (FPB-P e expansão (FPB-E do Programa], em 30 municípios do Brasil. Os quatro medicamentos analisados foram: captopril 25mg e hidroclorotiazida 25mg, para hipertensão, e metformina 500mg e glibenclamida 5mg, para diabetes. RESULTADOS: O FPB-E apresentou maior disponibilidade de medicamentos e o setor público, a menor. Tanto no setor público quanto na FPB-P o percentual de disponibilidade de similares foi maior que o de genéricos. A comparação de preços entre os setores mostrou menor preço de aquisição no FPB-E, seguido pelo FPB-P. O FPB-E apresentou economia superior a 90% em relação ao setor privado. O número de dias de trabalho necessários para aquisição de tratamentos para hipertensão e diabetes foi menor no FPB-E. CONCLUSÕES: A menor disponibilidade encontrada no setor público pode ser uma das justificativas para migração dos usuários do setor público para o FPB. Os altos preços praticados pelo setor privado também contribuem para que o Programa seja uma alternativa de acesso a medicamentos no País.OBJETIVO: Analizar el desempeño del Programa Farmacia Popular de Brasil frente a los sectores público y privado, con relación a: disponibilidad, precio y costo para el paciente, de medicamentos para hipertensión y diabetes. MÉTODOS: Fue utilizada la metodología desarrollada por la Organización Mundial de la Salud en conjunto con la Acción Internacional para Salud, para

Pharmacology of Bradykinin-Evoked Coughing in Guinea Pigs.

Science.gov (United States)

Hewitt, Matthew M; Adams, Gregory; Mazzone, Stuart B; Mori, Nanako; Yu, Li; Canning, Brendan J

2016-06-01

Bradykinin has been implicated as a mediator of the acute pathophysiological and inflammatory consequences of respiratory tract infections and in exacerbations of chronic diseases such as asthma. Bradykinin may also be a trigger for the coughing associated with these and other conditions. We have thus set out to evaluate the pharmacology of bradykinin-evoked coughing in guinea pigs. When inhaled, bradykinin induced paroxysmal coughing that was abolished by the bradykinin B2 receptor antagonist HOE 140. These cough responses rapidly desensitized, consistent with reports of B2 receptor desensitization. Bradykinin-evoked cough was potentiated by inhibition of both neutral endopeptidase and angiotensin-converting enzyme (with thiorphan and captopril, respectively), but was largely unaffected by muscarinic or thromboxane receptor blockade (atropine and ICI 192605), cyclooxygenase, or nitric oxide synthase inhibition (meclofenamic acid and N(G)-nitro-L-arginine). Calcium influx studies in bronchopulmonary vagal afferent neurons dissociated from vagal sensory ganglia indicated that the tachykinin-containing C-fibers arising from the jugular ganglia mediate bradykinin-evoked coughing. Also implicating the jugular C-fibers was the observation that simultaneous blockade of neurokinin2 (NK2; SR48968) and NK3 (SR142801 or SB223412) receptors nearly abolished the bradykinin-evoked cough responses. The data suggest that bradykinin induces coughing in guinea pigs by activating B2 receptors on bronchopulmonary C-fibers. We speculate that therapeutics targeting the actions of bradykinin may prove useful in the treatment of cough. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

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

Directory of Open Access Journals (Sweden)

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.

Role of α2-adrenoceptors in the lateral parabrachial nucleus in the control of body fluid homeostasis

International Nuclear Information System (INIS)

Andrade, C.A.F.; Andrade-Franzé, G.M.F.; De Paula, P.M.; De Luca, L.A. Jr.; Menani, J.V.

2014-01-01

Central α 2 -adrenoceptors and the pontine lateral parabrachial nucleus (LPBN) are involved in the control of sodium and water intake. Bilateral injections of moxonidine (α 2 -adrenergic/imidazoline receptor agonist) or noradrenaline into the LPBN strongly increases 0.3 M NaCl intake induced by a combined treatment of furosemide plus captopril. Injection of moxonidine into the LPBN also increases hypertonic NaCl and water intake and reduces oxytocin secretion, urinary sodium, and water excreted by cell-dehydrated rats, causing a positive sodium and water balance, which suggests that moxonidine injected into the LPBN deactivates mechanisms that restrain body fluid volume expansion. Pretreatment with specific α 2 -adrenoceptor antagonists injected into the LPBN abolishes the behavioral and renal effects of moxonidine or noradrenaline injected into the same area, suggesting that these effects depend on activation of LPBN α 2 -adrenoceptors. In fluid-depleted rats, the palatability of sodium is reduced by ingestion of hypertonic NaCl, limiting intake. However, in rats treated with moxonidine injected into the LPBN, the NaCl palatability remains high, even after ingestion of significant amounts of 0.3 M NaCl. The changes in behavioral and renal responses produced by activation of α 2 -adrenoceptors in the LPBN are probably a consequence of reduction of oxytocin secretion and blockade of inhibitory signals that affect sodium palatability. In this review, a model is proposed to show how activation of α 2 -adrenoceptors in the LPBN may affect palatability and, consequently, ingestion of sodium as well as renal sodium excretion

Role of α{sub 2}-adrenoceptors in the lateral parabrachial nucleus in the control of body fluid homeostasis

Energy Technology Data Exchange (ETDEWEB)

Andrade, C.A.F.; Andrade-Franzé, G.M.F.; De Paula, P.M.; De Luca, L.A. Jr.; Menani, J.V. [Departamento de Fisiologia e Patologia, Faculdade de Odontologia, Universidade Estadual Paulista, Araraquara, SP (Brazil)

2014-01-10

Central α{sub 2}-adrenoceptors and the pontine lateral parabrachial nucleus (LPBN) are involved in the control of sodium and water intake. Bilateral injections of moxonidine (α{sub 2}-adrenergic/imidazoline receptor agonist) or noradrenaline into the LPBN strongly increases 0.3 M NaCl intake induced by a combined treatment of furosemide plus captopril. Injection of moxonidine into the LPBN also increases hypertonic NaCl and water intake and reduces oxytocin secretion, urinary sodium, and water excreted by cell-dehydrated rats, causing a positive sodium and water balance, which suggests that moxonidine injected into the LPBN deactivates mechanisms that restrain body fluid volume expansion. Pretreatment with specific α{sub 2}-adrenoceptor antagonists injected into the LPBN abolishes the behavioral and renal effects of moxonidine or noradrenaline injected into the same area, suggesting that these effects depend on activation of LPBN α{sub 2}-adrenoceptors. In fluid-depleted rats, the palatability of sodium is reduced by ingestion of hypertonic NaCl, limiting intake. However, in rats treated with moxonidine injected into the LPBN, the NaCl palatability remains high, even after ingestion of significant amounts of 0.3 M NaCl. The changes in behavioral and renal responses produced by activation of α{sub 2}-adrenoceptors in the LPBN are probably a consequence of reduction of oxytocin secretion and blockade of inhibitory signals that affect sodium palatability. In this review, a model is proposed to show how activation of α{sub 2}-adrenoceptors in the LPBN may affect palatability and, consequently, ingestion of sodium as well as renal sodium excretion.

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)

Availability, price and affordability of cardiovascular medicines: A comparison across 36 countries using WHO/HAI data

Directory of Open Access Journals (Sweden)

Cameron Alexandra

2010-06-01

Full Text Available Abstract Background The global burden of cardiovascular disease (CVD continues to rise. Successful treatment of CVD requires adequate pharmaceutical management. The aim was to examine the availability, pricing and affordability of cardiovascular medicines in developing countries using the standardized data collected according to the World Health Organization/Health Action International methodology. Methods The following medicines were included: atenolol, captopril, hydrochlorothiazide, losartan and nifedipine. Data from 36 countries were analyzed. Outcome measures were percentage availability, price ratios to international reference prices and number of day's wages needed by the lowest-paid unskilled government worker to purchase one month of chronic treatment. Patient prices were adjusted for inflation and purchasing power, procurement prices only for inflation. Data were analyzed for both generic and originator brand products and the public and private sector and summarized by World Bank Income Groups. Results For all measures, there was great variability across surveys. The overall availability of cardiovascular medicines was poor (mean 26.3% in public sector, 57.3% private sector. Procurement prices were very competitive in some countries, whereas others consistently paid high prices. Patient prices were generally substantially higher than international references prices; some countries, however, performed well. Chronic treatment with anti-hypertensive medication cost more than one day's wages in many cases. In particular when monotherapy is insufficient, treatment became unaffordable. Conclusions The results of this study emphasize the need of focusing attention and financing on making chronic disease medicines accessible, in particular in the public sector. Several policy options are suggested to reach this goal.

Estudo de equivalÃncia farmacÃutica dos fÃrmacos captopril e cloridrato de propranolol comercializados no programa farmÃcia popular do brasil.

OpenAIRE

AndrÃa Vieira Pontes Rohleder

2009-01-01

A equivalÃncia farmacÃutica entre dois medicamentos relaciona-se à comprovaÃÃo de que ambos contÃm o mesmo fÃrmaco na mesma dosagem e forma farmacÃutica, o que pode ser avaliado por meio de testes in vitro. No Brasil, os medicamentos alopÃticos sÃo divididos em trÃs categorias quanto ao registro junto à AgÃncia Nacional de VigilÃncia SanitÃria: medicamentos novos, medicamentos similares e medicamentos genÃricos. A legislaÃÃo atual dispÃe que para o registro de novos medicamentos genÃricos e s...

Carnauba wax as a promising excipient in melt granulation targeting the preparation of mini-tablets for sustained release of highly soluble drugs.

Science.gov (United States)

Nart, Viviane; Beringhs, André O'Reilly; França, Maria Terezinha; de Espíndola, Brenda; Pezzini, Bianca Ramos; Stulzer, Hellen Karine

2017-01-01

Mini-tablets are a new tendency in solid dosage form design for overcoming therapeutic obstacles such as impaired swallowing and polypharmacy therapy. Among their advantages, these systems offer therapeutic benefits such as dose flexibility and combined drug release patterns. The use of lipids in the formulation has also drawn considerable interest as means to modify the drug release from the dosage form. Therefore, this paper aimed at developing sustained release mini-tablets containing the highly soluble drugs captopril and metformin hydrochloride. Carnauba wax was used as a lipid component in melt granulation, targeting the improvement of the drugs poor flowability and tabletability, as well as to sustain the drug release profiles in association with other excipients. To assist sustaining the drug release, Ethocel™ (EC) and Kollicoat® SR 30D associated with Opadry® II were employed as matrix-forming and reservoir-forming materials, respectively. The neat drugs, granules and the bulk formulations were evaluated for their angle of repose, compressibility index, Hausner ratio and tabletability. Mini-tablets were evaluated for their weight variation, hardness, friability, drug content and in-vitro drug release. The results indicated that melt granulation with carnauba wax improved the flow and the tabletability of the drugs, allowing the preparation of mini-tablets with adequate tensile strength under reduced compaction pressures. All mini-tablet formulations showed acceptable hardness (within the range of 1.16 to 3.93Kp) and friability (carnauba wax proved to be a promising excipient in melt granulation targeting the preparation of mini-tablets for sustained release of soluble drugs. Copyright © 2016 Elsevier B.V. All rights reserved.

Identification and analysis of antinutritional factors in possible interactions between medications and food/ nutrients in hospitalized patients

Directory of Open Access Journals (Sweden)

Adnny Fernanda Lima Campos

2011-09-01

Full Text Available Objective: To identify and analyze the presence of antinutritionalfactors in possible interactions between medications and foods/nutrients of the diets prescribed for patients of the Hospital Regional Justino Luz, in the city of Picos (PI in order to suggest their likely mechanisms. Methods: The sample was made up of 120 medical records of hospitalized patients. The charts were analyzed to verify the presence or absence of interactions between medications andfoods/nutrients of the diets prescribed to the patients at the Hospital Regional Justino Luz, emphasizing the action of antinutritional factors in these interactions. Results: Of the 189 medications prescribed, 128 (67.7% had a possible interaction with food, totaling up 98 possible interactions between nutrients/foods and medications. Therefore, 20 (20.4%, 12 (12.2% and 11 (11.2% possible interactions were identified with captopril, acetylsalicylic acid and spironolactone, respectively, representing, in this order, the greatest frequencies of possible interactions among drugs and foods. A total of nine antinutritional factors were found in seven vegetable foods prescribed to inpatients, in which five (55.6% were capable of interacting with the medications. Phytates and tannins had the largest quantity of possible interactions with drugs, each with 4 (26.7% in a total of 15 interactions. The medications aluminum hydroxide, digoxin, and paracetamol attained greater probability of interaction with antinutrients, with 5 (33.3%, 3 (20% and 3 (20% interactions, respectively. Conclusion: Due to the large quantity of antinutritional factors capable of interacting with drugs prescribed for inpatients, the involvement of a multiprofessional team is indispensable so that these possible interactions between foods, antinutritional factors and drugs might be foreseen, detected, and resolved.

Practical spectrophotometric assay for the dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase, a potential antibiotic target.

Science.gov (United States)

Heath, Tahirah K; Lutz, Marlon R; Reidl, Cory T; Guzman, Estefany R; Herbert, Claire A; Nocek, Boguslaw P; Holz, Richard C; Olsen, Kenneth W; Ballicora, Miguel A; Becker, Daniel P

2018-01-01

A new enzymatic assay for the bacterial enzyme succinyl-diaminopimelate desuccinylase (DapE, E.C. 3.5.1.18) is described. This assay employs N6-methyl-N2-succinyl-L,L-diaminopimelic acid (N6-methyl-L,L-SDAP) as the substrate with ninhydrin used to detect cleavage of the amide bond of the modified substrate, wherein N6-methylation enables selective detection of the primary amine enzymatic product. Molecular modeling supported preparation of the mono-N6-methylated-L,L-SDAP as an alternate substrate for the assay, given binding in the active site of DapE predicted to be comparable to the endogenous substrate. The alternate substrate for the assay, N6-methyl-L,L-SDAP, was synthesized from the tert-butyl ester of Boc-L-glutamic acid employing a Horner-Wadsworth-Emmons olefination followed by an enantioselective reduction employing Rh(I)(COD)(S,S)-Et-DuPHOS as the chiral catalyst. Validation of the new ninhydrin assay was demonstrated with known inhibitors of DapE from Haemophilus influenza (HiDapE) including captopril (IC50 = 3.4 [± 0.2] μM, 3-mercaptobenzoic acid (IC50 = 21.8 [±2.2] μM, phenylboronic acid (IC50 = 316 [± 23.6] μM, and 2-thiopheneboronic acid (IC50 = 111 [± 16] μM. Based on these data, this assay is simple and robust, and should be amenable to high-throughput screening, which is an important step forward as it opens the door to medicinal chemistry efforts toward the discovery of DapE inhibitors that can function as a new class of antibiotics.

Kininase enzymes of cat eye tissues

International Nuclear Information System (INIS)

Ryan, J.W.; Anderson, D.R.

1986-01-01

Eye tissues contain kininase activities, including an angiotensin converting enzyme (ACE)-like activity. The authors have begun further to characterize the ACE-like activity and to examine for another reputed kininase, carboxypeptidase N (CPN). Homogenates of tissues of 6 cat eyes and paired plasmas were assayed for ACE using 3 acyl-tripeptide substrates, 3 H-benzoylated F-A-P, F-G-P and A-G-P (respectively, BFAP, BFGP and BAGP). CPN was assayed using 3 H-benzoyl-A-R. All eye tissues and fluids contained ACE- and CPN-like activities. The ACE activity was clearly owing to ACE: relative values of Kc/Km for BFAP, BFGP and BAGP were those for pure ACE (2.213, 1.751 and 1.0); reactivities with inhibitors were as expected (Ki for captopril, MK 422 and RAC-X-65: 2.7, 0.62 and 0.31 nM). EDTA inhibited both ACE and CPN (I 50 's: 43 and 47 μM). CPN activity was inhibited by 2-mercaptomethyl-3-guanidinoethylthiopropionate (Ki 2.4 nM). However, distributions of the two enzymes differed markedly. Virtually all tissues contained ACE at specific activities higher than that of plasma. Specific activities appeared to be a function of tissue vascularity (for choroid, ciliary body, iris, retina and plasma: 7.31, 2.57, 1.98, 1.53 and 0.21 pmol/mg protein). Only iris contained more CPN that did plasma (23.0 v. 7.21 pmol/mg protein). The tissue distribution of ACE is that expected for an endothelial-associated enzyme. Plasma may be the major source of CPN in eye tissues other than iris

Komposisi Kimia, Kadar Albumin Dan Bioaktivitas Ekstrak Protein Ikan Gabus (Channa Striata Alam Dan Hasil Budidaya

Directory of Open Access Journals (Sweden)

Ekowati Chasanah

2015-12-01

Full Text Available Khasiat kesehatan ikan gabus (C. striata telah dikenal secara luas dan saat ini C. striata telah digunakan sebagai bahan baku industri produk suplemen. Tingginya permintaan akan produk suplemen tersebut menimbulkan masalah pada ketersediaan C. striata yang sebagian besar ditangkap dari sungai dan danau sebagai tempat hidupnya. Ikan gabus budidaya dipercaya memiliki kualitas tidak sebaik ikan gabus alam.Tujuan penelitian ini adalah untuk mendapatkan informasi mengenai komposisi kimia, termasuk albumin dan potensi ekstrak protein kasar ikan gabus alam dan hasil budidaya sebagai antioksidan dan anti hipertensi. Hasil analisis menunjukkan bahwa ikan gabus alam dan hasil budidaya memiliki kadar protein yang tidak berbeda secara nyata, tetapi berbeda pada kadar air, abu, dan lemak. Ikan gabus alam memiliki kadar lemak dan abu lebih rendah tetapi kadar air lebih tinggi dibanding ikan gabus budidaya. Ikan dari kedua sumber memiliki bagian yang dapat dimakan atau edible portion (EP sebesar 36%,dengan kadar mineral makro (Na, K, Ca dan mikro (Zn, Fe pada ikan hasil budidaya lebih tinggi dibanding kedua kelompok mineral pada ikan gabus alam. Kadar albumin ikan gabus alam lebih tinggi daripada kadar albumin ikan gabus budidaya. Namun demikian, hasil analisis asam amino menunjukkan bahwa ikan gabus hasil budidaya memiliki kuantitas asam amino yang lebih tinggi daripada ikan gabus alam. Asam amino non essensial dominan adalah alanin, asam aspartat, glisin, alloisoleusin, prolin, dan glutamin, sedangkan asam amino esensial didominasi oleh leusin, lisin, dan fenilalanin. Kedua ikan gabus yang diperoleh dari tempat yang berbeda tersebut memiliki bioaktivitas sebagai antioksidan yang lemah, namun berpotensi sebagai antihipertensi (penghambat Angiotensin Converting Enzyme (ACE dengan kekuatan 1/10 kekuatan kontrol obat hipertensi captopril.

Komposisi Kimia, Kadar Albumin dan Bioaktivitas Ekstrak Protein Ikan Gabus (Channa striata Alam dan Hasil Budidaya

Directory of Open Access Journals (Sweden)

Ekowati Chasanah

2015-12-01

Full Text Available Khasiat kesehatan ikan gabus (C. striata telah dikenal secara luas dan saat ini C. striata telah digunakan sebagai bahan baku industri produk suplemen. Tingginya permintaan akan produk suplemen tersebut menimbulkan masalah pada ketersediaan C. striata yang sebagian besar ditangkap dari sungai dan danau sebagai tempat hidupnya. Ikan gabus budidaya dipercaya memiliki kualitas tidak sebaik ikan gabus alam.Tujuan penelitian ini adalah untuk mendapatkan informasi mengenai komposisi kimia, termasuk albumin dan potensi ekstrak protein kasar ikan gabus alam dan hasil budidaya sebagai antioksidan dan anti hipertensi. Hasil analisis menunjukkan bahwa ikan gabus alam dan hasil budidaya memiliki kadar protein yang tidak berbeda secara nyata, tetapi berbeda pada kadar air, abu, dan lemak. Ikan gabus alam memiliki kadar lemak dan abu lebih rendah tetapi kadar air lebih tinggi dibanding ikan gabus budidaya. Ikan dari kedua sumber memiliki bagian yang dapat dimakan atau edible portion (EP sebesar 36%,dengan kadar mineral makro (Na, K, Ca dan mikro (Zn, Fe pada ikan hasil budidaya lebih tinggi dibanding kedua kelompok mineral pada ikan gabus alam. Kadar albumin ikan gabus alam lebih tinggi daripada kadar albumin ikan gabus budidaya. Namun demikian, hasil analisis asam amino menunjukkan bahwa ikan gabus hasil budidaya memiliki kuantitas asam amino yang lebih tinggi daripada ikan gabus alam. Asam amino non essensial dominan adalah alanin, asam aspartat, glisin, alloisoleusin, prolin, dan glutamin, sedangkan asam amino esensial didominasi oleh leusin, lisin, dan fenilalanin. Kedua ikan gabus yang diperoleh dari tempat yang berbeda tersebut memiliki bioaktivitas sebagai antioksidan yang lemah, namun berpotensi sebagai antihipertensi (penghambat Angiotensin Converting Enzyme (ACE dengan kekuatan 1/10 kekuatan kontrol obat hipertensi captopril.

Efeito de um programa de manejo farmacoterapêutico em um grupo de idosos com hipertensão em Aracaju-Sergipe

Directory of Open Access Journals (Sweden)

D. P. LYRA JúNIOR

2009-08-01

Full Text Available O presente estudo visou avaliar o efeito de um programa de manejo farmacoterapêutico no atendimento de idosos com hipertensão arterial sistêmica assistidos em unidade básica de saúde no município de Aracaju-Sergipe. Foram selecionados 30 idosos portadores de hipertensão, entre 60 e 75 anos de ambos os gêneros. Foi realizado um estudo de intervenção. Ao longo do estudo foram avaliadas as mudanças referentes ao manejo da farmacoterapia, de janeiro de 2007 a agosto de 2008. As variáveis analisadas foram: perfil sócio-demográfico e farmacoterapêutico e freqüência de comorbidades. A média de idade foi 69 ± 4 anos, com prevalência do gênero feminino. Os dados obtidos mostraram freqüência das comorbidades, especialmente nos sistema cardiovascular (100% e músculo-esquelético (90%. Com relação ao perfil farmacoterapêutico foram identificados 76 diferentes tipos de especialidades farmacêuticas. Os medicamentos mais consumidos foram a hidroclorotiazida (53,3% e o captopril (30%. Além disso, as intervenções reduziram o uso de AINEs (25,3% para 10% e de polifarmácia (de nove para seis pacientes. O levantamento do perfil farmacoterapêutico forneceu elementos relevantes para compreender o uso de medicamentos em uma unidade de saúde, bem como, para eleger prioridades no cuidado aos idosos com hipertensão e elaborar estratégias em que o farmacêutico possa intervir de modo a reduzir e prevenir problemas farmacoterapêuticos. Palavras-chave: Idoso. Hipertensão arterial sistêmica. Farmacoterapia.

A Novel Splice-Site Mutation in Angiotensin I-Converting Enzyme (ACE) Gene, c.3691+1G>A (IVS25+1G>A), Causes a Dramatic Increase in Circulating ACE through Deletion of the Transmembrane Anchor

Science.gov (United States)

Persu, Alexandre; Lambert, Michel; Deinum, Jaap; Cossu, Marta; de Visscher, Nathalie; Irenge, Leonid; Ambroise, Jerôme; Minon, Jean-Marc; Nesterovitch, Andrew B.; Churbanov, Alexander; Popova, Isolda A.; Danilov, Sergei M.; Danser, A. H. Jan; Gala, Jean-Luc

2013-01-01

Background Angiotensin-converting enzyme (ACE) (EC 4.15.1) metabolizes many biologically active peptides and plays a key role in blood pressure regulation and vascular remodeling. Elevated ACE levels are associated with different cardiovascular and respiratory diseases. Methods and Results Two Belgian families with a 8-16-fold increase in blood ACE level were incidentally identified. A novel heterozygous splice site mutation of intron 25 - IVS25+1G>A (c.3691+1G>A) - cosegregating with elevated plasma ACE was identified in both pedigrees. Messenger RNA analysis revealed that the mutation led to the retention of intron 25 and Premature Termination Codon generation. Subjects harboring the mutation were mostly normotensive, had no left ventricular hypertrophy or cardiovascular disease. The levels of renin-angiotensin-aldosterone system components in the mutated cases and wild-type controls were similar, both at baseline and after 50 mg captopril. Compared with non-affected members, quantification of ACE surface expression and shedding using flow cytometry assay of dendritic cells derived from peripheral blood monocytes of affected members, demonstrated a 50% decrease and 3-fold increase, respectively. Together with a dramatic increase in circulating ACE levels, these findings argue in favor of deletion of transmembrane anchor, leading to direct secretion of ACE out of cells. Conclusions We describe a novel mutation of the ACE gene associated with a major familial elevation of circulating ACE, without evidence of activation of the renin-angiotensin system, target organ damage or cardiovascular complications. These data are consistent with the hypothesis that membrane-bound ACE, rather than circulating ACE, is responsible for Angiotensin II generation and its cardiovascular consequences. PMID:23560051

Dissociation of thirst and sodium appetite in the furo/cap model of extracellular dehydration and a role for N-methyl-D-aspartate receptors in the sensitization of sodium appetite

Science.gov (United States)

Hurley, Seth. W.; Johnson, Alan Kim

2015-01-01

Depletion of extracellular fluids motivates many animals to seek out and ingest water and sodium. Animals with a history of extracellular dehydration display enhanced sodium appetite and in some cases thirst. The progressive increase in sodium intake induced by repeated sodium depletions is known as sensitization of sodium appetite. Administration of the diuretic and natriuretic drug, furosemide, along with a low dose of captopril (furo/cap), elicits thirst and a rapid onset of sodium appetite. In the present studies the furo/cap model was used to explore the physiological mechanisms of sensitization of sodium appetite. However, when thirst and sodium appetite were measured concurrently in the furo/cap model, individual rats exhibited sensitization of either thirst or sodium appetite. In subsequent studies, thirst and sodium appetite were dissociated by offering either water prior to sodium or sodium before water. When water and sodium intake were dissociated in time, the furo/cap model reliably produced sensitization of sodium appetite. It is likely that neuroplasticity mediates this sensitization. Glutamatergic N-methyl-d-aspartate receptor (NMDA-R) activation is critical for the development of most forms of neuroplasticity. Therefore, we hypothesized that integrity of NMDA-R function is necessary for the sensitization of sodium appetite. Pharmacological blockade of NMDA-Rs with systemic administration of MK-801 (0.15mg/kg) prevented the sensitization of fluid intake in general when water and sodium were offered concurrently, and prevented sensitization of sodium intake specifically when water and sodium intake were dissociated. The involvement of NMDA-Rs provides support for the possibility that sensitization of sodium appetite is mediated by neuroplasticity. PMID:24341713

Practical spectrophotometric assay for the dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase, a potential antibiotic target.

Directory of Open Access Journals (Sweden)

Tahirah K Heath

Full Text Available A new enzymatic assay for the bacterial enzyme succinyl-diaminopimelate desuccinylase (DapE, E.C. 3.5.1.18 is described. This assay employs N6-methyl-N2-succinyl-L,L-diaminopimelic acid (N6-methyl-L,L-SDAP as the substrate with ninhydrin used to detect cleavage of the amide bond of the modified substrate, wherein N6-methylation enables selective detection of the primary amine enzymatic product. Molecular modeling supported preparation of the mono-N6-methylated-L,L-SDAP as an alternate substrate for the assay, given binding in the active site of DapE predicted to be comparable to the endogenous substrate. The alternate substrate for the assay, N6-methyl-L,L-SDAP, was synthesized from the tert-butyl ester of Boc-L-glutamic acid employing a Horner-Wadsworth-Emmons olefination followed by an enantioselective reduction employing Rh(I(COD(S,S-Et-DuPHOS as the chiral catalyst. Validation of the new ninhydrin assay was demonstrated with known inhibitors of DapE from Haemophilus influenza (HiDapE including captopril (IC50 = 3.4 [± 0.2] μM, 3-mercaptobenzoic acid (IC50 = 21.8 [±2.2] μM, phenylboronic acid (IC50 = 316 [± 23.6] μM, and 2-thiopheneboronic acid (IC50 = 111 [± 16] μM. Based on these data, this assay is simple and robust, and should be amenable to high-throughput screening, which is an important step forward as it opens the door to medicinal chemistry efforts toward the discovery of DapE inhibitors that can function as a new class of antibiotics.

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

Directory of Open Access Journals (Sweden)

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

Selectivity of Inhibition of N-Succinyl- l , l -Diaminopimelic Acid Desuccinylase in Bacteria: The product of dapE-gene Is Not the Target of l -Captopril Antimicrobial Activity

OpenAIRE

Uda, Narasimha Rao; Creus, Marc

2011-01-01

The emergence of bacterial strains that are resistant to virtually all currently available antibiotics underscores the importance of developing new antimicrobial compounds. N-succinyl-l,l-diaminopimelic acid desuccinylase (DapE) is a metallohydrolase involved in the meso-diaminopimelate (mDAP)/lysine biosynthetic pathway necessary for lysine biosynthesis and for building the peptidoglycan cell wall. Because DapE is essential for Gram-negative and some Gram-positive bacteria, DapE has been pro...

A Novel Vasoactive Proline-Rich Oligopeptide from the Skin Secretion of the Frog Brachycephalus ephippium.

Science.gov (United States)

Arcanjo, Daniel Dias Rufino; Vasconcelos, Andreanne Gomes; Comerma-Steffensen, Simón Gabriel; Jesus, Joilson Ramos; Silva, Luciano Paulino; Pires Júnior, Osmindo Rodrigues; Costa-Neto, Claudio Miguel; Oliveira, Eduardo Brandt; Migliolo, Ludovico; Franco, Octávio Luiz; Restini, Carolina Baraldi Araújo; Paulo, Michele; Bendhack, Lusiane Maria; Bemquerer, Marcelo Porto; Oliveira, Aldeidia Pereira; Simonsen, Ulf; Leite, José Roberto de Souza de Almeida

2015-01-01

Proline-rich oligopeptides (PROs) are a large family which comprises the bradykinin-potentiating peptides (BPPs). They inhibit the activity of the angiotensin I-converting enzyme (ACE) and have a typical pyroglutamyl (Pyr)/proline-rich structure at the N- and C-terminus, respectively. Furthermore, PROs decrease blood pressure in animals. In the present study, the isolation and biological characterization of a novel vasoactive BPP isolated from the skin secretion of the frog Brachycephalus ephippium is described. This new PRO, termed BPP-Brachy, has the primary structure WPPPKVSP and the amidated form termed BPP-BrachyNH2 inhibits efficiently ACE in rat serum. In silico molecular modeling and docking studies suggest that BPP-BrachyNH2 is capable of forming a hydrogen bond network as well as multiple van der Waals interactions with the rat ACE, which blocks the access of the substrate to the C-domain active site. Moreover, in rat thoracic aorta BPP-BrachyNH2 induces potent endothelium-dependent vasodilatation with similar magnitude as captopril. In DAF-FM DA-loaded aortic cross sections examined by confocal microscopy, BPP-BrachyNH2 was found to increase the release of nitric oxide (NO). Moreover, BPP-BrachyNH2 was devoid of toxicity in endothelial and smooth muscle cell cultures. In conclusion, the peptide BPP-BrachyNH2 has a novel sequence being the first BPP isolated from the skin secretion of the Brachycephalidae family. This opens for exploring amphibians as a source of new biomolecules. The BPP-BrachyNH2 is devoid of cytotoxicity and elicits endothelium-dependent vasodilatation mediated by NO. These findings open for the possibility of potential application of these peptides in the treatment of endothelial dysfunction and cardiovascular diseases.

A Novel Vasoactive Proline-Rich Oligopeptide from the Skin Secretion of the Frog Brachycephalus ephippium.

Directory of Open Access Journals (Sweden)

Daniel Dias Rufino Arcanjo

Full Text Available Proline-rich oligopeptides (PROs are a large family which comprises the bradykinin-potentiating peptides (BPPs. They inhibit the activity of the angiotensin I-converting enzyme (ACE and have a typical pyroglutamyl (Pyr/proline-rich structure at the N- and C-terminus, respectively. Furthermore, PROs decrease blood pressure in animals. In the present study, the isolation and biological characterization of a novel vasoactive BPP isolated from the skin secretion of the frog Brachycephalus ephippium is described. This new PRO, termed BPP-Brachy, has the primary structure WPPPKVSP and the amidated form termed BPP-BrachyNH2 inhibits efficiently ACE in rat serum. In silico molecular modeling and docking studies suggest that BPP-BrachyNH2 is capable of forming a hydrogen bond network as well as multiple van der Waals interactions with the rat ACE, which blocks the access of the substrate to the C-domain active site. Moreover, in rat thoracic aorta BPP-BrachyNH2 induces potent endothelium-dependent vasodilatation with similar magnitude as captopril. In DAF-FM DA-loaded aortic cross sections examined by confocal microscopy, BPP-BrachyNH2 was found to increase the release of nitric oxide (NO. Moreover, BPP-BrachyNH2 was devoid of toxicity in endothelial and smooth muscle cell cultures. In conclusion, the peptide BPP-BrachyNH2 has a novel sequence being the first BPP isolated from the skin secretion of the Brachycephalidae family. This opens for exploring amphibians as a source of new biomolecules. The BPP-BrachyNH2 is devoid of cytotoxicity and elicits endothelium-dependent vasodilatation mediated by NO. These findings open for the possibility of potential application of these peptides in the treatment of endothelial dysfunction and cardiovascular diseases.

Casein Fermentate of Lactobacillus animalis DPC6134 Contains a Range of Novel Propeptide Angiotensin-Converting Enzyme Inhibitors▿

Science.gov (United States)

Hayes, M.; Stanton, C.; Slattery, H.; O'Sullivan, O.; Hill, C.; Fitzgerald, G. F.; Ross, R. P.

2007-01-01

This work evaluated the angiotensin-converting-enzyme (ACE)-inhibitory activities of a bovine sodium caseinate fermentate generated using the proteolytic capabilities of the porcine small intestinal isolate Lactobacillus animalis DPC6134 (NCIMB deposit 41355). The crude 10-kDa L. animalis DPC6134 fermentate exhibited ACE-inhibitory activity of 85.51% (±15%) and had a 50% inhibitory concentration (IC50) of 0.8 mg protein/ml compared to captopril, which had an IC50 value of 0.005 mg/ml. Fractionation of the crude L. animalis DPC6134 fermentate by membrane filtration and reversed-phase high-performance liquid chromatography (HPLC) generated three bioactive fractions from a total of 72 fractions. Fractions 10, 19, and 43 displayed ACE-inhibitory activity percentages of 67.53 (±15), 83.71 (±19), and 42.36 (±11), respectively, where ACE inhibition was determined with 80 μl of the fractions with protein concentrations of 0.5 mg/ml. HPLC and mass spectrometry analysis identified 25 distinct peptide sequences derived from α-, β-, and κ-caseins. In silico predictions, based on the C-terminal tetrapeptide sequences, suggested that peptide NIPPLTQTPVVVPPFIQ, corresponding to β-casein f(73-89); peptide IGSENSEKTTMP, corresponding to αs1-casein f(201212); peptide SQSKVLPVPQ, corresponding to β-casein f(166-175); peptide MPFPKYPVEP, corresponding to β-casein f(124133); and peptide EPVLGPVRGPFP, corresponding to β-casein f(210-221), contained ACE-inhibitory activities. These peptides were chosen for chemical synthesis to confirm the ACE-inhibitory activity of the fractions. Chemically synthesized peptides displayed IC50 values in the range of 92 μM to 790 μM. Additionally, a simulated gastrointestinal digestion confirmed that the ACE-inhibitory 10-kDa L. animalis DPC6134 fermentation was resistant to a cocktail of digestive enzymes found in the gastrointestinal tract. PMID:17483275

Synthesis and characterization of retrograded starch nanoparticles through homogenization and miniemulsion cross-linking.

Science.gov (United States)

Ding, Yongbo; Zheng, Jiong; Zhang, Fusheng; Kan, Jianquan

2016-10-20

A new and convenient route to synthesizing retrograded starch nanoparticles (RS3NPs) through homogenization combined with a water-in-oil miniemulsion cross-linking technique was developed. The RS3NPs were optimized using Box-Behnken experimental design. Homogenization pressure (X1), oil/water ratio (X2), and surfactant (X3) were selected as independent variables, whereas particle size was considered as a dependent variable. Results indicated that homogenization pressure was the main contributing variable for particle size. The optimum values for homogenization pressure, oil/water ratio, and surfactant were 30MPa, 9.34:1, and 2.54g, respectively, whereas the particle size was predicted to be 288.2 nm. Morphological, physical, chemical, and functional properties of the RS3NPs were the assessed. Scanning electron microscopy and dynamic light scattering images showed that RS3NP granules were broken down to size of about 222.2nm. X-ray diffraction results revealed a disruption in crystallinity. The RS3NPs exhibited a slight decrease in To, but Tp and Tc increased and narrowest Tc-To. The solubility and swelling power were also increased. New peaks at 1594.84 and 1403.65cm(-1) were observed in the FTIR graph. However, homogenization minimally influenced the antidigestibility of RS3NPs. The absorption properties improved, and the adsorption kinetic described the contact time on the adsorption of captopril onto RS3NPs. In vitro release experiment indicated that the drug was released as follows: 21% after 2h in SGF, 42.78% at the end of 8h (2h in SGF and 6h in SIF), and 92.55% after 12h in SCF. These findings may help better utilize RS3NP in biomedical applications as a drug delivery material. Copyright © 2016 Elsevier Ltd. All rights reserved.

In vivo hypotensive effect and in vitro inhibitory activity of some Cyperaceae species

Directory of Open Access Journals (Sweden)

Monica Lacerda Lopes Martins

2013-12-01

Full Text Available In 1820, French naturalist August Saint Hillaire, during a visit in Espírito Santo (ES, a state in southeastern Brazil, reported a popular use of Cyperaceae species as antidote to snake bites. The plant may even have a hypotensive effect, though it was never properly researched. The in vitro inhibitory of the angiotensin converting enzyme (ACE activity of eigth ethanolic extracts of Cyperaceae was evaluated by colorimetric assay. Total phenolic and flavonoids were determined using colorimetric assay. The hypotensive effect of the active specie (Rhychonospora exaltata, ERE and the in vivo ACE assay was measured in vivo using male Wistar Kyoto (ERE, 0.01-100mg/kg, with acetylcholine (ACh as positive control (5 µg/kg, i.v.. The evaluation of ACE in vivo inhibitory effect was performed comparing the mean arterial pressure before and after ERE (10 mg/kg in animals which received injection of angiotensin I (ANG I; 0,03, 03 and 300 µg/kg, i.v.. Captopril (30 mg/kg was used as positive control. Bulbostylis capillaris (86.89 ± 15.20% and ERE (74.89 ± 11.95%, ERE were considered active in the in vitro ACE inhibition assay, at 100 µg/mL concentration. ACh lead to a hypotensive effect before and after ERE's curve (-40±5% and -41±3%. ERE showed a dose-dependent hypotensive effect and a in vivo ACE inhibitory effect. Cyperaceae species showed an inhibitory activity of ACE, in vitro, as well as high content of total phenolic and flavonoids. ERE exhibited an inhibitory effect on both in vitro and in vivo ACE. The selection of species used in popular medicine as antidotes, along with the in vitro assay of ACE inhibition, might be a biomonitoring method for the screening of new medicinal plants with hypotensive properties.

Furosemide-131I-hippuran renography after angiotensin-converting enzyme inhibition for the diagnosis of renovascular hypertension

International Nuclear Information System (INIS)

Erbsloeh-Moeller, B.Du.; Dumas, A.; Roth, D.; Sfakianakis, G.N.; Bourgoignie, J.J.

1991-01-01

We have previously demonstrated the greater sensitivity of 131I-hippuran renography than 99mTC-DTPA scintigraphy to diagnose renovascular hypertension (RVH). This study assesses the predictive diagnostic value of furosemide-131I-hippuran renography after angiotensin-converting enzyme (ACE) inhibition in patients with and without RVH. All patients were investigated at the University of Miami/Jackson Memorial Medical Center. Twenty-eight patients had RVH and 22 did not. Twenty-eight patients had normal or minimally decreased renal function and 22 had renal insufficiency. Renography was performed 60 minutes after oral administration of 50 mg captopril or 10 minutes after intravenous injection of 40 micrograms/kg enalaprilat. Forty milligrams of furosemide were administered intravenously 2 minutes after injection of 131I-hippuran. The residual cortical activity (RCA) of 131I-hippuran was measured at 20 minutes. RVH was unlikely when RCA after ACE inhibition was less than 30% of peak cortical activity. Conversely, RVH was present when 131I-hippuran cortical activity steadily increased throughout the test to reach 100% at 20 minutes. In azotemic patients with RCA between 31% and 100%, RVH was differentiated from intrinsic renal disease by obtaining a baseline renogram without ACE inhibition and comparing RCA in that study and RCA after ACE inhibition. If RCA increased (indicating worsening renal function) after ACE inhibition, RVH was likely; whereas, intrinsic renal disease was more likely if RCA remained unchanged or decreased (indicating improved renal function) with ACE inhibition. The test had a specificity of 95% and a sensitivity of 96% in this population. There was a direct correlation between the results of angioplasty or surgery on high blood pressure and the changes in RCA before and after intervention (n = 20)

Bradykinin-induced lung inflammation and bronchoconstriction: role in parainfluenze-3 virus-induced inflammation and airway hyperreactivity.

Science.gov (United States)

Broadley, Kenneth J; Blair, Alan E; Kidd, Emma J; Bugert, Joachim J; Ford, William R

2010-12-01

Inhaled bradykinin causes bronchoconstriction in asthmatic subjects but not nonasthmatics. To date, animal studies with inhaled bradykinin have been performed only in anesthetized guinea pigs and rats, where it causes bronchoconstriction through sensory nerve pathways. In the present study, airway function was recorded in conscious guinea pigs by whole-body plethysmography. Inhaled bradykinin (1 mM, 20 s) caused bronchoconstriction and influx of inflammatory cells to the lungs, but only when the enzymatic breakdown of bradykinin by angiotensin-converting enzyme and neutral endopeptidase was inhibited by captopril (1 mg/kg i.p.) and phosphoramidon (10 mM, 20-min inhalation), respectively. The bronchoconstriction and cell influx were antagonized by the B(2) kinin receptor antagonist 4-(S)-amino-5-(4-{4-[2,4-dichloro-3-(2,4-dimethyl-8-quinolyloxymethyl)phenylsulfonamido]-tetrahydro-2H-4-pyranylcarbonyl}piperazino)-5-oxopentyl](trimethyl)ammonium chloride hydrochloride (MEN16132) when given by inhalation (1 and 10 μM, 20 min) and are therefore mediated via B(2) kinin receptors. However, neither intraperitioneal MEN16132 nor the peptide B(2) antagonist icatibant, by inhalation, antagonized these bradykinin responses. Sensitization of guinea pigs with ovalbumin was not sufficient to induce airway hyperreactivity (AHR) to the bronchoconstriction by inhaled bradykinin. However, ovalbumin challenge of sensitized guinea pigs caused AHR to bradykinin and histamine. Infection of guinea pigs by nasal instillation of parainfluenza-3 virus produced AHR to inhaled histamine and lung influx of inflammatory cells. These responses were attenuated by the bradykinin B(2) receptor antagonist MEN16132 and H-(4-chloro)DPhe-2'(1-naphthylalanine)-(3-aminopropyl)guanidine (VA999024), an inhibitor of tissue kallikrein, the enzyme responsible for lung synthesis of bradykinin. These results suggest that bradykinin is involved in virus-induced inflammatory cell influx and AHR.

Multidetector spiral CT renal angiography in the diagnosis of renal artery fibromuscular dysplasia

International Nuclear Information System (INIS)

Sabharwal, Rohan; Vladica, Philip; Coleman, Patrick

2007-01-01

Objective: The aim of this study was to evaluate the role and detection rate of multidetector spiral CT renal angiography (CTA) as compared with conventional angiography (CA), the commonly accepted gold standard, in the diagnosis of renal artery fibromuscular dysplasia (FMD). In addition, the role of CTA reconstructions (multiplanar reformatted images (MPR), maximum intensity projections (MIP) and shaded-surface display (SSD)) in the detection of FMD was also evaluated. Materials and methods: CTA results were retrospectively reviewed in 21 hypertensive patients with CA-proven FMD. Clinical indications for referral included resistant hypertension (requiring greater than three antihypertensive medications), labile hypertension, hypertension in combination with renal impairment and the presence of abdominal bruits in the context of systemic hypertension. In some cases, these clinical indications were supplemented by positive results in other tests, including plasma renin assay, captopril scintigraphy and/or Doppler ultrasound. The findings of CA in these 21 patients were compared to CTA. Results: Mean patient age was 62.33 + 14.32 years (range 24-85 years). CTA identified all 42 main renal arteries (100%) and all 10 accessory renal arteries (100%) visualized on CA. In the diagnosis of FMD, CTA detected all 40 (100%) lesions detected by CA. No single CTA reconstruction technique was able to detect all lesions noted on corresponding CA, however, upon review of all CTA reconstructions (MPR, MIP and SSD) in each case, every lesion was correctly identified by CTA. Conclusion: Our experience suggests that CTA is a non-invasive, reliable and accurate method for the diagnosis of renal artery fibromuscular dysplasia. Moreover, in our experience CTA has many advantages as a diagnostic screening tool over CA, including accessibility, speed, lower complication profile, versatility and cost-effectiveness. CTA shows great potential as a guiding tool for directing subsequent

Estudo de potenciais interações medicamentosas em pacientes hipertensos

Directory of Open Access Journals (Sweden)

Sally Cristina Moutinho MONTEIRO ; Wandson Rodrigues SOUSA1, Clemilson da Silva BARROS ; Karla Valéria Santos de CAMPOS

2015-01-01

Full Text Available Hipertensão arterial é uma elevação crônica da pressão arterial sistólica e diastólica e é provavelmente a doença crônica mais comum nos dias de hoje. Os portadores desse agravo necessitam de atenção especial, uma vez que muitos fazem uso de associação de medicamentos, aumentando assim o risco de interações medicamentosas. O objetivo do trabalho foi verificar potenciais interações medicamentosas com anti-hipertensivos em usuários hipertensos de uma estratégia de saúde da família, em São Luís. MA. Foi realizado um estudo quantitativo observacional de corte transversal com 60 hipertensos do Sistema de Cadastramento e Acompanhamento de Hipertensos e Diabéticos (SIS-HIPERDIA, vinculado a uma Unidade Básica de Saúde (UBS de São Luís, MA. A população estudada foi predominantemente do sexo feminino (71,67%, de cor parda (46,66%, com ensino fundamental incompleto (55% e renda familiar de até meio salário mínimo (65%. Foram observadas 70 potenciais interações medicamentosas, onde destacaram-se as interações moderadas (84,28%. As classes terapêuticas mais frequentemente envolvidas foram os anti-inflamatórios e as associações mais frequentes ocorreram entre ácido acetilsalicílico com losartana e hidroclorotiazida com captopril. Os resultados mostraram alta prevalência de potenciais interações medicamentosas na população estudada, ratificando dados encontrados na literatura. A busca do trabalho colaborativo entre prescritores e farmacêuticos deve ser constante objetivando a intensificação do processo de cuidados em saúde, o compartilhamento de conhecimentos e a integralidade do cuidado

Hyponatremic hypertensive syndrome secondary to renal ischemia – Case report

Directory of Open Access Journals (Sweden)

Joana Cunha Oliveira

2018-01-01

Full Text Available Hyponatremic hypertensive syndrome (HHS is characterized by hypertensive crisis, and hyponatremia secondary to unilateral renal damage with glomerular and tubular dysfunction. Elevated plasma levels of renin in most cases suggest that the stimulation of renin release from the ischemic kidney plays an important pathophysiologic role. Activation of the renin-angiotensin system results in hypertension and causes secondary hyperfiltration, pressure diuresis and sodium loss from contralateral non-damaged kidney. An elevated renin level is a pathognomonic finding in HHS. Potassium deficiency from hyperaldosteronism may further stimulate renin secretion and intensify this vicious circle.We report a female term newborn, who presented with hypertensive crisis on the seventh day after traumatic birth. The first three days of life were uneventful. Initial treatment with captopril resulted in severe hypotension and hemodynamic instability. Lab work revealed hyponatremia, hypokalemia, and elevated peripheral renin activity and aldosterone levels. Complementary sonography and magnetic resonance confirmed right adrenal gland hematoma and several ischemic areas in the upper pole of the right kidney. The diagnosis of HHS secondary to renal ischemia was evoked.HHS is a rare condition in the neonatal period, though still under-recognized. In the neonatal and early infancy period, renovascular disease is the most common cause of secondary hypertension. In this case, there was no sign of vascular disease, the renin-angiotensin system was activated secondary to direct renal ischemia and infarction. The intense renin stimulation and pressure through the contralateral normal kidney results in high pressure natriuresis facilitating a severe volume-depleted state. Although the use of renin-angiotensin system inhibitors is the treatment of choice, it is imperative to re-establish hydration and renal perfusion before starting this antihypertensive medication. We aimed to

Cuantificación de glibenclamida en muestras de limpieza de equipos farmacéuticos mediante cromatografía líquida de alta resolución

Directory of Open Access Journals (Sweden)

Alen Nils Baeza Fonte

2012-03-01

Full Text Available Objetivo: proponer un procedimiento analítico selectivo para la cuantificación de glibenclamida en muestras de limpieza de equipos farmacéuticos mediante cromatografía líquida de alta resolución. Métodos: la fase móvil consistió en una mezcla equivalente de volúmenes de acetonitrilo y solución amortiguadora KH2PO4 de concentración 0,037 mol/L a pH 5,25 y flujo 1,5 mL/min, en una columna Nucleosil 100 C8. La glibenclamida se inyectó con progesterona como estándar interno y empleando detector UV a una l= 230 nm. Resultados: el método resultó lineal en el intervalo de concentraciones de 0,4-150 mg/mL, teniendo como límites de detección y cuantificación 10 y 40 ng/mL respectivamente y siendo específico al analito en presencia del placebo, sus productos de degradación y a otros ingredientes farmacéuticamente activos. Se consideraron potenciales de interferencias para el método propuesto: captopril, clortalidona, dexametasona, digoxina, 8-cloroteofilina, difenhidramina HCl, fenobarbital, haloperidol, hidroclorotiazida, ácido fumárico, ketotifeno, metoclopramida HCl, piridoxina HCl, piroxicam, prednisona y nifedipino. Se identificaron: ibuprofeno, indometacina, trifluoperazina HCl, tioridazina HCl e imipramina HCl, como interferentes del procedimiento en concentraciones cercanas a 10 mg/mL. Conclusiones: el método desarrollado es sensible, rápido y especialmente selectivo para la evaluación de residuales del principio activo glibenclamida en equipos de producción de tabletas, empleando un muestreo por hisopado, y pudiera utilizarse potencialmente cuando exista sospecha de contaminación cruzada de glibenclamida con otros fármacos de los aquí descritos.

EXPERIENCE IN THE OBSERVATION OF ACUTE AND FULMINANT MYOCARDITIS IN CHILDREN

Directory of Open Access Journals (Sweden)

L. V. Bregel

2017-01-01

Full Text Available The results of observation of 17 patients aged 2 monthsto 16 years with acute and fulminant myocarditis(FM were analyzed. Patients were observed in the period 2013-2016. Diagnostics used clinical data, laboratory and instrumental studies. Of 17 patients, acute myocarditis was diagnosed in 14 children, fulminant in 3. Therapy included, first of all, measures for the treatment of heart failure – diuretics (furosemide, verospiron, triampur, angiotensin converting enzyme (ACE inhibitors (captopril, beta-blockers, digoxin inotropic agents. Intravenous human immunoglobulin was administered at a dose of 1-2 g/kg/course in 5 of 17 (29.4% patients. When the pathogen was verified, specific antiviral therapy (acyclovir, ganciclovir, cymevene was administered in a standard mode. Immunosuppressive therapy (prednisolone, delagil was prescribed for two of them. Nonsteroidal anti-inflammatory drugs (ibuprofen, diclofenac was obtained in children with acute myocarditis duration of over 2 weeks (13 children prior to 2016. Nonsteroidal antiinflammatory drugs were not administered to hemodynamically unstable patients, regardless of the time period of observation. Overall, 16 out of 17 (94.4% patients recovered with apparent regression of signs of myocarditis on the background of treatment – the symptoms of acute heart failure and cardiogenic shock were treated, and then manifestations of chronic congestive heart failure gradually decreased. 1 (5,6% child with fulminant myocarditis died. After 6 months to 3 years, 14 children were observed. Follow-up within 6 months to 3 years showed that the diameter of the left ventricle normalized in 10 out of 14 (71.4%. Two out of 14 children (14.3% formed postmyocardial dilated cardiomyopathy.

Furosemide- sup 131 I-hippuran renography after angiotensin-converting enzyme inhibition for the diagnosis of renovascular hypertension

Energy Technology Data Exchange (ETDEWEB)

Erbsloeh-Moeller, B.Du.; Dumas, A.; Roth, D.; Sfakianakis, G.N.; Bourgoignie, J.J. (Univ. of Miami/Jackson Memorial Medical Center, FL (USA))

1991-01-01

We have previously demonstrated the greater sensitivity of 131I-hippuran renography than 99mTC-DTPA scintigraphy to diagnose renovascular hypertension (RVH). This study assesses the predictive diagnostic value of furosemide-131I-hippuran renography after angiotensin-converting enzyme (ACE) inhibition in patients with and without RVH. All patients were investigated at the University of Miami/Jackson Memorial Medical Center. Twenty-eight patients had RVH and 22 did not. Twenty-eight patients had normal or minimally decreased renal function and 22 had renal insufficiency. Renography was performed 60 minutes after oral administration of 50 mg captopril or 10 minutes after intravenous injection of 40 micrograms/kg enalaprilat. Forty milligrams of furosemide were administered intravenously 2 minutes after injection of 131I-hippuran. The residual cortical activity (RCA) of 131I-hippuran was measured at 20 minutes. RVH was unlikely when RCA after ACE inhibition was less than 30% of peak cortical activity. Conversely, RVH was present when 131I-hippuran cortical activity steadily increased throughout the test to reach 100% at 20 minutes. In azotemic patients with RCA between 31% and 100%, RVH was differentiated from intrinsic renal disease by obtaining a baseline renogram without ACE inhibition and comparing RCA in that study and RCA after ACE inhibition. If RCA increased (indicating worsening renal function) after ACE inhibition, RVH was likely; whereas, intrinsic renal disease was more likely if RCA remained unchanged or decreased (indicating improved renal function) with ACE inhibition. The test had a specificity of 95% and a sensitivity of 96% in this population. There was a direct correlation between the results of angioplasty or surgery on high blood pressure and the changes in RCA before and after intervention (n = 20).

Late evaluation of the relationship between morphological and functional renal changes and hypertension after non-operative treatment of high-grade renal injuries

Directory of Open Access Journals (Sweden)

Pereira Júnior Gerson

2012-08-01

Full Text Available Abstract Objective To evaluate the anatomical and functional renal alterations and the association with post-traumatic arterial hypertension. Methods The studied population included patients who sustained high grades renal injury (grades III to V successfully non-operative management after staging by computed tomography over a 16-year period. Beyond the review of medical records, these patients were invited to the following protocol: clinical and laboratory evaluation, abdominal computed tomography, magnetic resonance angiography, DMSA renal scintigraphy, and ambulatory blood pressure monitoring. The hypertensive patients also were submitted to dynamic renal scintigraphy (99mTc EC, using captopril stimulation to verify renal vascular etiology. Results Of the 31 patients, there were thirteen grade III, sixteen grade IV (nine lacerations, and seven vascular lesions, and two grade V injuries. All the patients were asymptomatic and an average follow up post-injury of 6.4 years. None had abnormal BUN or seric creatinine. The percentage of renal volume reduction correlates with the severity as defined by OIS. There was no evidence of renal artery stenosis in Magnetic Resonance angiography (MRA. DMSA scanning demonstrated a decline in percentage of total renal function corresponding to injury severity (42.2 ± 5.5% for grade III, 35.3 ± 12.8% for grade IV, 13.5 ± 19.1 for grade V. Six patients (19.4% had severe compromised function ( Conclusions Late results of renal function after conservative treatment of high grades renal injuries are favorable, except for patients with grades IV with vascular injuries and grade V renal injuries. Moreover, arterial hypertension does not correlate with the grade of renal injury or reduction of renal function.

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.

A radioimmunoassay for vasopressin

International Nuclear Information System (INIS)

Glaenzer, K.

1989-01-01

Described are the development and RIA experimental clinical use of determination for an antidiuretic hormone, 8-arginine vasopressin. The lower limits of detection for this RIA were 0.3 pg/ml in the plasma and 0.6 pg/ml in the urine. For purposes of reference, plasma AVP levels were determined in 50 normal volunteers and found to average 1.2 ± 0.6 pg/ml in females and 1.7 ± 0.7 pg/ml in males. The average AVP excretion with the urine ws 73 ± 43 ng/day. AVP levels determined in urine and plasma samples from patients showing diabetes insipidus centralis or healthy subjects that had not been offered any drink for 24 hours provided evidence in confirmation of supposed physiological interactions. The plasma AVP concentrations of subjects, in which the osmotic processes were impaired by the effects of contrast media used for X-ray examinations, proved to be far above the maximum antidiuretic concentrations and were also very likely to be within the effective range for cardiovascular influences. A series of further examinations was to throw some light on the question whether dramatic surges in ADH during and after surgical replacement of the mitral valve would be accompagnied by the occurrence of a hypoosmolar syndrome. Other examinations were to give insights into the particular role of AVP in the regulation of blood pressure. The last series of examinations had the aim to elucidate the interactions between the angiotensin-renin system and AVP secretion, which were studied in healthy volunteers using the tilting table test both before and during suppression of angiotensin II formation by captopril. There was no conclusive evidence from these examinations that angiotensin II mediates the stimulation of plasma AVP under the conditions of passive orthostatism. (orig./MG) With 24 figs., 8 tabs [de

Confirmatory Tests for the Diagnosis of Primary Aldosteronism: A Prospective Diagnostic Accuracy Study.

Science.gov (United States)

Song, Ying; Yang, Shumin; He, Wenwen; Hu, Jinbo; Cheng, Qingfeng; Wang, Yue; Luo, Ting; Ma, Linqiang; Zhen, Qianna; Zhang, Suhua; Mei, Mei; Wang, Zhihong; Qing, Hua; Bruemmer, Dennis; Peng, Bin; Li, Qifu

2018-01-01

The diagnosis of primary aldosteronism typically requires at least one confirmatory test. The fludrocortisone suppression test is generally accepted as a reliable confirmatory test, but it is cumbersome. Evidence from accuracy studies of the saline infusion test (SIT) and the captopril challenge test (CCT) has provided conflicting results. This prospective study aimed to evaluate the diagnostic accuracy of the SIT and CCT using fludrocortisone suppression test as the reference standard. One hundred thirty-five patients diagnosed with primary aldosteronism and 101 patients diagnosed with essential hypertension who completed the 3 confirmatory tests were included for the diagnostic accuracy analysis. The areas under the receiver-operator characteristics curves of the CCT and SIT were 0.96 (95% confidence interval [CI], 0.92-0.98) and 0.96 (95% CI, 0.92-0.98), respectively, using post-test plasma aldosterone concentration (PAC) for diagnosis. However, the areas under the receiver-operator characteristics curves of the CCT decreased to 0.71 (95% CI, 0.65-0.77) when the PAC suppression percentage was used to diagnose primary aldosteronism. The optimal cutoff of PAC post-CCT was set at 11 ng/dL, resulting in a sensitivity of 0.90 (95% CI, 0.84-0.95) and a specificity of 0.90 (95% CI, 0.83-0.95), which were not significantly different from those of SIT (with PAC post-SIT set at 8 ng/dL, sensitivity: 0.85 [95% CI, 0.78-0.91], P =0.192; specificity: 0.92 [95% CI, 0.85-0.97], P =0.551). In conclusion, both CCT and SIT are accurate alternatives to the more complex fludrocortisone suppression test. Because CCT is safe and much easier to perform, it may serve as a more feasible alternative. When interpreting the results of CCT, PAC post-CCT is highly recommended. © 2017 American Heart Association, Inc.

Economic impact of an ultrasonographic contrast agent on the diagnosis and initial management of patients with suspected renal artery stenosis

International Nuclear Information System (INIS)

Levesque, J.; Lacourciere, Y.; Onrot, J.M.

2002-01-01

To determine resource use in the diagnosis and management of Canadian hypertensive patients with suspected renal artery stenosis and to estimate the impact of diagnosis with contrast-enhanced duplex Doppler ultrasonography (US) on resource use. Seventy-eight patients with suspected renal artery stenosis underwent usual diagnostic tests (captopril-enhanced renal scintigraphy or duplex Doppler US) and contrast-enhanced US. A management pathway ('planned') describing the medical resources required for further patient care was outlined on the basis of results from each test (separately), and a modified management pathway ('recommended'), which considered data from both diagnostic methods, was also outlined. Medical resources and productivity losses were assessed prospectively for a 3-month period after patients underwent both tests ('actual' management pathway). With usual diagnostic methods, 14 (18%) of the tests were inconclusive, whereas only 1 (1%) of the enhanced US examinations was inconclusive; the cost-efficacy ratio was $422 and $343 per successful diagnosis, respectively. Further management costs for patients with an inconclusive diagnosis were estimated at $6370 after the usual diagnostic tests, but only $1278 with enhanced US. Although the costs of the planned and recommended management pathways were similar ($227 and $294 per patient respectively), the proportion of patients requiring further resources was lower with enhanced US (56% v. 46%). Three-month actual management costs ranged from $121 to $1605 per patient (mean $360). Diagnostic tests and surgical procedures were the major cost drivers in all pathways, and costs wore highest for patients in whom stenosis was diagnosed. For patients with suspected renal artery stenosis, contrast-enhanced US had a higher diagnostic success rate than usual diagnostic methods and afforded savings through lower administrative costs and lower medical resource consumption for patients whose diagnosis was unclear after

Angiotensin II receptor one (AT1) mediates dextrose induced endoplasmic reticulum stress and superoxide production in human coronary artery endothelial cells.

Science.gov (United States)

Haas, Michael J; Onstead-Haas, Luisa; Lee, Tracey; Torfah, Maisoon; Mooradian, Arshag D

2016-10-01

Renin-angiotensin-aldosterone system (RAAS) has been implicated in diabetes-related vascular complications partly through oxidative stress. To determine the role of angiotensin II receptor subtype one (AT1) in dextrose induced endoplasmic reticulum (ER) stress, another cellular stress implicated in vascular disease. Human coronary artery endothelial cells with or without AT1 receptor knock down were treated with 27.5mM dextrose for 24h in the presence of various pharmacologic blockers of RAAS and ER stress and superoxide (SO) production were measured. Transfection of cells with AT1 antisense RNA knocked down cellular AT1 by approximately 80%. The ER stress was measured using the placental alkaline phosphatase (ES-TRAP) assay and western blot analysis of glucose regulated protein 78 (GRP78), c-jun-N-terminal kinase 1 (JNK1), phospho-JNK1, eukaryotic translation initiation factor 2α (eIF2α) and phospho-eIF2α measurements. Superoxide (SO) generation was measured using the superoxide-reactive probe 2-methyl-6-(4-methoxyphenyl)-3,7-dihydroimidazo[1,2-A]pyrazin-3-one hydrochloride (MCLA) chemiluminescence. In cells with AT1 knock down, dextrose induced ER stress was significantly blunted and treatment with 27.5mM dextrose resulted in significantly smaller increase in SO production compared to 27.5mM dextrose treated and sham transfected cells. Dextrose induced ER stress was reduced with pharmacologic blockers of AT1 (losartan and candesartan) and mineralocorticoid receptor blocker (spironolactone) but not with angiotensin converting enzyme inhibitors (captopril and lisinopril). The dextrose induced SO generation was inhibited by all pharmacologic blockers of RAAS tested. The results indicate that dextrose induced ER stress and SO production in endothelial cells are mediated at least partly through AT1 receptor activation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Protein kinase-dependent oxidative regulation of the cardiac Na+-K+ pump: evidence from in vivo and in vitro modulation of cell signalling.

Science.gov (United States)

Galougahi, Keyvan Karimi; Liu, Chia-Chi; Garcia, Alvaro; Fry, Natasha A S; Hamilton, Elisha J; Rasmussen, Helge H; Figtree, Gemma A

2013-06-15

The widely reported stimulation of the cardiac Na(+)-K(+) pump by protein kinase A (PKA) should oppose other effects of PKA to increase contractility of the normal heart. It should also reduce harmful raised myocyte Na(+) levels in heart failure, yet blockade of the β1 adrenergic receptor (AR), coupled to PKA signalling, is beneficial. We treated rabbits with the β1 AR antagonist metoprolol to modulate PKA activity and studied cardiac myocytes ex vivo. Metoprolol increased electrogenic pump current (Ip) in voltage clamped myocytes and reduced glutathionylation of the β1 pump subunit, an oxidative modification causally related to pump inhibition. Activation of adenylyl cyclase with forskolin to enhance cAMP synthesis or inclusion of the catalytic subunit of PKA in patch pipette solutions abolished the increase in Ip in voltage clamped myocytes induced by treatment with metoprolol, supporting cAMP/PKA-mediated pump inhibition. Metoprolol reduced myocardial PKA and protein kinase C (PKC) activities, reduced coimmunoprecipitation of cytosolic p47(phox) and membranous p22(phox) NADPH oxidase subunits and reduced myocardial O2(•-)-sensitive dihydroethidium fluorescence. Treatment also enhanced coimmunoprecipitation of the β1 pump subunit with glutaredoxin 1 that catalyses de-glutathionylation. Since angiotensin II induces PKC-dependent activation of NADPH oxidase, we examined the effects of angiotensin-converting enzyme inhibition with captopril. This treatment had no effect on PKA activity but reduced the activity of PKC, reduced β1 subunit glutathionylation and increased Ip. The PKA-induced Na(+)-K(+) pump inhibition we report should act with other mechanisms that enhance contractility of the normal heart but accentuate the harmful effects of raised cytosolic Na(+) in the failing heart. This scheme is consistent with the efficacy of β1 AR blockade in the treatment of heart failure.

Protein kinase-dependent oxidative regulation of the cardiac Na+–K+ pump: evidence from in vivo and in vitro modulation of cell signalling

Science.gov (United States)

Galougahi, Keyvan Karimi; Liu, Chia-Chi; Garcia, Alvaro; Fry, Natasha A S; Hamilton, Elisha J; Rasmussen, Helge H; Figtree, Gemma A

2013-01-01

The widely reported stimulation of the cardiac Na+–K+ pump by protein kinase A (PKA) should oppose other effects of PKA to increase contractility of the normal heart. It should also reduce harmful raised myocyte Na+ levels in heart failure, yet blockade of the β1 adrenergic receptor (AR), coupled to PKA signalling, is beneficial. We treated rabbits with the β1 AR antagonist metoprolol to modulate PKA activity and studied cardiac myocytes ex vivo. Metoprolol increased electrogenic pump current (Ip) in voltage clamped myocytes and reduced glutathionylation of the β1 pump subunit, an oxidative modification causally related to pump inhibition. Activation of adenylyl cyclase with forskolin to enhance cAMP synthesis or inclusion of the catalytic subunit of PKA in patch pipette solutions abolished the increase in Ip in voltage clamped myocytes induced by treatment with metoprolol, supporting cAMP/PKA-mediated pump inhibition. Metoprolol reduced myocardial PKA and protein kinase C (PKC) activities, reduced coimmunoprecipitation of cytosolic p47phox and membranous p22phox NADPH oxidase subunits and reduced myocardial O2•−-sensitive dihydroethidium fluorescence. Treatment also enhanced coimmunoprecipitation of the β1 pump subunit with glutaredoxin 1 that catalyses de-glutathionylation. Since angiotensin II induces PKC-dependent activation of NADPH oxidase, we examined the effects of angiotensin-converting enzyme inhibition with captopril. This treatment had no effect on PKA activity but reduced the activity of PKC, reduced β1 subunit glutathionylation and increased Ip. The PKA-induced Na+–K+ pump inhibition we report should act with other mechanisms that enhance contractility of the normal heart but accentuate the harmful effects of raised cytosolic Na+ in the failing heart. This scheme is consistent with the efficacy of β1 AR blockade in the treatment of heart failure. PMID:23587884

A network-based drug repositioning infrastructure for precision cancer medicine through targeting significantly mutated genes in the human cancer genomes.

Science.gov (United States)

Cheng, Feixiong; Zhao, Junfei; Fooksa, Michaela; Zhao, Zhongming

2016-07-01

Development of computational approaches and tools to effectively integrate multidomain data is urgently needed for the development of newly targeted cancer therapeutics. We proposed an integrative network-based infrastructure to identify new druggable targets and anticancer indications for existing drugs through targeting significantly mutated genes (SMGs) discovered in the human cancer genomes. The underlying assumption is that a drug would have a high potential for anticancer indication if its up-/down-regulated genes from the Connectivity Map tended to be SMGs or their neighbors in the human protein interaction network. We assembled and curated 693 SMGs in 29 cancer types and found 121 proteins currently targeted by known anticancer or noncancer (repurposed) drugs. We found that the approved or experimental cancer drugs could potentially target these SMGs in 33.3% of the mutated cancer samples, and this number increased to 68.0% by drug repositioning through surveying exome-sequencing data in approximately 5000 normal-tumor pairs from The Cancer Genome Atlas. Furthermore, we identified 284 potential new indications connecting 28 cancer types and 48 existing drugs (adjusted P < .05), with a 66.7% success rate validated by literature data. Several existing drugs (e.g., niclosamide, valproic acid, captopril, and resveratrol) were predicted to have potential indications for multiple cancer types. Finally, we used integrative analysis to showcase a potential mechanism-of-action for resveratrol in breast and lung cancer treatment whereby it targets several SMGs (ARNTL, ASPM, CTTN, EIF4G1, FOXP1, and STIP1). In summary, we demonstrated that our integrative network-based infrastructure is a promising strategy to identify potential druggable targets and uncover new indications for existing drugs to speed up molecularly targeted cancer therapeutics. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All

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

Blood-borne interleukin-1β acts on the subfornical organ to upregulate the sympathoexcitatory milieu of the hypothalamic paraventricular nucleus.

Science.gov (United States)

Wei, Shun-Guang; Yu, Yang; Felder, Robert B

2018-03-01

We previously reported that microinjection of the proinflammatory cytokine interleukin-1β (IL-1β) into the subfornical organ (SFO) elicits a pressor response accompanied by increases in inflammation and renin-angiotensin system (RAS) activity in the SFO and hypothalamic paraventricular nucleus (PVN). The present study sought to determine whether blood-borne IL-1β induces similar neurochemical changes in the SFO and PVN and, if so, whether increased inflammation and RAS activity at the SFO level orchestrate the sympathoexcitatory response to circulating IL-1β. In urethane-anesthetized male Sprague-Dawley rats, intravenous injection of IL-1β (500 ng) increased blood pressure, heart rate, renal sympathetic nerve activity, and mRNA for angiotensin-converting enzyme, angiotensin II type 1a receptor, cyclooxygenase-2, tumor necrosis factor-α, and IL-1β, as well as the tumor necrosis factor-α p55 receptor and the IL-1 receptor, in the SFO and PVN. Pretreatment with SFO microinjections of the angiotensin II type 1a receptor blocker losartan (1 µg), the angiotensin-converting enzyme inhibitor captopril (1 µg), or the cyclooxygenase-2 inhibitor NS-398 (2 µg) attenuated expression of these excitatory mediators in the SFO and downstream in the PVN and the IL-1β-induced pressor responses. An SFO lesion minimized the IL-1β-induced expression of inflammatory and RAS components as well as c-Fos, an indicator of neuronal excitation, in the PVN. These studies demonstrate that circulating IL-1β, which increases in cardiovascular disorders such as hypertension and heart failure, acts on the SFO to increase inflammation and RAS activity in the SFO and PVN and that intervening in these neurochemical processes in the SFO can significantly reduce the sympathetic response.

Pro-inflammatory cytokines upregulate sympathoexcitatory mechanisms in the subfornical organ of the rat

Science.gov (United States)

Wei, Shun-Guang; Yu, Yang; Zhang, Zhi-Hua; Felder, Robert B.

2015-01-01

Our previous work indicated that the subfornical organ (SFO) is an important brain sensor of blood-borne pro-inflammatory cytokines, mediating their central effects on autonomic and cardiovascular function. However, the mechanisms by which SFO mediates the central effects of circulating pro-inflammatory cytokines remain unclear. We hypothesized that pro-inflammatory cytokines act within the SFO to upregulate the expression of excitatory and inflammatory mediators that drive sympathetic nerve activity. In urethane-anesthetized Sprague-Dawley rats, direct microinjection of TNF-α (25 ng) or IL-1β (25 ng) into SFO increased mean blood pressure, heart rate and renal sympathetic nerve activity within 15–20 minutes, mimicking the response to systemically administered pro-inflammatory cytokines. Pretreatment of SFO with microinjections of the angiotensin II type 1 receptor (AT1R) blocker losartan (1 µg), angiotensin-converting enzyme (ACE) inhibitor captopril (1 µg) or cyclooxygenase (COX)-2 inhibitor NS-398 (2 µg) attenuated those responses. Four hours after the SFO microinjection of TNF-α (25 ng) or IL-1β (25 ng), mRNA for ACE, AT1R, TNF-α and the p55 TNF-α receptor TNFR1, IL-1β and the IL-1R receptor, and COX-2 had increased in SFO, and mRNA for ACE, AT1R and COX-2 had increased downstream in the hypothalamic paraventricular nucleus. Confocal immunofluorescent images revealed that immunoreactivity for TNFR1 and the IL-1 receptor accessory protein, a subunit of the IL-1 receptor, co-localized with ACE, AT1R-like, COX-2 and prostaglandin E2 EP3 receptor immunoreactivity in SFO neurons. These data suggest that pro-inflammatory cytokines act within the SFO to upregulate the expression of inflammatory and excitatory mediators that drive sympathetic excitation. PMID:25776070

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

Hipertensão arterial sistêmica no setor de emergência: o uso de medicamentos sintomáticos como alternativa de tratamento Systemic hypertension at emergency units: the use of symptomatic drugs as choice for management

Directory of Open Access Journals (Sweden)

Sandro Gonçalves de Lima

2005-08-01

Full Text Available OBJETIVO: Comparar a resposta terapêutica dos pacientes atendidos no Setor de Emergência com sintomas e pressão arterial (PA elevada, ao tratamento com medicação sintomática ou anti-hipertensiva. MÉTODOS: Ensaio clínico randomizado, cego, envolvendo 100 pacientes atendidos na Emergência Cardiológica do Hospital Universitário Oswaldo Cruz com sintomas associados à pressão arterial sistólica (PAS entre 180 e 200 mmHg e/ou pressão arterial diastólica (PAD entre 110 e 120 mmHg. Os pacientes foram randomizados para tratamento com medicação sintomática (dipirona ou diazepam ou anti-hipertensiva (captopril. Aqueles portadores de qualquer condição clínica associada, que necessitassem de tratamento imediato na Unidade de Emergência, foram excluídos do estudo. Atingiram o critério de alta os pacientes que, ao final do período de observação de noventa minutos, tornaram-se assintomáticos e tiveram seus níveis tensionais sistólicos reduzidos para abaixo de 180 mmHg e diastólicos para aquém de 110 mmHg. RESULTADOS: A idade média da população estudada foi 54,4 anos. A maioria dos pacientes era do sexo feminino, hipertensos crônicos em tratamento farmacológico irregular, com baixa taxa de aderência às medidas não farmacológicas e classificados quanto ao índice de massa corpórea (IMC, em sobrepeso e obesos grau I. Cefaléia, dor torácica tipo D (não anginosa e dispnéia foram as queixas mais freqüentes. A proporção de pacientes tratados com medicação sintomática que atingiu o critério de alta foi semelhante àquela de pacientes medicados com anti-hipertensivo (p=0,165. Não foi encontrada associação entre o diagnóstico prévio de hipertensão arterial sistêmica (HAS (p=0,192, tratamento farmacológico (p=0,687 e não-farmacológico e o critério de alta. CONCLUSÃO: Uma maior proporção (não significativa de pacientes tratados com medicação sintomática obtiveram redução da PA aquém dos n

Renovascular hypertension in children with neurofibromatosis type 1

Directory of Open Access Journals (Sweden)

Peco-Antić Amira

2003-01-01

Full Text Available Arterial hypertension in pediatric patients with neurofibromatosis type 1 (NF 1 is usually due to renal artery stenosis (RAS mainly involving the proximal part of the vessel. The treatment modalities are highly individualized. In severe and/or bilateral RAS, antihypertensive drugs are either ineffective or have the potential risk for acute renal failure, while percutaneous transluminal angioplasty (PTA has limited success due to the ostial localization of RAS and the tough fibrotic tissue involved that is refractory to dilatation Renal autotransplantation has potential advantages when medical control and PTA/or bypass techniques failed. Here we report 5 year-old girl with NF 1 and hyponatremic hypertensive syndrome due to severe bilateral disease, occluded proximal part of the right artery and ostial stenosis (80% of the left one. Only left kidney was identified on 99 in Tc DTP A, but the right one was visualized on the renal ultrasonography and in the late phase of arterial renography due to well developed collateral circulation. Multiple antihyper-tensive drugs (nifedipine, labetolol and minoxidil in maximal doses and PTA failed to normalize BP while short term therapy with ACEIwith NF1 and hyponatremic hypertensive syndrome due to severe bilateral renovascular disease; occluded proximal part of the right renal artery and ostial stenosis (80% of the left one. Only left kidney was identified on 99m Tc DTPA, but the right one was visualized on the renal ultrasonography and in the late phase of arterial renography due to well developed collateral circulation. Multiple antyphypertensive drugs (nifedipine, labetolol and minoxidil in maximal doses and PTA failed to normalize BP while. short term therapy with ACEI, captopril induced transient acute renal failure. Autotransplantation of right kidney saved its function and improved BP control. Our current case Autotransplantation of right kidney saved its function and improved BP control. Our current

Mechanism of antihypertensive effect of Mucuna pruriens L. seed extract and its isolated compounds.

Science.gov (United States)

Khan, Mohammad Yaseen; Kumar, Vimal

2017-06-21

Background In the search of safe and effective lead molecules from natural sources, Mucuna pruriens (MP) L. (Fabaceae) seeds were utilized for exploring the antihypertensive potential. Traditionally, it is used as diuretic and hypotensive. Methods Bioassay-guided fractions were utilized for the isolation of active compounds by column chromatography. IC50 value, enzyme kinetics and inhibition mechanism were determined. In vivo time and dose-dependent hypotensive study followed by changes in mean arterial pressure (MAP) induced by angiotensin I (3 nmol/kg), angiotensin II (3 nmol/kg), and bradykinin (10 nmol/kg) in anesthetized rats was done. Plasma and tissue angiotensin I-converting enzyme (ACE) activities were also determined. Results Phytochemical analysis by spectroscopic techniques revealed the presence of known compounds like genistein, ursolic acid and L-DOPA from the ethyl acetate and water fraction, respectively. In vitro study revealed MP ethyl acetate (MPEA) fraction and genistein as the most active fraction (IC50 156.45 µg/mL) and compound (IC50 253.81 µM), respectively. Lineweaver-Burk plots revealed a non-competitive mode of inhibition. ACE protein precipitation was the suggested mechanism for inhibition. The extract showed a time- and dose-dependent decrease in MAP. Genistein was able to dose-dependently reduce the MAP, up to 53±1.5 mmHg (40 mg/kg, i.v.). As compared to control, it showed a dose-dependent decrease in plasma ACE activity of 40.61 % and 54.76 % at 10 mg/kg and 20 mg/kg, respectively. It also decreased the ACE activity in the aorta (107.67nM/ml min at 10 mg, p<0.001; 95.33nM/ml min at 20 mg p<0.001). Captopril was used as a standard for various in vitro and in vivo assays. Conclusions The study revealed the antihypertensive potential of MP seed compounds via ACE inhibition.

Oxidative inhibition of the vascular Na+-K+ pump via NADPH oxidase-dependent β1-subunit glutathionylation: implications for angiotensin II-induced vascular dysfunction.

Science.gov (United States)

Liu, Chia-Chi; Karimi Galougahi, Keyvan; Weisbrod, Robert M; Hansen, Thomas; Ravaie, Ramtin; Nunez, Andrea; Liu, Yi B; Fry, Natasha; Garcia, Alvaro; Hamilton, Elisha J; Sweadner, Kathleen J; Cohen, Richard A; Figtree, Gemma A

2013-12-01

Glutathionylation of the Na(+)-K(+) pump's β1-subunit is a key molecular mechanism of physiological and pathophysiological pump inhibition in cardiac myocytes. Its contribution to Na(+)-K(+) pump regulation in other tissues is unknown, and cannot be assumed given the dependence on specific β-subunit isoform expression and receptor-coupled pathways. As Na(+)-K(+) pump activity is an important determinant of vascular tone through effects on [Ca(2+)]i, we have examined the role of oxidative regulation of the Na(+)-K(+) pump in mediating angiotensin II (Ang II)-induced increases in vascular reactivity. β1-subunit glutathione adducts were present at baseline and increased by exposure to Ang II in rabbit aortic rings, primary rabbit aortic vascular smooth muscle cells (VSMCs), and human arterial segments. In VSMCs, Ang II-induced glutathionylation was associated with marked reduction in Na(+)-K(+)ATPase activity, an effect that was abolished by the NADPH oxidase inhibitory peptide, tat-gp91ds. In aortic segments, Ang II-induced glutathionylation was associated with decreased K(+)-induced vasorelaxation, a validated index of pump activity. Ang II-induced oxidative inhibition of Na(+)-K(+) ATPase and decrease in K(+)-induced relaxation were reversed by preincubation of VSMCs and rings with recombinant FXYD3 protein that is known to facilitate deglutathionylation of β1-subunit. Knock-out of FXYD1 dramatically decreased K(+)-induced relaxation in a mouse model. Attenuation of Ang II signaling in vivo by captopril (8 mg/kg/day for 7 days) decreased superoxide-sensitive DHE levels in the media of rabbit aorta, decreased β1-subunit glutathionylation, and enhanced K(+)-induced vasorelaxation. Ang II inhibits the Na(+)-K(+) pump in VSMCs via NADPH oxidase-dependent glutathionylation of the pump's β1-subunit, and this newly identified signaling pathway may contribute to altered vascular tone. FXYD proteins reduce oxidative inhibition of the Na(+)-K(+) pump and may have an

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

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

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

Consumo de medicamentos por idosos segundo prescrição médica em Jaú-SP

Directory of Open Access Journals (Sweden)

A. C. Marques

2009-01-01

Full Text Available

Realizou-se este trabalho com o objetivo de conhecer as interações medicamentosas mais freqüentemente ocorridas no consumo de medicamentos por prescrição médica entre os idosos atendidos na rede municipal de saúde de Jaú-SP. Sabe-se que são os idosos que convivem mais freqüentemente com problemas crônicos de saúde, o que os leva a uma maior utilização de serviços de saúde e a um elevado consumo de medicamentos. Na presença de doenças concomitantes e na conseqüente prática da politerapia, aumenta a probabilidade de ocorrência de reações adversas e interações medicamentosas. A população estudada foi de 148 idosos com 65 anos ou mais, que compareceram à farmácia do Núcleo de Gestão Assistencial (NGA-25 da cidade de Jaú, no período de agosto a dezembro de 2004. Os dados foram coletados através da prescrição médica e as variáveis estudadas foram o sexo e a idade. Quanto aos medicamentos foram classificados, segundo a classe farmacológica e as interações medicamentosas.Como resultados observouse que consumo de medicamentos segundo o sexo foi de 3,8 medicamentos entre as mulheres e 3,9 entre os homens. Quanto a idade, o maior consumo foi no grupo de 75 a 84 anos, com 4,2 medicamentos. As classes terapêuticas mais prescritas, em ordem decrescente de ocorrência, foram: anti-hipertensivos, 25,0%, cardioterápicos, 15,5%, diuréticos, e antidiabéticos, 10,7%. Concluiu-se que as classes terapêuticas mais envolvidas com interações foram os cardioterápicos, diuréticos e antihipertensivos. Os princípios ativos mais problemáticos foram digoxina, amiodarona, furosemida, captopril, propranolol e nifedipina. Palavras-chave: Consumo medicamento, prescrição medicamento, idosos, interações medicamentos.

Angiotensin-converting enzyme inhibitory activity of Lactobacillus helveticus strains from traditional fermented dairy foods and antihypertensive effect of fermented milk of strain H9.

Science.gov (United States)

Chen, Yongfu; Liu, Wenjun; Xue, Jiangang; Yang, Jie; Chen, Xia; Shao, Yuyu; Kwok, Lai-yu; Bilige, Menghe; Mang, Lai; Zhang, Heping

2014-11-01

Hypertension is a major global health issue which elevates the risk of a large world population to chronic life-threatening diseases. The inhibition of angiotensin-converting enzyme (ACE) is an effective target to manage essential hypertension. In this study, the fermentation properties (titratable acidity, free amino nitrogen, and fermentation time) and ACE-inhibitory (ACEI) activity of fermented milks produced by 259 Lactobacillus helveticus strains previously isolated from traditional Chinese and Mongolian fermented foods were determined. Among them, 37 strains had an ACEI activity of over 50%. The concentrations of the antihypertensive peptides, Ile-Pro-Pro and Val-Pro-Pro, were further determined by ultra performance liquid chromatography with quadrupole-time-of-flight mass spectrometry. The change of ACEI activity of the fermented milks of 3 strains exhibiting the highest ACEI activity upon gastrointestinal protease treatment was assayed. Fermented milks produced by strain H9 (IMAU60208) had the highest in vitro ACEI activity (86.4 ± 1.5%), relatively short fermentation time (7.5 h), and detectable Val-Pro-Pro (2.409 ± 0.229 µM) and Ile-Pro-Pro (1.612 ± 0.114 µM) concentrations. Compared with the control, a single oral dose of H9-fermented milk significantly attenuated the systolic, diastolic, and mean blood pressure of spontaneously hypertensive rats (SHR) by 15 to 18 mmHg during the 6 to 12 h after treatment. The long-term daily H9-fermented milk intake over 7 wk exerted significant antihypertensive effect to SHR, but not normotensive rats, and the systolic and diastolic blood pressure were significantly lower, by 12 and 10 mmHg, respectively, compared with the control receiving saline. The feeding of H9-fermented milk to SHR resulted in a significantly higher weight gain at wk 7 compared with groups receiving saline, commercial yogurt, and captopril. Our study identified a novel probiotic L. helveticus strain originated from kurut sampled from Tibet

Mortality and morbidity remain high despite captopril and/or valsartan therapy in elderly patients with left ventricular systolic dysfunction, heart failure, or both after acute myocardial infarction - Results from the Valsartan in Acute Myocardial Infarction Trial (VALIANT)

NARCIS (Netherlands)

White, HD; Aylward, PEG; Huang, Z; Dalby, AJ; Weaver, WD; Barvik, S; Marin-Neto, JA; Murin, J; Nordlander, RO; van Gilst, WH; Zannad, F; McMurray, JJV; Califf, RM; Pfeffer, MA

2005-01-01

Background - The elderly constitute an increasing proportion of acute myocardial infarction patients and have disproportionately high mortality and morbidity. Those with heart failure or impaired left ventricular left ventricular function after acute myocardial infarction have high complication and

ABC gene-ranking for prediction of drug-induced cholestasis in rats

Directory of Open Access Journals (Sweden)

Yauheniya Cherkas

drugs that behaved very differently, and were distinct from both non-cholestatic and cholestatic drugs (ketoconazole, dipyridamole, cyproheptadine and aniline, and many postulated human cholestatic drugs that in rat showed no evidence of cholestasis (chlorpromazine, erythromycin, niacin, captopril, dapsone, rifampicin, glibenclamide, simvastatin, furosemide, tamoxifen, and sulfamethoxazole. Most of these latter drugs were noted previously by other groups as showing cholestasis only in humans. The results of this work suggest that the ABC procedure and similar statistical approaches can be instrumental in combining data to compare toxicants across toxicogenomics databases, extract similarities among responses and reduce unexplained data varation. Keywords: Cluster analysis, Cholestasis, Gene signature, Microarray, Prediction, Toxicogenomics

Effect of Uric Acid Lowering on Renin-Angiotensin-System Activation and Ambulatory BP: A Randomized Controlled Trial.

Science.gov (United States)

McMullan, Ciaran J; Borgi, Lea; Fisher, Naomi; Curhan, Gary; Forman, John

2017-05-08

Higher serum uric acid levels, even within the reference range, are strongly associated with increased activity of the renin-angiotensin system (RAS) and risk of incident hypertension. However, the effect of lowering serum uric acid on RAS activity in humans is unknown, although the data that lowering serum uric acid can reduce BP are conflicting. In a double-blind placebo-controlled trial conducted from 2011 to 2015, we randomly assigned 149 overweight or obese adults with serum uric acid ≥5.0 mg/dl to uric acid lowering with either probenecid or allopurinol, or to placebo. The primary endpoints were kidney-specific and systemic RAS activity. Secondary endpoints included mean 24-hour systolic BP, mean awake and asleep BP, and nocturnal dipping. Allopurinol and probenecid markedly lowered serum uric acid after 4 and 8 weeks compared with placebo (mean serum uric acid in allopurinol, probenecid, and placebo at 8 weeks was 2.9, 3.5, and 5.6 mg/dl, respectively). The change in kidney-specific RAS activity, measured as change in the median (interquartile range) renal plasma flow response to captopril (in ml/min per 1.73 m 2 ) from baseline to 8 weeks, was -4 (-25 to 32) in the probenecid group ( P =0.83), -4 (-16 to 9) in the allopurinol group ( P =0.32), and 1 (-21 to 17) in the placebo group ( P =0.96), with no significant treatment effect ( P =0.77). Similarly, plasma renin activity and plasma angiotensin II levels did not significantly change with treatment. The change in mean (±SD) 24-hour systolic BPs from baseline to 8 weeks was -1.6±10.1 with probenecid ( P =0.43), -0.4±6.1 with allopurinol ( P =0.76), and 0.5±6.0 with placebo ( P =0.65); there was no significant treatment effect ( P =0.58). Adverse events occurred in 9%, 12%, and 2% of those given probenecid, allopurinol, or placebo, respectively. In contrast to animal experiments and observational studies, this randomized, placebo-controlled trial found that uric acid lowering had no effect on kidney

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

[Effects of rhynchophylla alkaloids on vascular adventitial fibroblast apoptosis and proliferation in the thoracic aorta of spontaneously hypertensive rats].

Science.gov (United States)

Dai, Guo-Hua; Sun, Jing-Chang; Qi, Dong-Mei

2012-09-01

To study the effects of rhynchophylline, isorhynchophylline, and rhynchophylla alkaloids on the vascular adventitial fibroblasts (VAF) apoptosis and proliferation in thoracic aorta of spontaneously hypertensive rats (SHR), and on the Bcl-2, Bax, c-Fos, c-Myc, laminin (LN), and fibronectin (FN). Forty 8-week old male SHR were randomly divided into five groups, i. e., the model group, the captopril group (17.5 mg/kg), the isorhynchophylline group (5.0 mg/kg), the rhynchophylline group (5.0 mg/kg), and the rhynchophylla alkaloids group (50.0 mg/kg), 8 in each group. In addition, eight 8-week old male Wistar rats were selected as the normal group. Equal volume of normal saline was given to rats in the normal group and the model group by gastrogavage. Rats in the rest groups were perfused with isovolumic medication solution (10 mL/kg), six days per week for eight successive weeks. The dosage of drugs was adjusted according to the change of body weight. The VAF apoptosis rate of the thoracic aorta was measured by Annexin V-FITC combined with PI dyeing and flow cytometry. The protein expressions of thoracic aortic Bcl-2, Bax, c-Myc, c-Fos, FN, and LN were detected by immunohistochemical assay. The adventitial transforming growth factor beta1 (TGF-beta1) mRNA expression in the thoracic aorta was detected by in situ hybridization method. Compared with the model group, the tail arterial systolic pressure decreased, the VAF apoptosis and the protein expression of Bax increased, Bcl-2, c-Fos, FN, LN, and TGF-beta1 mRNA all decreased in the thoracic aorta of SHR in each treatment group after 4-and 8-week of intervention. Rhynchophylline, isorhynchophylline, and rhynchophylla alkaloids could inhibit the protein expression of c-Myc with statistical difference (Prhynchophylla alkaloids group (P>0.05). There was statistical difference in increased VAF apoptosis and decreased protein expressions of Bcl-2, c-Myc, and LN (Prhynchophylla alkaloids group (P>0.05). Rhynchophylline

The right choice of antihypertensives protects primary human hepatocytes from ethanol- and recombinant human TGF-β1-induced cellular damage

Directory of Open Access Journals (Sweden)

Ehnert S

2013-03-01

Full Text Available Sabrina Ehnert,1 Teresa Lukoschek,2 Anastasia Bachmann,2 Juan J Martínez Sánchez,1 Georg Damm,3 Natascha C Nussler,4 Stefan Pscherer,5 Ulrich Stöckle,1 Steven Dooley,2 Sebastian Mueller,6 Andreas K Nussler11Eberhard Karls Universität Tübingen, BG Trauma Center, Tübingen, Germany; 2Mol Hepatology - Alcohol Associated Diseases, Department of Medicine II, Medical Faculty, Mannheim, Germany; 3Department of General, Visceral, and Transplantation Surgery, Charité University Medicine, Berlin, Germany; 4Clinic for General, Visceral, Endocrine Surgery and Coloproctology, Clinic Neuperlach, Städtisches Klinikum München GmbH, Munich, Germany; 5Department of Diabetology, Klinikum Traunstein, Kliniken Südostbayern AG, Traunstein, Germany; 6Department of Medicine, Salem Medical Center, Ruprecht-Karls-Universität, Heidelberg, GermanyBackground: Patients with alcoholic liver disease (ALD often suffer from high blood pressure and rely on antihypertensive treatment. Certain antihypertensives may influence progression of chronic liver disease. Therefore, the aim of this study is to investigate the impact of the commonly used antihypertensives amlodipine, captopril, furosemide, metoprolol, propranolol, and spironolactone on alcohol-induced damage toward human hepatocytes (hHeps.Methods: hHeps were isolated by collagenase perfusion. Reactive oxygen species (ROS were measured by fluorescence-based assays. Cellular damage was determined by lactate-dehydrogenase (LDH-leakage. Expression analysis was performed by reverse-transcription polymerase chain reaction and Western blot. Transforming growth factor (TGF-β signaling was investigated by a Smad3/4-responsive luciferase-reporter assay.Results: Ethanol and TGF-β1 rapidly increased ROS in hHeps, causing a release of 40%–60% of total LDH after 72 hours. All antihypertensives dose dependently reduced ethanol-mediated oxidative stress and cellular damage. Similar results were observed for TGF-β1-dependent

Antimicrobial photodynamic activity and cytocompatibility of Au25(Capt18 clusters photoexcited by blue LED light irradiation

Directory of Open Access Journals (Sweden)

Miyata S

2017-04-01

Full Text Available Saori Miyata,1 Hirofumi Miyaji,1 Hideya Kawasaki,2 Masaki Yamamoto,2 Erika Nishida,1 Hiroko Takita,3 Tsukasa Akasaka,4 Natsumi Ushijima,3 Toshihiko Iwanaga,5 Tsutomu Sugaya1 1Department of Periodontology and Endodontology, Hokkaido University Graduate School of Dental Medicine, Kita-ku, Sapporo, 2Department of Chemistry and Materials Engineering, Faculty of Chemistry, Materials and Bioengineering, Kansai University, Suita-shi, Osaka, 3Support Section for Education and Research, Hokkaido University Graduate School of Dental Medicine, 4Department of Biomedical, Dental Materials and Engineering, Graduate School of Dental Medicine, Hokkaido University, 5Department of Anatomy, Laboratory of Histology and Cytology, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Japan Abstract: Antimicrobial photodynamic therapy (aPDT has beneficial effects in dental treatment. We applied captopril-protected gold (Au25(Capt18 clusters as a novel photosensitizer for aPDT. Photoexcited Au clusters under light irradiation generated singlet oxygen (1O2. Accordingly, the antimicrobial and cytotoxic effects of Au25(Capt18 clusters under dental blue light-emitting diode (LED irradiation were evaluated. 1O2 generation of Au25(Capt18 clusters under blue LED irradiation (420–460 nm was detected by a methotrexate (MTX probe. The antimicrobial effects of photoexcited Au clusters (0, 5, 50, and 500 µg/mL on oral bacterial cells, such as Streptococcus mutans, Aggregatibacter actinomycetemcomitans, and Porphyromonas gingivalis, were assessed by morphological observations and bacterial growth experiments. Cytotoxicity testing of Au clusters and blue LED irradiation was then performed against NIH3T3 and MC3T3-E1 cells. In addition, the biological performance of Au clusters (500 µg/mL was compared to an organic dye photosensitizer, methylene blue (MB; 10 and 100 µg/mL. We confirmed the 1O2 generation ability of Au25(Capt18 clusters through the fluorescence

Radioprotectors in Radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Nair, C.K.K. [Bhabha Atomic Research Centre, Mumbai (India); Parida, D.K.; Nomura, Taisei

2001-03-01

This review article focuses on clinically relevant radioprotectors and their mechanisms of radioprotection. Radiotherapy is the most common modality of human cancer therapy. Obtaining optimal results requires a judicious balance between the total dose of radiotherapy delivered and the threshold limit of critical surrounding normal tissues, and the normal tissues need to be protected against radiation injury to obtain better tumor control by using a higher dose. For this reason, radiation-protective agents play an important role in clinical radiotherapy. Radiation-protective agents can be classified into three groups: radioprotectors, adaptogens, and absorbents. The first group generally consists of sulfhydryl compounds and other antioxidants. They include several myelo-, entero-, and cerebro-protectors. Adaptogens act as promotors of radioresistance. They are natural protectors that offer chemical protection against low levels of ionizing radiation. Absorbents protect organs from internal radiation and chemicals. They include drugs that prevent incorporation of radioiodine by the thyroid gland and absorption of radionuclides. This article thoroughly describes the properties, mechanisms of action, and perspectives on clinical application of the following categories of radioprotectors: sulfhydryl compounds (e.g., cysteine, cysteamine, glutathione, AET, WR 2127, and other WR-compounds), antioxidants (e.g., tempace, Hoechst 33342, vitamin A, E, and C, TMG, melatonin), angiotensin-converting enzyme (ACE) inhibitors (e.g., captopril, elanopril, penicillamine, pentoxifylline, L-158, 809), cytoprotective agents (mesna, dexrazoxane, and amifostin), metalloelements (e.g., manganese chloride, cadmium salts, bismuth subnitrate), immunomodulators (gamma-interferon, polysaccharides AM5, AM218, heat-killed lactobacillus cells, broncho-vaxom, trehalose dicorynomycolate, and AS101), lipopolysaccharides and prostaglandins, plant extracts and compounds isolated from plants (curcmin

Corydalis hendersonii Hemsl. protects against myocardial injury by attenuating inflammation and fibrosis via NF-κB and JAK2-STAT3 signaling pathways.

Science.gov (United States)

Bai, Ruifeng; Yin, Xu; Feng, Xiao; Cao, Yuan; Wu, Yan; Zhu, Zhixiang; Li, Chun; Tu, Pengfei; Chai, Xingyun

2017-07-31

Corydalis hendersonii Hemsl. (CH) with heat clearing and detoxifying effects are well described in Tibetan folk medicine. It has been used for centuries in China largely for the treatment of high altitude polycythemia, a pathophysiological condition referred to "plethora" in Tibetan medicine, hypertension, hepatitis, edema, gastritis, and other infectious diseases. To investigate the cardioprotective effects of Corydalis hendersonii extract in an ICR mouse model of myocardial ischemic injury. Ethanol [85% (v/v)] extract of CH whole plant was prepared, and their chemical profile was analyzed with use of HPLC-DAD and IT-TOF-ESI-MS. A mouse model of AMI was established by ligation of the left ventricular dysfunction (LAD) coronary artery. Mice were randomly divided into six groups (n = 12 per group): sham group, model group, CH groups treated with three doses of CH (100, 200, and 400mg/kg, intragastric), and a positive control group (captopril, 16.67mg/kg, intragastric). Heart function was evaluated by measurement of ejection fraction (EF) and fractional shortening (FS) by echocardiography. Serum levels of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH), plasma levels of angiotensin II (AngII), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and expressions of matrix metalloproteinase-2 (MMP-2) and MMP-9 in the cardiac tissue homogenate, protein expressions of signal-transduction proteins, p65, IκBα, JAK2, and STAT3 in heart tissues were measured by ELISA and Western blot analyses. Inflammatory cell infiltration and changes in collagen deposition in the myocardial ischemic heart tissues were observed by histopathological examination. Platelet aggregation in vitro was also assessed. CH treatment showed a dose-dependent cardioprotective effect. It significantly reduced left ventricular end-diastolic diameter (LVEDd) and left ventricular end-diastolic diameter (LVEDs), improved EF and FS as compared to those in the model

Uso incorreto de medicamentos por pacientes após acidente vascular cerebral Uso incorrecto de medicamentos por pacientes después de un accidente cerebro vascular Incorrect use of medicines by patients post cerebrovascular accident

Directory of Open Access Journals (Sweden)

Lolita Dopico da Silva

2011-07-01

fueron: espironolactona, glibenclamida y atenolol (cada una con 100.0%, sinvastatina (87.5%, furosemida (83.3%, captropril (72.5% e insulina NPH (66.7%. Conclusión. Una gran proporción de pacientes después de un ACV usa incorrectamente los medicamentos prescritos para el tratamiento en el hogar.Objective. To evaluate how patients cerebrovascular accidents (CVA victims use their medicines at home. Methodology. Cross sectional study. A representative sample of 30 patients who received home care in the city of Rio de Janeiro (Brazil in 2008 was studied. Information about CVA risk factors and the medicines they were taking was collected using a structured interview to the patients, and the DRUGDEX® classification system was used to determine the correct or incorrect use of the medicines. Results. Participants were mostly elder women. The average of medicines per patient was of 3.3 medicines. The main reasons for mistaking were: taking medicines with food, and taking other medicines at the same time. The highest proportions of incorrect administration of medicines in more than 50% of the doses were: Spironolactone, glibenclamide, and atenolol (each of them with a 100.0%, simvastatin (87.5%, captopril (72.5% and NPH insulin (66.7%. Conclusion. A great proportion of patients after having suffered a CVA use their medicines prescribed for home treatment incorrectly.

Metabolismo de fármacos y lesión hepática

Directory of Open Access Journals (Sweden)

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