The role of atenolol in the modulation of the expression of genes encoding pro- (caspase-1) and anti- (Bcl2L1) apoptotic proteins in endothelial cells exposed to intestinal ischemia and reperfusion in rats

Purpose:To investigate the role of atenolol in the gene expression of caspase 1 (Casp1) and Bcl2L1 on vascular endothelium of rat intestine after ischemia and reperfusion (IR).Methods:Eighteen adult male Wistar rats were randomly divided into 3 groups (n=6): SG (Sham group): no clamping of the superior mesenteric artery; IRG: IR plus saline group: IRG+At: IR plus Atenolol group. Rats from IRG and IRG+At were subjected to 60 min of intestinal ischemia and 120 min of reperfusion. Atenolol (2mg/kg) or saline were injected in the femoral vein 5 min before ischemia, 5 min and 55 min after reperfusion. Thereafter, intestinal segments were appropriately removed and processed for Endothelial Cell Biology Rat RT2 Profiler PCR Array.Results:the anti-apoptotic Bcl2L1 gene expression was significantly down-regulated (-1.10) in the IRG and significantly up-regulated in the IRG+At (+14.15). Meanwhile, despite Casp1 gene expression was upregulated in both groups, it was significantly higher in the IRG (+35.06) than the IRG+At (+6.68).Conclusions:Atenolol presents antiapoptotic effects on rat intestine subjected to IR partly by the up-regulation of the anti-apoptotic Bcl2L1 gene expression. Moreover, atenolol can mitigate the pro-apoptotic and pro-inflammatory effects of Casp1 gene on rat intestine after IR.(AU)

Human pharmaceuticals in wastewaters from urbanized areas of Argentina.

The study contributes with a first survey of pharmaceuticals in municipal wastewaters discharging into fresh and estuarine waters from areas with varying degrees of urbanization of Argentina. Analyses were done on the soluble fraction by HPLC-MS after SPE extraction. In all of the samples were detected caffeine and ibuprofen within the range of 0.9-44.2 and 0.4-13.0 µg/L, and lower levels of carbamazepine, atenolol and diclofenac between 0.2-2.3, 0.2-1.7 and <0.03-1.2 µg/L, respectively. Profiles of compounds were similar in all studied locations.

Avaliação comparativa em longo prazo da eficácia, tolerabilidade e efeitos metabólicos de combinações de atenolol com anlodipino ou clortalidona no tratamento da hipertensão arterial ? subanálise do estudo ATENAS / Comparative evaluation in the long range of the efficacy, tolerability and metabolic effects of combinations of atenolol with amlodipine or chlorthalidone in the treatment of hypertension ? sub-analysis of ATENAS study

Em estudo multicêntrico, aberto, randomizado e comparativo (estudo ATENAS) foi avaliado no período de extensão (da 12ª a 48ª semanas) a eficácia anti-hipertensiva, a tolerabilidade, a segurança e o impacto sobre a sensibilidade à insulina da combinação galênica única de atenolol 25 a 50 mg e anlodipino 5 mg comparada à combinação livre de atenolol 50 a 100 mg com clortalidona 12,5 a 25 mg em hipertensos primários estágios 1 e 2. Observamos que a combinação de atenolol e anlodipino é segura, bem tolerada e proporciona em longo prazo maiores reduções da pressão arterial que o tratamento com a combinação de atenolol e clortalidona. A maior redução da pressão arterial permitiu que maior percentual de pacientes tivesse a pressão arterial controlada tanto para o critério de PAD < 90 mmHg (87,7% a 95,9%) quanto para PAD £ 85 mmHg (69,9% a 90,2%). Menor incidência de bradicardia, cefaleia, alterações lipídicas e glicêmicas foram relatadas nos pacientes tratados com a combinação de atenolol e anlodipino. A incidência de edema de membros inferiores neste grupo (6,1%) foi menor que a relatada na literatura para mesma dose de anlodipino em monoterapia. O tratamento com atenolol combinado com o anlodipino não alterou a sensibilidade à insulina. Concluindo, a combinação em formulação galênica única de atenolol e anlodipino em doses baixas a medianas constitui boa opção terapêutica da hipertensão arterial primária estágio 1 e 2 em longo prazo, é superior à combinação de atenolol e clortalidona, sendo opção preferencial para pacientes hipertensos com doença arterial coronariana.

Determination of atenolol by the micelle-stabilized room-temperature phosphorescence methodology.

A micellar-stabilized room-temperature phosphorescence (MS-RTP) method for the determination of atenolol has been developed in micellar solutions of sodium dodecylsulphate (SDS) in the presence of thallium(I) as a heavy atom and sodium sulphite as an oxygen scavenger. The effects of thallium(I) nitrate, SDS and sodium sulphite concentrations on atenolol MS-RTP intensity were studied. Optimized conditions to obtain maximum sensitivity were 0.015 mol/L thallium(I) nitrate, 0.1 mol/L SDS and 0.0075 mol/L sodium sulphite. The maximum phosphorescence signal was completely developed in 10 min and the intensity was measured at lambda(ex) = 272 nm and lambda(em) = 412 nm. The linear range of application obtained was 2.01-16.00 microg/mL. The detection limit estimated from the least-squares regression analysis was 0.86 microg/mL and the relative standard deviation of 10 replicates was 1.7%. The proposed method was applied to the determination of atenolol in a pharmaceutical formulation. The quantitation was carried out by means of standard calibration, standard-additions calibration and Youden calibration. These three experiments were necessary to evaluate the presence of constant and proportional errors due to the matrix.

Chemometric determination of amiloride hydrochloride, atenolol, hydrochlorothiazide and timolol maleate in synthetic mixtures and pharmaceutical formulations.

Different chemometric methods such as classical least squares (CLS), principal components regression (PCR) and partial least squares with one dependent variable (PLS-1) applied on UV spectral data (0 D) and on their first derivatives (1 D) were evaluated for the simultaneous quantification of samples containing mixtures of amiloride hydrochloride, atenolol, hydrochlorothiazide and timolol maleate. Their performances were compared by means of ANOVA tests, which evidenced that 0 D-PCR, 0D-PLS-1, 1D-PCR, 1D-PLS-1, were reproducible and gave statistically similar results, while 0 D-CLS and 1D-CLS displayed higher variances than the former and failed to comply with the Levene's variance homogeneity test at different stages of the method comparison and validation process. The four statistically equivalent procedures were successfully applied to the analysis of synthetic samples with two to four analytes and to commercial tablet preparations containing amiloride hydrochloride and hydrochlorothiazide alone or in association with atenolol or timolol maleate.

Chemometrics-assisted simultaneous determination of atenolol and chlorthalidone in synthetic binary mixtures and pharmaceutical dosage forms.

Resolution of binary mixtures of atenolol (ATE) and chlorthalidone (CTD) with minimum sample pre-treatment and without analyte separation has been successfully achieved, using a new and rapid method based on partial least squares (PLS1) analysis of UV spectral data. The simultaneous determination of both analytes was possible by PLS1 processing of sample absorbances between 255 and 300 nm for ATE and evaluation of absorbances in the 253-268 nm region for CTD. The mean recoveries for synthetic samples were 100.3 +/- 1.0% and 100.7 +/- 0.7% for ATE and CTD, respectively. Application of the proposed method to two commercial tablet preparations in the content uniformity test showed them to contain 103.5 +/- 0.8% and 104.9 +/- 1.8% ATE respectively, as well as 103.4 +/- 1.2% and 104.5 +/- 2.2% CTD. Use of this method also allowed the elaboration of dissolution profiles of the drugs in two commercial combined formulation products, through the simultaneous determination of both drugs during the dissolution test. At the dissolution time of 45 min specified by USP XXIV, both pharmaceutical formulations complied with the test.

Enantioselective analysis of atenolol in biologic fluids: comparison of liquid-liquid and solid-phase extraction methods.

In this study we evaluated a liquid-liquid extraction procedure and a solid-phase extraction procedure for sample preparation for the enantioselective analysis of atenolol in plasma and urine by high-performance liquid chromatography. A Chiralcel OD-H column was used for the resolution of atenolol enantiomers with hexane-ethanol (85:15, v/v) plus 0.1% diethylamine as the mobile phase. In the liquid-liquid extraction procedure, atenolol was extracted from alkalinized body fluids with 5 ml chloroform-2-propanol (4:1, v/v). In the solid-phase extraction procedure, atenolol was isolated from plasma using a C8 column and methanol. Both extraction procedures were efficient in recovering atenolol and removing endogenous interferents. The RSDs and deviation from nominal values were lower than 10% for both within-day and between-day assays. The results show that there were no statistically significant differences in between-day variation. The t-test showed that there were no significant differences between the real concentrations and the determined concentrations. The limit of quantitation was 10 ng/ml and the linear range was 10-5,000 ng/ml for both methods. These methods can be used in pharmacokinetic studies.

Development and validation of a chiral liquid chromatographic method for the determination of atenolol and metoprolol enantiomers in tablet preparations.

Atenolol (AT) and metoprolol (MT) are predominantly used in the treatment of angina pectoris, certain arrhythmias, systemic hypertension, and several other cardiovascular disorders. Both compounds are produced commercially in the racemic form, although the S-form is responsible for the desired biological effect. This paper describes a simple, rapid, precise, and accurate method for separating the enantiomers of AT and MT. AT isomers are separated by using a Chiralcel OD column (250 x 4.6 mm, 10 microm), hexane-ethanoldiethylamine-acetic acid (60 + 40 + 0.2 + 0.2, v/v/v/v) as the mobile phase, and a flow rate of 1.0 mL/min. MT isomers are separated by using a mobile phase with the same components in the following proportions (40 + 60 + 0.2 + 0.2, v/v/v/v) and a flow rate of 0.8 mL/min. Ultraviolet detection was at 276 nm for both analytes. The coefficients of variation (CVs) and average recoveries (ARs) for the R-enantiomers in samples A, B, C, D, and E were 1.15 and 101.06%, 0.74 and 99.25%, 1.05 and 102.57%, 0.84 and 101.57%, and 0.86 and 98.62%, respectively. The CVs and ARs for the S-enantiomers in samples A, B, C, D, and E were 1.33 and 98.87%, 0.99 and 100.76%, 1.17 and 101.69%, 1.26 and 100.39%, and 1.40 and 99.39%, respectively. The standard curves of R-AT, S-AT, R-MT, and S-MT showed good linearity over the concentration range studied with correlation coefficients of 0.9991, 0.998, 0.9988, and 0.999, respectively.