RESUMO

Environmental contamination by pharmaceuticals from industrial waste and anthropogenic activities poses adverse health effects on non-target organisms. We evaluated the neurobehavioral and biochemical responses accompanying exposure to ecological relevant concentrations of atenolol (0, 0.1, 1.0, and 10 µg/L) for seven uninterrupted days in adult zebrafish (Danio rerio). Atenolol-exposed fish exhibited anxiety-like behavior, characterized by significant bottom-dwelling with marked reduction in vertical exploration. Atenolol-exposed fish exhibited marked increase in the duration and frequency of aggressive events without altering their preference for conspecifics. Biochemical data using brain samples indicated that atenolol disrupted antioxidant enzyme activities and induced oxidative stress. Exposure to atenolol markedly decreased ATP and AMP hydrolysis without affecting ADP hydrolysis and acetylcholinesterase (AChE) activity. Atenolol significantly upregulated tryptophan hydroxylase 1 (tph1) mRNA expression but downregulated brain-derived neurotrophic factor (bdnf) mRNA. Collectively, waterborne atenolol elicits aggressive and anxiety-like responses in adult zebrafish, accompanied by oxidative stress, reduced nucleotide hydrolysis, altered tph1 and bdnf mRNA expression, which may impact the survival and health of fish in aquatic environment.

Assuntos

RESUMO

Introduction: Infantile hemangioma is the most frequent benign vascular tumor in childhood, with an incidence of 3 to 10%. When patients require treatment, oral propranolol, a non-selective lipophilic beta-blocker, is usually considered the therapy of choice. However, its use has been associated with several adverse events related to its ß-2 action and its ability to cross the blood-brain barrier. Because of this, oral atenolol, a hydrophilic ß-1 receptor-selective beta-blocker, may represent a valid treatment alternative. Nonetheless, there is still controversy regarding the efficacy and safety of atenolol when compared with propranolol as monotherapy for this condition. Methods: We searched Epistemonikos, the largest database of systematic reviews in health science, which is maintained by screening multiple sources of information, including MEDLINE/PubMed, EMBASE, and Cochrane, among others. Data were extracted from the identified reviews, data from the primary studies were analyzed, a meta-analysis was performed, and a summary table of the results was prepared using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. Results: Nine systematic reviews were identified, including 10 primary studies and three randomized trials. The three randomized trials were included in the analysis of this investigation. Conclusion: The use of oral atenolol compared with oral propranolol as monotherapies may result in little or no difference in terms of likelihood of complete remission, decrease in Hemangioma Activity Score, likelihood of post-treatment relapse, and risk of adverse events and severe adverse events, in infantile hemangioma (low certainty of evidence).

Introducción: El hemangioma infantil corresponde al tumor vascular benigno más frecuente de la infancia, con una incidencia de 3 a 10%. Entre los pacientes que requieren tratamiento el uso oral de propranolol, un betabloqueador no selectivo de tipo lipofílico, es usualmente considerado como la terapia de elección. Sin embargo, su uso se ha asociado a diversos efectos adversos, relacionados con su acción ß-2, y a su capacidad de cruzar la barrera hematoencefálica. Debido a esto, el uso oral de atenolol, un betabloqueador selectivo de receptores ß-1, de tipo hidrofílico, podría representar una alternativa válida de tratamiento. Sin embargo, aún existe controversia en relación con la eficacia y seguridad del tratamiento con atenolol como monoterapia, en comparación con el uso de propranolol como monoterapia para esta condición. Métodos: Se realizó una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el tamizaje de múltiples fuentes de información, incluyendo MEDLINE/PubMed, EMBASE, Cochrane, entre otras. Se extrajeron los datos desde las revisiones identificadas, se analizaron los datos de los estudios primarios, se realizó un metanálisis y se preparó una tabla de resumen de los resultados utilizando el método GRADE. Resultados: Se identificaron nueve revisiones sistemáticas, que en conjunto incluyeron 10 estudios primarios y tres ensayos aleatorizados. Se incluyeron los tres ensayos aleatorizados en el análisis del presente trabajo. Conclusiones: El uso de atenolol oral como monoterapia, comparado con el uso de propranolol oral como monoterapia, podría resultar en poca o nula diferencia en cuanto a la probabilidad de remisión completa, la disminución del , la probabilidad de recaída posterior al tratamiento y el riesgo de presentar efectos adversos y efectos adversos severos, en el hemangioma infantil (certeza de la evidencia baja).

Assuntos

RESUMO

INTRODUCCIÓN: El hemangioma infantil corresponde al tumor vascular benigno más frecuente de la infancia, con una incidencia de 3 a 10%. Entre los pacientes que requieren tratamiento el uso oral de propranolol, un betabloqueador no selectivo de tipo lipofílico, es usualmente considerado como la terapia de elección. Sin embargo, su uso se ha asociado a diversos efectos adversos, relacionados con su acción ß-2, y a su capacidad de cruzar la barrera hematoencefálica. Debido a esto, el uso oral de atenolol, un betabloqueador selectivo de receptores ß-1, de tipo hidrofílico, podría representar una alternativa válida de tratamiento. Sin embargo, aún existe controversia en relación con la eficacia y seguridad del tratamiento con atenolol como monoterapia, en comparación con el uso de propranolol como monoterapia para esta condición. MÉTODOS: Se realizó una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el tamizaje de múltiples fuentes de información, incluyendo MEDLINE/PubMed, EMBASE, Cochrane, entre otras. Se extrajeron los datos desde las revisiones identificadas, se analizaron los datos de los estudios primarios, se realizó un metanálisis y se preparó una tabla de resumen de los resultados utilizando el método , GRADE. RESULTADOS: Se identificaron nueve revisiones sistemáticas, que en conjunto incluyeron 10 estudios primarios y tres ensayos aleatorizados. Se incluyeron los tres ensayos aleatorizados en el análisis del presente trabajo. CONCLUSIONES: El uso de atenolol oral como monoterapia, comparado con el uso de propranolol oral como monoterapia, podría resultar en poca o nula diferencia en cuanto a la probabilidad de remisión completa, la disminución del , la probabilidad de recaída posterior al tratamiento y el riesgo de presentar efectos adversos y efectos adversos severos, en el hemangioma infantil (certeza de la evidencia baja).

INTRODUCTION: Infantile hemangioma is the most frequent benign vascular tumor in childhood, with an incidence of 3 to 10%. When patients require treatment, oral propranolol, a non-selective lipophilic beta-blocker, is usually considered the therapy of choice. However, its use has been associated with several adverse events related to its ß-2 action and its ability to cross the blood-brain barrier. Because of this, oral atenolol, a hydrophilic ß-1 receptor-selective beta-blocker, may represent a valid treatment alternative. Nonetheless, there is still controversy regarding the efficacy and safety of atenolol when compared with propranolol as monotherapy for this condition. METHODS: We searched Epistemonikos, the largest database of systematic reviews in health science, which is maintained by screening multiple sources of information, including MEDLINE/PubMed, EMBASE, and Cochrane, among others. Data were extracted from the identified reviews, data from the primary studies were analyzed, a meta-analysis was performed, and a summary table of the results was prepared using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. RESULTS: Nine systematic reviews were identified, including 10 primary studies and three randomized trials. The three randomized trials were included in the analysis of this investigation. CONCLUSION: The use of oral atenolol compared with oral propranolol as monotherapies may result in little or no difference in terms of likelihood of complete remission, decrease in Hemangioma Activity Score, likelihood of post-treatment relapse, and risk of adverse events and severe adverse events, in infantile hemangioma (low certainty of evidence).

Assuntos

RESUMO

BACKGROUND: 6-nitrodopamine released from rat isolated atria exerts positive chronotropic action, being more potent than noradrenaline, adrenaline, and dopamine. Here, we determined whether 6-nitrodopamine is released from rat isolated ventricles (RIV) and modulates heart inotropism. METHODS: Catecholamines released from RIV were quantified by LC-MS/MS and their effects on heart inotropism were evaluated by measuring left ventricular developed pressure (LVDP) in Langendorff's preparation. RESULTS: 6-nitrodopamine was the major released catecholamine from RIV. Incubation with L-NAME (100 µM), but not with tetrodotoxin (1 µM), caused a significant reduction in 6-nitrodopamine basal release. 6-nitrodopamine release was significantly reduced in ventricles obtained from L-NAME chronically treated animals. 6-nitrodopamine (0.01 pmol) caused significant increases in LVDP and dP/dtmax, whereas dopamine and noradrenaline required 10 pmol, and adrenaline required 100 pmol, to induce similar increases in LVDP and dP/dtmax. The infusion of atenolol (10 nM) reduced basal LVDP and blocked the increases in LVDP induced by 6-ND (0.01 pmol), without affecting the increases in LVDP induced by 10 nmol of dopamine and noradrenaline and that induced by adrenaline (100 nmol). CONCLUSIONS: 6-nitrodopamine is the major catecholamine released from rat isolated ventricles. It is 1000 times more potent than dopamine and noradrenaline and is selectively blocked by atenolol, indicating that 6-ND is a main regulator of heart inotropism.

RESUMO

Nebivolol could prevent dysfunction in patients suffering myocardial ischemia. However, influence of hyperthyroidism is not known. Consequences and mechanisms of nebivolol treatment were investigated in isolated hearts from euthyroid (EuT) and hyperthyroid (HpT) rats. Rats were orally treated during 1 week with 20 mg/kg/day nebivolol (O-Neb), 30 mg/kg/day atenolol (O-Ate), or not treated (C). Isolated perfused hearts were exposed to global ischemia and reperfusion (I/R) inside a flow calorimeter. Left diastolic ventricular pressure, developed contractile pressure (P), and total heat rate (Ht) were continuously measured, while infarct size was measured after 2-h R. EuT-C and HpT-C hearts developed similarly low post-ischemic contractile recovery and economy (P/Ht). Nebivolol totally prevented dysfunction and reduced infarction size in EuT hearts, but partially improved recovery in HpT rat hearts. Contrarily, oral atenolol totally prevented dysfunction in HpT hearts but partially in EuT hearts. Nebivolol effects were reversed by perfusing L-NAME in both conditions, but partially reduced by aminoguanidine in HpT. However, L-NAME increased P and P/Ht recoveries in EuT-C and HpT-C rat hearts, as well as melatonin. Oral nebivolol prevented post-ischemic dysfunction and infarction in EuT hearts due to adrenergic ß1 blockade and activation of iNOS and/or eNOS, but the effect was attenuated in HpT hearts by excessive iNOS-dependent nitrosative pathways.

RESUMO

Introducción: La hipertensión perioperatoria constituye una de las principales alteraciones detectadas durante la colecistectomía video endoscópica. Se presume del efecto protector que tiene el atenolol con su acción beta bloqueadora en reducir esta condición morbosa. Objetivo: Evaluar la eficacia del atenolol en prevenir la hipertensión perioperatoria durante la colecistectomía video endoscópica en la unidad quirúrgica del Hospital Clínico Quirúrgico "Lucía Íñiguez Landín" de Holguín Método: Se realizó un estudio observacional, analítico, longitudinal y prospectivo de tipo cohorte con dos grupos paralelos de estudio, uno de tratamiento y un grupo control, desde enero a diciembre de 2018. El universo estuvo constituido por los 697 pacientes (N=697) atendidos en la consulta de evaluación preoperatoria y se tomó como muestra a 183 hipertensos (n=183) que se operaron por cirugía video endoscópica de litiasis vesicular, de ellos aleatorizados 95 al grupo de tratamiento con atenolol y 88 al grupo control. A los pacientes del grupo tratamiento se les administró atenolol 25 mg diarios durante 15 días antes de la cirugía. Las variables principales que se monitorizaron fueron las presiones arteriales sistólica, diastólica y media, y se emplearon indicadores para evaluar la efectividad del tratamiento. Resultados: Las presiones arteriales preoperatorias disminuyeron de forma significativa en el grupo de tratamiento con atenolol. La hipertensión perioperatoria fue más frecuente en el grupo control. El atenolol es un bloqueador selectivo de los receptores beta 1, ejerce su efecto hipotensor a nivel central al deprimir los centros cardiovasculares simpáticos como el vasomotor bulbar. Conclusiones: El tratamiento con atenolol fue eficaz en reducir la incidencia de hipertensión perioperatoria.

Introduction: Perioperative hypertension represents one of the leading alterations detected performing endoscopic cholecystectomy. It is presumed that atenolol has a protective effect able to reduce this morbid condition, likely due to its beta-blocking action. Objective: To assess the efficacy of atenolol on preventing perioperative hypertension performing laparoscopic cholecystectomy in the surgical unit of the Hospital Clínico Quirúrgico "Lucía Íñiguez Landín" of Holguín. Method: An observational, analytical, longitudinal and prospective cohort study was conducted with two study groups at the same time, experimental group and control group, from January to December, 2018. A total of 697 patients (N=697) evaluated in the preoperative consultation were involved in the study, the sample included 183 hypertensive patients (n=183) who underwent endoscopic surgery for gallbladder lithiasis, of whom 95 were randomized to the atenolol treatment group and 88 to the control group. Patients in the treatment group were administered atenolol at 25 mg daily for 15 days before surgery. Leading variables used were systolic, diastolic and mean arterial pressures, and specific indicators were used to evaluate treatment effectiveness. Results: Preoperative arterial pressures decreased significantly with the use of atenolol in the treatment group. Perioperative hypertension was more frequent in the control group. Atenolol is a selective beta 1 receptor blocker, who causes a hypertensive effects in the central level, depressing the bulbar vasomotor center. Conclusions: The results of this investigation show that the use of atenolol in treatment was an effective alternative, thus effectiveness reduce perioperative hypertension rate.

Introdução: A hipertensão perioperatória é uma das principais alterações detectadas durante a colecistectomia videoendoscópica. Presume-se o efeito protetor que o atenolol tem com sua ação betabloqueadora na redução dessa condição mórbida. Objetivo: Avaliar a eficácia do atenolol na prevenção da hipertensão perioperatória durante a colecistectomia videoendoscópica na unidade cirúrgica do Hospital Clínico Quirúrgico "Lucía Íñiguez Landín" of Holguín. Método: Foi realizado um estudo de coorte observacional, analítico, longitudinal e prospectivo com dois estudos paralelos grupos, um para tratamento e um grupo controle, de janeiro a dezembro de 2018. O universo foi composto por 697 pacientes (N=697) atendidos na consulta de avaliação pré-operatória e 183 pacientes hipertensos (n=183) foram tomados como amostra submetidos à videocirurgia para litíase biliar, dos quais 95 foram randomizados para o grupo tratamento com atenolol e 88 para o grupo controle. Os pacientes do grupo de tratamento receberam atenolol 25 mg diariamente por 15 dias antes da cirurgia. As principais variáveis monitoradas foram a pressão arterial sistólica, diastólica e média, e indicadores foram usados para avaliar a eficácia do tratamento. Resultados: A pressão arterial pré-operatória diminuiu significativamente no grupo de tratamento com atenolol. A hipertensão perioperatória foi mais frequente no grupo controle. O atenolol é um bloqueador seletivo dos receptores beta 1, exerce seu efeito hipotensor em nível central deprimindo os centros cardiovasculares simpáticos, como o vasomotor bulbar. Conclusões: O tratamento com atenolol foi eficaz na redução da incidência de hipertensão perioperatória.

RESUMO

Human performance enhancing drugs (PEDs), frequently used in sport competitions, are strictly prohibited by the World Anti-Doping Agency (WADA). Biological samples collected from athletes and regular patients are continuously tested regarding the identification and/or quantification of the banned substances. Current work is focused on the application of a new analytical method, molecularly imprinted nanoparticles (nanoMIPs), to detect and determine concentrations of certain prohibited drugs, such as ß-blockers, in water and human urine samples. These medications are used in the treatment of cardiovascular conditions, negative effects of adrenaline (helping to relief stress), and hypertension (slowing down the pulse and softening the arteries). They can also significantly increase muscle relaxation and improve heart efficiency. The new method of the detection and quantification of ß-blockers is based on synthesis, characterization, and implementation of nanoMIPs (so-called plastic antibodies). It offers numerous advantages over the traditional methods, including high binding capacity, affinity, and selectivity for target molecules. Additionally, the whole process is less complicated, cheaper, and better controlled. The size and shape of the nanoMIPs is evaluated by dynamic light scattering (DLS) and transmission electron microscope (TEM). The affinity and selectivity of the nanoparticles are investigated by competitive pseudo enzyme-linked immunosorbent assay (pseudo-ELISA) similar to common immunoassays employing natural antibodies. To provide reliable results towards either doping detection or therapeutic monitoring using the minimal invasive method, the qualitative and quantitative analysis of these drugs is performed in water and human urine samples. It is demonstrated that the assay can detect ß-blockers in water within the linear range 1 nmol·L-1-1 mmol·L-1 for atenolol with the detection limit 50.6 ng mL-1, and the linear range 1 mmol·L-1-10 mmol·L-1 for labetalol with the detection limit of 90.5 ng·mL-1. In human urine samples, the linear range is recorded in the concentration range 0.1 mmol·L-1-10 nmol·L-1 for atenolol and 1 mmol·L-1-10 nmol·L-1 for labetalol with a detection limit of 61.0 ng·mL-1 for atenolol and 99.4 ng·mL-1 for labetalol.

RESUMO

The purpose of this work was to investigate, via DFT calculations, the molecularly imprinted polymer (MIP) for atenolol (ATL) ß-blocker evaluating distinct functional monomers (FMs), solvents, and cross-linker agents (CLAs). As the main result, we could determine from structural and thermodynamic data the best MIP synthesis protocol as being: p-vinyl benzoic acid (APV) as FM, toluene as solvent, and pentaerythritol triacrylate (PETRA) as CLA. We believe this rational design can be very useful for experimentalists in an attempt to perform an efficient synthesis of a MIP for this important ß-blocker drug.

Assuntos

RESUMO

Nanofiltration has been shown to be effective in removing pharmaceutical compounds from water and wastewater, so different mechanisms can influence treatment performance. In the present work, we carried out a case study evaluating the performance of two nanofiltration membranes in the removal of Atenolol (ATN)-a pharmaceutical compound widely used for the treatment of arterial hypertension-under different conditions such as operating pressure, ATN concentration, and solution pH. By determining the B parameter, which quantifies the solute/membrane affinity, we verified that the solution pH influenced the performance of the membranes, promoting attraction or repulsion between the ATN and the membranes. At pH 2.5, both membranes and ATN were positively charged, causing electrostatic repulsion, showing lower values of the B parameter and, consequently, higher ATN rejections. At such a pH, the mean ATN rejection for the loose membrane (NF270) was 82%, while for the tight membrane (NF90) it was 88%. On the other hand, at 12 bar pressure, the NF70 membrane (5.1 × 10 -5 m s-1) presented mean permeate fluxes about 2.8 times greater than the NF90 membrane (1.8 × 10-5 m s-1), indicating that NF270 is the most suitable membrane for this application.

RESUMO

ß-Adrenergic blockers are no longer recommended as first-line therapy due to the reduced cardioprotection of traditional ß-blockers compared with other antihypertensive drugs. It is unknown whether third-generation ß-blockers share the limitations of traditional ß-blockers. The aim of the present study was to compare the effects of nebivolol or atenolol on central and peripheral systolic blood pressure (SBP) and its variability and target organ damage (TOD) in N-nitro-L-arginine methyl ester (L-NAME) hypertensive rats. Male Wistar rats were treated with L-NAME for 8 weeks together with oral administration of nebivolol 30 mg/kg (n = 8), atenolol 90 mg/kg (n = 8), or vehicle (n = 8). The control group was composed of vehicle-treated Wistar rats. SBP and its variability, as well as echocardiographic parameters, were assessed during the last 2 weeks of treatment. Tissue levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and transforming growth factor ß (TGF-ß), and histopathological parameters were evaluated in the left ventricle and aorta. Nebivolol had a greater ability than atenolol to decrease central SBP and mid-term and short-term blood pressure variability (BPV) in L-NAME rats. Echocardiographic analysis showed that nebivolol was more effective than atenolol on E/A wave ratio normalization. Compared with atenolol treatment, nebivolol had a greater protective effect on different TOD markers, inducing a decrease in collagen deposition and a reduction in the proinflammatory cytokines IL-6 and TNF-α in the left ventricle and aorta. Our findings suggest that the adverse hemodynamic profile and the reduced cardiovascular protection reported with traditional ß-blockers must not be carried forward to third-generation ß-blockers.

Assuntos