Participation of COX-1 and COX-2 in the contractile effect of phenylephrine in prepubescent and old rats.

Vascular reactivity can be influenced by the vascular region, animal age, and pathologies present. Prostaglandins (produced by COX-1 and COX-2) play an important role in the contractile response to phenylephrine in the abdominal aorta of young rats. Although these COXs are found in many tissues, their distribution and role in vascular reactivity are not clear. At a vascular level, they take part in the homeostasis functions involved in many physiological and pathologic processes (e.g., arterial pressure and inflammatory processes). The aim of this study was to analyze changes in the contractile response to phenylephrine of thoracic/abdominal aorta and the coronary artery during aging in rats. Three groups of rats were formed and sacrificed at three distinct ages: prepubescent, young and old adult. The results suggest that there is a higher participation of prostanoids in the contractile effect of phenylephrine in pre-pubescent rats, and a lower participation of the same in old rats. Contrarily, there seems to be a higher participation of prostanoids in the contractile response of the coronary artery of older than pre-pubescent rats. Considering that the changes in the expression of COX-2 were similar for the three age groups and the two tissues tested, and that expression of COX-1 is apparently greater in older rats, COX-1 and COX-2 may lose functionality in relation to their corresponding receptors during aging in rats.

Insights on the role of boron containing moieties in the design of new potent and efficient agonists targeting the ß2 adrenoceptor.

The development of ß2 adrenoceptor (ß2AR) agonists is of increasing interest because of their wide-ranging applications in medicine, particularly for the treatment of pulmonary diseases. Regarding the relaxation of smooth muscle that lines airways of mammals, some boron-containing adducts have demonstrated greater potency and efficacy compared to well-known boron-free compounds. We herein report the design and synthesis as well as the chemical and pharmacological characterization of a new boron-containing compound: ((R)-6-((S)-2-(tert-butylammonio)-1-hydroxyethyl)-2-hydroxy-2-isobutyl-4H-benzo[d][1,3,2] dioxaborinin-2-uide). Compared to its precursor (salbutamol), this compound induced relaxation of smooth muscle in guinea pig tracheal rings with greater potency and efficacy (EC50⩽28.02nM). Theoretical studies suggest the potential selectivity of this boron containing compound on the orthosteric site of beta adrenoceptors and/or signaling pathways, as well as the importance of the tetracoordinated boron atom in its structure for binding recognition properties.

[Peak expiratory flow vs. spirometry for the diagnosis of asthma in adults]. / Flujometría versus espirometría para el diagnóstico de asma en adultos.

BACKGROUND: The diagnosis of asthma is confirmed with a spirometry: FEV1 ratio (forced expiratory volume in one second)/FVC (forced vital capacity) <80% with reversibility (FEV1 >12% or 200 mL) after using salbutamol. The peak expiratory flow is cheap and easy to use; it measures the forced expiratory flow, of which reversibility > 20% suggests asthma. OBJECTIVE: To know the sensitivity, specificity, and the positive and negative predictive values of the flowmeter. METHODS: A cross-sectional, observational, comparative study. Individuals aged >18 years without contraindications for spirometry were included. They underwent spirometry and peak expiratory flow, and the ACT (Asthma Control Test) questionnaire was applied to them. Sensitivity, specificity, positive predictive value and negative predictive value of the flowmetry were calculated. ROC curve was carried out in order to know the cut-off point of greater sensitivity and specificity. RESULTS: Of 150 patients, 66% were male; the median age was 38 years. According to the guidelines of GINA 2018 (Global Initiative for Asthma); 58.7% were controlled. The sensitivity of the peak expiratory flow was 47%, and the specificity was 87%, with a positive predictive value of 54.8% and a negative predictive value of 84%. The peak expiratory flow showed higher specificity with FEV1 <59%. The cut-off point of greater sensitivity and specificity was a reversibility of 8%, with an area under the curve of 0.70. CONCLUSIONS: The flowmeter has got greater sensitivity in airway obstructions; it is useful when a spirometer is not available.

Antecedentes: El diagnóstico de asma se confirma con espirometría: VEF1 (volumen espiratorio forzado del primer segundo)/CVF (capacidad vital forzada) < 80 %, con reversibilidad (VEF1 >12 % o 200 mL) tras utilizar salbutamol. El flujómetro es barato y fácil de utilizar, mide el flujo espiratorio forzado, cuya reversibilidad > 20 % sugiere asma. Objetivo: Conocer sensibilidad, especificidad y valores predictivos positivos y negativo del flujómetro. Métodos: Estudio transversal, observacional, comparativo. Se incluyó a individuos > 18 años sin contraindicaciones para espirometría, quienes fueron sometidos a espirometría y flujometría y se les aplicó el Asthma Control Test. Se calculó sensibilidad, especificidad y valores predictivos positivo y negativo de la flujometría. Se realizó curva ROC para conocer el punto de corte de mayor sensibilidad y especificidad. Resultados: De 150 pacientes, 66 % fue del sexo masculino; la mediana de edad fue de 38 años. Conforme los criterios de Global Initiative for Asthma 2018, 58.7 % estaba controlado. La sensibilidad de la flujometría fue de 47 %, la especificidad de 87 %, valor predictivo positivo de 54.8 % y negativo de 84 %. La flujometría mostró mayor especificidad con VEF1 < 59 %. El punto de corte de mayor sensibilidad y especificidad fue una reversibilidad de 8 %, con área bajo la curva de 0.70. Conclusiones: El flujómetro tiene mayor sensibilidad en obstrucciones de vía aérea; es de utilidad cuando no se cuenta con un espirómetro.

Effects of Allicin on Hypertension and Cardiac Function in Chronic Kidney Disease.

This work was performed to study the effect of allicin on hypertension and cardiac function in a rat model of CKD. The groups were control, CKD (5/6 nephrectomy), and CKD-allicin treated (CKDA) (40 mg/kg day/p.o.). Blood pressure was monitored (weekly/6 weeks). The cardiac function, vascular response to angiotensin II, oxidative stress, and heart morphometric parameters were determined. The CKD group showed hypertension and proteinuria. The coronary perfusion and left ventricular pressures were decreased in CKD group. In contrast, the vascular response to angiotensin II and expression of angiotensin II type 1 receptor (AT1R) were increased. These data were associated with the increment in morphometric parameters (weight of heart and left ventricle, heart/BW and left ventricular mass index, and wall thickness). Concurrently, the oxidative stress was increased and correlated inversely with the expression of Nrf2, Keap1, and antioxidant enzymes Nrf2-regulated. Allicin treatment attenuated hypertension and improved the renal and the cardiac dysfunctions; furthermore, it decreased the vascular reactivity to angiotensin II, AT1R overexpression, and preserved morphometric parameters. Allicin also downregulated Keap1 and increased Nrf2 expression, upregulated the antioxidant enzymes, and reduced oxidative stress. In conclusion, allicin showed an antihypertensive, nephroprotective, cardioprotective, and antioxidant effects, likely through downregulation of AT1R and Keap1 expression.