An Imidazoline 2 Receptor Ligand Relaxes Mouse Aorta via Off-Target Mechanisms Resistant to Aging.

Imidazoline receptors (IR) are classified into three receptor subtypes (I1R, I2R, and I3R) and previous studies showed that regulation of I2R signaling has neuroprotective potential. In order to know if I2R has a role in modulating vascular tone in health and disease, we evaluated the putative vasoactive effects of two recently synthesized I2R ligands, diethyl (1RS,3aSR,6aSR)-5-(3-chloro-4-fluorophenyl)-4,6-dioxo-1-phenyl-1,3a,4,5,6,6a-hexahydropyrrolo[3,4-c]pyrrole -1-phosphonate (B06) and diethyl [(1-(3-chloro-4-fluorobenzyl)-5,5-dimethyl-4-phenyl-4,5-dihydro-1H-imidazol-4-yl]phosphonate] (MCR5). Thoracic aortas from Oncins France 1 (3- to 4-months-old) and C57BL/6 (3- to 4- and 16- to 17-months-old mice) were mounted in tissue baths to measure isometric tension. In young mice of both strains, MCR5 induced greater relaxations than either B06 or the high-affinity I2R selective ligand 2-(2-benzofuranyl)-2-imidazoline (2-BFI), which evoked marginal responses. MCR5 relaxations were independent of I2R, as IR ligands did not significantly affect them, involved activation of smooth muscle KATP channels and inhibition of L-type voltage-gated Ca2+ channels, and were only slightly modulated by endothelium-derived nitric oxide (negatively) and prostacyclin (positively). Notably, despite the presence of endothelial dysfunction in old mice, MCR5 relaxations were preserved. In conclusion, the present study provides evidence against a functional contribution of I2R in the modulation of vascular tone in the mouse aorta. Moreover, the I2R ligand MCR5 is an endothelium-independent vasodilator that acts largely via I2R-independent pathways and is resistant to aging. We propose MCR5 as a candidate drug for the management of vascular disease in the elderly.

Body perception in a sample of nonclinical youngsters with joint hypermobility / Percepción corporal en una muestra de jóvenes no clínicos con hipermovilidad articular

BACKGROUND: Participants with Joint Hypermobility Syndrome (JHS) often suffer from anxiety, stress related illnesses and also from dysautonomia. The autonomic nervous system (ANS) is hypothesized to play a key role in the relationship between these variables. However, to date, no studies have assessed body awareness and the reactivity of autonomically-regulated organs in JHS using the Body Perception Questionnaire. METHOD: A cross sectional study including 117 nonclinical youngsters (mean age 16.96 ± 0.87 years old) assessed JHS in relation to body perception. JHS screening was done using the self-reported Screening Questionnaire for Collagen condition and Hypermobility assessment (SQCH) and body perception was assessed using the Spanish version of the Body Perception Questionnaire (BPQ). RESULTS: The JHS was found in 33.3% of the sample and it was significantly higher in females (χ2 = 12.15; p = <.001). Participants with JHS had higher scores in body awareness (p = .012), stress response (p = .007), ANS reactivity (p = .01), and in the health history inventory (p = <.001). In this last subscale, higher frequency of anxiety (p = <.001), unhappiness (p = <.001), depression (p = <.001), bulimia (p = .012), anorexia (p = .023), eczema (p = .003), and severe menstrual cramps (in females only) (p = .016) were found among the JHS participants. Moreover, JHS participants made significantly more visits to mental health professionals (p = .019) than their non JHS counterparts. CONCLUSIONS: Participants with JHS have a body perception profile characterized by higher body awareness and stress response and greater ANS reactivity. These participants also have higher frequency of anxiety, depression, bulimia, anorexia, unhappiness, severe menstrual cramps (in females only) and eczema. These findings support the hypothesis that the ANS and body perception may play a key role in the development of anxiety and somatic illnesses among participants with JHS, but this needs to be further evaluated in subsequent studies

ANTECEDENTES: Las personas con síndrome de hipermovilidad articular (SHA) padecen a menudo ansiedad, estrés relacionado con la enfermedad y también disautonomía. Se ha conjeturado que el sistema nervioso autónomo juega un papel clave en la relación entre estas variables, pero hasta la fecha ningún estudio ha evaluado la conciencia corporal y la reactividad de los órganos regulados autonómicamente en el SHA utilizando el cuestionario de imagen corporal. MÉTODO: Estudio transversal que incluyó a 117 jóvenes no clínicos (edad media 16,96 ± 0,87años) en quienes se valoró el SHA en relación con la imagen corporal. Se realizó un cribado de SHA utilizando el cuestionario autoinformado de cribado para la valoración del estado de colágeno e hipermovilidad (SQCH), evaluándose la percepción corporal mediante la versión española del cuestionario de imagen corporal (BPQ). RESULTADOS: Se encontró SHA en el 33,3% de la muestra, siendo significativamente superior en las mujeres (χ2=12,15; p ≤ 0,001). Las personas con SHA reflejaron mayores puntuaciones en cuanto a conciencia del cuerpo (p = 0,012), respuesta al estrés (p = 0,007), reactividad del sistema nervioso autónomo (p = 0,01) e inventario de antecedentes de salud (p ≤ 0,001). En esta última subescala se encontró una mayor frecuencia de ansiedad (p ≤ 0,001), infelicidad (p≤0,001), depresión (p ≤ 0,001), bulimia (p = 0,012), anorexia (p = 0,023), eccema (p = 0,003) y dolores menstruales severos (solo en mujeres) (p = 0,016) entre las personas con SHA. Además, las personas con SHA realizaron un número de visitas considerablemente superior a los profesionales sanitarios (p = 0,019) que los participantes sin SHA. CONCLUSIONES: Las personas con SHA tienen un perfil de percepción corporal caracterizado por una mayor conciencia sobre el cuerpo y una reactividad superior del sistema nervioso autónomo. Estos participantes también poseen una mayor frecuencia de ansiedad, depresión, bulimia, anorexia, infelicidad, dolores menstruales severos y eccema. Estos hallazgos respaldan la hipótesis de que el sistema nervioso autónomo y la imagen corporal pueden jugar un papel principal en el desarrollo de la ansiedad y las enfermedades somáticas entre las personas con SHA, aunque esto debe evaluarse en mayor profundidad en estudios futuros

Sugammadex ideal body weight dose adjusted by level of neuromuscular blockade in laparoscopic bariatric surgery.

BACKGROUND: Bariatric surgery patients are at risk of perioperative airway collapse. Neuromuscular blockade should be fully reversed before tracheal extubation. The optimal dosage of the reversal agent sugammadex in the morbidly obese is still unknown. This study explored the sugammadex dose adjusted according to train-of-four ratio (TOFR). METHODS: Prospective observational study of consecutive patients scheduled for laparoscopic bariatric surgery. To reverse a deep blockade (2 or fewer posttetanic twitches), a dose of sugammadex of 4 mg/kg ideal body weight (IBW) was followed by a second dose of 2 mg/kg IBW if the TOFR was less than 0.9 after 3 min. To reverse a moderate blockade (reappearance of the second twitch in the TOF), a 2 mg/kg IBW dose of sugammadex was followed by a second dose of 2 mg/kg IBW if the TOFR was less than 0.9 after 2 min. Sugammadex effectiveness was reflected by the time required to obtain a TOFr of 0.9 or more. RESULTS: A total of 120 patients were included. The blockade was deep at the end of surgery in 43 and moderate in 77. The median times (range) to TOFR of 0.9 or more were 167 (20-460) seconds and 113 (28-300) seconds in deep and moderate blockades, respectively (P < 0.05). The percentage of patients requiring a second dose of sugammadex were larger after deep blockades (39.5% [n = 17] vs. 23.4% [n = 18] after moderate blockades); the difference was not significant. CONCLUSION: A sugammadex dose calculated according to IBW is insufficient for reversing both deep and moderate blockades in morbidly obese patients.

Effectiveness of regular reporting of spirometric results combined with a smoking cessation advice by a primary care physician on smoking quit rate in adult smokers: a randomized controlled trial. ESPIROTAB study.

BACKGROUND: Undiagnosed airflow limitation is common in the general population and is associated with impaired health and functional status. Smoking is the most important risk factor for this condition. Although primary care practitioners see most adult smokers, few currently have spirometers or regularly order spirometry tests in these patients. Brief medical advice has shown to be effective in modifying smoking habits in a large number of smokers but only a small proportion remain abstinent after one year. The aim of this study is to evaluate the effectiveness of regular reporting of spirometric results combined with a smoking cessation advice by a primary care physician on smoking quit rate in adult smokers. METHODS/DESIGN: Intervention study with a randomized two arms in 5 primary care centres. A total of 485 smokers over the age of 18 years consulting their primary care physician will be recruited.On the selection visit all participants will undergo a spirometry, peak expiratory flow rate, test of smoking dependence, test of motivation for giving up smoking and a questionnaire on socio-demographic data. Thereafter an appointment will be made to give the participants brief structured advice to give up smoking combined with a detailed discussion on the results of the spirometry. After this, the patients will be randomised and given appointment for follow up visits at 3, 6, 12 and 24 months. Both arms will receive brief structured advice and a detailed discussion of the spirometry results at visit 0. The control group will only be given brief structured advice about giving up smoking on the follow up. Cessation of smoking will be tested with the carbon monoxide test. DISCUSSION: Early identification of functional pulmonary abnormalities in asymptomatic patients or in those with little respiratory symptomatology may provide "ideal educational opportunities". These opportunities may increase the success of efforts to give up smoking and may improve the opportunities of other preventive actions to minimise patient risk. Comparing adult smokers in the intervention group with those in the control group, a minimum improvement expected with respect to the rates of smoking cessation would represent a large number of avoided morbimortality. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01296295.