Sex-specific responses to mineralocorticoid receptor antagonism in hypertensive African American males and females.

BACKGROUND: African Americans (AA) develop hypertension (HTN) at an earlier age, have a greater frequency and severity of HTN, and greater prevalence of uncontrolled HTN as compared to the white population. Mineralocorticoid antagonists have been shown to be very effective in treating uncontrolled HTN in both AA and white patients, but sex-specific responses are unclear. METHODS: We evaluated the sex-specific impact of mineralocorticoid antagonism in an AA population. An AA cohort (n = 1483) from the Genetic Epidemiology Network of Arteriopathy study was stratified based on sex and whether they were taking spironolactone, a mineralocorticoid antagonist, in their antihypertensive regimen. RESULTS: As compared to AA women not prescribed a mineralocorticoid antagonist, AA women taking spironolactone (n = 9) had lower systolic and diastolic blood pressure despite having a similar number of antihypertensive medications. The proportion of AA women with uncontrolled HTN was significantly less for patients taking spironolactone than for patients not prescribed spironolactone. Interestingly, none of these associations were found in the AA males or in white females. CONCLUSIONS: Our data suggests that spironolactone is particularly effective in reducing blood pressure and controlling HTN in AA women. Further research into the impact of this therapy in this underserved and understudied minority is warranted.

Mixing medication into foodstuffs: identifying the issues for paediatric nurses.

Medication is often mixed into soft foods to aid swallowing in children. However, this can alter the physical/chemical properties of the active drug. This study reports on the prevalence of the modification procedure, the nature of foodstuffs routinely used and factors which influence how the procedure is performed by nurses working in the National Health Service in Scotland. Mixed methods were employed encompassing an online self-administered questionnaire and semi-structured interviews. One hundred and eleven nurses participated, of whom 87% had modified medication prior to administration. Fruit juice (diluted and concentrated) and yoghurts were most commonly used. The interviews (i) identified the limitations of the procedure; (ii) explored the decision-making process; and (iii) confirmed the procedure was a last resort. This study intends to address some of the uncertainty surrounding the medicine modification procedure within the paediatric population.

Discovery of AZD3199, An Inhaled Ultralong Acting ß2 Receptor Agonist with Rapid Onset of Action.

A series of dibasic des-hydroxy ß2 receptor agonists has been prepared and evaluated for potential as inhaled ultralong acting bronchodilators. Determination of activities at the human ß-adrenoreceptors demonstrated a series of highly potent and selective ß2 receptor agonists that were progressed to further study in a guinea pig histamine-induced bronchoconstriction model. Following further assessment by onset studies in guinea pig tracheal rings and human bronchial rings contracted with methacholine (guinea pigs) or carbachol (humans), duration of action studies in guinea pigs after intratracheal (i.t.) administration and further selectivity and safety profiling AZD3199 was shown to have an excellent over all profile and was progressed into clinical evaluation as a new ultralong acting inhaled ß2 receptor agonist with rapid onset of action.

Estudio in vitro de liberación de proteínas de AFCo1 y sus implicaciones en la inmunización mucosal / In vitro study of protein release from AFCo1 and implications in mucosal immunisation

El cocleato adyuvante Finlay (AFCo1) 1 es derivado de un proteopolisoma de Neisseria meningitidis serogrupo B. La transformación de los proteoliposomas en AFCo1 potencia la respuesta inmune de los antígenos de Neisseria cuando se administra por vía intranasal o intragástrica. Se ha demostrado, sin embargo, que la vía intranasal es más efectiva. Los objetivos de este trabajo fueron evaluar in vitro la liberación de proteínas del AFCo1 en líquido nasal o gástrico simulado, usando para ello la prueba de microdisolución y apoyar los resultados obtenidos cuando se administró AFCo1 por vía intranasal o intragástrica en ratones BALB/c. Los resultados demostraron que la dilución de AFCo1 en líquido gástrico o nasal simulado afecta la distribución de los antígenos de proteína de Neisseria , ya que estos se liberaron de las estructuras de cocleatos más rápido cuando se utilizó líquido nasal. Se concluyó que las condiciones que simulan el entorno gástrico afectan la distribución de los antígenos de proteínas de AFCo1 y este resultado puede explicar parcialmente porqué la administración intranasal es más efectiva in vivo que la inmunización intragástrica(AU)

Adjuvant Finlay Cochleate 1 (AFCo1) is a Proteoliposome-derived cochleate obtained from Neisseria meningitidisserogroup B. Transformation of proteoliposomes into AFCo1 potentiates the immune response on Neisseriaantigens when it is administered by intranasal or intragastric (i.g) routes. However, the i.n route has beendemonstrated to be more effective. The aim of this work is to evaluate in vitro the protein release from AFCo1, insimulated gastric fluid (SGF) or simulated nasal fluid (SNF) using a microdissolution test and to provide support for the results found when AFCo1 was administered by i.g or i.n routes in BALB/c mice. Results showed that dilution of AFCo1 in simulated gastric fluid affects the delivery of Neisseria protein antigens because they were released from cochleate structures faster than when simulated nasal fluid was used. In conclusion, conditions simulating gastric environment affect the delivery of protein antigens from AFCo1 and this result could partially explain whyin administration is more effective in vivo than in immunisation(AU)

Design driven HtL: The discovery and synthesis of new high efficacy ß2-agonists.

The design and synthesis of a new series of high efficacy ß(2)-agonists devoid of the key benzylic alcohol present in previously described highly efficacious ß(2)-agonists is reported. A hypothesis for the unprecedented level of efficacy is proposed based on considerations of ß(2)-adrenoceptor crystal structure, other biophysical data and modeling studies.