RESUMO
OBJECTIVE: Maternal asthma often complicates pregnancy and is linked with poorer quality of life. Additionally, individuals with asthma are at an increased risk of depression and anxiety. We examined whether asthma during pregnancy is related to parenting stress in the first year postpartum and if this relationship varies with level of asthma control. METHODS: This cohort survey-based study included mothers with (n = 157) and without (n = 79) asthma. Mothers with asthma participated in this study following participation in a randomized controlled trial of a novel asthma management strategy during pregnancy. Mothers completed the Parenting Stress Index - Short Form during the first 12 months postpartum. Mothers with asthma also completed the Asthma Control Questionnaire. RESULTS: Parenting stress did not differ between mothers with and without asthma. Additionally, for mothers with asthma, there were no differences in levels of parenting stress based on asthma control. CONCLUSIONS: This study suggests that mothers with asthma are not at an increased risk for excessive parenting stress. However, due to response and sampling bias, levels of parenting stress in asthmatic mothers may be underreported in our sample.
Assuntos
Asma , Poder Familiar , Asma/epidemiologia , Feminino , Humanos , Período Pós-Parto , Gravidez , Qualidade de Vida , Estresse Psicológico/complicações , Estresse Psicológico/epidemiologiaRESUMO
A search for a suitable replacement for the central norbornyl scaffold presented in the recently disclosed novel FLAP inhibitors is herein described, as well as the SAR study performed on the endo and exo-aryl groups.
Assuntos
Inibidores da Proteína Ativadora de 5-Lipoxigenase/síntese química , Proteínas Ativadoras de 5-Lipoxigenase/química , Alcanos/síntese química , Antialérgicos/síntese química , Derivados de Benzeno/síntese química , Inibidores da Proteína Ativadora de 5-Lipoxigenase/farmacocinética , Inibidores da Proteína Ativadora de 5-Lipoxigenase/farmacologia , Proteínas Ativadoras de 5-Lipoxigenase/metabolismo , Alcanos/farmacocinética , Alcanos/farmacologia , Animais , Antialérgicos/farmacocinética , Antialérgicos/farmacologia , Derivados de Benzeno/farmacocinética , Derivados de Benzeno/farmacologia , Humanos , Concentração Inibidora 50 , Injeções Intravenosas , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Ratos , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
Sulfonamide analogues of the potent CB1R inverse agonist taranabant were prepared and optimized for potency and selectivity for CB1R. They were variably more potent than the corresponding amide analogues. The most potent representative 22 had good pharmacokinetic and brain levels, but was modestly active in blocking CB1R agonist-mediated hypothermia.
Assuntos
Moduladores de Receptores de Canabinoides/síntese química , Receptor CB1 de Canabinoide/efeitos dos fármacos , Sulfonamidas/síntese química , Animais , Fármacos Antiobesidade/síntese química , Fármacos Antiobesidade/farmacologia , Química Encefálica , Moduladores de Receptores de Canabinoides/farmacologia , Humanos , Hipotermia/tratamento farmacológico , Concentração Inibidora 50 , Farmacocinética , Ratos , Receptor CB1 de Canabinoide/agonistas , Relação Estrutura-Atividade , Sulfonamidas/farmacologiaRESUMO
To investigate how specific amino acid residues affect human cannabinoid CB1 receptor binding and activation, CHO cell lines stably expressing wild type and the phenylalanine 200 to alanine mutant of human cannabinoid CB1 receptor (F200A) were examined. AM2233 functions as an agonist at the wild type receptor (EC50=0.93 nM), but behaves as an inverse agonist at F200A (EC50=4.8 nM). The F200A mutant has significantly lower forskolin-stimulated basal cAMP accumulation than that of the wild type, indicating that the F200A mutant possesses higher constitutive activity. F200 doesn't contribute substantially to the high affinity binding of AM2233 at human cannabinoid CB1 receptor. CP55940, HU-210 and Win55212-2 still function as agonists at the F200A mutant, with similar efficacy, potency, and apparent binding affinity for both wild type human cannabinoid CB1 receptor and F200A mutant. These data indicate that the phenylalanine 200 residue in human cannabinoid CB1 receptor is involved in the receptor activation induced by a specific class of agonists, and supports a model of agonist-structure-dependent conformational changes.
Assuntos
Substituição de Aminoácidos , Indóis/farmacologia , Piperidinas/farmacologia , Receptor CB1 de Canabinoide/agonistas , Alanina/genética , Animais , Sítios de Ligação/genética , Ligação Competitiva/genética , Células CHO , Colforsina/farmacologia , Cricetinae , Cricetulus , AMP Cíclico/metabolismo , Cicloexanóis/química , Cicloexanóis/metabolismo , Cicloexanóis/farmacologia , Relação Dose-Resposta a Droga , Expressão Gênica , Humanos , Indóis/química , Indóis/metabolismo , Estrutura Molecular , Toxina Pertussis/farmacologia , Fenilalanina/genética , Piperidinas/química , Piperidinas/metabolismo , Pirazóis/química , Pirazóis/metabolismo , Pirazóis/farmacologia , Receptor CB1 de Canabinoide/genética , Receptor CB1 de Canabinoide/metabolismo , TrítioRESUMO
Individuals scoring high (N=32) and low (N=27) on the unusual experiences (UnEx) scale of the Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE) were selected from a large sample (N=265) of normal volunteer undergraduates. The high- and low-UnEx groups were compared on two tasks, random generation and memory updating, which target executive functions that inhibit prepotent responses and update current information. The groups differed only on the R measure of random generation that assesses inequality in the relative frequencies of response alternatives, a result attributed to superstitious behaviour rather than to executive deficit. The results suggest that the executive impairments previously observed in high schizotypal individuals using the Wisconsin Card Sorting Test and other measures are selective rather than global.
