Objective The objective of this study was to determine the impact of nausea and vomiting of pregnancy (NVP) and other determinants on generic and NVP-specific health-related quality of life (QOL) in the first trimester of pregnancy.Design Prospective study.Setting Centre Hospitalier Universitaire (CHU) Sainte-Justine or René-Laennec clinics, Montreal, Quebec, Canada.Population Pregnant women attending the clinics for their prenatal care from 2004 to 2006. Women were eligible if they were ‡18 years of age and £16 weeks of gestation at the time of their first prenatal visit.Methods After their first prenatal visit, women were asked to fill out a questionnaire covering maternal characteristics, presence and severity of NVP, and health-related QOL.Main outcome measures QOL was measured by the generic 12-item Short Form Health Survey v.1 (SF-12) and the NVP-specific Quality of Life for Nausea and Vomiting during Pregnancy.Results Of the 367 pregnant women included in the study, 78.5% of women reported NVP in the first trimester of pregnancy. Multivariable linear models showed that presence of NVP in the first trimester of pregnancy was significantly associated with a lower physical component summary scale (P < 0.0001) and mental component summary scale (P = 0.0066) of the SF-12 scores. More severe NVP (moderate versus mild: P = 0.0002; severe versus mild: P = 0.0177 as measured by the validated modified Pregnancy-Unique Quantification of Emesis and Nausea index), intensity of nausea symptoms reported on a visual analogue scale (P < 0.0001), and nonpharmacological methods used to ease NVP symptoms in the first trimester of pregnancy (P = 0.0059) were significantly associated with poorer NVPspecific QOL among women suffering from NVP.Conclusion These findings show that presence and severity of NVP have a negative impact on health-related QOL, which emphasises the importance of an optimal management of NVP.

This study sought to assess putative pathways involved in the anti-inflammatory effects of 17,18-epoxyeicosatetraenoic acid (17,18-EpETE), as measured by a decrease in the contractile reactivity and Ca(2+) sensitivity of TNF-α-pretreated human bronchi. Tension measurements performed in the presence of 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), a soluble epoxide hydrolase (sEH)-specific inhibitor, demonstrated that 17,18-EpETE reduced the reactivity of TNF-α-pretreated tissues. The overexpression of sEH detected in patients with asthma and TNF-α-treated bronchi contributed to the maintenance of hyperresponsiveness in our models, which involved intracellular proinflammatory cascades. The inhibition of peroxisome proliferator-activated receptor (PPAR)γ by GW9662 abolished 17,18-EpETE + AUDA-mediated anti-inflammatory effects by inducing IκBα degradation and cytokine synthesis, indicating that PPARγ is a molecular target of epoxy-eicosanoids. Western blot analysis revealed that 17,18-EpETE pretreatment reversed the phosphorylation of p38 mitogen-activated protein kinase (p38-MAPK) induced by TNF-α in human bronchi. The Ca(2+) sensitivity of human bronchial explants was also quantified on β-escin permeabilized preparations. The presence of SB203580, a p38-MAPK inhibitor, reversed the effect induced by epoxy-eicosanoid in the presence of AUDA on TNF-α-triggered Ca(2+) hypersensitivity by increasing the phosphorylation level of PKC Potentiated Inhibitor Protein-17 (CPI-17) regulatory protein. Moreover, PPARγ ligands, such as rosiglitazone and 17,18-EpETE, decreased the expression of CPI-17, both at the mRNA and protein levels, whereas this effect was countered by GW9662 treatment in TNF-α-treated bronchi. These results demonstrate that 17,18-EpETE is a potent regulator of human lung inflammation and concomitant hyperresponsiveness, and may represent a valuable asset against critical inflammatory bronchial disorder.

The aim of the present study was to investigate the anti-inflammatory effects of 14,15-epoxyeicosatrienoic acid (EET) on reactivity and Ca(2+) sensitivity in TNF-alpha-stimulated human bronchi. Tension measurements performed on either control, TNF-alpha-, or TNF-alpha + EET-pretreated bronchi revealed that 100 nM 14,15-EET pretreatments significantly reduced the reactivity of TNF-alpha-pretreated tissues to contractile agonists. EET also normalized the relaxing response to isoproterenol in TNF-alpha-treated bronchi. Pretreatment with 100 nM 14,15-EET prevented TNF-alpha-induced IkappaBalpha degradation, as demonstrated by an increase in IkappaBalpha protein levels on Western blot analysis. The anti-inflammatory properties of EET were mediated by the inhibition of IkappaBalpha degradation, suggesting a lower activation of NF-kappaB. The Ca(2+) sensitivity of TNF-alpha-stimulated bronchi was also evaluated on beta-escin-permeabilized preparations. Observed mean responses demonstrated that EET pretreatments abolished Ca(2+) hypersensitivity developed by TNF-alpha-stimulated bronchial explants. Moreover, 14,15-EET significantly reduced PDBu-induced Ca(2+) sensitivity in TNF-alpha-stimulated bronchi. Western blot and RT-PCR analyses revealed that CPI-17 protein and transcript levels were increased in TNF-alpha-treated bronchi, as opposed to being decreased in the presence of 14,15-EET. This eicosanoid also reduced U-46619-induced Ca(2+) sensitivity, which is related to the activation of Rho-kinase pathway. These results were also correlated with an increase in protein staining and transcription level of p116(Rip), a RhoA inhibitory-binding protein. Altogether, these data demonstrate that 14,15-EET is a potent modulator of the hyperreactivity triggered by TNF-alpha in human airway smooth muscle cells.

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