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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Background: Studies that contributed to the epidemiology of nausea and vomiting of pregnancy have reported conflicting findings, and often failed to account for all possible co-variables necessary to evaluate the multidimensional associations. The objectives of this study were to: 1) Estimate the prevalence and the severity of nausea and vomiting of pregnancy during the 1 st and the 2 nd trimester of pregnancy, and 2) Identify determinants of presence and severity of nausea and vomiting of pregnancy during the 1 st and 2 nd trimesters separately, with a special emphasis on the impact of race/ethnicity.

Human cytochrome P-450 epoxygenase enzymes metabolize eicosapentaenoic acid (EPA), an omega-3-polyunsaturated fatty acid (PUFA), and leads to the production of 17(18)-epoxyeicosatetraenoic acid, or 17(18)-EpETE. The aim of the present study was to delineate the mode of action of 17(18)-EpETE on human pulmonary artery (HPA) and distal bronchi. Isometric tension measurements demonstrated that 17(18)-EpETE induced concentration-dependent relaxing effects in pulmonary artery and airway smooth muscles. Iberiotoxin (IbTx) and glyburide (Glyb), known BK(Ca) and K(ATP) channel inhibitors, respectively, reversed the relaxation induced by 17(18)-EpETE on both tissues types. Microelectrode measurements showed that exogenous addition of 17(18)-EpETE hyperpolarized the membrane potential of HPA and bronchial smooth muscle cells. These induced electrophysiological effects were reversed by the addition of 10 nM IbTx and 10 muM Glyb. Complementary experiments performed on human bronchi, using the planar lipid bilayer reconstitution technique, demonstrated that 17(18)-EpETE activated reconstituted BK(Ca) channels at low free Ca(2+) concentration. Moreover, in bronchi, the relaxing responses induced by 17(18)-EpETE were also related to reduced Ca(2+) sensitivity of the myofilaments, since free Ca(2+) concentration-response curves, performed on beta-escin-permeabilized cultured explants, were shifted toward higher Ca(2+). Together, these results provide new insight into the mode of action of 17(18)-EpETE in lung tissues and highlight this eicosanoid as a potent modulator of tone on both HPA and distal bronchi in vitro, which may be of clinical relevance in the pathophysiology of pulmonary hypertension and airway diseases.

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