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Maternal Infections (maternal + infections)
Selected AbstractsDual effect of nitric oxide on uterine prostaglandin synthesis in a murine model of preterm labourBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2010M Cella BACKGROUND AND PURPOSE Maternal infections are one of the main causes of adverse developmental outcomes including embryonic resorption and preterm labour. In this study a mouse model of inflammation-associated preterm delivery was developed, and used to study the relationship between nitric oxide (NO) and prostaglandins (PGs). EXPERIMENTAL APPROACH The murine model of preterm labour was achieved by assaying different doses of bacterial lipopolysaccharides (LPS). Once established, it was used to analyse uterine levels of prostaglandins E2 and F2, (by radioimmunoassay), cyclooxygenases (COX) and NOS proteins (by Western blot) and NO synthase (NOS) activity. Effects of inhibitors of COX and NOS on LPS-induced preterm labour were also studied. In vitro assays with a nitric oxide donor (SNAP) were performed to analyse the modulation of prostaglandin production by NO. KEY RESULTS Lipopolysaccharide increased uterine NO and PG synthesis and induced preterm delivery. Co-administration of meloxicam, a cyclooxygenase-2 inhibitor, or aminoguanidine, an inducible NOS inhibitor, prevented LPS-induced preterm delivery and blocked the increase in PGs and NO. Notably, the levels of NO were found to determine its effect on PG synthesis; low concentrations of NO reduced PG synthesis whereas high concentrations augmented them. CONCLUSIONS AND IMPLICATIONS An infection-associated model of preterm labour showed that preterm delivery can be prevented by decreasing PG or NO production. NO was found to have a dual effect on PG synthesis depending on its concentration. These data contribute to the understanding of the interaction between NO and PGs in pregnancy and parturition, and could help to improve neonatal outcomes. [source] Modulation of peroxisome proliferator-activated receptor-, activity by N -acetyl cysteine attenuates inhibition of oligodendrocyte development in lipopolysaccharide stimulated mixed glial culturesJOURNAL OF NEUROCHEMISTRY, Issue 3 2008Manjeet K. Paintlia Abstract Glial cells secrete proinflammatory mediators in the brain in response to exogenous stimuli such as infection and injury. Previously, we documented that systemic maternal lipopolysaccharide (LPS)-exposure at embryonic gestation day 18 causes oligodendrocyte (OL)-injury/hypomyelination in the developing brain which can be attenuated by N -acetyl cysteine (NAC; precursor of glutathione). The present study delineates the underlying mechanism of NAC-mediated attenuation of inhibition of OL development in LPS-stimulated mixed glial cultures. Factors released by LPS-stimulated mixed glial cultures inhibited OL development as shown by decrease in both proliferation 3bromo-deoxyuridine+/chondroitin sulfate proteoglycan,NG2+, hereafter BrdU+/NG+ and differentiation (O4+ and myelin basic protein+) of OL-progenitors. Correspondingly, an impairment of peroxisomal proliferation was shown by a decrease in the level of peroxisomal proteins in the developing OLs following exposure to LPS-conditioned media (LCM). Both NAC and WY14643, a peroxisome proliferator-activated receptor (PPAR)-, agonist attenuated these LCM-induced effects in OL-progenitors. Similar to WY14643, NAC attenuated LCM-induced inhibition of PPAR-, activity in developing OLs. Studies conducted with cytokines and diamide (a thiol-depleting agent) confirmed that cytokines are active agents in LCM which may be responsible for inhibition of OL development via peroxisomal dysfunction and induction of oxidative stress. These findings were further corroborated by similar treatment of developing OLs generated from PPAR-,(,/,) and wild-type mice or B12 oligodendroglial cells co-transfected with PPAR-, small interfering RNAs/pTK-PPREx3-Luc plasmids. Collectively, these data provide evidence that the modulation of PPAR-, activity, thus peroxisomal function by NAC attenuates LPS-induced glial factors-mediated inhibition of OL development suggesting new therapeutic interventions to prevent the devastating effects of maternal infections. [source] The influence of maternal respiratory infections during pregnancy on infant lung function,PEDIATRIC PULMONOLOGY, Issue 10 2007Nienke Van Putte-Katier MD Abstract Introduction We studied whether maternal respiratory infections during pregnancy adversely influence lung growth and development of the offspring, resulting in poor early life lung function. Methods Infants were participants of the Wheezing Illnesses Study Leidsche Rijn (WHISTLER). Lung function measurements (single occlusion technique) were performed during natural sleep. Questionnaire data were used to obtain information on maternal respiratory infections during pregnancy. Multivariate analysis was conducted to assess the relationship between maternal respiratory infections during pregnancy and resistance and compliance of the respiratory system, adjusting for potential confounding variables. Results Lower values of compliance (Crs) were found in infants of mothers with respiratory infections during pregnancy; Crs fell by 5.5% (P,=,0.031). The difference in Crs between infants of mothers with and without respiratory infections during pregnancy remained unchanged and statistically significant after adjusting for potential confounding variables. The more respiratory infections the mother experienced during pregnancy, the lower the value of Crs was in her offspring (P for trend,=,0.016). Using Crs corrected for body weight the relationship with maternal infections was non-significant, however still showing a trend. Conclusions The results of this study may indicate that mothers who experience respiratory infections during pregnancy have newborns with lower compliance of the respiratory system. Pediatr Pulmonol. 2007; 42:945,951. © 2007 Wiley-Liss, Inc. [source] The transplacental transfer of the macrolide antibiotics erythromycin, roxithromycin and azithromycinBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 6 2000Gynaecology), Tuija Heikkinen Consultant (Obstetrics Objective To investigate the transplacental transfer of the macrolide antibiotics erythromycin, roxithromycin and azithromycin. Methods Twenty-one term placentas were obtained with maternal consent immediately after delivery and a two-hour nonrecirculating perfusion of a single placental cotyledon was performed. Erythromycin (2 ,g/mL), roxithromycin (2 ,g/mL) and azithromycin (0.3 ,g/mL) were infused to the maternal inflow at a constant rate, with antipyrine as a reference compound, and their appearance in the fetal circulation was followed. Drug concentrations were measured by high performance liquid chromatography for 120 min. Results The mean transplacental transfers (TPTss) for erythromycin, roxithromycin and azithromycin were 3.0%, 4.3% and 2.6%, respectively, calculated as the ratio between the steady state concentrations in fetal venous and maternal arterial sides. Similar results were obtained when the TPT was calculated as the absolute amount of drug transferred across the placenta during 2-hour perfusion (TPTA). No significant differences were found among the three macrolides in TPTSS (P= 0.39) or TPTA (P= 0.35). The TPTSS of erythromycin, roxithromycin and azithromycin were 41%, 35% and 32% of the freely diffusable reference compound antipyrine, respectively. Steady state was reached in 60 minutes in each perfusion indicating sufficient perfusion time. Conclusion The limited transplacental transfer of erythromycin, roxithromycin and azithromycin suggests compromised efficacy in the treatment of fetal infections. On the other hand, the placenta seems to produce an effective barrier reducing the fetal exposure when these three macrolides are used to treat maternal infections. [source] | ||||||||||