ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Genetic factors cannot explain the recent rapid increase in the incidence of atopic diseases. The phenomenon has been explained by environmental factors, and there are data for and against the hypothesis that a decline in the pressure of microbial stimulation early in life could be behind the allergy epidemic. Changes have also occurred in maternity care, among them a rise in the caesarean section rate, which could diminish initial microbial exposure and thereby alter T helper 1 cell/T helper-2 cell development and affect the risk of developing atopy. In this study, we sought to establish whether mode of delivery does influence the development of atopic asthma. Finnish 1987 Medical Birth Register (n= 59,927 live births) information was linked between several national health registers to obtain information on asthma and mode of delivery in children registered. The data were adjusted for maternal age, previous deliveries, child’s sex, and birth size. Atopy was evaluated in the second study (Turku Birth Cohort), which involved 219 children born by vaginal delivery (n= 106) or caesarean section (n= 113); history of atopic symptoms was established by questionnaire and a clinical examination was conducted, including skin prick testing and determination of total and allergen-specific IgE in serum. The register study showed the cumulative incidence of asthma at the age of seven to be significantly higher in children born by caesarean section (4.2%) than in those vaginally delivered (3.3%), the adjusted odds ratio (OR) for confounding variables being 1.21 (1.08–1.36),p< 0.01. In the second study, significantly more positive allergy tests were reported in questionnaires in the caesarean (22%) than in the vaginal delivery group (11%), OR 2.22 (1.06–4.64),p< 0.01, and a trend toward more positive skin prick reactions was documented at clinical examination; 41%versus29%, OR 1.31 (0.65–2.65),p= 0.11. In conclusion, these results suggest that caesarean section delivery may be associated with an increased prevalence of atopic asthma.

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Human naive CD4+T helper (Th) and CD8+cytotoxic (Tc) T cells, which only produce IL-2, may differentiate into Th1/Tc1- or Th2/Tc2-like lymphocytes, characterized by their cytokine production profile. 1&agr;,25-dihydroxyvitamin D3(1&agr;, 25(OH)2D3) has been reported to inhibit Th1/Tc1-related, but increase Th2/Tc2-associated cytokines in T cells from adults. In industrialized countries, vitamin D supplementation for prevention of rickets is initiated within the first days of life and continued throughout the entire first year. Epidemiologic studies suggest an association of vitamin D exposure in newborns with the incidence of allergic diseases in later life. This study addresses the effects of 1&agr;, 25(OH)2D3on Th1/Tc1versusTh2/Tc2 differentiation in long term cell cultures of (naive) cord blood T lymphocytes. Our results show that in CD4+as well as CD8+cord blood cells, 1&agr;, 25(OH)2D3inhibits not only IL-12-generated IFN-&ggr; production, but also suppresses IL-4 and IL-13 expression induced by IL-4. Thus, in cord blood 1&agr;, 25(OH)2D3induces a T cell population without predominance of Th2 related cytokines.

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Oxygen constriction causes functional closure of the ductus arteriosus (DA) at birth. Although DA closure is crucial for postnatal adaptation, patency of the DA is critical for survival of newborns with duct-dependent cardiac malformations. In these cases, DA patency is achieved by i.v. infusion of prostaglandin E1, which, though effective, is often associated with complications. We hypothesized that sildenafil, a specific phosphodiesterase type 5 inhibitor, is an effective DA vasodilator. In isolated DA rings from term (d 30) fetal rabbits, sildenafil (10−6–10−4M) and diethylamine NONOate (10−7–10−5M) induced dose-dependent relaxation of oxygen-constricted DA (−52 ± 4% and −51 ± 6%, respectively) that was inhibited by the soluble guanylyl-cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (5 × 10−5M). Sildenafil increased cyclic GMP levels. Iberiotoxin (200 nM), an inhibitor of calcium-sensitive potassium channels, decreased the vasodilatory effect of sildenafil and diethylamine NONOate (−30 ± 2% and −27 ± 4%, respectively). Oxygen inhibition of whole-cell K+current and membrane depolarization were partially restored by sildenafil, and this was inhibited by iberiotoxin. Immunohistochemistry and immunoblotting confirmed the presence of phosphodiesterase type 5 and calcium-sensitive potassium channels in the DA smooth muscle cells. This is the first study to demonstrate that sildenafil dilates the DA by increasing soluble guanylyl-cyclase–derived cGMP levels and thereby activating calcium-sensitive potassium channels, causing membrane hyperpolarization. Sildenafil, already approved for human usage, might be an alternative or a useful adjunct to prostaglandin E1 as a bridge to cardiac surgery.

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Unilateral pneumonectomy leads to compensatory growth in the residual lung, the mediators of which are largely unknown. We hypothesized, based on its other known roles in lung cell growth, that platelet-derived growth factor (PDGF)-BB would be an essential mediator of postpneumonectomy compensatory lung growth. Left-sided pneumonectomies were performed on 21-d-old rats, for comparison with sham-operated or unoperated control animals. Body weights were not different between groups. Right lung weights and DNA content were significantly increased (p< 0.05), compared with controls, by 10 d after pneumonectomy. The rate of DNA synthesis was maximal on d 5 postpneumonectomy. Total right lung PDGF-B mRNA and PDGF-BB protein increased after pneumonectomy, but were apparently tightly regulated, relative to total right lung &bgr;-actin mRNA and protein content, respectively. However, PDGF-BB expression after pneumonectomy was apparently not purely constitutive, in that daily i.p. injections of a truncated soluble PDGF &bgr;-receptor both reduced activation of the native PDGF &bgr;-receptor, and attenuated increased lung DNA synthesis on d 3 after pneumonectomy. These findings are consistent with a critical role for PDGF-BB in postpneumonectomy lung growth.

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Differences in lung heme oxygenase-1 (HO-1) regulation have been demonstrated in newborn (<12 h old) and adult (>2 month old) rats after exposure to hyperoxia. Contrary to adults, neonates do not demonstrate increased lung HO-1 induction nor transcription factor activator protein-1 (AP-1) binding in hyperoxia. Because AP-1 activation can be posttranslationally modified by oxidants or reductants, we investigated whether differences in lung glutathione (GSH) content account for the maturational differences in AP-1 activation and subsequent HO-1 gene regulation after hyperoxia. Neonatal rats were injected with either 1-buthionine-[S,R] sulfoximine (BSO), diamide, or selenite during the 72-h hyperoxic exposure. Lung GSH content, glutathione disulfide (GSSG) content, AP-1 binding, and HO-1 mRNA were evaluated. The ratios of GSSG to GSH were used to reflect the GSH redox state in the lungs. Changes in lung GSSG/GSH ratio did not alter AP-1 binding but did increase HO-1 mRNA in neonates. These data suggest that the neonatal lung is relatively resistant to AP-1 activation and HO-1 induction by GSH perturbation.

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Hypoxia-ischemia leads to an acute depletion of high-energy phosphates in neonatal brain. After reperfusion, energy status is restored, but may show progressive secondary failure, associated with neuronal loss, brain damage, or death. Oxidants are produced on reperfusion. We investigated whether a biphasic energy failure develops in cultured neurons after oxidant exposure, and whether the degree of primary disturbance correlates with later ATP synthesis and mode of cell death. Embryonic rat cortical neurons were exposed to varying doses of hydrogen peroxide for 60 min and incubated for 12, 24, or 48 h. Adenine nucleotides and the incorporation of [14C]adenine into adenine nucleotides were quantified. Apoptosis was evaluated by DNA electrophoresis andin situend-labeling. A mild insult (10–50 &mgr;M) caused no ATP depletion or change in subsequent growth or energy metabolism, whereas an intermediate insult (100 &mgr;M) caused acute ATP depletion (49 ± 12% of control). This recovered to 91 ± 28% by 12 h, but then declined to 61 ± 18% at 24 h. A severe insult (1 mM) depleted ATP to 15 ± 3% of control, with no recovery. Moderate ATP depletion was associated with apoptotic cell death, whereas a severe insult caused acute necrosis. Transient oxidant exposure of embryonal cortical neurons causes a biphasic energy depletion followed by apoptosis in analogy with asphyxiated brains. This model may prove useful for the study of pathogenesis and treatment of hypoxic-ischemic encephalopathy.

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Previous studies have demonstrated increased oxidative damage to proteins and increased lipid peroxidation products in the plasma of hypoxic newborns at birth. We tested the hypothesis that hypoxic preterm newborns are at increased risk for oxidative stress in the first week of life. Heparinized blood samples of 34 hypoxic and 15 control preterm newborns were obtained at birth from the umbilical vein immediately after delivery and from a peripheral vein on postnatal d 7. Plasma levels of hypoxanthine, total hydroperoxide (TH), and advanced oxidation protein products (AOPP) were measured in cord blood and blood drawn on d 7. Hypoxanthine, TH, and AOPP levels were significantly higher in cord and d 7 blood samples of hypoxic newborn than control infants. Statistically significant correlations were observed between AOPP and hypoxanthine and between AOPP and TH plasma levels on d 7. AOPP and TH plasma levels significantly increased from cord to d 7 blood in neonates without hypoxia. These findings show that the oxidative stress observed in cord blood of hypoxic preterm newborns is still higher than control infants on d 7. The significant increase in TH and AOPP levels in nonhypoxic preterm newborns at the end of the first postnatal week indicates that damage caused by free radicals also occurs in nonhypoxic babies with normal clinical course. In summary, TH and AOPP production is prolonged for several days after birth in hypoxic preterm babies. The risk of free radical damage is lower but still exists in preterm neonates with normal clinical course.

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID