Major cause of prematurity is spontaneous preterm birth (PTB) associated with intrauterine inflammation. Our aim was to establish a model of endotoxin Lipopolysaccharide-induced PTB of live-born pups and to study early immune activation in fetal and maternal compartments. Expression of several proteins that bind microbes (Toll-like receptors TLR4, TLR2; surfactant proteins SP-A, SP-D) was analyzed. At 16 or 17 d of gestation, C57BL/6 dams received a single dose of intraperitoneal LPS, leading to PTB within 17 h. Cytokine levels increased in maternal serum, followed by a modest increase in fetal serum and in amniotic fluid. In uterus, placenta, and fetal membranes, LPS mostly increased the expressions of TLR, SPs, and cytokines. The number of TLR2-positive macrophages increased in labyrinthine placenta. In fetal lung, intestine, liver, and brain there were modest changes in cytokine expressions. In fetal lung, SP and TLR mRNAs decreased and TLR2-positive macrophages redistributed around vessels. LPS-induced fetal deaths associated with early age (16 d gestation) rather than with proinflammatory activation. Here we propose that maternal LPS response leads to PTB and acute decrease of immune proteins in epithelial lining of fetal lung. Instead, acceleration of lung maturity has been previously observed in intraamniotic inflammation. (Pediatr Res 63: 280-286, 2008) P rematurity is the main cause of perinatal morbidity and mortality in developed countries. Altogether, 50 -70% of preterm births (PTBs) in humans are due to spontaneous onset of premature labor (1). There is a strong relationship between systemic or intrauterine infection and preterm delivery. Lipopolysaccharide (LPS), an endotoxin of Gram-negative bacteria, causes PTB in animals and has been implicated as a factor triggering preterm labor in humans (2). Different model systems have been established to study the induced PTB in mammalian species (3,4). The inflammatory models applied to mice involve intraperitoneal, intrauterine, or intraamniotic administration of heat-killed bacteria or bacterial products (5-7). Depending on the dose, gestational age, and site of exposure, the consequences of LPS-induced inflammatory response are variable. However, the administration of LPS has mostly resulted in fetal death or the delivery of dead fetuses (6 -11).The proposed sequence of inflammatory mediators leading to preterm labor and delivery involves the production of proinflammatory cytokines in uterus, placental tissue, and fetal tissues as a response to bacterial toxins. The cytokines, in turn, initiate the synthesis of secondary mediators, e.g., prostaglandins and matrix metalloproteinases involved in the preterm delivery (2,4). It has been proposed that fetal death results from a maternal response rather than fetal sensitivity to LPS (12,13).The innate immune system involved in nonclonal host defense is likely to influence fetal outcome. Toll-like receptors (TLRs) and collectins serve as signaling receptors for pathogen-associated molecular patterns...
Mental disorders had many social risk factors which are interlinked. Although family difficulties increased the risk for mental disorders, they were clearly determined by the cohort member's low education and financial hardship. This study provides evidence for comprehensive preventative and supporting efforts. Families with social adversities and with parental mental health problems should be supported to secure children's development.
The studies reporting population-based estimates of the proportion of children with a parent suffering from cancer are very few. These children have been shown to suffer from psychological symptoms, but it is not known whether their use of psychiatric services is increased. Our study examined the prevalence of children affected by parental cancer at national level and whether these children use specialized psychiatric services more than their peers. The study is a retrospective population-based registry study. All 60,069 children born in Finland in 1987 were followed up with various health and social registers from 1987 to 2008. The associations of parental cancer treatments with children's psychiatric service use were analyzed with logistic regressions. During the 21-year follow-up 3,909 (6.6%) of the children had a parent suffering from cancer. The children of the cancer patients used more specialized psychiatric care than their peers and the service use depended on parent's gender, as well as cohort members' gender and the age at occurrence. The combination of parental cancer and psychiatric disorder, whether the ill parent or spouse, increased the children's psychiatric service use even more. Children affected by parental cancer comprise a substantial part of the population in society using increased level of psychiatric services. Parental cancer is clearly an illness which has to be taken into account in planning child-and parentingfocused prevention and promotion actions in adult health care. ''Parent's cancer is like a tsunami which rolls over the whole family. If it struck a thousand families at the same time the whole healthcare system would be mobilized. But when it strikes one family at a time you are left alone with your children'' (quote from a father during a family intervention). Weaver et al. 1 have reported that 14% of all cancer survivors in the USA have minor dependent children, representing a population of about 1.58 million survivors and 2.85 million children. A significant part of working age population is thus struggling with concerns related to serious illness, parenting and the wellbeing of children.
Endotoxin [lipopolysaccharide (LPS)] from Gram-negative bacteria is found in amniotic fluid in intrauterine infections that associate with the risk for spontaneous premature birth, bronchopulmonary dysplasia (BPD), and respiratory distress syndrome. Toll-like receptor 4 (TLR4) is the signaling receptor for LPS. The aim was to investigate the primary inflammatory response in mice shortly after administration of LPS to the dam (14 and 17 d of pregnancy), to the newborn, or into the amniotic fluid. The expression levels of TLR4, IL-1, tumor necrosis factor-␣, IL-6, IL-10, macrophage inflammatory protein-2, and IL-1 receptor 1 were studied with ribonuclease protection assay. In addition, TLR4 protein was analyzed with Western blotting. The fetal membranes expressed TLR4 mRNA and protein and showed an acute cytokine response to LPS when LPS was administrated into the amniotic fluid. There was distinct ontogeny in the responsiveness of fetal lung to LPS: on fetal day 14 (term 20 d), both the expression of TLR4 and the acute cytokine response were undetectable 5 h after LPS; they became detectable by fetal day 17. TLR4 and the cytokine response further increased after birth. In maternal lung, the TLR4 expression was strongest and upregulated in parallel with the induction of the cytokines. We propose that TLR4 controls the magnitude of the LPS-induced cytokine response during the perinatal period. Intrauterine infection and intrauterine inflammatory response syndrome are associated with preterm birth and bronchopulmonary dysplasia (BPD) in premature infants. Among the predisposing conditions, urinary tract infections and infections that affect the abdominal organs are often caused by Gram-negative bacteria. The onset of premature birth is associated with increased endotoxin and cytokine concentrations in amniotic fluid and inflammation in fetal membranes (1,2).The infection is detected by the host organism by recognizing specific structures produced only by microorganisms. These elements are called pathogen-associated molecular patterns (PAMPs) (3,4). Recognition of PAMPs is an innate mechanism that is mediated by specific pattern recognition receptors, which activate the acute inflammatory response. Lipopolysaccharide (LPS; also known as endotoxin) is one of the best known PAMPs. It is a constituent of the cell wall of Gram-negative bacteria that starts a complex cascade of events in inflammatory cells, particularly in monocytes and macrophages. This leads to the production of endogenous mediators, including the primary proinflammatory cytokines IL-1 and tumor necrosis factor-␣ (TNF-␣), and a number of other mediators that are induced in various cells (5-7).A principal LPS signaling receptor is a recently characterized transmembrane pattern recognition receptor, Toll-like receptor 4 (TLR4) (8 -11). TLR4 is a member of the mammalian Toll/IL-1 receptor family that is homologous to the Drosophila Toll family, which controls the dorsoventral patterning in the embryo and the antimicrobial response in the adult fly (12,13)....
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.