Immunobiology of Acute Chorioamnionitis.

Acute chorioamnionitis is characterized by neutrophilic infiltration and inflammation at the maternal fetal interface. It is a relatively common complication of pregnancy and can have devastating consequences including preterm labor, maternal infections, fetal infection/inflammation, fetal lung, brain, and gastrointestinal tract injury. In this review, we will discuss current understanding of the pathogenesis, immunobiology, and mechanisms of this condition. Most commonly, acute chorioamnionitis is a result of ascending infection with relatively low-virulence organisms such as the Ureaplasma species. Furthermore, recent vaginal microbiome studies suggest that there is a link between vaginal dysbiosis, vaginal inflammation, and ascending infection. Although less common, microorganisms invading the maternal-fetal interface via hematogenous route (e.g., Zika virus, Cytomegalovirus, and Listeria) can cause placental villitis and severe fetal inflammation and injury. We will provide an overview of the knowledge gleaned from different animal models of acute chorioamnionitis and the role of different immune cells in different maternal-fetal compartments. Lastly, we will discuss how infectious agents can break the maternal tolerance of fetal allograft during pregnancy and highlight the novel future therapeutic approaches

Sustained inflation at birth did not alter lung injury from mechanical ventilation in surfactant-treated fetal lambs.

BackgroundSustained inflations (SI) are used with the initiation of ventilation at birth to rapidly recruit functional residual capacity and may decrease lung injury and the need for mechanical ventilation in preterm infants. However, a 20 second SI in surfactant-deficient preterm lambs caused an acute phase injury response without decreasing lung injury from subsequent mechanical ventilation.HypothesisA 20 second SI at birth will decrease lung injury from mechanical ventilation in surfactant-treated preterm fetal lambs.MethodsThe head and chest of fetal sheep at 126±1 day GA were exteriorized, with tracheostomy and removal of fetal lung fluid prior to treatment with surfactant (300 mg in 15 ml saline). Fetal lambs were randomized to one of four 15 minute interventions: 1) PEEP 8 cmH2O; 2) 20 sec SI at 40 cmH2O, then PEEP 8 cmH2O; 3) mechanical ventilation with 7 ml/kg tidal volume; or 4) 20 sec SI then mechanical ventilation at 7 ml/kg. Fetal lambs remained on placental support for the intervention and for 30 min after the intervention.ResultsSI recruited a mean volume of 6.8±0.8 mL/kg. SI did not alter respiratory physiology during mechanical ventilation. Heat shock protein (HSP) 70, HSP60, and total protein in lung fluid similarly increased in both ventilation groups. Modest pro-inflammatory cytokine and acute phase responses, with or without SI, were similar with ventilation. SI alone did not increase markers of injury.ConclusionIn surfactant treated fetal lambs, a 20 sec SI did not alter ventilation physiology or markers of lung injury from mechanical ventilation

The Response of Serum Cortisol and Leptin Levels to Academic Stress

Background: Medical students are subjected to various types of stress during the academic course and they react differently. This study is an attempt to establish a relationship between the coping abilities, serum cortisol and leptin levels in response to academic examination stress in first year medical students. Methods: Thirty four 1st year medical students between 18 to 21 yrs of age were randomly selected and their coping abilities were assessed using the State Trait Anxiety Inventory. Two fasting blood samples were drawn, one on the day of examination (Situation I) and the second after the completion of the examination (Situation II). Serum cortisol and leptin levels were estimated using a standardized RIA Kit and the levels obtained were correlated with the psychometric data. Results: The results showed increased levels of cortisol prior to examination in the poor adjusters in comparison to the good adjusters. The levels of cortisol decreased after examination in both good and poor adjusters with the poor adjusters showing higher levels. On the other hand, leptin levels increased in good adjusters in comparison with poor adjusters in Situation I and in Situation II the good adjusters showed a marginal decrease and poor adjusters maintained the same levels of leptin. Conclusion: Cortisol and leptin respond inversely to academic stress. Cortisol levels sharply decline from stressful to post-stressful situation indicating the wane of stress

Property development in S.G iron by heat treatment

Cast iron is an alloy of iron containing more than 2% carbon as an alloying element. It has almost no ductility and must be formed by casting. ductile iron structure is developed from the melt of cast iron. The presence of Si in higher amount promote the graphitizarion inhibiting carbon to form carbides with carbide forming elements present the carbon forms into spheres when Ce, Mg, are added to the melt of iron with very low sulphur content having this special microstructure containing graphite in nodular form gives ductile irin thus the ductility and toughness superior to that of any cast iron and steel structure finding numerous success in industrial application however heat treatment is a valuable and versatile too for extending both the consistency and range of properties of ductile iron casting beyond the limits of those produced in as-cast condiotion. Thus to fully utilize the potentioal of ductile iron castings, the designer should be aware of wide range of heat treatment available for ductile irin and its response to this heat treatment. Although ductile iron and steel are superficially similar metallurgically, the high carbon and silicon level in ductile iron results in important differences in their respionses to heat treatment. The high carbon leels increase hardenibility, permitting heavier sections to be heat treated with lower requirements for expensive alloying or severe quenching media also may cause, quench cracking due to the formation of high C martensite. This undesireable phenomena maje the control of composition, austenitising temperature and quenching conditions more critical in ductile iron. Since the formation of martensite is accompanied byu internal stresses, tempering is necessary in order to relieve the internal stresses, decreases the amount of retained austenite and reduces the probability of cracking. Austempering is a critical heat treating process in which austenite transforms isothermally to lower bainite rather than martensite and thus objectively reduces distortion and cracks. It is possible to achieve much larger ranges of tensile strength, ductility with toughness by adopting austempering, heat treatment process of ductile iron

Association of Chorioamnionitis with Aberrant Neonatal Gut Colonization and Adverse Clinical Outcomes.

ObjectiveChorioamnionitis (inflammation of the placenta and fetal membranes) and abnormal gastrointestinal colonization have been associated with an increased risk of sepsis and death in preterm infants, but whether chorioamnionitis causes abnormal pioneering gastrointestinal colonization in infants is not known. We determined the relationship between chorioamnionitis, altered infant fecal microbiome indicating abnormal gastrointestinal colonization, and adverse outcomes.Study designPreterm infants ≤ 28 weeks at birth were enrolled from 3 level III NICUs in Cincinnati, Ohio and Birmingham, Alabama. Sequencing for 16S microbial gene was performed on stool samples in the first 3 weeks of life. Chorioamnionitis was diagnosed by placental histology. Late onset sepsis and death outcomes were analyzed in relation to fecal microbiota and chorioamnionitis with or without funisitis (inflammation of the umbilical cord).ResultsOf the 106 enrolled infants, 48 infants had no chorioamnionitis, 32 infants had chorioamnionitis but no funisitis (AC), and 26 infants had chorioamnionitis with funisitis (ACF). The fecal samples from ACF infants collected by day of life 7 had higher relative abundance of family Mycoplasmataceae (phylum Tenericutes), genus Prevotella (phylum Bacteroidetes) and genus Sneathia (phylum Fusobacteria). Further, AC and ACF infants had higher incidence of late-onset sepsis/death as a combined outcome. Presence of specific clades in fecal samples, specifically, order Fusobacteria, genus Sneathia or family Mycoplasmataceae, were significantly associated with higher risk of sepsis or death.ConclusionThe results support the hypothesis that specific alterations in the pioneering infant gastrointestinal microbiota induced by chorioamnionitis predispose to neonatal sepsis or death

Fetal skin as a pro-inflammatory organ: Evidence from a primate model of chorioamnionitis.

BackgroundIntrauterine infection is a primary cause of preterm birth and fetal injury. The pro-inflammatory role of the fetal skin in the setting of intrauterine infection remains poorly characterized. Whether or not inflammation of the fetal skin occurs in primates remains unstudied. Accordingly, we hypothesized that: i) the fetal primate skin would mount a pro-inflammatory response to preterm birth associated pro-inflammatory agents (lipopolysaccharides from Escherichia coli, live Ureaplasma parvum, interleukin-1β) and; ii) that inhibiting interleukin-1 signaling would decrease the skin inflammatory response.MethodsRhesus macaques with singleton pregnancies received intraamniotic injections of either sterile saline (control) or one of three pro-inflammatory agonists: E. coli lipopolysaccharides, interluekin-1β or live U. parvum under ultrasound guidance. A fourth group of animals received both E. coli lipopolysaccharide and interleukin-1 signaling inhibitor interleukin-1 receptor antagonist (Anakinra) prior to delivery. Animals were surgically delivered at approximately 130 days' gestational age.ResultsIntraamniotic lipopolysaccharide caused an inflammatory skin response characterized by increases in interluekin-1β,-6 and -8 mRNA at 16 hours. There was a modest inflammatory response to U. parvum, but interleukin-1β alone caused no inflammatory response in the fetal skin. Intraamniotic Anakinra treatment of lipopolysaccharide-exposed animals significantly reduced skin inflammation.ConclusionsIntraamniotic lipopolysaccharide and U. parvum were associated with modest increases in the expression of inflammatory mediators in primate fetal skin. Although administration of Interleukin-1β alone did not elicit an inflammatory response, lipopolysaccharide-driven skin inflammation was decreased following intraamniotic Anakinra therapy. These findings provide support for the role of the fetal skin in the development of the fetal inflammatory response

Oral, nasal and pharyngeal exposure to lipopolysaccharide causes a fetal inflammatory response in sheep.

BackgroundA fetal inflammatory response (FIR) in sheep can be induced by intraamniotic or selective exposure of the fetal lung or gut to lipopolysaccharide (LPS). The oral, nasal, and pharyngeal cavities (ONP) contain lymphoid tissue and epithelium that are in contact with the amniotic fluid. The ability of the ONP epithelium and lymphoid tissue to initiate a FIR is unknown.ObjectiveTo determine if FIR occurs after selective ONP exposure to LPS in fetal sheep.MethodsUsing fetal recovery surgery, we isolated ONP from the fetal lung, GI tract, and amniotic fluid by tracheal and esophageal ligation and with an occlusive glove fitted over the snout. LPS (5 mg) or saline was infused with 24 h Alzet pumps secured in the oral cavity (n = 7-8/group). Animals were delivered 1 or 6 days after initiation of the LPS or saline infusions.ResultsThe ONP exposure to LPS had time-dependent systemic inflammatory effects with changes in WBC in cord blood, an increase in posterior mediastinal lymph node weight at 6 days, and pro-inflammatory mRNA responses in the fetal plasma, lung, and liver. Compared to controls, the expression of surfactant protein A mRNA increased 1 and 6 days after ONP exposure to LPS.ConclusionONP exposure to LPS alone can induce a mild FIR with time-dependent inflammatory responses in remote fetal tissues not directly exposed to LPS

Unique transcriptomic landscapes identified in idiopathic spontaneous and infection related preterm births compared to normal term births.

Preterm birth (PTB) is leading contributor to infant death in the United States and globally, yet the underlying mechanistic causes are not well understood. Histopathological studies of preterm birth suggest advanced villous maturity may have a role in idiopathic spontaneous preterm birth (isPTB). To better understand pathological and molecular basis of isPTB, we compared placental villous transcriptomes from carefully phenotyped cohorts of PTB due to infection or isPTB between 28-36 weeks gestation and healthy term placentas. Transcriptomic analyses revealed a unique expression signature for isPTB distinct from the age-matched controls that were delivered prematurely due to infection. This signature included the upregulation of three IGF binding proteins (IGFBP1, IGFBP2, and IGFBP6), supporting a role for aberrant IGF signaling in isPTB. However, within the isPTB expression signature, we detected secondary signature of inflammatory markers including TNC, C3, CFH, and C1R, which have been associated with placental maturity. In contrast, the expression signature of the gestational age-matched infected samples included upregulation of proliferative genes along with cell cycling and mitosis pathways. Together, these data suggest an isPTB molecular signature of placental hypermaturity, likely contributing to the premature activation of inflammatory pathways associated with birth and providing a molecular basis for idiopathic spontaneous birth