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1.
Sci Rep ; 6: 21859, 2016 Feb 24.
Article in English | MEDLINE | ID: mdl-26905012

ABSTRACT

In animal models, neonatal exposure to general anesthetics significantly increased neuronal apoptosis with subsequent behavioral deficits in adulthood. Although the underlying mechanism is largely unknown, involvement of extracellular signal-regulated kinases (ERKs) is speculated since ERK phosphorylation is decreased by neonatal anesthetic exposure. Importance of ERK phosphorylation for neuronal development is underscored by our recent finding that transient suppression of ERK phosphorylation during the neonatal period significantly increased neuronal apoptosis and induced behavioral deficits. However, it is still unknown as to what extent decreased ERK phosphorylation contributes to the mechanism underlying anesthetic-induced toxicity. Here we investigated the causal relationship of decreased ERK phosphorylation and anesthetic-induced toxicity in the developing brain. At postnatal day 6 (P6), mice were exposed to sevoflurane (2%) or the blood-brain barrier-penetrating MEK inhibitor, α-[amino[(4-aminophenyl)thio]methylene]-2-(trifluoromethyl)benzeneacetonitrile (SL327) (50 mg/kg). Transient suppression of ERK phosphorylation by an intraperitoneal injection of SL327 at P6 significantly increased apoptosis similar to sevoflurane-induced apoptosis. Conversely, SL327 administration at P14 or P21 did not induce apoptosis, even though ERK phosphorylation was inhibited. Restoring ERK phosphorylation by administration of molecular hydrogen ameliorated sevoflurane-induced apoptosis. Together, our results strongly suggests that suppressed ERK phosphorylation is critically involved in the mechanism underlying anesthetic-induced toxicity in the developing brain.


Subject(s)
Anesthetics, Inhalation/toxicity , Brain/metabolism , Methyl Ethers/toxicity , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Oxidative Stress/drug effects , Aminoacetonitrile/analogs & derivatives , Aminoacetonitrile/pharmacology , Animals , Animals, Newborn , Apoptosis/drug effects , Behavior, Animal/drug effects , Blood-Brain Barrier/drug effects , Blood-Brain Barrier/metabolism , Blotting, Western , Brain/drug effects , Brain/pathology , Caspase 3/metabolism , Hydrogen/pharmacology , Mice , Mice, Inbred C57BL , Microscopy, Fluorescence , Mitogen-Activated Protein Kinase 1/antagonists & inhibitors , Mitogen-Activated Protein Kinase 3/antagonists & inhibitors , Phosphorylation/drug effects , Reactive Oxygen Species/metabolism , Sevoflurane , Time Factors
2.
Arch Gynecol Obstet ; 288(3): 521-5, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23525596

ABSTRACT

OBJECTIVE: We tried to identify the influence on the fetus infected with parvovirus B19 (PB19) and retrospectively analyze the severity of fetal infection. METHODS: Twenty pregnant women who developed maternal PB19 infection were included in this study. A total of 20 amniotic fluid samples were collected for measurement of PB19-DNA, erythropoietin (Epo) and troponin-T (TnT). RESULTS: Of the 5 fetuses with hydrops, 2 were rescued by fetal therapy. Significant differences between groups were found for Epo and TnT: Epo 107.1 ± 45.3 mU/ml and TnT 0.040 ± 0.028 ng/ml (mean ± standard deviation) for the symptomatic fetus group; and Epo 18.9 ± 13.7 mU/ml and TnT 0.008 ± 0.014 ng/ml for the asymptomatic fetus group (p = 0.043 for both variables). Setting Epo ≥50 mU/ml as the predictor of disease onset resulted in an Odds ratio of 56.0, with a 95 % confidence interval of 7.68-1,108.76. CONCLUSION: The study has determined an amniotic Epo level of ≥50 mU/ml as a factor of the influence on the fetus infected with PB19. The measurement of amniotic Epo level combined with amniotic TnT level is effective for determining the severity of fetal hypoxia.


Subject(s)
Erythropoietin/metabolism , Hydrops Fetalis/diagnostic imaging , Parvoviridae Infections/diagnostic imaging , Parvovirus B19, Human , Pregnancy Complications, Infectious/diagnostic imaging , Troponin T/metabolism , Biomarkers/metabolism , Female , Humans , Hydrops Fetalis/metabolism , Hydrops Fetalis/virology , Multivariate Analysis , Parvoviridae Infections/complications , Parvoviridae Infections/metabolism , Pregnancy , Pregnancy Complications, Infectious/metabolism , Retrospective Studies , Ultrasonography
3.
J Obstet Gynaecol Res ; 39(1): 166-9, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22672496

ABSTRACT

AIMS: Our study aims to estimate whether measurement of maternal anti-cytomegalovirus immunoglobulin-M antibody (CMV-IgM) levels are useful as a screening method for achieving early detection of congenital CMV infection. MATERIAL AND METHODS: Levels of maternal CMV-IgM were measured by enzyme immunoassay in all (n =2865) pregnant women who visited our hospital in the first trimester during the period from January 2005 to December 2009. RESULTS: Among them, 21 individuals (0.73%) had a CMV-IgM titer of ≥0.08 and were judged to be CMV-IgM-positive. Informed consent was obtained from all 21 individuals to perform the confirmation test that quantifies the levels of cytomegalovirus DNA (CMV-DNA) in amniotic fluid by real-time polymerase chain reaction. However, only one (0.03%) of the 21 individuals was CMV-DNA-positive (CMV-DNA concentration, 1.0 × 10(4) copies/ml). CONCLUSION: In order to detect congenital CMV infection in early pregnancy, it is considered appropriate to use ultrasound for close examination of embryo or fetal symptoms indicative of CMV instead of performing serological screening based on CMV-IgM.


Subject(s)
Antibodies, Anti-Idiotypic/analysis , Antibodies, Viral/analysis , Cytomegalovirus Infections/diagnosis , Cytomegalovirus/immunology , Immunoglobulin M/analysis , Pregnancy Complications, Infectious/diagnosis , Adult , Amniotic Fluid/immunology , Cytomegalovirus Infections/immunology , Cytomegalovirus Infections/transmission , Female , Fetus , Humans , Infectious Disease Transmission, Vertical , Pregnancy , Pregnancy Complications, Infectious/immunology , Pregnancy Complications, Infectious/virology
4.
Fetal Diagn Ther ; 29(3): 229-32, 2011.
Article in English | MEDLINE | ID: mdl-21124014

ABSTRACT

OBJECTIVE: There have been a number of studies on immunoglobulin injection into fetuses or mothers during pregnancy for the treatment of congenital cytomegalovirus infection. However, no study has examined the effect of injected immunoglobulin on fetal hemodynamics. In this study, we examined the effect of immunoglobulin injection on fetal hemodynamics by retrospectively measuring the concentrations of several igg subclasses in stored umbilical cord blood sera collected during fetal therapy. METHODS: Five patients who underwent immunoglobulin injection into the fetal abdominal cavity (IFAC) as a fetal therapy during pregnancy were included in this study. Frozen-stored umbilical venous blood samples collected from these patients during IFAC were measured for serum concentrations of each IgG subclass. RESULTS: The largest change was observed in the IgG2 concentration, with a mean increase of 221% following IFAC. The IgG4 concentration also showed a mean increase of 63%. In contrast, the concentration of IgG1, which has the strongest physiological activity of all IgG subclasses examined, only exhibited an overall mean increase of 1.4%. CONCLUSION: Our results confirmed that immunoglobulins are incorporated into the fetal circulation following IFAC.


Subject(s)
Cytomegalovirus Infections/drug therapy , Fetal Blood/metabolism , Immunoglobulin G/metabolism , Immunoglobulins/therapeutic use , Pregnancy Complications, Infectious/drug therapy , Abdominal Cavity/embryology , Blood Circulation/drug effects , Blood Group Incompatibility/drug therapy , Female , Fetal Therapies , Humans , Immunoglobulins/administration & dosage , Pregnancy , Umbilical Veins/chemistry
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