Cranial neurotransmitter alteration in newborn piglets exposed to oxygen.

BACKGROUND: To evaluate the influence of hyperoxia on neurotransmitters in the developing brain of newborn piglets. METHODS: Ten newborn piglets were randomly assigned to hyperoxia (inhaled 100% oxygen) or control (inhaled room air) groups and ventilated for 4 hours. Blood samples were obtained at 0, 15, 30, and then every 30 minutes for 4 hours. Extracts of whole brain tissue were assayed for dopamine, serotonin, and their metabolites using high-performance liquid chromatography. RESULTS: In comparison with the control group, there was a general trend of lower neurotransmitter content in the brains of the hyperoxia group. In addition, the levels of dopamine and 3,4-dihydroxyphenylacetic acid in the left frontal lobe, and serotonin in the right occipital lobe and left frontal lobe, of the hyperoxia group were significantly lower compared with the control group (p < 0.05). CONCLUSION: The results indicate that hyperoxia may alter the production or metabolism of dopamine and serotonin in some cortical areas of the neonatal central nervous system, and it tended to have some inhibitory effects. Therefore, pediatricians should be very judicious in using high oxygen on the developing brain.

The paracrine effect of exogenous growth hormone alleviates dysmorphogenesis caused by tbx5 deficiency in zebrafish (Danio rerio) embryos.

BACKGROUND: Dysmorphogenesis and multiple organ defects are well known in zebrafish (Danio rerio) embryos with T-box transcription factor 5 (tbx5) deficiencies, mimicking human Holt-Oram syndrome. METHODS: Using an oligonucleotide-based microarray analysis to study the expression of special genes in tbx5 morphants, we demonstrated that GH and some GH-related genes were markedly downregulated. Zebrafish embryos microinjected with tbx5-morpholino (MO) antisense RNA and mismatched antisense RNA in the 1-cell stage served as controls, while zebrafish embryos co-injected with exogenous growth hormone (GH) concomitant with tbx5-MO comprised the treatment group. RESULTS: The attenuating effects of GH in tbx5-MO knockdown embryos were quantified and observed at 24, 30, 48, 72, and 96 h post-fertilization. Though the understanding of mechanisms involving GH in the tbx5 functioning complex is limited, exogenous GH supplied to tbx5 knockdown zebrafish embryos is able to enhance the expression of downstream mediators in the GH and insulin-like growth factor (IGF)-1 pathway, including igf1, ghra, and ghrb, and signal transductors (erk1, akt2), and eventually to correct dysmorphogenesis in various organs including the heart and pectoral fins. Supplementary GH also reduced apoptosis as determined by a TUNEL assay and decreased the expression of apoptosis-related genes and proteins (bcl2 and bad) according to semiquantitative reverse-transcription polymerase chain reaction and immunohistochemical analysis, respectively, as well as improving cell cycle-related genes (p27 and cdk2) and cardiomyogenetic genes (amhc, vmhc, and cmlc2). CONCLUSIONS: Based on our results, tbx5 knockdown causes a pseudo GH deficiency in zebrafish during early embryonic stages, and supplementation of exogenous GH can partially restore dysmorphogenesis, apoptosis, cell growth inhibition, and abnormal cardiomyogenesis in tbx5 knockdown zebrafish in a paracrine manner.

Application of a molecular method for the classification of human enteroviruses and its correlation with clinical manifestations.

BACKGROUND/PURPOSE: A new molecular classification scheme has recently been adopted that groups all enteroviruses into four species, designated human enterovirus A (HEV-A) through D. In this study, we tried to demonstrate the correlation between this molecular classification scheme and clinical manifestations in patients. METHODS: We retrospectively reclassified the clinical isolates of enteroviruses from the preceding 4.5 years in our virology laboratory using reverse transcription-polymerase chain reaction, and reviewed the clinical manifestations of 138 pediatric patients. RESULTS: We reclassified 23 isolates of the five serotypes into the HEV-A group, 110 isolates of 16 sero-types into the HEV-B group, five isolates into the HEV-C group, and no isolate of the HEV-D group. HEV-A species caused significantly more hand-foot-and-mouth disease (p < 0.001), herpangina (p = 0.029), and myoclonic jerks (p < 0.001) compared with HEV-B species. However, HEV-B species caused significantly more pharyngitis (p = 0.043), respiratory tract infections (p = 0.046), nausea and vomiting (p = 0.007), and aseptic meningitis (p = 0.001). The only death in our report was caused by coxsackievirus A16, which belonged to the HEV-A group. CONCLUSION: The association between the molecular classification of enteroviruses and related disease patterns is an important finding. We suggest that this molecular classification could be applied in a clinical laboratory as an alternative method under certain circumstances, such as limited availability of antisera or questionable serotyping results, to identify the untypeable isolates.