Mechanism of Ca2+-influx and Ca2+/calmodulin-dependent protein kinase IV activity during in utero hypoxia in cerebral cortical neuronal nuclei of the guinea pig fetus at term.

Previously we showed that following hypoxia there is an increase in nuclear Ca(2+)-influx and Ca(2+)/calmodulin-dependent protein kinase IV activity (CaMK IV) in the cerebral cortex of term guinea pig fetus. The present study tests the hypothesis that clonidine administration will prevent hypoxia-induced increased neuronal nuclear Ca(2+)-influx and increased CaMK IV activity, by blocking high-affinity Ca(2+)-ATPase. Studies were conducted in 18 pregnant guinea pigs at term, normoxia (Nx, n=6), hypoxia (Hx, n=6) and clonidine with Hx (Hx+Clo, n=6).

Effect of hypoxia on the expression of procaspase-9 and procaspase-3 in neuronal nuclear, mitochondrial and cytosolic fractions of the cerebral cortex of newborn piglets.

Previous studies have shown that cerebral hypoxia results in increased activity of caspase-9, a key initiator of programmed cell death, in the cytosolic fractions of the cerebral cortex of newborn piglets. The present study tests the hypothesis that hypoxia results in increased expression of procaspase-9 and procaspase-3 in neuronal nuclear, mitochondrial and cytosolic fractions of the cerebral cortex of newborn piglets. To test this hypothesis, expression of procaspase-9 and procaspase-3 was determined in 10 newborn piglets divided into two groups: normoxic (Nx, n=5) and hypoxic (Hx, n=5).

Early-onset sepsis with Staphylococcus auricularis in an extremely low-birth weight infant - an uncommon pathogen.

Coagulase-negative staphylococci (CoNS) are often dismissed as a contaminant of blood cultures and are rarely considered as an etiology of perinatally acquired infections. We describe a case of early-onset sepsis with Staphylococcus auricularis in an extremely low-birth weight infant.

Class III beta-tubulin and gamma-tubulin are co-expressed and form complexes in human glioblastoma cells.

We have previously shown that the neuronal-associated class III beta-tubulin isotype and the centrosome-associated gamma-tubulin are aberrantly expressed in astrocytic gliomas (Cell Motil Cytoskeleton 2003, 55:77-96; J Neuropathol Exp Neurol 2006, 65:455-467). Here we determined the expression, distribution and interaction of betaIII-tubulin and gamma-tubulin in diffuse-type astrocytic gliomas (grades II-IV) (n = 17) and the human glioblastoma cell line T98G. By immunohistochemistry and immunofluorescence microscopy, betaIII-tubulin and gamma-tubulin were co-distributed in anaplastic astrocytomas and glioblastomas and to a lesser extent, in low-grade diffuse astrocytomas (P < 0.

Mechanisms of expression of apoptotic protease activating factor-1 (Apaf-1) in nuclear, mitochondrial and cytosolic fractions of the cerebral cortex of newborn piglets.

Apoptotic protease activating factor-1 (Apaf-1) is a critical regulator of apoptosis and a crucial part of the apoptosome that is assembled in response to several cellular stresses like hypoxia. We have previously shown that hypoxia results in increased influx of nuclear Ca(2+) and increased expression of nuclear apoptotic proteins. The present study investigates that Apaf-1 is expressed during hypoxia in the cerebral cortex of newborn piglets and that administration of clonidine prevents the hypoxia induced increase expression of Apaf-1.

Glioneuronal phenotype in a diencephalic pilomyxoid astrocytoma.

We report the presence of divergent populations of cells in a hypothalamic/chiasmatic pilomyxoid astrocytoma of an 11-month-old male, exhibiting differential immunohistochemical localizations for glial fibrillary acidic protein (GFAP) and synaptophysin. The tumor cells were negative for Neu-N and neurofilament protein. Ultrastructurally, the tumor comprised 2 cell types, one with features attributable to a neuronal phenotype alongside cells exhibiting an overt astroglial phenotype.

Nuclear Ca(++)-influx, Ca (++)/calmodulin-dependent protein kinase IV activity and CREB protein phosphorylation during post-hypoxic reoxygenation in neuronal nuclei of newborn piglets: the role of nitric oxide.

The present study tests the hypothesis that post-hypoxic reoxygenation results in an nitric oxide (NO)-mediated increase in nuclear Ca(++)-influx, increased calmodulin kinase (CaM kinase) IV activity, and increased Ser(133) phosphorylation of cyclic AMP response element binding (CREB) protein in neuronal nuclei of the cerebral cortex of newborn piglets. Piglets were divided into normoxic (Nx), hypoxic (Hx, FiO(2) = 0.07 for 1 h), hypoxic with 6 h reoxygenation (Hx + reox), and Hx + reox injected with 7-nitroindazole sodium salt (7-NINA), a nNOS inhibitor, immediately after hypoxia (Hx + 7-NINA).

Effect of 7-nitroindazole sodium on the cellular distribution of neuronal nitric oxide synthase in the cerebral cortex of hypoxic newborn piglets.

Cerebral hypoxia results in generation of nitric oxide (NO) free radicals by Ca(++)-dependent activation of neuronal nitric oxide synthase (nNOS). The present study tests the hypothesis that the hypoxia-induced increased expression of nNOS in cortical neurons is mediated by NO. To test this hypothesis the cellular distribution of nNOS was determined immunohistochemically in the cerebral cortex of hypoxic newborn piglets with and without prior exposure to the selective nNOS inhibitor 7-nitroindazole sodium (7-NINA).

Effect of nitric oxide synthase inhibition during post-hypoxic reoxygenation on Bax and Bcl-2 protein expression and DNA fragmentation in neuronal nuclei of newborn piglets.

Previous studies have shown that cerebral tissue hypoxia results in increased generation of oxygen-free radicals including nitric oxide (NO), expression of the proapoptotic protein Bax and fragmentation of nuclear DNA. The present study tests the hypothesis that post-hypoxic reoxygenation for 6 h following hypoxia (FiO2=0.06 for 1 h) results in continued hypoxia-induced, NO-mediated expression of the Bax protein and nuclear DNA fragmentation in the cerebral cortex of newborn piglets.

Nitric oxide-mediated mechanism of neuronal nitric oxide synthase and inducible nitric oxide synthase expression during hypoxia in the cerebral cortex of newborn piglets.

Previously, we have shown that hypoxia results in increased generation of nitric oxide free radicals in the cerebral cortex of newborn piglets that may be due to up-regulation of nitric oxide synthases, neuronal nitric oxide synthase and inducible nitric oxide synthase. The present study tests the hypothesis that hypoxia results in increased expression of neuronal nitric oxide synthase and inducible nitric oxide synthase in the cerebral cortex of newborn piglets and that the increased expression is nitric oxide-mediated. Newborn piglets, 2-4 days old, were divided to normoxic (n=4), hypoxic (n=4) and hypoxic-treated with 7-nitro-indazole-sodium salt, a selective neuronal nitric oxide synthase inhibitor (hypoxic-7-nitro-indazole-sodium salt, n=6, 1 mg/kg, 60 min prior to hypoxia).

Effect of neuronal nitric oxide synthase inhibition on caspase-9 activity during hypoxia in the cerebral cortex of newborn piglets.

Previous studies have shown that cerebral hypoxia results in increased activity of caspase-9, a key initiator of programmed cell death. We have also shown increased nitric oxide (NO) free radical generation during hypoxia in the cerebral cortex of newborn piglets. The present study tests the hypothesis that hypoxia-induced increase in caspase-9 activity in the cerebral cortex of newborn piglets is mediated by NO derived from neuronal nitric oxide synthase (nNOS).

Effects of magnesium sulfate administration during hypoxia on CaM kinase IV and protein tyrosine kinase activities in the cerebral cortex of newborn piglets.

The present study tested the hypothesis that magnesium sulfate administration prior to hypoxia prevents hypoxia-induced increase in Ca(2+)/Calmodulin-dependent-kinase (CaM Kinase) IV and Protein Tyrosine Kinase (PTK ) activities. Animals were randomly divided into normoxic (Nx), hypoxic (Hx) and magnesium-pretreated hypoxic (Mg(2+)-Hx) groups. Cerebral hypoxia was confirmed biochemically by measuring ATP and phosphocreatine (PCr) levels.

Sleep disorders, immunizations, sports injuries, autism.

Purpose Of Review: The purpose of this article is to summarize and synthesize the recent literature in four very important areas for pediatric office practice: sleep disorders, new immunizations, sports injuries, and autism. Important articles in each area are highlighted.

Recent Findings: The management of pediatric and adolescent sleep disorders is in the forefront of the pediatric literature.

Spondylolysis and spondylolisthesis in the child and adolescent: a new classification.

Spondylolysis and spondylolisthesis commonly are diagnosed in children and adolescents. The diagnostic workup and treatment plan vary widely among physicians. Although the orthopaedic literature is extensive on the topic, it is our opinion that a lack of clarity exists with regards to etiology, terminology, subtypes of spondylolysis and spondylolisthesis, and treatment.

Hypercapnia-induced modifications of neuronal function in the cerebral cortex of newborn piglets.

There is significant controversy over the effects of hypercapnia on the human newborn brain. Previous studies have shown that 1 h of an arterial CO2 pressure (Paco2) of 80 mm Hg alters brain cell membrane Na+K+-ATPase enzyme activity in the cerebral cortex of newborn piglets. The present study tests the hypothesis that hypercapnia (either a Paco2 of 65 or 80 mm Hg) results in decreased energy metabolism and alters neuronal nuclear enzyme activity and protein expression, specifically Ca++/calmodulin-dependent kinase (CaMK) IV activity, phosphorylation of cAMP response element binding protein (CREB), and expression of apoptotic proteins in cortical neuronal nuclei of newborn piglets.

Medical home, obesity, acute otitis media, and otitis media with effusion.

Four areas of pediatric office practice are reviewed: the medical home concept, obesity, acute otitis media, and otitis media with effusion. The concept of the medical home in the care of children with special health care needs, its effect on health care outcomes, and its application to office practice are discussed. The epidemiology and causes of obesity are covered along with options for obesity screening and prevention.

Effect of hypoxia on the expression and activity of mitogen-activated protein (MAP) kinase-phosphatase-1 (MKP-1) and MKP-3 in neuronal nuclei of newborn piglets: the role of nitric oxide.

Mitogen-activated protein kinase-1 (MAPK-1) and MAPK-3 regulate survival and programmed cell death of neurons under stress conditions. The activity of MAPK-1 and MAPK-3 is regulated by dual specificity phosphatases: MKP-1 and MKP-3. In previous studies, we have shown that cerebral hypoxia results in increased activation of MAPK-1 and MAPK-3.

Anesthetic management of a patient with asystolic spells.

Breathholding spells are common in infancy. In a subset of patients they may be associated with bradycardia and asystole. Management of these children necessitates placement of a permanent pacemaker.

ATP and cytochrome c-dependent inhibition of caspase-9 activity in the cerebral cortex of newborn piglets.

The present study investigates the mechanism of activation of caspase-9 during hypoxia and tests the hypothesis that ATP and cytochrome c regulate the activity of caspase-9 in the cerebral cortex of newborn piglets. Cerebral tissue hypoxia was documented by decreased levels of high energy phosphates, ATP and phosphocreatine (PCr). Cytosolic fractions were prepared from cerebral cortices and passed through a G50 column, to remove endogenous ATP and cytochrome c.

Nitric oxide-mediated alterations of protein tyrosine phosphatase activity and expression during hypoxia in the cerebral cortex of newborn piglets.

The present study tested the hypothesis that the hypoxia-induced decrease in protein tyrosine phosphatase (PTP) activity in the membranes and increased activity and expression of PTPs (PTP-1B, PTP-SH1 and 2) in the cytosol of the cerebral cortex of newborn piglets are mediated by nitric oxide (NO). To test this hypothesis, PTP activity in cell membranes and activity and expression were measured in the cytosol of normoxic (Nx, n = 5), hypoxic (Hx, n = 5), and 7-nitro-indazole sodium salt (7-NINA), a selective inhibitor of neuronal nitric oxide synthase (nNOS), pretreated hypoxic (7-NINA+Hx, n = 6) newborn piglets. PTP activity in cortical cell membranes was lower in the Hx group as compared to the Nx group and this decrease was prevented in the 7-NINA+Hx group.

Effect of neuronal nitric oxide synthase inhibition on CA2+/calmodulin kinase kinase and CA2+/calmodulin kinase IV activity during hypoxia in cortical nuclei of newborn piglets.

The present study tests the hypothesis that cerebral tissue hypoxia results in increased Ca(2+)/calmodulin (CaM) kinase kinase activity and that the administration of nitric oxide synthase inhibitors (N-nitro-l-arginine [NNLA], or 7-nitroindazole sodium [7-NINA]) prior to the onset of hypoxia will prevent the hypoxia-induced increase in the enzyme activity. To test this hypothesis, CaM kinase kinase and CaM kinase IV activities were determined in normoxic, hypoxic, NNLA-treated hypoxic, and 7-NINA-treated hypoxic piglets. Hypoxia was induced (FiO(2)=0.

A dysmorphic newborn infant with a complex rearrangement involving chromosomes 2, 4, and 6 detected by fluorescence in situ hybridization (FISH).

A newborn female infant with multiple congenital anomalies was found to have an unusual and abnormal karyotype. Cytogenetic studies revealed an apparent balanced translocation between chromosome 4q31.3 and chromosome 6q25.

Inositol tetrakisphosphate (IP4)- and inositol triphosphate (IP3)-dependent Ca2+ influx in cortical neuronal nuclei of newborn piglets following graded hypoxia.

Previous studies have shown that hypoxia results in a modification of the binding characteristics of the neuronal nuclear membrane inositol tetrakisphosphate (IP4) and inositol triphosphate (IP3) receptors. The present study tests the hypothesis that hypoxia-induced modification of the IP4 and IP3 receptors results in increased IP4 and IP3 dependent Ca2+ influx in neuronal nuclei as a function of the degree of cerebral tissue hypoxia in newborn piglets. Studies were performed in piglets, 3-5 days old, divided into normoxic (N = 5) and hypoxic (N = 6) groups.

Nitric oxide-mediated activation of extracellular signal-regulated kinase (ERK) and c-jun N-terminal kinase (JNK) during hypoxia in cerebral cortical nuclei of newborn piglets.

Previous studies have shown that mitogen-activated protein kinases, such as extracellular signal-related kinase (ERK) and c-Jun N-terminal kinase (JNK), mediate signal transduction from cell surface receptors to the nucleus and phosphorylate anti-apoptotic proteins thereby regulating programmed cell death. The present study tests the hypotheses that hypoxia activates ERK and JNK in neuronal nuclei of newborn piglets and the hypoxia-induced activation of ERK and JNK is mediated by nitric oxide (NO). Activated ERK and JNK were assessed by determining phosphorylated ERK and JNK using immunoblotting in six normoxic (Nx) and 10 hypoxic (Hx) and five N-nitro-L-arginine (a NOS inhibitor, 40 mg/kg,) -pretreated hypoxic (N-nitro-L-arginine [NNLA]-Hx) 3-5 day old piglets.