Effects of Cardiopulmonary Support With a Novel Pediatric Pump-Lung in a 30-Day Ovine Animal Model.

The scarcity of donor organs has led to the development of devices that provide optimal long-term respiratory or cardiopulmonary support to bridge recipients as they wait for lung and/or heart transplantation. This study was designed to evaluate the 30-day in vivo performance of the newly developed pediatric pump-lung (PediPL) for cardiopulmonary support using a juvenile sheep model. The PediPL device was placed surgically between the right atrium and descending aorta in eight sheep (25.

Shear-Induced Hemolysis: Species Differences.

The nonphysiological mechanical shear stress in blood-contacting medical devices is one major factor to device-induced blood damage. Animal blood is often used to test device-induced blood damage potential of these devices due to its easy accessibility and low cost. However, the differences in shear-induced blood damage between animals and human have not been well characterized.

Quantification of Shear-Induced Platelet Activation: High Shear Stresses for Short Exposure Time.

Thrombosis and thromboembolism are the life-threatening clinical complications for patients supported or treated with prosthetic cardiovascular devices. The high mechanical shear stress within these devices is believed to be the major contributing factor to cause platelet activation (PA) and function alteration, leading to thrombotic events. There have been limited quantitative data on how the high mechanical shear stress causes platelet activation.

Biocompatibility assessment of a long-term wearable artificial pump-lung in sheep.

The purpose of this study was to assess the biocompatibility of a newly developed long-term wearable artificial pump-lung (APL) in a clinically relevant ovine animal model. The wearable APL device was implanted in five sheep through left thoracotomy. The device was connected between the right atrium and pulmonary artery and evaluated for 30 days.

Pre-clinical evaluation of the infant Jarvik 2000 heart in a neonate piglet model.

Background: The infant Jarvik 2000 heart is a very small, hermetically sealed, intracorporeal, axial-flow ventricular assist device (VAD) designed for circulatory support in neonates and infants. The anatomic fit, short-term biocompatibility and hemodynamic performance of the device were evaluated in a neonate piglet model.

Methods: The infant Jarvik 2000 heart with two different blade profiles (low- or high-flow blade design) was tested in 6 piglets (8.

Murine missing in metastasis (MIM) mediates cell polarity and regulates the motility response to growth factors.

Background: Missing in metastasis (MIM) is a member of the inverse BAR-domain protein family, and in vitro studies have implied MIM plays a role in deforming membrane curvature into filopodia-like protrusions and cell dynamics. Yet, the physiological role of the endogenous MIM in mammalian cells remains undefined.

Principal Findings: We have examined mouse embryonic fibroblasts (MEFs) derived from mice in which the MIM locus was targeted by a gene trapping vector.

Abba promotes PDGF-mediated membrane ruffling through activation of the small GTPase Rac1.

Abba is a member of the I-BAR-domain protein family that is characterized by a convex-shaped membrane-binding motif. Overexpression of GFP-tagged Abba in murine fibroblasts potentiated PDGF-mediated formation of membrane ruffles and lamellipodia. Immunofluorescent microscopy and pull-down analysis revealed that GFP-Abba colocalized with an active form of Rac1 in the membrane ruffles and enhanced the Rac GTPase activity in response to PDGF stimulation.

In vitro and in vivo suppression of hepatocellular carcinoma growth by midkine-antisense oligonucleotide-loaded nanoparticles.

Aim: To synthesize antisense oligonucleotides (ASODNs) of midkine (MK), package the ASODNs with nanoparticles, and to inhibit hepatocellular carcinoma (HCC) growth using these nanoparticles.

Methods: HepG2 cell proliferation was analyzed in vitro using the 3-(4,5-dimethythiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2Htetrazolium, inner salt assay. The in vivo activity of nanoparticles delivering the MK-ASODNs was analyzed by histopathological and immunohistochemical staining and quantitative real time polymerase chain reaction (PCR).

Role of mitogen-activated protein kinase cascades in inducible nitric oxide synthase expression by lipopolysaccharide in a rat Schwann cell line.

It is well known that the mitogen-activated protein kinase (MAPK) signal transduction pathways is involved in the regulation of inducible nitric oxide synthase (iNOS) in many cellular systems. However, sufficient information describing the role of MAPKs on iNOS expression in rat Schwann cells (SCs) is lacking. Therefore the paper was sought to investigate the role of MAPK cascades in iNOS expression following treatment of lipopolysaccharide (LPS) in a rat Schwann cell line RSC 96.

Spatiotemporal expression of SSeCKS in injured rat sciatic nerve.

SSeCKS (src suppressed C kinase substrate) functions in the control of cell signaling and cytoskeletal arrangement. It is expressed in brain and spinal cord, but little is known about its expression in peripheral nerves. In this study, in rats, real-time polymerase chain reaction and Western blot analysis showed that expression of SSeCKS in crushed sciatic nerve reached its highest level 6 hr after crushing, whereas in a transection model, SSeCKS peaked at 2 days in the proximal stump and 12 hr in the distal stump.

Altered beta-1,4-galactosyltransferase I expression during early inflammation after spinal cord contusion injury.

Post-traumatic inflammation has been implicated in secondary tissue damage after spinal cord injury (SCI). beta-1,4-Galactosyltransferase I (beta-1,4-GalT-I) is a key inflammatory mediator that plays a critical role in the initiation and maintenance of inflammatory reaction in diseases. The aim of the current study was to investigate whether beta-1,4-GalT-I is expressed in SCI.

Spatiotemporal expression of Dexras1 after spinal cord transection in rats.

Dexras1, a brain-enriched member of the Ras subfamily of GTPases, as a novel physiologic nitric oxide (NO) effector, anchor neuronal nitric oxide synthase (nNOS) that increased after spinal cord injury (SCI), to specific targets to enhance NO signaling, and is strongly and rapidly induced during treatment with dexamethasone. It is unknown how the central nervous system (CNS) trauma affects the expression of Dexras1. Here we used spinal cord transection (SCT) model to detect expression of Dexras1 at mRNA and protein level in spinal cord homogenates by real-time PCR and Western blot analysis.

The role of beta-1,4-galactosyltransferase-I in the skin wound-healing process.

Cell-surface carbohydrate chains are known to contribute to cell migration, interaction, and proliferation. beta-1,4-galactosyltransferase-I (beta-1,4-GalT-I), which is one of the best-studied glycosyltransferases, plays a key role in the synthesis of type 2 chains in N-glycans and the core 2 branch in O-glycans. Recently, it has been reported that skin wound healing is significantly delayed in beta-1,4-GalT-I mice.

Involvement of CAPON and nitric oxide synthases in rat muscle regeneration after peripheral nerve injury.

Carboxy-terminal PDZ ligand of nNOS (CAPON) protein, as an adaptor, binds to nNOS via the PDZ domain helping regulate neuronal nitric oxide synthase (nNOS) activity at post-synaptic sites in neurons (Jaffrey et al., Neuron, 20, 115-124, 1998). Recently, it has been reported that CAPON is present in mouse muscle and may be involved in mouse muscle growth, injury, and repair possibly by regulating the stability, activity, or position of nNOS (Segalat et al.

Expression of CAPON after spinal cord injury in rats.

The adaptor protein, carboxy-terminal PDZ ligand of nNOS (CAPON), regulates the distribution of neuronal nitric oxide synthase (nNOS) that increased after spinal cord injury (SCI) and produces the key signaling molecule nitric oxide (NO). But little is known about the role of CAPON in the pathological process of SCI. The main objective of the present study was to investigate expression of CAPON and nNOS in a spinal cord contusion model in adult rats.

The role of TNF-alpha and its receptors in the production of Src-suppressed C kinase substrate by rat primary type-2 astrocytes.

Src-suppressed C kinase substrate (SSeCKS), an in vivo and in vitro protein kinase C substrate, is a major lipopolysaccharide (LPS) response protein which markedly upregulated in several organs, including brain, lung, heart, kidney, etc., indicating a possible role of SSeCKS in inflammatory process. In the central nervous system (CNS), astrocytes play a pivotal role in immunity as immunocompetent cells by secreting cytokines and inflammatory mediators, there are two types of astrocytes.

The role of TNF-alpha and its receptors in the production of beta-1,4 galactosyltransferase I and V mRNAs by rat primary astrocytes.

Glycosylation is one of the most important post-translational modifications. It is clear that the single step of beta-1,4-galactosylation is performed by a family of beta-1, 4-galactosyltransferases (beta-1,4-GalTs), and that each member of this family may play a distinct role in different tissues and cells. beta-1,4-GalT I and V are involved in the biosynthesis of N-linked oligosaccharides.

Developmental regulation of PSD-95 and nNOS expression in lumbar spinal cord of rats.

Postsynaptic density (PSD)-95 is originally isolated from glutamatergic synapse where it serves as a physical tether to allow neuronal nitric oxide synthase (nNOS) signaling by N-methyl-D-aspartate receptor (NMDAR) activity. Considering the physiological importance of glutamate receptor and nitric oxide (NO) during development, we examined the spatiotemporal expression of PSD-95 and nNOS in the lumbar spinal cord at a postnatal stage. Temporally, both gene and protein levels of them gradually increased with age after birth, peaked at the postnatal day 14 (P14), and then decreased to an adult level.

Altered gene expression of NIDD in dorsal root ganglia and spinal cord of rats with neuropathic or inflammatory pain.

Nitric oxide and nitric oxide synthases are key players in synaptic plasticity events in spinal cord (SC), which underlies the chronic pain states. To date, little is known about the molecular mechanisms regulating the activity of nitric oxide synthases in nociceptive systems. The present study was aimed at the determination of the gene expression of nNOS-interacting DHHC domain-containing protein with dendritic mRNA (NIDD), a recently identified protein regulating nNOS enzyme activity, in rat SC and dorsal root ganglia (DRG) and studying its regulation in states of nociceptive hypersensitivity in a rat model of neuropathic or inflammatory pain.

Effect of peripheral axotomy on gene expression of NIDD in rat neural tissues.

Peripheral nerve lesion-induced production of neuronal nitric oxide synthase (nNOS) was implicated to influence a range of postaxotomy processes necessary for neuronal survival and nerve regeneration (Zochodne et al., Neuroscience, 91:1515-1527, 1999; Keilhoff et al., Journal of Chemical Neuroanatomy, 24:181-187, 2002, Nitric Oxide, 10:101-111, 2004).

Developmental regulation of SSeCKS expression in rat brain.

SSeCKS (src suppressed C kinase substrate) was identified as a PKC substrate/PKC-binding protein, which plays a role in mitogenic regulatory activity and has a function in the control of cell signaling and cytoskeletal arrangement. Previous studies showed that expression of SSeCKS mRNA and protein levels were developmentally regulated in rat testis and the molecular might have some effects on the process of spermiogenesis. Here we carried out experiments to investigate the expression of SSeCKS in rat brain.

Changes in mRNA for CAPON and Dexras1 in adult rat following sciatic nerve transection.

Peripheral nerve transection has been implicated to cause a production of neuronal nitric oxide synthase (nNOS), which may influence a range of post-axotomy processes necessary for neuronal survival and nerve regeneration. Carboxy-terminal post synaptic density protein/Drosophila disc large tumor suppressor/zonula occuldens-1 protein (PDZ) ligand of neuronal nitric oxide synthase (CAPON), as an adaptor, interacts with nNOS via the PDZ domain helping regulate nNOS activity at postsynaptic sites in neurons. And Dexras1, a small G protein mediating multiple signal transductions, has been reported to form a complex with CAPON and nNOS.

The role of TNF-alpha and its receptors in the production of beta-1,4-galactosyltransferase I mRNA by rat primary type-2 astrocytes.

beta-1,4-galactosyltransferase I (beta-1,4-GalT I) plays an important role in the synthesis of the backbone structure of adhesion molecules involved in leukocyte-endothelial cell interaction. The expression of beta-1,4-GalT I mRNA increased in primary human endothelial cells after exposure to tumor necrosis factor-alpha (TNF-alpha). In the central nervous system (CNS), astrocytes play a pivotal role in immunity as immunocompetent cells by secreting cytokines and inflammatory mediators, there are two types of astrocytes.

Expression of beta-1,4-galactosyltransferase-I in rat during inflammation.

beta-1,4-Galactosyltransferase-I (beta-1,4-GalT-I) which is one of the best-studied glycosyltransferases, plays a key role in the synthesis of selectin ligands such as sialy Lewis (sLe( x )) and sulfated sLe( x ). Previous studies showed that inflammatory responses of beta-1,4-GalT-I-deficient mice were impaired because of the defect in selectin-ligand biosynthesis. However, the expression of beta-1,4-GalT-I during inflammation and its biological function remains to be elucidated.