Axonal regeneration is critical for functional recovery following neural injury. In addition to intrinsic differences between regenerative responses of axons in peripheral versus central nervous systems, environmental factors such as glial cells and related molecules in the extracellular matrix (ECM) play an important role in axonal regeneration. Schwann cells in the peripheral nervous system (PNS) are recognized as favorable factors that promote axonal regeneration, while astrocytes and oligodendrocytes in the central nervous system (CNS) are not. In this review, we evaluate the roles of Schwann cells and astrocytes in axonal regeneration and examine recent evidence that suggests a dual function of astrocytes in regenerative responses. We also discuss the role of Cdc2 pathways in axonal regeneration, which is commonly activated in Schwann cells and astrocytes. Greater insight on the roles of glial cells in axonal regeneration is key to establishing baseline interventions for improving functional recovery following neural injury.
Astrocytes ; Axons ; Central Nervous System ; Extracellular Matrix ; Neuroglia ; Oligodendroglia ; Peripheral Nervous System ; Regeneration ; Schwann Cells

Purpose: The goal of this study is to investigate the role of cyclin-dependent kinase 5 (Cdk5) in axonal regeneration in dorsal root ganglion (DRG) neurons after peripheral nerve injury. Methods: Crush injury was given on the sciatic nerve in rats. The DRG tissues were prepared 1, 3, and 7 days after injury and used for western blotting and immunofluorescence staining experiments. Primary DRG neurons were prepared and treated with Cdk5 inhibitor roscovitine or used for transfections with plasmid constructs. After immunofluorescence staining, neurite length of DRG neurons was analyzed and compared among experimental groups. In addition, roscovitine was injected into the DRG in vivo, and the sciatic nerve after injury was prepared and used for immunofluorescence staining to analyze axonal regeneration in nerve sections. Results: Levels of Cdk5 and p25 were increased in DRG neurons after sciatic nerve injury (SNI). Levels of S727-p-STAT3, but not Y705-p-STAT3, were increased in the DRG. Immunofluorescence staining revealed that Cdk5 and STAT3 proteins were mostly colocalized in DRG neurons and Y705-p-STAT3 signals were localized within the nucleus area of DRG neurons. A blockade of Cdk5 activity by roscovitine or by transfection with dominant negative Cdk5 (dn-Cdk5) and nonphosphorylatable forms of STAT3 (S727A or Y705F) resulted in significant reductions of the neurite outgrowth of cultured DRG neurons. In vivo administration of roscovitine into the DRG markedly attenuated distal elongation of regenerating axons in the sciatic nerve after injury. Conclusions Our study demonstrated that Cdk5 activity induced from DRG neurons after SNI increased phosphorylation of STAT3. The activation of Cdk5-STAT3 pathway may be involved in promoting axonal regeneration in the peripheral nerve after injury.

No abstract available.
Ductus Arteriosus, Patent* ; Imaging, Three-Dimensional*

A nucleobase adenine is a fundamental component of nucleic acids and adenine nucleotides. Various biological roles of adenine have been discovered. It is not produced from degradation of adenine nucleotides in mammals but produced mainly during polyamine synthesis by dividing cells. Anti-inflammatory roles of adenine have been supported in IgE-mediated allergic reactions, immunological functions of lymphocytes and dextran sodium sulfate-induced colitis. However adenine effects on Toll-like receptor 4 (TLR4)-mediated inflammation by lipopolysaccharide (LPS), a cell wall component of Gram negative bacteria, is not examined. Here we investigated anti-inflammatory roles of adenine in LPS-stimulated immune cells, including a macrophage cell line RAW264.7 and bone marrow derived mast cells (BMMCs) and peritoneal cells in mice. In RAW264.7 cells stimulated with LPS, adenine inhibited production of pro-inflammatory cytokines TNF-α and IL-6 and inflammatory lipid mediators, prostaglandin E₂ and leukotriene B₄. Adenine impeded signaling pathways eliciting production of these inflammatory mediators. It suppressed IκB phosphorylation, nuclear translocation of nuclear factor κB (NF-κB), phosphorylation of Akt and mitogen activated protein kinases (MAPKs) JNK and ERK. Although adenine raised cellular AMP which could activate AMP-dependent protein kinase (AMPK), the enzyme activity was not enhanced. In BMMCs, adenine inhibited the LPS-induced production of TNF-α, IL-6 and IL-13 and also hindered phosphorylation of NF-κB and Akt. In peritoneal cavity, adenine suppressed the LPS-induced production of TNF-α and IL-6 by peritoneal cells in mice. These results show that adenine attenuates the LPS-induced inflammatory reactions.
Adenine Nucleotides ; Adenine* ; Animals ; Bone Marrow ; Cell Line ; Cell Wall ; Colitis ; Cytokines ; Dextrans ; Gram-Negative Bacteria ; Hypersensitivity ; Inflammation ; Interleukin-13 ; Interleukin-6 ; Lymphocytes ; Macrophages ; Mammals ; Mast Cells ; Mice ; Mitogen-Activated Protein Kinases ; Nucleic Acids ; Peritoneal Cavity ; Phosphorylation ; Protein Kinases ; Sodium ; Toll-Like Receptor 4

Mast cells are major immune cells in allergy to secrete allergic mediators by a degranulation process and make and secrete inflammatory lipids and cytokines in response to antigen stimulation. An amino acid tryptophan regulates immune functions. Tryptophan ameliorates inflammatory colitis in which mast cells are engaged. However, its effects on mast cells remain to be solved. We investigated the effect of tryptophan on IgE-mediated allergic responses in the mast cells and mice. IgE-mediated passive cutaneous anaphylaxis (PCA) in mice were examined. Also IgE-mediated mast cell activation responses such as degranulation of stored granules and secretion of inflammatory lipid LTB₄ and cytokines (TNF-α and IL-4) were measured. Intraperitoneal administration of tryptophan suppressed PCA in mice. Also, in the cellular level tryptophan inhibited IgE-mediated mast cell activation such as IgE-mediated degranulation and the production of LTB₄. Also, it inhibited production of inflammatory cytokines TNF-α and IL-4. In summary, tryptophan suppressed IgE-mediated allergic activation in vivo and in vitro. Tryptophan supplementation is beneficial for IgE-mediated allergy.
Animals ; Colitis ; Cytokines ; Hypersensitivity ; Immunoglobulin E ; In Vitro Techniques ; Interleukin-4 ; Leukotriene B4 ; Mast Cells* ; Mice ; Passive Cutaneous Anaphylaxis ; Tryptophan*

Atrioventricular nodal reentrant tachycardia (AVNRT), caused by a reentry circuit involving fast and slow atrioventricular nodal pathways, is one of the most common types of paroxysmal supraventricular tachycardias. While familial Wolff-Parkinson-White syndrome has been well recognized, familial AVNRT has been rarely reported. We report a familial occurrence of AVNRT in a mother and her son, who were symptomatic and successfully treated with radiofrequency catheter ablation of slow pathway.
Catheter Ablation ; Humans ; Mothers ; Tachycardia, Atrioventricular Nodal Reentry ; Tachycardia, Supraventricular ; Wolff-Parkinson-White Syndrome

BACKGROUND/AIMS: Invasive coronary angiography remains the gold standard in the diagnosis of coronary artery disease. However, multidetector CT (MDCT) coronary angiography is an emerging technique that is available for the non-invasive detection of coronary artery stenoses. While the diagnostic accuracy of first generation MDCT is limited, recently released 64-slice MDCT has yielded promising results due to increased temporal and spatial resolution. The objective of this study was to investigate the diagnostic accuracy of non-invasive 64-slice MDCT for coronary artery disease. METHODS: One hundred one patients (63 males and 38 females; mean age, 63.7+/-10.5 years) undergoing conventional coronary angiography were included in this study. All coronary arteries, including the distal segments and side branches, were analyzed for the presence of significant stenosis (> or =50% diameter stenosis) and compared with of the quantitative coronary angiographic findings. RESULTS: Of the 1,440 coronary artery segments studied, 1,348 segments were assessed quantitatively by both MDCT and conventional coronary angiography (94%). Two hundred nine significant stenoses were detected by conventional coronary angiography. On a segment-based analysis, the senisitivity, specificity, and positive and negative predictive values of 64-slice MDCT were 96, 97, 85, and 99%, respectively. On a vessel-based analysis, the sensitivity, specificity, and positive and negative predictive values of 64-slice MDCT were 96, 97, 85, and 99%, respectively. The corresponding values obtained on a patient-based analysis were 100, 94, 97, and 100%, respectively. Coronary calcification was the major cause of false-positive findings. CONCLUSIONS: This study demonstrated that 64-slice MDCT coronary angiography is of similar accuracy as conventional coronary angiography for the detection of coronary artery disease. In selected groups of patients, 64-slice MDCT may replace the more invasive coronary angiography.
Constriction, Pathologic ; Coronary Angiography ; Coronary Artery Disease ; Coronary Stenosis ; Coronary Vessels ; Humans ; Male ; Sensitivity and Specificity

BACKGROUND AND OBJECTIVES: Arterial stiffness and wave reflections increase with advancing age, and the systolic and pulse pressures are elevated. These changes in aortic stiffness and pulse wave velocity with aging may change the cardiac function. The diastolic function of the left ventricle declines with aging even in normal healthy subjects too. This investigation was designed to assess the correlations between the left ventricular diastolic function and arterial stiffness with using echocardiography including doppler tissue imaging (DTI) and an applanation tonometer. SUBJECTS AND METHODS: The subjects were 100 healthy volunteers who had normal left ventricular systolic function and no major cardiovascular risk factors such as hypertension, hypercholesterolemia, diabetes, obesity and smoking. The left ventricular diastolic function was assessed with the mitral inflow indexes and DTI, and the pulmonary venous return was measured by echocardiography. The central aorta blood pressure, the augmentation index (AIx) and the pulse wave velocity (PWV) were evaluated by using an applanation tonometer (SphygmoCoR system). RESULTS: With advancing age, the left mitral E/A ratio decreased (r=-.738, p<0.05) and the DTI early/late diastolic velocity (E'/A') ratio decreased (r=-.759, p<0.05), which showed a significant change of the left ventricular diastolic function. The Aix (r=.406, p<0.05) and PWV (r=.614, p<0.05) increased with aging. The PWV correlated significantly with the E/A ratio (r=-.593, p<0.05) and the E'/A' ratio (r=-.559, p<0.05). CONCLUSION: This study showed that increases of the large conduit vessel stiffness with aging are associated with a decline of the left ventricular diastolic function in healthy subjects.
Aging ; Aorta ; Atherosclerosis ; Blood Flow Velocity ; Blood Pressure ; Diastole ; Echocardiography ; Healthy Volunteers ; Heart Ventricles ; Humans ; Hypercholesterolemia ; Hypertension ; Obesity ; Pulse Wave Analysis ; Risk Factors ; Smoke ; Smoking ; Vascular Stiffness*

Multiple mycotic pseudoaneurysms that develop after aortic surgery are a rare infectious complication. The clinical course of this disease is severe and associated with a high mortality. Few published cases have described mycotic pseudoaneurysms that are localized mainly in the brain, heart, and aorta. In this case, a 33-year-old woman was admitted with abdominal pain and mild fever after graft surgery for a ruptured thoracic aorta that occurred following a vehicle accident. Thoracoabdominal computed tomography (CT), angiography, and transesophageal echocardiography (TEE) demonstrated multiple pseudoaneurysms and thromboembolic obstructions in the thoracic aorta and its branches. She was treated with anticoagulation, coil embolization, and surgical resection. Microscopically, a resected pseudoaneurysm showed the characteristic features of fungal colonies with thrombi. This patient has been well for 2 months after removing the pseudoaneurysms and treatment with systemic antifungal agents.
Abdominal Pain ; Adult ; Aneurysm, False ; Angiography ; Antifungal Agents ; Aorta ; Aorta, Thoracic ; Brain ; Echocardiography, Transesophageal ; Female ; Fever ; Heart ; Humans ; Thromboembolism ; Transplants

Pervanadate, a complex of vanadate and H2O2, has an insulin mimetic effect, and acts as an inhibitor of protein tyrosine phosphatase. Pervanadate-induced phospholipase D (PLD) activation is known to be dependent on the tyrosine phosphorylation of cellular proteins and protein kinase C (PKC) activation, and yet underlying molecular mechanisms are not clearly understood. Here, we investigated the signaling pathway of pervanadate-induced PLD activation in Rat2 fibroblasts. Pervanadate increased PLD activity in dose- and time- dependent manner. Protein tyrosine kinase inhibitor, genistein, blocked PLD activation. Interestingly, AG-1478, a specific inhibitor of the tyrosine kinase activity of epidermal growth factor receptor (EGFR) blocked not only the PLD activation completely but also phosphorylation of p38 mitogen- activated protein kinase (MAPK). However, AG-1295, an inhibitor specific for the tyrosine kinase activity of pletlet drived growth factor receptor (PDGFR) did not show any effect on the PLD activation by pervanadate. We further found that pervanadate increased phosphorylation levels of p38, extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK). SB203580, a p38 MAPK inhibitor, blocked the PLD activation completely. However, the inhibitions of ERK by the treatment of PD98059 or of JNK by the overexpression of JNK interacting peptide JBD did not show any effect on pervanadate-induced PLD activation. Inhibition or down-regulation of PKC did not alter the pervanadate-induced PLD activation in Rat2 cells. Thus, these results suggest that pervanadate-induced PLD activation is coupled to the transactivation of EGFR by pervanadate resulting in the activation of p38 MAP kinase.
Animals ; Cell Line ; Enzyme Activation/drug effects ; Fibroblasts ; Mitogen-Activated Protein Kinases/metabolism ; Phospholipase D/*metabolism ; Rats ; Receptor, Epidermal Growth Factor/*agonists/*metabolism ; Vanadates/*pharmacology ; src-Family Kinases/metabolism