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3.A model of cyclic flow variations using canine coronary artery: An experimental model for ischemic heart disease syndrome.

Korean Circulation Journal 1993;23(3):415-425

BACKGROUND: Cyclic flow variations(CFVs) is defined as morphological evidence of wide flow velocity variations in the Doppler signals due rapid spontaneous changes showing cyclic reduction and abrupt reperfusion of blood flow velocity seen in the critically stenotic arteries. Since first development of the CFVs model using dog by Folts and Uchida, it has been widely used as exellent experiemental model for study of the Acute ischemic heart disease syndrome including unstable angina. Nowadays it has been well documented that these CFVs are closely associated with temporal platelet aggregation and followed thrombus formation at the stenotic arterial lesion with endothelial or medial injury and subsequent release of various chemical mediators, eg. thromboxan A2 and serotonin. Also the CFVs can be seen in some patients of coronary artery stenosis during underwent PTCA, femoral artery stenosis and carotid or cerebral artery stenosis as well as in animal models. Moreover, CFVs has been thought to be the natural preconditioning in the unstable angina. METHODS: We tried to make the CFVs model using left anterior descending coronary artery (LAD) in 6 dogs. Pericardial cradle was made through 5th intercostal thoracotomy. The LAD was isolated carefully and critically stenosed by plastic constrictor and Doppler velocimeter probe was placed under the constrictor. After then intimal and medial layer of the LAD was damaged by a forcep. After appearing of CFVs, we observed and recorded for an hour. Myeloperoxide(MPO) activity in the ischemic and non-ischemic area of the myocardium were studied and compared after sacrifice. RESULTS: CFVs was found in all 6 dogs within an hour. The mean frequency of the CFVs was 9.8+/-4.45 times/hour. The mean coronary blood flow was 5.7+/-2.7 ml/min. And MPO activity was 1.47+/-0.5 units/g tissue in the ischemic myocardium and 0.49+/-0.27 units/g tissue in the non-ischemic area with statistical significance(p<0.005). CONCLUSIONS: CFVs model using various animal models and arterial sites can widely provide usefulness to document pathophysiology and pharmacologic mechanism in human acute ischemic heart disease syndromes.
Angina, Unstable ; Animals ; Arteries ; Blood Flow Velocity ; Cerebral Arteries ; Constriction, Pathologic ; Coronary Stenosis ; Coronary Vessels* ; Dogs ; Femoral Artery ; Humans ; Models, Animal ; Models, Theoretical* ; Myocardial Ischemia* ; Myocardium ; Plastics ; Platelet Aggregation ; Reperfusion ; Serotonin ; Surgical Instruments ; Thoracotomy ; Thrombosis

Multipotent neural stem cells (NSCs) are operationally defined by their ability to self-renew, to differentiate into cells of all glial and neuronal lineages throughout the neuraxis, and to populate developing or degenerating CNS regions. Thus their use as a graft material can be considered analogous to hematopoietic stem cell-mediated reconstitution and gene transfer. The recognition that NSCs propagated in culture could be reimplanted into mammalian brain, where they might integrate appropriately throughout the mammalian CNS and stably express foreign genes, has unveiled a new role for neural transplantation and gene therapy and a possible strategy for addressing the CNS manifestations of diseases that heretofore has been refractory to intervention. We have tracked the response of host and transplanted NSCs to brain or spinal cord injury and explored the therapeutic potential of NSCs injected into the animal CNS subjected to focal hypoxic-ische-mic (HI) brain or spinal cord injury. Such cells integrated appropriately into the degenerating CNS, showed robust engraftment and foreign gene expression within the region of CNS injury, and appeared to have migrated preferentially to the site of injury, experienced limited proliferation, and differentiated into neural cells lost to injury, trying to repopulate the damaged CNS area. The transplantation of exogenous NSCs may, in fact, augment a natural self-repair process in which the damaged CNS "attempts" to mobilize its own pool of stem cells. Providing additional NSCs and trophic factors may optimize this response. Therefore, NSCs may provide a novel approach to reconstituting CNS damaged by HI brain or spinal cord injury. Preliminary data in animal models of hypoxic-ischemic brain injury or contusive spinal cord injury lend support to these hypotheses.
Animals ; Brain ; Brain Injuries ; Gene Expression ; Genetic Therapy ; Models, Animal ; Neural Stem Cells* ; Neurons ; Spinal Cord Injuries ; Stem Cells ; Transplants

7.Cytokine Pattern of the Peripheral Blood Mononuclear Cells ( PBMC's ) and Synovial Membrane in the Rheumatoid Arthritis Patients.

Won PARK

The Journal of the Korean Rheumatism Association 1998;5(1):1-10

OBJECTIVE: To investigate the specific cytokine pattern and its profiles in rheumatoid arthritis (RA), we measured the mRNA expression of the IL-4, IL- 2, IFN-r7 and IL-10 in the PBMC s and synovial tissue samples. METHOD: We analyzed the cytokine mRNA copy number semiquantitatively in the fresh PBMC s from 13 rheumatoid patients who were not treated with corticosteroid or DMARDs(disease modifying antirheumatic drugs) which may affect the expression of cytokine and 16 healthy normal controls. Mononuclear cells were separated into three compartment(total PBMC, CD4+ cells, and CD4 cells) by the magnetic bead method. Synovial tissues were obtained from surgical procedure freshly. RNA was extracted from 1x10 cells of each PBMC compartment and synovial tissue. To determine the copy number of cytokine mRNA expression, RT-PCR and dot blot hybridization was performed with the RNA extracted from the samples. RESULT: In CD4+ compartment IFN(interferon)-r mRNA was marginally lower in RA patients(143+114) than in normal control(742+1052, p=0.0517) but IL(interleukin)-4 mRNA expression was higher in RA group(73+50 vs. 32+23 in normal control, p=0.0066). Also in CD4- compartment IFN-r mRNA expression was lower in RA(479+850 vs. 6154+15,059 in normal control, p=0.1875) although it was not significant statistically and IL-4 expression was higher in RA group(308+277 vs. 150+100 in normal group, p=0.0428). In PBMC compartment IFN-1 mRNA expression was also decreased in RA group (148+145 vs. 712 +768, p=0.0148), but IL-4 mRNA expression was marginally increased(186+145 vs. 109+62, p=0.0652). In synovium, interestingly, there was virtually no de novo synthesis of IL-4. CONCLUSION: There is significant difference in cytokine pattern of peripheral PBMC between RA and control group. The main cellular IL-4 source in periph- eral blood is not the CD4+ cells. Also there is significant difference of cytokine pattern between the peripheral blood and eynovium in rheumatoid arthritis.
Arthritis, Rheumatoid* ; Humans ; Interleukin-10 ; Interleukin-4 ; RNA ; RNA, Messenger ; Synovial Membrane*