BACKGROUND: The role of platelet in the pathogenesis of acute coronary syndrome and cerebral thrombosis is well known and the platelet inhibitors are used widely for primary and sccondary prevention of cardiovascular disease. Aspirin is the least expensive and most widely used antiplatelet agent and its effect is associated with its ability to inhibit plateletthromboxane A2 synthesis. The effectiveness of aspirin is dependent on its ability to block the formation of thromboxane A2. Ticlopidine is another popular antiplatelet agent used today in the era of stent implantation for treating coronary artery obstructive disease(CAOD) with aspirin. The mechanism of action of ticlopidine is clearly different from that of aspirin. It is concluded recently that ticlopidine is an inhibitor of ADP binding to platelets. The inhibition of ADP binding to platelets by ticlopidine is very nicely correlated with its does and the inhibition of platelet aggregation. Therefore, in this study, antiplatelet effect of low dose enteric-coated aspirin in place of aspirin and combined therapy with low does enteric-coated aspirin plus ticlopidine were evaluated in the normal subjects. METHOD: IN twenty normal subjects, platelet aggregation tests with adenosine diphosphate(ADP) and collagen were performed baseline, after I week adminisrtation of enteric-coated aspirin, and in randomly selected ten among twenty normal subjects, I week administration of enteric-coated aspirin and ticlopidine. The maximal aggregation rate was calculated by measuring the maximal change of the light transmittance after addition of aggregating agents. RESULT: Low does enteric-coated aspirin inhibited platelet aggregation in response to collagen significantly. Less than 25% of antiaggregation effect was noted in about 50% of subjects with low dose enteric-coated aspirin when platelet aggregation was induced by ADP. Ticlopidine in combination with low does enteric-coated aspirin potentiated the inhibitory effect significantly on platelet aggregation in response to ADP. CONCLUSION: Effect of low dose enteric-coated aspirin alone on platelet aggregation in response to ADP stimulation was weak and showed variablity, comparing to collagen stimulation. The combined treatment of ticlopidine plus aspirin was synergistically inhibited platelet aggregation responding to ADP stimulation. Therefore to achieve the synergistic inhibition of platelet aggregation to ADP and collagen stimulation, combination theraphy might be a effective regimen.
Acute Coronary Syndrome ; Adenosine ; Adenosine Diphosphate ; Aspirin* ; Blood Platelets* ; Cardiovascular Diseases ; Collagen ; Coronary Vessels ; Intracranial Thrombosis ; Platelet Aggregation ; Platelet Aggregation Inhibitors ; Stents ; Thromboxane A2 ; Ticlopidine*

BACKGROUND: Women with end-stage renal disease have low fertility. Following renal transplantation, the reproductive function returns to normal, and pregnancy becomes possible. METHOD: At our medical center, between June 1990 and February 1998, 263 female patients underwent renal transplantations, and 14 of them later became pregnant. The outcomes from 23 pregnancies in these 14 kidney transplant recipients were analyzed. RESULT: Forty-three percent (43%) of the pregnancies ended in artificial (9 cases) or spontaneous abortion (1 case), and 11 of 13 deliveries were successful. A vaginal delivery was performed in 9 cases (69%) and a cesarian section was done in 4 cases (31%). All of the 11 pregnancies that continued over 30 weeks ended successfully. The mean age of the recipients at the first pregnancy was 29.4 +/- 4.6 years (23-37). The mean time to first pregnancy since renal transplantation was 22.6 +/- 12.3 months (1-50). Thirteen (13) recipients were maintained on cyclosporin-based immunosuppressive regimens before and during pregnancy. One recipient, who was considered to have developed immune tolerance later, stopped the immunosuppressive drug at 3 months prior to the first pregnancy. The renal function remained stable and unchanged in all the recipients, and no rejection episodes occurred during and after pregnancy in any of the recipients. Preeclamsia occurred in 8 cases (35%) and a previous rupture of membrane in 1 case (4%). Of the 11 live births, 4 (36%) were premature (<37 weeks), 1 (9%) had a lowbirth-weight (<2500 gm), 1 (9%) had transient apnea, and 3 (27%) had transient neutropenia. The mean Apgar score at 1 minute was 7.8 (7-9), with only 2 children having a score below 7. No congenital anomalies were documented. The later development and health of all of the children were good during a mean follow-up of 16.6 +/- 10 (1-38) months. Two (2) recipients who had a successful first pregnancy had a second baby. CONCLUSION: From these results, we can conclude that pregnancy does not adversely affect graft function and fetal development, provided that the graft function was stable at the time of conception and prudent fetal monitoring could be done.
Abortion, Spontaneous ; Apgar Score ; Apnea ; Child ; Female ; Fertility ; Fertilization ; Fetal Development ; Fetal Monitoring ; Follow-Up Studies ; Humans ; Immune Tolerance ; Kidney ; Kidney Failure, Chronic ; Kidney Transplantation ; Live Birth ; Membranes ; Neutropenia ; Pregnancy* ; Rupture ; Transplantation ; Transplants

Neovascularization of the adventitial vasa vasorum with extension into the intima of atherosclerotic lesions is frequently observed, but its pathophysiological significance is still subject to debate. Recently, leptin, the product of the Ob gene, was identified. Leptin, via activation of the endothelial receptor (Ob-R), generates a growth signal involving a tyrosine kinase-dependent intracellular pathway and promotes angiogenic processes. We hypothesized that a high concentration of leptin within vasa vasorum and plaque itself, may influence inflammatory and vascular neovascularization coupling with functional upregulation of the vascular endothelial growth factor (VEGF). Microscopic computerized tomography was utilized for the spatial distribution of vasa vasorum and intimal neovascularization from atherosclerotic human coronary arteries. Atherosclerotic coronary arteries showed a dense plexus of microvessels in the adventitia and plaque itself. Microscopic analysis from human atherosclerotic aortas revealed an increase in the intimal thickness with neovascularization. The immunoreactivity for Ob-R, VEGF and matrix metalloproteinase (MMP) increased in atherosclerotic plaque, predominantly in the endothelial lining of the intimal neovessel and macrophages/foam cells. Our observation of a prominent colocalization between Ob-R, VEGF and MMP supports this hypothesis and these factors participate in the neovascularization of atherosclerotic lesions. The present study is the first report on vascular tissue and it opens a promising perspective concerning future investigations of leptin-dependent modulation of atherogenesis and vascular neovascularization under pathophysiolgical conditions.
Adult ; Arteriosclerosis/physiopathology ; Arteriosclerosis/pathology ; Arteriosclerosis/metabolism* ; Blood Vessels/pathology ; Blood Vessels/metabolism ; Carrier Proteins/physiology ; Carrier Proteins/metabolism* ; Human ; Middle Age ; Neovascularization, Pathologic/physiopathology

Inflammation appears to have a major role in the development of atherosclerosis. Cyclooxygenase-2 (COX-2) is involved in the inflammatory response via the generation of prostanoids that, in turn, are involved in the production of matrix metalloproteinases (MMPs). This study aimed to investigate atherosclerosis in human aortas for in situ tissue distribution of COX-2, MMPs including MMP-9 and membrane type 1 MMP (MT1-MMP), and tissue inhibitor of metalloproteinase-2 (TIMP-2). Immunohistochemical studies were performed on atherosclerotic lesions of aortas from patients with aortic aneurysms (n = 4) and dissections (n = 3) by using antibodies to COX-2, MMP-9, MT1-MMP, and TIMP-2. Control tissues were obtained from traumatically dissected aortas (n = 2). All specimens from diseased aortas had atherosclerotic lesions ranging from fatty streak to atheromatous plaques. In control, there was no expression of COX-2, MMP-9, and MT1-MMP in all aortic layers. Immunoreactivity for COX-2 was predominantly noted in macrophages and smooth muscle cells (SMCs) of the intima including atherosclerotic plaque itself and the medial layer of the plaque base, as well as in SMCs and endothelial lining of the vasa vasorum in the adventitia. Immunoreactivity for MMP-9 and MT1-MMP was found in the same distribution as that of COX-2. Additionally, the expression of TIMP-2 increased in relation to MMP-9 expression. This study demonstrates that COX-2 is coexpressed with MMP-9 and MT1-MMP, not only by macrophages and SMCs in atherosclerotic lesions, but also in endothelial lining of the vasa vasorum of human aortas. Thus, vascular inflammatory reactions may influence extracellular matrix remodeling by coactivation of MMPs in the development of atherosclerosis and, in turn, the progression of disease.
Animal ; Aorta/enzymology* ; Aortic Diseases/pathology ; Aortic Diseases/enzymology* ; Arteriosclerosis/pathology ; Arteriosclerosis/enzymology* ; Female ; Guinea Pigs ; Human ; Immunochemistry ; Isoenzymes/metabolism* ; Male ; Matrix Metalloproteinases/metabolism* ; Middle Age ; Prostaglandin-Endoperoxide Synthase/metabolism*

BACKGROUND/AIMS: Many patients with positive anti-HBc, but negative HBsAg, are known to harbor occult HBV infection, which may transmit the virus through the graft in liver transplantation. We examined the change of HBV DNA within the liver allograft tissue of the donor with positive anti-HBc, but negative HBsAg, before and after the transplantation and assessed its significance. METHODS: Twenty-eight patients with available posttransplant biopsies that received anti-HBc positive liver allografts between April 2000 and November 2003 were enrolled in the study. Intraoperative wedge biopsy of donor liver and needle biopsy of the recipient around the 12th postoperative day were used. HBV DNA within the liver tissue was identified by polymerase chain reaction technique using paraffin-embedded liver tissue. RESULTS: Among 13 patients that showed positive amplification before transplantation, 10 turned negative and 3 remained positive after transplantation. One patient, who was negative, became positive after transplantation. Three patients had recurrent HBV infection, but none had positive PCR before or after transplantation and recurrence was not associated with PCR results. Donors with low anti-HBs titer were more likely to be PCR positive compared to donors with high anti-HBs serology (P<0.05). CONCLUSIONS: Under adequate prophylactic measures, the presence of HBV DNA within the liver tissue does not affect recurrence and most allografts harboring HBV DNA before transplantation will eventually show viral clearance. However, many anti-HBc positive allografts are infected by HBV at subclinical level so vigilant surveillance is essential.
Middle Aged ; Male ; *Living Donors ; *Liver Transplantation ; Liver/virology ; Humans ; Hepatitis B, Chronic/diagnosis/immunology/virology ; Hepatitis B virus/*genetics ; Hepatitis B Core Antigens/*immunology ; Hepatitis B Antibodies/*analysis ; Female ; DNA, Viral/*analysis ; Adult

The purpose of this study was to visualize the spatial patterns and connection of channels created after percutaneous transmyocardial revascularization (PTMR) in normal porcine hearts, and to estimate the relative contributions of transmyocardial and coronary perfusion. Six pigs underwent PTMR creating channels using radiofrequency ablative energy. Three-dimensional computed tomography imaging of channels 1 hr after PTMR showed the direct connection of PTMR channels to the myocardial capillary network and to epicardial coronary vessels. In the heart, examined 28 day after PTMR, there was a fine, extensive, network of microvessels originating from the site of the original PTMR channel, also connecting the left ventricular cavity to myocardial capillaries. Histopathologic examination of the 1-hr specimens showed numerous regions of myocardial hemorrhage and associated inflammatory cell infiltration. In the 28-day specimens, newly developed new vascular network suggested neovascularization within the core of these channel remnants. The immunoreactivity for basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) were intense within myocardium and neovascular structure surrounding PTMR channel remnants. The vascular connections occur by direct communication with existing myocardial vasculature acutely, and angiogenesis in these channel remnant chronically.
Animal ; Coronary Angiography ; Coronary Circulation ; Coronary Vessels/pathology ; Heart/radiography* ; Heart Ventricle/radiography ; Image Enhancement/methods ; Immunohistochemistry ; Myocardial Revascularization/methods* ; Myocardium/pathology* ; Neovascularization, Pathologic/radiography ; Neovascularization, Pathologic/pathology* ; Perfusion ; Swine ; Tomography, X-Ray Computed