BACKGROUND: This study investigated the protective mechanism of Prostagladin E1 (PGE1) against intimal hyperplasia after vein interposition grafts in rabbits. It has been demonstrated that active oxygen species contribute to vascular smooth muscle cell growth via early cell cycle gene activation. We attempted to study whether PGE1 had an effect on the inhibition of the oxidative stress injury index (8-OHdG, MDA). METHODS: Forty-eight jugular vein grafts were inserted into the carotid arteries of male hyperlipidemic New Zealand white rabbits, which were divided into 2 groups (saline group and PGE1 group). Saline and Prostaglandin E1 (0.1 microgram/kg/min) were administered as a continuous infusion for 2 hours every day from just before graft interposition to harvest. The vein grafts were harvested at 6 hour, 1 day, 1 week, and 2 week after grafting and rapidly stored in liquid nitrogen ( 70oC). 8-OHdG was measured by using high performance liquid chromatography coupled with electrochemical detection (HPLC-EC), and malondialdehyde (MDA) was measured by using thiobarbituric acid (TBA) assay. PC 10 index and intimal thickness of the grafts were measured with a computer digitalized image analyzer. RESULTS: There was no difference in 8-OHdG levels between the saline and the PGE1 groups. PGE1 had more inhibitory effect on the MDA level as an oxidative stress injury index, but its action was restricted to 1 day. A morphometric analysis and an immunohistochemical study showed that the PGE1 group had more suppressive effects both in intimal thickeness and proliferating cell nuclear antigen (PCNA) expression than the saline group (p<0.05). CONCLUSION: These results suggest that PGE1 is effective in preventing intimal hyperplasia after vein interposition grafts in rabbits and may play a role in inhibiting oxidative stress injury.
Alprostadil ; Carotid Arteries* ; Chromatography, Liquid ; Genes, cdc ; Humans ; Hyperplasia ; Jugular Veins ; Male ; Malondialdehyde ; Muscle, Smooth, Vascular ; Nitrogen ; Oxidative Stress* ; Proliferating Cell Nuclear Antigen* ; Rabbits ; Reactive Oxygen Species ; Transplants* ; Veins*

OBJECTIVE: The objective of this study is to estimate the effects of Inclear, a feminine cleanser, on sperm motility. METHODS: Semen samples were obtained from infertile male patients. Following liquefaction, the raw semen samples were diluted with Ham's F-10 nutrient mixture medium containing 0.4% human serum albumin solution at a ratio of 1:3. The semen samples were subsequently centrifuged to separate the seminal plasma from the serum. The supernatant was discarded, and the pellet was resuspended. The sample was again centrifuged to remove cell debris, and the supernatant was removed. The final pellet was gently loosened by resuspension and incubated in medium alone as a control, and in a 10% solution of the medium plus Inclear. A sampling time of 30 minutes was selected on the basis of sperm transport studies. Sperm motility was evaluated with computer-assisted sperm analysis. RESULTS: A total of 20 samples were analyzed. The mean age of patients was 34.40+/-2.96 years. There was no difference in sperm concentration and motility in the two samples at 0 minute and 30 minutes of incubation. In both semen samples, the sperm concentration and motility decreased after an incubation period of 30 minutes. However, there was no statistical difference between the samples. Sperm concentration and motility were not significantly different between the control and Inclear samples after 0 minute and 30 minutes of incubation. CONCLUSION: Inclear has no negative effects on sperm motility. This product can be recommended to pregnancy planners for vaginal hygiene and as a vaginal lubricant.
Feminine Hygiene Products ; Humans ; Hygiene ; Lubricants ; Male ; Pregnancy ; Prospective Studies* ; Semen ; Serum Albumin ; Sperm Motility* ; Sperm Transport ; Spermatozoa

PURPOSE: Among the theories in the pathogenesis of abdominal aortic aneurysms, matrix metalloproteinase (MMP)- induced excessive degradation of extracellular matrix protein has been widely recognized. Normally, MMPs keep a balance with their endogenous tissue inhibitors of metalloproteinases (TIMPs). Recently, the MMP-TIMP imbalance has been investigated for potential etiological role in AAA formation. The aim of this study was to define the role of the imbalance between the expressions of the specific MMPs and their physiologic inhibitors (TIMPs) in the formation of human abdominal aortic aneurysm (AAA). METHODS: Aortic tissues from 12 patients with AAAs, 4 age-matched patients with aortoiliac occlusive diseases (AODs), and 6 cadaveric organ donors, as normal controls, were obtained and prepared. The productions and expressions of MMP-2, 9, MT1-MMP and TIMP-1, 2, and 4 were analyzed using gelatin zymography, Western blotting, and immunohistochemistry. RESULTS: In the gelatin zymography, the net matrix-degrading activities were higher in the AAAs and AODs than in the normal control group due to the higher presence of MMP-2 and 9. From the Western blot analysis and immunohistochemistry, those with AAAs and AODs showed significantly higher expressions of MMP-2, 9, and MT1-MMP than the normal control group. However, no differences in the TIMP-1 and 2 expressions were found between the all groups. In contrast, TIMP-4 protein was expressed at a significantly lower level in the AAAs and AODs than in the normal control group. MMP-9/TIMP-1, MMP-2/TIMP-2, and MMP-2/TIMP-4 were significantly different between AAAs and normal control group. From the densitometric analysis of the Western blotting, no significant differences were found in tissue expressions of MMPs and TIMPs between the AAAs and AODs groups, but, in the immunohistochemistry, the AAAs group showed a different distribution of the MMP expression confined to sites of overt medial damage compared with that in the intimal plaque in AODs. CONCLUSION: The imbalance of expression between specific MMPs and their endogenous inhibitors plays an etiological role in the formation of AAAs. In addition, TIMP-4 may suppress the MMP-induced aneurysmal formation. Our results suggest that the eventual formation of aneurysms or occlusive lesions appears not to result from an ongoing difference in the proteolytic activities, but from differences in other factors, as-yet-undefined, including the distribution of MMPs expression within the aortic walls.
Aneurysm ; Aortic Aneurysm, Abdominal* ; Blotting, Western ; Cadaver ; Extracellular Matrix ; Gelatin ; Humans* ; Immunohistochemistry ; Matrix Metalloproteinase 14 ; Matrix Metalloproteinases* ; Metalloproteases ; Tissue Donors ; Tissue Inhibitor of Metalloproteinase-1

Proliferation of vascular smooth muscle cells (VSMCs) is the utmost important pathophysiologic mechanism of intimal hyperplasia and atherosclerosis. With a hyperlipidemic rabbit model of jugular vein graft to carotid artery, we invesigated the oxidative stress injury in intimal hyperplasia and correlation of PCNA expression with VSMCs proliferation and intimal hyperplasia. Twenty jugular vein grafts were inserted into the carotid arteries of male New Zealand White rabbit and the vein grafts were harvested at 6 hr, 1 day, 7 days, 14 days, respectively after grafting and rapidly stored in buffered formalin for morphometric analysis, PCNA expression or frozen in liquid nitrogen for MDA (Malondialdehyde) analysis. Total wall and intimal thickness of grafts were measured with an computer digitalized image analyzer. Intimal thickening was rapidly increased at 7 days and peaked at 14 days (125.05 19.80 and 180.25 6.38 mum, respectively) and significantly thicker than control group or 6 hr, 1day after graft implantation (p<0.05). MDA level was significantly higher in vein grafting groups than control group (9.13 1.80 vs. 6.08 1.00 muM/mg protein, p=0.011) by Ohkawa method. In immunohistochemical staining, expression for PCNA (PC10 index: %) in media was peaked at 7 days (12.91 1.22) and significantly higher than control group or 6 hr, 1 day (0, 0.66 0.90, and 3.00 1.22, respectively) after graft implantation (p<0.05) and decreased thereafter. Expression for PCNA (PC10 index) in intima was markedly noted at 7 days (8.60 0.95), peaked at 14 days (16.90 2.14) and significantly higher than control group or 6 hr, 1 day (0, 0.31 0.63, and 1.44 1.00, respectively) after graft implantation (p<0.05). In conclusion, oxidative stress injury by active oxygen species increased in this model of vein graft suggests a role of this oxidant in intimal hyperplasia. PCNA expression was well correlated with the proliferation and migration of VSMCs from media to intima as the pathophysiology of intimal hyperplasia. Therefore, use of PCNA expression in this model of vein graft provides a reproducible method of assessing cellular proliferation after vascular injury. This experimental models of vessel wall injury are helpful in understanding the pathophysiologic mechanism of intimal hyperplasia and are useful in initial assessment of agents intended for reducing intimal hyperplasia.
Atherosclerosis ; Carotid Arteries ; Cell Proliferation ; Formaldehyde ; Humans ; Hyperplasia* ; Jugular Veins ; Male ; Malondialdehyde ; Models, Theoretical ; Muscle, Smooth, Vascular ; New Zealand ; Nitrogen ; Oxidative Stress* ; Proliferating Cell Nuclear Antigen* ; Reactive Oxygen Species ; Transplants* ; Vascular System Injuries ; Veins*

Background: Tacrolimus is the most commonly used immunosuppressive drug in solid organ transplantation. After administering a conventional twice-daily dose of tacrolimus, peak levels were achieved within the first 1.5 to 2 hours. A group of patients showed different early absorption phase of tacrolimus after kidney transplantation. Methods: Trough(C0 ) and 1.5-hour blood levels (C1.5 ) of tacrolimus were measured in 95 kidney transplantation recipients. Patients with a C1.5 /C0 < 1.5 and > 1.5 were defined as those having flat pattern peaks and as controls, respectively. Transplantation outcomes were compared between the groups. Whole exome sequencing was performed to investigate the genetic susceptibility to flat pattern peaks. Results: Twenty-eight patients showed flat pattern peaks. The mean C1.5 /C0 values were 1.13 ± 0.22 and 3.78 ± 1.25 in the flat pattern peak and control groups, respectively. In multivariate analysis, flat pattern peak was an independent risk factor for biopsy-proven acute rejection (BPAR) and/or borderline change (P = 0.014). Patients having flat pattern peaks showed significantly lower post-transplant 36-month estimated glomerular filtration rate (P = 0.001). Two single nucleotide variants in ABCB1 genes, rs1922242 and rs2235035, were associated with flat pattern peaks (P = 0.019 and P = 0.027, respectively). Conclusion Both of C1.5 and C0should be measured to distinguish the patients showing unique initial absorption. A C1.5 /C0 ratio lower than 1.5 was associated with an increased risk of BPAR and/or borderline change. Single nucleotide variants s in ABCB1 gene might influence the flat pattern peaks of tacrolimus absorption.

BACKGROUND/AIMS: This study investigated the expression of nuclear factor kappaB (NF-kappaB) and the chemokine receptor (CXCR4) in patients with diffuse large B-cell lymphoma (DLBCL) who received rituximab-based therapy. METHODS: Seventy patients with DLBCL and treated with rituximab-CHOP (R-CHOP) were included, and immunohistochemistry was performed to determine the expression of NF-kappaB (IkappaB kinase alpha, p50, and p100/p52) and CXCR4. To classify DLBCL cases as germinal center B-cell-like (GCB) and non-GCB, additional immunohistochemical expression of CD10, bcl-6, or MUM1 was used in this study. The expression was divided into two groups according to the intensity score (negative, 0 or 1+; positive, 2+ or 3+). RESULTS: The median age of the patients was 66 years (range, 17 to 87), and 58.6% were male. Twenty-seven patients (38.6%) had stage III or IV disease at diagnosis. Twenty-three patients (32.9%) were categorized as high or high-intermediate risk according to their International Prognostic Indexs (IPIs). The overall incidence of bone marrow involvement was 5.7%. Rates of positive NF-kappaB and CXCR4 expression were 84.2% and 88.6%, respectively. High NF-kappaB expression was associated with CXCR4 expression (p = 0.002), and 56 patients (80.0%) showed coexpression. However, the expression of NF-kappaB or CXCR4 was not associated with overall survival and EFS. On multivariate analysis that included age, gender, performance status, stage, and the IPI, no significant association between the grade of NF-kappaB or CXCR4 expression and survival was observed. CONCLUSIONS: The current study suggests that the tissue expression of NF-kappaB and CXCR4 may not be an independent prognostic marker in DLBCL patients treated with R-CHOP.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal, Murine-Derived/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use ; Chi-Square Distribution ; Cyclophosphamide/administration & dosage ; Disease Progression ; Disease-Free Survival ; Doxorubicin/administration & dosage ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lymphoma, Large B-Cell, Diffuse/chemistry/*drug therapy/mortality/pathology ; Male ; Middle Aged ; Multivariate Analysis ; NF-kappa B/*analysis ; Neoplasm Staging ; Predictive Value of Tests ; Prednisone/administration & dosage ; Proportional Hazards Models ; Receptors, CXCR4/*analysis ; Retrospective Studies ; Risk Factors ; Time Factors ; Treatment Outcome ; Tumor Markers, Biological/*analysis ; Vincristine/administration & dosage ; Young Adult

BACKGROUND: Simultaneous liver and kidney transplants have proved to be a favorable treatment for combined renal and hepatic end-stage diseases. However, it is extremely difficult to find a simultaneous liver and kidney donor in Korea due to the narrow requirements. This study had three aims: to explore the therapeutic experience of simultaneous liver and kidney transplants in Seoul National University Hospital (SNUH), to compare the overall survival outcome between simultaneous liver and kidney transplants and liver transplants alone in patients with liver and renal failure, and to determine the indications for simultaneous liver and kidney transplants. METHODS: The clinical data of 8 simultaneous liver and kidney transplants at SNUH from November 2004 to October 2010 were retrospectively studied. Indications for simultaneous liver and kidney transplants, patient and graft survival, and the causes of death were analyzed and compared with 5 liver transplants alone performed on patients experiencing liver and renal failure. RESULTS: The clinical characteristics of the recipients for simultaneous liver and kidney transplants and liver transplants alone were similar with regards to age, renal function, and the Model for End-Stage Liver Disease (MELD) score (all P>0.05). One patient died at 15 months after simultaneous liver and kidney transplants due to HBV related HCC recurrence, and three patients died at 2, 3, and 21 months after liver transplants due to ARDS, bleeding, and hepatic failure, respectively. Only one liver graft loss in simultaneous liver and kidney transplant cases occurred on POD 3 due to primary non-function. The outcome analysis demonstrated a superior overall survival in simultaneous liver and kidney transplants recipients compared with recipients of only liver transplants (P=0.041). CONCLUSIONS: Simultaneous liver and kidney transplants showed a superior outcome in patients with end-stage liver disease and chronic renal failure compared with liver transplants alone. The allocation criteria of simultaneous liver and kidney transplants in Korea should be changed to expand its indications.
Cause of Death ; Graft Survival ; Hemorrhage ; Humans ; Kidney ; Kidney Failure, Chronic ; Korea ; Liver ; Liver Diseases ; Liver Failure ; Recurrence ; Renal Insufficiency ; Retrospective Studies ; Tissue Donors ; Transplants

BACKGROUND: Simultaneous liver and kidney transplants have proved to be a favorable treatment for combined renal and hepatic end-stage diseases. However, it is extremely difficult to find a simultaneous liver and kidney donor in Korea due to the narrow requirements. This study had three aims: to explore the therapeutic experience of simultaneous liver and kidney transplants in Seoul National University Hospital (SNUH), to compare the overall survival outcome between simultaneous liver and kidney transplants and liver transplants alone in patients with liver and renal failure, and to determine the indications for simultaneous liver and kidney transplants. METHODS: The clinical data of 8 simultaneous liver and kidney transplants at SNUH from November 2004 to October 2010 were retrospectively studied. Indications for simultaneous liver and kidney transplants, patient and graft survival, and the causes of death were analyzed and compared with 5 liver transplants alone performed on patients experiencing liver and renal failure. RESULTS: The clinical characteristics of the recipients for simultaneous liver and kidney transplants and liver transplants alone were similar with regards to age, renal function, and the Model for End-Stage Liver Disease (MELD) score (all P>0.05). One patient died at 15 months after simultaneous liver and kidney transplants due to HBV related HCC recurrence, and three patients died at 2, 3, and 21 months after liver transplants due to ARDS, bleeding, and hepatic failure, respectively. Only one liver graft loss in simultaneous liver and kidney transplant cases occurred on POD 3 due to primary non-function. The outcome analysis demonstrated a superior overall survival in simultaneous liver and kidney transplants recipients compared with recipients of only liver transplants (P=0.041). CONCLUSIONS: Simultaneous liver and kidney transplants showed a superior outcome in patients with end-stage liver disease and chronic renal failure compared with liver transplants alone. The allocation criteria of simultaneous liver and kidney transplants in Korea should be changed to expand its indications.
Cause of Death ; Graft Survival ; Hemorrhage ; Humans ; Kidney ; Kidney Failure, Chronic ; Korea ; Liver ; Liver Diseases ; Liver Failure ; Recurrence ; Renal Insufficiency ; Retrospective Studies ; Tissue Donors ; Transplants