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1.
J Clin Med ; 12(3)2023 Jan 27.
Article in English | MEDLINE | ID: mdl-36769625

ABSTRACT

This study was conducted to determine the correlations between health literacy, transplant effects, and compliance to treatment in organ transplant recipients and to identify the factors influencing compliance to treatment. The participants (n = 130; males = 66.9%; mean age = 56.4 years) were organ transplant recipients visiting an organ transplantation center in Seoul, South Korea. The regression model explained 32% of the variance in participants' compliance to treatment. Among the health literacy variables, "Scale 3: Actively managing my health" (ß = 0.38, p = 0.001) and "Scale 4: Social support for health" (ß = 0.25, p = 0.019) had a significant effect on compliance to treatment. In this study, health literacy was identified as a key factor influencing compliance to treatment. Therefore, patients' health literacy should be assessed prior to transplantation to identify potential high-risk patients for treatment nonadherence. In addition, after transplantation surgery, patient-tailored interventions should be developed and provided for self-management that reflects the patient's health literacy level to ultimately enhance patient outcomes.

2.
J Clin Med ; 10(16)2021 Aug 11.
Article in English | MEDLINE | ID: mdl-34441826

ABSTRACT

Advances in patient care and immunosuppressive drugs have improved graft survival, resulting in an increase in kidney transplantation (KT); however, persistent immunosuppression is thought to cause late occurrence of cancer. This population-based study consisted of a total of 14,842 patients whose data from the years 2002 to 2017 were collected from the National Health Information Database in South Korea. Malignancies occurred in 7.6% of the total KT patients. Prostate and thyroid cancers were the most common in males and females, respectively. From the age-adjusted incidence analysis, Kaposi's sarcoma showed the highest standardized incidence ratio in both male and female patients. According to the linear regression model, cancer incidence in KT recipients under immunosuppressive conditions increased by approximately 0.1% each month. Patients' age over 39 and the use of prednisolone as an initial steroid regimen were associated with increased risk of cancer development after KT. Our regression and proportional hazards models will help clinicians to predict the approximate cancer incidence risk when monitoring KT recipients. Based on the largest available national database, screening or monitoring methods for cancer detection and prevention can be established for KT patients by considering the factors involved in cancer development.

3.
Sleep Breath ; 24(1): 127-134, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31667682

ABSTRACT

PURPOSE: Respiratory inductive plethysmography (RIP) is recommended as an alternative respiratory sensor for the identification of each apnea and hypopnea event in polysomnography. Using this sensor, the cumulative RIP results from the chest and abdomen (RIP sum) and time-derived results of the RIP sum (RIP flow) are calculated to track respiratory flow. However, the effectiveness of this sensor and the calculated respiratory results is still unclear, and validation studies for the scoring of respiratory events in polysomnography are rare. METHODS: Two hundred subjects were selected according to the severity of obstructive sleep apnea. A sleep specialist re-evaluated the respiratory events based on RIP flow data in a single-blind study. Statistical analysis was conducted with paired respiratory events scored in each of the RIP flow and polysomnography datasets. RESULTS: All respiratory events scored from the RIP flow were strongly correlated with those identified with standard sensors of polysomnography, regardless of disease severity. Most of the respiratory parameters from RIP flow trended toward underestimation. The RIP flow obtained from the alternative RIP sensor was appropriate for the diagnosis of obstructive sleep apnea based on a receiver operating characteristic curve. CONCLUSIONS: Scored respiratory events from RIP flow data effectively reflected the respiratory flow and statistically correlated with the results from standard polysomnography sensors. Therefore, analyzing RIP flow utilizing an RIP sensor is considered a reliable method for respiratory event scoring.


Subject(s)
Plethysmography, Impedance/instrumentation , Polysomnography/methods , Sleep Apnea, Obstructive/diagnosis , Adult , Aged , Cardiography, Impedance/instrumentation , Female , Humans , Male , Middle Aged , Reproducibility of Results , Sleep Apnea, Obstructive/physiopathology
4.
Transplant Proc ; 51(10): 3297-3303, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31732215

ABSTRACT

BACKGROUND: Graft biopsy is the gold standard for the differential diagnosis of graft dysfunction. The time interval between transplant surgery and biopsy often provides clinicians with diagnostic clues. However, the clinicopathologic features of late graft biopsy, especially those obtained at more than 5 years after kidney transplant, are not well understood. MATERIALS AND METHODS: We retrospectively collected graft biopsy tissues obtained from kidney transplant recipients who underwent indication biopsy between February 2012 and March 2017. Patients were divided according to their post-transplant period, and their clinical characteristics, pathologic diagnosis, and Banff scores were compared across groups. RESULTS: A total of 410 indication biopsy specimens obtained from 321 kidney transplant recipients were analyzed in this study. Overall, the incidence of T cell-mediated rejection, borderline rejection, and BK virus-associated nephropathy decreased while that of antibody-mediated rejection, nonspecific interstitial fibrosis and tubular atrophy, and glomerulonephritis increased over time. Most samples obtained over 5 years after kidney transplant exhibited chronic glomerular and tubulointerstitial injuries irrespective of their pathologic diagnosis. In patients whose post-transplant period was less than 5 years, urine protein-to-creatinine ratio was significantly elevated in the glomerulonephritis and chronic active antibody-mediated rejection groups only. In contrast, patients who underwent graft biopsy more than 5 years after kidney transplant showed significantly high levels of proteinuria irrespective of the pathologic diagnosis, and there was no statistical difference between groups. CONCLUSION: We demonstrated that the etiology of graft dysfunction is largely influenced by the biopsy time point.


Subject(s)
Biopsy/methods , Graft Rejection/diagnosis , Kidney Transplantation/adverse effects , Postoperative Complications/diagnosis , Time Factors , Adult , Female , Graft Rejection/etiology , Humans , Kidney/pathology , Male , Middle Aged , Postoperative Complications/etiology , Retrospective Studies , Young Adult
5.
Ann Surg Treat Res ; 97(5): 239-244, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31742208

ABSTRACT

PURPOSE: An enhanced recovery after surgery (ERAS) protocol incorporates up-to-date perioperative care principles; the primary aim in using an ERAS protocol is to reduce issues that delay the recovery and cause the complications. The aim of this study was to compare outcomes associated with head and neck cancer surgery with free-flap reconstruction before and after implementation of an ERAS protocol. METHODS: Outcomes were analyzed by dividing patients into 2 groups: 29 patients in the non-ERAS group and 60 patients in the ERAS group. The ERAS group performed a prospective observational cohort study of patients who underwent a head and neck cancer surgery with free-flap reconstruction in Ajou University Hospital from August 2015 to December 2017. The non-ERAS group retrospectively reviewed the medical records of patients who had undergone the same surgery from August 2012 to July 2015. RESULTS: Demographics, comorbidities, hospital length of stay (LOS), postoperative complications, starting time of rehabilitation, and postoperative periods before radiotherapy for the non-ERAS and ERAS groups were compared. Hospital LOS was significantly lower for patients whose care followed the ERAS protocol than for patients in the non-ERAS group (30.87 ± 20.72 days vs. 59.66 ± 40.43 days, P < 0.0001). CONCLUSION: In this study, hospital LOS was reduced through fast recovery after the implementation of the ERAS protocol. Therefore, the ERAS protocol appeared feasible and safe in head and neck cancer surgery with free-flap reconstruction.

6.
Laryngoscope ; 129(2): 470-476, 2019 02.
Article in English | MEDLINE | ID: mdl-30208201

ABSTRACT

OBJECTIVES: To investigate the change of hearing threshold over time and analyze factors that could affect hearing, this longitudinal study of pure-tone threshold changes in the same subjects at a 9-year interval was performed. STUDY DESIGN: Retrospective longitudinal study in a single center (n = 1,978). METHODS: A total of 1,978 subjects were included; they received pure-tone audiometry at a 9-year interval. The degree of the threshold changes was examined and compared between age groups. The subjects' data, such as the level of cholesterol, were analyzed to find risk factors on hearing. RESULTS: The average of the threshold changes was 3.35 dB in the 20s to 30s; 4.38 dB in the 30s to 40s; 5.75 dB in the 40s to 50s; 7.21 dB in the 50s to 60s; and 10.00 dB in the 60s to 70s (all P < 0.05). If the low-density lipoprotein cholesterol (LDL-C) was maintained below 100 mg/dl, the difference in the weighted four-frequency average was 5.45 dB, whereas it was 6.15 dB in the subjects whose LDL-C was over 100 mg/dl (P = 0.032, age-adjusted). In current smokers, the thresholds increased more than in never- or ex-smokers (P = 0.026 in the weighted four-frequency average and P = 0.011 at 8,000 Hz, age-adjusted). CONCLUSION: The degree of the threshold changes exhibited an exponential increase with age. Cessation of smoking is advisable to prevent increased aggravation of hearing. Strict management of the low-density lipoprotein cholesterol may have a positive effect on hearing. LEVEL OF EVIDENCE: 3 Laryngoscope, 129:470-476, 2019.


Subject(s)
Aging/physiology , Audiometry, Pure-Tone/statistics & numerical data , Auditory Threshold/physiology , Hearing/physiology , Adult , Age Factors , Aged , Female , Humans , Lipids/blood , Longitudinal Studies , Male , Middle Aged , Retrospective Studies , Smoking/adverse effects , Young Adult
7.
Medicine (Baltimore) ; 97(36): e12211, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30200133

ABSTRACT

To evaluate the outcomes and prognostic factors of endovascular management in immature arteriovenous fistula (AVF) for hemodialysis.From April 2007 to September 2017, 54 patients (male:female = 31:23, mean age 65.63 years, range 33-90 years) who underwent endovascular management for the salvage of immature AVF were retrospectively reviewed. Clinical data, procedural details, and results were evaluated. Primary and secondary patency rates and factors influencing the patency were also analyzed.Technical and clinical success rates were 88.9% (48/54) and 85.2% (46/54), respectively. Mean primary and secondary patency was 42.10 (±8.85) and 91.5 (±14.77) months, respectively. Primary and secondary patency rates were 66% and 89% in 1 year, 66% and 78% in 2 years, and 51% and 78% in 3 years. In multivariate analysis, only brachiocephalic AVF and antegrade access procedures showed significantly shorter primary patency (HR 5.196; 95% CI (1.04-25.77); P = .044, HR 8.096; 95% CI (1.36-48.00); P = .021). There was no statistically significant factor associated with secondary patency in the multivariate study.Endovascular management in immature AVF is safe and effective to make the AVF available. Brachiocephalic AVF and antegrade access procedures are the factors influencing the patency in multivariate analysis.


Subject(s)
Arteriovenous Fistula/surgery , Endovascular Procedures , Renal Dialysis , Adult , Aged , Aged, 80 and over , Arteriovenous Fistula/diagnosis , Female , Follow-Up Studies , Humans , Male , Middle Aged , Multivariate Analysis , Prognosis , Retrospective Studies , Treatment Outcome
8.
World Neurosurg ; 114: e1152-e1160, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29614363

ABSTRACT

OBJECTIVE: Stent-assisted coil embolization (SAC) is one of the treatment options for patients with intracranial aneurysms. The purpose of this study was to assess clinical outcomes of patients who underwent coil embolization for acutely ruptured aneurysms without antiplatelet premedication. METHODS: A total of 449 patients with acutely ruptured aneurysms underwent endovascular treatment without antiplatelet premedication between April 2006 and October 2015. Among them, 55 patients underwent SAC (SAC group) and 394 underwent coiling without stent assistance (non-SAC group). Periprocedural complications and clinical outcomes at postictal 6 months were compared between the 2 groups. RESULTS: The rate of hemorrhagic complications showed no significant difference (SAC group vs. non-SAC group, 9.1% vs. 4.8%). Although procedural thromboembolism occurred more frequently in the SAC group (25.5% vs. 12.4%; P = 0.01), poor clinical outcomes (modified Rankin scale score ≥3) were comparable (30.9% vs. 22.1%). In the multivariate analysis, Hunt-Hess grade (odds ratio [OR] = 4.22; P < 0.001), hemorrhagic complications (OR = 4.01; P = 0.018), and age (OR = 1.04, P = 0.001) were independent predictors of poor clinical outcomes, but stent-assisted coil embolization and procedural thromboembolism were not. CONCLUSIONS: Although procedure-related thromboembolism occurred more frequently, comparable treatment outcomes could be achieved with antiplatelet premedication-free SAC in patients with acutely ruptured aneurysms. The use of stents and thromboembolic complications were not significant risk factors for poor clinical outcome.


Subject(s)
Aneurysm, Ruptured/diagnostic imaging , Aneurysm, Ruptured/surgery , Endovascular Procedures/instrumentation , Platelet Aggregation Inhibitors , Pre-Exposure Prophylaxis , Stents , Acute Disease , Adult , Aged , Embolization, Therapeutic/instrumentation , Embolization, Therapeutic/methods , Endovascular Procedures/methods , Female , Humans , Male , Middle Aged , Platelet Aggregation Inhibitors/administration & dosage , Retrospective Studies , Stents/statistics & numerical data , Treatment Outcome
9.
Neurosurgery ; 83(5): 981-988, 2018 11 01.
Article in English | MEDLINE | ID: mdl-29301051

ABSTRACT

BACKGROUND: The use of antiplatelet medications to prevent thrombosis in the treatment of cerebral aneurysms with stents has become widely emphasized. OBJECTIVE: To compare low-dose prasugrel with clopidogrel in stent-assisted coil embolization of intracranial aneurysms. METHODS: This is a retrospective review of 311 aneurysms from 297 patients who underwent stent-assisted endovascular coil embolization of unruptured intracranial aneurysm between November 2014 and March 2017. Thromboembolic and hemorrhagic adverse events were compared between 207 patients who received low-dose prasugrel (PSG group) and 90 patients who received clopidogrel (CPG group). RESULTS: P2Y12 reaction unit (PRU) values were significantly lower in the PSG group (PSG group vs CPG group, 132.3 ± 76.9 vs 238.1 ± 69.1; P < .001); the percentage of inhibition was also statistically higher in the PSG group (54.0 ± 26.0% vs 20.8 ± 18.6%; P < .001). Thromboembolic events occurred less frequently in the PSG group than in the CPG group (0.9% vs 6.4%; P = .01), whereas there was no significant difference in the percentage of hemorrhagic complications (0.5% vs 2.2%; P = .22). In the multivariate analysis, clopidogrel as the antiplatelet medication was the sole significant risk factor for thromboembolism in this series of patients undergoing stent-assisted coil embolization. CONCLUSION: Use of low-dose PSG as an antiplatelet premedication is quick, effective, and safe for stent-assisted coil embolization of unruptured intracranial aneurysms. Prasugrel premedication significantly lowered the frequency of thromboembolic events without increasing the risk of hemorrhage.


Subject(s)
Clopidogrel/therapeutic use , Intracranial Aneurysm/surgery , Platelet Aggregation Inhibitors/therapeutic use , Prasugrel Hydrochloride/therapeutic use , Premedication/methods , Thromboembolism/prevention & control , Adult , Aged , Embolization, Therapeutic/adverse effects , Endovascular Procedures/adverse effects , Female , Humans , Intracranial Aneurysm/complications , Male , Middle Aged , Retrospective Studies , Risk Factors , Stents , Thromboembolism/etiology
10.
Clin Nephrol ; 86 (2016)(12): 319-327, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27781419

ABSTRACT

AIMS: The tablet form (500 mg) of mycophenolate mofetil (MMF) provides more convenience of taking drugs and cost-effectiveness than the capsule form (250 mg). We examined the efficacy and safety of MMF in its different forms combined with tacrolimus in kidney transplant recipients. METHODS: This multicenter, 26-week, randomized trial was performed to compare the efficacy and safety of the tablet form of MMF versus the capsule form of MMF in 156 kidney transplant recipients. Allograft function, the incidence of efficacy failure (biopsy-proven acute rejection (BPAR), death, graft loss, or loss to follow-up), and adverse events were compared. RESULTS: The mean dose (mg/day) of MMF at 26 weeks was comparable: 1,052.6 ± 194.2 in the tablet group vs. 1,155.6 ± 298.1 in the capsule group (p = 0.063). Trough levels of tacrolimus at 26 weeks were comparable. The mean estimated glomerular filtration rate of the tablet group at 26 weeks post-transplant was not inferior to that of the capsule group. The incidence of efficacy failure was similar in the two groups: tablet group, 5.2% and capsule group, 7.7% (difference -2.5%; 95% confidence interval -5.22 - 10.21%). The incidence of BPAR until 26 weeks post-transplant in the tablet group was 3.9%, compared to 7.7% in the capsule group (p = 0.346). There was no significant difference in the incidence of discontinuations and serious adverse events between the groups. CONCLUSION: Low-dose MMF in tablet form combined with tacrolimus can be considered as an efficacious and safe immunosuppressive regimen in the early period after kidney transplantation.
.


Subject(s)
Immunosuppressive Agents/administration & dosage , Mycophenolic Acid/administration & dosage , Tacrolimus/therapeutic use , Adult , Capsules , Drug Therapy, Combination , Female , Glomerular Filtration Rate , Graft Rejection/prevention & control , Humans , Immunosuppressive Agents/therapeutic use , Kidney Transplantation , Male , Middle Aged , Mycophenolic Acid/therapeutic use , Prospective Studies , Tablets , Tacrolimus/blood
11.
Medicine (Baltimore) ; 95(23): e3711, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27281070

ABSTRACT

Acute cellular rejection after liver transplantation (LT) can be treated with steroid pulse therapy, but there is no ideal treatment for steroid-resistant acute rejection (SRAR). We aimed to determine the feasibility and potential complications of rabbit anti-thymocyte globulin (rATG) application to treat SRAR in liver transplant recipients. We retrospectively reviewed medical records of 429 recipients who underwent LT at Severance Hospital between January 2010 and March 2015. We compared clinical features and graft survival between patients with steroid-sensitive acute rejection (SSAR; n = 23) and SRAR (n = 11). We also analyzed complications and changes in laboratory findings after 2.5 mg/kg rATG treatment in patients with SRAR for 6 to 10 days. There were no significant differences in gender, age, model for end-stage liver disease score, Child-Turcotte-Pugh score, or original liver diseases between patients with SSAR and SRAR, although deceased donors were more frequently associated with the SRAR group (P = 0.004). All SRAR patients responded positively to rATG treatment; after treatment, the patients' median AST levels decreased from 138 to 63 IU/L, and their median ALT levels dropped from 327 to 70 IU/L 1 day after rATG treatment (P = 0.022 and 0.017, respectively). Median aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin levels significantly decreased 1 month post-treatment (P = 0.038, 0.004, and 0.041, respectively). Median survival after LT was 23 months, and median survival after rATG was 22 months in patients with SRAR. Adverse effects included hepatitis C virus (HCV) reactivation, fungemia, and cytomegalovirus (CMV) infection. Nine SRAR patients survived with healthy liver function, 1 died from a traffic accident during follow-up, and 1 died from graft-versus-host disease and fungemia. Administration of rATG is an effective therapeutic option for SRAR with acceptable complications in liver transplant recipients. However, the occurrence of HCV reactivation and CMV infection in LT patients should be monitored after rATG treatment in these patients.


Subject(s)
Antilymphocyte Serum/therapeutic use , Drug Resistance , Glucocorticoids/pharmacology , Graft Rejection/therapy , Graft Survival , Liver Transplantation/adverse effects , Acute Disease , Adolescent , Adult , Aged , Animals , Child , Child, Preschool , Female , Follow-Up Studies , Graft Rejection/immunology , Humans , Immunologic Factors/therapeutic use , Infant , Infant, Newborn , Male , Middle Aged , Rabbits , Retrospective Studies , Time Factors , Treatment Outcome , Young Adult
12.
Medicine (Baltimore) ; 94(38): e1569, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26402818

ABSTRACT

To reduce hepatitis B virus reinfection after liver transplantation (LT), patients often receive antihepatitis B immunoglobulin (HBIG) alone or combined with antiviral nucleoside/nucleotide analogs (NUCs); however, proximal renal tubular dysfunction (RTD) that was induced by NUCs in liver recipients was rarely reported. Here, we analyzed RTD and renal impairment (RI) following adefovir (ADV) and lamivudine (LAM) treatment in liver recipients. We retrospectively reviewed medical records of patients treated with HBIG alone (group 1, n = 42) or combined with ADV or LAM (group 2, n = 21) after LT. We compared RTD and RI incidence during the 12 months after LT. An RTD diagnosis required manifestation of at least 3 of the following features: hypophosphatemia, RI, hypouricemia, proteinuria, or glucosuria. No significant differences were observed regarding sex, age, donor type, model of end-stage liver score, and estimated glomerular filtration rate at pre-LT between the 2 groups. Hepatitis B virus recurrence within 12 months was 4.8% in both groups (P = 1.000); however, the RTD incidence was 0% in group 1 and 19.0% in group 2 (P = 0.010). RI occurrence did not differ between the groups. The only risk factor for RI was HBIG administration combined with both LAM and ADV (odds ratio 11.27, 95% confidence interval 1.13-112.07, P = 0.039, vs HBIG alone). RTD occurred more frequently in patients treated with HBIG combined with LAM or ADV compared with HBIG alone. Thus, LAM or ADV therapy can induce RTD after LT, and when administered, liver recipients should be monitored.


Subject(s)
Hepatitis B/prevention & control , Kidney Diseases/chemically induced , Liver Transplantation , Postoperative Complications/chemically induced , Reverse Transcriptase Inhibitors/adverse effects , Adenine/adverse effects , Adenine/analogs & derivatives , Female , Hepatitis B/epidemiology , Humans , Incidence , Kidney Diseases/blood , Kidney Diseases/mortality , Lamivudine/adverse effects , Male , Middle Aged , Organophosphonates/adverse effects , Postoperative Complications/blood , Postoperative Complications/mortality , Recurrence , Republic of Korea/epidemiology , Retrospective Studies , Risk Factors
13.
J Korean Med Sci ; 30(6): 682-7, 2015 Jun.
Article in English | MEDLINE | ID: mdl-26028917

ABSTRACT

The optimal immunosuppressive strategy for renal transplant recipients at high immunologic risk remains a topic of investigation. This prospective single arm pilot study was undertaken to evaluate the safety and efficacy of a combined tacrolimus and sirolimus regimen in recipients at immunological high risk and to compare outcomes with a contemporaneous control group received tacrolimus and mycophenolate mofetil. Patients that received a renal allograft between 2010 and 2011 at high risk (defined as panel reactive antibodies > 50%, 4 or more human leukocyte antigen mismatches, or retransplantation) were enrolled. All patients received basiliximab induction and corticosteroids. A total of 28 recipients treated with tacrolimus and sirolimus were enrolled in this study and 69 recipients were retrospectively reviewed as a control group. The sirolimus group showed a higher, but not statistically significant, incidence of biopsy proven acute rejection and a lower glomerular filtration rate than the control group. Furthermore, sirolimus group was associated with significant increases in BKV infection (P = 0.031), dyslipidemia (P = 0.004), and lymphocele (P = 0.020). The study was terminated prematurely due to a high incidence of adverse events. A de novo tacrolimus/sirolimus combination regimen may not be an ideal choice for recipients at high immunological risk.


Subject(s)
Graft Rejection/etiology , Graft Rejection/prevention & control , Kidney Transplantation/adverse effects , Sirolimus/administration & dosage , Tacrolimus/administration & dosage , Adult , Drug Therapy, Combination/methods , Female , Graft Rejection/diagnosis , Humans , Immunocompromised Host , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/adverse effects , Longitudinal Studies , Male , Middle Aged , Sirolimus/adverse effects , Survival Rate , Tacrolimus/adverse effects , Treatment Outcome
14.
Ann Surg Treat Res ; 88(2): 100-5, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25692121

ABSTRACT

PURPOSE: Preformed circulating donor-specific antibodies (DSAs) immunologically challenge vascular endothelium and the bile duct. However, the liver is an immune-tolerant organ and can avoid immunological challenges. This study was undertaken to analyze the effects of DSAs after adult living donor liver transplantation (LDLT). METHODS: We retrospectively reviewed 219 LDLT patients' records treated at our center. RESULTS: Of the 219 patients, 32 (14.6%) were DSA (+) and 187 (85.4%) were DSA (-). Class I DSAs were present in 18 patients, class II in seven patients, and both in seven patients. Seven patients (3.2%) showed DSA to HLA-A, four (1.8%) to HLA-B, seven (3.2%) to HLA-DR, and 14 (6.4%) to two or more HLAs. More DSAs were observed in female recipients than male recipients in the DSA (+) group. The DSA (+) group showed significantly higher levels of class I and II panel reactive antibody (PRA) than did the DSA (-) group. No significant intergroup differences were found between incidences of primary nonfunction, acute rejection, vascular complication, or biliary complication. There were no significant differences in graft survival rates between the two groups. However, the recipients with multiple DSAs tended to have more acute rejection episodes and events of biliary stricture and lower graft survival rates than did patients in the DSA (-) group. CONCLUSION: In LDLT, the presence of multiple DSAs and high PRA seemed to be associated with poor graft outcomes, although our results did not reach statistical significance. Large cohort studies are necessary to clarify the impact of DSA and PRA in LDLT.

15.
Biochem Pharmacol ; 80(7): 982-9, 2010 Oct 01.
Article in English | MEDLINE | ID: mdl-20599784

ABSTRACT

Hypoxia-inducible factor HIF-1 is responsible for radiation resistance and poor prognosis in cancer therapy. As part of our drug discovery program, a novel HIF inhibitor, LW6, was identified as a small compound that inhibits the accumulation of HIF-1alpha. We found that LW6 decreased HIF-1alpha protein expression without affecting HIF-1beta expression. MG132, a proteasome inhibitor, protected HIF-1alpha from LW6-induced proteasomal degradation, indicating that LW6 affects the stability of the HIF-1alpha protein. We found that LW6 promoted the degradation of wild type HIF-1alpha, but not of a DM-HIF-1alpha with modifications of P402A and P564A, at hydroxylation sites in the oxygen-dependent degradation domain (ODDD). LW6 did not affect the activity of prolyl hydroxylase (PHD), but induced the expression of von Hippel-Lindau (VHL), which interacts with prolyl-hydroxylated HIF-1alpha for proteasomal degradation. In the presence of LW6, knockdown of VHL did not abolish HIF-1alpha protein accumulation, indicating that LW6 degraded HIF-1alpha via regulation of VHL expression. In mice carrying xenografts of human colon cancer HCT116 cells, LW6 demonstrated strong anti-tumor efficacy in vivo and caused a decrease in HIF-1alpha expression in frozen-tissue immunohistochemical staining. These data suggest that LW6 may be valuable in the development of a HIF-1alpha inhibitor for cancer treatment.


Subject(s)
Acetanilides/pharmacology , Adamantane/analogs & derivatives , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Hypoxia-Inducible Factor 1/antagonists & inhibitors , von Hippel-Lindau Disease/genetics , Adamantane/pharmacology , Animals , Aryl Hydrocarbon Receptor Nuclear Translocator , Cell Line , Colonic Neoplasms/genetics , Colonic Neoplasms/metabolism , Female , Humans , Hypoxia-Inducible Factor 1/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Mice , Mice, Nude , Oxygen/metabolism , Procollagen-Proline Dioxygenase/genetics , Procollagen-Proline Dioxygenase/metabolism , Proteasome Endopeptidase Complex/genetics , Proteasome Endopeptidase Complex/metabolism , Proteins/genetics , Proteins/metabolism , Up-Regulation , von Hippel-Lindau Disease/metabolism
16.
Free Radic Biol Med ; 49(3): 323-31, 2010 Aug 01.
Article in English | MEDLINE | ID: mdl-20430097

ABSTRACT

We have identified a novel anti-inflammatory signaling pathway that leads to the expression of heme oxygenase-1 (HO-1) in response to bisdemethoxycurcumin (BDMC), an analog of curcumin. Treatment with BDMC suppressed inducible nitric oxide synthase expression and nitric oxide (NO) production by down-regulating NF-kappaB activity in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. These effects were reversed by blocking HO-1 activity or expression. The signaling pathway involved in BDMC-mediated HO-1 induction included Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and extracellular signal-regulated kinase 1/2 (ERK1/2). BDMC induced phosphorylation of ERK1/2 in a CaMKII-dependent manner. Pretreatment with the mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor, U0126, inhibited CaMKII-induced stimulation of HO-1 promoter activity, suggesting that ERK1/2 is a downstream mediator of CaMKII in BDMC signaling to HO-1 expression. Furthermore, the CaMKII-ERK1/2 cascade targets the transcription factor, NF-E2-related factor-2 (Nrf2). Finally, inhibition of the Ca(2+)-CaMKII-ERK1/2-linked cascade attenuated significantly suppression by BDMC of LPS-induced iNOS expression and subsequent NO production. Collectively, our findings identify a Ca(2+)/calmodulin-CaMKII-ERK1/2-Nrf2 cascade as a novel anti-inflammatory pathway mediating BDMC signaling to HO-1 expression in macrophages.


Subject(s)
Calcium-Calmodulin-Dependent Protein Kinase Type 2/physiology , Curcumin/analogs & derivatives , Heme Oxygenase-1/biosynthesis , Macrophages/metabolism , Mitogen-Activated Protein Kinase 1/physiology , Mitogen-Activated Protein Kinase 3/physiology , NF-E2-Related Factor 2/physiology , Animals , Butadienes/pharmacology , Calcium/metabolism , Cell Line , Curcumin/pharmacology , Diarylheptanoids , Gene Expression Regulation, Enzymologic/drug effects , Heme Oxygenase-1/genetics , Inflammation/drug therapy , Lipopolysaccharides/pharmacology , Macrophages/drug effects , Mice , NF-kappa B/drug effects , NF-kappa B/physiology , Nitriles/pharmacology , Signal Transduction/drug effects , Up-Regulation
17.
Bioorg Med Chem Lett ; 15(18): 4037-42, 2005 Sep 15.
Article in English | MEDLINE | ID: mdl-16039123

ABSTRACT

We report the synthesis of a series of monoanionic phosphotyrosyl (pTyr) mimetic-containing tripeptides based on 'Fmoc-Glu(OBn)-Xxx-Leu-amide' (where Xxx = pTyr mimetic) and their N-terminally modified derivatives. The inhibitory potencies of compounds were tested against YopH and human PTP1B enzymes. Several compounds exhibited noteworthy activity against both YopH and PTP1B. Among the N-terminally modified analogues, 5-methylindole derivative 30 was found to be the best moiety to replace base-labile Fmoc group. A mode of binding with YopH is proposed for tripeptides 21, 30, and 31.


Subject(s)
Bacterial Outer Membrane Proteins/antagonists & inhibitors , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacology , Oligopeptides/chemical synthesis , Oligopeptides/pharmacology , Protein Tyrosine Phosphatases/antagonists & inhibitors , Yersinia/enzymology , Bacterial Outer Membrane Proteins/chemistry , Bacterial Outer Membrane Proteins/metabolism , Binding Sites , Enzyme Inhibitors/chemistry , Humans , Inhibitory Concentration 50 , Models, Molecular , Molecular Structure , Oligopeptides/chemistry , Protein Binding , Protein Structure, Tertiary , Protein Tyrosine Phosphatase, Non-Receptor Type 1 , Protein Tyrosine Phosphatases/chemistry , Protein Tyrosine Phosphatases/metabolism , Structure-Activity Relationship
18.
Waste Manag Res ; 21(3): 278-89, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12870647

ABSTRACT

A series of tests were conducted to investigate the fate of heavy metals and gasoline components in a simulated landfill, consisting of a 30 cm thick clay liner and a leachate collection layer containing tyres as well as in two test cells installed in a landfill. Arsenic, selenium, mercury, barium, and lead concentrations were lower while zinc concentration was higher in the tank containing tyre-chips than the tank without tyre-chips. When samples were filtered, however, concentrations of zinc as well as other inorganics were lower in the tank containing tyre-chips, indicating that metals in the leachate exposed to tyre-chips travel more slowly in a subsurface environment due to filtering effect. In a test cell study, arsenic, cobalt, lead and nickel concentrations were lower in the cell containing tyre-chips than in the cell without tyre-chips, except iron and zinc. Both tests indicate that some inorganic contaminants are sorbed to tyre-chips. Gasoline components were also significantly sorbed by tyre-chips in field cell tests. Although tyre-chips are known to leach organic and inorganic contaminants, concentrations in field conditions will be lower than the reported experimental results since the tests were performed under worst-case scenarios. If tyre-chips are used in areas where contamination levels are high, then they can be used as a sorbent for environmental clean-up.


Subject(s)
Conservation of Natural Resources , Environmental Pollutants/isolation & purification , Refuse Disposal/methods , Water Pollution/prevention & control , Adsorption , Filtration , Materials Testing , Motor Vehicles , Rubber , Soil Pollutants/analysis , Water Movements
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