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1.
Korean J Transplant ; 37(4): 306-309, 2023 Dec 31.
Article in English | MEDLINE | ID: mdl-38153256

ABSTRACT

Liver transplantation is a critical procedure for patients with end-stage liver disease, but it is often hindered by ABO-incompatibility between the donor and recipient, which can lead to immediate humoral rejection. We present a unique case involving a 10-month-old patient who, by accident, received an ABO-incompatible partial liver transplant from a type A mother without undergoing desensitization. Remarkably, during a 21-year follow-up period, the patient exhibited no signs of humoral or graft rejection, despite nonadherence to medication. This case highlights the possibility of dual tolerance in pediatric ABO-incompatible liver transplantation and provides insights into immune tolerance mechanisms, with implications for enhancing patient care and reducing healthcare costs. Further research is necessary to clarify these mechanisms and to evaluate the long-term durability of tolerance in pediatric transplant recipients.

2.
Article in English | MEDLINE | ID: mdl-38013393

ABSTRACT

Breslow thickness, ulceration, and mitotic rate are well-known prognostic factors for sentinel lymph node (SLN) metastasis in cutaneous melanoma. We investigated risk factors, including especially the degree of pigmentation, for SLN metastasis in Korean melanoma patients. We enrolled 158, composed of Korean 107 acral and 51 non-acral melanoma patients who underwent SLN biopsy. Clinicopathologic features such as Breslow thickness, ulceration, mitotic rate, and the degree of pigmentation were evaluated. The recurrence-free survival (RFS) rate and date of recurrence were determined. Fifty-four patients (34.2%) had a positive SLN biopsy result. In a multivariate analysis, Breslow thickness (odds ratio [OR] 1.93; 95% confidence interval [CI], 1.12-3.47; p = .022) and heavy pigmentation (OR 13.14; 95% CI, 2.96-95.20, p = .002) were associated with SLN metastasis. Positive SLN patients had a higher rate of loco-regional and/or distant recurrence (hazard ratio 6.32; 95% CI, 3.39-11.79; p < .001). Heavy pigmentation was associated with poor RFS. Heavy pigmentation is an independent predictor of SLN metastasis in both acral and non-acral melanoma. Our results suggest the need for in-depth SLN evaluation of cutaneous melanoma patients with heavy pigmentation and provide clinicians with important information for determining patient prognosis.

3.
Medicine (Baltimore) ; 102(41): e34639, 2023 Oct 13.
Article in English | MEDLINE | ID: mdl-37832135

ABSTRACT

The purpose of this study was to evaluate the proper position of single large hepatocellular carcinoma (HCC) in the Barcelona Clinic Liver Cancer (BCLC) staging system. The data were collected from the nationwide multicentre database of the Korean Liver Cancer Association. Patients with single large (≥5 cm) HCC were separated from BCLC stage A patients and designated as Group X. The remaining BCLC stage A and stage B patients were classified as Group A and Group B, respectively. The survival outcomes of propensity score-matched groups were compared. Among the 3965 randomly selected patients, the number of patients in Group X, Group A, and Group B was 414, 2787, and 760, respectively. TriMatch analysis allowed us to obtain 116 well-balanced triplets. The 1-, 3-, and 5-year overall survival rates in Group X were worse than in Group A (91%, 71%, and 48% vs 90%, 78%, and 64%, respectively; P < .000). However, the rates were not different compared with those in Group B (91%, 71%, and 48% vs 90%, 69%, and 48%, respectively; P < .09). In multivariate analysis, Group X, Group B, age over 60 years, prothrombin time-international normalized ratio, and creatinine level were independent predictors of worse overall survival. Our findings suggest that Group X should be relocated to BCLC stage B rather than BCLC stage A.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Middle Aged , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Neoplasm Staging , Survival Rate , Prothrombin Time , Retrospective Studies , Hepatectomy , Prognosis
4.
Medicina (Kaunas) ; 59(9)2023 Aug 23.
Article in English | MEDLINE | ID: mdl-37763634

ABSTRACT

Actinomycosis is a rare, chronic, suppurative, and granulomatous bacterial disease. The Actinomyces species exist as normal flora in the oropharynx, gastrointestinal tract, and the female genital tract. They are incapable of penetrating the normal mucous membranes and become pathogenic only when this barrier has been destroyed by trauma, surgery, immunosuppression, or after viscus perforation. We report the first case of an actinomycotic abscess after laparoscopic sleeve gastrectomy. A 29-year-old man underwent a laparoscopic sleeve gastrectomy with no intra-operative complications. On postoperative day 3, the patient had a fever with elevated inflammatory markers. Abdominal computerized tomography (CT) with oral water-soluble contrast media showed no extra-luminal leakage and no fluid collection adjacent to the resected stomach, other than the fluid collection in the right subhepatic space. Percutaneous drainage was attempted, but the procedure failed due to the patient's thick abdominal wall. After two weeks of weight loss of about 12 kg, percutaneous drainage was successfully performed, and A. odontolyticus was identified through pus culture. After effective abscess drainage and high-dose antibiotics, the patient's symptoms improved and the abscess pocket disappeared. We reported Actinomyces infection after gastric sleeve surgery. In the case of abscess formation after gastric sleeve surgery caused by actinomycete infection, antibiotic treatment and percutaneous drainage are effective together.

5.
Transplant Proc ; 53(7): 2238-2241, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34420782

ABSTRACT

BACKGROUND: The purpose of this study was to identify factors influencing changes in the body mass index (BMI) of kidney transplant (KT) patients and provide data for the management of the BMI of patients who have undergone KT. METHOD: The participants were 106 patients who underwent KT at a single center from August 2014 to June 2017. BMIs were compared and analyzed for 6 months and 24 months after KT, and the survey details were collected through medical records. Analysis was performed between 2 groups, one with increased BMI and the other without. Multivariate logistic regression analysis was performed to identify the factors related to an increase in BMI. RESULTS: BMI increased from 22.60 ± 2.72 kg/m2 at 6 months to 23.18 ± 3.06 kg/m2 2 years after KT. The group with increased BMI (n = 39) had more patients with higher low-density cholesterol levels at the time of KT (low-density cholesterol ≥100 mg/dL; 34 [54.0%] vs 10 [26.3]; P = .008) and without statin drug use than the other group (n = 67) (statin drug use, 48 [70.6%] vs 34 [87.2%], P = .044). Multiple logistic regression analysis showed that age >50 years (odds ratio [OR] = 2.942; 95% confidence interval [CI], 1.075-8.055; P = .036), low-density lipoprotein >100 mg/dL at KT (OR = 6.618; 95% CI, 2.225-19.682; P = 0.001), and no statin drugs (OR = 5.094; 95% CI, 1.449-17.911, P = .011) were the risk factors for an increased BMI after KT. CONCLUSIONS: After KT, to prevent an increase in the BMI, clinicians should strongly recommend the use of drugs to treat hyperlipidemia, especially in elderly patients with high low-density lipoprotein levels before KT.


Subject(s)
Kidney Transplantation , Aged , Body Mass Index , Factor Analysis, Statistical , Humans , Kidney Transplantation/adverse effects , Middle Aged , Risk Factors , Transplant Recipients
6.
Vasc Specialist Int ; 37: 15, 2021 Jun 25.
Article in English | MEDLINE | ID: mdl-34168097

ABSTRACT

Adventitial cystic disease (ACD) of the veins is a rare vascular disease. Most cases of venous ACD are located adjacent to the joint area, such as the common femoral, external iliac, and popliteal veins. To the best of our knowledge, 67 cases of venous ACD have been reported, and ACD of the superficial femoral vein (SFV) has never been reported. Herein, we report the case of a 57-year-old male who presented with swelling and discomfort in the left leg. Computed tomography venography revealed multiple cystic lesions in the left distal SFV. The patient underwent cyst excision, which relieved the compression in the vein, although mild stenosis prevailed in the SFV. After a week, thrombosis developed in the popliteal vein. The thrombosis resolved after three months of anticoagulant therapy, and the patient showed no recurrence of ACD during three years of follow-up.

7.
Ann Surg Treat Res ; 100(3): 166-174, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33748030

ABSTRACT

PURPOSE: Initial conservative treatment with selective endovascular or surgical intervention has shown successful outcomes in the treatment of spontaneous isolated superior mesenteric artery dissection (SISMAD). However, the benefits of antithrombotic therapy as a part of conservative treatment have not been clarified. This study aimed to investigate the clinical course of SISMAD patients and determine differences in clinical outcomes between the antithrombotic and no-antithrombotic groups. METHODS: We retrospectively reviewed 79 cases of SISMAD that were treated conservatively from January 2004 to December 2019 at Chonnam National University Hospital. Clinical outcomes, including the length of hospital stay, pain resolution time, image remodeling, and maximal remodeling time, were compared between the antithrombotic and no-antithrombotic groups. RESULTS: There were 30 patients in the no-antithrombotic group and 49 patients in the antithrombotic group. There was no significant difference in clinical characteristics between the 2 groups, except for dyslipidemia (P = 0.011). The follow-up period (32.6 months vs. 14.6 months, P = 0.009) and imaging follow-up period (31.6 months vs. 13.9 months, P = 0.011) were longer in the antithrombotic group than in the no-antithrombotic group. The length of hospital stay (5.1 days vs. 7.7 days, P = 0.002) was significantly shorter in the no-antithrombotic group than in the antithrombotic group because patients in the antithrombotic group required longer hospitalization for warfarin titration. CONCLUSION: In patients with SISMAD, conservative treatment without antithrombotic therapy may have clinical benefits such as decreased length of hospital stay compared with conservative treatment with antithrombotic therapy.

8.
Diagn Interv Radiol ; 26(5): 476-481, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32209509

ABSTRACT

PURPOSE: We aimed to evaluate the utility of and complications associated with the double microcatheter technique for the treatment of wide-necked visceral and renal artery aneurysms (VRAAs). METHODS: Nine patients (mean age, 58 years; age range, 42-69 years; 4 men, 5 women) with wide-necked VRAAs who underwent treatment with the double microcatheter technique from January 2016 to July 2018 were included in the study. For all patients, anatomical features were confirmed using cone-beam computed tomography (CT) with rotational angiography. The aneurysmal location, size, volume, neck-to-dome ratio, number of coils used, and coil packing density were investigated. Technical success, complications (coil migration and organ ischemia), changes in the complete blood count or serum creatine level, and recurrence were also evaluated. RESULTS: Three renal artery aneurysms and 6 splenic artery aneurysms were treated by the double microcatheter technique. The mean size of the aneurysms was 26.09±4.76 mm, mean volume was 6.19±3.69 cm3, and mean neck-to-dome ratio was 1.53±0.24. The number of coils used ranged from 7 to 16. The mean packing density was 11.32%±3.72%. Technical success was achieved in all 9 patients. Renal ischemia occurred in two patients with renal artery aneurysm, one of whom showed minimal scar formation on follow-up CT after infarction. No coil migrations or disease recurrences were observed. CONCLUSION: The double microcatheter technique for the treatment of wide-necked VRAAs appears to be relatively safe and useful. However, complex renal artery aneurysm should be carefully managed in order to prevent infarction.


Subject(s)
Aneurysm , Embolization, Therapeutic , Endovascular Procedures , Intracranial Aneurysm , Adult , Aged , Aneurysm/diagnostic imaging , Aneurysm/surgery , Female , Humans , Male , Middle Aged , Renal Artery/diagnostic imaging , Stents , Treatment Outcome
9.
Transplant Proc ; 51(8): 2842-2844, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31526531

ABSTRACT

All over the world there is serious concern about the shortage of organs available for transplantation. In an effort to address this, transplantation with grafts, which was previously considered a contraindication, are now performed. In some cases, this practice has contributed to increasing the organ pool. Fibromuscular dysplasia (FMD) is the second-most-common cause of renovascular hypertension and is observed in 2%-6.6% of potential live kidney donors. Kidney with FMD is generally considered to be a contraindication for renal transplantation because renal artery stenosis may progress after transplantation and cause graft loss. Here, we report on a successful case of kidney transplantation using a graft with FMD of a deceased donor who had multiple aneurysms in the renal artery.


Subject(s)
Fibromuscular Dysplasia , Kidney Failure, Chronic/surgery , Kidney Transplantation , Adult , Female , Humans , Kidney Transplantation/methods , Treatment Outcome
11.
Ann Surg Treat Res ; 92(6): 440-443, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28580350

ABSTRACT

Coil migration is an extremely rare but hazardous complication of aneurysmal coil embolization. Only 1 case report has described coil migration following endovascular exclusion to gastrointestinal (GI) tract. We report the experience of a case of colon penetration caused by embolization coil placed for internal iliac aneurysm. A 66-year-old man visited the Emergency Department for hematochezia that had persisted for 3 months. Stent insertion and coil embolization of left internal iliac artery aneurysm had been performed on the patient 18 months ago. Colonoscopy was performed. It suggested penetration of sigmoid colon by embolization coil and diverticulum. Angiography revealed extravasation of contrast media at left internal iliac artery. Covered stent deployment was done in the left internal iliac artery. One week after the stent insertion, the patient underwent anterior resection, aneurysm resection, and coil removal. The patient recovered without complications. He was discharged at 2 weeks after the operation.

12.
Vasc Specialist Int ; 33(4): 160-165, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29354627

ABSTRACT

PURPOSE: To evaluate patients who underwent surgical or endovascular treatment after vascular injury related to posterior lumbar disc surgery. MATERIALS AND METHODS: We retrospectively reviewed seven cases of vascular injuries (four lacerations, one arteriovenous fistula [AVF], and two pseudoaneurysms) related to lumbar disc surgery by a posterior approach from January 1997 to December 2016 at Chonnam National University Hospital. Information of patient characteristics, diagnosis, treatment strategies, and outcomes were analyzed. RESULTS: Five out of seven cases were inhospital cases. In three laceration cases, each patient instantly became hypotensive and a life-threatening arterial injury was suspected. Therefore, the patient was immediately turned to the supine position and surgical repair was performed. The patients with pseudoaneurysm and AVF were treated by endovascular intervention. Remaining two were referred cases under the impression of vascular injuries. One laceration case of them was in preshock condition, and the left common iliac artery was surgically repaired. The other referred patient showed pseudoaneurysm which was treated with stent graft insertion. There was no surgery or endovascular intervention related death and none of the patients suffered any sequela related to vascular injury. CONCLUSION: Vascular injury associated with posterior lumbar disc surgery is not common, but can be fatal. Early recognition, diagnosis, and prompt treatment are essential to prevent fatal outcomes. Recently, endovascular intervention is increasingly and preferably used because of its low morbidity and mortality. However surgery is still the best option for the patients with unstable vital sign and endovascular approach can be applied to stable patients.

14.
Cardiovasc Intervent Radiol ; 38(1): 227-31, 2015 Feb.
Article in English | MEDLINE | ID: mdl-24488154

ABSTRACT

This study was designed to evaluate the efficacy and safety of CT-guided embolization of internal iliac artery aneurysm (IIAA) after repair of abdominal aortic aneurysm by transretroperitoneal approach using the lidocaine injection technique to iliacus muscle, making window for safe needle path for three patients for whom CT-guided embolization of IIAA was performed by transretroperitoneal approach with intramuscular lidocaine injection technique. Transretroperitoneal access to the IIAA was successful in all three patients. In all three patients, the IIAA was first embolized using microcoils. The aneurysmal sac was then embolized with glue and coils without complication. With a mean follow-up of 7 months, the volume of the IIAAs remained stable without residual endoleaks. Transretroperitoneal CT-guided embolization of IIAA using intramuscular lidocaine injection technique is effective, safe, and results in good outcome.


Subject(s)
Embolization, Therapeutic , Iliac Aneurysm/therapy , Lidocaine , Postoperative Complications/therapy , Radiography, Interventional/methods , Aged, 80 and over , Anesthetics, Local , Aortic Aneurysm, Abdominal/therapy , Female , Follow-Up Studies , Humans , Iliac Aneurysm/diagnostic imaging , Iliac Artery/diagnostic imaging , Injections, Intramuscular , Male , Middle Aged , Pain/prevention & control , Postoperative Complications/diagnostic imaging , Retroperitoneal Space/diagnostic imaging , Tomography, X-Ray Computed , Treatment Outcome
15.
Ann Surg Treat Res ; 87(4): 197-202, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25317415

ABSTRACT

PURPOSE: We investigated whether suprarenal and infrarenal aortic angles change after the endovascular aneurysm repair (EVAR) procedure and during follow-up, and investigated the correlation between infrarenal aortic angle after EVAR and type Ia endoleaks. METHODS: Data collected on 70 EVAR procedures for a fusiform infrarenal aortic aneurysm performed between May 2006 and December 2012 were supplemented with a retrospective review of charts and radiographs. RESULTS: The greater the preoperative infrarenal aortic angle, the greater the suprarenal aortic angle (r = 0.72, P < 0.001). The infrarenal aortic angle decreased after the EVAR procedure and continued to decrease slowly thereafter (all P < 0.001). Suprarenal aortic angle decreased immediately after the EVAR procedure and continued to decrease during the first month (P < 0.001). No differences in angulation were observed based on stent graft type. Type Ia endoleaks occurred with significantly greater incidence in patients with a larger post EVAR infrarenal angle (P = 0.037). CONCLUSION: The infrarenal aortic angle decreased significantly immediately after the EVAR procedure and continued to decrease slowly thereafter. Suprarenal aortic angle decreased immediately after the EVAR procedure and continued to decrease during the first month. We found a correlation between infrarenal and suprarenal aortic angle. Type Ia endoleaks occurred with greater incidence in patients with a larger infrarenal angle immediately after EVAR.

16.
J Korean Surg Soc ; 85(4): 161-8, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24106682

ABSTRACT

PURPOSE: This study investigated the Jurkat T cell line expresses cytotoxicity when treated with different concentrations of FK506, and analyzed the expression pattern of microRNA when stimulated by FK506 using the microRNAs microarray, as well as the expression pattern of a gene that is related to the differentiation, activation and proliferation of T cells after being affected by the change of microRNAs. METHODS: To investigate the effects of FK506 on microRNA expression, we purified total RNA of Jurkat cells treated with 20 µM FK506 for 72 hours and used to analyze microRNA profiling by using Agilent's chip. RESULTS: These results demonstrated that treatment with FK506 markedly induced the down-regulation of 20 microRNAs as well as the up-regulation of 20 microRNAs in a time-dependent manner. The genes that down-regulated by FK506 include let-7a(*), miR-20a(*), and miR-487a. Otherwise miR-202, miR-485-5p, and miR-518c(*) are gradually up-regulated in expression. Sanger Institute and DAVIDs bioinformatics indicated that microRNAs regulated the several transcriptomes including nuclear factor of activated T cell-related, T cell receptor/interleukin-2 signaling, and Ca(2+)-calmodulin-dependent phosphatase calcineurin pathways. CONCLUSION: As a result of treating FK506 to a Jurkat cell line and running the microRNA microarray, it was found that FK506 not only took part in the suppression of T cell proliferation/activation by inhibiting calcineurin in Jurkat apoptosis, but also affected the microRNAs that are involved in the regulation of various signal transduction pathways.

17.
J Korean Surg Soc ; 81(4): 235-41, 2011 Oct.
Article in English | MEDLINE | ID: mdl-22111078

ABSTRACT

PURPOSE: This study demonstrated that apoptosis induced by mycophenolic acid (MPA) is mediated by mitochondrial membrane potential transition (MPT) changes in Jurkat cells. METHODS: Cell viability and MPT changes were measured by flow cytometry. Western blotting was performed to evaluate the expression of Bcl-2 family proteins, Bid, truncated Bid (tBid), cytochrome c, voltage dependent anion channel (VDAC), poly ADP-ribose polymerase (PARP), and protein kinase C-δ (PKC-δ). The catalytic activity of caspase-9 and -3 was also measured. RESULTS: Cell viability was decreased in time- and dose-dependent manners. Bcl-2 protein expression was decreased, but Bax protein expression was identified. A decreased Bcl-X(L) /Bcl-X(S) ratio was also noted. The expression of tBid protein also increased in a time-dependent manner in Jurkat cells treated with MPA. While normal MPT appeared as orange fluorescence, abnormal MPT corresponded to green fluorescence. Green fluorescence increased as orange decreased in the MPA-treated cells. Significantly increased concentrations of MPA induced the release of cytosolic cytochrome c. MPA also augmented the catalytic activity of caspase-9 and caspase-3 in Jurkat cells. Our findings demonstrated that MPA-induced apoptosis is mediated by MPT changes accompanied by decreased Bcl-XL expression and the appearance of tBid protein. The release of cytosolic cytochrome c from mitochondria and increased catalytic activity of caspase-9 and caspase-3 were observed in MPA-treated Jurkat cells. CONCLUSION: These results suggest that mitochondrial dysfunction caused by MPA induces human T lymphocyte apoptosis.

18.
J Neurosci ; 30(11): 3933-46, 2010 Mar 17.
Article in English | MEDLINE | ID: mdl-20237264

ABSTRACT

In our previous study, we clearly demonstrated the roles of pro-inflammatory cytokines, including tumor necrosis factor-alpha, interleukin-1beta (IL-1beta), and IL-6, and subsequent reactive oxygen species (ROS) generation on the pathogenesis of cisplatin ototoxicity in vitro and in vivo. ROS generation in cisplatin-treated HEI-OC1 auditory cells was also correlated with changing mitochondrial membrane potential. However, the roles of NADPH oxidase in cisplatin-induced ROS generation and ototoxicity have not been fully elucidated. Herein, immunohistochemical studies demonstrated that treatment of cisplatin induced the expression of NADPH oxidase isoforms NOX-1 and NOX-4 in HEI-OC1 auditory cells. Expression of mRNA for NOX-1, NOX-4, NOXO1, NOXA1, p47(phox), and p67(phox) was also increased. Inhibition of NADPH oxidase with diphenyleniodonium chloride or apocynin abolished ROS production and the subsequent apoptotic cell death in cisplatin-treated cells. Furthermore, suppression of NOX1 and NOX4 expression by small interfering RNA transfection markedly abolished the cytotoxicity and ROS generation by cisplatin. Together, our data suggest that ROS generated, in part, through the activation of NADPH oxidase plays an essential role in cisplatin ototoxicity.


Subject(s)
Cisplatin/toxicity , Hair Cells, Auditory, Outer/drug effects , Hair Cells, Auditory, Outer/enzymology , NADPH Oxidases/physiology , Oxidative Stress/physiology , Reactive Oxygen Species/metabolism , Animals , Apoptosis/drug effects , Apoptosis/physiology , Cell Line, Transformed , Cisplatin/administration & dosage , Cisplatin/antagonists & inhibitors , Hearing Loss/chemically induced , Hearing Loss/metabolism , Injections, Intraperitoneal , Male , Mice , Mice, Inbred BALB C , Organ Culture Techniques , Oxidative Stress/drug effects , Random Allocation , Rats , Rats, Sprague-Dawley , Reactive Oxygen Species/antagonists & inhibitors
19.
Hear Res ; 251(1-2): 70-82, 2009 May.
Article in English | MEDLINE | ID: mdl-19286452

ABSTRACT

Ebselen, an organoselenium compound that acts as a glutathione peroxidase mimetic, has been demonstrated to possess antioxidant and anti-inflammatory activities. However, the molecular mechanism underlying this effect is not fully understood in auditory cells. The purpose of the present study is to investigate the protective effect of ebselen against cisplatin-induced toxicity in HEI-OC1 auditory cells, organotypic cultures of cochlear explants from two-day postnatal rats (P(2)) and adult Balb/C mice. Pretreatment with ebselen ameliorated apoptotic death induced by cisplatin in HEI-OC1 cells and organotypic cultures of Corti's organ. Ebselen pretreatment also significantly suppressed cisplatin-induced increases in intracellular reactive oxygen species (ROS), intracellular reactive nitrogen species (RNS) and lipid peroxidation levels. Ebselen dose-dependently increased the expression level of an antioxidant response element (ARE)-luciferase reporter in HEI-OC1 cells through the translocation of Nrf2 into the nucleus. Furthermore, we found that pretreatment with ebselen significantly restored Nrf2 function, whereas it ameliorated the cytotoxicity of cisplatin in cells transfectants with either a pcDNA3.1 (control) or a DN-Nrf2 (dominant-negative) plasmid. We also observed that Nrf2 activation by ebselen increased the expression of phase II antioxidant genes, including heme oxygenase (HO-1), NAD(P)H:quinine oxidoreductase, and gamma-glutamylcysteine synthetase (gamma-GCS). Treatment with ebselen resulted in an increased expression of HO-1 and intranuclear Nrf2 in hair cells of organotypic cultured cochlea. After intraperitoneal injection with cisplatin, auditory brainstem responses (ABRs) threshold was measured on 8th day in Balb/C mice. ABR threshold shift was marked occurred in mice injected with cisplatin (16 mg/kg, n=5; Click and 8-kHz stimuli, p<0.05; 4, 16 and 32 kHz, p<0.01), whereas that of animal group which was treated with cisplatin and ebselen was not significantly changed. These results suggest that ebselen activates the Nrf2-ARE signaling pathway, which ultimately prevents free radical stresses from cisplatin and further contributes to protect auditory sensory hair cells from free radicals produced by cisplatin.


Subject(s)
Azoles/pharmacology , NF-E2-Related Factor 2/metabolism , Neuroprotective Agents/pharmacology , Organ of Corti/drug effects , Organ of Corti/metabolism , Organoselenium Compounds/pharmacology , Animals , Antineoplastic Agents/toxicity , Apoptosis/drug effects , Cell Line, Transformed , Cisplatin/toxicity , Evoked Potentials, Auditory, Brain Stem/drug effects , Gene Expression/drug effects , Genes, Reporter , Isoindoles , Lipid Peroxidation/drug effects , Luciferases/genetics , Mice , Mice, Inbred BALB C , NF-E2-Related Factor 2/genetics , Organ Culture Techniques , Organ of Corti/cytology , Phenols/metabolism , Plant Extracts/genetics , Plant Extracts/metabolism , Reactive Oxygen Species/metabolism , Transfection
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