Laparoscopic iliopubic tract repair for asymptomatic contralateral occult inguinal hernia.

PURPOSE: Metachronous contralateral inguinal hernia (MCIH) may occur after unilateral inguinal hernia (IH) repair, potentially as a result of occult IH (OIH). Contralateral OIH can be checked for during laparoscopic transabdominal hernioplasty for the treatment of unilateral IH. This study aims to assess the efficacy of laparoscopic iliopubic tract repair (IPTR) in treating contralateral OIH to reduce MCIH. METHODS: The medical charts of 3165 patients aged > 18 years who underwent laparoscopic transabdominal hernioplasty for unilateral IH from January 2013 to December 2021 were retrospectively reviewed. The patients were categorized into two groups based on contralateral OIH presence: negative OIH (nOIH, 2657 patients) and OIH (508 patients). In cases of OIH, IPTR was performed, involving suturing of the iliopubic tract and transversalis fascia arch. RESULTS: MCIH was indirect in 26 and direct in 4 patients in the nOIH group, and was direct in 3 patients in the OIH group. The incidence of indirect MCIH was higher in the nOIH group than in the OIH (1.0% [n = 26/2657] vs. 0.0% [n = 0/508], p = 0.048). There was no difference in postoperative complication rates, pain scores, return to daily life, or duration of hospitalization between the nOIH and OIH groups. CONCLUSION: Laparoscopic IPTR for OIH treatment is an effective method for reducing the risk of indirect MCIH.

Laparoscopic reoperation for pediatric recurrent inguinal hernia after previous laparoscopic repair.

PURPOSE: Recurrence is a concerning area in pediatric inguinal hernia repair. Various laparoscopic repair methods are available to treat recurrent pediatric inguinal hernia. We analyzed previous laparoscopic hernia repairs and report the outcomes of laparoscopic inguinal hernia reoperations in patients with recurrent inguinal hernia. METHODS: Fifty-one patients who presented for recurrent inguinal hernia after laparoscopic hernia repair from September 2012 to May 2017 were retrospectively evaluated. Previous laparoscopic procedures were analyzed with respect to sac removal (removal vs. leaving in place), suture material (absorbable vs. nonabsorbable), and high ligation method (purse string vs. multiple stitches). We removed the hernia sac from all patients and performed suture repair of the muscular arch of the internal inguinal ring using nonabsorbable material. RESULTS: All patients (38 male, 13 female) had indirect inguinal hernias. No conversion to open surgery occurred. Forty-three (84.3%) patients developed recurrence within 1 year after the previous operation [mean 8.7 ± 6.9 (range 3-33) months]. Twenty patients had concurrent hydroceles (39.2%); 16 were cord hydroceles and 4 were canal of Nuck hydroceles. In the previous operations, the hernia sac was not removed in 100% (51/51) of patients, absorbable suture material was used in 58.8% (30/51), and purse string high ligation was performed in 88.2% (45/51). No re-recurrence developed during a mean follow-up of 25.0 ± 12.6 (range 13-54) months. CONCLUSION: Laparoscopic reoperation with hernia sac removal and suture repair of the muscular arch of the internal inguinal ring with nonabsorbable material is an effective operation with few recurrences and complications.

Impact of operative time on early joint infection and deep vein thrombosis in primary total hip arthroplasty.

PURPOSE: Infections and deep vein thrombosis (DVT) after total hip arthroplasty (THA) are challenging problems for both the patient and surgeon. Previous studies have identified numerous risk factors for infections and DVT after THA but have often been limited by sample size. We aimed to evaluate the effect of operative time on early postoperative infection as well as DVT rates following THA. We hypothesized that an increase in operative time would result in increased odds of acquiring an infection as well as a DVT. METHODS: We conducted a retrospective analysis of prospectively collected data using the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database from 2006 to 2015 for all patients undergoing primary THA. Associations between operative time and infection or DVT were evaluated with multivariable logistic regressions controlling for demographics and several known risks factors for infection. Three different types of infections were evaluated: (1) superficial surgical site infection (SSI), an infection involving the skin or subcutaneous tissue, (2) deep SSI, an infection involving the muscle or fascial layers beneath the subcutaneous tissue, and (3) organ/space infection, an infection involving any part of the anatomy manipulated during surgery other than the incisional components. RESULTS: In total, 103,044 patients who underwent THA were included in our study. Our results suggested a significant association between superficial SSIs and operative time. Specifically, the adjusted odds of suffering a superficial SSI increased by 6% (CI=1.04-1.08, p<0.0001) for every 10-minute increase of operative time. When using dichotomized operative time (<90minutes or >90minutes), the adjusted odds of suffering a superficial SSI was 56% higher for patients with prolonged operative time (CI=1.05-2.32, p=0.0277). The adjusted odds of suffering a deep SSI increased by 7% for every 10-minute increase in operative time (CI=1.01-1.14, p=0.0335). No significant associations were detected between organ/space infection, wound dehiscence, or DVT and operative time either as continuous or as dichotomized. CONCLUSION: Prolonged operative times (>90min) are associated with increased rates of superficial SSIs, but not deep SSIs, organ/space infections, wound dehiscence, or DVT. LEVEL OF EVIDENCE: III.

Benefits of laparoscopic posterior wall suture repair in treating adolescent indirect inguinal hernias.

PURPOSE: Adolescent inguinal hernias are treated using high ligation or posterior wall suture repair with laparoscopic mesh implantation. This study aimed to evaluate the efficacy of laparoscopic intracorporeal posterior wall suture repair without mesh implantation for treating adolescent indirect inguinal hernias. METHODS: Laparoscopic herniorrhaphy was performed between September 2012 and April 2015 in 244 patients aged 11-18 years who were diagnosed with indirect inguinal hernias at Damsoyu Hospital, Seoul, Korea. The patients were stratified by surgical procedure into the high-ligation (115 patients) and wall suture (129 patients) groups. RESULTS: Four (3.5%) of the 115 patients in the high-ligation group experienced recurrence, but those in the wall suture group did not. The difference in recurrence rates between these groups was significant (p < 0.001). The wall suture procedures were longer (mean 28.2 min) than the high-ligation procedures (mean 17.4 min) (p < 0.001). The lengths of postoperative hospital stays were similar in both groups. Few complications were observed: one patient developed hematoma and one developed seroma in the high-ligation group; two patients developed inguinal hematomas and one developed seroma in the wall suture group. Visual analog scale scores at 1 week after surgery and the mean times to return to normal activities were similar in both groups. No chronic inguinodynia after the operation in either group was observed. CONCLUSIONS: Laparoscopic intracorporeal posterior wall suture repair without mesh implantation was effective for treating adolescent indirect inguinal hernias and resulted in fewer recurrences than those with high ligation.

Efficacy of laparoscopic herniorrhaphy for treating incarcerated pediatric inguinal hernia.

PURPOSE: Inguinal hernia repair is one of the most common elective surgeries. Most patients present with reducible inguinal bulging; however, in cases of incarcerated inguinal hernia (IIH), an emergency surgery is required. Here, we report the surgical outcomes of a laparoscopic approach for IIH. METHODS: Laparoscopic herniorrhaphy was performed in 4782 pediatric patients from September 2012 to December 2016 at Damsoyu Hospital, Seoul, Korea. Among them, the surgical outcomes of 164 IIH patients were retrospectively analyzed. RESULTS: Incarcerated organs comprised 51 ovaries, 103 intestines, and 10 omentums. The ovary (51/66) and intestine (88/98) were the most common incarcerated organs in females and males, respectively. The intestines, ovaries, and omentums were preserved in most cases. An oophorectomy was performed in one female patient with an unrecovered ischemic ovary, and an orchiectomy was performed in a male patient with ischemic testis because of cord vessel compression caused by intestine incarceration. In male pediatric patients, an age of <12 months and symptom duration of >1 week were risk factors for IIH, whereas in female pediatric patients, an age of <12 months and symptom duration of ≤1 week were risk factors for IIH. CONCLUSIONS: The intestines and ovaries were the most commonly herniated organs in male and female pediatric patients, respectively. Intracorporeal organ reduction was easily performed with a laparoscopic instrument.

Sequential chemotherapy/radiotherapy was comparable with concurrent chemoradiotherapy for stage I/II NK/T-cell lymphoma.

Background: In stage I/II natural killer (NK)/T-cell lymphoma, concurrent chemoradiotherapy (CCRT) had previously been shown to result in superior outcome compared with anthracycline-containing regimens, which have since been considered ineffective. The role of CCRT in comparison with approaches employing nonanthracycline-containing chemotherapy (CT) and sequential radiotherapy (RT) in such patients remains to be defined. Patients and methods: Three hundred and three untreated patients (207 men, 96 women; median age: 51, 18-86 years) with stage I/II NK/T-cell lymphoma who had received nonanthracycline-containing regimens were collected from an international consortium and retrospectively analyzed. Treatment included single modality (CT and RT), sequential modalities (CT + RT; RT + CT) and concurrent modalities (CCRT; CCRT + CT). The impact of clinicopathologic parameters and types of treatment on complete response (CR) rate, progression-free-survival (PFS) and overall-survival (OS) was evaluated. Results: For CR, stage (P = 0.027), prognostic index for NK/T-cell lymphoma (PINK) (P = 0.026) and types of initial treatment (P = 0.011) were significant prognostic factors on multivariate analysis. On Cox regression analysis, ECOG performance score (P = 0.021) and PINK-EBV DNA (PINK-E) (P = 0.002) significantly impacted on PFS; whereas ECOG performance score (P = 0.008) and stage (P < 0.001) significantly impacted on OS. For comparing CCRT ± CT and sequential CT + RT, CCRT ± CT patients (n = 190) were similar to sequential CT + RT patients (n = 54) in all evaluated clinicopathologic parameters except two significantly superior features (higher proportion of undetectable circulating EBV DNA on diagnosis and lower PINK-E scores). Despite more favorable pre-treatment characteristics, CCRT ± CT patients had CR rate, PFS and OS comparable with sequential CT + RT patients on multivariate and Cox regression analyses. Conclusions: In stage I/II NK/T-cell lymphomas, when effective chemotherapeutic regimens were used, CCRT and sequential CT + RT gave similar outcome.

The efficacy of laparoscopic intracorporeal linear suture technique as a strategy for reducing recurrences in pediatric inguinal hernia.

PURPOSE: Pediatric laparoscopic herniorrhaphy has rare complications, but recurrence might occur. The purpose of this manuscript is to evaluate the efficacy of linear suture technique of laparoscopic pediatric herniorrhaphy in reducing recurrences. METHODS: Laparoscopic surgery was performed on 2223 pediatric patients (under 10 years old) from September 2012 to December 2014 in Damsoyu Hospital, Seoul, Republic of Korea. The causes of recurrence were investigated case by case. The patients were categorized into two groups according to the suture method used in closing the hernia orifice: Group 1 (purse-string suture, 1009 patients) and Group 2 (linear suture, 1214 patients). RESULTS: There were 1413 (63.6%) male and 810 (36.4%) female patients. Mean age was 30.5 ± 29.2 months. A significantly higher proportion of male patients, contralateral patent processus vaginalis, and less proportion of recurrence were observed in Group 2. There were ten cases of recurrence in Group 1 because the internal ring suture could not endure the tension. One recurrence occurred in Group 2. The suture technique and age were found to be a significant risk factor for recurrence. Linear suture technique had a lower recurrence rate (odds ratio = 0.07, with 95% confidence interval 0.01-0.53, and p = 0.004). CONCLUSIONS: Purse-string suture technique causes significantly higher occurrence of hernia recurrences than linear suture technique. Linear suture technique can reduce recurrence by increasing the endurance to tension around the internal ring by distributing pressure to a wider area along the linear suture line. Linear suture technique can effectively reduce recurrence in pediatric inguinal herniorrhaphy.

Robotic-assisted single incision myomectomy in large myoma cases.

INTRODUCTION: Laparo-endoscopic single-incision surgery (LESS) has been developed and gradually adopted for both benign and malignant gynecological procedures. However, LESS has been hindered for use in procedures like myomectomy by limitations in natural architecture and instrumentation, especially in suturing. The da Vinci system features a single-site platform and wristed needle driver, which may help overcome conventional LESS limitations. This case report study describes the feasibility of this robotic single-site (RSS) platform in large myoma cases and offers suggestions. RESULTS: Two cases of myomectomy with large myomas (with maximum diameters of 160 and 120 mm) with different locations, were addressed by RSS. Operative time was 180 and 240 minutes. Estimated blood loss was 200 and 150 ml. Pathologic analysis revealed uterine leiomyomas of 910 and 870 grams. No serious peri- or post-operative complications occurred. DISCUSSION: Myomectomy with large myoma has presented a surgical challenge. RSS myomectomy appears to be a safe and feasible technique for it regardless of its localization. Advantages include less postoperative pain, fast recovery, less impact on quality of life, and improved cosmesis. LESS surgery has been challenging concerning suturing and multi-laparoscopic or multi-port robotic myomectomy can be difficult to extract myoma, especially with morcellation. RSS could be a solution that enables ease of manipflation and extraction.

Spontaneous resolution of post-transplant localized cytomegalovirus lymphadenitis mimicking tumor recurrence.

Compromised T-cell immunity persists for up to 1 year after autologous stem cell transplantation (ASCT), and patients treated with ASCT are more likely to develop atypical lymphoid hyperplasia that mimics tumor recurrence. Here, we present a case of cervical lymphadenitis due to cytomegalovirus (CMV) reactivation in a patient who had undergone ASCT for Burkitt lymphoma, which mimicked tumor recurrence on computed tomography and positron emission tomography-computed tomography 6 months after ASCT. This lesion was confined to the regional lymph nodes and was not accompanied by signs of systemic involvement, such as fever, splenomegaly, an elevated C-reactive protein level, or viremia. The localized CMV lymphadenitis resolved spontaneously without treatment after 6 months (12 months after ASCT) and the elevated CMV immunoglobulin-M titer normalized 6 months after resolution. Our experience with this case suggests that cautious follow-up without anti-CMV treatment should be considered in cases of post-ASCT localized CMV lymphadenitis without systemic involvement in patients with complete engraftment.

Mitochondrial modulation decreases the bortezomib-resistance in multiple myeloma cells.

Multiple myeloma (MM) is an incurable hematological malignancy that causes most patients to eventually relapse and die from their disease. The 20S proteasome inhibitor bortezomib has emerged as an effective drug for MM treatment; however, intrinsic and acquired resistance to bortezomib has already been observed in MM patients. We evaluated the involvement of mitochondria in resistance to bortezomib-induced cell death in two different MM cell lines (bortezomib-resistant KMS20 cells and bortezomib-sensitive KMS28BM cells). Indices of mitochondrial function, including membrane potential, oxygen consumption rate and adenosine-5'-triphosphate and mitochondrial Ca(2+) concentrations, were positively correlated with drug resistance of KMS cell lines. Mitochondrial genes including CYPD, SOD2 and MCU were differentially expressed in KMS cells. Thus, changes in the expression of these genes lead to changes in mitochondrial activity and in bortezomib susceptibility or resistance, and their combined effect contributes to differential sensitivity or resistance of MM cells to bortezomib. In support of this finding, coadministration of bortezomib and 2-methoxyestradiol, a SOD inhibitor, rendered KMS20 cells sensitive to apoptosis. Our results provide new insight into therapeutic modalities for MM patients. Studying mitochondrial activity and specific mitochondrial gene expression in fresh MM specimens might help predict resistance to proapoptotic chemotherapies and inform clinical decision-making.

A comparison of intra-operative blood loss and acid-base balance between vasopressor and inotrope strategy during living donor liver transplantation: a randomised, controlled study.

Administration of vasopressors or inotropes during liver transplant surgery is almost universal, as this procedure is often accompanied by massive haemorrhage, acid-base imbalance, and cardiovascular instability. However, the actual agents that should be used and the choice between a vasopressor and an inotrope strategy are not clear from existing published evidence. In this prospective, randomised, controlled and single-blinded study, we compared the effects of a vasopressor strategy on intra-operative blood loss and acid-base status with those of an inotrope strategy during living donor liver transplantation. Seventy-six adult liver recipients with decompensated cirrhosis were randomly assigned to receive a continuous infusion of either phenylephrine at a dose of 0.3-0.4 µg.kg(-1).min(-1) or dopamine and/or dobutamine at 2-8 µg.kg(-1).min(-1) during surgery. Vascular resistance was higher over time in the phenylephrine group than in the dopamine/dobutamine group. Estimated blood loss was significantly lower in the phenylephrine group than in the dopamine/dobutamine group (mean (SD) 4.5 (1.8) l vs 6.1 (3.4) l, respectively, p=0.011). Patients in the phenylephrine group had lower lactate levels in the late pre-anhepatic and the early anhepatic phase and needed less bicarbonate administration than those in the dopamine/dobutamine group (median (IQR [range]) 40 (0-100 [0-160]) mEq vs 70 (40-163 [0-260]) mEq, respectively, p=0.018). Postoperative clinical outcomes and laboratory-measured hepatic and renal function did not differ between the groups. Increased vascular resistance and reduction of portal blood flow by intra-operative phenylephrine infusion is assumed to decrease the amount of intra-operative bleeding and thereby ameliorate the progression of lactic acidosis during liver transplant surgery.

Ependymal cyst in the cerebrum of an African green monkey (Chlorocebus aethiops).

A focal lesion was detected by magnetic resonance imaging in the right caudal occipital lobe of the cerebrum in an African green monkey (Chlorocebus aethiops). Neurological signs were not observed in this animal. At necropsy examination, an 8mm wedge-shaped intracranial cavity was found, which apparently did not communicate with the ventricles. Microscopically, the inner surface of the cavity was lined by ciliated cuboidal epithelium with positive immunoreactivity for S100 protein, glial fibrillary acidic protein and cytokeratin. Based on the gross, microscopical and immunohistochemical findings the lesion was classified as an ependymal cyst. To the best of our knowledge, this is the first report of an ependymal cyst in an African green monkey.

Use of laryngeal mask airway and its removal in a deeply anaesthetized state reduces emergence agitation after sevoflurane anaesthesia in children.

This study investigated the effect of laryngeal mask airway (LMA) and removal while in a deeply anaesthetized state (deep removal) compared with endotracheal tube and extubation when awake or deeply anaesthetized on the incidence of emergence agitation in children after sevoflurane anaesthesia for subumbilical surgery. Patients (2 - 7 years) were randomly assigned to one of three groups: ET-A group (n = 56, endotracheal tube and extubation whilst awake); ET-D group (n = 56, endotracheal tube and deep extu bation); LMA-D group (n = 56, experienced LMA and deep removal). The incidence of postoperative emergence agitation was significantly lower in the LMA-D patients compared with patients in the ET-A group (21.4% and 41.1%, respectively). Patients in the LMA-D group required a significantly shorter stay in the postanaesthetic care unit (PACU) than ET-A patients. There were no significant differences in the incidence of postoperative emergence agitation or length of stay in the PACU between the ET-A and ET-D groups, or between the ET-D and LMA-D groups. In conclusion, using an LMA and deep removal decreased postoperative emergence agitation compared with using an endotracheal tube and awake extubation after paediatric sevoflurane anaesthesia.

Evaluation of a rapid, point-of-care test device for the diagnosis of hepatitis C infection.

BACKGROUND: Despite considerable evolution in the quality of laboratory-based testing for detection of HCV, the availability of rapid, point-of-care tests may increase diagnoses by increasing opportunities for testing outside of traditional laboratory settings. OBJECTIVES: We evaluated the performance of a new, rapid HCV test that can be used with venous blood, finger stick blood, serum, plasma, or oral fluid and compared it to FDA-approved laboratory methods. STUDY DESIGN: HCV positive subjects as well as subjects at low risk for HCV were tested with the rapid test using all 5 specimen types and results compared to FDA-approved laboratory methods. In addition, performance was assessed in commercially available seroconversion panels. RESULTS: Sensitivity and specificity of the rapid test was equivalent to laboratory EIA and performance was comparable across all 5 specimen types. CONCLUSIONS: The OraQuick HCV Rapid Antibody Test appears suitable as an aid in the diagnosis of HCV infection.

Effects of Asparagus officinalis extracts on liver cell toxicity and ethanol metabolism.

Asparagus officinalis is a vegetable that is widely consumed worldwide and has also long been used as a herbal medicine for the treatment of several diseases. Although A. officinalis is generally regarded as a supplement for the alleviation of alcohol hangover, little is known about its effects on cell metabolism. Therefore, this study was conducted to analyze the constituents of the young shoots and the leaves of asparagus and to compare their biochemical properties. The amino acid and inorganic mineral contents were found to be much higher in the leaves than the shoots. In addition, treatment of HepG2 human hepatoma cells with the leaf extract suppressed more than 70% of the intensity of hydrogen peroxide (1 mM)-stimulated DCF fluorescence, a marker of reactive oxygen species (ROS). Cellular toxicities induced by treatment with hydrogen peroxide, ethanol, or tetrachloride carbon (CCl(4)) were also significantly alleviated in response to treatment with the extracts of A. officinalis leaves and shoots. Additionally, the activities of 2 key enzymes that metabolize ethanol, alcohol dehydrogenase and aldehyde dehydrogenase, were upregulated by more than 2-fold in response to treatment with the leaf- and shoot extracts. Taken together, these results provide biochemical evidence of the method by which A. officinalis exerts its biological functions, including the alleviation of alcohol hangover and the protection of liver cells against toxic insults. Moreover, the results of this study indicate that portions of asparagus that are typically discarded, such as the leaves, have therapeutic use.

Outcomes after combined laparoscopic gastrectomy and laparoscopic cholecystectomy in gastric cancer patients.

BACKGROUND/AIMS: The purpose of this study was to determine the effect of performing laparoscopic cholecystectomy on patients undergoing laparoscopic-assisted gastrectomy for gastric cancer. METHODS: This single center study involved a retrospective review of a database of 400 patients who underwent consecutive laparoscopic-assisted gastrectomy for early gastric cancer from June 2003 to July 2007. Outcomes in 26 patients who underwent both laparoscopic-assisted gastrectomy and laparoscopic cholecystectomy were compared with outcomes from 364 patients who underwent laparoscopic-assisted gastrectomy without laparoscopic cholecystectomy. RESULTS: There were no postoperative 30-day mortalities in the combined cholecystectomy group. The mean surgery duration, time to first flatus and postoperative hospital stay for the laparoscopic gastric resection without combined operation were 181.7 min, 2.7 days and 9.7 days, respectively, and 196.7 min, 2.6 days and 8.8 days, respectively, for the combined cholecystectomy group. None of the postoperative complications was related to combined cholecystectomy. CONCLUSION: Performing a combined cholecystectomy prolonged the mean surgery duration by approximately 15 min, but had no effect on surgical outcomes. It appears that performing a cholecystectomy at the same time as laparoscopic gastric resection is safe and feasible in patients with both early gastric cancer and gallbladder disease.

Concurrent chemoradiotherapy with S-1 and cisplatin in advanced esophageal cancer.

How best to manage advanced esophageal cancer remains unresolved, especially in palliative care. Here, in a pilot study, we evaluated the efficacy and safety of concurrent chemoradiotherapy with S-1 and cisplatin in advanced esophageal cancer. Patients with locally advanced or metastatic squamous cell carcinoma of the esophagus received S-1 and cisplatin at doses of 70 mg/m(2)/day for 14 days and 70 mg/m(2) on day 1, respectively, every 3 weeks. Concurrently, radiotherapy was started at a dose of 200 cGy/day, up to a total of 5400 cGy. After concurrent chemoradiotherapy, additive chemotherapy was repeated up to six cycles. Thirty patients were enrolled in this study; of the 27 in whom efficacy could be evaluated, an objective response rate was seen in 20 (74.1%), including five (18.5%) complete pathologic responses in primary lesions. Improvement of dysphagia was seen in 21 (76%) patients. In patients with stage II or III esophageal cancer, the median progression-free survival and overall survival were 10.6 +/- 0.6 months (95% CI: 9.4-11.8) and 23.0 +/- 5.1 months (95% CI: 13.0-32.9), respectively. In patients with stage IV esophageal cancer, the median progression-free survival and overall survival were 5.4 +/- 1.6 months (95% CI: 2.2-8.6) and 11.6 +/- 1.6 months (95% CI: 8.4-14.8), respectively. The main hematological toxicity was neutropenia, but no neutropenic fever was observed. The major non-hematological toxicities were asthenia and vomiting, mostly of grades 1 and 2. Thus, concurrent chemoradiotherapy with S-1 and cisplatin may be a promising nonsurgical treatment in advanced esophageal cancer.

TRAF6 deficiency promotes TNF-induced cell death through inactivation of GSK3beta.

TNF receptor-associated factor 6 (TRAF6) plays a key role in the regulation of innate immune responses by mediating signals from both TNF receptors (TNFRs) and interleukin-1 receptors (IL-1Rs)/Toll-like receptors (TLRs). Here, we define a new role for TRAF6 in antagonizing cell death during TNF signaling. In TRAF6-deficient 3T3 (T6(-/-) 3T3) cells, TNF stimulation leads to the accumulation of reactive oxygen species (ROS), which in turn results in prolonged c-Jun N-terminal kinase (JNK) activation and accelerated cell death. Furthermore, TNF-induced p65/RelA phosphorylation as well as transcriptional activity of nuclear factor-kappaB (NF-kappaB) was significantly downregulated in T6(-/-) 3T3 cells. Interestingly, TRAF6 deficiency leads to constitutive phosphorylation and inactivation of glycogen synthase kinase 3beta (GSK3beta). Restoration of GSK3beta activity through exogenous expression of a GSK3beta constitutive active form rescued cell death in TRAF6-null 3T3 cells. These data suggest a role for TRAF6 in the maintenance of cell survival by regulating GSK3beta activity in TNF signaling.

Polyphenol (-)-epigallocatechin gallate protection from ischemia/reperfusion-induced renal injury in normotensive and hypertensive rats.

INTRODUCTION: The effect of epigallocatechin gallate (EGCG) in an in vivo renal model of ischemia with reperfusion (I/R) was compared between normotensive (WKR) and hypertensive (SHR) rats. METHODS: WKR (groups I, II, III) and SHR groups (groups IV, V, VI) were divided into three types. Groups I and IV were sham-operated animals; groups II and V were subjected to 45 minutes of renal I/R; and groups III and VI received 10 mg/kg EGCG intravenously at the time of reperfusion. Three days after renal I/R, we compared renal function markers, malondialdehyde (MDA), and histologic changes. RESULTS: Following renal I/R, levels of blood urea nitrogen (BUN) and serum creatinine (sCr) were increased and serum creatinine clearance (CrCl) decreased in group V compared to group II (P < .001). Those receiving EGCG treatment (groups III and VI) had decreased BUN and sCr compared to non-EGCG I/R groups (P < .001), but not surprisingly, higher than sham groups. CrCl was lowest in the SHR groups. The MDA was significantly decreased after EGCG treatment (P = .028 in group III, P = .002 in group VI). Following renal I/R, tissue necrosis was more severe among SHR (P < .001). However, the ratio of regeneration to damage significantly increased in SHR after EGCG treatment. CONCLUSIONS: The reperfusion injury was greater among SHR compared with WKR in terms of renal function, lipid peroxidation, and tissue damage. EGCG treatment significantly ameliorated renal impairment and promoted tissue regeneration following renal I/R.