Lactobacillus fermentum attenuates the alveolar bone loss in ligature-induced periodontitis in mice.

OBJECTIVE: This study investigated the effects of Lactobacillus fermentum BELF11 on periodontitis in mice (LIP). METHODS: Sixty mice were randomly assigned to a control group (CTL), LIP/PBS group (LIP and PBS applied), or LIP/BELF11 group (LIP and L. fermentum BELF11 applied). For 14 days, PBS or L. fermentum BELF11 was applied twice daily to the mice in the LIP/PBS or LIP/BELF11 group, respectively. After 14 days, radiographic, histological, and pro-inflammatory cytokine assessments were conducted. RESULTS: The LIP/PBS and LIP/BELF11 groups demonstrated greater alveolar bone loss than the CTL group (p < 0.05). The LIP/BELF11 group showed significantly reduced alveolar bone loss on the mesial side compared to the LIP/PBS group. Histologically, the LIP/BELF11 group showed consistent patterns of connective tissue fiber arrangement, lower levels of inflammatory infiltration, less alveolar bone loss, and higher alveolar bone density than the LIP/PBS group, despite showing more signs of destruction than the CTL group. The LIP/BELF11 group also exhibited significantly lower levels of pro-inflammatory cytokines than the LIP/PBS group. CONCLUSIONS: L. fermentum BELF11 inhibits alveolar bone loss and periodontitis progression by regulating pro-inflammatory cytokine production. These findings suggest that L. fermentum BELF11 may be a potential adjunctive therapy in periodontal treatment.

Tat-CIAPIN1 Prevents Pancreatic ß-Cell Death in hIAPP-Induced RINm5F Cells and T2DM Animal Model.

It is well known that the cytokine-induced apoptosis inhibitor 1 (CIAPIN1) protein plays an important role in biological progresses as an anti-apoptotic protein. Human islet amyloid peptide (hIAPP), known as amylin, is caused to pancreatic ß-cell death in type 2 diabetes mellitus (T2DM). However, the function of CIAPIN1 protein on T2DM is not yet well studied. Therefore, we investigated the effects of CIAPIN1 protein on a hIAPP-induced RINm5F cell and T2DM animal model induced by a high-fat diet (HFD) and streptozotocin (STZ). The Tat-CIAPIN1 protein reduced the activation of mitogen-activated protein kinase (MAPK) and regulated the apoptosis-related protein expression levels including COX-2, iNOS, Bcl-2, Bax, and Caspase-3 in hIAPP-induced RINm5F cells. In a T2DM mice model, the Tat-CIAPIN1 protein ameliorated the pathological changes of pancreatic ß-cells and reduced the fasting blood glucose, body weight and hemoglobin Alc (HbAlc) levels. In conclusion, the Tat-CIAPIN1 protein showed protective effects against T2DM by protection of ß-cells via inhibition of hIAPP toxicity and by regulation of a MAPK signal pathway, suggesting CIAPIN1 protein can be a therapeutic protein drug candidate by beneficial regulation of T2DM.

Neuroprotective Effects of Ethanol Extract of Polyscias fruticosa (EEPF) against Glutamate-Mediated Neuronal Toxicity in HT22 Cells.

In traditional herbal medicine, the Polyscias fruticosa has been frequently used for the treatment of ischemia and inflammation. Oxidative stress mediated by elevated glutamate levels cause neuronal cell death in ischemia and various neurodegenerative diseases. However, so far, the neuroprotective effects of this plant extract against glutamate-mediated cell death have not been investigated in cell models. The current study investigates the neuroprotective effects of ethanol extracts of Polyscias fruticosa (EEPF) and elucidates the underlying molecular mechanisms of EEPFs relevant to neuroprotection against glutamate-mediated cell death. The oxidative stress-mediated cell death was induced by 5 mM glutamate treatment in HT22 cells. The cell viability was measured by a tetrazolium-based EZ-Cytox reagent and Calcein-AM fluorescent dye. Intracellular Ca2+ and ROS levels were measured by fluorescent dyes, fluo-3 AM and 2',7'-dichlorodihydrofluorescein diacetate (DCF-DA), respectively. Protein expressions of p-AKT, BDNF, p-CREB, Bax, Bcl-2, and apoptosis-inducing factor (AIF) were determined by western blot analysis. The apoptotic cell death was measured by flow cytometry. The in vivo efficacy of EEPF was evaluated using the Mongolian gerbil mouse by surgery-induced brain ischemia. EEPF treatment showed a neuroprotective effect against glutamate-induced cell death. The EEPF co-treatment reduced the intracellular Ca2+ and ROS and apoptotic cell death. Furthermore, it recovered the p-AKT, p-CREB, BDNF, and Bcl-2 levels decreased by glutamate. The EEPF co-treatment suppressed the activation of apoptotic Bax, the nuclear translocation of AIF, and mitogen-activated protein kinase (MAPK) pathway proteins (ERK1/2, p38, JNK). Further, EEPF treatment significantly rescued the degenerative neurons in the ischemia-induced Mongolian gerbil in vivo model. EEPF exhibited neuroprotective properties that suppress glutamate-mediated neurotoxicity. The underlying mechanism of EEPF is increasing the level of p-AKT, p-CREB, BDNF, and Bcl-2 associated with cell survival. It has therapeutic potential for the treatment of glutamate-mediated neuropathology.

Validation of the prognostic performance in various nodal staging systems for gallbladder cancer: results of a multicenter study.

BACKGROUND: Although the current nodal staging system for gallbladder cancer (GBC) was changed based on the number of positive lymph nodes (PLN), it needs to be evaluated in various situations. METHODS: We reviewed the clinical data for 398 patients with resected GBC and compared nodal staging systems based on the number of PLNs, the positive/retrieved LN ratio (LNR), and the log odds of positive LN (LODDS). Prognostic performance was evaluated using the C-index. RESULTS: Subgroups were formed on the basis of an restricted cubic spline plot as follows: PLN 3 (PLN = 0, 1-2, ≥ 3); PLN 4 (PLN = 0, 1-3, ≥ 4); LNR (LNR = 0, 0-0.269, ≥ 0.27); and LODDS (LODDS < - 0.8, - 0.8-0, ≥ 0). The oncological outcome differed significantly between subgroups in each system. In all patients with GBC, PLN 4 (C-index 0.730) and PLN 3 (C-index 0.734) were the best prognostic discriminators of survival and recurrence, respectively. However, for retrieved LN (RLN) ≥ 6, LODDS was the best discriminator for survival (C-index 0.852). CONCLUSION: The nodal staging system based on PLN was the optimal prognostic discriminator in patients with RLN < 6, whereas the LODDS system is adequate for RLN ≥ 6. The following nodal staging system considers applying different systems according to the RLN.

Protective role of hypoxia-inducible factor-1α-dependent CD39 and CD73 in fulminant acute liver failure.

Acute liver failure (ALF) is a severe life-threatening disease which usually arises in patients with-irreversible liver illnesses. Although human ectonucleotide triphosphate diphosphohydrolase-1, E-NTPDase1 (CD39) and ecto-5'-nucleotidase, Ecto5'NTase (CD73) are known to protect tissues from ALF, the expression and function of CD39 and CD73 during ALF are currently not fully investigated. We tested whether CD39 and CD73 are upregulated by hypoxia inducible factor (HIF)-1α, and improve ischemic tolerance to ALF. To test our hypothesis, liver biopsies were obtained and we found that CD39 and CD73 mRNA and proteins from human specimens were dramatically elevated in ALF. We investigated that induction of CD39 and CD73 in ALF-related with wild type mice. In contrast, deletion of cd39 and cd73 mice has severe ALF. In this study, we concluded that CD39 and CD73 are molecular targets for the development of drugs for ALF patients care.

Biliary stricture is the only concern in ABO-incompatible adult living donor liver transplantation in the rituximab era.

BACKGROUND & AIMS: With the introduction of rituximab prophylaxis, the survival of ABO-incompatible (ABOi) adult living donor liver transplant (ALDLT) has been strikingly improved due to the decreased incidence of antibody-mediated rejection. However, biliary stricture (BS) related to ABO incompatibility remains an unresolved concern. METHODS: Excluding 105 dual graft ALDLTs, 1102 ALDLT cases including 142 ABOi recipients were included in this study. The desensitization protocol for overcoming the ABO blood group barrier comprised pretransplant plasma exchange, and rituximab (300-375 mg/m(2) BSA). RESULTS: The mean follow-up period was 34.2 ± 15.4 months. The cumulative graft and patient survival rates were comparable in the two groups. The 1- and 3-year BS-free survival rates of ABOi ALDLT were 81.5 and 79.0%, respectively, lower than those of ABOc ALDLT (87.6 and 85.7%, respectively, p=0.022). In the risk factor analysis, diameter of graft bile duct opening <5mm, antecedent acute cellular rejection, and ABO incompatibility were independent risk factors for BS. Diffuse intrahepatic biliary stricture (DIHBS) exclusively occurred in 12 patients (8.5%) receiving ABOi ALDLT. The deaths of 3 patients and 4 cases of re-transplantation were related to DIHBS. Graft and patient survival rates were significantly reduced in ABOi ALDLT recipients with DIHBS. However, we failed to identify any significant risk factors for DIHBS. CONCLUSIONS: The incidence of BS in ABOi ALDLT is higher than in ABOc, mainly due to the fact of DIHBS which significantly affected survival outcomes. To predict and prevent DIHBS, we need further studies to identify significant risk factors.

Prevalence analysis of de novo hepatic steatosis following pylorus-preserving pancreaticoduodenectomy.

BACKGROUND: Prevalence of hepatic steatosis following pylorus-preserving pancreaticoduodenectomy (PPPD) is high. This study intended to reveal the prevalence and patterns of de novo hepatic steatosis following PPPD. METHODS: We investigated postoperative de novo hepatic steatosis following PPPD (n = 101) with a control group of bile duct resection (BDR) (n = 54). RESULTS: At postoperative 1 year, hepatic steatosis occurred in 21 of 82 patients (25.6%) of PPPD group and in 2 of 47 patients (4.3%) of BDR group (p = 0.001). Thereafter, at 2 to 5 years, a high prevalence of hepatic steatosis persisted in the PPPD group, but no further occurrence developed in BDR group. Once steatosis developed, it persisted until the end of the study period or patient death. Five-year cumulative incidence of hepatic steatosis was 26.7% in the PPPD group and 3.7% in BDR group (p < 0.001). Univariate analyses showed that patient sex, age, body mass index, blood lipid profile, recurrence of tumor, and diabetes did not have significant influence on the development of hepatic steatosis following PPPD. CONCLUSIONS: De novo hepatic steatosis may develop in a not negligible proportion of patients undergone PPPD. Multicenter studies with a high number of patients are needed to elucidate its pathogenesis and to find effective treatment for pancreaticoduodenectomy-associated hepatic steatosis.

Survival differences between Milan criteria after down-staging and De novo Milan in living donor liver transplantation for hepatocellular carcinoma.

BACKGROUND/AIMS: This study reports our experiences of adult living donor liver transplantation (LDLT) corresponding to downstaging. METHODOLOGY: Between July 1992 and April 2008, we performed 553 adult LDLTs (35.1%, 553/1575) for HCC. Sixty-five patients was not treated before LDLT and belonged to Milan criteria, classified as De novo Milan group (De novo-M); 22 HCC patients did not meet Milan criteria initially, but subsequently met the criteria after downstaging, classified as artificial Milan group (Artificial-M). The evaluation of downstaging was based on preoperative CT scan and explanted liver biopsy, and excluded the patients having unclear treatment history on analysis. RESULTS: Artificial-M showed significantly less Child C patients (25%) than De novo-M (64.5%) (0.037). Artificial-M had greater tumor burden than De novo-M in maximal tumor size (2.5 +/- 1.2 versus 2.2 +/- 0.95 cm), sum of tumor diameter (3.4 +/- 1.4 versus 2.4 +/- 1.0 cm), number of nodules (1.8 +/- 0.9 versus 1.2 +/- 0.5), respectively. Five-year cumulative survival was not different between Artificial-M and De novo-M (83.9% versus 93.9%), but 5-year disease free survival were significantly different (71.1% versus 96.5%) (p = 0.0016). CONCLUSIONS: Five year overall survival rates after LDLT were good in both groups. However, stricter follow-up is necessary in Artificial-M considering greater tumor burden and higher recurrence rate compared to De novo-M.

Temporal changes of periodontal tissue pathology in a periodontitis animal model.

PURPOSE: This study aimed to characterize the early stages of periodontal disease and determine the optimal period for its evaluation in a mouse model. The association between the duration of ligation and its effect on the dentogingival area in mice was evaluated using micro-computed tomography (CT) and histological analysis. METHODS: Ninety mice were allocated to an untreated control group or a ligation group in which periodontitis was induced by a 6-0 silk ligation around the left second maxillary molar. Mice were sacrificed at 1, 2, 3, 4, 5, 8, 11, and 14 days after ligature placement. Alveolar bone destruction was evaluated using micro-CT. Histological analysis was performed to assess the immune-inflammatory processes in the periodontal tissue. RESULTS: No significant difference in alveolar bone loss was found compared to the control group until day 3 after ligature placement, and a gradual increase in alveolar bone loss was observed from 4 to 8 days following ligature placement. No significant between-group differences were observed after 8 days. The histological analysis demonstrated that the inflammatory response was evident from day 4. CONCLUSIONS: Our findings in a mouse model provide experimental evidence that ligature-induced periodontitis models offer a consistent progression of disease with marginal attachment down-growth, inflammatory infiltration, and alveolar bone loss.

A Multicenter, Randomized, Open-Label Study to Compare the Efficacy and Safety of Tacrolimus and Corticosteroids in Combination With or Without Mycophenolate Mofetil in Liver Transplantation Recipients Infected With Hepatitis B Virus.

BACKGROUND: Mycophenolate mofetil exhibits pharmacologic mechanisms different from calcineurin inhibitors. Therefore, the dose of calcineurin inhibitors can be reduced along with side effects for effective immunosuppression. We aimed to evaluate the efficacy and safety of tacrolimus and corticosteroid in combination with or without mycophenolate mofetil in living donor liver transplantation (LDLT) recipients infected with hepatitis B virus (HBV). METHODS: A randomized, open-label, comparative, multicenter, phase IV study was conducted with 119 patients from January 2014 to September 2017. In the full analysis set population, 58 and 59 patients were included in the study group (triple-drug regimen: TacroBell + My-rept + corticosteroid) and the control group (dual-drug regimen: TacroBell + corticosteroid), respectively. In the per protocol set population, 49 and 42 patients were included in the study and control groups, respectively. RESULTS: In the full analysis set population, the incidence of biopsy-proven acute cellular rejection (rejection activity index score ≥4) was 3.4% in the study group; however, this finding was not observed in the control group (P = .468). Hepatitis B virus recurrence was observed in one patient in the control group. No cases of biopsy-proven acute cellular rejection and HBV recurrence were observed in the per protocol set population. The incidences of serious adverse events were 25.9% and 18.0% in the study and control groups, respectively; however, the difference between the groups was not statistically significant (P = .376). CONCLUSION: Although the study involved a small number of patients, the triple-drug regimen can be considered safe and effective for immunosuppression after living donor liver transplantation in patients infected with HBV.

Application time and persistence of transcranial direct current stimulation (tDCS) against neuronal death resulting from transient cerebral ischemia.

BACKGROUND: Transcranial direct current stimulation (tDCS) has been studied as a tool to stimulate the functional recovery of neurons after stroke. Although this device has recently begun to be utilized for providing neuroprotection in stroke, research on its application conditions is lacking. This study aimed to examine the effects of various tDCS application conditions on cerebral ischemia. Ischemia was induced for 5 min in a gerbil model. The application of tDCS comprised a 20 min stimulation-20 min rest-20 min stimulation protocol, which was implemented simultaneously with the induction of cerebral ischemia. Application time of the tDCS effect on ischemia was confirmed by sampling brain tissues after stimulation using 0.2 mA tDCS at 0, 5, 10 and 60 min after ischemia. RESULTS: Persistence of the tDCS effect on ischemia was confirmed by sampling brain tissues 5, 7, and 10 days post stimulation, with 0.2 mA tDCS after ischemia. Furthermore, the tissues were stained with cresyl violet and Fluoro-Jade C so as to determine the reduction in neuronal death under all application conditions. CONCLUSIONS: The application of tDCS can be used as a useful intervention for acute phase stroke due to its sustained neuroprotective effect.

The Effect of Botulinum Toxin on Hair Follicle Cell Regeneration Under Continuous Stress Conditions: a Pilot Animal Study.

We analyzed the effect of botulinum toxin (BTX) type A on the regeneration of hair follicle cells under continuous stress conditions. Thirty 6-week-old C57BL/6 mice were used, and hair loss was induced on their backs (10 control (CTL) mice, reared under normal conditions without stress; 10 mice, exposed to continuous stress (STRESS) by fixing in an enclosed space; 10 BTX + STRESS mice, injected subcutaneously with 1 IU of BTX (0.1 cc) where the hair follicles were removed under the same stress conditions). There was less hair growth in the STRESS and BTX + STRESS groups compared to that in the CTL group at 2 weeks. At 3 weeks, the telogen stage was mainly observed in the STRESS group whereas the anagen stage was observed in the CTL and BTX + STRESS groups. A substantial increase in terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells was observed in the STRESS group compared to that in the CTL and BTX + STRESS groups. Substance P (SP) immunoreactivity cell levels increased in the STRESS group at 2 and 3 weeks compared to those in the BTX + STRESS group. SP expression increased at 2 and 3 weeks in the STRESS group compared to that in the CTL and BTX + STRESS groups. A delay in the regeneration cycle of the hair follicle cells occurred when stress was applied, and an almost normal regeneration cycle occurred when BTX was injected subcutaneously. Therefore, BTX may be a positive indicator for hair loss treatment.

Effects of ibuprofen-loaded TiO2 nanotube dental implants in alloxan-induced diabetic rabbits.

PURPOSE: Some systemic conditions, especially diabetes mellitus (DM), adversely affect dental implant success. This study aimed to investigate the effects of ibuprofen-loaded TiO2 nanotube (ILTN) dental implants in alloxan-induced diabetic rabbits. METHODS: Twenty-six New Zealand white rabbits were treated with alloxan monohydrate to induce DM. At 2 weeks following DM induction, 3 types of implants (sandblasted, large-grit, and acid-etched [SLA], ILTN, and machined) were placed into the proximal tibia in the 10 rabbits that survived following DM induction. Each type of implant was fitted randomly in 1 of the holes (round-robin method). The animals were administered alizarin (at 3 weeks) and calcein (at 6 weeks) as fluorescent bone markers, and were sacrificed at 8 weeks for radiographic and histomorphometric analyses. RESULTS: TiO2 nanotube arrays of ~70 nm in diameter and ~17 µm in thickness were obtained, and ibuprofen was loaded into the TiO2 nanotube arrays. A total of 26 rabbits were treated with alloxan monohydrate and only 10 rabbits survived. The 10 surviving rabbits showed a blood glucose level of 300 mg/dL or higher, and the implants were placed in these diabetic rabbits. The implant stability quotient (ISQ) and bone-to-implant contact (BIC) values were significantly higher in the ILTN group (ISQ: 61.8, BIC: 41.3%) and SLA group (ISQ: 62.6, BIC: 46.3%) than in the machined group (ISQ: 53.4, BIC: 20.2%), but the difference in the BIC percentage between the SLA and ILTN groups was not statistically significant (P=0.628). However, the bone area percentage was significantly higher in the ILTN group (78.0%) than in the SLA group (52.1%; P=0.000). CONCLUSIONS: The ILTN dental implants showed better stability (ISQ) and BIC than the machined implants; however, these values were similar to the commercially used SLA implants in the 2-week diabetic rabbit model.

Effect of Weissella cibaria on the reduction of periodontal tissue destruction in mice.

BACKGROUND: Periodontitis is associated with dysbiosis of microbial flora in the oral cavity. We evaluated the effects of an oral care probiotic, Weissella cibaria CMU, on periodontal tissue destruction and regulation of inflammatory cytokines in mice with ligature-induced periodontitis (LIP). METHODS: Fourteen-day LIP model was used. Ninety animals were randomly divided into six groups: negative control (Ctrl), positive control (LIP/Ctrl), PBS-treated (LIP/PBS), W. cibaria-low (1 × 107 colony forming unit (CFU)/d; LIP/WC-L), W. cibaria-medium (1 × 108 CFU/d; LIP/WC-M), and W. cibaria-high (1 × 109  CFU/d; LIP/WC-H). After the 14-day treatment, alveolar bone loss was determined using micro-computed tomography. The gingival tissue and serum samples from Ctrl, LIP/Ctrl, and LIP/WC-H groups were immunoassayed for cytokines. Measurements of Porphyromonas gingivalis, total bacteria, and W. cibaria in the gingiva were performed using real-time polymerase chain reaction. RESULTS: Mice in the LIP/WC-H group showed significant reduction in alveolar bone loss at the distal aspect of the ligatured teeth compared to those in the LIP/Ctrl group. There was a dose-dependent reduction (non-significant) in periodontal tissue destruction with increased W. cibaria concentration. Pro- and anti-inflammatory cytokines were significantly lower in LIP/WC-H than in LIP/Ctrl. The LIP/WC-H group showed significantly fewer total bacteria compared to the LIP/Ctrl group but it was similar to that in Ctrl groups, and P. gingivalis was not detected in the gingival tissue. CONCLUSIONS: W. cibaria CMU reduces periodontal tissue destruction apparently by regulating the production of inflammatory cytokines and by reducing oral bacteria in a model for periodontal disease.

Clinical implication of tumor site in terms of node metastasis for intrahepatic cholangiocarcinoma.

BACKGROUND: The clinical implication of lymph node (LN) dissection of intrahepatic cholangiocarcinoma (ICCA) is still controversial, and LN metastasis (LNM) based on tumor site has not been confirmed yet. METHODS: Patients who underwent curative-intent surgery at 10 tertiary referral centers were identified and divided into peripheral (PP) and near second confluence level tumor (NC) groups on the basis of the distance from the second confluence and oncological outcomes were compared. RESULTS: Of 179 patients, 121 patients with LND were divided into the NC (n = 89) and PP groups (n = 32) on the basis of 4.5 cm from the second confluence. NC group showed higher LNM rate than PP group (46.1 vs 21.9%, p = 0.016) and NC was a risk factor for LNM (odds ratio: 4.367; 95% confidence interval: 1.234-15.453, p = 0.022). The 5-year overall survival (OS) rate (38.0% vs. 27.8%, p = 0.777) and recurrence-free survival (RFS) rates (22.8% vs. 25.8%, p = 0.742) showed no differences between the PP and NC groups. In the NC group, N1 patients showed worse 5-year OS (12.7% vs 39.0%, p = 0.004) and RFS (8.8% vs 28.6%, p = 0.004) than the N0 patients. In the PP group, discordant results in 5-year OS (48.9% vs. 50.0%, p = 0.462) and RFS (41.3% vs. 0%, p = 0.056) were found between the N0 and N1 patients. CONCLUSION: The NC group was an independent risk factor for LNM and LNM worsened prognosis in NC group for ICCA. In the PP group, LND should not be omitted because of high LNM rate and insufficient oncologic evidence.

Ginsenoside Rb2 suppresses the glutamate-mediated oxidative stress and neuronal cell death in HT22 cells.

BACKGROUND: The objective of our study was to analyze the neuroprotective effects of ginsenoside derivatives Rb1, Rb2, Rc, Rd, Rg1, and Rg3 against glutamate-mediated neurotoxicity in HT22 hippocampal mouse neuron cells. METHODS: The neuroprotective effect of ginsenosides were evaluated by measuring cell viability. Protein expressions of mitogen-activated protein kinase (MAPK), Bcl2, Bax, and apoptosis-inducing factor (AIF) were determined by Western blot analysis. The occurrence of apoptotic and death cells was determined by flow cytometry. Cellular level of Ca2+ and reactive oxygen species (ROS) levels were evaluated by image analysis using the fluorescent probes Fluor-3 and 2',7'-dichlorodihydrofluorescein diacetate, respectively. In vivo efficacy of neuroprotection was evaluated using the Mongolian gerbil of ischemic brain injury model. RESULT: Reduction of cell viability by glutamate (5 mM) was significantly suppressed by treatment with ginsenoside Rb2. Phosphorylation of MAPKs, Bax, and nuclear AIF was gradually increased by treatment with 5 mM of glutamate and decreased by co-treatment with Rb2. The occurrence of apoptotic cells was decreased by treatment with Rb2 (25.7 µM). Cellular Ca2+ and ROS levels were decreased in the presence of Rb2, and in vivo data indicated that Rb2 treatment (10 mg/kg) significantly diminished the number of degenerated neurons. CONCLUSION: Our results suggest that Rb2 possesses neuroprotective properties that suppress glutamate-induced neurotoxicity. The molecular mechanism of Rb2 is by suppressing the MAPKs activity and AIF translocation.

Duodenal Penetration by the Ringed Expanded Polytetrafluoroethylene Graft for Middle Hepatic Vein Reconstruction During Living-Donor Liver Transplant: A Case Report.

Expanded polytetrafluoroethylene grafts are widely used for middle hepatic vein reconstruction during living-donor liver transplant because they have comparable patency to autologous or cryopreserved vessels. Mechanical complications like gastric or duodenal penetration by expanded polytetrafluoroethylene grafts have been infrequently reported. We recently experienced a case of duodenal penetration by the expanded polytetrafluoroethylene graft. The patient was a 57-year-old man who had undergone a living-donor liver transplant for cryptogenic liver cirrhosis. At an annual follow-up computed tomography scan performed 3 years after transplant, the expanded polytetrafluoroethylene graft appeared to have penetrated into the first to the second portion of the duodenum, and abnormal air shadow and partial thrombus were identified within the expanded polytetrafluoroethylene graft. The patient underwent exploratory laparotomy, the expanded polytetrafluoroethylene graft was removed, and the perforated duodenum was repaired. Pyloric exclusion with gastrojejunostomy and feeding jejunostomy was additionally performed because of a wide defect in the duodenum. Adjacent organ injuries such as duodenal or gastric penetration by the expanded polytetrafluoroethylene graft after living-donor liver transplant is rare but not uncommon. Because the use of expanded polytetrafluoroethylene grafts is essential when an adequate vessel allograft is unavailable, we can consider transposition of the omental flap between the expanded polytetrafluoroethylene graft and the stomach or duodenum to reduce this unexpected complication.

Determination of the optimal diabetes duration for bone regeneration experiments in an alloxan-induced diabetic rabbit calvarial defect model.

PURPOSE: The purpose of this study was to evaluate the optimal diabetes duration for bone regeneration experiments in an alloxan monohydrate (ALX)-induced diabetic rabbit calvarial defect model by evaluating the association between diabetes duration and bone healing capacity. METHODS: Twenty-four New Zealand white rabbits were used. Twenty-two rabbits were injected with 100 mg/kg of ALX to induce experimental diabetes. These rabbits were divided into 4 groups, including a control group and groups with diabetes durations of 1 week (group 1), 2 weeks (group 2), and 4 weeks (group 3). Calvarial defects were created at 1, 2, and 4 weeks after ALX injection and in the control rabbits. Cone-beam computed tomography (CBCT) scanning was performed on the day of surgery and at 2 and 4 weeks after surgery. The rabbits were sacrificed 4 weeks after surgery, followed by histological and immunofluorescence analysis. RESULTS: The diabetic state of all diabetic rabbits was well-maintained throughout the experiment. Reconstructed 3-dimensional CBCT imaging showed more rapid and prominent bone regeneration in the control group than in the experimental groups. Histological staining showed notable bone regeneration in the control group, in contrast to scarce bone formation in the experimental groups. The appearance and immunoreactivity of receptor activator of nuclear factor-kappa B and osteoprotegerin did not show notable differences among the groups. CONCLUSION: ALX administration at 100 mg/kg successfully induced experimental diabetes in rabbits. The effect of diabetes on bone healing was evident when the interval between diabetes induction and the intervention was ≥1 week.