Role of the p38 pathway in mineral trioxide aggregate-induced cell viability and angiogenesis-related proteins of dental pulp cell in vitro.

AIM: To investigate the influence of mineral trioxide aggregate (MTA) on angiogenesis of primary human dental pulp cells (hDPCs) via the MAPK pathway, in particular p38. METHODOLOGY: Human dental pulp cells were cultured with MTA to angiogenesis, after which cell viability, ion concentration, osmolality, NO secretion, the von Willebrand factor (vWF) and angiopoietin-1 (Ang-1) protein expression were examined. PrestoBlue(®) was used for evaluating the proliferation of hDPCs. An enzyme-linked immunosorbent assay was employed to determine vWF and Ang-1 protein secretion in hDPCs cultured on MTA and the control. Cells cultured on the tissue culture plate without the cement were used as the control. The t-test was used to evaluate the significance of the differences between the mean values. RESULTS: Mineral trioxide aggregate elicited a significant (P < 0.05) increased viability compared with the control (15%, 16% and 13% on days 1, 3 and 5 of cell seeding, respectively). MTA consumed calcium and phosphate ions, and released more Si ions in the medium. MTA significantly (P < 0.05) increased the osmolality of the medium to 313, 328 and 341 mOsm kg(-1) after 1, 3 and 5 days, respectively. P38 was activated through phosphorylation, and the phosphorylation kinase was investigated in the cell system after being cultured with MTA. Expression levels for Ang-1 and vWF in hDPCs on MTA were higher than those of the MTA + p38 inhibitor (SB203580) group (P < 0.05) at all of the time-points. CONCLUSIONS: Mineral trioxide aggregate was able to activate the p38 pathway in hDPCs cultured in vitro. Moreover, Si increased the osmolality required to facilitate the angiogenic differentiation of hDPCs via the p38 signalling pathway. When the p38 pathway was blocked by SB203580, the angiogenic-dependent protein secretion decreased. These findings verify that the p38 pathway plays a key role in regulating the angiogenic behaviour of hDPCs cultured on MTA.

The synergistic effects of fibroblast growth factor-2 and mineral trioxide aggregate on an osteogenic accelerator in vitro.

AIM: To examine the effects of mineral trioxide aggregate (MTA)/fibroblast growth factor-2 (FGF-2) on material properties and in vitro human dental pulp cell (hDPCs) behaviour. METHODOLOGY: The setting time and diametral tensile strength (DTS) of MTA and MTA/FGF-2 were measured. The structure of specimens before and after soaking in DMEM was examined under a scanning electron microscope. Alamar Blue was used for evaluating hDPCs proliferation. An enzyme-linked immunosorbent assay was employed to determine ALP and osteocalcin (OC) expression in hDPCs cultured on cements. The effect of small interfering RNA (siRNA) transfection targeting fibroblast growth factor receptor (FGFR) was also evaluated. One-way analysis of variance was used to evaluate the significance of the differences between the mean values. RESULTS: Setting time and DTS data were not found to be significant (P > 0.05) between MTA with and without FGF-2. Cell proliferation and differentiation increased significantly (P < 0.05) with FGF-2 mixed MTA. After siRNA transfection with FGFR, the proliferation and differentiation behaviour of the hDPCs appreciably decreased when cultured on an MTA/FGF-2 composite. In contrast, no significant amounts (P > 0.05) of ALP and OC were secreted by hDPCs seeded on MTA. CONCLUSIONS: Mineral trioxide aggregate with FGF-2 content enhanced the higher expression of hDPCs proliferation and osteogenic differentiation as compared to pure MTA cement.

Impact of chronic advanced aortic regurgitation on the perioperative outcome of noncardiac surgery.

BACKGROUND: Whether and how chronic advanced aortic regurgitation (AR) impacts the perioperative outcome of noncardiac surgery remains unclear. METHODS: From November 1999 to December 2006, all patients undergoing noncardiac operations and ever examined by echocardiography within the last 6 months were screened. Those with chronic moderate-severe or severe AR were enrolled, provided they were not already trachea-intubated or aortic valve operated, and the surgery was not performed under local anesthesia. Case-matched subjects without significant AR served as controls. The perioperative outcomes of these patients were analyzed, and independent prognostic correlates were investigated by multivariate logistic regression analysis. RESULTS: A total of 167 patients (male 131, mean age of 75 years) complying with the enrollment criteria were studied. Compared with the other 167 case-matched control peers, patients with advanced AR risked potential hazards of serious hemodynamic instability (0.6%) and circulatory collapse (1.2%) during surgery despite the similar incidence of overall cardiac adverse events, and were further distressed with more cardiopulmonary complications (16.2% vs. 5.4%, P=0.003) and in-hospital deaths (9% vs. 1.8%, P=0.008) post-operatively. Multivariate regression analysis confirmed the correlation of advanced AR with perioperative mortality, and identified depressed left ventricular function, renal dysfunction, high surgical risk, and lack of cardiac medication as predictors of in-hospital death. CONCLUSION: Chronic advanced AR complicates the perioperative outcome of noncardiac surgery as reflected by frequent cardiopulmonary morbidities and in-hospital deaths, especially when coexisting with specified high-risk clinical and surgical characteristics.

Electrodeposited defect chemistry superlattices.

Nanometer-scale layered structures based on thallium(III) oxide were electrodeposited in a beaker at room temperature by pulsing the applied potential during deposition. The conducting metal oxide samples were superlattices, with layers as thin as 6.7 nanometers. The defect chemistry was a function of the applied overpotential: High overpotentials favored oxygen vacancies, whereas low overpotentials favored cation interstitials. The transition from one defect chemistry to another in this nonequilibrium process occurred in the same potential range (100 to 120 millivolts) in which the rate of the back electron transfer reaction became significant. The epitaxial structures have the high carrier density and low electronic dimensionality of high transition temperature superconductors.

Scanning tunneling microscopy of electrodeposited ceramic superlattices.

Cleaved cross sections of nanometer-scale ceramic superlattices fabricated from materials of the lead-thallium-oxygen system were imaged in the scanning tunneling microscope (STM). The apparent height differences between the layers were attributed to composition-dependent variations in local electrical properties. For a typical superlattice, the measured modulation wavelength was 10.6 nanometers by STM and 10.8 nanometers by x-ray diffraction. The apparent height profile for potentiostatically deposited superlattices was more square than that for galvanostatically deposited samples. These results suggest that the composition follows the applied potential more closely than it follows the applied current. The x-ray diffraction pattern of a superlattice produced under potential control had satellites out to the fourth order around the (420) Bragg reflection.

Reappraisal of HLA antibody analysis and crossmatching in kidney transplantation.

Enzyme-linked immunosorbent assay (ELISA) and flow cytometric techniques have been introduced to overcome the limited sensitivity and specificity of the CDC assay. This retrospective study used lambda antigen tray-mixed screening and Luminex HLA class I and II specificity assays to re-examine: (1) the accuracy with which detection of HLA antibody and specificity by ELISA predicts pretransplantation National Institutes of Health (NIH)/Centers for Disease Control and Prevention (CDC) crossmatch; and (2) a comparison of Luminex and ELISA methods to detect HLA antibodies. Sera from 481 patients awaiting kidney transplantation were tested using the ELISA method lambda antigen tray-mixed and using NIH-CDC to determine how well HLA antibodies detected using ELISA predicted crossmatches using CDC. Pretransplantation sera from 48 patients with follow-up data were retested using both ELISA lambda antigen tray-mixed and Luminex to compare the efficacy of the 2 methods.

Eighteen-year follow-up of a retrospective study of HLA antibody on kidney graft survival.

An increasing number of studies have demonstrated adverse graft survival in patients who have anti-HLA antibodies, whether preformed or developed posttransplantation. This retrospective study used Lambda antigen tray-mixed (LAT-M) screening and Luminex HLA class I and II specificity assay to re-examine the impact of pretransplantation HLA antibody on long-term graft survival. In this study, pretransplantation sera from 288 renal patients were tested using the enzyme-linked immunosorbent assay (ELISA) method, LAT-M. Among the 234 of the patients who did not have pretransplantation antibodies, 85% enjoyed 5-year functional graft survival, 76% 10-year functional graft survival, and 56% 15-year functional graft survival. The corresponding functional graft survival for the 54 patients who tested HLA antibody-positive was 65%, 53%, and 28%, respectively (P = .0021).

Does immunosuppressive pharmacotherapy affect isoagglutinin titers?

OBJECTIVE: Preoperative reduction of isoagglutinins leads to successful ABO-incompatible (ABOi) renal transplantation. The strategy includes pretransplantation plasmapheresis, more potent immunosuppressive drugs, splenectomy, and anti-CD20 antibody. It has been reported that low isoagglutinin antibody titers posttransplant were observed among ABOi renal transplants with favorable outcome. The isoagglutinin titers may increase slightly when plasmapheresis is discontinued; however, it never returns to the pretreatment level under immunosuppressive therapy. This raises the question of what occurs to the isoagglutinin titer in ABO-compatible renal transplants under maintenance immunosuppressive pharmacotherapy. METHODS: We analyzed 10 renal transplant recipients, including seven living and three cadaveric donors. Patients were treated with basiliximab (20 mg) intravenously on day 0 and day 4. Maintenance immunosuppressive therapy involved a calcineurin inhibitor, mycophenolate mofetil, and steroid. Anti-human globulin isoagglutinin titers were routinely examined 1 day before and day 0 and 1, 2, 3, 4, 8, 12, and 24 weeks posttransplant. No ALG or intravenous immunoglobulin or plasmapheresis treatment was provided in the follow-up period. RESULTS: Our preliminary data showed nearly no influence on isoagglutinin titer levels in 6-month follow-up under maintenance immunosuppressive therapy. In addition, no significant difference in isoagglutinin titer was observed between tacrolimus and cyclosporine groups. CONCLUSION: Maintenance immunosuppressive pharmacotherapy did not affect isoagglutinin titer levels in ABO-compatible kidney transplants. Further study is needed to investigate the mechanisms of persistent low-level isoagglutinin titers among successful ABOi renal transplantation patients.

Influence of preoperative allograft function (effective renal plasma flow) on the short-term outcome following living donor kidney transplantation.

OBJECTIVES: Predonation kidney function is supposed to be an important factor affecting graft outcome. Controversial evidence suggests that higher predonation glomerular filtration rate (GFR) positively correlated with posttransplant graft outcome. The purpose of this study was to examine the relationship between living donor graft kidney function as measured by effective renal plasma flow (ERPF) and short-term graft function. METHODS: We performed a retrospective analysis of 45 patients who underwent living donor renal transplantation at our institution from 2001 to 2007. The comprehensive nuclear medicine evaluation of donors' ERPF was performed before laparoscopic nephrectomy. The preoperative absolute ERPF-recipient body surface area (F/BSA) ratio and absolute ERPF-recipient body weight (F/Wt) ratio were determined for each donor-recipient pair. Posttransplant graft function was estimated by the four-variable Modification of Diet in Renal Disease (Chinese MDRD) equation. RESULTS: Estimated GFR correlated with F/BSA ratio at 3 months and 6 months (Pearson r = .495, P = .001 and r = .441, P = .012). Estimated GFR correlated with F/Wt ratio at 3 months and 6 months (r = .567, P < .001 and r = .453, P = .009). The correlations between the estimated GFR at 3 months and other variables were investigated. However, in the final multivariate model, F/BSA ratio and F/Wt ratio were the independent predictors of graft function. CONCLUSION: Preoperative ERPF can be used to calculate F/BSA and F/Wt ratios before living donor kidney transplantation. Our study provided evidence that F/BSA and F/Wt ratios may be considered predictive indices for short-term outcomes. An extreme discrepancy should be avoided between preoperative allograft function (absolute ERPF) and recipient body surface area or body weight.

Five-year experience of adoption and evolution of laparoscopic living donor nephrectomy: results from a center without large volume of patients.

OBJECTIVES: Despite the advantages of laparoscopic living donor nephrectomy (LDN), this technique is known to have a steep learning curve that makes worldwide adoption challenging, especially in institutions without a large patients volume. Herein, we have reviewed our 5-year experience of adoption and evolution of this surgical technique, examining the donor and recipient outcomes. METHODS: Between September 2002 and June 2007, 40 LDNs were performed consecutively. Our surgical technique was mainly derived from the University of California San Francisco method. We retrospectively reviewed the donor demographics, operative characteristics, perioperative complication of donors/recipients, and outcomes of donors and recipients. RESULTS: Among the 40 cases, 36 (90.0%) were left-sided LDNs. Mean operative time was 335.1 +/- 66.9 minutes, blood loss was 303.9 +/- 333.2 mL, and warm ischemia time was 243.2 +/- 127.0 seconds. Multiple renal arteries required bench arterial reconstruction in 7 (17.5%) donor kidneys. Three renovascular injuries occurred intraoperatively, and 2 (5.0%) required open conversion. The overall postoperative complication rate was 20.0%. Postoperative donor serum creatinine was 1.5 times higher than preoperative serum creatinine. All but one recipient was discharged with adequate renal function. Graft function continues in 36 of the 38 harvested kidneys (94.7%) during the follow-up period. One (2.5%) recipient developed ureteral necrosis, and no recipients developed vascular thrombosis. CONCLUSIONS: LDNs can be performed with careful adoption and evolution in institutions without a large patient volume. The intraoperative complication rate of LDN can be reduced with experience.

Role of right hepatic lobectomy in the treatment of isolated right-sided hepatolithiasis.

BACKGROUND: The role of right hepatic lobectomy is evaluated in the treatment of selected patients with isolated right-sided hepatolithiasis. METHODS: During the past 7 years right hepatic lobectomy was performed in five patients who had isolated right-sided hepatolithiasis. The rationale and indications of this procedure are discussed. The efficacy of preoperative evaluations, the operative findings, and the operative results are analyzed. RESULTS: All the patients were female with a mean age of 49.2 years (range, 33 to 63 years). The main symptoms were upper abdominal pain (n = 5), fever (n = 4), and jaundice (n = 2). The mean operative time was 166.4 minutes, and the mean blood loss was 880 ml. The complete stone clearance rate was 100%. No operative deaths occurred. Right subphrenic abscess with reactive pleural effusion developed in two patients. Echo-guided percutaneous drainage was applied to one patient, and no surgical intervention was needed. The mean follow-up period from the treatment was 13.4 months (range, 6 to 18 months). During the follow-up period no stone recurrence was found. CONCLUSIONS: Right hepatic lobectomy is indicated in patients who have localized right-sided hepatolithiasis with irreversible biliary stricture involving the right hepatic duct, an atrophied right lobe of the liver, multiple cholangitic abscesses, or possible presence of cholangiocarcinoma. Preoperative evaluations, including cholangiography, abdominal ultrasonography, and computed tomography, are important for the accurate selection of patients and successful treatment.

Rhabdomyolysis-induced acute renal failure after morphine overdose--a case report.

The 39-year-old male in this report was a victim of C4 spinal cord injury for 7 years. He was regularly followed up at our pain clinic and psychiatric out-patient department (OPD) for treatment of his chronic pain with morphine, anticonvulsant and sedatives. At the night of December 15, 1997, he took approximately 0.1 gm of morphine and a certain number of flurazepam pills. On the next day, he experienced numbness and paresis in both legs in association with painful swelling of both thighs. Then he sought medical advice at our hospital and was admitted for investigation on December 20, 1997. Laboratory examination revealed elevated creatine kinase activity, increased urine myoglobin concentration and raised plasma creatinine, signifying the development of acute muscle damage. The excreted urine morphine concentration was as high as 6,384 ng/mL. Increased PYP uptake in the proximal portion of both thighs was noted on muscle scan. These abnormalities were resolved gradually over two weeks under conservative treatment. Morphine-induced rhabdomyolysis complicated by acute renal failure was highly suspected.

Will epidural with light general anesthesia increase the incidence of awareness with recall or dream postoperatively.

BACKGROUND: The incidence of awareness with recall during general combined with epidural anesthesia has not been previously reported. The purpose of this study was to quantify the incidence. MATERIALS & METHODS: One hundred patients were divided into two groups. Group 1 (N = 50) received general anesthesia (GA), Group 2 (N = 50) received GA and epidural anesthesia (EA) intraoperatively. No premedication was given. These patients were induced with thiopentol (5 mg/kg) or propofol (2.0 mg/kg) and anectine (1.2 mg/kg) for smooth tracheal intubation and maintained with N2O:O2 = 1.5:1.5, and isoflurane and muscle relaxant of either pavulon or atracurium. No sedatives was given. Before anesthesia, we introduced an epidural catheter into the group 2 patients. After induction, headphones with soft music were given to the patients, in both groups, throughout the operation. 20-36 hours after operation or when the patients were fully awake, we asked the patients if they had heard anything or dreamed intraoperatively. RESULTS: We found that not one of the one hundred patients heard anything or dreamed intraoperatively.

Co-administration of midazolam decreases propofol dose during anesthesia in endoscopic laryngeal microsurgery.

BACKGROUND: Propofol is commonly used in total intravenous anesthesia (TIVA) for brief surgical procedures because it offers rapid recovery and has fewer side effects. However, concomittent use of other adjuvant agents has been considered so that the same anesthetic effects can be achieved at lower doses of propofol which is more expensive without compromising rapid recovery and increasing the adverse effects. This study was therefore designed to evaluate the co-administration of midazolam and propofol during anesthesia for endoscopic microsurgery and test its influences on the consumption of propofol and the quality of anesthesia. METHODS: Forty-two patients receiving selective endoscopic microsurgery were enrolled in this study. All patients received high frequency jet ventilation (HFJV) under TIVA. The control group (n = 21) received propofol (20 mg/5 s) during induction and 10 mg/kg/h as maintenance. The study group (n = 21) received midazolam (0.06 mg/kg) and propofol (20 mg/5 s) for induction with propofol 8 mg/kg/hr for maintenance. Doses of propofol, vital signs, recovery time, post-anesthetic high cortical function, and adverse events were evaluated and compared. RESULTS: Co-administration of midazolam and propofol in TIVA could reduce the induction dose and the total dose of propofol by 51% and 26% respectively but still achieve the same anesthetic effects. Vital signs and recovery were not influenced, and incidence of adverse effects did not increase. CONCLUSIONS: Our result suggests that co-administration of midazolam and propofol in TIVA appears to be safe, effective, and economic alternative to that with propofol alone. The effects were synergic but side effects were not.

Peliosis hepatis in a kidney transplant recipient with manifestation as massive ascites and liver dysfunction: case report.

We report a case of 59-year-old woman who received a kidney transplant 7 years earlier without evidence of viral hepatitis history. She was asymptomatic initially and a newly developed nodule, ∼2.3 cm in size, was discovered in the right liver during routine sonographic examination. Computerized tomography-guided biopsy was inconclusive at that time. However, the lesion grew to 6.8 cm and bilobular multiple nodules developed with concomitant massive ascites and hyperbilirubinemia months later. Laparoscopy showed typical bluish-reddish-blackish nodules. Needle-biopsy histology showed severe sinusoid dilation and dropout of centrilobular hepatocytes consistent with peliosis hepatis. Reticulin staining also demonstrated disruption of sinusoidal reticulin fibers. We tried to withdraw possible offending drugs to anticipate regression of peliosis, but it failed and liver dysfunction progressed, leaving liver transplant as the last resort in such rare circumstances.

Kidney grafts with multiple renal arteries is no longer a relative contraindication with advance in surgical techniques of laparoscopic donor nephrectomy.

OBJECTIVES: Kidney grafts with multiple renal arteries were considered as a relative contraindication. We retrospectively reviewed our experience of kidney grafts with multiple renal arteries to clarify the usefulness of these grafts. METHODS: Between September 2002 and June 2011, 100 laparoscopic donor nephrectomies (LDNs) were performed consecutively. Three-dimensional computed tomographic angiography was routinely performed preoperatively. Donor demographics, operative characteristics, donor and recipients perioperative complications, and donor and recipient outcomes were reviewed retrospectively. RESULTS: Eighty-nine donors had single (group A1) and 11 donors had multiple renal arteries (group B1). Multiple arteries caused by application of the vascular stapler were found in another six donors. Overall, 17 kidney grafts required bench arterial reconstruction (group B2). The other 83 donors with single renal artery did not require further arterial reconstruction (group A2). There was a significant increase of warm ischemic time in the group of multiple renal arteries. There were no significant difference between groups A1 and B1 in regard to donor demographics, operative characteristics, and donor outcome. Kidney grafts requiring vascular reconstruction experienced equal immediate and long-term allograft outcomes with those of group A2. The actuarial 1-, 3-, and 5-year allograft survival rates were also comparable in both groups (95.4%, 92.6%, 92.6% in group A2 and 100%, 100%, 100% in group B2). CONCLUSION: LDN in the presence of multiple renal arteries is feasible and safe. Both immediate and long-term allograft outcomes are comparable between kidney grafts with and without vascular reconstruction. Kidney grafts with multiple renal arteries are no longer a relative contraindication with advanced LDN surgical techniques.

Association between preoperative allograft function (effective renal plasma flow) and the change in glomerular filtration rate among living-donor kidney transplant recipients.

BACKGROUND: Predonation kidney function may be an important factor affecting graft outcome. Increased baseline allograft function may be more effective than strategies to slow the decline in glomerular filtration rate (GFR). However, the role of donor effective renal plasma flow (ERPF) on long-term outcome is less well understood. The purpose of this study was to examine the relationship between preoperative allograft function as measured by ERPF and the decline of allograft function as defined by the annualized change in GFR among living-donor kidney transplant recipients. METHODS: We performed a retrospective analysis of 83 patients who underwent living donor renal transplantation at our institution from March 2001 to October 2010. A time series analysis of autoregressive integrated moving average (ARIMA) model was applied to determine the annualized change in GFR after transplantation. Univariate and stepwise multivariate analyses were performed using linear regression between preoperative ERPF and annualized change in GFR after transplantation. We also investigated the influence on annualized change in GFR of other donor or recipient variables. RESULTS: The ARIMA model revealed that the annualized change in GFR was -1.344 ± 12.476 mL/min/1.73 m(2) per year. Pearson correlation coefficient for the association between predonation ERPF of the transplanted kidney and the annualized change in GFR was 0.033 (P = .777). CONCLUSIONS: Poor predonation kidney function was not associated with an increased rate of decline of allograft function. Neither donor age nor renal function (preoperative ERPF value) was a valid predictor of change in GFR among living-donor kidney transplant recipients.

The clinical significance of human leukocyte antigen antibody development in kidney transplantation.

BACKGROUND: This retrospective study uses the LAT-M (One Lambda Inc., Calif) screen assay to reexamine the impacts (a), of pretransplant human leukocyte antigen (HLA) antibody on long-term graft survival; (b) posttransplant HLA antibody on long-term graft survival and (c) immunosuppressive regimen on posttransplant HLA antibody development. PATIENTS AND METHODS: Pretransplant sera from 222 renal transplant recipients and posttransplant sera from 216 renal transplant recipients were studied for the impact of HLA antibody on long-term graft survival. RESULTS: Among the patients who did not display pretransplant HLA antibodies, 85% enjoyed 5-year and 59% 10-year graft survival, whereas the patients who tested positive were 83% and 83% (P = .5596). Among the patients who did not show posttransplant HLA antibodies, 99% enjoyed 5-, 91% 10-, and 65% 15-year graft survival, whereas for the 44 patients who tested positive they were 59%, 44%, and 30%, respectively (P < .0001). Patients prescribed cyclosporine + myfortic (odds ratio 0.17, P = .05) or FK + Cellcept (odds ratio 0.36, P = .04) showed the lowest posttransplant HLA antibody development. CONCLUSION: Both regimens improve graft survival.

Cyclosporine or tacrolimus: which is the better partner for myfortic or cellcept?

BACKGROUND: Mycophenolic acid (MPA) pharmacokinetics using the mycophenolate mofetil (CellCept) formulation are known to differ between patients receiving tacrolimus (FK) or cyclosporine (CyA), but only limited data exist concerning concomitant use of FK or CyA with enteric-coated mycophenolate sodium (EC-MPS; Myfortic). This retrospective study compared the drug interactions with the mycophenolic acid blood levels using different immunosuppressants and their relation to graft survival. PATIENTS AND METHODS: We studied MPA levels in posttransplant sera from 298 renal transplant recipients. RESULTS: Patients receiving immunosuppression with CyA + Myfortic showed 94% at 5- and 10-year graft survivals, which were better than CyA + CellCept (75%, 63%). This combination suppressed posttransplant human leukocyte antigen (HLA) antibody development significantly (P = .03) with higher MPA levels. CONCLUSION: Patients immunosuppressed with CyA + Myfortic showed higher MPA levels and lower posttransplant HLA antibody development as well as the best graft survival. CyA + Myfortic or FK + Cellcept may be better combinations.