Oxidative stress induced by iron released from transferrin in low pH peritoneal dialysis solution

Background. Transferrin binds extracellular iron and protectstissues from iron-induced oxidative stress. The binding of ironand transferrin is pH dependent and conventional peritonealdialysis (PD) solutions have unphysiologically low pH values.Herein, we investigated whether conventional PD solution releasesiron from transferrin and if the released iron causes oxidativestress. Methods. Effects of PD solutions on iron binding to transferrinwere examined with purified human transferrin and transferrinin dialysates drained from PD patients. Oxidative stress inducedby iron released from transferrin was evaluated in terms ofthe formation of thiobarbituric acid reactive substance (TBARS)and protein carbonylation in the human red blood cell (RBC)membrane. The iron deposition in peritoneal tissue from PD patientswas evaluated by Perls' staining with diaminobenzidine intensification. Results. Low pH PD solution released iron from transferrin.This iron release occurred within 1 min. Iron release was notobserved in neutralized PD solution. Iron released from transferrinin low pH PD solution increased TBARS formation and proteincarbonylation in the human RBC membrane. Iron deposition, whichis prominent in the fibrotic area facing the peritoneal cavity,was observed in the peritoneum of PD patients. Conclusions. Iron released from transferrin in low pH PD solutioncan produce oxidative stress in the peritoneum of a PD patient.Neutralizing PD solution can avoid this problem. Iron depositionin the peritoneum may participate in the pathogenesis of peritonealfibrosis in PD patients.     

A basic consideration for porcine liver preservation using a novel continuous machine perfusion device

Introduction

The aims of this study were to compare extracellular and intracellular-type University of Wisconsin (UW) solutions for liver grafts and to assess oxygenation in this perfusion system.

Materials and Methods

The organ preservation system consisted of 3 circulating systems for the portal vein, hepatic artery, and maintenance of the perfusion solution. The portal vein or hepatic artery system had a roller pump, a flow meter, and a pressure sensor. In this study, we perfused livers with UW or extracellular type UW-gluconate at 4°C-6°C for 4 hours. The flow rates at the entrance were 0.5 mL/min/g liver in the portal vein and 0.2 mL/min/liver in the hepatic artery. Orthotopic liver transplantation was performed in pigs: group 1-a, grafts procured after acute hemorrhagic shock were preserved by a solution without O₂; group 1-b, grafts were preserved with O₂; group 2-a, grafts were perfused using intracellular type solution (UW); and group 2-b, grafts were perfused using extracellular-type solution (UW-gluconate).

Results

Effluent aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) levels in group 1-b were lower than those in group 1-a. Survival rates in group 2-a and group 2-b were 1/4 and 3/3, respectively. Effluent AST and LDH levels in the perfusate of group 2-b were lower than group 2-a. Histological study revealed necrosis of hepatocytes and sinusoidal congestion in group 2-a.

Conclusion

A beneficial effect of extracellular-type solution with oxygenation in a novel continuous machine preservation system yielded well-preserved liver graft function.     

Interfacial shear strength of bioactive‐coated carbon fiber reinforced polyetheretherketone after in vivo implantation

Despite the excellent osseointegration of carbon‐fiber‐reinforced polyetheretherketone (CFR/PEEK) with a surface hydroxyapatite (HA) coating, the bone‐implant interfacial shear strength of HA‐coated CFR/PEEK after osseointegration is unclear. We examined the interfacial shear strength of HA‐coated CFR/PEEK implants after in vivo implantation in a rabbit femur‐implant pull‐out test model. HA coating was performed by a newly developed method. Uncoated CFR/PEEK, HA‐coated blasted titanium alloy, and uncoated blasted titanium alloy were used as control implants. The implants were inserted into drilled femoral cortex, and pull‐out tests were conducted after 6 and 12 weeks of implantation to determine maximum interfacial shear strength. The HA‐coated CFR/PEEK (15.7 ± 4.5 MPa) and HA‐coated titanium alloy (14.1 ± 6.0 MPa) exhibited significantly larger interfacial shear strengths than the uncoated CFR/PEEK (7.7 ± 1.8 MPa) and the uncoated titanium alloy (7.8 ± 2.1 MPa) at 6 weeks. At 12 weeks, only the uncoated CFR/PEEK (8.3 ± 3.0 MPa) exhibited a significantly smaller interfacial shear strength, as compared to the HA‐coated CFR/PEEK (17.4 ± 3.6 MPa), HA‐coated titanium alloy (14.2 ± 4.8 MPa), and uncoated titanium alloy (15.0 ± 2.6 MPa). Surface analysis of the removed implants revealed detachment of the HA layer in both the HA‐coated CFR/PEEK and titanium alloy implants. The proposed novel HA coating method of CFR/PEEK significantly increased interfacial shear strength between bone and CFR/PEEK. The achieved interfacial shear strength of the HA‐coated CFR/PEEK implant is of the same level as that of grit‐blasted titanium alloy with HA. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1618–1625, 2012     

Recurrent lung cancer with interstitial pneumonia treated with percutaneous radiofrequency ablation

We performed computed tomography (CT)-guided percutaneous radiofrequency ablation (RFA) for postoperative recurrent pulmonary metastases developed in a 77-year-old man with interstitial pneumonia. He had received left upper segmentectomy with ND 2a nodal dissection. RFA was safely performed for pulmonary metastases in right S6 and left S6. There was no evidence to suggest any deterioration on interstitial pneumonia, including KL 6 and CT findings. Autopsy revealed residual cancer cells in peripheral lesion in 1 of 2 tumors treated by RFA. Although RFA is palliative, it is a promising treatment for local control of pulmonary malignancy in high-risk patients.     

Prediction of iopromide reduction rates during haemodialysis using an in vitro dialysis system.

BACKGROUND: In clinical studies, it has been difficult to evaluate the influence of haemodialysis (HD) parameters on HD clearance (CL(HD)) and reduction rate (RR) of non-ionic contrast medium during HD sessions. We therefore predicted clinical values of CL(HD) and RR of iopromide, a non-ionic contrast medium, from findings obtained from in vitro experiments, and confirmed that these predictive values were comparable with the actual values in clinical cases. METHODS: We developed a correlation equation for predicting CL(HD) on the basis of in vitro HD experiments by varying blood flow rates between 100 and 200 ml/min with a cuprammonium rayon dialyser (AM-SD-10H). Total body clearance of iopromide (CL(PT)) was estimated by the Cockroft-Gault equation. The volume of distribution (V(d)) was obtained from the reported value. By using the HD and three pharmacokinetic parameters (CL(HD), CL(PT) and V(d)), we predicted CL(HD) and RR for seven patients undergoing HD after the administration of iopromide. RESULTS: In the in vitro study, the mean values (+/-SD) of iopromide clearance at blood flow rates of 100, 150 and 200 ml/min were 45.35 (2.54), 53.88 (6.46) and 57.61 (4.72) ml/min, respectively. There were highly significant correlations between clearance and blood flow rate (r = 0.975). Although the predicted CL(HD) showed a tendency towards underestimation, a good correlation was found. Predicted RR values were similar to observed values except for one case. CONCLUSION: The in vitro model used in the present study provides pertinent information about CL(HD) and is helpful for predicting RR during HD in individual patients undergoing HD.     

New epitope peptides derived from parathyroid hormone-related protein which have the capacity to induce prostate cancer-reactive cytotoxic T lymphocytes in HLA-A2+ prostate cancer patients

BACKGROUND: Parathyroid hormone-related protein (PTHrP) is produced by cancer cells and has been suggested to be responsible for malignancy-associated hypercalcemia and osteolysis after bone metatsases. Therefore, PTHrP is a promising target in the treatment of metastatic prostate cancer. METHODS: Seven PTHrP-derived peptides were prepared based on the HLA-A2 binding motif. These peptide candidates were screened by their ability to induce peptide-specific cytotoxic T lymphocytes (CTLs), and their ability to be recognized by immunoglobulin G (IgG). RESULTS: Both the PTHrP59-67 and PTHrP42-51 peptides were found to efficiently induce peptide-specific CTLs from peripheral blood mononuclear cells of HLA-A2+ prostate cancer patients with several HLA-A2 subtypes. These CTLs showed HLA-A2-restricted cytotoxicity toward prostate cancer cells. IgG reactive to the PTHrP42-51 peptide was frequently detected in prostate cancer patients. CONCLUSIONS: These results indicate that these two new PTHrP peptides will be useful in the peptide-based immunotherapy of HLA-A2+ prostate cancer patients, especially those with bone metastases.     

Granular cell tumor of the neurohypophysis with optic tract edema

Granular cell tumor of the neurohypophysis is a rare disease entity. To our knowledge, this is the first report concerning a granular cell tumor of the neurohypophysis associated with optic tract edema. A 55-year-old man underwent brain magnetic resonance imaging (MRI) for a medical check-up, and a suprasellar tumor was detected. Brain computed tomography (CT) demonstrated a well delineated, homogenous, slightly hyperdense suprasellar tumor. MRI detected a lobular tumor that was isointense on T1-weighted images, hypointense on T2-weighted images, and showed homogeneous enhancement after administration of a gadopentetate dimeglumine. T2-weighted images and fluid-attenuated inversion recovery (FLAIR) images demonstrated a hyperintense region in the optic tract. Subtotal tumor resection was performed, and histological examination confirmed the diagnosis of granular cell tumor. Postoperative MRI showed that the tumor volume was reduced and optic tract edema diminished compared with the preoperative findings. We also review the literature focusing on radiographic findings, and compare the effectiveness of MRI and CT for diagnosing granular cell tumor of the neurohypophysis.     

Adrenal ganglioneuroma: a case report

A patient with an incidentally diagnosed adrenal ganglioneuroma is reported. A 37-year-old man who underwent abdominal computed tomography (CT) in the course of evaluating liver dysfunction was found to have a right adrenal tumor. Laboratory data including results of endocrinologic tests were normal except for a slight elevation of plasma aldosterone. With a preoperative diagnosis of non-functioning right adrenal tumor, resection was performed. The tumor specimen was noncystic weighing 150 g and measuring 10 x 8 x 3 cm. The histopathologic diagnosis was ganglioneuroma originating from the adrenal gland. Adrenal ganglioneuroma is relatively rare, 147 cases including ours have been reported in Japan. Increasing numbers of these tumors are being found incidentally by ultrasonography or CT. Ganglioneuroma is a benign tumor, and disagreement exists concerning diagnosis and indications for surgery.     

Intraluminal lavage to remove exfoliated tumor cells after colorectal endoscopic submucosal dissection

Background

Endoscopic submucosal dissection (ESD) involves dissection of tumors and manipulation of them in an exposed condition for prolonged periods. A large number of tumor cells are exfoliated into the intestinal lumen after colorectal ESD. The aim of this study was to determine whether lavage volume has an influence on tumor cell clearance after colorectal ESD.

Methods

Twenty patients who underwent colorectal ESD at our hospital between July 2013 and December 2014 were studied. Cytological examination of intraluminal lavage samples associated incremental increases in lavage volume was collected. This prospective study was approved by the ethics committee of our hospital.

Results

No patients had exfoliated tumor cells in their samples before ESD. Four patients (20 %) had exfoliated tumor cells in their samples after lavage with 500 ml, while one patient (5 %) had exfoliated tumor cells after lavage with 1000 or 1500 ml.

Conclusion

Tumor cells are exfoliated into the intestinal lumen by tumor manipulation during colorectal ESD. There seems to be a risk for implantation after ESD, as well as rectal surgery. Sufficient intraluminal lavage of more than 1000 ml may be desirable to remove exfoliated tumor cells after colorectal ESD.