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.     

The relationship between the soluble Klotho protein and the residual renal function among peritoneal dialysis patients

Background

Klotho has been investigated as an anti-aging protein that is predominantly expressed in the distal convoluted tubules in the kidneys and in the choroid plexus of the brain. The purpose of the present study was to determine the relationship between the soluble form of Klotho and renal function in chronic peritoneal dialysis (PD) patients, a relationship which remains poorly understood.

Methods

The soluble Klotho levels in the serum, urine, and peritoneal dialysate obtained from thirty-six PD patients were determined by a sandwich enzyme-linked immunosorbent assay system.

Results

The amount of urinary excreted soluble Klotho over 24?h ranged from 1.54 to 1774.4?ng/day (median 303.2?ng/day; interquartile range [IR] 84.1–498.5), while the serum soluble Klotho concentration ranged from 194.4 to 990.4?pg/ml (mean 553.7?±?210.4?pg/ml). The amount of urinary Klotho excretion was significantly correlated with residual renal function. However, there was no apparent correlation between the serum soluble Klotho levels and the residual renal function. Klotho was also detected in the 24-h dialysate collections. There was a significant correlation between the peritoneal Klotho excretion and the amount of albumin contained in the dialysate collections (r?=?0.798, p?Conclusions The total amount of urinary excreted Klotho, but not the serum level of soluble Klotho, may be a potential biomarker for assessing the residual renal function among PD patients. Whether our findings are also valid for chronic kidney disease patients overall should therefore be evaluated in greater detail.     

A case of secondary Paget's disease of the glans penis originating from bladder cancer

An 81-year-old man had undergone total cystectomy and bilateral ureterocutaneostomy at the age of 66 years. Furthermore, no recurrence or metastasis was observed; but at the age of 80 years he observed a painless rash around the external urethral orifice. As urothelial cancer was suspected, the urethra and glans were biopsied. Through immunohistochemical staining (cytokeratin 7 and 20), the glans biopsy indicated secondary Paget's disease of transitional epithelial origin. A urethrectomy was performed as progression from the urethra was suspected. The pathological examination revealed Paget cells at the glans, but the tumor was not observed permeating into the corpus cavernosum. This presents a rare case of secondary Paget's disease originating from a bladder tumor, and appearing in the glans without intraurethral progression.     

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     

Subarachnoid hemorrhage in a case of segmental arterial mediolysis with coexisting intracranial and intraabdominal aneurysms

The authors report the rare case of a 58-year-old man with segmental arterial mediolysis (SAM) with associated intracranial and intraabdominal aneurysms, who suffered subarachnoid hemorrhage (SAH) due to rupture of an intracranial aneurysm. This disease primarily involves the intraabdominal arterial system, resulting in intraabdominal and retroperitoneal hemorrhage in most cases. The patient presented with severe headache and vomiting. The CT scans of the head revealed SAH. Cerebral angiography revealed 3 aneurysms: 1 in the right distal anterior cerebral artery (ACA), 1 in the distal portion of the A(1) segment of the right ACA, and 1 in the left vertebral artery. The patient had a history of multiple intraabdominal aneurysms involving the splenic, gastroepiploic, gastroduodenal, and bilateral renal arteries. He underwent a right frontotemporal craniotomy and fibrin coating of the dissecting aneurysm in the distal portion of the A(1) segment of the right ACA, which was the cause of the hemorrhage. Follow-up revealed no significant changes in the residual intracranial and intraabdominal aneurysms. An SAH due to SAM with associated multiple intraabdominal aneurysms is extremely rare. The authors describe their particular case and review the literature pertaining to SAM with associated intracranial and intraabdominal aneurysms.     

Pineal xanthogranuloma

A 64-year-old man presented a large pineal cystic lesion manifesting as headache and exhibiting unusual neuroradiological findings. Magnetic resonance imaging showed a cystic lesion appearing as hyperintense on both T1- and T2-weighted images, and a nodular lesion which was hypointense on T1-and mixed intensity on T2-weighted images. The cystic mass was removed via a right occipital transtentorial approach. Histological examination disclosed that the inner surface of the cystic part consisted of bi-layered epithelial lining, portions of which had changed to stratified squamous epithelium. The solid part showed the characteristics of xanthogranuloma such as cholesterol clefts, hemosiderin-laden macrophages, and foreign body giant cells.     

Sentinel lymph node mapping for gastric cancer using a dual procedure with dye- and gamma probe-guided techniques

BACKGROUND: Increasing evidence supports the sentinel lymph node (SN) concept for melanoma and breast cancers. SN biopsy may replace routine lymph node dissection in the treatment of these cancers. But there are little data evaluating this concept in patients with gastric cancer. The objective of this study was to test the feasibility of SN mapping in gastric cancers by using the dual-mapping procedure with dye and radioactive colloid. STUDY DESIGN: Thirty-one consecutive patients preoperatively diagnosed as T1-2 and N0 underwent SN biopsy using the dual-mapping procedure. Distributions of SNs identified by the dye-guided technique (blue nodes; BNs) were compared with those identified by the gamma probe guided technique (hot nodes; HNs). RESULTS: Among the 31 patients, 7 were found to have lymph node metastases. All positive nodes were detected by SN biopsy using the dual method. So, an accuracy rate of 100% was achieved in predicting the status of regional lymph nodes. Both BNs and HNs were identified in 28 of 31 patients (90%), but significant discrepancy of distribution was noted between BNs and HNs. Among the 28 patients with identified BNs, there was one metastasis in a non-BN. So the accuracy rate was 96% for the dye-guided technique. In contrast, among the 28 patients with identified HNs, 2 patients had metastasis in non-HNs, making the accuracy rate 93% for the gamma probe-guided technique. CONCLUSIONS: SN mapping is feasible in gastric cancer, but the dye-guided and gamma probe-guided techniques are complementary. So we recommend the dual-mapping procedure.     

Prognostic factors in patients who survived more than 10 years after undergoing surgery for metastatic brain tumors: report of 5 cases and review of the literature

BACKGROUND: Although the overall prognosis of patients with metastatic brain tumors is dismal, a small number survive longer than 10 years after craniotomy. We report 5 patients who survived for more than 10 years after undergoing treatment for metastatic brain tumor. METHODS: The 5 patients who survived for more than 10 years after undergoing craniotomy were among 56 consecutively treated patients with solitary metastatic brain tumors. We retrospectively examined their clinical course, treatment, and variables associated with their longer survival and compared these 5 patients with other reported cases of metastatic brain tumor. RESULTS: The histologic tumor types and the sites of origin of the primary tumor varied: two were from lung cancer and one each was from colon cancer, renal cell, and cervical carcinoma of the uterus. Common features among the long-term survivors were: systemic disease was absent, the metastatic tumor was located in the non-eloquent area of the non-dominant hemisphere, they were in good neurologic condition before surgery, there was a long interval between the diagnosis and treatment of the primary lesion and the diagnosis of the brain metastasis, and the patients received postoperative irradiation/chemotherapy. CONCLUSION: Aggressive surgical treatment may be justified in young patients with a solitary metastatic brain tumor, as long as they are free of active systemic metastases.     

Cytokine expression in the renal tubular epithelial cells stimulated by Shiga toxin 2 of Escherichia coli O157:H7

Hemolytic uremic syndrome (HUS) is the most common cause of acute renal failure in children worldwide. Shiga toxin (Stx) associated HUS, the most common type, is now known to be caused by Escherichia coli O157:7, which produces Stxl or the more potent, Stx2. Since the renal tubule is the major tissue affected in the course of HUS and Stx2 is known to be toxic to the renal tubular cells (RTC), we attempted to elucidate the mechanism of renal injury in HUS by studying the alteration of cytokines in the RTC evoked by Stx2. cDNA-array is a powerful tool for evaluating changes in the expression of a group of critical genes and also gives insights on the overview of the gene activation. In this study, we purified Stx2 from the E. coli O157:7, which was isolated from a typical diarrhea-associated HUS patient and then tried to compare the cytokine gene expression between the stimulated RTC and un-stimulated RTC using cDNA-array. Our results showed that one third of the examined cytokine genes were up regulated at least twice by the addition of Vtx2. These up-regulated genes represented the chemokines (macrophage related cytokines), fibrosis-related cytokine (TNF, PDGF) and leukemia inhibitory factors. However, the expression of IL-6, one of the pleiotropic cytokines, was significantly decreased and this finding was confirmed by northern analysis. Our results suggest that VT2 up-regulates the pro-inflammatory cytokines and fibrosis prone growth factors in RTC and that the inhibition of the activation of these cytokines may ameliorate the renal tubular injury in the HUS caused by E. coli O157:7.     

Role of β2 integrins in glomerular leucocytes in Henoch-Schoenlein purpura nephritis: an age-matched comparative study with immunoglobulin A nephropathy

SUMMARY: A comparative immunohistological study was performed for the glomerular deposition of complements (C1q and C3c), fibrin/fibrinogen‐related antigen (FRA), the expression of intercellular adhesion molecule‐1 (ICAM‐1), and the infiltration of leucocytes bearing β₂ integrins (leucocyte function associated antigen‐1 (LFA‐1), complement receptor 3 (CR3) and complement receptor 4 (CR4)) on renal biopsy specimens from 49 cases with Henoch‐Schoenlein purpura nephritis (HSPN), and 49 age‐matched cases with immunoglobulin A nephropathy (IgAN). the glomerular expression of ICAM‐1 was signifcantly correlated with the glomerular infiltration of leucocyte function associated antigen (LFA)‐1⁺ leucocytes in both diseases, and with that of CR3⁺ leucocytes in HSPN. the expression of ICAM‐1 was closely localized with the infiltration of LFA‐1⁺ leucocytes in the study with double immunostaining. the incidence and intensity of glomerular deposition of FRA were significantly higher in HSPN than in IgAN (P< 0.001), and those of C3c were significantly lower in HSPN than in IgAN (P< 0.001). the glomerular deposition of FRA was significantly correlated with the glomerular infiltration of CR4⁺ leucocytes in HSPN (P<0.05) but not in IgAN. In contrast, the glomerular deposition of C3c was significantly correlated with the glomerular infiltration of CR4⁺ leucocytes in IgAN (P<0.05), but not in HSPN. Studies with double immunostaining revealed a close association of CR4⁺ leucocytes with FRA deposition in HSPN and with C3c deposition in IgAN, respectively. the number of glomerular leucocytes bearing β₂ integrins was significantly correlated with urinary protein at the time of renal biopsy in both diseases. These results suggested the differential roles of β₂ integrins in the induction of glomerular injury in HSPN and IgAN. the ICAM‐1/LFA‐1 interaction may commonly be involved in the glomerular infiltration of leucocytes in both diseases. the ICAM‐1/CR3 interaction may be involved only in HSPN. Complement receptor 4 may function as a fibrin/fibrinogen receptor in HSPN, while CR4 may function as a complement receptor in IgAN.