Role of plasma protein and low-molecular weight substances in the change of hydroxyl radical scavenging activity in hemodialysis patients

While it is well known that hemodialysis (HD) patients with end stage renal failure are exposed to high oxidative stress, there is not a general opinion regarding whether antioxidant activity is high or low in these patients. We evaluated the variation of plasma hydroxyl radical scavenging activity (p-HRSA) by a single-session of HD in 69 patients by using a new system, reactive flow-injection electron spin resonance. And then comparing p-HRSA with their biochemical parameters, we tried to elucidate what components affected p-HRSA in the HD patients. The average of p-HRSA significantly increased after HD and the variation of p-HRSA by HD was correlated with that of plasma total protein (TP). In 5 patients however, their p-HRSA decreased after HD, in spite of increasing TP. In pre-HD, the p-HRSA values and hydroxyl radical scavenging activity of low-molecular weight fraction of plasma were significantly higher in these 5 patients than in patients whose p-HRSA increased after HD. These 5 patients were in an inflammatory state. These findings suggest that p-HRSA is mainly affected by TP, but caution should be exercised in patients who have high p-HRSA before HD and whose p-HRSA does not increase after HD.     

Caval invasion by liver tumor is limited

BACKGROUND: Successful hepatic resection with combined inferior vena cava (IVC) resection has been reported. The necessity of a combined IVC resection for hepatic malignancies that have attached to the IVC has not been fully evaluated. STUDY DESIGN: In this retrospective study, 162 lesions for which preoperative CT findings suggested attachment to the IVC were evaluated. Patient survival rates were examined according to type of tumor and the operative procedure. For adenocarcinoma lesions, several CT findings, including extent of the IVC circumference attached to the tumor compared with the whole IVC circumference (E(IVC)), were evaluated in conjunction with IVC resection. RESULTS: Among 162 lesions, 18 adenocarcinoma lesions were resected in combination with an IVC resection. Histologic IVC invasion was confirmed in eight patients. None of the 67 hepatocellular carcinoma lesions required concomitant IVC resection. Overall 5-year survival rate of the patients who underwent concomitant liver and IVC resections was 33.1%. Among the adenocarcinoma lesions, the positive predictive factors for IVC resection were an E(IVC) value > 25% and a peaked deformity of the IVC wall, according to a multivariate analysis. CONCLUSIONS: Most hepatic malignancies attached to the IVC wall can be completely removed without IVC resection. E(IVC) and deformity of the IVC on CT can be useful indicators for a concomitant liver and IVC resection. Careful separation of the liver and IVC is a key point for minimizing the size of the resected IVC and to avoid unnecessary IVC resection.     

Identification of glutathione depletion-responsive genes using phorone-treated rat liver

To identify candidate biomarker gene sets to evaluate the potential risk of chemical-induced glutathione depletion in livers, we conducted microarray analysis on rat livers administered with phorone (40, 120 and 400 mg/kg), a prototypical glutathione depletor. Hepatic glutathione content was measured and glutathione depletion-responsive gene probe sets (GSH probe sets) were identified using Affymetrix Rat Genome 230 2.0 GeneChip by the following procedure. First, probe sets, whose signal values were inversely correlated with hepatic glutathione content throughout the experimental period, were statistically identified. Next, probe sets, whose average signal values were greater than 1.5-fold compared to those of controls 3 hr after phorone treatment, were selected. Finally, probe sets without unique Entrez Gene ID were removed, ending up with 161 probe sets in total. The usefulness of the identified GSH probe sets was verified by a toxicogenomics database. It was shown that signal profiles of the GSH probe sets in rats treated with bromobenzene were strongly altered compared with other chemicals. Focusing on bromobenzene, time-course profiles of hepatic glutathione content and gene expression revealed that the change in gene expression profile was marked after the bromobenzene treatment, whereas hepatic glutathione content had recovered after initial acute depletion, suggesting that the gene expression profile did not reflect the hepatic glutathione content itself, but rather reflects a perturbation of glutathione homeostasis. The identified GSH probe sets would be useful for detecting glutathione-depleting risk of chemicals from microarray data.     

Transhepatic approach for a small paracaval tumor in repeat resection

To resect a small liver tumor located in the paracaval portion, we adopted transhepatic enucleation, i.e. enucleation of the tumor from the transected plane along the main portal fissure. In contrast to caudate lobectomy, this procedure can save dissection around the liver and vena cava, which would increase operation time and blood loss especially in repeat surgery after removal of Couinaud's segment VII or the right lateral sector. It can also minimize the liver parenchymal volume to be resected. The transhepatic enucleation would be a safe and recommendable surgical technique for a small paracaval tumor in repeat resection and/or in patients with poor liver functional reserve.     

Risk factors for the association of intracranial and aortic aneurysms

Summary This study investigated the association of intracranial aneurysms and abdominal aortic aneurysms to elucidate the incidence and independent risk factors for this association. Ultrasonography of the abdominal aorta was performed in 181 patients with 224 intracranial aneurysms. Six patients had suffered subarachnoid haemorrhage and the others had chronic disease or no symptoms. Magnetic resonance angiography was performed for confirmation if abdominal aortic aneurysm was identified by ultrasonography. Thirteen patients (7.2%) with 23 intracranial aneurysms had abdominal aortic aneurysms. Univariate analysis demonstrated that age (p < 0.01), size of intracranial aneurysms (p < 0.001), male sex (p < 0.01), multiplicity of intracranial aneurysms (p < 0.001), history of cerebrovascular diseases (p < 0.05), and current smoking (p < 0.0001) were significantly different between patients with and without this association. Multiple logistic analysis indicated that age (odds ratio [OR] 1.27, 95% confidence interval 1.08–1.48, p < 0.01), multiplicity (OR 22.1, 95% confidence interval 1.83–266.3, p = 0.01), size of intracranial aneurysms (OR 1.30, 95% confidence interval 1.10–0.54, p < 0.01), and current smoking (OR 33.3, 95% confidence interval 2.43–456.7, p = 0.01) were independent risk factors for the association. Patients with intracranial aneurysms who are older males with multiple or large intracranial aneurysms, and current smokers should be examined for abdominal aortic aneurysms using ultrasonography.     

Boutonniere deformity of the second toe after planter dislocation of proximal interphalangeal joint: a case report

The boutonniere deformity is a well-known deformity in the fingers, however, its appearance on a lessor toe is extremely rare. In the present case, the deformity resulted from a rupture of the central slip of the extensor tendon and the shift of the lateral bands to the planter side after reduction of a traumatic planter dislocation of the PIP joint of the second toe. Surgical repair of the extensor mechanism brought good results.     

Mixed peptide–chitosan membranes to mimic the biological activities of a multifunctional laminin α1 chain LG4 module

Laminin α1 chain LG4 module is multifunctional and interacts with syndecans and integrin α2β1 via AG73 (RKRLQVQLSIRT) and EF-I (DYATLQLQEGRLHFMFDLG) sites, respectively. Here, we conjugated the AG73 and EF1zz (ATLQLQEGRLHFXFDLGKGR, X: Nle) peptides on a chitosan membrane in various ratios to develop an LG4 mimic biomaterial. The AG73–chitosan membrane promoted strong cell attachment with membrane ruffling and the EF1zz–chitosan membrane promoted integrin-mediated cell adhesion with well-organized actin stress fibers. When AG73 and EF1zz were conjugated on a chitosan membrane with 1:9 molar ratio, the mixed peptide–chitosan membrane promoted the strong cell attachment and neurite outgrowth similar to that on the recombinant LG4 protein. Well-organized actin stress fibers and vinculin accumulated focal contacts were observed in the cells attached on the AG73:EF1zz (molar ratio = 1:9)–chitosan membrane. These results suggest that the mixed peptide–chitosan membrane interacts with both syndecans and integrin α2β1 and mimics the cell adhesion of a multifunctional LG4 protein. The mixed peptide–chitosan approach has potential as a multifunctional biomaterial for cell and tissue engineering.     

RANTES (CCL5) regulates airway responsiveness after repeated allergen challenge

RANTES (CC chemokine ligand 5) contributes to airway inflammation through accumulation of eosinophils, but the exact role of RANTES (CCL5) is not defined. C57BL/6 mice, sensitized by injection of ovalbumin (OVA) on Days 1 and 14, were challenged with OVA on Days 28, 29, and 30 (3 challenges, short-term-challenge model) or on Days 28, 29, 30, 36, 40, 44, and 48 (7 challenges, repeated-challenge model) and evaluated 48 h later. Anti-mouse RANTES was given intravenously, and recombinant mouse RANTES or PBS was given intratracheally. These reagents were given on Days 28, 29, and 30 in the short-term-challenge study and on Days 44 and 48 in the repeated-challenge study. After short-term challenge, there were no effects after administration of anti-RANTES or RANTES. In the repeated-challenge study, although control mice showed a decrease in airway hyperresponsiveness, administration of anti-RANTES sustained and enhanced airway hyperresponsiveness and increased goblet cell numbers. In contrast, administration of RANTES normalized airway function but reduced goblet cell numbers. IL-12 and IFN-gamma levels in BAL decreased in the anti-RANTES group and increased in the RANTES group. IFN-gamma-producing CD4 T cells in lung, and IFN-gamma production from lung T cells in response to OVA in the anti-RANTES group, were significantly decreased but were increased in the RANTES group. Anti-IFN-gamma, administered with RANTES, decreased the effects of RANTES on AHR after repeated challenge. These data indicate that RANTES plays a role in the regulation of airway function after repeated allergen challenge, in part through modulation of levels of IFN-gamma and IL-12.     

Toll-like receptors on hematopoietic progenitor cells stimulate innate immune system replenishment

Toll-like receptors (TLRs) are best known for their ability to recognize microbial or viral components and initiate innate immune responses. We showed here that TLRs and their coreceptors were expressed by multipotential hematopoietic stem cells, whose cell cycle entry was triggered by TLR ligation. TLR expression also extended to some of the early hematopoietic progenitors, although not the progenitor cells dedicated to megakaryocyte and erythroid differentiation. TLR signaling via the Myd88 adaptor protein drove differentiation of myeloid progenitors, bypassing some normal growth and differentiation requirements, and also drove lymphoid progenitors to become dendritic cells. CD14 contributed to the efficiency of lipopolysaccharide (LPS) recognition by stem and progenitor cells, and LPS interacted directly with the TLR4/MD-2 complex on these cells in bone marrow. Thus, the preferential pathogen-mediated stimulation of myeloid differentiation pathways may provide a means for rapid replenishment of the innate immune system during infection.