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 value and limitation of resting 201Tl reinjection after stress-redistribution imaging for the assessment of myocardial viability: comparison with wall motion improvement by revascularization]

Clinical value and limitation of resting reinjection of small dose of thallium (37 MBq) for the assessment of myocardial viability were evaluated. The results were compared with the degree of wall motion improvement by revascularization to infarcted myocardium supplied by chronic total vessels in 12 patients with old myocardial infarction. Thallium uptake was visually scored and judged as normal, reversible defect (Group 1), new fill in after reinjection (Group 2A), and no fill in even after reinjection (Group 2B). Among 53 segments with initial perfusion abnormality, 21 segments reverted to almost normal, while 32 segments remained abnormal on redistribution images. New fill in after reinjection was observed in 11 segments of 32 segments showing persisting defect on stress and delayed image (37%). Wall motion score index of Group 2A improved significantly higher than Group 2B (p less than 0.01) and almost equal to Group 1, suggesting the utility of reinjection for the assessment of tissue viability which may be underestimated by conventional imaging. But significant wall motion improvement (greater than or equal to 0.6 mean SD/chords) was observed in 6 segments (29%) of 21 segments showing neither redistribution nor fill in after reinjection. These data indicate that small dose of thallium reinjection may enhance detection of viable but jeopardized myocardium, although some underestimation of viability remained to be resolved.     

Diversity in DNA rearrangements and in RNA expressions of immunoglobulin gene on common variable immunodeficiency.

Six heterogeneous common variable immunodeficiency (CVID) patients were analysed for germ-line DNA, DNA rearrangements, and RNA expressions of immunoglobulin (Ig) gene by Southern or northern blotting using appropriate probes. We detected no polymorphism in neutrophil DNA hybridized to a C mu and a C gamma probe. In three patients, both serum Ig and Ig-bearing cells were scarcely detected, and by northern hybridization methods, neither mu mRNA, gamma mRNA, alpha mRNA nor kappa mRNA was detected. However, one Epstein-Barr virus-transformed B lymphoblastoid cell line (LCL) of these three patients was different from the germ line in the region of JH, C gamma, and C kappa, and expressed mu mRNA at a higher level. The B cell defects of these three patients lay on the B cell maturation stage similar to X-linked agammaglobulinaemia (XLA). In two others among the six CVID patients, serum IgM and IgM-bearing cells were detected to a certain degree, and by northern hybridization, mu mRNA was detected at a lower level, but neither mu mRNA, alpha mRNA, nor kappa mRNA was detected. One LCL of these two patients could express mu mRNA at the normal level. In the last patient, the serum IgM was normal, serum IgG and IgA were somewhat low, Ig-bearing cells were normal, mu mRNA and kappa mRNA were detected at the normal level, and gamma mRNA and alpha mRNA were detected at a lower level. The defect of this patient affected the class switch stage. These results showed that primary B cell defects in CVID occurred at several B cell differentiation stages which could be classified by expression of the Ig gene, and at the degree of clonal diversity in the B cell repertoire. Furthermore, this study provides support for the idea that the CVID defect is related to a more generalized cellular function, such as regulating the proliferation and/or clonal expansion of cells of the B lymphoid lineage.     

An experimental study on direct revascularization of bronchial circulation by microvascular anastomosis.

The effects of direct revascularization of the bronchial artery after bronchoplasty were estimated by laser Doppler velocimetry and india ink injection in dogs. Bronchoplastic surgery at the right main bronchus was performed in all dogs, and the bronchial artery was reconstructed using the internal thoracic artery in the reconstruction group. The mucosal blood flow was measured at the distal side of the anastomosis. India ink was injected into the aorta in the nonreconstruction group and into the internal thoracic artery in the reconstruction group. The peripheral blood flow had diminished immediately after surgeries to 59% of the baseline value and took 14 days to recover to the baseline value in the nonreconstruction group. However, in the reconstruction group, the blood flow recovered at once to 78% of the baseline value and had returned to that value in 5 days. Statistically significant differences were noted between the groups from just after operation to day 7. India ink data confirmed these findings. In the nonreconstruction group, no ink was observed in the peripheral bronchial vessels on day 3; it was noted in part of the vessels on day 7 and in most on day 14. On the other hand, a relatively large number of vessels were stained just after operation in the reconstruction group. Thus reconstruction of the bronchial artery by means of the anastomosis with the internal thoracic artery can be said to be a useful and effective method for preventing airway ischemia.     

Comparison of anticonvulsant effects of valproic acid entrapped in positively and negatively charged liposomes in amygdaloid-kindled rats

Intraperitoneal injection of free valproic acid (VPA) suppressed amygdaloid-kindled seizure 1 h after injection in rats, but had no effect at 24 h. VPA entrapped in positively charged liposomes showed a prolonged anticonvulsant effect lasting for 2 days, while the effect evaluated at 1 h was not different from that with free VPA. VPA entrapped in negatively charged liposomes exerted a significantly stronger effect at 1 h than did free VPA, while it had no significant effect at 24 h. These results suggest that surface charges on liposomes play an important role in modifying the anticonvulsant effect of VPA.     

Enhanced clearance of lactic dehydrogenase-5 in severe combined immunodeficiency (SCID) mice: effect of lactic dehydrogenase virus on enzyme clearance.

The lactic dehydrogenase (LDH) level in plasma and the clearance of LDH in C.B-17 scid (severe combined immunodeficiency; SCID) mice were compared with those in C.B-17 or BALB/cCrSlc mice with or without lactic dehydrogenase virus (LDV) infection. The resting enzyme level in SCID mice showed little difference from that in C.B-17 or BALB/cCrSlc mice. The degree of increased plasma LDH level in SCID mice was lower than that in C.B-17 and BALB/cCrSlc mice after LDV infection. To assess the mechanisms of decrease in LDH elevation in SCID mice infected with LDV, virus replication was compared in SCID and BALB/cCrSlc mice. The infectivity titre of plasma in SCID mice was higher (more than 10 times) than that in BALB/cCrSlc mice. Moreover, the percentage of virus antigen positive Kupffer cells was higher in SCID mice than that in BALB/cCrSlc mice. The level of endogenous LDH release as a result of carbon tetrachloride treatment was similar in the SCID and BALB/cCrSlc mice. The clearance rate of endogenous LDH was greater in SCID mice than in BALB/cCrSlc mice with or without LDV infection. The rate of clearance of intravenously injected porcine LDH-5, but not porcine LDH-1, was enhanced in SCID mice as compared with that in BALB/cCrSlc mice. Furthermore, carbon clearance was higher in SCID mice than that in BALB/cCrSlc mice. These results suggest that the smaller increase of plasma LDH after infection might be due, at least in part, to the enhanced LDH-5 clearance function by macrophages in SCID mice.     

Alterations of nuclear pores in preneoplastic and neoplastic rat liver lesions induced by 2-acetylaminofluorene

The nuclear pore density and area were measured on freeze-fracturednuclei of ACI/N rat liver altered foci, adenomas and carcinomasinduced by 2-acetylaminofluorene, and compared with those ofnormal hepatocytes. The pore density of nuclei from these preneoplasticand neoplastic lesions was significantly higher than that ofhepatocytes, but there was no difference between lesions. Thearea of nuclear pores of the focus cells did not differ fromnormal hepatocytes, whereas the areas of pores of adenoma andcarcinoma cells were increased. Moreover, the nuclear pore areaof carcinomas was significantly greater than that of adenomas.These results suggest that some changes may occur in nuclearpores in the progress of tumorigenesis.     

Teaching nurses about neuromotor development: an evaluative study.

A neuromotor screening tool, The Chandler Movement Assessment of Infants Screening Test (CMAI-ST), was selected to teach nurses who care for premature infants about neuromotor development. After training with the CMAI-ST, the nurses were more adept at recognizing major components of neuromotor development.