Background-Blood transfusion has been recognised as a risk factor for the development of retinopathy of prematurity (ROP) or chronic lung disease (CLD) in preterm infants, but the precise mechanism involved is not understood. Aim-To investigate the level of nontransferrin bound "free" iron, which has the potential to promote the generation of reactive oxygen species, and its redox status in the plasma of preterm infants immediately before and after blood transfusion. Methods-Twenty one preterm infants with a median gestational age and birth weight of 27 weeks and 1021 g respectively were prospectively enrolled in the study. Sixteen of the 21 infants developed ROP and/or CLD. The infants were transfused with concentrated red blood cells at a median age of 32 days. The plasma concentration of total bleomycin detectable iron (BDI) was measured and also the ferrous iron (Fe 2+ ) activity by bleomyciniron complex dependent degradation of DNA. Results-Even before blood transfusion, BDI was detectable in one third of the blood samples, and all but one sample had ferrous iron activity. After transfusion, both BDI and ferrous iron activity were significantly increased, in contrast with the situation in full term infants. Plasma ascorbic acid (AA) concentration was significantly decreased after blood transfusion, whereas the level of its oxidation product, dehydroascorbic acid (DHAA), and the DHAA/AA ratio were significantly increased compared with before the transfusion. The activity of plasma ferroxidase, which converts iron from the ferrous to the ferric state, was appreciably decreased in preterm infants, as expected from their very low plasma caeruloplasmin concentration. Conclusions-Plasmanon-transferrin bound iron was significantly increased in preterm infants after blood transfusion and existed partly in the ferrous form, because of the low ferroxidase activity and the reduction of ferric iron (Fe 3+ ) by ascorbic acid. This finding was specific to preterm infants and was not observed in full term infants after blood transfusion. Non-transferrin bound "free" iron may catalyse the generation of reactive oxygen species, which may be responsible for the clinical association of blood transfusion with ROP and CLD. (Arch Dis Child Fetal Neonatal Ed 2001;84:F188-F193)
Early apoptotic Jurkat T cells undergo capping of CD43, and its polylactosaminyl saccharide chains serve as ligands for phagocytosis by macrophages. This suggests the presence of a polylactosaminoglycan-binding receptor on macrophages. Here we show that this receptor is nucleolin, a multifunctional shuttling protein present in nucleus, cytoplasm, and on the surface of some types of cells. Nucleolin was detected at the surface of macrophages, and antinucleolin antibody inhibited the binding of the early apoptotic cells to macrophages. Nucleolin-transfected HEK293 cells expressed nucleolin on the cell surface and bound the early apoptotic cells but not phosphatidylserine-exposing late apoptotic cells. This binding was inhibited by anti-nucleolin antibody, by polylactosamine-containing oligosaccharides, and by anti-CD43 antibody. Deletion of the antibody binding region of nucleolin resulted in loss of the apoptotic cell-binding ability. Moreover, truncated recombinant nucleolin in solution containing this region blocked the apoptotic cell binding to macrophages, and the blocking effect was cancelled by the oligosaccharides. These results indicate that nucleolin is a macrophage receptor for apoptotic cells.Macrophages and other phagocytes recognize and ingest apoptotic cells in tissue, preventing their lysis and subsequent release of harmful or immunogenic intracellular components. Therefore, clearance of apoptotic cells by phagocytes is crucial in the maintenance of tissue turnover and homeostasis. Moreover, it has been suggested that the apoptotic cell-ingested phagocytes play a role in suppression or resolution of inflammation (1-5).Cells undergoing apoptosis display a variety of "eat me" signals, namely cell-surface changes to be recognized by phagocytes. These include externalization of phosphatidylserine (PS),3 as yet little identified alterations of carbohydrates, and unidentified alterations of other membrane components such as intercellular adhesion molecule-3 and "thrombospondin binding sites" (1-5). Among these, the most common and the best-characterized change is externalization of PS, although the mechanism of externalization has not been fully understood (6, 7).In contrast to the poor understanding of the nature of eat me signals, various proteins of phagocyte membrane or in extracellular fluid have been reported as receptors or bridging factors for apoptotic cells. For externalized PS on apoptotic cells, CD36 (8), CD68 (9), CLA-1 (10), LOX-1 (11), and PS receptor (12) have been reported as phagocyte receptors; a serum protein  2 -glycoprotein I (13), complement component C3bi (14), and milk fat globule-epidermal growth factor-factor 8 (15) have been reported to bridge apoptotic cells and phagocytes through exposed PS. For intercellular adhesion molecule-3 on apoptotic cells, CD14 was suggested to be a macrophage receptor (16). Thrombospondin is also known as a bridging protein between unidentified sites on apoptotic cells and CD36 or vitronectin receptor (␣ v  3 integrin) on phagocytes (17). In addi...
Forty healthy individuals with a low defecation frequency were selected, and the effects of intake of a fermented milk beverage that contains Lactobacillus casei strain Shirota (LcS) at 4 × 10 9 bacteria/bottle for 2 weeks (1 bottle/day) on the defecation frequency and intestinal microflora were evaluated by the placebo-controlled double-blind cross-over scheme. Defecation frequency both in times per week and days per week significantly increased in the LcS beverage period compared with the frequency before the beginning of intake. The differences were more notable in those with a stronger tendency to constipation (frequency of defecation before intake ≤ 4.0 times/week, n=21), and the frequency of defecation in the LcS beverage period was significantly higher than in the placebo period. The stool smell and feeling of completion of voiding improved significantly in the LcS beverage period compared with the placebo period, and in those with a stronger tendency to constipation, the stools were significantly softened compared with the state before intake. The number of bifidobacteria and their percentage in the total number of fecal bacteria in the LcS beverage period increased significantly compared with the levels before intake and were significantly higher than the values in the placebo period. No marked change due to the intake of the LcS beverage was observed in the other components of the microflora, the organic acid contents, stool pH, water content, or contents of putrefactive metabolites. These results suggest that intake of the probiotic fermented milk beverage conditions the intestines by improving the state of bowel movements and stool quality and increasing the fecal population level of bifidobacteria.
Objective: To examine the effect of purple sweet potato (PSP) beverage rich in acylated anthocyanins on serum hepatic biomarkers in healthy Japanese men. Design: A randomized, double-blind, placebo-controlled, parallel study. Setting: Kumamoto in Japan. Subjects: Healthy adult men (30-60 years) with borderline hepatitis who had one or more of serum g-glutamyl transferase (GGT), aspertate aminotransferase (AST) and alanine aminotransferase (ALT) levels over normal ranges, and who were negative for hepatitis virus were openly recruited by an advertisement. Of the 48 persons enrolled, 38 (mean age 43.0 years (30-54 years)) completed the study. Methods: The subjects were randomly assigned to the PSP group and the placebo group. During the 8-week intervention, the subjects in the PSP group consumed two bottles of the PSP beverage with acylated anthocyanins (200.3 mg anthocyanins per 125 ml per bottle) per day, and the subjects in the placebo group, two bottles of a placebo beverage (1.7 mg anthocyanins per 125 ml per bottle). All of the data measured were analyzed by two-way repeated measures analysis of variance (ANOVA) with groups and times. The data of the hepatic markers were analyzed using the Dunnett multiple comparison among the time points and t-test between groups at the same time point. Two-sided Po0.05 were defined as the level of significance. Results: Serum GGT, AST and ALT levels showed interactions (Po0.05) between the beverage groups and time; the others were not affected. The PSP beverage group showed lower hepatic marker levels than the placebo group during the ingestion period, particularly the GGT level (À14.1 IU/l, 95% Confidence intervel (CI) À25.4 to À2.7, P ¼ 0.017 at 2 weeks; À16.8 IU/l, 95% CI À36.2 to 2.5, P ¼ 0.081 at 4 weeks; À26.7 IU/l, 95% CI À47.6 to À5.7, P ¼ 0.014 at 6 weeks and À27.9 IU/l, 95% CI À49.9 to À5.9; P ¼ 0.014 at 8 weeks). No correlation between alcohol consumption and each hepatic biomarker level before and after the ingestion was observed. Conclusion: The intake of the PSP beverage significantly decreased the serum levels of hepatic biomarkers, particularly the GGT level, in healthy men with borderline hepatitis.
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