Effect of intravenous iron administration frequency on AOPP and inflammatory biomarkers in chronic hemodialysis patients: a pilot study

ObjectivesIntravenous iron administration (IVIR) is effective for correcting anemia in hemodialysis (HD) patients, but it also enhances the generation of hydroxyl radicals. Previously we demonstrated that IVIR increases oxidized serum albumin levels in HD patients. However, the effect of IVIR frequencies on the oxidative stress has never been studied before. Therefore, we compared the two IVIR schedules recommended by the Japanese Society for Dialysis Therapy guideline 2004 by measuring oxidized albumin in chronic HD patients.Design and methodsTwenty-two HD patients were divided into two IVIR protocol groups (group I: 40 mg of iron 3 times a week for 4 weeks, group II: 40 mg of iron once a week for 3 months). These protocols differ in IVIR frequency, but receive the same amount of iron (total 520 mg). We compared these two regimens by determining the levels of hemoglobin, serum ferritin, advanced oxidation protein products (AOPP), and oxidized albumin at 0, 4, 8, 12, 16, and 20 weeks.ResultsBoth patient groups resulted in a similar and significant increase in hemoglobin levels, whereas group I markedly induced AOPP and oxidation of serum albumin than group II at 4 weeks (P < 0.05). AOPP and oxidation of serum albumin was also gradually declined by 20 weeks, while the oxidized albumin and AOPP in group II was not significantly changed during the entire experimental period. Transferrin saturation and serum ferritin levels were also increased in group I compared with group II at 4 weeks (P < 0.001). In addition, we found a strong positive correlation between oxidized albumin and serum ferritin levels (r = 0.615, P < 0.05), suggesting the possibility that the accumulation of iron stores has a causative role in the progression of oxidative stress in HD patients treated with IVIR.ConclusionsThe results of this study indicate that lower frequency IVIR protocol is recommended to reduce IVIR-induced oxidative stress in HD patients.     

Depressed-type （0-IIc） colorectal neoplasm in patients with family history of first-degree relatives with colorectal cancer： A cross-sectional study

AIM: To investigate the correlation of depressed-type (0-IIc) colorectal neoplasm and family history of first-degree relatives (FDR) with colorectal cancer (CRC). METHODS: This cross-sectional study was conducted from June 2000 to October 2002 at National Cancer Center Hospital East. Eligible patients undergoing initial total colonoscopy were surveyed regarding family history of CRC among FDR by a questionnaire prior to colonoscopic examinations. All endoscopic findings during colonoscopy were recorded and the macroscopic classification of the early stage neoplasm/cancer was classified into two types (0-IIc vs non 0-IIc). Odds ratios (OR) and 95% confidence intervals (CI) were calculated by univariate and multivariate logistic regression to estimate the association between macroscopic features and clinicopathological data including gender, age, and family history of FDR with CRC. RESULTS: The OR of an association between family history of FDR with CRC and overall early stage neoplasm adjusted by gender and age was 1.85 (95% CI: 1.31-2.61, P = 0.0004), that for non 0-IIc neoplasm was 1.71 (95% CI: 1.22-2.41, P = 0.0017) and for 0-IIc colorectal neoplasm was 2.78 (95% CI: 1.49-5.16, P = 0.0031). CONCLUSION: Our study shows a significant association between a family history of FDR with CRC and 0-IIc colorectal neoplasm. When patients with a family history of FDR with CRC undergo colonoscopy, colonoscopists should check carefully for not only polypoid, but also depressed-type (0-IIc) lesions.     

Microsatellite instability, prognosis and metastasis in gastric cancers from a low-risk population

We examined 169 cases of gastric adenocarcinoma for microsatellite instability (MSI), using a panel of 8 microsatellite markers. Of these cases, 142 were from the United States, a country of relatively low risk for gastric cancer. Comparing microdissected tumors to normal cells from the same patient, we classified tumors as being microsatellite-stable (MSS) or having a low frequency of MSI (MSI-L, up to 30% of markers different in the tumor) or a high frequency of MSI (MSI-H, 30% or more of markers different). Among our American cases, we identified 26 (18.2%) showing MSI-H and 15 (10.6%) showing MSI-L. Twenty cases were from Korean patients, and they showed no significant differences in proportions of MSI-H and MSI-L from the American cases. MSI-H tumors in the American patients were characterized by elevated frequencies of band shifts in repeat sequences of the BAX (50%), transforming growth factor-beta receptor type II (TGFbetaRII, 68.9%), beta(2)-microglobulin (21.4%) and E2F4 (51.7%) genes. Alterations in E2F4 in MSI-H tumors were always integral multiples of 3 nucleotides lost or gained, which would not cause a frameshift mutation, and within the range of normal polymorphisms for this sequence. North American patients (n = 127) with MSI-H and MSI-L tumors had a longer median survival of 541 days and 587 days, respectively, compared to 265 days for patients with MSS tumors (p = 0.027). This survival difference may result from a significantly greater tendency for metastases in the MSS group (p = 0.031).     

Identification of cytochrome P450 isoform involved in the metabolism of YM992, a novel selective serotonin re-uptake inhibitor, in human liver microsomes

1. In vitro studies were conducted to identify the hepatic cytochrome P450 isoform involved in the metabolism of YM992, ((S)-2-[[(fluoro-4-indanyl)oxy]methyl]morpholine monohydrochloride), a novel serotonin re-uptake inhibitor, in human liver microsomes. 2. Microsomes prepared from yeast expressing CYP1A1, CYP1A2 and CYP2D6 effectively metabolized YM992. A significant correlation was observed between the rate of YM992 metabolism and 7-ethoxyresorufin O-deethylation, CYP1A1/2 specific activity, in liver microsomes from 16 individual donors (r2 = 0.628, p < 0.001). Alpha-naphtoflavone and isosafrole, CYP1A1/2 inhibitors, suppressed the metabolism of YM992 in human liver microsomes in a concentration-dependent manner. 3. The metabolism of YM992 in human liver microsomes was inhibited by approximately 95% by antibodies which recognize both CYP1A1 and CYP1A2 whereas antibodies specific for CYP1A1 did not show inhibitory effects. 4. The same major metabolites, M6 and M7, were generated from YM992 after incubation with human liver microsomes and recombinant human CYP1A2. 5. These results suggest that the metabolism of YM992 in human liver microsomes is mainly catalysed by CYP1A2, and that YM992 might increase plasma concentration of concomitant drugs metabolized by CYP1A2 due to competitive inhibition.