Vascular function and the role of oxidative stress in heart failure, heart transplant, and beyond

Using flow-mediated vasodilation (FMD), reactive hyperemia, and an acute oral antioxidant cocktail (AOC; vitamins C and E and α-lipoic acid), this study aimed to provide greater insight into altered vascular function and the role of oxidative stress in chronic heart failure patients with reduced ejection fraction (HFrEF) and at several time points beyond heart transplantation (HTx). A total of 61 age-matched subjects (12 healthy controls, 14 New York Heart Association class II and III HFrEF, and 35 HTx recipients [<3 years post-HTx, 5-10 years post-HTx, and >14 years post-HTx]) ingested either placebo (PL) or an AOC before FMD and reactive hyperemia testing of the brachial artery. Vascular function, as measured by FMD, was not different among the controls (6.8±1.9%), recent <3-year post-HTx group (8.1±1.2%), and the 5- to 10-year post-HTx group (5.5±1.0%). However, PL FMD was lower in the HFrEF (4.5±0.7%) and in the >14-year post-HTx group (2.9±0.8%). The AOC increased plasma ascorbate levels in all of the groups but only increased FMD in the controls (PL, 6.8±1.9%; AOC, 9.2±1.0%) and >14-year post-HTx recipients (PL, 2.9±0.8%; AOC, 4.5±1.3%). There were no differences in reactive hyperemia in any of the groups with PL or AOC. This cross-sectional study reveals that, compared with controls, vascular function is blunted in HFrEF, is similar soon after HTx, but is decreased with greater time post-HTx with free radicals implicated in this progression.     

Comparison of ER/PR and HER2 statuses in primary and paired liver metastatic sites of breast carcinoma in patients with or without treatment

Purpose  

The aim of this study was to determine whether estrogen receptor (ER)/progesterone receptor (PR) and human epidermal growth factor receptor type 2 (HER2) statuses between primary tumors and paired liver metastatic localizations of breast carcinoma were modified by treatment or during the natural metastatic process.     

Pharmacogenetic assessment of clinical outcome in patients with metastatic breast cancer treated with docetaxel plus capecitabine

Purpose

Docetaxel plus capecitabine, a commonly used chemotherapeutic regimen for metastatic breast cancer (MBC), is highly variable in its effectiveness. We aimed to investigate whether allelic variants of cytochrome P450 (CYP450) affected objective response, progression-free survival (PFS), and overall survival (OS) in MBC.

Patients and methods

79 SNPs in CYP450, whose minor allele frequency were ≥10%, were genotyped in 69 MBC patients who were treated with docetaxel plus capecitabine. Pearson’s χ² test or Fisher’s exact test was used to investigate the influence of SNPs on objective response as appropriate. Log-rank test was used to assess the association between SNPs and survival outcomes.

Results

There is no significant association between polymorphisms and both objective response and OS. Only one SNP, CYP1A1 rs1048943 A>G (Ile462Val), was significantly associated with PFS (P?=?0.0003). Multivariate analysis confirmed its prognostic significance for PFS (P?=?0.004).

Conclusion

CYP1A1 rs1048943 A>G (Ile462Val) polymorphism is a potential prognostic marker for survival outcome after docetaxel plus capecitabine chemotherapy in MBC patients. However, confirmatory study is needed to validate this finding.     

Downregulation of Notch-1/Jagged-2 in human colon tissues from Hirschsprung disease patients

Purpose  

Recent studies have shown that the Notch pathways play important roles in the differentiation and development of neurons. Hirschsprung disease (HSCR) is characterized by the absence of intramural ganglion cells in the nerve plexuses of the distal gut. However, putative Notch function in enteric nervous system (ENS) development and the etiology of HSCR is unknown.     

老年亲属供肾肾移植临床效果分析

目的 了解老年人供肾亲属肾移植临床效果. 方法 回顾性分析我院肾移植科2005年11月至2011年6月亲属活体肾移植的临床资料,按供者情况分为老年亲属供肾组36例(老年组),非老年亲属供肾组208例(非老年组).比较两组受者术后3d、7d、1个月、3个月、6个月、12个月、24个月、36个月血肌酐(SCr)水平和外科并发症、急性排斥、钙调磷酸酶抑制剂(CNI)肾毒性、移植肾功能延迟(DGF)发生率,并观察1年、3年人和(或)肾存活率. 结果 老年组受者SCr术后3d为(245.2±135.2)μmol/L、7d为(150.5±86.8)μmol/L、1个月为(140.6±42.5)μmol/L,高于非老年组的(185.6±148.4)μmol/L、(122.2±136.8)μmol/L、(117.8±33.2)μmol/L(分别为t=84.07、31.90、21.54,均P=0.000);CNI肾毒性发生率分别为22.2％(8/36)、1.9％(4/208),差异有统计学意义(x2=27.04,P=0.000);但两组受者术后3个月、6个月、12个月、24个月、36个月SCr水平和外科并发症、急性排斥、DGF发生率及1年、3年人和(或)肾存活率比较,差异无统计学意义(均P＞0.05). 结论 术前对老年供者进行严格筛选和综合评估,健康老年人亲属供者不应作为供者禁忌;但对老年人供肾亲属肾移植受者应注意CNI肾毒性.     

SEX DIFFERENCES IN DNA METHYLATION MAY CONTRIBUTE TO RISK OF PTSD AND DEPRESSION: A REVIEW OF EXISTING EVIDENCE

There are well‐established sex differences in the prevalence of certain mental disorders. Work in animal models has provided us with an emerging understanding of the role that epigenetic factors play in establishing sex differences in the brain during development. Similarly, work in animal models, and a more limited but growing literature based on human studies, has demonstrated that DNA methylation (DNAm) changes occur in response to environmental stress, with some of these occurring in a sex‐specific manner. In this review, we explore whether DNAm plays a role in contributing to the observed sex differences in prevalence of mental disorders in which stress contributes significantly to their etiologies, specifically posttraumatic stress disorder (PTSD) and depression. We propose that investigating sex differences in DNAm among genes known to influence brain development may help to shed light on the sexually dimorphic risk for, or resilience to, developing PTSD and depression.