The effect of iron on the biodistribution of bone scanning agents in humans

Nine patients with chronic iron overload, resulting from either repeated transfusions or hemochromatosis, had bone scans that were characterized by a reduction of bony uptake, marked increase in renal activity, and a significant increase in soft-tissue accumulation of 99mTc-labeled bone-seeking agents. These findings were supported by semiquantitative computer analysis. The probable mechanisms of altered biodistribution and the possible role of serum ferritin are discussed. The importance of realizing the effect of excess iron on skeletal scintigraphy is further emphasized by the results of bone scanning in another patient in whom acute iron overload following infusion of iron-dextran resulted in excessive blood pool labeling.     

Oxidative stress and antioxidant defenses in goldfish liver in response to short-term exposure to arsenite

Arsenic is an environmental pollutant capable of causing oxidative stress, disturbance of metabolism, and cancer development. The present study was undertaken to investigate the effects of exposure to sodium arsenite on the glutathione pool, lipid peroxidation, protein carbonyl levels, global DNA methylation, and activities of six antioxidant enzymes in goldfish liver. In a preliminary experiment, 7-day exposure to 200 microM sodium arsenite, but not 10 or 100 microM, disturbed the glutathione status. A detailed investigation of oxidative stress development and antioxidant responses was further examined during different periods of exposure to 200 microM sodium arsenite. This treatment increased lipid peroxide levels after 1 and 4 days of exposure but did not affect thiobarbituric acid reactive substances and protein carbonyls. Oxidized glutathione and the oxidative stress index rose after 4 days, but de novo glutathione synthesis decreased both parameters after 7 days. Activities of the main antioxidant enzymes-superoxide dismutase, catalase, and glutathione peroxidase, were elevated after longer periods of exposure, indicating an enhanced antioxidant response. Arsenite exposure led to DNA hypomethylation, which is an early marker of disturbed epigenetic regulations. The findings suggest that goldfish livers cope with arsenic-induced oxidative stress mainly through adaptive changes in the glutathione pool and antioxidant enzymes.     

Ablating the Imperceptible: A Novel Application of Para‐Hisian Pacing

In some elderly patients with atrial fibrillation, especially in combination with heart failure, a rate control strategy may be preferred. When pharmacological therapy is ineffective or not tolerated, it is reasonable to perform atrioventricular (AV) node ablation with ventricular pacing. We describe a case in which this approach was necessary for management. However, the presence of periprocedural, drug‐induced AV block just before ablation provided a unique and challenging circumstance. We discuss the steps taken to ensure a successful procedure.     

五子衍宗复方总多糖抗细胞氧化应激损伤和细胞凋亡的研究

目的 对具有肝脏保护作用的中药五子衍宗复方进行分离,考察五子衍宗复方提取物中总多糖抗氧化应激损伤和细胞凋亡的活性.方法 本实验对中药五子衍宗复方的原药材用50%乙醇提取后,通过水提醇沉得到总多糖.利用t -BHP染毒HepG2细胞建立氧化应激损伤模型,检测不同浓度五子衍宗复方总多糖对细胞活力、细胞内活性氧组ROS、脂质...     

Aloe vera non-decolorized whole leaf extract-induced large intestinal tumors in F344 rats share similar molecular pathways with human sporadic colorectal tumors

Aloe vera is one of the most commonly used botanicals for various prophylactic and therapeutic purposes. Recently, NTP/NCTR has demonstrated a dose-dependent increase in large intestinal tumors in F344 rats chronically exposed to Aloe barbadensis Miller (Aloe vera) non-decolorized whole leaf extract (AVNWLE) in drinking water. The morphological and molecular pathways of AVNWLE-induced large intestinal tumors in the F344 rats were compared to human colorectal cancer (hCRC) literature. Defined histological criteria were used to compare AVNWLE-induced large intestinal tumors with hCRC. The commonly mutated genes (Kras, Ctnnb1, and Tp53) and altered signaling pathways (MAPK, WNT, and TGF-β) important in hCRC were evaluated within AVNWLE-induced large intestinal tumors. Histological evaluation of the large intestinal tumors indicated eight of twelve adenomas (Ads) and four of twelve carcinomas (Cas). Mutation analysis of eight Ads and four Cas identified point mutations in exons 1 and 2 of the Kras gene (two of eight Ads, two of four Cas), and in exon 2 of the Ctnnb1 gene (three of eight Ads, one of four Cas). No Tp53 (exons 5-8) mutations were found in Ads or Cas. Molecular pathways important in hCRC such as MAPK, WNT, and TGF-β signaling were also altered in AVNWLE-induced Ads and Cas. In conclusion, the AVNWLE-induced large intestinal tumors in F344 rats share several similarities with hCRC at the morphological and molecular levels.     

澳门特别行政区初三学生的睡眠质量、睡眠模式与抑郁、焦虑情绪

目的:了解澳门特别行政区初三年级学生的睡眠质量、模式与抑郁、焦虑情绪的关系。方法:抽取澳门535名初中三年级学生,用匹兹堡睡眠质量指数量表(PSQI)评估睡眠质量,爱泼沃斯思睡量表(ESS)以及清晨型和夜晚型量表(MEQ)调查白天思睡与睡眠模式,用贝克抑郁量表(BDI)、状态-特质焦虑量表(STAI)调查抑郁、焦虑状况。结果:PSQI和ESS得分分别为(5.2±2.6)和(8.4±4.7),女生PSQI[(5.5±2.5)vs.(4.8±2.6)]和ESS[(8.9±4.6)vs.(8.0±4.8)]得分高于男生(均P0.05)。MEQ平均得分(13.3±3.1),女生得分低于男生[(12.8±3.0)vs.(13.7±3.2),P0.01]。学生周末和假日的总睡眠时间长于平日总睡眠时间[(608±106)min,(605±109)min vs.(457±75)min],女生周末[(628±110)min vs.(590±97)min]和假期[(631±109)min vs.(581±103)min]平均睡眠时间长于男生(均P0.01)。BDI和STAI得分分别为(13.5±10.3)、(78.9±17)。睡眠质量差和白天思睡者MEQ得分、上学日睡眠时间低于睡眠质量好和无白天思睡者MEQ得分,而睡眠质量差和白天思睡者BDI得分高于睡眠质量好和无白天思睡者BDI得分(均P0.05)。PSQI分别与ESS、BDI,以及STAI中的TAI分呈正相关(r=0.27、0.37、0.12,均P0.05),而与M EQ和上学日总睡眠时间呈负相关(r=-0.30、-0.30,均P0.05)。结论:睡眠质量差和白天思睡在澳门初三学生中较为普遍,他们在上学日的平均睡眠时间不足,但在周末和假日则延长睡眠时间以作补充,其中女生更易出现上述睡眠模式。大部分学生有轻度抑郁,睡眠质量差可能与其抑郁、焦虑状况相关。     

Acute intoxications in two university hospitals in Burkina Faso

Introduction

Acute intoxications become more and more a serious problem in developing countries. However, epidemiologic data are very scarce in these countries.

Objective

To describe the characteristics of acute intoxications in two University Hospitals of Ouagadougou (Burkina Faso).

Methods

All cases admitted to the emergency services of the two sole University Hospitals of Ouagadougou from July 1, 2006 to June 30, 2007, were included. We analysed the medical records for demographical and etiological characteristics of the acute poisoned-patients.

Results

Acute poisoned-patients (436) represented 1.9% of the patients admitted to these services. The majority of acute poisoned-patients were pre-school children followed by young adults. Accidental intoxications (70.8%) were more common than intentional (28.9) and suicidal attempts (0.3%). Among poisoned-patients, female patients represented a great majority. Pharmaceuticals were the most common cause of acute intoxication, followed by chemicals, animals'' toxins, food, alcohol and addictive drugs.

Conclusion

Our study revealed that pharmaceuticals were the most common cause of acute intoxications. The great majority of poisoned-patients were young. Female patients were the major poisoned-patients. Most admissions in the emergency services due to acute intoxications resulted from accidental poisoning.     

Epigenetic alterations in liver of C57BL/6J mice after short-term inhalational exposure to 1,3-butadiene

Background

1,3-Butadiene (BD) is a high-volume industrial chemical and a known human carcinogen. The main mode of BD carcinogenicity is thought to involve formation of genotoxic epoxides.

Objectives

In this study we tested the hypothesis that BD may be epigenotoxic (i.e., cause changes in DNA and histone methylation) and explored the possible molecular mechanisms for the epigenetic changes.

Methods and Results

We administered BD (6.25 and 625 ppm) to C57BL/6J male mice by inhalation for 2 weeks (6 hr/day, 5 days a week) and then examined liver tissue from these mice for signs of toxicity using histopathology and gene expression analyses. We observed no changes in mice exposed to 6.25 ppm BD, but glycogen depletion and dysregulation of hepatotoxicity biomarker genes were observed in mice exposed to 625 ppm BD. We detected N-7-(2,3,4-trihydroxybut-1-yl)guanine (THB-Gua) adducts in liver DNA of exposed mice in a dose-responsive manner, and also observed extensive alterations in the cellular epigenome in the liver, including demethylation of global DNA and repetitive elements and a decrease in histone H3 and H4 lysine methylation. In addition, we observed down-regulation of DNA methyltransferase 1 (Dnmt1) and suppressor of variegation 3–9 homolog 1, a histone lysine methyltransferase (Suv39h1), and up-regulation of the histone demethylase Jumonji domain 2 (Jmjd2a), proteins responsible for the accurate maintenance of the epigenetic marks. Although the epigenetic effects were most pronounced in the 625-ppm exposure group, some effects were evident in mice exposed to 6.25 ppm BD.

Conclusions

This study demonstrates that exposure to BD leads to epigenetic alterations in the liver, which may be important contributors to the mode of BD carcinogenicity.     

Role of epigenetic events in chemical carcinogenesis--a justification for incorporating epigenetic evaluations in cancer risk assessment

Recent advances in field of cancer research have established that all major human cancers, in addition to having a large number of genetic alterations, exhibit prominent epigenetic abnormalities that can be used as biomarkers for the molecular diagnosis of cancer. Currently, epigenetic markers have shown promise in establishing the diagnosis and prognosis of all major human cancers. Additionally, accumulating evidence suggests that epigenetic alterations may be early indicators of genotoxic and non-genotoxic carcinogenic exposure and may be used as biomarkers in the assessment of the carcinogenic potential of environmental chemical and physical agents. This review presents current evidence on the role of epigenetic alterations in chemical carcinogenesis and highlights a number of advantages of epigenetic biomarkers over traditionally used methods in cancer risk assessment.