Genotoxicity studies of glycidol fatty acid ester (glycidol linoleate) and glycidol

Glycidol fatty acid esters (GEs) are found in refined edible oils. Safety concerns have been alleged due to the possible release of glycidol (G), an animal carcinogen.     

Analysis of hepatitis C virus quasispecies transmission and evolution in patients infected through blood transfusion

BACKGROUND & AIMS: Studies on hepatitis C virus (HCV) quasispecies dynamics in the natural course of infection are rare owing to difficulties in obtaining samples from the early phase of infection. METHODS: We studied 15 patients from the Transfusion-Transmitted Viruses Study who seroconverted to anti-HCV after receiving infected blood. Follow-up serum samples were collected every 2-3 weeks for 6 months, at 10 months, and at 11-16 years. Viral quasispecies in the second envelope hypervariable region 1 (E2/HVR1) and 5' untranslated region (5'UTR) were analyzed with single-strand conformation polymorphism (SSCP) and heteroduplex mobility assay (HMA). RESULTS: Seven patients cleared infection within 7-24 weeks (mean, 14.0 wk) and 3 patients eventually became anti-HCV negative. In 6 patients with resolving hepatitis the SSCP band pattern remained stable, whereas in one patient minor changes appeared before clearance. In contrast, in all 8 patients progressing to chronicity, major changes in the E2/HVR1 quasispecies developed at 8-22 weeks (mean, 13.1 wk). Shannon entropy and medium mobility shift values derived from HMA gels remained stable in patients with resolving hepatitis but changed in those who developed chronic infection. Only 2 patients showed minor changes in 5'UTR. A decrease in E2/HVR1 complexity at the time of transmission (bottleneck) was found in 5 patients altogether. CONCLUSIONS: Changes in E2/HVR1 quasispecies 8-22 weeks after infection, likely caused by mounting immune pressure, were predictive of ensuing chronic infection, whereas stability was associated with resolution. Our study also showed that composition of HCV quasispecies may be preserved during transmission from host to host.     

Mutagenic potency of MMS‐induced 1meA/3meC lesions in E. coli

The mutagenic activity of MMS in E. coli depends on the susceptibility of DNA bases to methylation and their repair by cellular defense systems. Among the lesions in methylated DNA is 1meA/3meC, which is recently recognized as being mutagenic. In this report, special attention is focused on the mutagenic properties of 1meA/3meC which, by the activity of AlkB‐dioxygenase, are quickly and efficiently converted to natural A/C bases in the DNA of E. coli alkB⁺ strains, preventing 1meA/3meC‐induced mutations. We have found that in the absence of AlkB‐mediated repair, MMS treatment results in an increased frequency of four types of base substitutions: GC→CG, GC→TA, AT→CG, and AT→TA, whereas overproduction of PolV in CC101–106 alkB^?/pRW134 strains leads to a markedly elevated level of GC→TA, GC→CG, and AT→TA transversions. It has been observed that in the case of AB1157 alkB^? strains, the MMS‐induced and 1meA/3meC‐dependent argE3→Arg⁺ reversion occurs efficiently, whereas lacZ^?→ Lac⁺ reversion in a set of CC101–106 alkB^? strains occurs with much lower frequency. We considered several reasons for this discrepancy, namely, the possible variance in the level of the PolV activity, the effect of the PolIV contents that is higher in CC101–106 than in AB1157 strains and the different genetic cell backgrounds in CC101–106 alkB^? and AB1157 alkB^? strains, respectively. We postulate that the difference in the number of targets undergoing mutation and different reactivity of MMS with ssDNA and dsDNA are responsible for the high (argE3→Arg⁺) and low (lacZ^? → Lac⁺) frequency of MMS—induced mutations. Environ. Mol. Mutagen. 2009. © 2009 Wiley‐Liss, Inc.     

Genotoxicity and subchronic toxicity evaluation of dried Euglena gracilis ATCC PTA-123017

Euglena gracilis is a microalga capable of synthesizing various nutrients of interest in human and animal nutrition. When cultivated aerobically in the dark, Euglena synthesize paramylon, a storage polysaccharide comprised of high molecular weight beta-1,3-D-glucose polymers organized in cytoplasmic granules. Beta-glucans have been shown to have immune modulation effects, including anti-microbial, anti-tumor, and anti-oxidant properties, and metabolic effects, such as regulation of cholesterol and blood sugar levels. Preparations of E. gracilis and paramylon may therefore have potential utility as functional food ingredients for human and animal nutrition. A battery of toxicological studies was conducted on a dried preparation of E. gracilis and paramylon to support their safe food use. The dried alga was not genotoxic in a bacterial reverse mutation test and mammalian micronucleus test. In the subchronic toxicity study, rats were provided E. gracilis in the diet at levels of 0, 12,500, 25,000 or 50,000 ppm. Paramylon was provided at a concentration of 50,000 ppm. No effects that could be attributable to treatment were observed in clinical observations, body weight, food consumption, ophthalmology, hematology and clinical chemistry, urinalysis, and macroscopic and microscopic findings. A NOAEL of 50,000 ppm in the diet was determined for both ingredients.     

First-generation neuronal precursors in the crayfish brain are not self-renewing

Adult-born neurons in crayfish (Procambarus clarkii) are the progeny of 1st-generation precursor cells (functionally analogous to neuronal stem cells in vertebrates) that are located in a neurogenic niche on the ventral surface of the brain. The daughters of these precursor cells migrate along the processes of bipolar niche cells to proliferation zones in the cell clusters where the somata of the olfactory interneurons reside. Here they divide again, producing offspring that differentiate into olfactory local and projection neurons. The features of this neuronal assembly line, and the fact that it continues to function when the brain is isolated and perfused or maintained in organotypic culture, provide opportunities unavailable in other organisms to explore the sequence of cellular and molecular events leading to the production of new neurons in adult brains. Further, we have determined that the 1st-generation precursor cells are not a self-renewing population, and that the niche is, nevertheless, not depleted as the animals grow and age. We conclude, therefore, that the niche is not a closed system and that there must be an extrinsic source of neuronal stem cells. Based on in vitro studies demonstrating that cells extracted from the hemolymph are attracted to the niche, as well as the intimate relationship between the niche and vasculature, we hypothesize that the hematopoietic system is a likely source of these cells.     

Mohs' micrographic surgery as treatment for squamous dysplasia of the nail unit

We report a series of 14 cases of nail unit squamous cell carcinoma in situ/ Bowen's disease and squamous cell carcinoma (SCC) treated with Mohs micrographic surgery (MMS). MMS has been previously reported as an ideal treatment for nail unit SCC. This series adds to the current literature substantiating this claim, and also demonstrates the good outcomes achieved with secondary intention healing.     

中医“恐伤肾”模型血浆中分子物质与巯基含量的变化

探讨了“恐伤肾”模型动物血浆中分子物质与巯基含量的变化,结果表明,“恐伤肾”组小鼠血浆中分子物质升高、巯基降低,与正常对照组的差异有统计学意义,提示中分子物质和巯基均参与了“恐伤肾”的发病机理,且二者一的改变可作为“恐伤肾”所致肾虚亏损的敏感之一。     

大蒜素对甲基磺酸甲酯和环磷酰胺诱发果蝇伴性隐性致死的影响

用果蝇伴性隐性致死试验进行大蒜素的抗诱变性研究。大蒜素与甲基磺酸甲酯(MMS)同时喂饲果蝇,未能抑制MMS诱导的伴性隐性致死效应。而在先给MMS 24h后再给大蒜素则有抑制效应。大蒜素与环磷酰胺(Cy)同时给药有一定的抑制作用。提示大蒜素有一定抗诱变作用。     

油酸肺损伤所致RDS对肾功能的影响

目的：探讨油酸肺损伤所致ＲＤＳ时动脉血氧分压（ＰａＯ２）和中分子物质（ＭＭＳ）的改变对肾脏的影响。方法：用油酸（ＯＡ）０．１ｍｌ／ｋｇ体重静脉缓慢注入复制家兔ＲＤＳ模型，检测平均动脉血压（ＭＡＢＰ）、血气、肾功能和肾组织电镜以及血浆和肾组织ＭＭＳ的变化。结果：随着ＰａＯ２进行性下降，ＢＵＮ和ＰＣｒ明显增高，同时血浆和肾组织中的ＭＭＳ也相应明显增高，而且ＢＵＮ和ＰＣｒ与肾组织ＭＭＳ呈正相关关系。此外，ＭＡＢＰ亦进行性下降并与ＰａＯ２下降呈正相关关系。电镜下肾组织在ＲＤＳ早期和晚期有不同的改变。结论：油酸所致单纯ＲＤＳ过程可伴发急性肾功能障碍，此变化与ＰａＯ２下降、ＭＡＢＰ降低和ＭＭＳ增高有关