Species differences in the hydrolysis of 2-cyanoethylene oxide, the epoxide metabolite of acrylonitrile

The carcinogenic effects of acrylonitrile in rats are believedto be mediated by its DNA-reactive epoxide metabolite, 2-cyanoethyleneoxide (CEO). Previous studies have shown that conjugation withglutathione is the major detoxication pathway for both acrylonitrileand CEO. This study investigated the role of epoxide hydrolasein the hydrolysis of CEO by HPLC analysis of the products from[2,3-¹⁴C]CEO. CEO is a relatively stable epoxide with a half-lifeof 99 min at 37°C in sodium phosphate buffer (0.1 M), pH7.3. Incubation with hepatic microsomes or cytosols from maleF-344 rats or B6C3F1 mice did not enhance the rate of hydrolysisof CEO (0.69 nmol/min). Human hepatic microsomes significantlyincreased the rate of hydrolysis of CEO, whereas human hepaticcytosols did not. Human hepatic microsomal hydrolysis activitywas heat-sensitive and potently inhibited by 1,1,1-trichloropropeneoxide (IC₅₀ of 23 µM), indicating that epoxide hydrolasewas the catalyst. The hydrolysis of CEO catalyzed by hepaticmicrosomes from six individuals exhibited normal saturationkinetics with K_M ranging from 0.6 to 3.2 mM and V _max from 8.3to 18.8 nmol hydrolysis products/min/mg protein. Pretreatmentof rodents with phenobarbital or acetone induced hepatic microsomalhydrolysis activity toward CEO, whereas treatment with ß-naphthoflavone,dexamethasone or acrylonitrile itself was without effect. Thesedata show that humans possess an additional detoxication pathwayfor CEO that is not active in rodents (but is inducible). Thepresence of an active epoxide hydrolase hydrolysis activitytoward CEO in humans should be considered in assessments ofcancer risk from acrylonitrile exposure.     

LHRH-A对孕中期大鼠抗妊娠作用的研究

本文观察了[D-Ala⁶,Pro⁹-Ethylamide¹⁰]-LHRH(LHRH-A)对孕中期大鼠的抗妊娠作用。结果显示:在孕9～11d sc 200μg/d LHRH-A,血浆孕酮水平自第二次给药后明显下降(P<0.05),给药大鼠均流产终止妊娠;LHRH-A的抗妊娠作用可被醋酸甲地孕酮所拮抗;LHRH-A对体外培养的假孕大鼠和孕d 9大鼠黄体细胞分泌孕酮有明显的直接抑制作用。     

Path analysis and sib-pair linkage

When the distance between linked loci is expressed in terms of the correlation between the identity-by-descent (idb) values of the loci, then a path model may be used to order loci with data on sib-pairs and their parents. The relationship between the recombination fraction and the correlation coefficient is developed and a method for fitting a covariance matrix predicted by a specific ordering of loci to an observed covariance matrix is proposed. © 1993 Wiley-Liss. Inc.     

Do ethnicity and gender have an impact on pain thresholds in minor dermatologic procedures?

Background and Objectives: The perception of pain is a personal experience influenced by many factors, including genetic, ethnic and cultural issues. Understanding these perceptions is especially important in dermatologic patients undergoing minor surgical operations and who often differ in their pain response to surgical treatments. Little is known about how these differences affect the perception of experimental pain. The purpose of this study was to determine experimental pain perception differences in three distinct East Asian ethnic populations.
Methods: Pain thresholds were examined with a psychophysical computerized quantitative thermal sensory testing device (TSA 2001) in healthy volunteers recruited from three different Asian ethnic groups. Using the methods of limits, experimental pain perception threshold was measured on the forehead and volar aspect of the forearm in 49 healthy subjects. The measurements were then repeated after skin barrier perturbation with adhesive tape stripping of the stratum corneum. All three ethnic groups were analyzed separately with respect to age, gender educational level and skin type.
Results: A total of 20 Chinese, 14 Malay and 15 Indian subjects completed the study. Thermal pain thresholds were similar in all three ethnic groups before and after tape strippings. No significant differences were noted between genders.
Conclusions: Using quantitative sensory thermal testing, we demonstrated that no significant differences in pain occur between different races and genders.     

Quantification of perfusion fMRI using a numerical model of arterial spin labeling that accounts for dynamic transit time effects.

A new approach to modeling the signal observed in arterial spin labeling (ASL) experiments during changing perfusion conditions is presented in this article. The new model uses numerical methods to extend first-order kinetic principles to include the changes in arrival time of the arterial tag that occur during neuronal activation. Estimation of the perfusion function from the ASL signal using this model is also demonstrated. The estimation algorithm uses a roughness penalty as well as prior information. The approach is demonstrated in numerical simulations and human experiments. The approach presented here is particularly suitable for fast ASL acquisition schemes, such as turbo continuous ASL (Turbo-CASL), which allows subtraction pairs to be acquired in less than 3 s but is sensitive to arrival time changes. This modeling approach can also be extended to other acquisition schemes.     

The Bermuda offshore market in transition

In summary, the Bermuda insurance industry is undergoing a major upheaval, with the ultimate outcome being presently unclear. However, offshore markets have been at the forefront of innovation in international insurance for the past decade, and this innovation is likely to continue. The successful companies of the future will take full advantage of the regulatory and accounting freedoms offered in Bermuda, the Cayman Islands, and other Caribbean locations. In the end, the offshore captive industry could well be transformed into an offshore specialty insurance market. The players will be fewer, but the business volume may be larger than ever.     

新生小猪脑含氧量和O-酪氨酸在双侧颈动脉结扎和失血中的变化

采用小猪双侧颈动脉结扎伴失血模型检测双侧颈动脉的结扎伴失血对脑氧分压和O-酪氨酸变化的影响,结果发现小猪脑氧分压为(51±4)托.颈动脉结扎和失血后60min降为(10±1.5)托(P<0.001),当颈动脉恢复通畅和失血再灌注后,脑氧分压增至(40±6)托,此值与预试验时的脑氧分压无明显差异.对照组中脑纹状体中的O-酪氨酸的含量为(0.57±0.19)nmoles/g组织.缺血试验后1h其含量明显升为(29±0.5)nmoles/g组织(P<0.005),显示缺血后再灌注导致脑纹状体O-酪氨酸显著上升.提示组织中羟基产生增加,可能与新生小猪脑缺血和再灌注损伤有一定作用.     

In vivo anti-melanoma activities of the Melan-A/MART-1101–115 T CD4+ cell peptide

Malignant melanoma causes significant health problems. The identification of tumour-associated antigens has led to novel approaches to increase T cell mediated anti-tumour immune response. Melan-A/MART-1 has been use as target antigen for several T cell based immunotherapeutic treatments. More recently, the critical role of CD4+ T cells in inducing and maintaining anti-tumour immunity has been increasingly recognized. In order to optimize tumour immunotherapy, greater efforts have been concentrated on the identification of tumour antigens presented by MHC class II molecules to CD4+ T cells. In a publication, Tiwari et al. (2004) [1] have identified by a computational approach the 15-mer amino-acid sequence 101–115 (PPAYEKLSAEQSPPP) of the Melan-A/MART-1 as a good target for a vigorous and safe immunotherapy. Therefore, we have investigated the in vivo anti-tumour activity of this peptide in a murine melanoma model. For the prophylactic treatment, 20 μg or 50 μg peptide was subcutaneously injected in mice once a week during 3 weeks before tumour induction. Treatment with 50 μg peptide significantly affected tumour development. Thus, our preliminary data demonstrate potential in vivo prophylactic activity of the 101–115 peptide-based vaccine to control melanoma growth.