Effect of liposome surface charge on the stability of technetium (99mTc) radiolabelled liposomes

Using liposomes radiolabelled by the 99mTechnetium-stannous chloride technique we have investigated the effect of surface charge on the stability of the isotope in vitro and in vivo. Dialysis of 99mTc-labelled positive, negative and neutral liposomes, which had been incubated in either saline or normal rat serum showed no significant loss of the isotope from the liposome surface with only 2 per cent of the isotope dialysed. A comparison of gel chromatography with dialysis confirmed that most of the isotope remained attached to the liposome surface, but it did reveal greater loss of the isotope, between 15 and 23 per cent. The liposome clearance rates obtained from 125I-egg phosphatidylcholine (EPC) and 99mTc dual-labelled positive or neutral liposomes were significantly different. The 99mTc marker was cleared five times faster from the positive liposomes and twice as fast from the neutral liposomes as the 125I-EPC integral membrane marker. The 99mTc attached to liposomes with a negative surface charge was stable in vivo and had the same clearance rate from the circulation as the 125I-EPC marker. These results indicate that the commonly used in vitro techniques for assessing liposome radiolabel stability are unsuitable for predicting the stability of the 99mTc in vivo.     

The use of a subperiosteal tissue expander in rib reconstruction of an atrophic mandible

A technique is described that provides adequate coverage for rib grafts used in reconstruction of the atrophic mandible. The flaps are highly vascular and thick because of the fibrous capsule that forms around the tissue expander. A one-stage expansion technique is used that reduces the total time needed for reconstruction.     

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.     

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.