X-Message-Number: 30199 Date: Sat, 22 Dec 2007 20:14:56 -0800 (PST) From: Subject: a new vitrification solution is developed [Osmotic toxicity eliminated glycerol from this test. A glycerol/methanol combination was not tested. Best solution overall consisted of 20% DMSO, 10% propylene glycol, and 10% methanol. A straight substitution of ethylene glycol for the propylene glycol was not tested. With nine cryoprotectants (only five mentioned in the abstract) under test at four concentrations (0%, 10%, 20%, 30%), a complete test of all these combinations yielding a 40% total concentration would have to test several thousand separate solutions . This illustrates how futile it would be to try exhaustive testing, without regard to or paying much attention to the different modes of cryoprotectant toxicity. The following is my own admittedly amateur attempt at factoring in toxicity considerations to eliminate solutions from consideration. Since osmotic damage was a significant factor in this test, there was no point in testing any solution which did not have at least some methanol in it, since methanol was the only cryoprotectant which could rapidly penetrate cell membranes, and limit this form of damage when nonramped solutions are abruptly added to medium. However methanol itself has a high extrinsic toxicity, as well as little ability to vitrify, so there is also little point in testing solutions with more than 10% methanol in them. 21'st Century Medicine has found that vitrification solutions with ethylene glycol are less toxic than those containing propylene glycol, possibly because of a reduced intrinsic (denaturing) toxicity. Therefore there was no point in even considering any solution containing propylene glycol. This all points out how little thought has been given to the three different types of toxicity, which I can osmotic, intrinsic, and extrinsic. Indeed some would even deny there are three different types of toxicity, which gives an idea of how little is really known about the nature of cryoprotectant toxicity. Aside from some attempts by Fahy et al, the theoretic basis of cryoprotectant toxicity has been virtually ignored in medical journals.] Theriogenology. 2007 Sep 15;68(5):702-8. Epub 2007 Jul 2. Preliminary studies on the vitrification of red sea bream (Pagrus major) embryos. Ding FH, Xiao ZZ, Li J. Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China. The objective was to identify an appropriate cryoprotectant and protocol for vitrification of red sea bream (Pagrus major) embryos. The toxicity of five single-agent cryoprotectants, dimethyl sulfoxide (DMSO), propylene glycol (PG), ethylene glycol (EG), glycerol (GLY), and methyl alcohol (MeOH), as well as nine cryoprotectant mixtures, were investigated by comparing post-thaw hatching rates. Two vitrifying protocols, a straw method and a solid surface vitrification method (copper floating over liquid nitrogen), were evaluated on the basis of post-thaw embryo morphology. Exposure to single-agent cryoprotectants (10% concentration for 15 min) was not toxic to embryos, whereas for higher concentrations (20 and 30%) and a longer duration of exposure (30 min), DMSO and PG were better tolerated than the other cryoprotectants. Among nine cryoprotectant mixtures, the combination of 20% DMSO+10% PG+10% MeOH had the lowest toxicity after exposure for 10 min or 15 min. High percentages of morphologically intact embryos, 50.6+/-16.7% (mean+/-S.D.) and 77.8+/-15.5%, were achieved by the straw vitrifying method (20.5% DMSO+15.5% acetamide+10% PG, thawing at 43 degrees C and washing in 0.5M sucrose solution for 5 min) and by the solid surface vitrification method (40% GLY, thawing at 22 degrees C and washing in 0.5M sucrose solution for 5 min). After thawing, morphological changes in the degenerated embryos included shrunken yolks and ruptured chorions. Furthermore, thawed embryos that were morphologically intact did not consistently survive incubation. PMID: 17606292 Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=30199