Ischemic preconditioning protects against paraplegia after transient aortic occlusion in the rat.

BACKGROUND: Paraplegia can result from operations requiring transient occlusion of the thoracic aorta. A rat model of paraplegia with the characteristics of delayed paraplegia and transient ischemic dysfunction was developed to determine whether ischemic preconditioning (IPC) improved neurologic outcome. METHODS: Rats underwent balloon occlusion of the upper descending thoracic aorta. One group (2 minute IPC, n = 19) underwent 2 minutes of IPC and a second group (5 minute IPC, n = 19) had 5 minutes of IPC 48 hours before 10 minutes of occlusion. The control group (n = 31) had no IPC prior to 10 minutes of occlusion. RESULTS: Paraplegia occurred in 68% of the control animals (21 of 31 paraplegic: 6 delayed and 15 immediate paraplegia). Both the 2-minute IPC and 5-minute IPC groups had a decreased incidence of paraplegia when compared to controls (32%, p = 0.011 and 26%, p = 0.009, respectively). CONCLUSIONS: A rat model of spinal cord ischemia demonstrating both delayed paraplegia and transient ischemic dysfunction was characterized. Both 2-minute and 5-minute periods of IPC were found to protect against paraplegia.

Nonoxidative enzymes in the metabolism of insecticides.

Two major classes of enzymes, i.e., hydrolases and transferases, comprise all the nonoxidative enzymes, and together these enzymes catalyze a wide variety of biotransformations of insecticides. The hydrolytic enzymes involved in insecticide metabolism are carboxylesterase (EC 3.1.1.1), arylesterase alkylamidase, and DFPase (EC 3.8.2.1). Recent experimental evidence suggests that carboxylesterase enzyme(s), formerly known to hydrolyze malathion-type insecticides, can also catalyze hydrolysis of a variety of diversified insecticidal esters such as benzilic acid derivatives, carbanilate compounds, and pyrethroids. These organophosphate-sensitive esterases, with the exception of the enzyme which hydrolyzes malathion, are all present in microsomes. Similarly, the action of amidases now extends to those insecticidal compounds of their intermediates which contain an aminoformyl (N-CHO) moiety. Arylesterase and DFPase catalyze the P-anhydride bond cleavage of the leaving group, a major hydrolytic pathyway for organophosphate insecticides. Transferal enzymes which are presently know to metabolize insecticidal organophosphates are GSH-S-alkyltransferase (EC 2.5.1.12) and GSH-S-aryltransferase (EC 2.5.1.13). These enzymes cleave P-O-R (R = alkyl) or P-0-X (X = aromatic), with subsequent transfer of the R or X group to glutathione. Regarding the other conjugating enzymes, UDP-glucuronyltransferase (EC 2.4.L.17), UDP-glucosyltransferase (EC 2.4.1.35), and arylamine acetyltransferase (EC 2.3.1.5), much work is needed to understand their interactions with insecticidal compounds. There is some evidence that arylsulfotransferase (EC 2.8.2.1) MAY PLAY A PROMINENT ROLE IN THE CONJUGATIVE MECHANISMS OF INSECTS.

Nonoxidative enzymes in the metabolism of insecticides.

Two major classes of enzymes, i.e., hydrolases and transferases, comprise all the nonoxidative enzymes, and together these enzymes catalyze a wide variety of biotransformations of insecticides. The hydrolytic enzymes involved in insecticide metabolism are carboxylesterase (EC 3.1.1.1), arylesterase (EC 3,1.1.2), alkylamidase, and DFPase (EC 3.8.2.1). Recent experimental evidence suggests that carboxylesterase enzymes(s), formerly known to hydrolyze malathion-type insecticides, can also catalyze hydrolysis of a variety of diversified insecticidal esters such as benzilic acid derivatives, carbanilate compounds, and pyrethroids. These organo-phosphate-sensitive esterases, with the exception of the enzyme which hydrolyzes malathion, are all present in microsomes. Similarly, the action of amidases now extends to those insecticidal compounds or their intermediates which contain an aminoformyl (N--CHO) moiety. Arylesterase and DFPase catalyze the P--anhydride bond cleavage of the leaving group, a major hydrolytic pathway for organophosphate insecticides. Transferal enzymes which are presently known to metabolize insecticidal organophosphates are GSH-S-alkyltransferase (EC 2.5.1.12) and GSH-S-aryltransferase (EC 2.5.1.13). These enzymes cleave P--O--R (R = alkyl) or P--O--X (X = aromatic), with subsequent transfer of the R or X group to glutathione. Regarding the other conjugating enzymes, UDP-glucuronyltransferase (EC 2.4.1.17), UDP-glucosyltransferase (EC 2.4.1.35), and arylamine acetyltransferase (EC 2.3.1.5), much work is needed to understand their interactions with insecticidal compounds. There is some evidence that arylsulfotransferase (EC 2.8.2.1) may play a prominent role in the conjugative mechanisms of insects.

Environmental impact of mosquito pesticides: influence of temefos on the brain acetylcholinesterase of killifish.

Temefos and six of its metabolites were tested for their capacity to inhibit the in vitro activity of brain acetylcholinesterase (AChE) of Fundulus heteroclitus. While temefos was not inhibitory at levels up to 10.7 mM in brain homogenate samples, its metabolites were active within the range of 2 X 10(-4)mM to 1.26 mM in causing a 50% reduction in the enzyme activity. Exposure of F. heteroclitus to temefos under laboratory conditions caused a reduction in AChE activity, which was proportional to the pesticide concentration and the exposure period. Visible symptoms of organophosphate poisoning were apparent only after the AChE inhibition reached 80%. F. heteroclitus and Cyprinidon variegatus exposed to 10 biweekly applications of temefos granules in the field showed no inhibition of brain AChE. However, exposure of F. heteroclitus to biweekly applications (four) of temefos emulsion caused a reduction in the enzyme (50%), but only in the pre-third application samples. A gradual increase in brain AChE occurred both in F. heteroclitus and C. variegatus as the season progressed from April to October.

Lindane: metabolism to a new isomer of pentachlorocyclohexene.

Two of the hexane-soluble products of metabolism of lindane in susceptible and resistant houseflies were tentatively identified as isomers of pentachlorocyclohexene by gas-liquid chromatography and mass spectroscopy. One isomer was identical with the pentachlorocyclohexene obtained by mild alkaline dehydrochlorination of lindane and is apparently the form found in previous studies of metabolism; the second is now reported for the first time.