Lipoic and dihydrolipoic acids as antioxidants. A critical evaluation.

A detailed evaluation of the antioxidant and pro-oxidant properties of lipoic acid (LA) and dihydrolipoic acid (DHLA) was performed. Both compounds are powerful scavengers of hypochlorous acid, able to protect alpha 1-antiproteinase against inactivation by HOCl. LA was a powerful scavenger of hydroxyl radicals (OH.) and could inhibit both iron-dependent OH. generation and peroxidation of ox-brain phospholipid liposomes in the presence of FeCl3-ascorbate, presumably by binding iron ions and rendering them redox-inactive. By contrast, DHLA accelerated iron-dependent OH. generation and lipid peroxidation, probably by reducing Fe3+ to Fe2+. LA inhibited this pro-oxidant action of DHLA. However, DHLA did not accelerate DNA degradation by a ferric bleomycin complex and slightly inhibited peroxidation of arachidonic acid by the myoglobin-H2O2 system. Under certain circumstances, DHLA accelerated the loss of activity of alpha-antiproteinase exposed to ionizing radiation under a N2O/O2 atmosphere and also the loss of creatine kinase activity in human plasma exposed to gas-phase cigarette smoke. Neither LA nor DHLA reacted with superoxide radical (O.2-) or H2O2 at significant rates, but both were good scavengers of trichloromethylperoxyl radical (CCl3O2.). We conclude that LA and DHLA have powerful antioxidant properties. However, DHLA can also exert pro-oxidant properties, both by its iron ion-reducing ability and probably by its ability to generate reactive sulphur-containing radicals that can damage certain proteins, such as alpha 1-antiproteinase and creatine kinase.

Antioxidant actions of thymol, carvacrol, 6-gingerol, zingerone and hydroxytyrosol.

Antioxidants minimize oxidation of the lipid components in foods. There is an increasing interest in the use of natural and/or synthetic antioxidants in food preservation, but it is important to evaluate such compounds fully for both antioxidant and pro-oxidant properties. The properties of thymol, carvacrol, 6-ginerol, hydroxytyrosol and zingerone were characterized in detail. Thymol, carvacrol, 6-gingerol and hydroxytyrosol decreased peroxidation of phospholipid liposomes in the presence of iron(III) and ascorbate, but zingerone had only a weak inhibitory effect on the system. The compounds were good scavengers of peroxyl radicals (CCl3O2; calculated rate constants > 10(6) M-1 sec-1) generated by pulse radiolysis. Thymol, carvacrol, 6-gingerol and zingerone were not able to accelerate DNA damage in the bleomycin-Fe(III) system. Hydroxytyrosol promoted deoxyribose damage in the deoxyribose assay and also promoted DNA damage in the bleomycin-Fe(III) system. This promotion was inhibited strongly in the deoxyribose assay by the addition of bovine serum albumin to the reaction mixtures. Our data suggest that thymol, carvacrol and 6-gingerol possess useful antioxidant properties and may become important in the search for 'natural' replacements for 'synthetic' antioxidant food additives.

Administrative fellowships in emergency medicine.

Physicians today need to be effective managers, as well as clinicians. In previous years, physicians gained managerial experience either through on-the-job training, degree programs, or continuing medical education courses. The specialty of emergency medicine began its first administrative fellowship in 1990 in California. Currently, three administrative fellowships exist nationally in emergency medicine. This article will describe the purpose of the fellowships and their curricula. Each fellowship has a different emphasis, with the goal to educate physicians who are interested in developing administrative skills to manage emergency departments or management groups or accept roles in hospital leadership. The existence of these fellowships will ideally influence the establishment of administrative fellowships in other specialties.

An in vivo preparation (Thiry-Vella fistula) suitable for the measurement of intestinal absorption in the guinea pig.

A thiry-Vella isolated intestinal loop was constructed in the guinea pig. The procedure consisted of removal of a 30-cm segment of the jejunem, restoration of intestinal continuity by a jejunojejunostomy, and exteriorization of the segment through stomata sutured to the skin. The procedure was performed on seven guinea pigs of which three survived. The three survivors remained normal in maintenance of hair, feeding, and weight gain over a long period.

Evaluation of the antioxidant actions of ferulic acid and catechins.

We have evaluated the abilities of ferulic acid, (+/-) catechin, (+) catechin and (-) epicatechin to scavenge the reactive oxygen species hydroxyl radical (OH.), hypochlorous acid (HOCl) and peroxyl radicals (RO2.). Ferulic acid tested at concentrations up to 5 mM inhibited the peroxidation of phospholipid liposomes. Both (+/-) and (+) catechin and (-) epicatechin were much more effective. All the compounds tested reacted with trichloromethyl peroxyl radical (CCl3 O2.) with rate constants > 1 x 10(6) M-1 s-1. A mixture of FeCl3-EDTA, hydrogen peroxide (H2O2) and ascorbic acid at pH 7.4, has often been used to generate hydroxyl radicals (OH.) which are detected by their ability to cause damage to the sugar deoxyribose. Ferulic acid, (+) and (+/-) catechin and (-) epicatechin inhibited deoxyribose damage by reacting with OH. with rate constants of 4.5 x 10(9)M-1 s-1, 3.65 x 10(9) M-1 s-1, 2.36 x 10(9) M-1 s-1 and 2.84 x 10(9) M-1 s-1 respectively. (-) Epicatechin, ferulic acid and the (+) and (+/-) catechins exerted pro-oxidant action, accelerating damage to DNA in the presence of a bleomycin-iron complex. On a molar basis, ferulic acid was less effective in causing damage to DNA compared with the catechins. A mixture of hypoxanthine and xanthine oxidase generates O2-. which reduces cytochrome c to ferrocytochrome c. (+) Catechin and (-) epicatechin inhibited the reduction of cytochrome c in a concentration dependent manner. Ferulic acid and (+/-) catechin had only weak effects. All the compounds tested were able to scavenge hypochlorous acid at a rate sufficient to protect alpha-1-antiproteinase against inactivation. Our results show that catechins and ferulic acid possess antioxidant properties. This may become important given the current search for "natural" replacements for synthetic antioxidant food additives.