Proceso de fabricación de puertas y portones

Stocks et al®^ have studied the antioxidant capacity of plasma using a tissue preparation of ox brain in which the rate of malondialdehyde (a secondary product of lipid peroxidation - see chapter 3) production was used as an index of peroxidation. Caeruloplasmin and transferrin were reported in these studies as the major preventative antioxidants in plasma. Tocopherol had little effect as an antioxidant as measured by this test system. Both caeruloplasmin and transferrin are acute phase proteins which may be raised in malnourished populations®®*®®. These findings presumably reflect the capacity of caeruloplasmin and transferrin to bind metal ions. The production of malondialdehyde from the ox brain lipid in this test system will be dependent upon the presence of free metal ions and it is no surprise, therefore, that efficient metal chelators function as efficient "antioxidants" in this system.

Wayner et al®^ have used a different approach. They measured the total radical trapping (TRAP) activity of plasma by studying its ability to prevent lipid peroxidation initiated by the water soluble azo compound 2,2'-azo-bis-(2-amidino propane hydrochloride) [ABAP]. Peroxidation was assessed by measuring oxygen uptake with a Clark type oxygen electrode. This reaction is NOT Fe dependent and hence Is not inhibited by Fe chelating materials. The TRAP activity of plasma was mainly due to four components: a tocopherol, ascorbate, urate, and the sulphydryl content of proteins®®. In addition, carotenes®® and bilirubin^® can also trap lipid free radicals. Using the TRAP technique, Burton and Ingold®^ demonstrated that vitamin E is the only lipid soluble antioxidant in human blood plasma. In terms of concentration however, proteins are the largest single antioxidant component in blood plasma, but if trapping efficiency is taken into account, then urate has the largest capacity^\ Ames' group in California have studied the temporal order of antioxidant consumption in human blood plasma exposed to a constant flux of aqueous peroxyl radicals^^. The order of consumption of antioxidants was ascorbate = protein thiols > bilirubin > urate > a - tocopherol, and lipid peroxidation (measured as the appearance of lipid hydroperoxides) did not start until after the ascorbate had been completely consumed. They were able to demonstrate that plasma which was depleted of ascorbate was extremely vulnerable to oxidative

stress.

1.7.1 Studies in malnourished chiidren

Thurnham has reported the results of the TRAP assay in malnourished Nigerian children (with trivial infections) and Caucasian adults^^. The TRAP values were significantly lower in the malnourished children. Concentrations of urate and glutathione (GSH + GSSG) were similar in the two groups, whilst those of tocopherol and ascorbate were lower in the malnourished children.

Low levels of ascorbate are commonly found in malnourished populations^^, and the impact of this on the antioxidant capacity of plasma may previously have been underestimated. The recycling of ascorbate within the erythrocyte to maintain the antioxidant capacity of plasma has been discussed already^®. It is worth making the point here, however, that the recycling of ascorbate / dehydroascorbate across the erythrocyte membrane in vivo may constitute a pitfall of the TRAP assay - the system does not contain any erythrocytes.

Golden et al^® have measured CuSOD activity in erythrocytes from 93 severely malnourished children and found this to be significantly depressed in about 40% of individuals. There was no difference between the infants with marasmus and kwashiorkor, and the authors were unable to correlate this finding with any particular clinical feature. The concentration of glutathione peroxidase in erythrocytes is quantitatively related to the dietary content / absorption of selenium^^. Levels of this enzyme have been reported in malnourished children in the West Indies^® and were low in 45% of individuals studied, although there were no differences between individuals with kwashiorkor and marasmus. Manganese superoxide dismutase has not, to date, been measured in malnourished children, although low levels of hepatic manganese have been reported in South African children with kwashiorkor^® but not in non oedematous malnourished children. Zinc, in the form of zinc metallothionein is a very effective free radical sink in vitro and probably in vivo, but levels have not been measured in malnutrition. Levels of zinc are however uniformly low in kwashiorkor^^

Glutathione 8 transferase may be induced (almost two fold) in kwashiorkor^^ Detoxification of aliphatic aldehydes by this method results in the consumption of glutathione, and low levels of glutathione have also been reported in kwashiorkor^V The ratio of oxidised glutathione / total glutathione [2GSSG / (GSH+2GSSG)] is

reported as being normal in malnourished children, although the ratio gives no information about the rate of glutathione recycling / turnover. The hexose monophosphate shunt (which reduces NADP to NADPH to provide reducing equivalents for the regeneration of GSH from GSSG [vide supra]) is induced^^ in kwashiorkor. Golden has proposed that these findings represent a paradox in that although levels of GPX are low, the enzyme may be working at an increased capacity fuelled by the induced hexose monophosphate shunt. Confirmatory evidence for this is lacking.

There is very little information on levels of antioxidants in malnourished infants with PDD at presentation to hospital in the Western world. A prospective case controlled study is currently underway at the Hospital for Sick Children, Great Ormond Street, London. The preliminary data®° suggest that there are compromised antioxidant defences in over half of the children at presentation to this hospital.

1.8 A unifying hypothesis for the vicious cycle of malnutrition, malabsorption and