J.E. Fincham

Could control of soil-transmitted helminthic infection influence the HIV/AIDS pandemic

In May 2001, the World Health Assembly (WHA) estimated that two billion people were infected by soil-transmitted helminths (S-THs) and schistosomiasis, worldwide. The WHA urged member states to recognise that there can be synergy between public health control programmes for S-THs, schistosomiasis and other diseases. This is particularly relevant to the new dimension created by the HIV/AIDS epidemics in the same impoverished communities and countries where helminthiasis is hyperendemic. Immunological adaptation between humans and parasitic helminths has developed during evolution. Review of 109 research papers, 76% (83/109) of which, were published between 1995 and February 2002, revealed increasing evidence that this relationship may have created an opportunity for more rapid infection by the human immunodeficiency virus (HIV), as well as quicker progression to AIDS. Moreover, the efficacy of some vaccines against HIV is likely to be impaired by chronic helminthiasis. For this, there is strong, indirect evidence. There is an urgent need for parasitologists, epidemiologists, immunologists and virologists to undertake comprehensive, transdisciplinary research. On the other hand, there is no current evidence that immunosuppression by HIV facilitates helminthic infection. The situation in regard to strongyloidiasis, however, is not yet clear.

Atherogenic effects in a non-human primate of Fusarium moniliforme cultures added to a carbohydrate diet.

Adding less than 0.5% w/w of culture material of strain MRC 826 of the fungus Fusarium moniliforme to a carbohydrate diet low in fat resulted in an atherogenic plasma lipid profile in a non-human primate. Simultaneously increased plasma fibrinogen and activity of blood coagulation factor VII could enhance atherogenesis. This unique potential for promotion of atherosclerosis was probably secondary to chronic hepatotoxicity as indicated by liver fibrosis and elevated cholesterol, albumin and the enzymes AST, ALT, LD, GGT and ALP in serum. The cholesterol and enzymes responded in proportion to the calculated doses of fumonisin mycotoxins in the F. moniliforme MRC 826 cultures. Fumonisins are water soluble and heat stable. Thrombotic, hepatotoxic, carcinogenic and cerebral effects of MRC 826 culture material and fumonisins are well known in non-primates. The estimated fumonisin concentrations tested fall within a range due to natural contamination of human foods. The results suggest that all maize grain products should be analysed for fumonisins.

Atherosclerosis. Chronic effects of fish oil and a therapeutic diet in nonhuman primates.

Prolonged testing of marine fish oil (FO) as a dietary supplement is necessary because of widespread claims that it is antiatherogenic. The basis for such claims is inadequate because atherogenesis is chronic and may not respond to short-term changes induced by dietary treatments. A proven (vervet) model of atherosclerosis promoted by an atherogenic diet (AD) was used to test dietary supplementation with Atlantic pilchard FO for 20 months in 47 omnivorous nonhuman primates. Responses were controlled against known favorable effects of changing from the AD to a therapeutic diet (TD). Compliance was achieved, and tissue responses to the FO dose were confirmed. Compromise of reflex vasoconstriction by atherosclerosis was demonstrated for the first time in the model. Aortic, peripheral, coronary, and cerebral atherosclerosis were assessed by light microscopy and computerized image analysis. No component of atherosclerosis regressed after dietary FO, and several deteriorated. After a change to the TD, stainable lipid was cleared from aortas and there were few lipophages, but advanced atherosclerosis was not reduced. Male vervets developed more severe atherosclerosis than did females, and the association among aortic, peripheral, and coronary atherosclerosis was positive in males. Females were resistant to coronary atherosclerosis. Only mild cerebral atherosclerosis was detected. In conclusion, the FO used was not antiatherogenic in the model, and there is a need for caution. The TD regresses some components of atherosclerosis, but it was not effective against fibrosis, mineralization, and cholesterol crystals within 20 months.

Plasma low density lipoprotein composition in relation to atherosclerosis in nutritionally defined Vervet monkeys

An atherogenic diet (AD) consisting entirely of normal foods for westernized people was fed to female Vervet monkeys for 4 years. The plasma low density lipoprotein (LDL) cholesterol pool was increased and progression of atherosclerosis was enhanced by the AD compared to a more prudent Western diet. The increased LDL-cholesterol was carried by a 3-fold increase in particles of relatively normal composition and not by packing cholesterol esters into the cores of enlarged LDL particles, as has been reported after feeding semisynthetic diets loaded with extra cholesterol. Nevertheless, these LDL particles were atherogenic. The AD changed the fatty acid composition of LDL-cholesterol esters and triacylglycerol, notably by increasing arachidonic and reducing linoleic acid. Multivariate analysis showed that measures and scores of atherosclerosis were significantly dependent on sphingomyelin and phosphatidylcholine in LDL and on arachidonic acid in LDL-triacylglycerol. Although apolipoprotein B, free cholesterol, esterified cholesterol and lysophosphatidylcholine in plasma LDL and atherosclerosis were significantly positively correlated in bivariate analysis they were not selected by multivariate analysis as the strongest determinants of atherogenesis. Cholesterol in plasma high density lipoprotein was not changed by the AD and lecithin:cholesterol acyltransferase activity in plasma was inversely linked to atherosclerosis. Subcutaneous fatty acids reflected dietary fatty acids.

Diets realistic for westernised people significantly effect lipoproteins, calcium, zinc, vitamins C, E, B6 and haematology in Vervet monkeys

This report describes measurements of 50 variables in adult, female, reproductively inactive Vervet monkeys during prolonged nutrition realistic for westernized people. Dietary treatments consisted of an atherogenic Western diet (WD) and a prudent Western diet (PD). Ingredients were normal foods for man and no extra cholesterol was added. Fortification of both diets with vitamin C after cooking was necessary to prevent deficiency. Randomised groups of Vervet monkeys received either the PD or WD for 47 months, while a third group was fed WD for 20 months and then PD for 27 months (WD-PD). Before the dietary treatments nourishment was by a high carbohydrate diet (HCD) and baseline and reference values (RV) apply to this nutritional status. Plasma total cholesterol (mg/dl) was increased from 147 (HCD) to 174 (PD) and 376 (WD). Individual cholesterolaemio response ranged from mild to severe and was stable (PD and WD). Dietary reversal (WD-PD) reduced cholesterolaemia promptly. Statistically significant increases in calcium, zinc and vitamin E and decreased vitamin B6 were associated with the WD relative to the PD (in serum and plasma). Two cholesterol metabolising microsomal enzymes in liver were notably increased and one unchanged (WD). There were no dietary effects on triglycerides, vitamin A and glucose in plasma; insulin, glucagon, electrolytes, copper, magnesium or enzymes reflecting liver, muscle or brain cell damage in serum. Red blood cells, platelets and directly associated parameters increased (WD), haemoglobin was the same and haemoglobin per red cell decreased. Bleeding time was not affected. Bivariate correlations across the diets confirmed that Western nutrition promoted inherent individual susceptibility to cholesterolaemia. There were notable differences from RVs in total cholesterol, calcium, packed cell volume and haemoglobin, which emphasise excesses and deficiencies of the WD and PD.

Low density lipoprotein kinetics in African Green monkeys showing variable cholesterolaemic responses to diets realistic for westernised people

African Green (vervet) monkeys were fed either an atherogenic Western diet (WD), a prudent diet (PD), or a high carbohydrate diet (HCD) for various lengths of time. Monkeys differed greatly in their response to the WD, and a strong negative correlation was observed between the fractional catabolic rates (FCR) of low density lipoprotein (LDL) and the total plasma cholesterol concentrations (r = -0.83 P = 0.0029). Similarly the individual synthetic rates (SR) of LDL plotted against the total plasma cholesterol concentrations showed a correlation coefficient of r = 0.94 P = 0.01 for WD animals. There was no correlation for PD or HCD animals for either SR or FCR and the total plasma cholesterol concentrations. The aortic lesion scores correlated with the SRs (r = 0.66 P = 0.040) but not with the FCRs. LDL turnover was also studied using 125I-labelled native LDL and methylated 131I-labelled LDL in African Green monkeys showing high or low cholesterolaemic response to an atherogenic Western diet. Measurements after 4 weeks and again after 6 months on the diet showed a decrease in both total and non-receptor mediated clearance of LDL. Receptor-mediated catabolism was significantly lowered in the hyperresponding group (P = 0.0011) and not in the hyporesponding group with a resultant significant difference between the two groups being P = 0.0355 after 6 months. Non-receptor mediated catabolism of LDL was similarly affected in that there was no significant difference between the two groups at 4 weeks but the clearance of methylated LDL was markedly lowered at 6 months, for the hyporesponding group P = 0.0003 and for the hyperresponding group P = 0.0184. Furthermore the hyperresponding group was depressed to a significantly greater extent when compared to the hyporesponding group (P = 0.0241).

Semen characteristics of vervet monkeys

Semen samples (91) from 47 vervet monkeys were collected by electroejaculation over a 2 year period. Seventy-eight of these were from 37 singly caged males of unknown fertility and 13 from 10 breeding males of known fertility. Mean values for semen characteristics of the singly caged males were: volume 0·45 ml, pH 7·8, concentration 184×106/ml, forward progression rating 2·95 (scale 0-4), motility 55·4%, live 68% and abnormal morphology 3·5%. Mean values for semen characteristics for the breeding males were: volume 0·86 ml, pH 9·00, concentration 117×15·106/ml, forward progression rating 3·00 (scale 0-4), motility 43·6%, live 53·3% and abnormal morphology 6%. Semen volumes in the singly caged males were lower than the volumes reported in other studies.

Folic acid and vitamin B12 status of vervet monkeys used for nutritional research

Plasma and red blood cell (RBC) folic acid levels, as well as plasma vitamin B12 levels were determined in Vervet monkeys (Cercopithecus aethiops). All the vervets were apparently healthy and without symptoms or lesions typical of folic acid and/or vitamin B12 deficiencies. Competitive protein binding radioassays were used to determine folate and vitamin B12 values in animals fed 4 different diets. The B12 levels for all the groups ranged between 866 and 5867 pg/ml and showed an inverse relationship with the FA measurements. The lowest mean RBC folic acid content in a group fed an atherogenic diet for 3 years was 12·8 ng/ml. For the other 3 diets, mean RBC folic acid levels were 90·7, 132·3 and 152·8 ng/ml, respectively. A megadose of 25·6 mg of folic acid per day for 99 days was given to 3 adult males. No obvious toxic effects were observed in these animals although mean RBC folic acid levels increased to 1013 ng/ml.