Application of growth models to South African Boer goat castrates and does under feedlot conditions.

Mathematical models may aid researchers in describing biological processes, like growth, in animals. This study aimed to collect the body weight data of 18 Boer goat castrates and 20 Boer goat does, from birth until maturity, to model growth and determine growth trends. This is a novel investigation as sufficient information on an age-weight database for these two Boer goat sexes from birth to maturity, is lacking. Using age-weight data, four nonlinear models, namely the Brody, Gompertz, Logistic and Von Bertalanffy growth models, were plotted and evaluated. The model parameters of each growth model were compared for differences between the two sexes. The statistical effectiveness of fit was determined for each model using AIC and RMSE, with R2 also being considered. All models except the Brody model, predicted significantly heavier mature weights for castrates. The Brody model was deemed unfit to describe Boer goat growth as the function severely over-predict weights from birth until maturity for both sexes. The Von Bertalanffy (R2 = 91.3) and Gompertz functions (R2 = 91.3) showed the best fit for Boer goat castrates, while the Gompertz model (R2 = 95.1) showed the best fit for Boer goat does. The Gompertz function is the preferred model to depict Boer goat growth overall, as it accurately characterized growth of both sexes. According to the Gompertz model the age at which the inflection point of the growth curve was reached, did not differ significantly between castrates and does (141.80 days versus 136.31 days). There was also no significant difference in maturation rate between the two sexes.

Characterization of endogenous folate and incorporation of labelled folates into the brain of the South African fruit bat.

Folate in the brain of the South African fruit bat consists of 10-formyltetrahydropteroyglutamic acid and the tri-, tetra- and penta- forms of 5-methyltetrahydropteroylglutamic acid. Following parenteral injection, only 5-[3H]-methyltetrahydropteroylglutamic acid was taken up by the brain, but none of a dose of 14C-labelled tetrahydropteroylglutamic acid was detectable. Only trace smounts of the 5-methyltetrahydropteroylglutamic acid were converted into the formyl compounds and a small amount of methyltetrahydropteroyltriglutamic acid appeared after 96 h. There was no significant difference in vitamin B-12-deficient animals.

Utilization of [2-14C]tetrahydropteroylglutamic acid and 5-[G-3H]methyltetrahydropteroylglutamic acid as substrates for folate polyglutamate synthesis in fruit bats: effect of vitamin B-12-deficiency.

[2-14C]Tetrahydropteroylglutamic acid and 5-[G-3H]methyltetrahydropteroylglutamic acid were given intraperitoneally to fruit bats. Folate polyglutamates were formed in the liver from both substrates in different amounts and at different rates. The methylfolate pool appeared to remain separate from the tetrahydrofolate pool. More polyglutamate was formed from tetrahydropteroylglutamic acid than from 5-methyltetrahydropteroylglutamic acid. There was a fall in the folate content of the liver in the vitamin B-12-deficient bat and a more rapid incorporation of folates into polyglutamates but thereafter a more rapid loss of the labelled folate from liver.

Intestinal absorption of thiamin from yeast-containing sorghum beer.

The rate of absorption of 14C-thiamin added to sorghum beer has been studied in isolated loops of rat duodenum and adjacent jejunum. Appreciable amounts of the vitamin were absorbed in spite of the presence in the beer of alcohol and live yeast cells avid for the vitamin. These results suggest that commercially brewed sorghum beer, a beverage consumed widely by Third World populations, can be fortified with thiamin to prevent the development of deficiency of the vitamin in habitual consumers of the beer.

Oxidation of low density lipoprotein in hemodialysis patients: effect of dialysis and comparison with matched controls.

End stage renal failure is associated with lipoprotein abnormalities and a high prevalence of premature atherosclerosis. Oxidative modification of low density lipoprotein (LDL) may be promoted by hemodialysis increasing its atherogenicity. The oxidative status of LDL was therefore examined in female subjects before and after routine hemodialysis (HD; n = 10) and compared with women of similar age without significant renal disease (n = 19). There were no significant differences between the groups in the LDL fatty acid composition, or in the content of reactive amino acid groups (lysine) before or after exposure to Cu2+. The kinetics of LDL oxidation by Cu2+ showed no significant differences between the groups with respect to the lag time, the level of conjugated dienes before and after oxidation, or the maximal rate of oxidation during the propagation phase. No acute effects of HD were demonstrated. The present study provides no evidence that circulating LDL isolated from HD patients is more extensively modified or more susceptible to oxidation in vitro than gender-matched controls without renal failure.

Effect of lipid-lowering dietary recommendations on the nutritional intake and lipid profiles of chronic peritoneal dialysis and hemodialysis patients.

Patients with end-stage renal failure are a high-risk group for atherosclerotic cardiovascular disease and commonly have dyslipidemia as a major factor. Dietary manipulation is the recommended first line of therapy for reducing lipid levels in people with normal renal function; however, complex dietary requirements of dialysis-treated patients with end-stage renal failure impose significant constraints. In this study, we evaluated the effect of trying to comply with established lipid-lowering recommendations superimposed on our normally prescribed dialysis diet over 14 weeks in stable subjects treated with either hemodialysis (HD) or chronic peritoneal dialysis (PD). Of 306 dialysis patients screened, 75 subjects were enrolled; 8 subjects did not complete the study. In the remainder, HD subjects (n = 41) decreased saturated fat intakes by 18% overall and cholesterol intakes by 16%. This was associated with a decrease in total cholesterol levels from 232 +/- 8 to 209 +/- 4 mg/dL (mean +/- SEM; P = 0.007) and low-density lipoprotein cholesterol levels from 147 +/- 4 to 131 +/- 4 mg/dL (P = 0.009). However, energy intakes decreased by almost 10%. There were no statistically significant changes in PD patients (n = 26). Only 24.4% of HD (10 of 41 patients) and 15.4% of PD patients (4 of 26 patients) normalized their lipid levels. Considerable problems were encountered in maintaining compliance with the modified dialysis diets. This study shows that if adhered to, properly constructed dialysis diets are close to optimal lipid-lowering recommendations. Further dietary manipulation is difficult, leads to little benefit in the majority, and is accompanied by added problems of adherence. We conclude that the vast majority of dyslipidemic patients with end-stage renal failure require pharmacological therapy.

Effect of preoperative supplementation with alpha-tocopherol and ascorbic acid on myocardial injury in patients undergoing cardiac operations.

Augmentation of antioxidant defenses may help protect tissues against ischemia-reperfusion injury associated with operations involving cardiopulmonary bypass. In this study we examined the effect of pretreating patients with alpha-tocopherol (vitamin E) and ascorbic acid (vitamin C) or placebo on injury to the myocardium. Seventy-six subjects undergoing elective coronary artery bypass grafting participated in a prospective, double-blind, placebo-controlled randomized trial, receiving either placebo or both 750 IU dl-alpha-tocopherol per day for 7 to 10 days and 1 gm ascorbic acid 12 hours before the operation. Plasma alpha-tocopherol concentrations, raised fourfold by supplementation, fell by 70% after the operation in the supplemented group and to negligible levels in the placebo group. There were no significant differences between the groups with respect to release of creatine kinase MB isoenzyme over 72 hours, nor in the reduction of the myocardial perfusion defect determined by thallium 201 uptake. Electrocardiography provided no evidence of a benefit from antioxidant supplementation. Thus the supplementation regimen prevented the depletion of the primary lipid soluble antioxidant in plasma, but provided no measurable reduction in myocardial injury after the operation.

Lipid composition and sphingolipid fatty acids of myelin in fruit bat brain.

Myelin was isolated from the brain of adult fruit bats (Rousettus aegyptiacus) in a discontinuous sucrose gradient. Cholesterol comprised 189.0 mol/100 mol lipid phosphorus, galactolipids 60.3 mol/100 mol phosphorus and plasmalogens 32.5 mol/100 mol phosphorus. Choline and ethanolamine glycerophosphatide were present in nearly equal amounts followed by serine glycerophosphatide, sphingomyelin and inositol glycerophosphatides. The fatty acid composition of sphingomyelin and non-hydroxy cerebroside was determined by gas-liquid chromatography. Fatty acids were mainly saturated or mono-unsaturated with a small percentage of polyunsaturated fatty acids present. The lipid composition and sphingolipid fatty acid distribution in bat myelin was fairly similar to that of other species.

The effects of a mixed fish diet on platelet function, fatty acids and serum lipids.

Eight healthy subjects were fed a diet containing 1-4 g eicosapentaenoic acid (EPA) daily for 8-21 days. The EPA was derived from 300-400 g per day of sardines, pilchards, herring and/or kabeljou. Sources of arachidonic acid (AA) in the diet were reduced. At the end of the experimental period there was an increase in the ratio of EPA to AA in the platelets and a decrease in platelet aggregation to ADP, epinephrine and collagen. Aggregation to AA was not reduced. Thromboxane production in response to all four agonists was reduced. Serum total and HDL cholesterol levels fell significantly but platelet counts, LDL cholesterol and triglyceride values did not change. We conclude that even a relatively modest intake of EPA derived from a mixed fish diet together with a reduction in AA intake can alter in vitro platelet function and serum lipids significantly. A long term controlled trial of a palatable mixed fish diet to assess possible antithrombotic and antiatherogenic effects is justifiable.

Tubular nephrotoxicity after cardiac surgery utilising cardiopulmonary bypass.

Markers of renal tubular injury were examined in 21 patients (16 male, 5 female, mean age 57.4 years) undergoing cardiac surgery utilising cardiopulmonary bypass. Postoperative urine outputs were very high (200-250 ml/h at 1-2 h), decreasing to 100 ml/h by 6 h. Although creatinine clearances did not vary significantly in the postoperative period (P = 0.16), significant changes were noted in the urinary concentrations of three tubular markers relative to creatinine concentration (P < 0.001). Urinary beta 2-microglobulin increased from negligible levels (median 0.01 mg/mmol creatinine) to peak at 4 h (median 4.55 mg/mmol), in part due to interference with its reabsorption by the plasma volume expander Haemaccel. Concentrations of the brush border antigen adenosine deaminase binding protein increased 6-fold, from a median of 5.03 arbitrary units (AU)/mumol to 31.2 AU/mumol at 48 h. The lysosomal enzyme N-acetyl-beta-D-glucosaminidase increased nearly 4-fold, from 0.68 units/mmol to 2.64 units/mmol at 48 h. Our results suggest that cardiac surgery utilising cardiopulmonary bypass is associated with acute tubular injury which can occur in the absence of overt changes in creatinine clearance.

Cobalamin inactivation by nitrous oxide produces severe neurological impairment in fruit bats : protection by methionine and aggravation by folates.

Nitrous oxide, which inactivates cobalamin when administered to fruit bats, results in severe neurological impairment leading to ataxia, paralysis and death. This occurs after about 6 weeks in animals depleted of cobalamin by dietary restriction, and after about 10 weeks in cobalamin replete bats. Supplementation of the diet with pteroylglutamic acid caused acceleration of the neurological impairment - the first unequivocal demonstration of aggravation of the neurological lesion in cobalamin deficiency by pteroylglutamic acid. The administration of formyltetrahydropteroylglutamic acid produced similar aggravation of the neurological lesion. Supplementation of the diet with methionine protected the bats from neurological impairment, but failed to prevent death. Methionine supplementation protected against the exacerbating effect of folate, preventing the development of neurological changes. These findings lend support to the hypothesis that the neurological lesion in cobalamin deficiency may be related to a deficiency in the methyl donor S-adenosylmethionine which follows diminished synthesis of methionine.

Fatty acid composition of human milk from South African black mothers consuming a traditional maize diet.

Fatty acid composition of mature human milk of rural and urban black South African mothers was determined by gas-liquid chromatography. Rural mothers consumed traditional diets low in animal protein and fat, and high in carbohydrate and fibre. Urban mothers consumed more varied, partially westernized diets, and two-thirds were overweight. Plasma cholesterol concentrations were significantly lower in the rural group (3.64 vs 4.75 mmol/l, P less than 0.01). Milk of rural mothers contained significantly higher percentages of C10:0, C12:0, and total saturated fatty acids. Fatty acids C8:0-C14:0 synthesized de novo in the mammary gland were substantially higher in the milk of the rural mothers (24.7 vs 15.9 per cent). Conversely, the milk of the urban group contained higher percentages of monounsaturated fatty acids, 18:3 omega 3 and 20:2 omega 6. The ratio of polyunsaturated to saturated fatty acids in rural samples was 0.36 +/- 0.13 compared to 0.41 +/- 0.15 in urban samples (P greater than 0.1). It is concluded that maternal dietary intake significantly affects milk composition, as demonstrated by the high percentages of fatty acids synthesized de novo in the mammary gland of rural mothers habituated to low-fat, high-carbohydrate intakes.

Comparative response to single or divided doses of parenteral iron for functional iron deficiency in hemodialysis patients receiving erythropoietin (EPO).

EPO treatment rapidly corrects anemia in patients with end-stage renal failure treated with hemodialysis, as long as sufficient iron is available. Absolute and relative (to demand) iron deficiency blunts the erythropoietic response and parenteral iron is frequently required during the course of therapy to restore EPO efficacy. Since the optimum time course of iron administration to restore EPO response in the short term is unknown, we compared three protocols of i.v. iron dextran administration in apparent functionally iron-deficient HD patients on oral iron therapy (hemoglobin < 10.0 g/dl plus ferritin < 100 micrograms/l and/or transferrin saturation < 20%). Intravenous iron (Imferon; Fisons Pty Ltd.) was given either as a single 600 mg dose (n = 15, Group I) or in divided doses of 100 mg administered on 6 successive dialyses (n = 14, Group II) or weekly for 6 weeks (n = 14, Group III). Response was monitored for 8 weeks. No adverse effects were observed. Collectively, mean hemoglobin increased (p < 0.01) by 0.4-0.5 g/dl plateauing at 4 weeks (between group comparison, p = 0.92). Mean ferritin concentrations changed with time (p < 0.01), peaking at 2 weeks in Groups I and II and at 4 weeks in Group III. Mean transferrin saturation levels also increased during the study (p < 0.001). The between group comparisons for the trends in iron indices were significant (p < 0.01 and 0.05 respectively). As there were no clinically significant differences in hemoglobin response at 4 weeks, single dose iron infusion would seem to be the most expedient in the short term, however frequent small doses are similarly effective.

Effect of withdrawal of folic acid supplementation in maintenance hemodialysis patients.

The requirement of patients on maintenance hemodialysis for dietary supplements of folic acid is controversial. High levels of folate carry the risk of toxicity as well as being unnecessary. We followed a group of 41 patients, not receiving erythropoietin, for 16 months after the cessation of folate supplementation (5 mg/day). Diet supplied 60-80 g protein and 120-260 micrograms folic acid/day. Red cell folate levels decreased linearly from a mean of 1931 +/- 888 micrograms/l (+/- SD) to 676 +/- 294 micrograms/l after 6 months before levelling off at 455 +/- 222 micrograms/l after 9 months. Mean values were unchanged 7 months later (491 +/- 319 micrograms/l). No patient developed folate deficiency. Hemoglobin values at 6, 9 and 16 months were slightly higher than the baseline value of 8.3 +/- 1.8 g/dl (p < 0.05). Mean corpuscular volumes were generally within normal limits, and vitamin B12 status was satisfactory. We conclude that folic acid supplements are unnecessary in adequately nourished hemodialysis patients who are not receiving erythropoietin.

The oxidation hypothesis of atherosclerosis: an update.

Hypercholesterolemia is associated with an increased risk of atherosclerosis. The oxidation hypothesis suggests that oxidative modification of lipoprotein, and in particular low-density lipoprotein (LDL), increases its atherogenicity by altering receptor-mediated uptake by cells in the intima of blood vessels. Oxidized LDL is taken up by scavenger receptors on monocytes, smooth muscle cells, and macrophages in an uncontrolled process leading to accumulation of lipid and the formation of foam cells, an early feature of atherosclerotic plaque. Recent research on the oxidation of LDL lipids, the effect of antioxidants, hypertensives, and other agents, the interaction of LDL with extrinsic factors, as well as patient studies which bear on the oxidation hypothesis, are summarised in this review.

Review: Biology and relevance of C-reactive protein in cardiovascular and renal disease.

C-reactive protein (CRP) is a member of the pentraxin family of proteins, which are characterised by a cyclic pentameric structure and radial symmetry. The five identical 24-kDa protomers consist of 206 amino acids, and are noncovalently linked. CRP binds to a range of substances such as phosphocholine, fibronectin, chromatin, histones, and ribonucleoprotein in a calcium-dependent manner. It is a ligand for specific receptors on phagocytic leukocytes, mediates activation reactions on monocytes and macrophages, and activates complement. Plasma CRP is the classical acute-phase protein, increasing 1,000-fold in response to infection, ischemia, trauma, burns, and inflammatory conditions. A growing number of studies suggest that CRP is an independent risk factor for atherosclerotic vascular disease. Plasma CRP concentrations in the highest quartile are associated, depending on the subject group, with 1.5- to 7-fold increases in relative risk. In the high-risk endstage renal failure population, a raised CRP is associated with up to 5.5-fold increased relative risk of CVD and 4.6-fold increased relative risk of death. This review examines the relationships between CRP, cardiovascular disease, and mortality, with special reference to renal disease.

Are metalloproteins and acute phase reactants associated with cardiovascular disease in end-stage renal failure?

End-stage renal failure (ESRF) is associated with a higher risk of cardiovascular disease (CVD) than predicted by the major risk factors. We investigate the hypothesis that metalloproteins such as transferrin and ceruloplasmin and the inflammatory response are associated with CVD risk in this population. In this cross-sectional study of 81 subjects stable on haemodialysis (HD), 43 with CVD and/or peripheral vascular disease (PAD) were compared to 38 subjects without clinical evidence of CVD/PAD. Serum concentrations of metalloproteins and acute phase reactants were compared by univariate analysis and logistic regression modelling. Body mass index, gender ratios, prevalence of diabetes, iron status, and homocysteine concentrations did not differ significantly between the groups. Those with CVD were older (P< 0.001) and had been on dialysis for longer (P = 0.004). CVD subjects had significantly higher concentrations of ceruloplasmin (325 vs 284 mg/L, P = 0.011), copper (18.2 vs 15.7 micromol/L, P = 0.002), and C-reactive protein (CRP) (median 9.0 vs 3.8 mg/L, P = 0.002). Transferrin iron binding capacity tended to be higher in the CVD group (P = 0.088). CVD risk for subjects with serum concentrations in the upper tertile was increased 9.4-fold (CI 2.8-31.0) for copper, 4.2-fold (CI 1.5-12.2) for ceruloplasmin, 3.9-fold (CI 1.3-12.1) for transferrin iron binding capacity, and 2.3-fold (CI 0.9-6.1) for CRP. In multivariate logistic regression models, age (P = 0.001) and time on dialysis (P = 0.002) were the strongest risk factors for CVD. After adjustment for age and time on dialysis, transferrin iron binding capacity (P = 0.013) and copper (P = 0.019) continued to be associated with CVD risk but ceruloplasmin (P = 0.065) and CRP (P = 0.634) were not. Total cholesterol was associated with a lower risk of CVD (ie protective), presumably due to cholesterol-lowering therapy in high-risk patients. In conclusion, copper and transferrin iron binding capacity may be associated with CVD risk in HD subjects.

Neurotoxicity of folates: implications for vitamin B12 deficiency and Huntington's chorea.

Recent work has shown that several folates interact with excitatory kainic acid receptors in the mammalian brain and appear to have agonist activity at these receptors. Since kainic acid is a potent neurotoxin it is possible that folates share this toxicity and that high levels of folates result in neuronal damage. Levels of methyltetrahydrofolate are markedly elevated in vitamin B12 deficiency, a disease associated with neuronal destruction. We propose that this destruction occurs as a result of a neurotoxic action of methyltetrahydrofolate. Injection of kainic acid into the basal ganglia of experimental animals produces a pattern of damage similar to that found in patients dying of Huntington's chorea. It is possible that the underlying defect in this disease resides in the pathways of folate metabolism such that a neurotoxic excess of folates accumulates in the central nervous system. Such a disease process might be arrested by antifolate drugs.

Evaluation of a novel vitamin E coated cellulosic membrane hollow fiber dialyzer.

Adverse physiologic effects accompany hemodialysis. Biocompatible dialyzer membranes may both limit oxidative stress and decrease beta2-microglobulin production, thereby reducing patient morbidity. We compared standard solute clearance, lipid, and antioxidant effects of a novel cellulosic membrane dialyzer modified with covalently bonded vitamin E (Excebrane Clirans E15, Terumo Australia) with standard cellulosic and polysulphone membrane dialyzers. Stable adult hemodialysis patients taking no lipid lowering or antioxidant therapy (n = 17; 9 male, 8 female) were recruited into a 10 week, prospective, unblinded study. Measurements were made at baseline on their usual dialyzer and after 2, 4, and 10 weeks of Excebrane use. Excebrane demonstrated good in vivo clearance of standard solutes relative to surface area. Predialysis beta2-microglobulin levels were unchanged with time and were significantly lower postdialysis than with cellulose acetate (p < 0.05). Oxidized low density lipoprotein levels as measured by nitrotyrosine residues were high predialysis, but tended to decrease with both membranes (p > 0.05). Total antioxidant status fell during dialysis (p < 0.0005), but plasma vitamin A and E concentrations increased (p = 0.007 and p = 0.02, respectively). Baseline vitamin A levels were high in all patients and, along with vitamin E, total antioxidant status and lipid profiles did not change over time with Excebrane use. Excebrane is an efficient, biocompatible membrane with no deleterious effects on beta2-microglobulin or lipids. More long-term study is merited.

Niacin status of schoolchildren in Transvaal Province, South Africa.

Niacin status was evaluated in groups of school children (n = 25) in Transvaal Province, South Africa, by measuring the urinary excretion of the metabolite 2-pyridone. In an urban Indian group of low socioeconomic status, and a white middle-class group, 12% and 4% respectively exhibited low or deficient levels of the metabolite. In a rural black village, 28% had evidence of low or deficient levels of niacin, even though two of the 3 locally available brands of maize meal (their dietary staple) claimed to be fortified with nicotinamide. It is concluded that external monitoring of the voluntary maize meal fortification scheme will be necessary to effectively combat deficiency of niacin in traditional maize meal consumers.