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Biomedical subjects

D C Roberts

Publications and source records attributed to D C Roberts.

At least 91 records · Page 5Linked to original sources

Dietary factors in the fall in coronary heart disease mortality.

The role of dietary change in the fall in heart disease mortality has been hotly debated. Three countries, Australia, USA and UK with equal 'care' and sophistication of surgical techniques have shown different timing in the beginning of the decline of this 'epidemic'; around the mid 1960s in the first two countries, but not until the late 1970s for the UK. The cause of this difference may be the changing food habits of their populations. Using food disappearance data, apparent consumption of butter and margarine show opposite trends (butter down and margarine up) predating the decline in mortality in both the USA and Australia by at least 7 years and also in the UK, but at a later time, (about 1970). Changes in adipose tissue linoleate, a marker for polyunsaturated fat intake, support this indirect evidence, with depot levels rising in the USA from the 1960s and 10 years later in the UK. Other evidence support the view of decreasing saturated fat intake and increasing polyunsaturated intake prior to 1960 in the USA. Although many factors must contribute to the decline in mortality from CHD, change in dietary P/S ratio would seem to be the major dietary contributor.

Adipose Tissue↗

Erythrocyte eicosapentaenoic acid versus docosahexaenoic acid as a marker for fish and fish oil consumption.

The fatty acid composition of erythrocyte membranes was investigated in 21 healthy men after 6 wk of varying intakes of eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3). In one experiment, 12 subjects were fed three diets in a 3 x 3 crossover design: an essentially fish-free control diet, a fish diet (0.15 g EPA/d, 0.41 g DHA/d) and the same fish-based diet supplemented with 5 g/d fish oil (Fish + Oil: 0.99 g EPA/d, 0.99 g DHA/d). A 6 wk wash-out period was allowed between each diet. In another experiment, 11 subjects were supplemented with 5 g/d fish oil alone for 6 wk (0.84 g EPA/d, 0.48 g DHA/d). After fish or fish oil feeding, the percent proportion of EPA and DHA in the erythrocyte membranes rose at the expense of linoleic and arachidonic acids. After 6 wk on the fish-based diets, EPA incorporation approached saturation, with the incremental increases being proportional to the amounts supplied by the diets. In contrast, parallel increases were observed for erythrocyte DHA even though the Fish + Oil diet was supplying twice as much DHA as the fish alone diet. These observations imply different metabolic rates for EPA and DHA and their importance is discussed in terms of the value of erythrocyte EPA versus DHA as markers for fish and fish oil consumption.

Adolescent↗

Persistent changes in the fatty acid composition of erythrocyte membranes after moderate intake of n-3 polyunsaturated fatty acids: study design implications.

To examine the incorporation of n-3 polyunsaturated fatty acids (PUFAs) into erythrocyte membranes during and after moderate n-3 PUFA intake, 12 healthy men were fed three diets for 6-wk periods in a 3 x 3 crossover design, supplying different amounts of eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3): a control diet, a fish diet (0.15 g EPA/d, 0.41 g DHA/d), and a fish + oil diet (5 g fish oil/d; 0.99 g EPA/d and 0.99 g DHA/d). A 6-wk washout period was allowed between diets. Between 6 and 12 wk after the fish + oil diet, erythrocyte EPA and DHA were still declining and it was only after 18 wk that erythrocyte EPA had returned to baseline whereas DHA had not. Investigators examining variables that are influenced by altered membrane fatty acid composition should be aware of these prolonged effects when designing studies. Protracted washout periods (greater than 18 wk) make the classic crossover design prohibitive and a parallel design becomes essential.

Adult↗

Low-glycemic index foods improve long-term glycemic control in NIDDM.

OBJECTIVE: To compare high- and low-glycemic index (GI) diets in the treatment of non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: Sixteen subjects with well-controlled NIDDM and normal lipid profile, 10 of whom continued oral hypoglycemic medication, participated in the study. A diet that emphasized low-GI foods (e.g., porridge, pasta) was compared with a high-GI diet (e.g., processed cereals, potatoes). The GI of the low-GI diet was 15% lower than the high-GI diet (77 +/- 3 vs. 91 +/- 1) but otherwise similar in macronutrient composition and fiber, as determined by a 4-day weighed record. The diets were instituted under instruction from a dietitian who visited subjects at home on a weekly basis. Body weight was maintained within 1-2 kg. RESULTS: Glycemic control was improved on the low-GI diet compared with the high-GI diet (statistically significant findings, P less than 0.05). Mean glycosylated hemoglobin at the end of the low-GI diet was 11% lower (7.0 +/- 0.3%) than at the end of the high-GI diet (7.9 +/- 0.5%), and the 8-h plasma glucose profile was lower (area under the curve above fasting 128 +/- 23 vs. 148 +/- 22 mmol.h-1.L-1, respectively). Mean fasting plasma glucose, total cholesterol triglycerides, and lipoproteins did not show important differences. CONCLUSIONS: A low-GI diet gives a modest improvement in long-term glycemic control but not plasma lipids in normolipidemic well-controlled subjects with NIDDM.

Blood Glucose↗

Break-points on a progressive ratio schedule reinforced by intravenous cocaine increase following depletion of forebrain serotonin.

The effect of intracerebral injections of 5,7-dihydroxy-tryptamine (5,7-DHT) on cocaine self-administration behavior was assessed. Rats were tested on a progressive ratio (PR) schedule for cocaine reinforcement. The first response on the lever each day produced an IV infusion of cocaine (0.6 mg/injection) after which the requirements of the schedule escalated with each reinforcement until the behavior extinguished. The final ratio completed was defined as the breaking point. Bilateral injections of 5,7-DHT into either the medial forebrain bundle (MFB) or amygdala (AMY) significantly increased the breaking points on the PR schedule compared to vehicle-injected control animals. We interpret these data to indicate that depletion of forebrain serotonin increases the incentive value of cocaine.

5,7-Dihydroxytryptamine↗

A mixed Australian fish diet and fish-oil supplementation: impact on the plasma lipid profile of healthy men.

Twelve healthy men were fed in turn three diets for 6 wk each in a 3 x 3 randomized block design: a control diet (essentially fish free), a fish diet (200 g lean Australian fish flesh/d), and the same fish-based meal but supplemented with 5 g fish oil/d. Dietary eicosapentaenoic acid [EPA, 20: 5n-3 (omega-3)] was strongly associated with erythrocyte membrane EPA (r = 0.908 at 6 wk), strengthening its value as a measure of compliance in fish and fish-oil feeding trials. On the fish diet, subjects had increased incorporation of n-3 polyunsaturated fatty acids (PUFAs) at the expense of n-6 PUFAs in their erythrocyte membranes. When the fish-based diet was supplemented with fish oil (5 g/d), there was a significant lowering of plasma triacylglycerol (-0.16 +/- 0.24 mmol/L; mean +/- SD). No change in plasma total cholesterol was detected although the fish + oil diet produced a reduction in very-low-density-lipoprotein cholesterol (-0.24 +/- 0.26 mmol/L).

Adult↗

Dietary protein and cholesterol metabolism--interaction of minerals.

Increased dietary zinc has been shown to reduce plasma total cholesterol in rabbits fed casein. However, the mechanism is not clear. The minerals associated with casein and soya protein are different and present in amounts which can alter the overall mineral composition of the diet. In particular, casein has a much higher ratio of zinc/copper than soy protein. Utilising a range of copper concentrations (2-80 micrograms/g diet) in 14 experiments with casein diets showed a linear relationship between the cholesterolaemic response and copper concentration (when both log transformed) in groups (n = 6) of rabbits fed for 12 weeks (r = -0.70, p less than 0.05). The lower the copper, the greater the response. In no case was the copper content deficient, indicating some interaction must be reducing its availability. Similar analysis utilising the range of zinc (10-125 micrograms/g) in the diets also showed an enhanced response at low intakes (r = -0.85, p less than 0.05). To elucidate the mechanism, 2 groups of rabbits were fed casein diets containing 21 and 68 mg zinc/kg diet for 12 weeks. Low density apolipoprotein B (LDL-apoB) turnover was carried out using 125I labelled LDL-apoB and data was fitted to the 2 pool model. The production of LDL-apoB was reduced in animals fed the higher dietary zinc. Zinc appears to act by enhancing the production of LDL-apoB in casein fed animals, perhaps by reducing the availability of copper.

Animals↗

Adrenal demedullation blocks and brain norepinephrine depletion potentiates the hyperglycemic response to a variety of stressors.

The role of adrenal hormones in mediating the increase in blood glucose levels following several stressful stimuli (environmental and pharmacological) was studied. The role for brain norepinephrine systems in the initiation of the BG response to these challenges was investigated as well. There is disagreement as to whether stress-induced increases in blood glucose levels are mediated primarily by hormonal or neural stimulation of the liver. A stressful stimulus probably causes increases in blood glucose levels by activating neural connections from the brain to both the liver and the adrenal medulla. The relative contribution that each of these pathways makes to the overall blood glucose response may be dependent on certain factors, such as the type of preparation used (awake or anesthetized, fasted or fed) and the intensity of the stimulus used to induce hyperglycemia. In the experiments reported here, which were performed in awake male rats, we found that increases in blood glucose levels following brief footshock stress, injection of 2-deoxy-D-glucose, exposure to the odor of a predator, and electrical stimulation of the hypothalamus were almost entirely eliminated by removal of the adrenal medullae, a procedure that does not damage hypothalamic norepinephrine systems or the multi-synaptic neural pathways from the hypothalamus to the liver. Furthermore, rather than having impaired blood glucose responses, rats that were depleted of brain norepinephrine showed normal responses to the injection of adrenergic agonists (including epinephrine), and potentiated responses to stressful stimuli compared to non-depleted controls. We conclude that: (1) rapid changes in blood glucose levels that occur following the stressful stimuli used here are mediated mainly by the release of epinephrine from the adrenal medullae and (2) intact brain norepinephrine systems are not required for these increases in blood glucose to occur.

Adrenal Medulla↗

Self-administration of cocaine on a progressive ratio schedule in rats: dose-response relationship and effect of haloperidol pretreatment.

Intravenous cocaine self-administration behavior in rats was investigated using a progressive ratio (PR) schedule of reinforcement. The first response on the lever each day produced a drug infusion, whereupon the requirements of the schedule escalated with each reinforcement until the behavior extinguished. The final ratio completed each day was found to be relatively stable, sensitive to changes in dose, and drastically reduced by pretreatment with haloperidol (0.05 mg/kg). We conclude that self-administration behavior of rats reinforced on a progressive ratio schedule can provide useful information about changes in the reinforcing efficacy of specific drugs.

Animals↗

The estrous cycle affects cocaine self-administration on a progressive ratio schedule in rats.

Although it has been demonstrated that many of the behavioral responses to psychomotor stimulants are gender dependent and hormonally sensitive, few studies have examined the possibility that the estrous cycle interacts with drug reinforcement in laboratory animals. The present experiment assessed the effect of the estrous cycle on two aspects of cocaine self-administration behavior: the breaking point on a progressive ratio (PR) schedule and the rate of cocaine intake on a fixed ratio one (FR1) schedule. On the PR schedule, the first lever response produced a drug infusion. Subsequent response requirements escalated with each injection until the behavior extinguished. Breaking points were defined as the final ratio completed. On a FR1 schedule, the estrous cycle had no effect on the rate of drug intake. On a PR schedule, female rats reached higher breaking points during estrus than during other stages of the estrous cycle. Furthermore, female rats displayed higher breaking points than male rats. It appears that the estrous cycle influences an animal's motivation to self-administer cocaine.

Animals↗

Breaking points on a progressive ratio schedule reinforced by intravenous apomorphine increase daily following 6-hydroxydopamine lesions of the nucleus accumbens.

It has been shown previously that 6-hydroxydopamine (6-OHDA)-induced lesions of the nucleus accumbens cause extinction of cocaine self-administration behavior, yet fail to affect the rate of apomorphine self-administration on a Fixed Ratio 1 schedule of reinforcement. Since the dopamine (DA) receptors in this nucleus should become supersensitive, and since these receptors are thought to mediate the reinforcing effects of apomorphine, then some change in apomorphine self-administration would be expected. We have therefore reinvestigated the effect of 6-OHDA lesions on apomorphine self-administration using a progressive ratio schedule of reinforcement. Rats were trained to self-administer apomorphine (0.033 mg/inj, IV) on a schedule in which the response requirements increased after each reinforcement. The breaking point was defined as the final ratio completed during each daily session. Sham lesions had no effect on the breaking points, and a steady increase in the breaking point was observed in the 6-OHDA-lesioned animals which may parallel the development of DA receptor supersensitivity.

Animals↗

Lifestyle factors in monozygotic and dizygotic twins.

In examining genetic influences on biological variables using twins, it may be important to examine the distribution between and within twin pairs of demographic and lifestyle factors that may themselves affect the biological variable being studied. We explored the distribution of demographic and lifestyle factors that may affect blood lipid levels or ischaemic heart disease (IHD) risk among a sample of 106 monozygotic (MZ) and 94 like-sex dizygotic (DZ) twin pairs. In our sample, MZ twins were statistically significantly different from DZ twins only in marital status, cigarette smoking habits, and the ratio of polyunsaturated to saturated fat (P:S ratio) in their dietary intake. The latter variable was among many dietary variables examined (using 4-day weighed food diaries), and the size of the difference in intake was small. When comparisons were made of the similarities within twin pairs, we found members of MZ twin pairs to be statistically significantly closer than DZ twins in educational achievement, occupation, cigarette smoking, and exercise habits, and the number of days a week on which alcohol was consumed. These last three variables were consistently closer among twins with closer contact than among those with a smaller degree of current shared environment. For 12 of the 13 nutrients examined, the within-pair correlations were higher for MZ than for DZ twins, although our test for significant genetic variance showed statistical significance only for intake of complex carbohydrates. We conclude that MZ twins share demographic and lifestyle factors that might influence the risk of IHD and blood lipid levels to a greater degree than do DZ twins, although it is difficult to say if these similarities in lifestyle result from genetic influences or not. Nevertheless, ascribing differences between correlations in MZ and DZ twin pairs for lipid levels as being purely "genetic"--as implicit in conventional measures of heritability--is likely to overestimate the influence of genetic factors.

Adolescent↗

Twin study of genetic and environmental effects on lipid levels.

A study of 106 pairs of monozygotic (MZ) and 94 pairs of dizygotic (DZ) twins tested the hypothesis that part of the previously described genetic influence on blood lipid levels can be ascribed to closer similarities among MZ than among DZ twin pairs in environmental factors that affect lipid levels. Participants were adult twin volunteers (age 17-66; 64 male and 136 female pairs) who were selected from the NH & MRC Twin Registry or were respondents to advertisements. They completed a 4-day weighed food diary from which mean nutrient intake was derived. Information on lifestyle and demographic variables was obtained by questionnaire and a nonfasting blood sample was taken for measures of total, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol and the HDL2 and HDL3 subfractions. Height and weight were measured, and body mass index (BMI) was calculated (kg/m2). Estimates of the heritability of sex-adjusted lipid levels were 0.72 for total cholesterol, 0.79 for HDL cholesterol, 0.69 for HDL2, 0.20 for HDL3, 1.06 for LDL cholesterol, and 0.44 for sex-adjusted BMI. In all cases except for HDL3, genetic variance was statistically significant. After adjusting for the effects of environmental variables in three different ways, the estimates of heritability were somewhat lower for total cholesterol, HDL2, and BMI, and those for HDL cholesterol (borderline) and LDL cholesterol (definitely) remained statistically significant but were decreased. A genetic influence on HDL3 was not found. Adjusted heritability estimates obtained from one method of analysis were 0.35 for total cholesterol, 0.49 for HDL, 0.04 for HDL2, -0.34 for HDL3, 0.66 for LDL, and 0.32 for BMI. These results suggest that the assumptions made in the classical twin study approach are not appropriate when examining genetic effects on lipid levels or BMI, or indeed on any biological variable that may be affected by environmental factors that tend to be more similar in MZ twins than in DZ twins. In these circumstances, more complex models may be needed to differentiate between genetic and environmental influences.

Adolescent↗

The effect of zinc supplements on lipoproteins and copper status.

As part of a study to determine the effect of 150 mg zinc/day on plasma lipoproteins, healthy young female (n = 26; mean age 27 years) and male (n = 21; mean age 28 years) volunteers took part in a double-blind cross-over trial lasting 12 weeks. During 6 weeks of supplementation, plasma Zn rose significantly in both groups, indicating compliance. Plasma total cholesterol remained unchanged in both males and females. However, mean LDL-cholesterol decreased from 2.38 to 2.17 mmol/l in females and there was a trend for total HDL-cholesterol to be redistributed in that HDL2 rose and HDL3 fell slightly. In parallel with these changes in females, Zn supplements reduced the ferroxidase activity of serum caeruloplasmin (from 13.0 to 11.3 U/ml) and the antioxidant activity of erythrocyte superoxide dismutase (E-SOD) (from 4557 to 3638 U/g Hb) and CuZn E-SOD (from 2184 to 1672 U/g Hb). Plasma Cu and haematocrit were unaffected. No such changes were seen in males in either lipoproteins or these indicators of Cu status. Since the females were lighter than the males but received the same dose, a dose-response effect rather than a sex difference cannot be ruled out. Overall, Zn supplements significantly decrease a major risk factor for CHD in females but reduced their Cu status.

Administration, Oral↗

Alpha 2-adrenergic receptors mediate the increase in blood glucose levels induced by epinephrine and brief footshock stress.

1. The purpose of the present experiments was to determine which adrenergic receptor(s) mediated the blood glucose surge following administration of epinephrine and brief footshock stress. 2. It was found that the order of potency of adrenergic agonists to increase blood glucose levels was: clonidine (alpha 2) much greater than epinephrine (alpha + beta) much greater than isoproterenol (beta) greater than phenylephrine (alpha 1). 3. The blood glucose increases caused by both epinephrine and footshock stress were greatly attenuated by the alpha-adrenergic antagonist, phentolamine (1.0 and 5.0 mg/kg ip), while the beta-adrenergic antagonist, propranolol (1.0 or 5.0 mg/kg ip), was without effect. Furthermore, it was found that the alpha 2-adrenergic antagonist, yohimbine (5.0 mg/kg ip), attenuated the epinephrine-induced increase in blood glucose levels, whereas the alpha 1 antagonist, phenoxybenzamine (5.0 mg/kg ip) dramatically potentiated the rise in glucose levels. 4. We conclude that the increase in blood glucose levels following brief footshock stress or injection of epinephrine is mediated by alpha 2-adrenergic receptors.

Animals↗

The effect of zinc supplements on plasma zinc and copper levels and the reported symptoms in healthy volunteers.

Information from animal studies has demonstrated the harmful effects of zinc supplementation on copper transport. Although some studies have been carried out in humans, the effect on humans has not been as well documented as the effect on animals. Forty-seven healthy volunteers (26 women and 21 men) took part in a double-blind cross-over trial which lasted for 12 weeks. The subjects were asked to take 50 mg of elemental zinc (as 220 mg zinc sulphate) or placebo, three times a day for six weeks. Venous blood was collected for the analysis of plasma levels of copper and zinc. Symptoms, which included headaches, abdominal cramps, nausea, loss of appetite and vomiting, were registered from 84% of women and 18% of men. Six female volunteers discontinued the trial; five owing to gastric irritation and one owing to consistent headaches. Plasma zinc levels rose significantly in both men and women, the increase being 36% and 57%, respectively. Plasma copper levels did not change significantly. Our study suggests that the gastric discomfort that is associated with zinc supplementation may be related to body weight as symptoms were reported from the lower-weight volunteers. Our study also shows no detrimental effect of 150 mg of zinc a day on plasma copper levels in healthy volunteers over a period of six weeks.

Adult↗