Prolonged neglect following unilateral disruption of a prefrontal cortical-dorsal striatal system.

We investigated the potential function of the system formed by connections between the medial prefrontal cortex and the dorsomedial striatum in aspects of attentional function in the rat. It has been reported previously that disconnection of the same corticostriatal circuit produced marked deficits in performance of a serial, choice reaction-time task while sparing the acquisition of an appetitive Pavlovian approach behaviour in an autoshaping task (Christakou et al., 2001). Here, we hypothesized that unilateral disruption of the same circuit would lead to hemispatial inattention, contrasting with the global attention deficit following complete disconnection of the system. Combined unilateral lesions of the medial prefrontal cortex (mPFC) and the medial caudate-putamen (mCPu) within the same hemisphere produced a severe and long-lasting contralesional neglect syndrome while sparing the acquisition of autoshaping. These results provide further evidence for the involvement of the medial prefrontal-dorsomedial striatal circuit in aspects of attentional function, as well as insight into the nature of neglect deficits following lesions at different levels within corticostriatal circuitry.

Effects of prolonged conditioning on dormancy and germination of Striga hermonthica

The impact of environment on the germination biology of Striga hermonthica was studied in the laboratory by conditioning seeds at various water potentials and urea concentrations at 17.5 to 37.5°C for up to 133 days. The experimental results presented in this research are related to the effects of temperature, water potential and urea nitrogen concentration during conditioning on subsequent germination percentage of S. hermonthica. Maximum germination in S. hermonthica seeds was observed at conditioning temperatures of 20 to 25°C within the range investigated of 17.5 to 37.5°C. Water stress and also urea during conditioning suppressed maximum germination. However, the conditioning temperature ranges at which maximum germination percentages occur vary with water stress and also urea concentration. In the presence of a high concentration of urea (3.16 mM), temperatures required for maximum germination narrowed to between 17.5 to 20°C. The optimum period of conditioning decreased with increase in water stress and also urea concentration similar to previous reports. The implications of these findings on Striga hermonthica field infestations have been investigated and being reported in another paper. Germination was greatly suppressed by conditioning environments including 3.16 mM urea and at 37.5°C. At the high concentration of 3.16 mM, temperatures required for maximum germination narrowed to between 17.5 and 20°C. Optimum conditioning period decreased with water stress and with increase in urea concentration.

Modelling effects of prolonged conditioning on dormancy and germination of Striga hermonthica

The impact of environment on the germination biology of the parasite was studied in the laboratory with seeds conditioned at various water potentials, urea concentrations and at 17.5 to 37.5°C for up to 133 days. Maximum germination was observed at 20 to 25°C. Water stress and urea suppressed maximum germination. The final percentage germination response to period of conditioning showed a non-linear relationship and suggests the release of seeds from dormancy during the initial period and later on dormancy induction. Germination percentage increased with increase in conditioning period to a threshold and remained stable for variable periods followed by a decline with further extension of conditioning time. The decline in germination finally terminated in zero germination in most treatments before the end of experimentation. The investigated factors of temperature, water potential and urea showed clear effects on the expression of dormancy pattern of the parasite. The effects of water potential and urea were viewed as modifying a primary response of seeds to temperature during conditioning. The changes in germinability potential during conditioning were consistent with the hypothesis that dormancy periods are normally distributed within seed populations and that loss of primary dormancy precedes induction of secondary dormancy. Hence an additive mathematical model of loss of primary dormancy and induction of secondary as affected by environment was developed as: G = {[Φ-1 (Kp+ (po+pnN+pwW) (T-Tb) t)]-[Φ-1 (Ks+ ((swW+sa)+sorT)t)]}[Φ-1(aT2+bT+c+cwW)].

Effect of prolonged intravenous glucose and essential amino acid infusion on nitrogen balance, muscle protein degradation and ubiquitin-conjugating enzyme gene expression in calves

Background: Intravenous infusions of glucose and amino acids increase both nitrogen balance and muscle accretion. We hypothesised that co-infusion of glucose ( to stimulate insulin) and essential amino acids (EAA) would act additively to improve nitrogen balance by decreasing muscle protein degradation in association with alterations in muscle expression of components of the ubiquitin-proteasome proteolytic pathway. Methods: We examined the effect of a 5 day intravenous infusions of saline, glucose, EAA and glucose + EAA, on urinary nitrogen excretion and muscle protein degradation. We carried out the study in 6 restrained calves since ruminants offer the advantage that muscle protein degradation can be assessed by excretion of 3 methyl-histidine and multiple muscle biopsies can be taken from the same animal. On the final day of infusion blood samples were taken for hormone and metabolite measurement and muscle biopsies for expression of ubiquitin, the 14-kDa E2 ubiquitin conjugating enzyme, and proteasome sub-units C2 and C8. Results: On day 5 of glucose infusion, plasma glucose, insulin and IGF-1 concentrations were increased while urea nitrogen excretion and myofibrillar protein degradation was decreased. Co-infusion of glucose + EAA prevented the loss of urinary nitrogen observed with EAA infusions alone and enhanced the increase in plasma IGF-1 concentration but there was no synergistic effect of glucose + EAA on the decrease in myofibrillar protein degradation. Muscle mRNA expression of the ubiquitin conjugating enzyme, 14-kDa E2 and proteasome sub-unit C2 were significantly decreased, after glucose but not amino acid infusions, and there was no further response to the combined infusions of glucose + EAA. Conclusion: Prolonged glucose infusion decreases myofibrillar protein degradation, prevents the excretion of infused EAA, and acts additively with EAA to increase plasma IGF-1 and improve net nitrogen balance. There was no evidence of synergistic effects between glucose + EAA infusion on muscle protein degradation or expression of components of the ubiquitin-proteasome proteolytic pathway.

Meal ingestion provokes entry of lipoproteins containing fat from the previous meal: possible metabolic implications

Background: Prolonged and exaggerated postprandial plasma triacylglycerol (TAG) concentrations are considered as an independent risk factor for coronary artery disease. Western populations eat many meals at regular intervals, and can be in a postprandial state for at least 17h of a 24h period. After consuming 2 meals an early plasma TAG peak has been observed after the second meal, the origin of which is unclear. Aim of the study: To test the hypothesis that the early TAG peak observed following sequential meals was of intestinal origin and represented fat derived from the previous meal. Methods: Postprandial plasma lipaemic responses of 17 healthy postmenopausal women were studied by giving a test breakfast followed by a lunch. Watermiscible retinyl palmitate (RP) was added to the breakfast, but not the lunch test meal. Plasma TAG, retinyl esters (RE) and apo B-48 were determined for a 10h period following breakfast. Results: In response to the test meals, RE, apo B-48 and TAG showed multiple peaks. Despite omission of RP from the lunch, RE showed an early peak response after ingestion of lunch in 15 of 17 subjects. The peak response after lunch of all three markers appeared significantly earlier compared with their respective peak responses after the breakfast (P < 0.0001). The area of RE response after lunch was significantly correlated with the RE lipaemic response to the breakfast (r = 0.67; P < 0.004) and to the fasting TAG concentration (r = 0.48; P < 0.05). Conclusions: Since the lunch did not contain RP, the distinctive second influx of RE after lunch was believed to have originated from the breakfast. This, together with the fact that all three markers showed an earlier response to the lunch than the breakfast, supports the view that ingestion of a second meal provokes entry of fat from the previous meal, from an as yet unidentified site (gut, enterocytes, lymph). The results indicate that the degree of TAG "storage" from previous meals might be a function of TAG tolerance and provide a possible site of regulation of the entry of fat into the systemic circulation.

Apolipoprotein B-48: comparison of fasting concentrations measured in normolipidaemic individuals using SDS-PAGE, immunoblotting and ELISA

Raised levels of chylomicrons and chylomicron remnants, which circulate following a meal, have been implicated in the development of atherosclerosis. Apolipoprotein (apo) B-48 is exclusively associated with chylomicron particles and provides a specific direct measurement of the number of intestinally derived lipoproteins in the circulation. The quantification of apo B-48 in biological samples is difficult due to the very low concentration in plasma, structural similarity to the N-terminal 48% of apo B-100 and lack of an appropriate standard for apo B-48. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), followed by coomassie blue staining, has been used for many years to measure apo B-48 levels in triacylglycerol (TAG)-rich lipoprotein samples. The raising of antiserum to apo B-48 has led to development of more sensitive and specific methods including immunoblotting and enzyme-linked immunosorbant assays (ELISAs). This has enabled direct measurement of apo B-48 in plasma without the need for separation into TAG-rich lipoproteins. A high degree of variability was observed in the apo B-48 concentrations reported in the literature both within and between the SDS-PAGE, immunoblotting and ELISA methods. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

Plant- and marine-derived n-3 polyunsaturated fatty acids have differential effects on fasting and postprandial blood lipid concentrations and on the susceptibility of LDL to oxidative modification in moderately hyperlipidemic subjects

Background: Dietary a-linolenic acid (ALA) can be converted to long-chain n-3 polyunsaturated fatty acids (PUFAs) in humans and may reproduce some of the beneficial effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on cardiovascular disease risk factors. Objective: This study aimed to compare the effects of increased dietary intakes of ALA and EPA+DHA on a range of atherogenic risk factors. Design: This was a placebo-controlled, parallel study involving 150 moderately hyperlipidemic subjects randomly assigned to 1 of 5 interventions: 0.8 or 1.7 g EPA+DHA/d, 4.5 or 9.5 g ALA/d, or an n-6 PUFA control for 6 mo. Fatty acids were incorporated into 25 g of fat spread and 3 capsules to be consumed daily. Results: The change in fasting or postprandial lipid, glucose, or insulin concentrations or in blood pressure was not significantly different after any of the n-3 PUFA interventions compared with the n-6 PUFA control. The mean (+/-SEM) change in fasting triacylglycerols after the 1.7-g/d EPA+DHA intervention (-7.7 +/- 4.99%) was significantly (P < 0.05) different from the change after the 9.5-g/d ALA intervention (10.9 +/- 4.5%). The ex vivo susceptibility of LDL to oxidation was higher after the 1.7-g/d EPA+DHA intervention than after the control and ALA interventions (P < 0.05). There was no significant change in plasma a-tocopherol concentrations or in whole plasma antioxidant status in any of the groups. Conclusion: At estimated biologically equivalent intakes, dietary ALA and EPA+DHA have different physiologic effects.

Impact of menstrual cycle phase on insulin sensitivity measures and fasting lipids

There is evidence to suggest that insulin sensitivity may vary in response to changes in sex hormone levels. However, the results Of human studies designed to investigate changes in insulin sensitivity through the menstrual cycle have proved inconclusive. The aims of this Study were to 1) evaluate the impact of menstrual cycle phase on insulin sensitivity measures and 2) determine the variability Of insulin sensitivity measures within the same menstrual cycle phase. A controlled observational study of 13 healthy premenopausal women, not taking any hormone preparation and having regular menstrual cycles, was conducted. Insulin sensitivity (Si) and glucose effectiveness (Sg) were measured using an intravenous glucose tolerance test (IVGTT) with minimal model analysis. Additional Surrogate measures Of insulin sensitivity were calculated (homoeostasis model for insulin resistance [HOMA IR], quantitative insulin-to-glucose check index [QUICKI] and revised QUICKI [rQUICKI]), as well as plasma lipids. Each woman was tested in the luteal and follicular phases of her Menstrual cycle, and duplicate measures were taken in one phase of the cycle. No significant differences in insulin sensitivity (measured by the IVGTT or Surrogate markers) or plasma lipids were reported between the two phases of the menstrual cycle or between duplicate measures within the same phase. It was Concluded that variability in measures of insulin sensitivity were similar within and between menstrual phases.

Interactions between age and apoE genotype on fasting and postprandial triglycerides levels

Objective The influences of genetic determinants on the magnitude of postprandial lipaemia are presently unclear. Here the impact of the common apolipoprotein (apo)E epsilon mutation on the postprandial triglyceride (TG) response is determined, along with an assessment of genotype penetrance according to age, body mass index and gender. Methods and results Healthy adults (n = 251) underwent a postprandial investigation, in which blood samples were taken at regular intervals after a test breakfast (0 min, 49 g fat) and lunch (330 min, 29 g fat) until 480 min after the test breakfast. There was a significant impact of apoE genotype on fasting total cholesterol (TC), (P = 0.027), LDL-cholesterol (LDL-C), (P = 0.008), and %LDL3 (P = 0.001), with higher and lower levels in the E4 and E2 carriers respectively relative to the E3/E3 genotype. Reflective of a higher fasting TG (P = 0.001), a significantly higher area under the curve for the postprandial TG response (TG AUC) was evident in the E4 carriers relative to the E3/E3 group (P = 0.038). In the group as a whole, a significant age × genotype interaction was observed for fasting TC (P = 0.021). In the participants >50 years there was a significant impact of genotype on TC (P = 0.005), LDL-C (P = 0.001) and TAG AUC (P = 0.028). Conclusions It is possible that an exaggerated postprandial lipaemia contributes to the increased coronary heart disease risk associated with carriers of the E4 allele; an effect which is more evident in older adults.

Altered expression of cell cycle proteins and prolonged duration of cardiac myocyte hyperplasia in p27KIP1 knockout mice

The precise role of cell cycle-dependent molecules in controlling the switch from cardiac myocyte hyperplasia to hypertrophy remains to be determined. We report that loss of p27(KIP1) in the mouse results in a significant increase in heart size and in the total number of cardiac myocytes. In comparison to p27(KIP1)+/+ myocytes, the percentage of neonatal p27(KIP1)-/- myocytes in S phase was increased significantly, concomitant with a significant decrease in the percentage of G(0)/G(1) cells. The expressions of proliferating cell nuclear antigen, G(1)/S and G(2)/M phase-acting cyclins, and cyclin-dependent kinases (CDKs) were upregulated significantly in ventricular tissue obtained from early neonatal p27(KIP1)-/- mice, concomitant with a substantial decrease in the expressions of G(1) phase-acting cyclins and CDKs. Furthermore, mRNA expressions of the embryonic genes atrial natriuretic factor and alpha-skeletal actin were detectable at significant levels in neonatal and adult p27(KIP1)-/- mouse hearts but were undetectable in p27(KIP1)+/+ hearts. In addition, loss of p27(KIP1) was not compensated for by the upregulation of other CDK inhibitors. Thus, the loss of p27(KIP1) results in prolonged proliferation of the mouse cardiac myocyte and perturbation of myocyte hypertrophy.

Prolonged effects of modified sham feeding on energy substrate mobilization

Background: Vagal stimulation in response to nutrients is reported to elicit an array of digestive and endocrine responses, including an alteration in postprandial lipid metabolism. Objective: The objective of this study was to assess whether neural stimulation could alter hormone and substrate metabolism during the late postprandial phase, with implications for body fat mobilization. Design: Vagal stimulation was achieved by using the modified sham feeding (MSF) technique, in which nutrients are chewed and tasted but not swallowed. Ten healthy subjects were studied on 3 separate occasions, 4 wk apart. Five hours after a high-fat breakfast (56 g fat), the subjects were given 1 of 3 test meals allocated in random order: water, a lunch containing a modest amount of fat (38 g), or MSF (38 g fat). Blood was collected for 3 h poststimulus for hormone and metabolite analyses. Results: Plasma insulin and pancreatic polypeptide concentrations peaked at 250% and 209% of baseline concentrations within 15 min of MSF. The plasma glucose concentration increased significantly (P = 0.038) in parallel with the changes observed in the plasma insulin concentration. The nonesterified fatty acid concentration was significantly suppressed (P = 0.006); maximum suppression occurred at a mean time of 114 min after MSF. This fall in nonesterified fatty acid was accompanied by a fall in the plasma glucagon concentration from 122 to 85 pmol/L (P = 0.018) at a mean time of 113 min after MSF. Conclusions: Effects on substrate metabolism after MSF in the postprandial state differ from those usually reported in the postabsorptive state. The effects of MSF were prolonged beyond the period of the cephalic response and these may be relevant for longer-term metabolic regulation.

The effect of the daily intake of inulin on fasting lipid, insulin and glucose concentrations in middle-aged men and women

The present study was carried out to examine the effect of the daily intake of 10 g inulin on fasting blood lipid, glucose and insulin levels in healthy middle-aged men and women with moderately raised total plasma cholesterol (TC) and triacylglycerol (TAG) levels. This study was a doubleblind randomized placebo-controlled parallel study in which fifty-four middle-aged subjects received either inulin or placebo for a period of 8 weeks. Fasting blood samples were collected before the supplementation period (baseline samples 1 and 2, separated by 1 week) and at weeks 4 and 8, with a follow-up at week 12. Compared with baseline values, insulin concentrations were significantly lower at 4 weeks (P,0×01) in the inulin group. There was a trend for TAG values, compared with baseline, to be lower in the inulin group at 8 weeks (P,0×08) returning to baseline concentrations at week 12. On comparison of the inulin and placebo groups, the fasting TAG responses over the 8-week test period were shown to be significantly different (P,0×05, repeated measures ANOVA), which was largely due to lower plasma TAG levels in the inulin group at week 8. The percentage change in TAG levels in the inulin group during the 8-week study was shown to correlate with the initial TAG level of the subjects (rs -0×499, P = 0×004). We therefore conclude that the daily addition of 10 g inulin to the diet significantly reduced fasting insulin concentrations during the 8-week test period and resulted in lower plasma TAG levels, particularly in subjects in whom fasting TAG levels were greater than 1×5 mmol/l. These data support findings from animal studies that fructans influence the formation and/or degradation of TAG-rich lipoprotein particles, and the insulin data are also consistent with recent studies showing attenuation of insulin levels in fructan-treated rats.