The effect of excess cobalt on milk fatty acid profiles and transcriptional regulation of SCD, FASN, DGAT1 and DGAT2 in the mammary gland of lactating dairy cows.

The main objective of this study was to investigate the effect of excess cobalt (Co) on gene expression of stearoyl-CoA desaturase (SCD), fatty acid synthase (FASN), diacylglycerol acyltransferase 1 (DGAT1) and diacylglycerol acyltransferase 2 (DGAT2) of lactating dairy cows in relation to milk fatty acid profile. Seven multiparous cows of the Norwegian Red cattle breed (NRF) had their basal diet supplemented with 1.4 g Co as a 24 g/l solution of Co-acetate per os twice daily for 7 days followed by a 9-day depuration period. Udder biopsies were performed prior to the treatment period, after 1 week of treatment and immediately after the depuration period. Excess Co reduced the proportion of all cis-9 monounsaturated fatty acids and increased the proportion of 18:0 in milk. However, gene expression levels of SCD, DGAT1, DGAT2 and FASN were not significantly altered. Our results indicate that the effect of Co on milk fatty acid profile is mediated at the post-transcriptional level by reduced activity of SCD in the mammary gland. Potential mechanisms explaining how Co might reduce stearoyl-CoA desaturation are discussed.

Cobalt reduces the Δ9-desaturase index of sow milk.

The main objective of this study was to examine if cobalt (Co) reduces Δ(9) -desaturase indices in milk and blood lipids in sows. The experimental design consisted of a repeated measurement consisting of a pre-treatment period of a minimum of 9 days, a treatment period of 5 days and a post-treatment period of 6 days. Experimental animals consisted of 10 lactating sows; five sows had an intramuscular injection of 59 mg Co diluted in 5 ml 0.9% saline solution twice a day, whereas the other five had an intramuscular injection of 5 ml 0.9% saline solution twice a day as a control. Milk Δ(9) -desaturase indices for cis-9 18:1, cis-9 16:1 and cis-9 14:1 were significantly reduced (p < 0.0001) as a result of the Co-treatment, contrasting with the plasma Δ(9) -desaturase indices, which were unaffected. Potential mechanisms explaining how Co might reduce milk Δ(9) -desaturase indices are discussed. Moreover, the toxicological level of Co and potential implications of using Co-ethylenediaminetetraacetic acid as a liquid marker in digestibility experiments are addressed.

Lipids, myocardial infarction and ischaemic stroke in patients with rheumatoid arthritis in the Apolipoprotein-related Mortality RISk (AMORIS) Study.

OBJECTIVES: To examine the rates of acute myocardial infarction (AMI) and ischaemic stroke (IS) and to examine the predictive value of total cholesterol (TC) and triglycerides (TG) for AMI and IS in patients with rheumatoid arthritis (RA) and people without RA. METHODS: In the Apolipoprotein MOrtality RISk (AMORIS) Study 480 406 people (including 1779 with RA, of whom 214 had an AMI and 165 an IS) were followed for 11.8 (range 7-17) years. Cox regression analysis was used to calculate HR per SD increase in TC or TG with 95% CI. All values were adjusted for age, diabetes and hypertension. RESULTS: The levels of TC and TG were significantly lower in patients with RA than in people without RA. Despite this, the rate of AMI and IS per 1000 years was at least 1.6 times higher in RA than non-RA. TC was nearly significantly predictive for AMI (HR/SD 1.13 (95% CI 0.99 to 1.29), p=0.07) and significantly predictive for future IS in RA (HR/SD 1.20 (95% CI 1.03 to 1.40), p=0.02). TG had no relationship to development of AMI (1.07, 0.94 to 1.21, p=0.29), but was weakly related to IS (1.13, 0.99 to 1.27, p=0.06). In contrast, both TC and TG were significant predictors of AMI and IS in people without RA. CONCLUSIONS: Patients with RA had 1.6 times higher rate of AMI and IS than people without RA. TC and TG were significant predictors of AMI and IS in people without RA, whereas the predictive value in RA was not consistent.

Intravenous injections of cobalt reduce fatty acid desaturation products in milk and blood of lactating cows.

The objective of this study was to determine whether intravenous infusion of Co affects levels of fatty acid desaturation products in bovine milk. Six cows were assigned to two replicated 3 × 3 Latin squares with 14-day periods. Treatment occurred on days 1 to 5 and depuration occurred on days 6-14. Two treatments were tested, the first consisting of per os supplementation of 3.5 g Co daily in the form of Co acetate and the second consisting of intravenous injection of 175 mg Co daily in the form of Co acetate diluted in saline solution. The third treatment was a control. Both Co treatments decreased cis-9 18:1 levels from approximately 18 to 14 g/100 g fatty acids, and increased 18:0 levels from 11 to 17 g/100 g fatty acids in milk fat (p < 0.001). The proportions of cis-9 10:1, cis-9 12:1, cis-9 14:1, cis-9 16:1 and cis-9 17:1 decreased (p < 0.001), whereas 17:0 and trans-11 18:1 increased (p < 0.001). In blood plasma, levels of cis (6,9,12) 18:3 (p < 0.001) and cis (8,11,14,17) 20:4 (p = 0.008) decreased after both the Co treatments. It is concluded that intravenous supply of Co reduces levels of fatty acid desaturation products in both bovine milk and blood.

Uric acid and risk of myocardial infarction, stroke and congestive heart failure in 417,734 men and women in the Apolipoprotein MOrtality RISk study (AMORIS).

OBJECTIVES: Few studies have simultaneously analysed the influence of elevated serum uric acid (UA) on acute myocardial infarction (AMI), ischaemic and haemorrhagic stroke (IS, HS) and congestive heart failure (CHF) in large healthy populations. We, here, examine UA as a risk factor for AMI, stroke and CHF by age and gender in the Apolipoprotein MOrtality RISk (AMORIS) Study. DESIGN: Prospective study (11.8 years, range 7-17) of fatal and nonfatal acute myocardial infarction, stroke and CHF through linkage with Swedish hospital discharge and mortality registers. SETTINGS: Measurements of uric acid in 417,734 men and women from health check-ups in Stockholm area. RESULTS: There was a gradual increase in risk of AMI, stroke and CHF by increasing UA levels. Women had a stronger relationship between UA and both AMI and IS than men. Predictions of AMI were at least as powerful in the elderly as in the young, but not so for IS. Associations were markedly attenuated when adjusted for total cholesterol, triglycerides, hospital hypertension and diabetes status. The association between UA and HS was U-shaped in both genders. CHF was more strongly related to UA than AMI and stroke and less affected by the adjustment factors. CONCLUSIONS: Already moderate levels of UA appear to be associated with an increased incidence of AMI, stroke and CHF in middle-aged subjects without prior cardiovascular disease. These associations seem to increase gradually from lower to higher levels of UA. UA may be an important complementary indicator of cardiovascular risk in the general population.

Relationships between lipoprotein components and risk of ischaemic and haemorrhagic stroke in the Apolipoprotein MOrtality RISk study (AMORIS).

OBJECTIVES: To compare lipoprotein components associated with ischaemic and haemorrhagic stroke by age and gender in the Apolipoprotein MOrtality RISk (AMORIS) Study (n=148 600). DESIGN: Prospective follow-up study (11.8, range 7-17 years) of fatal and nonfatal ischaemic and haemorrhagic stroke through linkage with Swedish hospital discharge and mortality registers. SETTING: Measurements of lipoprotein components from health check-ups in the larger Stockholm area. RESULTS: Ischaemic stroke was more common than haemorrhagic stroke (5 :1), but case fatality was higher in haemorrhagic stroke. An elevated apoB/apoA-1 ratio and triglycerides, non-HDL cholesterol, low HDL cholesterol, and the total cholesterol to high-density cholesterol (TC/HDL-C) ratio were associated with increased incidence of nonfatal and fatal ischaemic stroke as well as all cerebrovascular events (n=7480) in both genders. The associations were somewhat stronger for nonfatal than fatal events. In ischaemic stroke the apoB/apoA-1 ratio was a stronger predictor than the TC/HDL-C ratio in all subjects, in those below 65 years of age and in those with LDL-C below 3 mmol L(-1). Haemorrhagic stroke was not associated with elevated atherogenic lipoproteins except for increased risk of fatal haemorrhagic stroke in women with a high apoB/apoA-I ratio. CONCLUSIONS: Dyslipidaemia is associated with an increased risk of ischaemic stroke but few relations were seen in haemorrhagic stroke. Use of the apoB/apoA-I ratio as a marker of dyslipidaemia is at least as efficient as conventional lipids, for the identification of subjects at increased risk of stroke, especially ischaemic stroke. Practical advantages, fasting is not needed, speak in favour of using apoB and apoA-1 in stroke risk prediction.

Prediction of fat, muscle and value in Norwegian lamb carcasses using EUROP classification, carcass shape and length measurements, visible light reflectance and computer tomography (CT).

One hundred and twenty carcasses were sampled to compare different techniques or methods for prediction of lamb carcass composition and value. Four methods that are used at the Norwegian Meat Research Centre, Animalia, were selected. These were the basic EUROP classification, the advanced EUROP classification using carcass shape and length measurements, visible light reflectance probing (GP) and Computer Tomography (CT). The different technologies were tested using an iterative approach, selecting calibration and validation data sets from the 120 carcasses randomly, where 90 carcasses were used for calibration, and 30 for validation. The best prediction models were obtained using CT, with respect to prediction error and correlation between predicted and measured value of carcass fat and muscle (in kg), and value (in NOK). Due to high cost and low operating speeds of CT, optical probing (GP) may be the second best solution of the technologies used in this study, combined with a CT dissection reference as an alternative to manual dissection.

Cobalt supplied per os reduces the mammary Delta9-desaturase index of bovine milk.

Results indicated that the dual marker system of Yb-acetate and Co-EDTA supplied per os reduced the proportion of fatty acids in bovine milk that were products of Delta (9)-desaturase. To verify this effect and identify the responsible marker component, 18 cows (3 cows per treatment) were administered per os a 0.25-L solution of either Co-acetate, Co-EDTA, Co-EDTA + Yb-acetate, EDTA, Yb-acetate, or water twice daily for 5 d. The daily amounts of Co, Yb, and EDTA were, respectively, 3.50, 3.44, and 21.00 g per cow. Milk and blood were sampled and analyzed for content of fatty acids, and blood was sampled and analyzed for Co and cobalamin. Only solutions containing Co had a reducing effect (P < or = 0.01) on fatty acids that were products of Delta(9)-desaturase in milk--cis-9 10:1, cis-9 14:1, cis-9 16:1, cis-9, trans-11 18:2, and cis-9 18:1--with the exception of the solution containing Co-EDTA + Yb-acetate for cis-9 18:1. Of the substrate fatty acids of Delta (9)-desaturase, only 18:0 increased (P < 0.001) in all groups supplied with Co-containing solutions. Thus, Co had a reducing effect (P < or = 0.004) on the Delta (9)-desaturase indices [(product of Delta(9)-desaturase)/(product of Delta(9)-desaturase + substrate of Delta(9)-desaturase)] of milk for cis-9 14:1, cis-9 16:1, cis-9 18:1, and cis-9, trans-11 18:2. There were no differences in Delta(9)-desaturase indices between Co-EDTA and Co-acetate. None of the marker solutions influenced the fatty acid composition of blood plasma, and Co was detected only in the blood samples from cows treated with solutions containing Co. On the basis of these results, we concluded that Co given per os decreased the Delta(9)-desaturase indices of bovine milk.

Relationships between lipoprotein components and risk of myocardial infarction: age, gender and short versus longer follow-up periods in the Apolipoprotein MOrtality RISk study (AMORIS).

OBJECTIVES: Examine and compare lipoprotein components associated with fatal and nonfatal acute myocardial infarction (AMI) by time period in the Apolipoprotein MOrtality RISk (AMORIS) Study. DESIGN: Prospective follow-up study of nonfatal and fatal myocardial infarction through linkage with Swedish hospital discharge and Swedish mortality registers. SETTING: Measurements of lipoprotein components from health check-ups in the larger Stockholm area. SUBJECTS: The AMORIS subjects (n = 149 121) free of AMI at blood sampling were followed from 1985 to 2002 with respect to n = 6794 first cases of AMI. RESULTS: Hazard ratios of nonfatal and fatal AMI by lipoprotein parameters were highly significant and about equally strong in both genders. Apolipoprotein B (apoB), nonhigh density cholesterol and low density cholesterol predicted nonfatal AMI (NFAMI) better than fatal AMI, but high density cholesterol or apolipoprotein A-1 did not. Atherogenic components were weaker predictors after 1997 than before. In multivariate analyses apoB/apoA-1 was a better predictor than TC/HDL-C. ApoB/apoA-1 added clinically significant information to TC/HDL-C in men as reflected by a net reclassification improvement (NRI) of 9.4% (P < 0.0001). CONCLUSION: ApoB, apoB/apoA-1 and non-HDL-C were found about equally predictive with LDL-C being slightly less, but multivariate analyses showed apoB/apoA-1 to be the strongest predictor. Attenuation of prediction ability between nonfatal and fatal AMI may be due to modern treatment of CHD after a NFAMI and attenuation of hazard ratios after 1997 may be due to selection of lower risk subjects surviving to 1997.

Errors that result from using the TC/HDL C ratio rather than the apoB/apoA-I ratio to identify the lipoprotein-related risk of vascular disease.

The objective of this analysis was to demonstrate the frequency and extent of error that results from using the TC/HDL C ratio rather than the apoB/apoA-I ratio to estimate the lipoprotein-related risk of vascular disease within 94,667 men and 75,675 women in the Apoprotein-related Mortality Risk (AMORIS) cohort. The odds ratio (OR) for the risk of fatal myocardial infarction was determined for 1 SD change in the apoB/apoA-I ratio and all the conventional cholesterol ratios--TC/HDL C ratio, LDL C/HDL C ratio, non-HDL C/HDL C ratio. In both men and women, the apoB/apoA-I ratio was significantly greater than any of the cholesterol ratios, which, in fact, differed little. Therefore, the apoB/apoA-I ratio was taken as the most accurate index of the lipoprotein-related risk of vascular disease. Using Receiver Operating Characteristic analysis, it was demonstrated that the diagnostic accuracy of the apoB/apoA-I ratio was significantly greater than any cholesterol ratio in those with an LDL cholesterol <3.6 mmol L(-1) compared to those with an LDL cholesterol >3.6 mmol L(-1). Indeed, the difference between the apoB/apoA-I OR compared with the TC/HDL C OR progressively widened as risk increased. This suggests that the advantage of the apoB/apoA-I ratio is greatest in the population at highest risk. The distribution of subjects by quintiles showed in both genders that whilst agreement was greatest at the extremes, even at these points there was substantial discordance between the TC/HDL C and the apoB/apoA-I ratios. Within the middle of the distribution, less than 50% of the values were concordant. Finally, when comparing the ORs, the TC/HDL C ratio underestimated risk in 69.4% of male subjects and overestimated risk in 26.1% of male subjects, whereas in the female subjects, the TC/HDL C ratio underestimated risk in 84.9% of the subjects and overestimated risk in 12.0%. Thus, using the conventional cholesterol ratios rather than the apoB/apoA-I ratio results in frequent and substantial error in the estimation of the lipoprotein-related risk of vascular disease.

Stroke mortality and the apoB/apoA-I ratio: results of the AMORIS prospective study.

OBJECTIVES: LDL cholesterol is a well-established risk factor for myocardial infarction, but not for stroke. The main objective of the present study was to determine if the risk of stroke is related to the balance between the proatherogenic apoB lipoprotein particles and the antiatherogenic apoA-I particles as is the case for myocardial infarction. SUBJECTS AND DESIGN: A total of 98 722 men and 76 831 women were recruited from screening programmes. The prospective risk and the relationships between five different types of fatal strokes and the lipid fractions, apoB, apoA-I and the apoB/apoA-I ratio (automated immunoturbidimetry) were examined. The results were compared with the risks of other ischaemic and non-ischaemic fatalities. RESULTS: Mean follow-up was 10.3 years. High apoB and low apoA-I values were significantly related to risk of stroke. The odds ratio comparing the upper 10th versus the 1st decile of the apoB/apoA-I ratio for all strokes adjusted for age, gender, total cholesterol (TC) and triglycerides (TG) was 2.07 (95% CI: 1.49-2.88), P < 0.0001. The strongest association was for ischaemic stroke. Low apoA-I was a common abnormality in all stroke subtypes including subarachnoidal and haemorrhagic strokes. In multivariate analyses the apoB/apoA-I ratio was a stronger risk predictor than total/HDL and LDL/HDL cholesterol ratios. The apoB/apoA-I ratio was linearly related to the risk of stroke although the slope was less than observed for the risk of fatal myocardial infarction. For all ischaemic events pooled together the age-, gender-, TC- and TG-adjusted odds ratio, 10th vs. 1st decile, was 3.13 (95% CI: 2.66-3.69), P < 0.0001. By contrast, there was no relationship between the apoB/apoA-I ratio and risk of cancer or any other non-ischaemic causes of death. CONCLUSIONS: These observations link the apoB/apoA-I ratio to the risk of fatal stroke in a similar fashion as for myocardial infarction and other ischaemic events. Our findings indicate that the apoB/apoA-I ratio, which indicates the 'cholesterol balance', is a robust and specific maker of virtually all ischaemic events.

Genetic evaluation of mastitis resistance using a first-passage time model for wiener processes for analysis of time to first treatment.

A Wiener process is a Brownian-motion process initiated in a certain state in a state space, and the first passage time is defined as the time of the process to reach a predefined absorbing state where the process stops. Time from 31 d prepartum to first treatment of clinical mastitis (CM) was modeled as first passage times of such Wiener processes. Two processes were used to allow for several risk factors, and for each process, initiation was at some arbitrary time point, in a certain health state with drift toward or away from absorption (disease). The drift parameter of each process was expressed as linear functions of covariates (year of calving and sire). First passage time was defined as the time from process initiation until the first health status process reached zero (absorption). The model was fitted to records for 36,178 first-lactation daughters of 245 Norwegian cattle sires using a Bayesian approach and Markov chain Monte Carlo methods. Genetic evaluation of sires was carried out by calculating the posterior probability of no CM (the value of the survival function) by d 331, i.e., 300 d after first calving. Alternatively, sire evaluation was based on the integrated area under the survival curve. These measures were highly correlated (0.999), which indicates a small degree of crossings of the sire-dependent survival curves. Hence, sire-specific hazards were close to proportional, resulting in a higher rank-correlation to sire evaluations from a survival model with proportional hazards than to the results from a multivariate threshold model.

High apolipoprotein B, low apolipoprotein A-I, and improvement in the prediction of fatal myocardial infarction (AMORIS study): a prospective study.

BACKGROUND: Apolipoprotein B (apoB) and apolipoprotein A-I (apoA-I) are thought to be better predictors of acute myocardial infarction than total cholesterol and LDL-cholesterol. We investigated whether apoB and apoA-I are predictors of risk of fatal myocardial infarction. We also aimed to establish whether apoB and apoA-I add further information about risk of fatal myocardial infarction to that obtained with total cholesterol, triglycerides, and LDL-cholesterol. METHODS: We recruited 175553 individuals mainly from screening programmes. We measured concentrations of apoB, apoA-I, total cholesterol, and triglycerides, and calculated apoB/apoA-I ratio and concentrations of LDL-cholesterol and HDL-cholesterol. The relation between death from acute myocardial infarction and initial values for apoB, apoA-I, and the other lipids was examined. FINDINGS: Mean follow-up was 66.8 months (SD 41.3) for 98722 men and 64.4 months (41.4) for 76831 women. 864 men and 359 women had fatal myocardial infarction. In univariate analyses adjusted for age and in multivariate analyses adjusted for age, total cholesterol, and triglycerides, the values for apoB and apoB/apoA-I ratio were strongly and positively related to increased risk of fatal myocardial infarction in men and in women. ApoA-I was noted to be protective. In multivariate analysis, apoB was a stronger predictor of risk than LDL-cholesterol in both sexes. INTERPRETATION: Although LDL-cholesterol and HDL-cholesterol are known risk factors, we suggest that apoB, apoB/apoA-I, and apoA-I should also be regarded as highly predictive in evaluation of cardiac risk. Although increased throughout the range of values of LDL-cholesterol, apoB and apoA-I might be of greatest value in diagnosis and treatment in men and women who have common lipid abnormalities, but have normal or low concentrations of LDL-cholesterol.

Effects of genotype-environment interactions on genetic correlations.

The objective of the work presented here was to investigate the influence of genotype-environment interaction on genetic correlations. In our theoretical models we have considered plant populations consisting of random samples of lines from chromosome-doubled haploids produced from F 1 gametes, highly inbred SSD-lines, and clones of randomly breeding populations grown in two and multiple environments. The results of our theoretical considerations are that if genotype-environment interaction exists, great differences are expected to occur in the estimates of genetic correlation coefficients obtained in different environments. Based on the variance and covariance components for genotype-environment interaction we suggest a new type of correlation coefficient, called genotype-environment correlation, r ge . Our theory has been applied to several series of experiments. Estimates are presented from two series, both of which demonstrate clearly the consequences of genotype-environment interaction on the genetic correlations.

Theory and application of open-pollination and polycross in forage grass breeding.

Progeny testing and selection of forage grasses by means of growing half-sib (HS) families from openpollination and polycross have been considered from theoretical and practical points of view. Special attention has been paid to the genetic variation within half-sib families, which is expected to be large as compared to the genetic variation between families. Based on observations of individual plants within plots, the environmental component of the variation is expected to be large and nonestimatable. The results of an experiment in meadow fescue (Festuca pratensis Huds.) are presented. In this experiment, randomly selected individual plants within HS families were cloned and laid out in randomized blocks. For the characters observed (earliness and raw matter yield) no significant variance component for dominance was found. The highly significant additive component estimated for earliness, as well as for yield, after each of three cuts and in total were about three times as large within as between families, as expected from the theoretical considerations. The estimated response to selection was much higher for a combination of between- and within-family selection as compared to free clone or family mean selection alone. It is suggested that a program for progeny testing and selection in a base population of perennial forage grasses should start with an experiment in which a large number of randomly selected parental clones and a fixed number of clones from each of the half-sib families derived from the mother genotypes are grown simultaneously. The selected clones within superior families could later on be further cloned, placed in a polycross field, and the new HS-families could be sown in ordinary field trials at various locations for further selection.