Randomized controlled trial investigating the effect of 2 selective dry-cow therapy protocols on udder health and performance in the subsequent lactation.

The objective of this study was to compare culture- and algorithm-guided selective dry-cow therapy (SDCT) programs with blanket dry-cow therapy (BDCT) in a multi-site, randomized, natural exposure clinical trial for the following cow-level outcomes: clinical mastitis, removal from the herd, and Dairy Herd Improvement Association (DHIA) test-day milk yield and SCC measures during the first 120 d in milk (DIM). Two days before planned dry-off, cows in each of 7 herds were randomly allocated to BDCT, culture-guided SDCT (cult-SDCT), or algorithm-guided SDCT (alg-SDCT). At dry-off, BDCT cows received an intramammary antibiotic (500 mg of ceftiofur hydrochloride) in all 4 quarters. Antibiotic treatments were selectively allocated to quarters of cult-SDCT cows by only treating quarters from which aseptically collected milk samples tested positive on a rapid culture system after 30 to 40 h of incubation. For alg-SDCT cows, antibiotic treatments were selectively allocated at the cow level, with all quarters receiving antibiotic treatment if the cow met at least one of the following criteria: (1) any DHIA test with a somatic cell count >200,000 cells/mL during the current lactation, and (2) ≥2 clinical mastitis cases during the current lactation. All quarters of all cows were treated with an internal teat sealant. Clinical mastitis and removal from the herd events (i.e., culling or death) and DHIA test-day data from dry-off to 120 DIM were extracted from herd records. Hazard ratios (HR) for the effect of treatment group on clinical mastitis and removal from the herd during 1 to 120 DIM were determined using Cox proportional hazards regression. The effects of treatment group on test-day loge-transformed SCC and milk yield were determined using linear mixed models. Final models indicated that either SDCT program was unlikely to increase clinical mastitis risk (HRcult-SDCT/BDCT = 0.82, 95% CI: 0.58, 1.15; HRalg-SDCT/BDCT = 0.83, 95% CI: 0.63, 1.09) or test-day logeSCC (cult-SDCT minus BDCT = 0.05, 95% CI: -0.09, 0.18; alg-SDCT minus BDCT = 0.07, 95% CI: -0.07, 0.21). Risk of removal from the herd and test-day milk yield were similar between treatment groups. Findings from this study indicate that culture- or algorithm-guided SDCT can be used at dry-off without negatively affecting cow health and performance in early lactation.

Differential effects of a single dose of oral calcium based on postpartum plasma calcium concentration in Holstein cows.

Our objectives were to determine (1) the effect of a single dose of an oral Ca bolus within 24 h after parturition on plasma Ca concentration, (2) the response of primiparous (PP) and multiparous (MP) cows to this supplementation strategy, and (3) differential responses based on plasma Ca at enrollment. For objective 1, cows from 1 commercial dairy in New York State were enrolled within 19 h after parturition (mean ± standard deviation = 8.3 ± 5.3 h) and randomized within parity group (first, second, and ≥third) to control [CON (n = 25); no placebo] or a single dose bolus treatment [BOL (n = 25); 3 oral Ca boluses supplying 54 to 64 g of Ca]. Plasma Ca was measured repeatedly between 1 and 24 h following treatment. For objectives 2 and 3, cows on 6 commercial farms in New York State were assigned to treatment as for objective 1 (CON, n = 1,973; BOL, n = 1,976). Herd records for health, reproduction, and Dairy Herd Improvement Association test day milk production were collected. Mixed effect multivariable models were developed using repeated measures ANOVA, Poisson regression, or proportional hazard models. Objective 2 analyses considered treatment with periparturient risk factors, whereas objective 3 analyses also considered Ca status. No difference was observed for plasma Ca between 1 and 24 h after treatment. Primiparous cows assigned to BOL calving at >712 d old had decreased risk of one or more health disorders [≤30 d in milk; risk ratio (RR) = 0.65, 95% confidence interval (CI) = 0.51 to 0.84] and those with body condition score >3.5 responded to BOL with increased milk production (CON = 31.7 ± 1.1, BOL = 35.1 ± 1.1 kg/d), as did those with days carried calf >277 (CON = 31.9 ± 1.0, BOL = 34.7 ± 1.0 kg/d). Reduced risk of one or more health disorders was observed in parity ≥3 (RR = 0.85, 95% CI = 0.81 to 0.89) and MP cows with body condition score >3.5 (retained placenta; RR = 0.70, 95% CI = 0.58 to 0.84) or that were lame (displaced abomasum; RR = 0.49, 95% CI = 0.32 to 0.75). Differential responses for PP cows by Ca status were minimal. For MP cows with low plasma Ca, BOL decreased risk of additional Ca treatment (≤1.8 mmol/L; RR = 0.57, 95% CI = 0.40 to 0.80) as well as risk of one or more health disorders (≤2.15 mmol/L; RR = 0.90, 95% CI = 0.85 to 0.95). Supplementation with a single oral dose of Ca could be targeted to periparturient risk groups for improved health. Calcium status did not differentiate responses of PP cows, but MP cows with low Ca at parturition had improved health status when supplemented.

Pro-oxidant effect of vitamin E in cigarette smokers consuming a high polyunsaturated fat diet.

Dietary polyunsaturated fats and vitamin E are associated with reduced risk for atherosclerosis, but in smokers, they could promote lipid oxidation. Therefore, we examined the effects of a high polyunsaturated fat diet and vitamin E supplementation on measures of lipid oxidation in cigarette smokers. Ten subjects who smoked >1 pack of cigarettes per day were sequentially fed the following: a baseline diet in which the major fat source was olive oil, a diet in which the major fat source was high-linoleic safflower oil, and finally, the safflower oil diet plus 800 IU vitamin E per day. LDL oxidation lag time and rate and plasma total F(2)-isoprostanes and prostaglandin F(2alpha) (PGF(2alpha)) were determined after 3 weeks on each diet. The safflower oil diet increased total F(2)-isoprostanes from 53.0+/-7.2 to 116.2+/-11.2 nmol/L and PGF(2alpha) from 3.5+/-0.2 to 5.5+/-0.5 nmol/L, without changing LDL oxidation parameters. Addition of vitamin E prolonged mean LDL oxidation lag time but, paradoxically, further increased F(2)-isoprostanes to 188.2+/-10.9 nmol/L and PGF(2alpha) to 7.8+/-0.4 nmol/L. These data suggest that vitamin E may function as a pro-oxidant in cigarette smokers consuming a high polyunsaturated fat diet.

Isoprostane levels in lipids extracted from atherosclerotic arteries of nonhuman primates.

Nonhuman primates used in these studies had been fed for 5 years diets enriched with cholesterol and one of three classes of fatty acids: saturated, monounsaturated, or polyunsaturated fatty acids. Atherosclerotic iliac artery lipid extracts were quantitatively analyzed for cholesterol, cholesteryl esters, fatty acid composition, and a marker of lipid oxidation, the F(2)-isoprostanes. There was no significant difference in the mean accumulation of F(2)-isoprostanes among the different diet groups. To account for the small, individual variation in the arachidonate concentration the F(2)-isoprostane mass from each sample was normalized by dividing by arachidonate mass: F(2)-isoprostane mass/(mass arachidonate). At lower levels of cholesterol accumulation, the F(2)-isoprostane mass/(mass arachidonate) ratio was greater in lipids from POLY arteries compared to SAT arteries, but the reverse was true at high levels of cholesterol. F(2)-isoprostane/(mass arachidonate) increased with mole fraction linoleate for the SAT group, but decreased for the POLY group. In summary, these studies demonstrated that there is no simple explanation of how F(2)-isoprostane accumulation did not depend on the concentration of oxidizable lipids that promote free-radical lipid oxidation.

Unlocking the mechanisms of transcription factor YY1: are chromatin modifying enzymes the key?

The transcription factor YY1 is a complex protein that is involved in repressing and activating a diverse number of promoters. Numerous studies have attempted to understand how this one factor can act both as a repressor and an activator in such a wide set of different contexts. The fact that YY1 interacts with a number of key regulatory proteins (e.g. TBP, TFIIB, TAFII55, Sp1, and E1A) has suggested that these interactions are important for determining which particular function of YY1 is displayed at a specific promoter. Two groups of proteins, previously known to function as corepressors and coactivators, that now seem likely to modulate YY1's functions, are the histone deacetylases (HDAC) and histone acetyltransferases (HAT). These two groups of enzymes modify histones, and this modification is proposed to alter chromatin structure. Acetylated histones are typically localized to active chromatin while deacetylated histones colocalize with transcriptionally inactive chromatin. When these enzymes are directed to a promoter through a DNA binding factor such as YY1, that promoter can be activated or repressed. This review will discuss the recent work dealing with the different proteins that interact with YY1, with particular emphasis on ones that modify chromatin, and how they could be involved in regulating YY1's activities.

Antioxidant effects of a supplemented very low protein diet in chronic renal failure.

Increased peroxidation of lipids in red blood cells (RBC) in patients with advanced chronic renal failure (CRF) reflects increased generation of reactive oxygen species (ROS), which may contribute to the metabolic damage induced by CRF and to its progression. We have evaluated parameters indicative of lipoperoxidation (LPO) of RBC at baseline in patients with CRF compared to controls, and the effects of a very low protein diet supplemented with amino and keto acids and vitamins A, C, E (VLPD) over a 6-month period. The presence of peroxidation damage in CRF patients before the administration VLPD was demonstrated by elevated levels of free malondialdehyde (MDA) (p < .0003) and decreased levels of polyunsaturated fatty acids (PUFA), particularly C20:4 (p < .001), C22:4 (p < .0001) and C22:5 (p < .0001) when compared to controls. Similarly, RBC vitamin E content was significantly decreased (p < .0001) while enzymatic activities were unalterated. VLPD reduced erythrocyte LPO as suggested by (a) decreased levels of free and total RBC MDA (p < .003 and p < .03, respectively), (b) increased levels of PUFA, particularly C22:4 and C22:5 (p < .003 and p < .03, respectively), and (c) increased levels of vitamins A and E (p < .001 and p < .04, respectively) as compared to prediet results. Antioxidant enzyme activities were not modified. These results suggest that VLPD has a protective role against LPO of erythrocytes in patients with CRF.

Fatty acids and plasma antioxidants in HIV-positive patients: correlation with nutritional and immunological status.

OBJECTIVE: To investigate red blood cell (RBC) and plasma fatty acids (FA) in HIV-positive patients in relation to oxidative stress and nutritional or immunological status. DESIGN AND METHODS: FA, plasma selenium, vitamins A and E were measured in 95 patients divided into four groups according to CD4 cells. RESULTS: Poly- and di-unsaturated FA (PUFA, DUFA) decreased and saturated FA (SFA) increased in RBC in the patients below 400/mm3 and in plasma in the patients below 50/mm3. RBC SFA correlated to CD4 cells, PUFA to MDA. Unlike vitamin E, plasma vitamin A and selenium decreased in most groups. Plasma SFA and MUFA correlated negatively to selenium and PUFA and DUFA to vitamin E. No correlation was found between PUFA and nutritional markers. CONCLUSION: FA seem to be modified during HIV infection by oxidative stress and disease evolution, but not by denutrition.

Fatty acid composition of low-density lipoprotein influences its susceptibility to autoxidation.

Low-density lipoprotein (LDL) oxidation was studied using copper or the water-soluble initiator azobis(2-amidinopropane) dihydrochloride (ABAP) to catalyze the reaction. These studies were carried out with purified, native LDLs that had a well-defined composition and which contained different concentrations of polyunsaturated fatty acids (PUFA) and alpha-tocopherol. The LDL was obtained from nonhuman primates fed diets enriched in cholesterol and one of four types of fatty acids: saturated (Sat), monounsaturated (Mono), omega-6 (omega-6FA), or omega-3 (omega-3FA) fatty acids. The PUFA concentration of the LDLs depended upon the diet and had the following order: omega-6FA > Sat approximately Mono approximately omega-3FA. Linoleic acid was the predominant PUFA in all of the LDLs. The rates of oxidation were linearly dependent upon the concentration of PUFA. When ABAP was used to initiate oxidation the lag time was linearly related to the amount of alpha-tocopherol. However, with copper catalysis no linear correlation was evident. If the different enrichments were analyzed independently, it was found that copper-catalyzed oxidation of LDLs enriched with omega-6 and omega-3 fatty acids showed a linear correlation between the lag time and the amount of alpha-tocopherol but that LDLs enriched with Sat or Mono fatty acids did not show a correlation. These results demonstrate that the rate of oxidation is dependent upon PUFA concentration and that the ability of alpha-tocopherol to inhibit oxidation depends upon the lipid environment and the mode of initiation.

Relationship between dietary retinol and alpha-tocopherol and lipid peroxidation in rat liver cytosol.

The effects of retinol and alpha-tocopherol-deficient and supplemented diets on the cytosolic concentration of thiobarbituric acid reactive substances (TBARS) in rat liver have been studied. Physiological lipoperoxidation (LPO) was observed in liver cytosol of control rats (TBARS = 0.315 +/- 0.034 nmol of MDA equivalents/mg of liver cytosolic proteins). In retinol-deficient diets there was a decrease in retinolaemia and the absence of retinol in liver cytosol while cytosolic TBARS increased significantly (P less than 0.001). Vitamin E was not found in cytosolic fractions, except in alpha-tocopherol-supplemented diet rats. alpha-Tocopherol-deficient diets induced an absence of vitamin E in the serum and cytosolic TBARS were increased compared to controls (P less than 0.001). Supplementation of the diet with retinol and alpha-tocopherol or both in combination induced a significant decrease in liver cytosolic TBARS (P less than 0.001). Finally the combination of low dietary supplementation with retinol and alpha-tocopherol (ten times the normal diet each) induced the maximum anti-LPO effect.

Mineral oil (follicular) lipidosis: II. Histologic studies of spleen, liver, lymph nodes, and bone marrow.

Tissues obtained from 600 routine autopsies were studied. Mineral oil lipidosis was present in the spleen (76 per cent), liver (45 per cent), bone marrow (26 per cent), and lymph nodes; more than 50 per cent of the lymph nodes from the mesentery, porta hepatis, and mediastinum were affected. Mineral oil and its metabolic products produce a nonfibrogenic reaction in these tissues. The differential diagnosis of mineral oil lipidosis in lymph nodes with reaction to radiopaque oils and Whipple's disease is discussed. The presence of mineral oil in para-aortic (42 per cent) and internal iliac (15 per cent) lymph nodes could result in false-positive readings after lymphangiography.