Growth of the corn ethanol industry has created a need for alternatives to corn for lactating dairy cows. Concurrent expansion in soydiesel production is expected to increase availability and promote favorable pricing for glycerol, a primary co-product material. The objective of this study was to determine the feeding value of glycerol as a replacement for corn in diets fed to lactating dairy cattle. Sixty lactating Holstein cows housed in individual tie stalls were fed a base diet consisting of corn silage, legume forages, corn grain, soyhulls, roasted soybeans, and protein supplements. After a 2-wk acclimation period, cows were fed diets containing 0, 5, 10, or 15% refined glycerol for 56 d. Cows were milked twice daily and weekly milk samples were collected. Milk production was 36.3, 37.2, 37.9, and 36.2 +/- 1.6 kg/d and feed intake was 23.8, 24.6, 24.8, and 24.0 +/- 0.7 kg/d for 0, 5, 10, and 15% glycerol treatments, respectively, and did not differ except for a modest reduction in feed intake during the first 7 d of the trial for 15% glycerol (treatment x time effect). Milk composition was not altered by glycerol feeding except that milk urea nitrogen was decreased from 12.5 +/- 0.4 to 10.2 +/- 0.4 mg/dL with glycerol addition. Cows fed diets containing 10 and 15% glycerol gained more weight than those fed rations containing 0 or 5% glycerol but body condition scores did not differ with glycerol feeding. The data indicate that glycerol is a suitable replacement for corn grain in diets for lactating dairy cattle and that it may be included in rations to a level of at least 15% of dry matter without adverse effects on milk production or milk composition.

One hundred fifty-one patients with primary biliary cirrhosis (PBC) grouped into four strata based on entry serum bilirubin ( < 2 mg/dL vs. 2 md/dL or greater) and liver histology (stages I, II vs. stages III, IV-Ludwig criteria) were randomized within each stratum to ursodiol or placebo given in a single dose of 10 to 12 mg/kg at bedtime for 2 years. Placebo- (n = 74) and ursodiol- treated (n = 77) patients were well matched at baseline for demographic and prognostic factors. Ursodiol induced major improvements in biochemical tests of the liver in strata 1 and 2 (entry bilirubin < 2), but had less effect on laboratory tests in patients with entry serum bilirubin of > or +2 (strata 3 and 4). Histology was favorably affected by ursodiol in patients in strata 1 and 2 but not in strata 3 and 4. Ursodiol enrichment in fasting bile obtained at the conclusion of the trail was approximately 40% and comparable in all strata. Thus, differences in ursodiol enrichment of the bile acid pool do not explain better responses of laboratory tests and histology found in patients with less advanced PBC. Patients treated will ursodiol tended to develop a treatment failure less frequently that those who received placebo, particularly in strata 1 and 2 (ursodiol 42%, placebo 60%, P = .078). Development of severe symptoms (fatigue/pruritus) and doubling of serum bilirubin were reduced significantly in ursodiol-treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatitis B virus-specific nucleic acid sequences and proteins have been detected in extrahepatic tissues of acutely and chronically infected patients. However, apart from peripheral blood mononuclear cells and bone marrow cells, little is known about the specific cell types that permit viral replication. In this study, we assessed the extrahepatic tissues of four patients who died with chronic hepatitis B virus infection and two uninfected controls by means of in situ hybridization and immunohistochemical study. Three of these patients had diffuse extrahepatic distribution of the virus. Hepatitis B virus nucleic acid sequences and proteins were detected in the lymph nodes, spleen, bone marrow, kidney, skin, colon, stomach, testes and periadrenal ganglia. The following cell types were found to be positive for hepatitis B virus: endothelial cells, macrophages/monocytes, hematopoietic precursors, basal keratinocytes, mucosal epithelial cells, stromal fibroblasts and sustentacular and neuronal cells. It is probable that these cells could support viral replication because hepatitis B virus DNA replicative intermediates, viral transcripts and HBsAg and HBcAg proteins were detected in most. These findings may be relevant to the initiation of extrahepatic syndromes associated with chronic hepatitis B virus infection such as vasculitis, glomerulonephropathy, neuropathy and dermatitis.

The transition to lactation period in dairy cattle is characterized by metabolic challenges, negative energy balance, and adipose tissue mobilization. Metabolism of mobilized adipose tissue is part of the adaptive response to negative energy balance in dairy cattle; however, the capacity of the liver to completely oxidize nonesterified fatty acids may be limited and is reflective of oxaloacetate pool, the carbon carrier of the tricarboxylic acid cycle. Alternative metabolic fates of acetyl-CoA from nonesterified fatty acids include esterification to triacylglycerides and ketogenesis, and when excessive, these pathways lead to fatty liver and ketosis. Examination of the anaplerotic and cataplerotic pull of oxaloacetate by the tricarboxylic acid cycle and gluconeogenesis may provide insight into the balance of oxidation and esterification of acetyl-CoA within the liver of periparturient dairy cows.

Expansion of the biofuels industry has increased the availability of glycerol as an alternative feed for dairy cows. The objective of this study was to determine the effects of glycerol on feed intake, milk production, rumen volatile fatty acids, and metabolic parameters in transition dairy cows. Multiparous Holstein cows were fed diets containing either high-moisture corn (n=11) or glycerol (n=12) from -28 to +56 d relative to calving. Glycerol was included at 11.5 and 10.8% of the ration dry matter for the pre- and postpartum diets, respectively. Prepartum feed intake was not changed by glycerol feeding (14.9 vs. 14.6 kg/d, control vs. glycerol) nor did postpartum feed intake differ (19.8 vs. 20.7 kg/d, control vs. glycerol). Overall milk yield did not differ (35.8 vs. 37 kg/d, control vs. glycerol) and milk composition, milk urea nitrogen, somatic cells, and energy balance were not different with glycerol feeding. Blood glucose content was decreased in cows fed glycerol during the prepartum period (59.1 vs. 53.4 mg/dL), and β-hydroxybutyrate concentration was increased (0.58 vs. 0.82 mmol/L, control vs. glycerol). Concentrations of blood nonesterified fatty acids did not differ between the treatment groups, and no response to glycerol for blood metabolites during the postpartum period was observed. Total rumen volatile fatty acid concentrations (mmol/L) did not differ between treatments, but proportions of rumen propionate and butyrate were greater for cows fed glycerol (22.7 vs. 28.6% of propionate, control vs. glycerol; and 11.5 vs. 15.3% of butyrate, control vs. glycerol) at the expense of acetate (61.4 vs. 51.5%, control vs. glycerol). These data indicate that glycerol is a suitable replacement for corn grain in diets for transition dairy cows.

Although cowside testing strategies for diagnosing hyperketonemia (HYK) are available, many are labor intensive and costly, and some lack sufficient accuracy. Predicting milk ketone bodies by Fourier transform infrared spectrometry during routine milk sampling may offer a more practical monitoring strategy. The objectives of this study were to (1) develop linear and logistic regression models using all available test-day milk and performance variables for predicting HYK and (2) compare prediction methods (Fourier transform infrared milk ketone bodies, linear regression models, and logistic regression models) to determine which is the most predictive of HYK. Given the data available, a secondary objective was to evaluate differences in test-day milk and performance variables (continuous measurements) between Holsteins and Jerseys and between cows with or without HYK within breed. Blood samples were collected on the same day as milk sampling from 658 Holstein and 468 Jersey cows between 5 and 20 d in milk (DIM). Diagnosis of HYK was at a serum β-hydroxybutyrate (BHB) concentration ≥1.2 mmol/L. Concentrations of milk BHB and acetone were predicted by Fourier transform infrared spectrometry (Foss Analytical, Hillerød, Denmark). Thresholds of milk BHB and acetone were tested for diagnostic accuracy, and logistic models were built from continuous variables to predict HYK in primiparous and multiparous cows within breed. Linear models were constructed from continuous variables for primiparous and multiparous cows within breed that were 5 to 11 DIM or 12 to 20 DIM. Milk ketone body thresholds diagnosed HYK with 64.0 to 92.9% accuracy in Holsteins and 59.1 to 86.6% accuracy in Jerseys. Logistic models predicted HYK with 82.6 to 97.3% accuracy. Internally cross-validated multiple linear regression models diagnosed HYK of Holstein cows with 97.8% accuracy for primiparous and 83.3% accuracy for multiparous cows. Accuracy of Jersey models was 81.3% in primiparous and 83.4% in multiparous cows. These results suggest that predicting serum BHB from continuous test-day milk and performance variables could serve as a valuable diagnostic tool for monitoring HYK in Holstein and Jersey herds.

Intersections in hepatic methyl group metabolism pathways highlights potential competition or compensation of methyl donors. The objective of this experiment was to examine the expression of genes related to methyl group transfer and lipid metabolism in response to increasing concentrations of choline chloride (CC) and DL-methionine (DLM) in primary neonatal hepatocytes that were or were not exposed to fatty acids (FA). Primary hepatocytes isolated from 4 neonatal Holstein calves were maintained as monolayer cultures for 24 h before treatment with CC (61, 128, 2028, and 4528 μmol/L) and DLM (16, 30, 100, 300 μmol/L), with or without a 1 mmol/L FA cocktail in a factorial arrangement. After 24 h of treatment, media was collected for quantification of reactive oxygen species (ROS) and very low-density lipoprotein (VLDL), and cell lysates were collected for quantification of gene expression. No interactions were detected between CC, DLM, or FA. Both CC and DLM decreased the expression of methionine adenosyltransferase 1A (MAT1A). Increasing CC did not alter betaine-homocysteine S-methyltranferase (BHMT) but did increase 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) and methylenetetrahydrofolate reductase (MTHFR) expression. Increasing DLM decreased expression of BHMT and MTR, but did not affect MTHFR. Expression of both phosphatidylethanolamine N-methyltransferase (PEMT) and microsomal triglyceride transfer protein (MTTP) were decreased by increasing CC and DLM, while carnitine palmitoyltransferase 1A (CPT1A) was unaffected by either. Treatment with FA decreased the expression of MAT1A, MTR, MTHFR and tended to decrease PEMT but did not affect BHMT and MTTP. Treatment with FA increased CPT1A expression. Increasing CC increased secretion of VLDL and decreased the accumulation of ROS in media. Within neonatal bovine hepatocytes, choline and methionine differentially regulate methyl carbon pathways and suggest that choline may play a critical role in donating methyl groups to support methionine regeneration. Stimulating VLDL export and decreasing ROS accumulation suggests that increasing CC is hepato-protective.

Extensive efforts have been made to identify more feed-efficient dairy cows, yet it is unclear how selection for feed efficiency will influence metabolic health. The objectives of this research were to determine the relationships between residual feed intake (RFI), a measure of feed efficiency, body condition score (BCS) change, and hyperketonemia (HYK) incidence. Blood and milk samples were collected twice weekly from cows 5 to 18 d postcalving for a total of 4 samples. Hyperketonemia was diagnosed at a blood β-hydroxybutyrate (BHB) ≥1.2 mmol/L and cows were treated upon diagnosis. Dry period, calving, and final blood sampling BCS was recorded. Prior mid-lactation production, body weight, body weight change, and dry matter intake (DMI) data were used to determine RFI phenotype, calculated as the difference between observed DMI and predicted DMI. The maximum BHB concentration (BHB) for each cow was used to group cows into HYK or not hyperketonemic. Lactation number, BCS, and RFI data were analyzed with linear and quadratic orthogonal contrasts. Of the 570 cows sampled, 19.7% were diagnosed with HYK. The first positive HYK test occurred at 9 ± 0.9 d postpartum and the average BHB concentration at the first positive HYK test was 1.53 ± 0.14 mmol/L. In the first 30 d postpartum, HYK-positive cows had increased milk yield and fat concentration, decreased milk protein concentration, and decreased somatic cell count. Cows with a dry BCS ≥4.0, or that lost 1 or more BCS unit across the transition to lactation period, had greater BHB than cows with lower BCS. Prior-lactation RFI did not alter BHB. Avoiding over conditioning of dry cows and subsequent excessive fat mobilization during the transition period may decrease HYK incidence; however, RFI during a prior lactation does not appear to be associated with HYK onset.