Surgical and oncologic outcomes in dogs with malignant peripheral nerve sheath tumours arising from the brachial or lumbosacral plexus.

Malignant peripheral nerve sheath tumours (MPNST) of a plexus nerve or nerve root cause significant morbidity and present a treatment challenge. The surgical approach can be complex and information is lacking on outcomes. The objective of this study was to describe surgical complication rates and oncologic outcomes for canine MPNST of the brachial or lumbosacral plexus. Dogs treated for a naïve MPNST with amputation/hemipelvectomy with or without a laminectomy were retrospectively analysed. Oncologic outcomes were disease free interval (DFI), overall survival (OS), and 1- and 2-year survival rates. Thirty dogs were included. The surgery performed was amputation alone in 17 cases (57%), and amputation/hemipelvectomy with laminectomy in 13 cases (43%). Four dogs (13%) had an intraoperative complication, while 11 dogs (37%) had postoperative complications. Histologic margins were reported as R0 in 12 dogs (40%), R1 in 12 dogs (40%), and R2 in five dogs (17%). No association was found between histologic grade and margin nor extent of surgical approach and margin. Thirteen dogs (46%) had recurrence. The median DFI was 511 days (95% CI: 140-882 days). The median disease specific OST was 570 days (95% CI: 467-673 days) with 1- and 2-year survival rates of 82% and 22% respectively. No variables were significantly associated with recurrence, DFI, or disease specific OST. These data show surgical treatment of plexus MPNST was associated with a high intra- and postoperative complication rate but relatively good disease outcomes. This information can guide clinicians in surgical risk management and owner communication regarding realistic outcomes and complications.

Metabolic changes in vitamin D receptor knockout mice.

VDR expression has been found in many cell types involved in metabolism, including the beta-cells of the pancreatic islets. Activated vitamin D and its interactions with the vitamin D receptor (VDR) are implicated in glucose homeostasis. We investigated the metabolic phenotype of the VDR-null (VDRKO) mouse at early and middle age. All offspring of heterozygote VDRKO breeding-pairs were fed 'rescue diet' from weaning to normalize calcium and phosphate levels in VDRKO and to avoid confounding by different diets. Glucose tolerance testing was performed at 7 and 24 weeks of age. Insulin tolerance testing, glucose-stimulated insulin secretion, body-composition studies and islet isolation were performed at 25-27 weeks. Glucose-stimulated insulin secretion was tested in isolated islets. VDRKO mice had reduced bone density, subcutaneous fat mass and muscle weights compared to WT mice. Despite reduced fat mass, glucose tolerance did not differ significantly. Male but not female VDRKO had improved insulin sensitivity. Global loss of VDR has significant effects on organs involved in energy metabolism and glucose homeostasis. In the setting of decreased fat mass, a clear effect on glucose tolerance was not present.

Iron chelation increases beige fat differentiation and metabolic activity, preventing and treating obesity.

Beige and brown fat consume glucose and lipids to produce heat, using uncoupling protein 1 (UCP1). It is thought that full activation of brown adipose tissue (BAT) may increase total daily energy expenditure by 20%. Humans normally have more beige and potentially beige-able fat than brown fat. Strategies to increase beige fat differentiation and activation may be useful for the treatment of obesity and diabetes. Mice were fed chow or high-fat diet (HFD) with or without the iron chelator deferasirox. Animals fed HFD + deferasirox were markedly lighter than their HFD controls with increased energy expenditure (12% increase over 24 h, p < 0.001). Inguinal fat from HFD + deferasirox mice showed increased beige fat quantity with greater Ucp1 and Prdm16 expression. Inguinal adipose tissue explants were studied in a Seahorse bioanalyser and energy expenditure was significantly increased. Deferasirox was also effective in established obesity and in ob/ob mice, indicating that intact leptin signalling is not needed for efficacy. These studies identify iron chelation as a strategy to preferentially activate beige fat. Whether activating brown/beige fat is effective in humans is unproven. However, depleting iron to low-normal levels is a potential therapeutic strategy to improve obesity and related metabolic disorders, and human studies may be warranted.

Comparison of bacteriologic culture results for skin wound swabs and skin wound biopsy specimens.

OBJECTIVE: To compare bacteriologic culture results for superficial swab and tissue biopsy specimens obtained from dogs with open skin wounds. ANIMALS: 52 client-owned dogs. PROCEDURES: For each dog, 1 wound underwent routine preparation prior to collection of 2 specimens, 1 by superficial swab (Levine) technique and 1 by tissue biopsy. Specimens were processed for bacteriologic culture. Two observers determined whether any detected difference in culture results for the 2 types of specimen would have resulted in differing treatment plans. RESULTS: Culture results of swab and tissue biopsy specimens were identical in 11/52 (21.2%) cases. Tissue biopsy specimen and swab cultures yielded positive results for 44 (84.6%) and 40 (76.9%) wounds, respectively. With regard to mean recovery rates of bacteria from wounds with positive culture results, both the biopsy specimens and swabs yielded 3.4 bacterial species/wound. All wounds for which swab cultures yielded no growth also had negative culture results for biopsy specimens. Biopsy specimen and swab culture results were in agreement with regard to the most common bacteria cultured. In 7/52 (13%) wounds, the observers would have treated the patient differently on the basis of the results of the 2 cultures. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that culture of a swab collected by the Levine technique is an appropriate noninvasive alternative to culture of a tissue biopsy specimen. A negative result obtained from culture of a swab is likely to be reliable. Disagreement between the results of swab and tissue biopsy specimen cultures is likely of low clinical importance.

The Shoulder Joint and Common Abnormalities.

The shoulder is a complex joint composed mostly of static and dynamic capsuloligamentous structures and plays an important role in forelimb lameness. Its complex anatomy and biomechanics necessitate thorough examination and diagnostic work-up for accurate diagnosis. This article provides an updated review of common canine shoulder pathologies, including osteochondrosis, bicipital and supraspinatus tendinopathies, infraspinatus contracture, medial shoulder syndrome, and luxation.

Myeloid cell deletion of Aryl hydrocarbon Receptor Nuclear Translocator (ARNT) induces non-alcoholic steatohepatitis.

BACKGROUND AND AIM: Non-alcoholic steatohepatitis (NASH) is predicted to become the most common cause of cirrhosis and liver failure. Risk factors include obesity, insulin resistance and diabetes. Macrophages and other myeloid cells play crucial roles in initiating and driving inflammation. Aryl hydrocarbon Receptor Nuclear Translocator (ARNT) is a transcription factor which binds to a range of partners to mediate responses to environmental signals, including the diet. In people with diabetes it is decreased in liver. We hypothesised that myeloid cell ARNT activity may contribute to the development of liver pathology. METHODS: Floxed-ARNT mice were bred with LysM-Cre mice to generate mice with reduced ARNT in myeloid cells. Animals were fed a high fat diet (HFD) and liver pathology was assessed. Histology, mRNA, fat accumulation and metabolism were studied. RESULTS: Animals with reduced myeloid ARNT developed steatohepatitis on a HFD, with additional alterations of metabolism and fat deposition. Steatohepatitis was accompanied by hepatic macrophage infiltration and expression of both M1 and M2 markers. Expression of mRNAs for Cxcl1, Mcp-1, Tnf-α and Tgf-ß1 were increased. Human livers from controls and people with NASH were tested; ARNT mRNA was decreased by 80% (p = 0.0004). CONCLUSIONS: Decreased myeloid ARNT may play a role in the conversion from non-alcoholic fatty liver to steatohepatitis. Increasing ARNT may be a therapeutic strategy to reduce NASH.

Effects of maternal supplementation with an injectable trace mineral on subsequent calf performance and inflammatory response1.

Newly weaned, commercial Angus steers [body weight (BW) = 204 ± 19 kg; n = 24; 12 steers from dams administered an injectable trace mineral (MM; Mulimin90) and 12 steers from control (CON) dams] were utilized to determine the effects of maternal supplementation with an injectable trace mineral on the inflammatory response of subsequent steers subjected to a lipopolysaccharide (LPS) challenge at the initiation of a 42-d receiving period. On day -2 steers were weaned, and the following day, shipped 354 km to the Beef Cattle and Sheep Field Laboratory in Urbana, IL. On day 0, steers were administered an intravenous LPS challenge. Body temperature and blood samples were collected from steers prior to LPS administration (0 h) and again at 0.5, 1, 2, 3, 4, 5, and 6 h. Blood samples were analyzed for trace mineral and cortisol at 0 and 2 h and glucose, insulin, LPS-binding protein (LBP), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), haptoglobin, ceruloplasmin, and fibrinogen at 0, 0.5, 1, 2, 3, 4, 5, and 6 h. Calf BW was collected at trial initiation and subsequently every 14 d. Dry matter intake was collected daily and average daily gain (ADG) and feed efficiency were assessed. Initial plasma Zn tended (P = 0.06) to be greater for MM steers. However, there was no difference (P ≥ 0.31) in trace mineral status or serum cortisol at any other time. Total area under the curve (TAUC) for body temperature was lesser (P > 0.01) for MM steers. Basal LBP concentrations and TAUC for LBP tended (P ≤ 0.10) to be greater for MM steers. Peak concentration of IL-6 tended (P = 0.09) to be reached earlier for CON steers. However, there was no difference (P ≥ 0.11) in glucose, insulin, IL-6, ceruloplasmin, haptoglobin, and fibrinogen concentrations between treatments. Calf performance and feed efficiency did not differ (P ≥ 0.17) between treatments except ADG from day 28 to 42, which was greater (P = 0.03) for CON steers. Maternal supplementation with an injectable trace mineral tended to improve steer plasma Zn status at 0 h and tended to increase basal concentrations of LBP and overall LBP production when steers were administered an LPS challenge. Additionally, MM steers exhibited a more favorable change in body temperature following LPS administration. However, injectable trace mineral supplementation of dams during gestation had minimal to no effect on cytokine and acute-phase protein concentrations, as well as overall calf performance and efficiency during a 42-d receiving period.

Mice with myocyte deletion of vitamin D receptor have sarcopenia and impaired muscle function.

BACKGROUND: It has long been recognized that vitamin D deficiency is associated with muscle weakness and falls. Vitamin D receptor (VDR) is present at very low levels in normal muscle. Whether vitamin D plays a direct role in muscle function is unknown and is a subject of hot debate. Myocyte-specific deletion of VDR would provide a strategy to answer this question. METHODS: Myocyte-specific vitamin D receptor (mVDR) null mice were generated by crossing human skeletal actin-Cre mice with floxed VDR mice. The effects of gene deletion on the muscle phenotype were studied in terms of body tissue composition, muscle tissue histology, and gene expression by real-time PCR. RESULTS: Unlike whole-body VDR knockout mice, mVDR mice showed a normal body size. The mVDR showed a distinct muscle phenotype featuring reduced proportional lean mass (70% vs. 78% of lean mass), reduced voluntary wheel-running distance (22% decrease, P = 0.009), reduced average running speed, and reduced grip strength (7-16% reduction depending on age at testing). With their decreased voluntary exercise, and decreased lean mass, mVDR have increased proportional fat mass at 20% compared with 13%. Surprisingly, their muscle fibres showed slightly increased diameter, as well as the presence of angular fibres and central nuclei suggesting ongoing remodelling. There were, however, no clear changes in fibre type and there was no increase in muscle fibrosis. VDR is a transcriptional regulator, and changes in the expression of candidate genes was examined in RNA extracted from skeletal muscle. Alterations were seen in myogenic gene expression, and there was decreased expression of cell cycle genes cyclin D1, D2, and D3 and cyclin-dependent kinases Cdk-2 and Cdk-4. Expression of calcium handling genes sarcoplasmic/endoplasmic reticulum calcium ATPases (SERCA) Serca2b and Serca3 was decreased and Calbindin mRNA was lower in mVDR muscle. CONCLUSIONS: This study demonstrates that vitamin D signalling is needed for myocyte function. Despite the low level of VDR protein normally found muscle, deleting myocyte VDR had important effects on muscle size and strength. Maintenance of normal vitamin D signalling is a useful strategy to prevent loss of muscle function and size.

ß Cell Hypoxia-Inducible Factor-1α Is Required for the Prevention of Type 1 Diabetes.

The development of autoimmune disease type 1 diabetes (T1D) is determined by both genetic background and environmental factors. Environmental triggers include RNA viruses, particularly coxsackievirus (CV), but how they induce T1D is not understood. Here, we demonstrate that deletion of the transcription factor hypoxia-inducible factor-1α (HIF-1α) from ß cells increases the susceptibility of non-obese diabetic (NOD) mice to environmentally triggered T1D from coxsackieviruses and the ß cell toxin streptozotocin. Similarly, knockdown of HIF-1α in human islets leads to a poorer response to coxsackievirus infection. Studies in coxsackievirus-infected islets demonstrate that lack of HIF-1α leads to impaired viral clearance, increased viral load, inflammation, pancreatitis, and loss of ß cell mass. These findings show an important role for ß cells and, specifically, lack of ß cell HIF-1α in the development of T1D. These data suggest new strategies for the prevention of T1D.

Effects of spring administration of extended-release eprinomectin on fescue toxicosis, performance, and reproduction of fall-born beef heifers.

The objective of this experiment was to assess the effects of eprinomectin, an extended-release injectable parasiticide, on fescue toxicosis and its impacts on beef heifer performance and reproduction. Fall-born Angus × Simmental heifers (age = 246.3 ± 22.4 d; 264.8 ± 21.1 kg body weight [BW]) were randomly assigned to one of two treatments: extended-release eprinomectin injection (ERE; n = 100) or control (CON; saline; n = 99). Treatments were administered at a rate of 1 mL/50 kg BW. Prior to experiment, heifers were dosed with oral fenbendazole to minimize parasite load. All heifers grazed endophyte-infected tall fescue as a single group and were offered a 50:50 supplement mix of corn gluten feed and soybean hulls (2.7 kg as fed per heifer per day). Body condition scores (BCS), BW, hair coat score (HCS), blood, and fecal samples were collected throughout the experiment. A subset of 40 heifers were randomly selected (20 per treatment) to assess respiration rate (RR). On d 138, heifers began a 14-d controlled internal drug release + prostaglandin synchronization protocol. Following artificial insemination (AI), heifers were exposed to five bulls for 71 d. On d 214 and 291, AI and overall pregnancy rates, respectively, were determined. There was a treatment × time interaction (P < 0.01) for BW, BCS, and average daily gain (ADG). The ERE heifers had greater (P < 0.04) BW and BCS compared to CON heifers from d 55 and 112, respectively. In addition, ERE heifers had greater (P ≤ 0.04) ADG from d 0 to 56, 56 to 112, 112 to 171, and 171 to 214; however CON heifers had greater (P < 0.01) ADG from d 214 to 291. There was no treatment × time interaction or treatment difference (P ≥ 0.27) for HCS, RR, and serum prolactin concentrations. However, serum prolactin decreased (P < 0.01) in all heifers over time. There was a treatment × time interaction (P<0.01) for fecal egg counts (FEC). The FEC did not differ (P ≥ 0.32) on d -1 or 55; however, ERE heifers had decreased (P < 0.01) FEC compared with CON heifers on d 111 (1.52 vs. 13.56 eggs per gram). The ERE heifers tended (P = 0.10) to have greater AI pregnancy rates (69% vs. 58%) and had greater (P = 0.01) overall pregnancy rates (84% vs. 68%) than CON heifers. Spring administration of extended-release eprinomectin improved BW, ADG, BCS, and AI and overall pregnancy rates in fall-born beef heifers. However, the underlying mechanism is still unclear, as there were minimal to no differences in HCS, RR, serum prolactin, and FEC.

Influence of repeated trace mineral injections during gestation on beef heifer and subsequent calf performance.

Commercial Angus heifers (n = 190; body weight (BW) = 315 ± 49.3 kg) were used to determine the effects of trace mineral injections during gestation on heifer and subsequent calf performance. Heifers received three previous subcutaneous trace mineral (Multimin 90 [MM]; n = 93) or sterilized physiological saline (CON; n = 97) injections approximately 90 d apart. These treatments were maintained and subsequent injections were given 205, 114, and 44 ± 26 d prepartum. Heifers were provided free-choice inorganic minerals. Heifer BW and body condition scores (BCS) were collected at trial initiation (296 ± 26 d prepartum) and 5- to 10-week intervals thereafter. Liver samples were collected at trial initiation, 5 and 176 ± 3 d postpartum from a subset of cows to determine trace mineral status. Milk production was assessed on 80 cow-calf pairs (40/treatment) at 71 ± 15 d postpartum. Cows were artificially inseminated (AI) 82 d postpartum and then exposed to bulls for 38 d. Data were reported from 174 calves (n = 87 calves/treatment). Calf liver samples were collected 5 and 147 ± 3 d postpartum to determine trace mineral status. Calf weaning BW was collected at 159 ± 26 d postpartum. Calf performance including calving date, birth BW, weaning BW, average daily gain (ADG), and health data were collected. Heifer BW and BCS did not differ (P ≥ 0.72) throughout the experiment. Multimin heifers tended (P = 0.08) to have greater initial liver Se and tended to have decreased (P = 0.08) initial liver Zn compared with CON. At calving, MM cows had increased (P ≤ 0.01) liver Cu and Se. There was no difference (P ≥ 0.47) in Julian calving date, calving percent, or unassisted births. Calf birth BW was lesser (P = 0.02) for MM than CON calves, and MM calves had greater (P = 0.03) liver Cu concentrations at birth than CON calves. Despite MM cows having increased (P < 0.01) milk production, calf weaning BW and ADG were not different (P ≥ 0.87). In addition, calf morbidity and mortality were not different (P ≥ 0.43) between treatments. Calf mineral status was not different (P ≥ 0.57) at the time of weaning regardless of treatment; however, MM cows had decreased (P = 0.03) liver Zn. Multimin cows had decreased (P = 0.05) AI pregnancy rates, yet there was no difference (P = 0.34) in overall pregnancy rate. Supplementing an injectable trace mineral during heifer development and gestation increased cow milk production and resulted in decreased AI pregnancy rates; however, there was no effect on overall pregnancy rates or preweaning calf health or performance.

Effects of extended-release eprinomectin on fescue toxicosis, performance, and reproduction on fall-calving beef cows.

The objective of this experiment was to evaluate effects of extended-release eprinomectin on fescue toxicosis and impacts on performance and reproduction in fall-calving beef cows. Fall-calving Angus × Simmental multiparous cows [n = 335; age = 5.8 ± 2.1 yr; 586.5 ± 6.0 kg body weight (BW); 5.48 ± 0.05 body condition score (BCS)] were stratified by BW, age, and BCS and randomly assigned to one of three treatments. Treatments included a spring injection of extended-release eprinomectin (SERE) on day 0, a fall injection of extended-release eprinomectin injection (FERE) on day 84, and a saline control (CON). All treatments were administered at a rate of 1 mL/50 kg BW. Prior to the experiment, all cows were treated with oral fenbendazole to minimize parasite load. Cows grazed endophyte-infected tall fescue. Hair coat score (HCS), BW, and BCS were recorded on all cattle. Fecal egg count (FEC), respiration rate (RR), horn fly and tick count, hematocrit (% packed cell volume, PCV), and serum prolactin were analyzed on a subset of cows (35/treatment). On day 194, cows were artificially inseminated (AI) and 11 d following AI were exposed to bulls for 51 d. Milk production was estimated on day 210 on a subset of 85 cow-calf pairs (28-29/treatment). There was a tendency for a treatment × time interaction (P = 0.07) for FEC likely driven by an increase in FEC of the CON cattle at day 126 compared to SERE and FERE. There was a tendency for a treatment × time interaction (P = 0.06) for cow BW, largely driven by time differences; however, there was no effect of treatment (P = 0.84) on BW. There was no difference (P ≥ 0.13) in cow PCV, fly and tick count, BCS, HCS, RR, and serum prolactin throughout the experiment. Additionally, there was no difference (P ≥ 0.46) in Julian calving date, calf birth BW, or milk production between treatments. Interestingly, heifer calves born to FERE dams tended to have greater (P = 0.06) weaning BW compared to heifer calves born to CON dams. In addition, there was no difference (P ≥ 0.17) in heat patch scores, AI conception rates, or overall pregnancy rates between treatments. Extended-release eprinomectin did not impact cow growth performance, reproductive performance or fescue toxicity symptoms when grazing endophyte-infected tall fescue; however, calf weaning BW tended to be improved.

Evaluation of two-stage weaning and trace mineral injection on receiving cattle growth performance and behavior.

The objective was to evaluate the effects of two-stage weaning and injectable trace mineral (ITM) on receiving cattle growth performance and behavior. Angus and Simmental × Angus steers (n = 136; body weight [BW] = 200 ± 26 kg) were utilized in a 2 × 2 factorial design. Calves were blocked by source, and assigned to one of four treatments: 1) two-stage weaning and ITM (2MM), 2) two-stage weaning and saline injection (2SAL), 3) abrupt weaning and ITM (AbtMM), or 4) abrupt weaning and saline injection (AbtSAL). On d-6, calves were weighed, plastic calf weaner devices (used to prevent calf from nursing) were inserted in two-stage weaned calves, and ITM or saline injections (1 mL/45.4 kg BW) were administered. On day 0, plastic calf weaner devices were removed, and calves were weighed and shipped 272 km to Urbana, IL. Steer behavior was observed the 2 d following separation from dam. Receiving period was day 0 to 42 and growing period was day 42 to 124. Data were analyzed using the MIXED procedure of SAS and pen (six per treatment) was the experimental unit. Abruptly weaned calves had greater (P < 0.01) preweaning average daily gain (ADG) than two-stage weaned calves. Treatment did not affect (P ≥ 0.16) ADG during the receiving or growing period; however, calves that received ITM tended (P 0.06) to have greater ADG from day 0 to 124. During the receiving period, abruptly weaned calves tended (P = 0.08) to eat more than two-stage calves and ITM calves ate more (P = 0.03) than calves that received saline. There was a weaning strategy × ITM interaction (P < 0.01) for dry matter intake (DMI) from day 0 to 124; 2MM calves ate more (P < 0.01) than 2SAL, but DMI was not different (P = 0.58) between AbtMM and AbtSAL calves. There was a weaning strategy × ITM interaction (P < 0.01) for gain-to-feed ratio (G:F) from day 0 to 124; 2SAL calves had greater (P = 0.05) G:F than AbtSAL, with 2MM and AbtMM calves being intermediate and not different (P = 0.38) than each other. Two-stage weaning decreased (P ≤ 0.02) the percentage of calves walking, standing, and vocalizing, and increased (P ≤ 0.02) the percentage of calves lying and eating following separation from dam. Two-stage weaning decreased preweaning ADG and behavioral signs of stress at feedlot arrival, but had no effect on overall growth. In addition, ITM had no effect on calf BW or behavior, but increased overall DMI in two-stage weaned calves compared to abruptly weaned calves and tended to increase overall ADG regardless of weaning strategy.

Effects of a Saccharomyces cerevisiae fermentation product in receiving diets of newly weaned beef steers. II. Digestibility and response to a vaccination challenge1.

Thirty-six newly weaned, crossbred beef steers (323 ± 12 kg; SD) from a single-source were used in a 56-d study to examine the effects of a Saccharomyces cerevisiae fermentation product (SCFP; Original XPC, Diamond V, Cedar Rapids, IA) on total tract nutrient digestibility and response to a vaccination challenge. Twelve days after arrival, steers were blocked by body weight (BW) and randomly assigned to treatments: SCFP at 0 (CON), 14 (SCFP14), or 28 (SCFP28) g·steer-1·d-1. Steers were fed via bunks that measured individual intake and received ear tags (CowManager, Select Sires, Plain City, OH) that recorded rumination and activity. BWs were collected on days 1, 0, 14, 28, 42, 55, and 56. Titanium dioxide was fed as an indigestible marker to all steers from days 12 to 27, followed by consecutive day fecal samples, for determination of total tract nutrient digestibility. On day 34, steers received a Mannheimia haemolytica vaccination (One Shot, Zoetis, Kalamazoo, MI) to induce an acute phase protein response. Blood was collected from all steers on day 34 (prior to vaccination) and 3, 6, 9, 11, and 14 d post-vaccination. Data were analyzed using Proc Mixed of SAS (experimental unit = steer; n = 12 per treatment); the model included the fixed effect of treatment and block and the random effect of steer. Blood measures, ear tag, and dry matter intake (DMI) data for the 15-d vaccination period were analyzed as repeated measures. Contrast statements (CON vs. SCFP14; SCFP14 vs. SCFP28) were used to compare treatment means. Digestibility of dry matter (DM) and organic matter was greater for SCFP14 vs. SCFP28 (P ≤ 0.03). Steers fed SCFP14 exhibited greater crude protein digestibility compared with CON (P < 0.01). Steers fed SCFP14 exhibited greater DMI for 15 d post-vaccination (P = 0.02) and greater average daily gain from days 28 to 56 (P = 0.05) vs. SCFP28-fed steers. Post-vaccination, steers fed SCFP14 spent less time ruminating per kg of DM, neutral detergent fiber (NDF), and physically effective NDF consumed than CON or SCFP28 (P ≤ 0.07). Serum IL-8 and haptoglobin concentrations tended to be lesser for steers fed SCFP14 vs. SCFP28 (P ≤ 0.08). Ceruloplasmin concentrations were lesser on day 14 post-vaccination for steers fed SCFP14 vs. CON or SCFP28 (treatment × d; P = 0.004); there were no differences on other sampling days due to treatment. Although no overall performance benefit was noted, steers fed SCFP14 responded better to a vaccination challenge vs. SCFP28-fed steers.

Effects of a Saccharomyces cerevisiae fermentation product in receiving diets of newly weaned beef steers. I. Growth performance and antioxidant defense1.

To evaluate the effects of a Saccharomyces cerevisiae fermentation product (SCFP; Original XPC, Diamond V, Cedar Rapids, IA) on growth performance and antioxidant defense of newly weaned beef cattle, 180 single-source steers (278 ± 21 kg; SD) were used in a 56-d receiving study. Seven days after arrival, steers were blocked by body weight (BW) to pens of 6 and randomly assigned to treatments: SCFP at 0 (CON), 14 (SCFP14), or 28 (SCFP28) g·steer-1·d-1. Pen was the experimental unit (n = 10 per treatment). On day 0, steers were boostered against Bovine Viral Diarrhea Virus (BVDV) Type 1 and 2 (Vista Once, Merck, Madison, NJ). Weights were collected on days 1, 0, 14, 27, 42, 55, and 56. One steer per pen was bled on days 0, 14, 27, 42, and 56 for analysis of BVDV antibody titers; blood from days 0, 27, and 56 was analyzed for red blood cell lysate superoxide dismutase (SOD) activity and glutathione (total = tGSH, oxidized = GSSG, and reduced = GSH) concentrations, plasma malondialdehyde (MDA) concentrations, and serum lysozyme activity. Performance and blood data were analyzed as a randomized complete block design using Proc Mixed of SAS with fixed effects of treatment and block and random effect of pen. Linear and quadratic contrast statements were used. Antibody titers were log transformed and analyzed as repeated measures. There were no treatment by day interactions (P ≥ 0.16), and no linear or quadratic effects of SCFP on feedlot performance, antibody titers, or lysozyme activity (P > 0.10). Day 27 MDA concentrations tended to linearly increase (P = 0.09). A quadratic effect of SCFP on day 56 SOD activity (P = 0.004) was driven by lesser activity for SCFP14-fed steers. On day 27, a tendency for a quadratic effect of SCFP (P = 0.09) on GSH was driven by greater concentrations for SCFP14-fed steers resulting in a lesser GSSG:GSH ratio (P = 0.05). Greater GSH for SCFP14-fed steers caused a tendency for a quadratic effect on day 56 (P = 0.07); however, this did not result in an effect of SCFP on the GSSG:GSH ratio (P ≥ 0.25). A tendency for a linear effect of SCFP on tGSH was noted on day 56 (P = 0.09). Morbidity data were analyzed using Proc Glimmix of SAS. There was a quadratic effect of SCFP on percentage of respiratory treatments prior to day 14 (P = 0.04). These results could indicate lesser levels of oxidative stress for steers receiving SCFP at 14 vs. 0 or 28 g/d. Under the conditions of this study, no performance benefit of SCFP was noted.

Vitamin D and the Liver-Correlation or Cause?

Vitamin D is becoming increasingly accepted as an important physiological regulator outside of its classical role in skeletal homeostasis. A growing body of evidence connects vitamin D with hepatic disease. This review summarises the role of vitamin D in liver homeostasis and disease and discusses the therapeutic potential of vitamin D-based treatments to protect against hepatic disease progression and to improve response to treatment. While pre-clinical experimental data is promising, clinical trials around liver diseases have mostly been under-powered, and further studies will be required to clarify whether vitamin D or vitamin D analogues have beneficial effects on liver disease.

Effect of repeated trace mineral injections on beef heifer development and reproductive performance.

To determine the effects of repeated trace mineral injections on heifer development and reproductive performance, commercial Angus heifers (n = 290; 199 ± 34.3 kg; 221 ± 22 d of age) were utilized in a completely randomized design. Heifers were stratified by body weight (BW) and were administered an injectable trace mineral (MM; Multimin 90) or saline (CON) given subcutaneously, post-weaning at 221, 319, 401, and 521 ± 22 d of age. Throughout development, heifers grazed endophyte-infected fescue, red clover pastures and were supplemented with corn distillers grains (2.7 kg per heifer per day) and given access to free choice inorganic minerals. Heifer BW and body condition scores (BCS) were collected at trial initiation and 4- to 7-wk intervals thereafter. Hair coat scores (HCS) and respiration rates (n = 30 heifers per treatment) were collected at 269, 310, and 361 ± 22 d of age. Blood and liver samples were collected at trial initiation and estrous synchronization from 30 heifers per treatment to determine trace mineral status. At 319, 372, and 421 ± 22 d of age, antral follicle count and ovarian size were determined via ultrasonography. Two blood samples from all heifers were collected 10 d apart, concurrent with ultrasound dates, for cyclicity determination. Estrous synchronization was initiated, and reproductive tract scores (RTS) were collected at 421 ± 22 d of age, and heifers were bred via artificial insemination (AI) at 430 ± 22 d of age. Heifer BW, BCS, and HCS did not differ (P ≥ 0.12) throughout development, except at 268 ± 22 d of age when BCS was greater (P = 0.03) for MM than CON heifers. Respiratory rates were greater (P = 0.05) for MM than CON heifers at 269 ± 22 d of age but did not differ (P ≥ 0.66) at 310 and 361 ± 22 d of age. Plasma Mn and Zn concentrations did not differ (P ≥ 0.54). However, MM heifers had greater (P ≤ 0.01) plasma and liver concentrations of Cu and Se compared to CON. Interestingly, MM decreased (P = 0.02) liver Zn concentrations compared to CON, and there was no difference (P = 0.60) in liver Mn. Antral follicle count and ovarian size did not differ (P ≥ 0.51) due to treatment. Throughout development, number of heifers cycling was lesser (P < 0.01) for MM than CON heifers. However, there was no difference (P ≥ 0.19) in RTS, AI pregnancy rates, or overall pregnancy rates. Supplementing an injectable trace mineral increased heifer Cu and Se status; however, no effect was noted on ovarian development or pregnancy rates.

Hepatic Aryl hydrocarbon Receptor Nuclear Translocator (ARNT) regulates metabolism in mice.

BACKGROUND & AIMS: Aryl hydrocarbon Receptor Nuclear Translocator (ARNT) and its partners hypoxia-inducible factors (HIF)-1α and HIF-2α are candidate factors for the well-known link between the liver, metabolic dysfunction and elevation in circulating lipids and glucose. Methods: Hepatocyte-specific ARNT-null (LARNT), HIF-1α-null (LHIF1α) and HIF-2α-null (LHIF2α) mice were created. RESULTS: LARNT mice had increased fasting glucose, impaired glucose tolerance, increased glucose production, raised post-prandial serum triglycerides (TG) and markedly lower hepatic ATP versus littermate controls. There was increased expression of G6Pase, Chrebp, Fas and Scd-1 mRNAs in LARNT animals. Surprisingly, LHIF1α and LHIF2α mice exhibited no alterations in any metabolic parameter assessed. CONCLUSIONS: These results provide convincing evidence that reduced hepatic ARNT can contribute to inappropriate hepatic glucose production and post-prandial dyslipidaemia. Hepatic ARNT may be a novel therapeutic target for improving post-prandial hypertriglyceridemia and glucose homeostasis.

Transplantation sites for porcine islets.

AIMS/HYPOTHESIS: Xenotransplantation has great potential to provide beta cell replacement and thereby provide a cure for large numbers of people with type 1 diabetes. Crucial to the success of xenotransplantation is establishment of the most viable sites for transplantation. METHODS: We compared porcine islet tissue transplanted into kidney, liver and spleen in pig recipients as assessed by blood glucose levels and IVGTT. RESULTS: Kidney was the superior site for porcine islet tissue transplantation, followed by liver then spleen. This was demonstrated by IVGTTs showing significant difference between the peak glucose levels: 22.8 ± 2.9 mmol/l for kidney compared with 26.8 ± 1.3 mmol/l for spleen and 24.7 ± 1.7 mmol/l for liver. CONCLUSIONS/INTERPRETATION: Kidney grafts are not as feasible in humans and liver results were relatively poorer than spleen. For islet transplantation to be viable and successful in the longer term, there remains a need for future investigation of alternative sites.

Transplantation sites for human and murine islets.

AIMS/HYPOTHESIS: Beta cell replacement is a potential cure for type 1 diabetes. In humans, islet transplants are currently infused into the liver via the portal vein, although this site has disadvantages. Here, we investigated alternative transplantation sites for human and murine islets in recipient mice, comparing the portal vein with quadriceps muscle and kidney, liver and spleen capsules. METHODS: Murine islets were isolated from C57BL6/J mice and transplanted into syngeneic recipients. Human islets were isolated and transplanted into either severe combined immunodeficiency (SCID) or recombination-activating gene 1 (RAG-1) immunodeficient recipient mice. All recipient mice were 8-12 weeks of age and had been rendered diabetic (defined as blood glucose concentrations ≥20 mmol/l on two consecutive days before transplantation) by alloxan tetrahydrate treatment. Islets were transplanted into five different sites (portal vein, quadriceps muscle, kidney, liver and spleen capsules). Blood glucose concentrations were monitored twice weekly until mice were killed. Dose-response studies were also performed to determine the minimum number of islets required to cure diabetes ('cure' is defined for this study as random fed blood glucose of <15 mmol/l). RESULTS: For transplantation of murine islets into the different sites, the kidney yielded 100% success, followed by muscle (70%), portal vein (60%), spleen capsule (29%) and liver capsule (0%). For human islets, transplantation into the kidney cured diabetes in 75-80% of recipient mice. Transplantation into muscle and portal vein had intermediate success (both 29% at 2000 islet equivalents), while transplantation into liver and spleen capsule failed (0%). With increased islet mass, success rates for muscle grafts improved to 52-56%. CONCLUSIONS/INTERPRETATION: For both human and murine islets, equivalent or superior glucose lowering results were obtained for transplantation into skeletal muscle, compared with the portal vein. Unfortunately, kidney grafts are not feasible in human recipients. Skeletal muscle offers easier access and greater potential for protocol biopsies. This study suggests that human trials of muscle as a transplant site may be warranted.