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1.
Crit Rev Oncol Hematol ; 175: 103701, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35533817

ABSTRACT

The uterine carcinosarcoma (UCS) is a rare entity with poor prognosis. Treatment of FIGO I-II UCS usually consists of surgery with or without adjuvant treatment. Due to the high metastatic potential, aggressive combined modality adjuvant treatment approaches, consisting of chemo- and radiotherapy, have been of interest. Our systematic review aims to compare survival, disease control and toxicity profiles in patients receiving adjuvant chemoradiation to other adjuvant strategies (e.g.observation, chemotherapy or radiotherapy). A total of ten studies were included for a combined cohort size of 6520 patients. Generally, the studies showed a trend towards improved disease control and survival in patients undergoing adjuvant multimodal treatment, although statistical significance was often not reached. Selection bias and non-randomized treatment allocation pose serious challenges to extrapolate these outcomes to clinical practice. We recommend additional prospective research on the role of adjuvant chemoradiation in FIGO I-II UCS.


Subject(s)
Carcinosarcoma , Uterine Neoplasms , Carcinosarcoma/drug therapy , Carcinosarcoma/pathology , Chemotherapy, Adjuvant , Combined Modality Therapy , Female , Humans , Neoplasm Staging , Prospective Studies , Radiotherapy, Adjuvant , Retrospective Studies , Uterine Neoplasms/pathology , Uterus/pathology
2.
J Steroid Biochem Mol Biol ; 198: 105574, 2020 04.
Article in English | MEDLINE | ID: mdl-31881310

ABSTRACT

High intestinal calcium (Ca) absorption efficiency is associated with high peak bone mass in adolescents and reduced bone loss in adulthood. Transepithelial intestinal Ca absorption is mediated by 1,25-dihydroxyvitamin D (1,25(OH)2D, calcitriol) through the vitamin D receptor (VDR). Most research on Ca absorption focuses on the proximal small intestine but evidence shows that large intestine plays a crucial role in whole body Ca homeostasis. We directly assessed and compared Ca absorption capacity at the proximal colon and duodenum using in situ ligated loops (2 mM Ca, 10 min). In C57BL/6 J mice, the proximal colon (26.2 ±â€¯3.7 %) had comparable ability to absorb Ca as the duodenum (30.0 ±â€¯6.7 %). In VDR knockout (KO) mice, Ca absorption efficiency was reduced by 67 % in duodenum and 48 % in proximal colon. These data suggest that large intestine could be targeted to improve Ca absorption and protect bone in at risk-groups (e.g. bariatric patients). Glycoside forms of calcitriol found in Solanum Glaucophyllum (Sg) leaf are biologically inert but can be activated in the colon upon bacterial cleavage of the glycosides. We conducted a study to test whether Sg leaf, as well as a novel, synthetic 1,3-diglucuronide form of calcitriol (1,3-diG) could target the proximal colon and upregulate genes involved in Ca absorption (i.e. Trpv6, S100g). 13-week-old female C57BL6/J mice were fed AIN93 G diet containing increasing levels of one of the two compounds for 2 weeks (delivering 0, 0.25, 0.5, 1, or 2 ng calcitriol equivalent per day). Both compounds induced a dose-dependent upregulation of Cyp24a1 and Trpv6 gene expression in the proximal colon. 1,3-diG also induced S100g gene expression in the proximal colon. Duodenal expression of Trpv6 was upregulated at higher doses of 1,3-diG but not Sg leaf. These data suggest that both glycosylated and glucuronidated calcitriol could be used to target the proximal colon but that dosing must be optimized to limit systemic effects that could cause hypercalcemia. Future studies will test the translational potential of these compounds to determine if they can increase Ca absorption at proximal colon and whether this can help protect bone.


Subject(s)
Calcitriol/analogs & derivatives , Calcium/metabolism , Colon/drug effects , Glucuronides/pharmacology , Intestinal Absorption/drug effects , Animals , Calcitriol/administration & dosage , Calcitriol/chemistry , Calcitriol/pharmacology , Colon/metabolism , Female , Glucuronides/administration & dosage , Glucuronides/chemistry , Mice, Inbred C57BL , Solanum glaucophyllum/chemistry
3.
J Vet Intern Med ; 31(6): 1796-1803, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28941306

ABSTRACT

BACKGROUND: Low blood 25-hydroxyvitamin D (25(OH)D) concentrations have been associated with cancer in dogs. Little research has examined what other factors may affect 25(OH)D concentrations. OBJECTIVES: (1) To determine whether the presence of cancer (lymphoma, osteosarcoma, or mast cell tumor [MCT]) in dogs is associated with plasma 25(OH)D concentrations and (2) identify other factors related to plasma 25(OH)D concentrations in dogs. ANIMALS: Dogs newly diagnosed with osteosarcoma (n = 21), lymphoma (n = 27), and MCT (n = 21) presented to a tertiary referral oncology center, and healthy, client-owned dogs (n = 23). METHODS: An observational study design was used. Dietary vitamin D intake, sex, age, body condition score (BCS), muscle condition score (MCS), and plasma concentrations of 25(OH)D, 24,25-dihydroxyvitamin D (24,25(OH)2 D) (a marker of CYP24A1 activity), as well as ionized calcium (ICa), parathyroid hormone, and parathyroid hormone-related protein concentrations were measured. An analysis of covariance was used to model plasma 25(OH)D concentrations. RESULTS: Cancer type (P = 0.004), plasma 24,25(OH)2 D concentrations (P < 0.001), and plasma ICa concentrations (P = 0.047) had significant effects on plasma 25(OH)D concentrations. Effects of age, sex, body weight, BCS, MCS, and plasma PTH concentrations were not identified. A significant interaction between ICa and cancer was found (P = 0.005). Plasma 25(OH)D concentrations increased as ICa concentrations increased in dogs with cancer, whereas plasma 25(OH)D concentrations decreased as ICa concentrations increased in healthy dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Results support a relationship between cancer and altered vitamin D metabolism in dogs, mediated by plasma ICa concentrations. The CYP24A1 activity and plasma ICa should be measured in studies examining plasma 25(OH)D concentrations in dogs.


Subject(s)
Calcium/blood , Dog Diseases/blood , Neoplasms/veterinary , Vitamin D/analogs & derivatives , Animals , Dogs , Female , Lymphoma/blood , Lymphoma/veterinary , Male , Mast-Cell Sarcoma/blood , Mast-Cell Sarcoma/veterinary , Neoplasms/blood , Osteosarcoma/blood , Osteosarcoma/veterinary , Parathyroid Hormone/blood , Vitamin D/blood , Vitamin D3 24-Hydroxylase/blood
4.
J Dairy Sci ; 97(3): 1520-8, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24418271

ABSTRACT

Subclinical hypocalcemia may affect half of all multiparous cows, and clinical hypocalcemia or milk fever affects approximately 5% of dairy cows each year. This disorder of calcium homeostasis can be induced by several dietary factors. Recent studies implicate high dietary potassium and high dietary cation-anion difference (DCAD) with increased risk of milk fever. The hypothesis tested in this study was that high-DCAD diets fed to prepartum cows reduce tissue sensitivity to parathyroid hormone (PTH), inducing a pseudohypoparathyroid state that diminishes calcium homeostatic responses. Multiparous Jersey cows were fed low- or high-DCAD diets in late gestation, creating a compensated metabolic alkalosis in the high-DCAD cows and a compensated metabolic acidosis in the low-DCAD cows. They then received synthetic PTH injections at 3-h intervals for 48 h. Parathyroid hormone is expected to cause an increase in plasma calcium by increasing renal production of 1,25-dihydroxyvitamin D and increasing bone calcium resorption. Plasma calcium concentration increased at a significantly lower rate in cows fed the high-DCAD diet. Cows fed the high-DCAD diet also produced significantly less 1,25-dihydroxyvitamin D in response to the PTH injections than cows fed the low-DCAD diet. Serum concentrations of the bone resorption marker carboxyterminal telopeptide of type I collagen were numerically lower in cows fed the high-DCAD diet but this difference was not statistically significant. These data provide direct evidence that high-DCAD diets reduce tissue sensitivity to PTH. The metabolic alkalosis associated with high-DCAD diets likely induces a state of pseudohypoparathyroidism in some dairy cows at the onset of lactation, resulting in hypocalcemia and milk fever.


Subject(s)
Cattle Diseases/blood , Diet/adverse effects , Diet/veterinary , Hypocalcemia/veterinary , Parturient Paresis/pathology , Pseudohypoparathyroidism/veterinary , Animals , Calcium/blood , Calcium/urine , Cathepsin K/metabolism , Cattle , Cattle Diseases/etiology , Cattle Diseases/pathology , Creatinine/urine , Female , Hypocalcemia/etiology , Lactation , Magnesium/blood , Magnesium/urine , Parathyroid Hormone/administration & dosage , Parathyroid Hormone/blood , Parturient Paresis/blood , Parturient Paresis/etiology , Pregnancy , Pseudohypoparathyroidism/etiology , Risk Factors , Vitamin D/analogs & derivatives , Vitamin D/blood
5.
J Anim Sci ; 92(1): 152-63, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24243907

ABSTRACT

Four experiments were conducted to investigate the effects of varying concentrations of supplemental vitamin D3 on pig growth, feed preference, serum 25-hydroxycholecalciferol [25(OH)D3] , and bone mineralization of nursing and weanling pigs. In Exp. 1, 270 pigs (1.71 ± 0.01 kg BW) were administered 1 of 3 oral vitamin D3 dosages (none, 40,000, or 80,000 IU vitamin D3) on d 1 or 2 of age. Increasing oral vitamin D3 increased serum 25(OH)D3 on d 10 and 20 (quadratic, P < 0.01) and d 30 (linear, P < 0.01). No differences were observed in ADG before weaning or for nursery ADG, ADFI, or G:F. Vitamin D3 concentration had no effect on bone ash concentration or bone histological traits evaluated on d 19 or 35. In Exp. 2, 398 barrows (initially 7 d of age) were used in a 2 × 2 split plot design to determine the influence of vitamin D3 before (none or 40,000 IU vitamin D3 in an oral dose) or after weaning (1,378 or 13,780 IU vitamin D3/kg in nursery diets from d 21 to 31 of age) in a 45-d trial. Before weaning (7 to 21 d of age), oral vitamin D3 dose did not influence growth but increased (P < 0.01) serum 25(OH)D3 at weaning (d 21) and tended (P = 0.08) to increase 25(OH)D3 on d 31. Increasing dietary vitamin D3 concentration from d 21 to 31 increased (P < 0.01) serum 25(OH)D3 on d 31. Neither the oral vitamin D3 dose nor nursery vitamin D3 supplements influenced nursery ADG, ADFI, or G:F. In Exp. 3, 864 pigs (initially 21 d of age) were allotted to 1 of 2 water solubilized vitamin D3 treatments (none or 16,516 IU/L vitamin D3 provided in the drinking water from d 0 to 10) in a 30-d study. Providing vitamin D3 increased serum 25(OH)D3 concentrations on d 10, 20, and 30; however, vitamin D3 supplementation did not affect overall (d 0 to 30) ADG, ADFI, or G:F. In Exp. 4, 72 pigs were used in a feed preference study consisting of 2 feed preference comparisons. Pigs did not differentiate diets containing either 1,378 or 13,780 IU vitamin D3/kg but consumed less (P < 0.01) of a diet containing 44,100 IU vitamin D3/kg compared with the diet containing 1,378 IU vitamin D3/kg. Overall, these studies demonstrate that supplementing vitamin D3 above basal concentrations used in these studies is effective at increasing circulating 25(OH)D3, but the supplement did not influence growth or bone mineralization. Also, concentrations of vitamin D3 of 44,100 IU/kg of the diet may negatively affect feed preference of nursery pigs.


Subject(s)
Calcifediol/blood , Calcification, Physiologic/drug effects , Cholecalciferol/pharmacology , Feeding Behavior/drug effects , Sus scrofa/physiology , Vitamins/pharmacology , Animal Feed/analysis , Animal Nutritional Physiological Phenomena/drug effects , Animals , Cholecalciferol/administration & dosage , Diet/veterinary , Dietary Supplements/analysis , Female , Male , Sus scrofa/growth & development , Vitamins/administration & dosage
6.
J Dairy Sci ; 93(11): 5082-90, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20965322

ABSTRACT

This study determined the vitamin D(3) content and variability of retail milk in the United States having a declared fortification level of 400 IU (10 µg) per quart (qt; 1 qt=946.4 mL), which is 25% daily value per 8 fluid ounce (236.6 mL) serving. In 2007, vitamin D(3) fortified milk (skim, 1%, 2%, whole, and 1% fat chocolate milk) was collected from 24 statistically selected supermarkets in the United States. Additionally, 2% milk samples from an earlier 2001 USDA nationwide collection were reanalyzed. Vitamin D(3) was determined using a specifically validated method involving HPLC with UV spectroscopic detection and vitamin D(2) as an internal standard. Quality control materials were analyzed with the samples. Of the 120 milk samples procured in 2007, 49% had vitamin D(3) within 100 to 125% of 400 IU (10 µg)/qt (label value), 28% had 501 to 600 IU (12.5-15 µg)/qt, 16% had a level below the label amount, and 7% had greater than 600 IU (15 µg)/qt (>150% of label). Even though the mean vitamin D(3) content did not differ statistically between milk types, a wide range in values was found among individual samples, from nondetectable [<20 IU (0.5 µg)/qt] for one sample to almost 800 IU (20 µg)/qt, with a trend toward more samples of whole milk having greater than 150% of the labeled content. On average, vitamin D(3) in 2% milk was higher in 2007 compared with in 2001 [473 vs. 426 IU (11.8 vs. 10.6 µg)/qt].


Subject(s)
Cholecalciferol/analysis , Cholecalciferol/standards , Food, Fortified/standards , Milk/chemistry , Animals , Databases, Factual , Food, Fortified/analysis , Milk/standards , Nutritional Requirements , Quality Control , Reference Standards , United States , United States Department of Agriculture
7.
J Dairy Sci ; 93(6): 2684-90, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20494177

ABSTRACT

Effects of growth rate on fat-soluble vitamin and macro- and micromineral concentrations in the circulation of preruminant dairy calves were evaluated. Dietary treatments were designed to achieve 3 targeted rates of gain [no growth (NG)=0.0 kg/d; low growth (LG)=0.55 kg/d; or high growth (HG)=1.2 kg/d] over a 7-wk period. Milk replacer (MR) intakes necessary to achieve these growth rates were estimated using the National Research Council's Nutrient Requirements of Dairy Cattle calf model computer program. All of the calves were fed a 30% crude protein, 20% fat MR reconstituted to 14% dry matter. The diets were formulated to ensure that protein was not a limiting nutrient. No-growth and LG calves were supplemented additionally with vitamins A, D, and E to compensate for treatment differences in dry matter intake relative to the HG calves; however, no attempt was made to adjust mineral intake based on MR consumption. Growth rates for NG (0.11 kg/d), LG (0.58 kg/d), and HG (1.16 kg/d) calves differed during the study. Health was minimally affected by growth rate and this was reflected by comparable and relatively low serum haptoglobin concentrations in all calves during the 7-wk period. Concentrations of serum retinol, 25-(OH)-vitamin D(3), and zinc were unaffected by growth rate. The HG calves had lower RRR-alpha-tocopherol concentrations than NG and LG calves at wk 7, suggesting that the increased growth rate of HG calves was associated with increased utilization of vitamin E. Serum concentrations of all vitamins increased with age. Copper, calcium, and phosphorous concentrations in HG calves exceeded those in LG and NG calves during the latter weeks of the study, likely because of increased MR intake by HG calves. Fat-soluble vitamin and mineral concentrations for all treatment groups remained within ranges considered normal for preruminant calves.


Subject(s)
Cattle/growth & development , Diet/veterinary , Minerals/blood , Vitamins/blood , Animal Feed , Animals , Animals, Newborn/blood , Animals, Newborn/growth & development , Calcium/blood , Cattle/blood , Copper/blood , Female , Haptoglobins/analysis , Magnesium/blood , Male , Phosphorus/blood , Vitamin A/blood , Vitamin D/blood , Zinc/blood , alpha-Tocopherol/blood
8.
J Dairy Sci ; 92(12): 6134-43, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19923616

ABSTRACT

The physiological response of the preruminant calf to sustained exposure to moderate cold has not been studied extensively. Effects of cold on growth performance and health of preruminant calves as well as functional measures of energy metabolism, fat-soluble vitamin, and immune responsiveness were evaluated in the present study. Calves, 3 to 10 d of age, were assigned randomly to cold (n = 14) or warm (n = 15) indoor environments. Temperatures in the cold environment averaged 4.7 degrees C during the study. Frequent wetting of the environment and the calves was used to augment effects of the cold environment. Temperatures in the warm environment averaged 15.5 degrees C during the study. There was no attempt to increase the humidity in the warm environment. Preventative medications or vaccinations that might influence disease resistance were not administered. Nonmedicated milk replacer (20% crude protein and 20% fat fed at 0.45 kg/d) and a nonmedicated starter grain fed ad libitum were fed to all calves. Relative humidity was, on average, almost 10% higher in the cold environment. Warm-environment calves were moderately healthier (i.e., lower respiratory scores) and required less antibiotics. Scour scores, days scouring, and electrolyte costs, however, were unaffected by environmental temperature. Growth rates were comparable in warm and cold environments, although cold-environment calves consumed more starter grain and had lower blood glucose and higher blood nonesterified fatty acid concentrations. The nonesterified fatty acid and glucose values for cold-stressed calves, however, did not differ sufficiently from normal values to categorize these calves as being in a state of negative-energy balance. Levels of fat-soluble vitamin, antibody, tumor necrosis factor-alpha, and haptoglobin were unaffected by sustained exposure to moderate cold. These results support the contention that successful adaptation of the dairy calf to cold is dependent upon the availability of adequate nutrition.


Subject(s)
Cattle/physiology , Cold Temperature , Environment , Animals , Blood Glucose/analysis , Cattle/growth & development , Cattle/immunology , Cattle/metabolism , Fatty Acids, Nonesterified/blood , Haptoglobins/metabolism , Immunoglobulin G/blood , Male , Tumor Necrosis Factor-alpha/blood , Vitamins/blood
9.
J Anim Sci ; 86(7): 1637-48, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18344286

ABSTRACT

The objective of this trial was to determine how 25-hydroxyvitamin D(3) (25-OH D(3)) supplementation, altering supplemental dietary calcium, or their combination influence postmortem biochemical and tenderness changes in muscles from the round of mature cows. Twenty-seven Angus cows (3 to 7 yr old) were allotted randomly to 9 pens with 3 cows per pen. Treatments were arranged in a 3 x 3 factorial design with 3 dosages of 25-OH D(3) (0, 250, or 500 mg of 25-OH D(3) administered as a 1-time oral bolus 7 d before slaughter) and 3 percentages of supplemental limestone (0.5, 0.75, and 1.0%) replenished in the diet for 3 d before slaughter and after a 2-wk limestone withdrawal. Plasma samples were obtained during the feeding period. Upon slaughter, adductor, gracilus, pectineus, sartorius, semimembranosus, vastus intermedius, and vastus lateralis muscles were obtained and aged for 1, 3, or 7 d. Calcium concentrations were increased in plasma when 250 or 500 mg of 25-OH D(3) were administered (P

Subject(s)
Calcifediol/administration & dosage , Calcium, Dietary/administration & dosage , Cattle/metabolism , Meat/standards , Muscle, Skeletal/metabolism , Animals , Calcifediol/blood , Calcifediol/metabolism , Calcitriol/blood , Calcium, Dietary/blood , Calcium, Dietary/metabolism , Calcium-Binding Proteins/metabolism , Cattle/blood , Dietary Supplements , Electrophoresis, Polyacrylamide Gel/veterinary , Female , Random Allocation , Troponin T/analysis
10.
J Anim Sci ; 86(7): 1649-57, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18344288

ABSTRACT

The objective of this trial was to determine whether a single bolus of 25-hydroxyvitamin D(3) (25-OH D(3)), vitamin E, or a combination of the 2 would improve the tenderness of steaks from the LM of beef heifers. Forty-eight Angus crossbred heifers were allotted randomly to 8 pens. Six heifers were in each pen, and there were 2 pens per treatment. The 4 treatments included control (no 25-OH D(3) or vitamin E); 25-OH D(3) (500 mg of 25-OH D(3) administered as a one-time oral bolus 7 d before slaughter); vitamin E (1,000 IU of vitamin E administered daily as a top-dress for 104 d before slaughter); or combination (500 mg of 25-OH D(3) administered as a one-time oral bolus 7 d before slaughter and 1,000 IU of vitamin E administered daily as a top-dress for 104 d before slaughter). Blood samples were obtained on the day that heifers were allotted to treatments, on the day 25-OH D(3) was administered, and on the day before slaughter. Plasma calcium concentration was increased when 25-OH D(3) was administered with or without vitamin E (P < 0.007). In LM, calcium concentration tended to increase (P = 0.10) when 25-OH D(3) was administered alone but not when 25-OH D(3) was administered with vitamin E. Concentrations of 25-OH D(3) and 1,25-dihydroxyvitamin D(3) in plasma were increased when 25-OH D(3) was administered with or without vitamin E (P < 0.001). Steaks from heifers treated with 25-OH D(3) or vitamin E, but not both, tended to have lower Warner-Bratzler shear force than steaks in the control group at 14 d postmortem (P = 0.08). Postmortem protein degradation as measured by Western blot of the 30-kDa degradation product of troponin-T was increased with all treatments after 3 d postmortem (P

Subject(s)
Calcifediol/administration & dosage , Cattle/metabolism , Meat/standards , Muscle, Skeletal/metabolism , Vitamin E/administration & dosage , Animals , Calcifediol/blood , Calcifediol/metabolism , Calcitriol/blood , Calcium/blood , Dietary Supplements , Electrophoresis, Polyacrylamide Gel/veterinary , Female , Muscle, Skeletal/drug effects , Random Allocation , Shear Strength , Thiobarbituric Acid Reactive Substances/analysis , Troponin T/metabolism , Vitamin E/metabolism
11.
J Dairy Sci ; 90(11): 5159-64, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17954756

ABSTRACT

A major factor predisposing the cow to periparturient hypocalcemia, or milk fever, is being fed a prepartum ration with a high dietary cation-anion difference (DCAD). The DCAD can be favorably altered to prevent milk fever by decreasing K and Na or increasing Cl and S in forages for cows in late gestation. The objective of this study was to test the hypothesis that application of Cl to alfalfa could increase Cl in forage, thereby lowering DCAD. We conducted a field experiment at 2 Iowa locations in which established plots of alfalfa were treated in April 2001 with 0, 56, 112, or 168 kg of Cl/ha using ammonium chloride, calcium chloride, or a mix of the 2 sources with equal amounts of chloride coming from each source. Plots were harvested 4 times in 2001 and once in 2002 and plant tissue analyzed for mineral composition. Applying chloride from either source once in the spring resulted in increased plant chloride content over all 4 cuttings for that year. Averaged across both locations, chloride levels were elevated from 0.52% in control plots to 0.77, 0.87, and 0.89% Cl in plots treated with 56, 112, and 168 kg of Cl/ha, respectively. Chloride application had no effect on plant potassium, sodium, calcium, magnesium, or phosphorus. These results suggest chloride application can elevate chloride content and lower DCAD values of alfalfa, and also maintain crop yield.


Subject(s)
Ammonium Chloride/pharmacology , Anions/analysis , Calcium Chloride/pharmacology , Cations/analysis , Medicago sativa/drug effects , Medicago sativa/chemistry , Medicago sativa/growth & development , Minerals/analysis
12.
Lett Appl Microbiol ; 44(6): 631-6, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17576225

ABSTRACT

AIMS: Experiments were designed to evaluate the potential of rumen-simulating conditions to reduce PrP(Sc) levels. METHODS AND RESULTS: Scrapie-positive brain material was incubated under rumen-simulating conditions. Time points were taken over a 24-h period and PrP(Sc) levels were analysed by Western blot. No loss of PrP(Sc) was observed over a 24-h time period. CONCLUSIONS: Our results indicate that a fully developed rumen fermentation does not provide significant protection against prion infection via the oral route. Developmental changes including senescence of immune system function or other developmental changes in the gastrointestinal tract are potential mechanisms by which relative bovine spongiform encephalopathy (BSE) susceptibility might vary with age. SIGNIFICANCE AND IMPACT OF THE STUDY: Epidemiology of the BSE outbreak in the United Kingdom indicates that younger animals were at higher risk of infection. The rumen undergoes pronounced developmental changes early in life, coinciding with the introduction of fibre into the diet. The timeframe of highest risk of infection overlaps the time in life prior to full rumen development. This work indicates that a fully developed rumen does not provide significant protection against prion infection via the oral route of infection. This result implicates other developmental changes that are responsible for the age-dependent susceptibility of cattle to BSE.


Subject(s)
Brain Chemistry , PrPSc Proteins/analysis , Rumen/chemistry , Rumen/microbiology , Scrapie/immunology , Animals , Blotting, Western , Cattle , Cell Extracts/chemistry , PrPSc Proteins/metabolism , Sheep, Domestic
13.
Res Vet Sci ; 83(2): 244-50, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17307209

ABSTRACT

Two trials were conducted to determine if thiram-induced tibial dyschondroplasia (TD) in chickens was linked to a vitamin D deficiency and calcium homeostasis dysregulation, and whether feeding vitamin D fortified diets may prevent it. Day-old chickens were given grower diets containing different vitamin D products throughout the experiment until necropsy on day 16. Half of the birds in each feed group received thiram at levels of 100 ppm (trial 1) or 50 ppm (trial 2) between days 7-9 to induce TD. The birds were weighed, bled, and euthanized to determine TD incidences and severity by examining the growth plates. Tibial bones were used to measure biomechanical strength and ash content. Blood concentrations of 25-hydroxyvitamin D, Ca, P, alkaline phosphatase, and creatine kinase were measured in serum that showed no differences between different groups. Thiram reduced body weight and induced TD regardless of any vitamin D treatment to the same extent as untreated birds.


Subject(s)
Calcitriol/therapeutic use , Chickens , Cholecalciferol/therapeutic use , Osteochondrodysplasias/veterinary , Poultry Diseases/chemically induced , Poultry Diseases/diet therapy , Thiram/toxicity , Animal Feed , Animal Nutritional Physiological Phenomena , Animals , Body Weight , Bone and Bones/pathology , Cholecalciferol/metabolism , Diet/veterinary , Dietary Supplements , Dose-Response Relationship, Drug , Minerals/analysis , Osteochondrodysplasias/chemically induced , Osteochondrodysplasias/diet therapy , Osteochondrodysplasias/prevention & control , Poultry Diseases/prevention & control , Vitamin D/analogs & derivatives , Vitamin D/blood
14.
Arch Biochem Biophys ; 438(2): 182-94, 2005 Jun 15.
Article in English | MEDLINE | ID: mdl-15913539

ABSTRACT

Determinants involved in the activation and repression of 1,25-dihydroxyvitamin D (1,25(OH)(2)D(3)) synthesis in renal cortex by changes in extracellular Ca were studied. Cortical kidney RNA isolated from hypocalcemic (LC) rats generated by a low Ca diet, and hypercalcemic (HC) rats generated by a normal Ca diet and two sequential 1 microg doses of 1,25(OH)(2)D(3). Among the genes up-regulated were 1alpha-OHase (4.6-fold) in the LC group and high differential gene expression of VDR (4.0-fold) and 24-OHase (10.4-fold) in the HC group. Moreover, the exposure of renal cortex to LC versus HC conditions revealed a high differential expression of a PKA-dominated pathway involving CBP interacting protein, GATA-1 and CREB transcription factors in the LC model. In the HC model, elevated renal cortex gene expression of several growth factors, peptide receptors, and intracellular signaling molecules depicts a role for CaSR activation and receptor tyrosine kinase signaling in 1,25(OH)(2)D(3)-mediated gene activation and repression of 1alpha-OHase.


Subject(s)
Calcium/deficiency , Gene Expression Profiling/methods , Hypercalcemia/metabolism , Kidney Cortex/metabolism , Vitamin D/analogs & derivatives , Vitamin D/metabolism , Animal Feed , Animal Nutritional Physiological Phenomena , Animals , Calcium/metabolism , Cytochrome P-450 Enzyme System/metabolism , Gene Expression Regulation , Hypocalcemia/metabolism , Kidney/metabolism , Kidney Tubules/metabolism , Models, Biological , Oligonucleotide Array Sequence Analysis , RNA/metabolism , Rats , Receptors, Calcitriol/metabolism , Receptors, Fibroblast Growth Factor/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction , Sodium-Phosphate Cotransporter Proteins , Steroid Hydroxylases/metabolism , Symporters/metabolism , Transcriptional Activation , Transfection , Up-Regulation , Vitamin D3 24-Hydroxylase
15.
J Dairy Sci ; 88(5): 1741-4, 2005 May.
Article in English | MEDLINE | ID: mdl-15829666

ABSTRACT

The objectives of this study were to measure the changes in protein expression of the mammary Ca2+-ATPases during the periparturient period and to determine whether Ca2+-ATPase protein expression in the mammary gland is related to milk fever (MF) development. Abundance of Ca2+-ATPase in mammary tissue and milk fat globule membranes was determined by Western blotting. The secretory pathway Ca2+-ATPase was elevated prepartum in mammary tissue from cows that developed MF compared with non-MF cows.


Subject(s)
Calcium-Transporting ATPases/analysis , Cattle Diseases/enzymology , Mammary Glands, Animal/enzymology , Parturient Paresis/enzymology , Parturition , Animals , Blotting, Western , Cattle , Female , Glycolipids/analysis , Glycoproteins/analysis , Lipid Droplets , Pregnancy
16.
J Dairy Sci ; 88(4): 1364-9, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15778304

ABSTRACT

Sixteen crossbred (British x Continental; average un-shrunk body weight = 507.9 kg; SD = 45.6 kg) beef heifers fed a steam-flaked corn-based finishing diet with melengestrol acetate (0.4 mg/heifer daily) included to suppress estrus were used in a completely random design to evaluate the efficacy of buccal administration of 0, 10, 100, or 1000 mg of 25-hydroxyvitamin D3, (25-OH D3). Serum Ca, P, Mg, 25-OH D3, 1,25-dihydroxyvitamin D [1,25-(OH)2 D3], albumin, and protein were measured 24 h before dosing (-24 h), at dosing (0 h), and 6 and 24 h after dosing, after which the cattle were slaughtered at a commercial facility. Samples of kidneys, liver, longissimus lumborum, and triceps brachii were collected and evaluated for concentrations of 1,25-(OH)2 D3. With -24 and 0 h as baseline covariates, a significant time x treatment interaction was observed for serum 25-OH D3 and Ca concentrations, but not for serum 1,25-(OH)2 D3. Supplemental 25-OH D3 doses of 100 and 1000 mg significantly increased serum 25-OH D3 at 24 h after dosing, 1,25-(OH)2 D3 at 6 and 24 h after dosing, and serum Ca at 24 h after dosing. Similarly, buccal dosing of 1000 mg of supplemental 25-OH D3 significantly increased (approximately 2- to 3-fold) concentrations of 1,25-(OH)2 D3 in the kidney, liver, and longissimus lumborum relative to the other 3 treatments but not in triceps brachii. Serum albumin, protein, P, and Mg were not affected by treatment. Based on these results, buccal administration of 100 and 1000 mg 25-OH D3 increased vitamin D3 metabolites in serum and tissues, and it should be an effective method of delivering the vitamin.


Subject(s)
Cattle/metabolism , Vitamin D/analogs & derivatives , Vitamin D/administration & dosage , Vitamin D/metabolism , Administration, Buccal , Animal Feed , Animals , Cattle/blood , Cholecalciferol/administration & dosage , Cholecalciferol/metabolism , Cholecalciferol/pharmacokinetics , Dose-Response Relationship, Drug , Female , Kidney/metabolism , Liver/metabolism , Meat/standards , Muscle, Skeletal/metabolism , Random Allocation , Vitamin D/blood , Vitamin D/pharmacokinetics
17.
J Anim Sci ; 82(9): 2742-9, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15452920

ABSTRACT

The effect of supplementing diets with various levels of vitamin D3 to provide 0, 0.5, 1, and 5 million IU/(steer x d) for 8 d before slaughter on the mineral content and localization of Ca in LM and muscle fragments was studied during the postmortem aging process. Twelve feedlot steers of three biological types were given access to the four levels of vitamin D for 8 d before slaughter. Differential centrifugation techniques were used to determine the concentrations of minerals relative to protein in different muscle fragments on d 3 and 21 postmortem. Electron microscopy visualization of bound Ca indicated that vitamin D3 mobilized Ca from the sarcoplasmic reticulum and transverse tubule system into the myofibrils. Bound Ca was concentrated near the Z-line at the A-band/I-band juncture within the sarcomere. Supplementing steers with 1 and 5 million IU/(steer x d) of vitamin D3 increased (P < 0.05) Ca, P, and Mg concentrations per unit of protein in the cytosol. Soluble cytosolic Ca concentrations were greater (P < 0.05) on d 21 than on d 3 postmortem only when steers were supplemented with 5 million IU/d. Concentrations of Ca, P, and Mg in isolated tissues were increased (P < 0.05) in nuclei and myofibrilar proteins by supplementing steers with 1 and 5 million IU/ (steer x d) of vitamin D3. All supplemental vitamin D3 treatments also increased (P < 0.001) Mg concentrations in the cytosol, regardless of aging treatment, and increased Mg concentrations (P < 0.04) within the mitochondria at d 3 postmortem. Thus, supplementation of feedlot steers with vitamin D3 at levels of 0.5 to 5 million IU/(steer x d) increased Ca concentrations within respiring muscle, resulting in increased bound tissue Ca concentrations. When the respiring muscle was converted to meat, the increased bound tissue Ca resulting from vitamin D3 treatment released Ca concentrations into the cytosol during aging (P < 0.05). Results of this study indicate that vitamin D3 supplementation increased total cytosolic Ca, P, and Mg concentrations in meat.


Subject(s)
Calcium/metabolism , Cattle/metabolism , Cholecalciferol/pharmacology , Magnesium/metabolism , Muscle, Skeletal/metabolism , Phosphorus/metabolism , Animals , Cholecalciferol/administration & dosage , Cytosol/chemistry , Dose-Response Relationship, Drug , Male , Meat/analysis , Meat/standards , Microscopy, Electron/veterinary , Muscle, Skeletal/drug effects , Muscle, Skeletal/ultrastructure , Postmortem Changes
18.
J Anim Sci ; 82(7): 2043-9, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15309951

ABSTRACT

Feedlot steers (n = 36) from three biological types (Bos indicus, Bos taurus-Continental, and Bos taurus-English) were used to determine the Ca, P, and vitamin D3 status of feedlot cattle. The USDA yield and quality grade traits were measured at slaughter, and the concentrations of vitamin D3 (VITD) and the metabolites 25-hydroxyvitamin D3 (25-OH D) and 1,25-dihydroxyvitamin D3 (1,25-(OH)2 D) were determined in LM, liver, kidney, and plasma. Plasma and muscle Ca and P concentrations also were determined. Biological type of cattle affected a number of carcass traits. Carcasses from Bos taurus-English cattle had more marbling, resulting in higher quality grades (P < 0.05). Carcasses from Bos taurus-Continental cattle had lower calculated yield grades (P < 0.05) than did carcasses from cattle in the other biological types. In general, differences in carcass traits resulting from biological type were consistent with other reports. Plasma and LM Ca and P concentrations were not affected (P = 0.06) by biological type of cattle, indicating that Ca and P homeostasis is a conserved trait across the different types of cattle. Plasma VITD and 25-OH D concentrations were not affected (P = 0.41) by biological type, whereas plasma 1,25-(OH)2 D concentration was lower (P < 0.05) in Bos taurus-English cattle than in Bos taurus-Continental and Bos indicus cattle. Liver VITD and 25-OH D were not affected by biological type (P = 0.76), but liver 1,25-(OH)2 D concentration was greater (P < 0.05) in Bos indicus cattle than in Bos taurus-Continental cattle. Kidney vitamin D metabolite concentrations were not affected by biological type of cattle (P = 0.21). Muscle VITD concentration was greater (P < 0.05) in Bos taurus-English cattle than in the other two biological types, and muscle 25-OH D concentrations were greater (P < 0.05) in Bos taurus-English cattle than in Bos indicus cattle. Muscle 1,25-(OH)2 D concentration was less (P < 0.05) in the Bos taurus-Continental cattle than in the other two biological types. Cooking eliminated vitamin D metabolite differences among the biological types. Our results suggest that Bos indicus cattle had greater 1,25-(OH)2 D (the biologically active form) in tissues, and greater 1,25-(OH)2 D plasma concentrations than Bos taurus cattle. Thus, the need for VITD supplementation and optimal levels of Ca and P in feedlot diets might differ between Bos indicus and Bos taurus cattle.


Subject(s)
Breeding , Calcium/analysis , Cattle/metabolism , Meat/standards , Phosphorus/analysis , Vitamin D/analysis , Animal Feed , Animal Nutritional Physiological Phenomena , Animals , Calcium/metabolism , Cattle/classification , Cholecalciferol/analysis , Cholecalciferol/metabolism , Kidney/chemistry , Kidney/metabolism , Liver/chemistry , Liver/metabolism , Male , Meat/analysis , Meat/classification , Muscle, Skeletal/chemistry , Muscle, Skeletal/metabolism , Nutritional Requirements , Nutritional Status , Phosphorus/metabolism , United States , United States Department of Agriculture , Vitamin D/analogs & derivatives , Vitamin D/metabolism
19.
J Anim Sci ; 82(7): 2050-8, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15309952

ABSTRACT

Because of the Ca dependency of the calpains, oral supplementation of vitamin D3 (VITD) can increase the Ca content of muscle to activate the calpains and improve tenderness. Feedlot steers (n = 142) were arranged in a 4 x 3 factorial arrangement consisting of four levels of VITD (0, 0.5, 1, and 5 million IU/[steer x d]) for eight consecutive days antemortem using three biological types (Bos indicus, Bos taurus-Continental, and Bos taurus-English). Feedlot performance factors of ADG, DMI, and G:F were measured, and carcass quality, yield, and color data were collected. Plasma Ca and P concentrations were measured during d 4 to 6 of supplementation and at exsanguination, and carcass pH and temperature were measured in the LM at 3 and 24 h postmortem. Vitamin D3 treatment at 5 million IU/(steer x d) decreased ADG (P < 0.05) over the supplementation and feed intake for the last 2 d of feeding compared with untreated control steers. Likewise, G:F was decreased (P = 0.03) in steers supplemented with 5 million IU/d compared with controls. Overall, there was a linear decrease (P < 0.01) in ADG and G:F as a result of VITD supplementation. Plasma concentrations of Ca and P were increased (P < 0.05) by VITD concentrations of 1 and 5 million IU/(steer x d). All VITD treatments increased (P < 0.05) LM temperature at 3 h postmortem and pH at 24 h postmortem. Vitamin D3 treatments did not affect (P = 0.07) any other carcass measurements, including USDA yield and quality grade; thus, any improvements in meat tenderness as a result of VITD supplementation can be made without adversely affecting economically important carcass factors. Biological type of cattle did not interact with VITD treatment for any carcass or feedlot performance trait. Although feeding 5 million IU/(steer x d) of VITD for eight consecutive days had negative effects on performance, supplementing VITD at 0.5 million IU/ (steer x d) did not significantly alter feedlot performance.


Subject(s)
Breeding , Cattle/growth & development , Cholecalciferol/administration & dosage , Meat/standards , Animal Feed , Animals , Body Constitution , Calcium/blood , Calcium/metabolism , Calpain/drug effects , Calpain/metabolism , Cattle/genetics , Cattle/metabolism , Cholecalciferol/adverse effects , Cholecalciferol/metabolism , Dietary Supplements , Dose-Response Relationship, Drug , Energy Intake/drug effects , Hydrogen-Ion Concentration , Male , Meat/analysis , Meat/classification , Phosphorus/blood , Phosphorus/metabolism , Pigmentation , Postmortem Changes , Random Allocation , Time Factors , United States , United States Department of Agriculture , Weight Gain/drug effects
20.
J Anim Sci ; 82(7): 2092-104, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15309957

ABSTRACT

Vitamin D3 was orally supplemented to determine the supplemental dose that improved beef tenderness in different cattle breed types. Feedlot steers (n = 142) were arranged in a 4 x 3 factorial arrangement consisting of four levels of supplemental vitamin D3 (0, 0.5, 1, and 5 million IU/steer daily) administered for eight consecutive days antemortem using three biological types (Bos indicus, Bos Taurus-Continental, and Bos Taurus-English). Warner-Bratzler shear force (WBSF) was measured at 3, 7, 10, 14, and 21 d postmortem, and trained sensory analysis was conducted at 7 d postmortem on LM, semimembranosus, gluteus medius, and supraspinatus steaks. Concentrations of vitamin D3 and the metabolites 25-hydroxyvitamin D3, and 1,25-dihydroxyvitamin D3 were determined in the LM, liver, kidney, and plasma. Biological type of cattle did not interact (P > 0.10) with vitamin D3 supplementation for sensory or tenderness traits, suggesting that feeding vitamin D3 for 8 d before slaughter affected the different biological types of cattle similarly. Supplementing steers with 0.5, 1, or 5 million IU/(steer(d) decreased (P < 0.05) LM WBSF at 7, 10, 14, and 21 d postmortem compared with controls, and vitamin D3 treatments of 0.5, 1, and 5 million IU decreased (P < 0.05) semimembranosus WBSF at 3, 7, and 14 d postmortem. In general, vitamin D3-induced improvements in WBSF were most consistent and intense in LM steaks. Sensory panel tenderness was improved (P < 0.05) by all vitamin D3 treatments in LM steaks. Sensory traits ofjuiciness, flavor, connective tissue, and off-flavor were not (P > 0.05) affected by vitamin D3 treatments. All vitamin D3 treatments decreased micro-calpain activity and increased muscle Ca concentrations (P < 0.05). Vitamin D3 concentrations were increased (P < 0.05) by supplementation in all tissues tested (liver, kidney, LM, and plasma); however, cooking steaks to 71 degrees C decreased (P < 0.05) treatment residue effects. The vitamin D metabolite 1,25-dihydroxyvitamin D3 was increased (P < 0.05) only in plasma samples as a result of the vitamin D3 treatments. These results indicate that supplementation with vitamin D3 at 0.5 million IU/steer daily for eight consecutive days before slaughter improved tenderness in steaks from different subprimal cuts by affecting muscle Ca concentrations, micro-calpain activities, and muscle proteolysis, with only a small effect on tissue residues of vitamin D3.


Subject(s)
Cattle/metabolism , Cholecalciferol/administration & dosage , Meat/analysis , Meat/standards , Muscle, Skeletal/drug effects , Administration, Oral , Animals , Calcifediol/analysis , Calcifediol/metabolism , Calcitriol/analysis , Calcitriol/metabolism , Cattle/genetics , Dietary Supplements , Dose-Response Relationship, Drug , Drug Residues/analysis , Male , Muscle, Skeletal/metabolism , Postmortem Changes , Random Allocation , Taste
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