Reducing gut microbiome-driven adipose tissue inflammation alleviates metabolic syndrome.

BACKGROUND: The gut microbiota contributes to macrophage-mediated inflammation in adipose tissue with consumption of an obesogenic diet, thus driving the development of metabolic syndrome. There is a need to identify and develop interventions that abrogate this condition. The hops-derived prenylated flavonoid xanthohumol (XN) and its semi-synthetic derivative tetrahydroxanthohumol (TXN) attenuate high-fat diet-induced obesity, hepatosteatosis, and metabolic syndrome in C57Bl/6J mice. This coincides with a decrease in pro-inflammatory gene expression in the gut and adipose tissue, together with alterations in the gut microbiota and bile acid composition. RESULTS: In this study, we integrated and interrogated multi-omics data from different organs with fecal 16S rRNA sequences and systemic metabolic phenotypic data using a Transkingdom Network Analysis. By incorporating cell type information from single-cell RNA-seq data, we discovered TXN attenuates macrophage inflammatory processes in adipose tissue. TXN treatment also reduced levels of inflammation-inducing microbes, such as Oscillibacter valericigenes, that lead to adverse metabolic phenotypes. Furthermore, in vitro validation in macrophage cell lines and in vivo mouse supplementation showed addition of O. valericigenes supernatant induced the expression of metabolic macrophage signature genes that are downregulated by TXN in vivo. CONCLUSIONS: Our findings establish an important mechanism by which TXN mitigates adverse phenotypic outcomes of diet-induced obesity and metabolic syndrome. TXN primarily reduces the abundance of pro-inflammatory gut microbes that can otherwise promote macrophage-associated inflammation in white adipose tissue. Video Abstract.

Metabotypes with elevated protein and lipid catabolism and inflammation precede clinical mastitis in prepartal transition dairy cows.

Clinical mastitis (CM), the most prevalent and costly disease in dairy cows, is diagnosed most commonly shortly after calving. Current indicators do not satisfactorily predict CM. This study aimed to develop a robust and comprehensive mass spectrometry-based metabolomic and lipidomic workflow using untargeted ultra-performance liquid chromatography high-resolution mass spectrometry for predictive biomarker detection. Using a nested case-control design, we measured weekly during the prepartal transition period differences in serum metabolites, lipids, inflammation markers, and minerals between clinically healthy Holstein dairy cows diagnosed with mastitis postcalving (CMP; n = 8; CM diagnosis d 1 = 3 cows, d 2 = 2 cows, d 4 = 1 cow; d 25 = 1 cow, and d 43 = 1 cow that had subclinical mastitis since d 3) or not (control; n = 9). The largest fold differences between CMP and control cows during the prepartal transition period were observed for 3'-sialyllactose in serum. Seven metabolites (N-methylethanolamine phosphate, choline, phosphorylcholine, free carnitine, trimethyl lysine, tyrosine, and proline) and 3 metabolite groups (carnitines, AA metabolites, and water-soluble phospholipid metabolites) could correctly classify cows for their future CM status at both 21 and 14 d before calving. Biochemical analysis using lipid and metabolite-specific commercial diagnostic kits supported our mass spectrometry-based omics results and additionally showed elevated inflammatory markers (serum amyloid A and visfatin) in CMP cows. In conclusion, metabolic phenotypes (i.e., metabotype) with elevated protein and lipid metabolism and inflammation may precede CM in prepartal transition dairy cows. The discovered serum metabolites and lipids may assist in predictive diagnostics, prevention strategies, and early treatment intervention against CM, and thereby improve cow health and welfare.

Effects of feeding pregnant beef cows selenium-enriched alfalfa hay on selenium status and antibody titers in their newborn calves.

In newborn dairy calves, it has been demonstrated that supranutritional maternal and colostral Se supplementation using Se yeast or sodium selenite, respectively, improves passive transfer of IgG. In beef cattle, agronomic biofortification with Se is a more practical alternative for Se supplementation, whereby the Se concentration of hay is increased through the use of Se-containing fertilizer amendments. It has been previously demonstrated that agronomic Se biofortification is an effective strategy to improve immunity and performance in Se-replete weaned beef calves. The objective of this experiment was to determine the effects of feeding beef cows Se-enriched alfalfa () hay during the last 8 to 12 wk of gestation on passive transfer of antibodies to calves. At 10 wk ± 16 d before calving, 45 cows were assigned to 1 of 3 treatment groups with 3 pens (5 cows/pen) per treatment: Control cows were fed non-Se-fortified alfalfa hay plus a mineral supplement containing 120 mg/kg Se from sodium selenite, Med-Se cows were fed alfalfa hay fertilized with 45.0 g Se/ha as sodium selenate, and High-Se cows were fed alfalfa hay fertilized with 89.9 g Se/ha as sodium selenate; both the Med-Se and the High-Se groups received mineral supplement without added Se. Colostrum and whole blood (WB) were collected from cows at calving, and WB was collected from calves within 2 h of calving and at 12, 24, 36, and 48 h of age. Concentrations of IgG1 and J-5 antibody in cow colostrum and calf serum were quantified using ELISA procedures. Selenium concentrations linearly increased in WB ( < 0.001) and colostrum ( < 0.001) of cows and in WB of newborn calves ( < 0.001) with increasing Se concentration in alfalfa hay. Colostrum concentrations of IgG1 ( = 0.03) were increased in cows fed Se-biofortified alfalfa hay, but J-5 antibody ( = 0.43) concentrations were not. Calf serum IgG1 ( = 0.43) and J-5 antibody ( = 0.44) concentrations during the first 48 h of age were not affected by prior Se treatment of cows. These data suggest that feeding Se-biofortified alfalfa hay promotes the accumulation of Se and antibodies in colostrum but does not affect short-term serum antibody concentrations in calves.

Nutritional Interventions that Slow the Age-Associated Decline in Renal Function in a Canine Geriatric Model for Elderly Humans.

OBJECTIVE: To determine the effects of feeding traditional and renal protective foods (RPF) supplemented with functional food bioactives on glomerular filtration rate (GFR), lean body percent (LB%), and selected circulating biomarker and metabolite concentrations in a geriatric dog model. DESIGN: Randomized block design and cross-sectional study. SETTING: Hill's Pet Nutrition, Inc. dog colony. PARTICIPANTS: Eighty-one geriatric dogs (mean age, 10.4; range, 7.9-14.2 years) and 30 mature-adult dogs (mean age, 5.0; range, 3.3-6.9 years). INTERVENTION: Geriatric dogs were fed one of three foods (n = 27 per group) for 6 months: a traditional RPF (control) that was energy dense and mildly protein-restricted, or control food supplemented with increasing amounts of functional food bioactives: fish oil, lipoic acid, fruits and vegetables, and higher quality protein sources [functional foods one (FF1) and two (FF2)]. Geriatric dogs were compared before and after the feeding trial with mature adult dogs. MEASUREMENTS: Renal function was assessed by GFR, LB% was determined by dual energy x-ray absorptiometry, and circulating biomarkers and metabolites were measured in blood. RESULTS: Before the feeding trial, GFR (+28.2%), LB% (+18.6%), and serum total protein (+10.0%) were higher in mature versus healthy geriatric dogs (all P<0.001). Geriatric dogs consuming all three foods increased (P<0.001) GFR over time; group averages ranged from 13.0-16.9%. Dogs fed the highest supplemented level of bioactives (FF2) had lower (P<0.001) symmetric dimethylarginine (SDMA) concentrations (-14.3%). Feeding functional foods did not alter body weight, but increased (P<0.001) serum protein concentration (+6.7%). CONCLUSION: Supplementation with functional food bioactives can temporarily reverse the age-associated decline in renal function and serum total protein.

Rumen Microorganisms Decrease Bioavailability of Inorganic Selenium Supplements.

Despite the availability of selenium (Se)-enriched trace mineral supplements, we have observed low Se status in cattle and sheep offered traditional inorganic Se supplements. Reasons for this may include inadequate intake or low bioavailability of inorganic Se sources. The objective of this study was to determine whether rumen microorganisms (RMO) alter the bioavailability of Se sources commonly used in Se supplements. Rumen microorganisms were isolated from ewes (n = 4) and incubated ex vivo with no Se (control), with inorganic Na selenite or Na selenate, or with organic selenomethionine (SeMet). Total Se incorporated into RMO and the amount of elemental Se formed were determined under equivalent conditions. Incorporation of Se from Na selenite, Na selenate, or SeMet into RMO was measured as fold change compared with control (no added Se). Incorporation of Se into microbial mass was greater for SeMet (13.2-fold greater than no-Se control) compared with inorganic Se supplements (P = 0.02); no differences were observed between inorganic Na selenate (3.3-fold greater than no-Se control) and Na selenite (3.5-fold greater than no-Se control; P = 0.97). Formation of non-bioavailable, elemental Se was less for RMO incubated with SeMet compared with inorganic Se sources (P = 0.01); no differences were observed between Na selenate and Na selenite (P = 0.09). The clinical importance of these results is that the oral bioavailability of organic SeMet should be greater compared with inorganic Se sources because of greater RMO incorporation of Se and decreased formation of elemental Se by RMO.

Use of computed tomography to compare two femoral head and neck excision ostectomy techniques as performed by two novice veterinarians.

OBJECTIVES: To compare the results of femoral head and neck excision (FHNE) ostectomy performed by two novice veterinarians using an osteotome and mallet or microsagittal saw. METHODS: In this ex vivo cadaveric study, hindlimbs of eight canine cadavers were randomized to FHNE with osteotome or micro sagittal saw as performed by two recently graduated veterinarians. The hindimbs were imaged by computed tomography (CT) before and after the osteotomy. Post FHNE CT images were evaluated by a board certified radiologist blinded to the ostectomy technique for assessment of the number of bone fragments, fissures, smoothness of osteotomy margination, and volume of residual femoral neck. RESULTS: Femoral head and neck excision performed with the osteotome produced more peri-ostectomy bone fragments, cortical fissures, irregular margins, and residual femoral neck volume, compared with osteotomy using a saw. CLINICAL RELEVANCE: Compared to FHNE performed with a sagittal saw, osteotome FHNE resulted in a greater bone trauma and residual neck bone volume, which would require post-ostectomy modification in a clinical setting.

Evaluation of the diagnostic accuracy of four-view radiography and conventional computed tomography analysing sacral and pelvic fractures in dogs.

OBJECTIVE: The purpose of our study was (1) to determine whether four-view radiography of the pelvis is as reliable and accurate as computed tomography (CT) in diagnosing sacral and pelvic fractures, in addition to coxofemoral and sacroiliac joint subluxation or luxation, and (2) to evaluate the effect of the amount of training in reading diagnostic imaging studies on the accuracy of diagnosing sacral and pelvic fractures in dogs. METHODS: Sacral and pelvic fractures were created in 11 canine cadavers using a lateral impactor. In all cadavers, frog-legged ventro-dorsal, lateral, right and left ventro-45°-medial to dorsolateral oblique frog leg ("rollover 45-degree view") radiographs and a CT of the pelvis were obtained. Two radiologists, two surgeons and two veterinary students classified fractures using a confidence scale and noted the duration of evaluation for each imaging modality and case. The imaging results were compared to gross dissection. RESULTS: All evaluators required significantly more time to analyse CT images compared to radiographic images. Sacral and pelvic fractures, specifically those of the sacral body, ischiatic table, and the pubic bone, were more accurately diagnosed using CT compared to radiography. Fractures of the acetabulum and iliac body were diagnosed with similar accuracy (at least 86%) using either modality. CLINICAL SIGNIFICANCE: Computed tomography is a better method for detecting canine sacral and some pelvic fractures compared to radiography. Computed tomography provided an accuracy of close to 100% in persons trained in evaluating CT images.

Effect of transport on blood selenium and glutathione status in feeder lambs.

Stress from transport may be linked to increased generation of reactive oxygen species, the removal of which requires reduced glutathione and selenium. The aim of this experiment was to examine the effect of transport on glutathione and Se status of feeder lambs. Recently weaned lambs (n = 40) were blocked by gender and BW on d 0 of the experiment and randomly assigned to 2 treatment groups: group 1, no transport and full access to feed and water (control), and group 2, 8-h road transport followed by another 16 h of feed deprivation (transport). After 24 h, both treatment groups were treated the same. All lambs were weighed, and blood samples were collected at 0, 8, 24, and 72 h and analyzed for whole-blood (WB) and serum Se concentrations, serum NEFA concentrations, and erythrocyte concentrations of glutathione. Transport of feeder lambs for 8 h followed by another 16 h of feed deprivation transiently (significant at 24 h but no longer different at 72 h) decreased BW and erythrocyte glutathione concentrations and increased serum NEFA and blood Se concentrations compared with control lambs. Our results suggest that 8 h of transport followed by another 16 h of feed deprivation results in fatty acid and Se mobilization from tissue stores with a coincident decrease in erythrocyte glutathione concentrations.

Potential risk indicators of retained placenta and other diseases in multiparous cows.

Retained placenta (RP), defined as fetal membranes not being expelled within 24 h after calving, is a costly disease in multiparous dairy cows that has been linked to immune suppression, infections, elevated lipid mobilization, and depleted status of antioxidants including α-tocopherol, and that increases the risk of other diseases (OD) in early lactation. Early detection of cows at increased risk of developing RP, OD, or both in early lactation could improve treatment success and result in improved milk production and reproductive performance. To identify risk indicators of RP, OD, or both, we used a nested case-control design and compared multiparous dairy cows that developed RP (n=32) with cows that remained healthy (H; n=32) or cows that developed OD (n=32) in early lactation. We compared peripartal body condition score (BCS) as well as serum concentrations of α-tocopherol, metabolites [ß-hydroxybutyrate (BHBA), cholesterol, glucose, nonesterified fatty acids (NEFA), and urea N], haptoglobin, and macrominerals (i.e., calcium, magnesium, and phosphorus) on d -21, -14, -7, -3, -1, 0, 1, 3, 7, 14, 21, 28, 35, 42, and 49 postpartum. In addition, average serum concentrations were calculated for each cow for the last 3 wk prepartum, for 3 and 2 wk prepartum combined, for the last week prepartum, and for the morning after calving and compared between groups. The RP cows had lower BCS than the H or OD cows until 2 wk postpartum. During the prepartal periods, RP and OD cows had lower α-tocopherol concentrations (corrected or not for cholesterol concentration) and higher NEFA and BHBA concentrations than H cows. Thus, lower prepartal BCS could be an early predictor for RP risk, and lower α-tocopherol concentrations and higher NEFA and BHBA concentrations could be early predictors for disease.

Effects of feeding various dosages of Saccharomyces cerevisiae fermentation product in transition dairy cows.

Feeding 56 versus 0 g/d of Saccharomyces cerevisiae fermentation product (SCFP; Diamond V Original XP; Diamond V, Cedar Rapids, IA) can increase feed intake and milk production in transition dairy cows. To evaluate the effects of various dosages of SCFP, Holstein cows were given individually a supplement containing 0 (n=14), 56 (n=15), or 112 g (n=13) of SCFP daily during morning lockup as a topdressing to their total mixed ration. The supplement consisted of 0, 56, or 112 g of SCFP mixed with 84 g of molasses and 168, 112, or 56 g of corn meal, respectively. Supplement feeding began 28 d before predicted calving date (no less than 14 d) and ended 28 d postpartum, and supplement intake was evaluated daily. Blood samples were collected at d -21, -14, -7, -3, -1, 0, 1, 3, 7, 14, 21, and 28 to measure serum concentrations of macrominerals, metabolites, acute-phase proteins, immunoglobulin, and hormones. Milk weights were measured and milk samples were collected 2 times/wk on nonconsecutive days and analyzed for milk fat, protein, lactose, and somatic cell count (SCC). During the first day after calving, feeding SCFP versus no SCFP decreased serum cortisol concentrations and at least tended to increase supplement intake and serum concentrations of calcium, glucose, urea N, and serum amyloid A. During the first 4 wk postpartum, feeding SCFP versus no SCFP decreased milk SCC and increased milk production and serum phosphorus concentrations. Feeding 112 versus 56 g of SCFP/d did not show additional effects. Feeding SCFP may have a dosage-independent beneficial effect in supporting the physiologic adaptations after parturition, resulting in higher milk production and lower milk SCC.

Growth factor treated tensioned synoviocyte neotissues: towards meniscal bioscaffold tissue engineering.

Meniscal injury is a common cause of osteoarthritis, pain, and disability in dogs and humans, but tissue-engineered bioscaffolds could be a treatment option for meniscal deficiency. The objective of this study was to compare meniscus-like matrix histology, composition, and biomechanical properties of autologous tensioned synoviocyte neotissues (TSN) treated with fetal bovine serum (TSNfbs) or three chondrogenic growth factors (TSNgf). Fourth passage canine synoviocytes from 10 dogs were grown in hyperconfluent monolayer culture, formed into TSN, and then cultured for 3 weeks with 17.7% FBS or three human recombinant TSNgf (bFGF, TGF-ß1, and IGF-1). Cell viability was determined with laser microscopy. Histological architecture and the composition of fibrocartilage matrix were evaluated in TSN by staining tissues for glycosaminoglycan (GAG), α-smooth muscle actin, and collagen 1 and 2; quantifying the content of GAG, DNA, and hydroxyproline; and measuring the gene expression of collagens type 1α and 2α, the GAG aggrecan, and transcription factor Sry-type Homeobox Protein-9 (SOX9). Biomechanical properties were determined by materials testing force-deformation curves. The TSN contained components and histological features of mensical fibrocartilage extracellular matrix. Growth factor-treated TSN had higher DNA content but lower cell viability than TSNfbs. TSNgf had greater fibrocartilage-like matrix content (collagen 2 and GAG content with increased collagen 2α and SOX9 gene expression). Additionally, TSNgf collagen was more organized histologically and so had greater tensile biomechanical properties. The results indicate the potential of TSN when cultured with growth factors as implantable bioscaffolds for the treatment of canine meniscal deficiency.

Depleted serum vitamin E concentrations precede left displaced abomasum in early-lactation dairy cows.

Cows with left displaced abomasum (LDA), a costly disease occurring primarily in multiparous dairy cows during early lactation, have been reported to have 40% lower circulating concentrations of vitamin E. It is unknown, however, whether the lower circulating α-tocopherol concentrations precede LDA or remain after LDA. Using a nested case-control design, blood samples taken at d -21, -14, -7, -3, -1, 0, 1, 3, 7, 14, 21, 28, 35, 42, and 49 postpartum from 7 multiparous Holstein cows diagnosed with LDA between d 6 and 32 postpartum and 10 healthy Holstein cows from the same herd were analyzed for serum concentrations of α-tocopherol and indicators of energy and nutrient status and inflammation. In addition to indicators of negative energy balance and inflammation, lower serum α-tocopherol concentrations preceded LDA and persisted after LDA correction. At the last blood sampling before LDA diagnosis, cows had serum α-tocopherol concentrations 45% lower (5.0 ± 0.9 vs. 9.1 ± 0.9 µM) and α-tocopherol to cholesterol molar ratios 39% lower (1.90 ± 0.19 vs. 3.09 ± 0.26) than those of healthy cows. Serum α-tocopherol concentrations remained lower (<10 vs. ~15 µM) up to d 49 postpartum in cows that had LDA. These findings indicate that lower serum α-tocopherol concentrations are a potential early indicator for the development of LDA in multiparous cows.

Organic and inorganic selenium: IV. passive transfer of immunoglobulin from ewe to lamb.

Newborn lambs depend on their dams for passive transfer of immunoglobulins, primarily IgG, for protection from harmful pathogens until their own immunological defenses have developed. Previous studies have suggested that supplementation with Se results in a modest increase in IgG concentration in serum of newborn calves and lambs. To evaluate the effect of the Se source and supplementation rate in ewes during pregnancy on passive transfer of IgG to their lambs, 210 Polypay, Suffolk, or Suffolk × Polypay cross ewes were divided into 7 treatment groups (n = 30 each) and drenched weekly with no Se, at the maximum FDA-allowed concentration with inorganic Na-selenite or organic Se-yeast (4.9 mg Se/wk), or with inorganic Na-selenite and organic Se-yeast at supranutritional concentrations (14.7 and 24.5 mg Se/wk). Ewe serum IgG concentrations were measured within 30 d of parturition, ewe colostrum and lamb serum IgG concentrations were measured at parturition before suckling, and lamb serum IgG concentrations were measured again at 48 h postnatal. Ewes receiving 24.5 mg Se/wk tended to have or had, independent of Se source, greater colostral IgG concentrations than ewes receiving 4.9 mg Se/wk overall (81.3 vs. 66.2 mg/mL; P = 0.08) and for Polypay ewes only (90.1 vs. 60.7 mg/mL; P = 0.03). Polypay ewes receiving Se-yeast at 24.5 mg Se/wk transferred a greater calculated total IgG amount to their lambs than Polypay ewes receiving Se-yeast at 4.9 mg Se/wk (15.5 vs. 11.6 g; P = 0.02), whereas the converse was true (interaction between Se source and dose concentration; P = 0.03) for Polypay ewes receiving inorganic Na-selenite at 24.5 mg Se/wk vs. Na-selenite at 4.9 mg/wk (11.6 vs. 15.7 g; P = 0.08). Our results suggest that supranutritional Se supplementation of Polypay ewes during pregnancy increases colostral IgG concentrations but that the optimal supplementation rate for IgG transfer from ewe to lamb may differ for Na-selenite and Se-yeast.

Flavonoid intake and risk of pancreatic cancer in the National Institutes of Health-AARP Diet and Health Study Cohort.

BACKGROUND: Limited epidemiological studies show inverse associations between dietary flavonoid intake and pancreatic cancer risk, but results are inconsistent and are based on few cases. We examined the association between intake of flavonoids and pancreatic cancer risk in the large, prospective National Institutes of Health-AARP Diet and Health Study Cohort. METHODS: During follow-up through 2006 (median follow-up 10.6 years), 2379 pancreatic cancer cases were identified. We used Cox proportional hazards modelling to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: We found no association between total flavonoid intake (Q5 vs Q1 HR=1.09, 95% CI: 0.96-1.24) or any flavonoid subtypes and pancreatic cancer risk. Significant interactions were not observed by age, sex, smoking status, BMI or diabetes. CONCLUSION: Our results do not support the hypothesis that flavonoids have a protective role in pancreatic cancer carcinogenesis.

Effect of flaxseed supplementation rate and processing on the production, fatty acid profile, and texture of milk, butter, and cheese.

Health and nutrition professionals advise consumers to limit consumption of saturated fatty acids and increase the consumption of foods rich in n-3 fatty acids. Researchers have previously reported that feeding extruded flaxseed, which is high in C18:3n-3, improves the fatty acid profile of milk and dairy products to less saturated fatty acids and to more C18:3n-3. Fat concentrations in milk and butter decreased when cows were fed higher concentrations of extruded flaxseed. The objective of this study was to determine the optimal rate of flaxseed supplementation for improving the fatty acid profile without decreasing production characteristics of milk and dairy products. By using a double 5 × 5 Latin square design, 10 mid- to late-lactation Holstein cows were fed extruded (0, 0.91, 1.81, and 2.72 kg/d) and ground (1.81 kg/d) flaxseed as a top dressing for 2-wk periods each. At the end of each 2-wk treatment period, milk and serum samples were taken. Milk was subsequently manufactured into butter and fresh Mozzarella cheese. Increasing supplementation rates of extruded flaxseed improved the fatty acid profile of milk, butter, and cheese gradually to less saturated and atherogenic fatty acids and to more C18:3n-3 by increasing concentrations of C18:3n-3 in serum. The less saturated fatty acid profile was associated with decreased hardness and adhesiveness of refrigerated butter, which likely cause improved spreadability. Supplementation rates of extruded flaxseed did not affect dry matter intake of the total mixed ration, milk composition, and production of milk, butter, or cheese. Flaxseed processing did not affect production, fatty acid profile of milk, or texture of butter and cheese. Feeding up to 2.72 kg/d of extruded flaxseed to mid- to late-lactation Holstein cows may improve nutritional and functional properties of milk fat without compromising production parameters.

Organic and inorganic selenium: III. Ewe and progeny performance.

Selenium is an essential micronutrient in sheep, and deficiency can limit lamb growth and survival. To evaluate how different chemical forms of Se administered to mature ewes at comparative dosages affect ewe and progeny performance, 240 ewes were divided into 8 treatment groups (n = 30 each) and drenched weekly with no Se; at the maximum FDA-allowed concentration with inorganic Na-selenite or organic Se-yeast (4.9 mg Se/wk); with inorganic Na-selenate (8.95 mg Se/wk); or with inorganic Na-selenite and organic Se-yeast at supranutritional concentrations (14.7 and 24.5 mg Se/wk, respectively). The treatment period started approximately 2 wk before breeding and lasted for 62.5 wk. Ewes of the no-Se and Se-yeast groups continued treatments for another 21 to 24 wk through a second lambing season. Chemical form or dosage of Se did not affect ewe reproductive performance based on proportion of ewes lambing in each treatment group, or number of lambs born, nursed, or weaned per ewe (all P > 0.10). Ewes receiving the highest supplementation rate of Se-yeast at 24.5 mg Se/wk had higher BCS (scale 1 to 5) at the end of yr 1 (2.95 vs. 2.66; P = 0.05) than ewes receiving Se-yeast at 4.9 mg Se/wk. Performance was better in lambs from ewes receiving Se-yeast at 24.5 mg Se/wk than in lambs from ewes receiving Se-yeast at 4.9 mg Se/wk or no Se. In yr 1, lambs from ewes receiving Se-yeast at 24.5 vs. 4.9 mg Se/wk were heavier at 120 d of age (37.0 vs. 34.2 kg; P = 0.05). In yr 2, lambs from ewes receiving Se-yeast at 24.5 mg Se/wk were or tended to be heavier at 60 d of age than lambs from ewes receiving no Se (21.2 vs. 19.0 kg; P = 0.04) or lambs from ewes receiving Se-yeast at 4.9 mg Se/wk (19.2 kg; P = 0.09). This effect was more pronounced in ewes raising multiple lambs. We conclude that supranutritional supplementation of ewes with Se-yeast at 24.5 mg Se/wk improves lamb growth and ewe health without negatively affecting reproductive performance.

Organic and inorganic selenium: II. Transfer efficiency from ewes to lambs.

Adequate Se transfer from ewes to lambs is important to prevent Se-deficiency diseases. To evaluate how different chemical forms of Se administered at comparative dosages to mature ewes affect Se status of their lambs, 240 ewes were divided into 8 treatment groups (n = 30 each) and drenched weekly (at an amount equal to their summed daily intake) with no-Se (controls); at recommended amounts (4.9 mg of Se/wk) with inorganic Na-selenite, inorganic Na-selenate, or organic Se-yeast; or at supranutritional amounts (14.7 and 24.5 mg of Se/wk) with Na-selenite or Se-yeast for 1 yr. Weekly drenching of Se was effective at increasing (P < 0.002) Se concentrations in ewe colostrum and milk at 30 d of lactation and in improving (P < 0.001) the Se status of lambs (whole-blood and serum-Se concentrations at birth, and skeletal-muscle Se concentrations at 14 d of age). Selenium concentrations in lacteal secretions were greater in ewes drenched with Se-yeast (colostrum: 374, 436, and 982 ng/mL at 4.9, 14.7, and 24.5 mg of Se/wk, respectively; milk: 26, 39, 64 ng/mL) compared with ewes drenched with Na-selenite (colostrum: 204, 334, 428 ng/mL; milk: 16, 21, 24 ng/mL), and were also greater (P < 0.001) in their lambs. Selenium concentrations continued to increase (P < 0.001) in lamb whole blood (558 and 695 ng/mL at 14.7 and 24.5 mg of Se/wk, respectively), serum (126, 183 ng/mL), and skeletal muscle (991, 1,696 ng/mL) with supranutritional concentrations of Se-yeast, whereas Se concentrations did not differ in whole blood (304, 332 ng/mL), serum (77, 85 ng/mL), or skeletal muscle (442, 482 ng/mg) of lambs from ewes drenched with 14.7 or 24.5 mg of Se/wk of Na-selenite. We conclude that weekly oral drenching of ewes during gestation and lactation with organic Se-yeast results in a more efficient transfer of Se (over a wide range of supplementation rates) from ewe to lamb than does inorganic Na-selenite.

Organic and inorganic selenium: I. Oral bioavailability in ewes.

Although the essentiality of dietary Se for sheep has been known for decades, the chemical source and Se dosage for optimal health remain unclear. In the United States, the Food and Drug Administration (FDA) regulates Se supplementation, regardless of the source of Se, at 0.3 mg of Se/kg of diet (as fed), which is equivalent to 0.7 mg of Se/d or 4.9 mg of Se/wk per sheep. The objectives of this study were to evaluate the effects of Se source (inorganic vs. organic) and supplementation rate (FDA vs. supranutritional rates of 14.7 and 24.5 mg of Se/wk) on whole-blood (WB) and serum-Se concentrations. Mature ewes (n = 240) were randomly assigned to 8 treatment groups (n = 30 each) based on Se supplementation rate (4.9, 14.7, and 24.5 mg of Se•wk(-1)•sheep(-1)) and source [Na-selenite, Na-selenate (4.9 mg/wk only), and organic Se-yeast] with a no-Se control group (0 mg of Se/wk). Treatment groups were balanced for healthy and footrot-affected ewes. For 1 yr, ewes were individually dosed once weekly with 0, 4.9, 14.7, or 24.5 mg of Se, quantities equivalent to their summed daily supplementation rates. Serum- and WB-Se concentrations were measured every 3 mo in all ewes; additionally, WB-Se concentrations were measured once monthly in one-half of the ewes receiving 0 or 4.9 mg of Se/wk. Ewes receiving no Se showed a 78.8 and 58.8% decrease (P < 0.001) in WB- (250 to 53 ng/mL) and serum- (97 to 40 ng/mL) Se concentrations, respectively, over the duration of the study. Whole-blood Se decreased primarily during pregnancy (-57%; 258 to 111 ng/mL) and again during peak lactation (-44%; 109 to 61 ng/mL; P < 0.001). At 4.9 mg of Se/wk, Se-yeast (364 ng/mL, final Se concentration) was more effective than Na-selenite (269 ng/mL) at increasing WB-Se concentrations (P < 0.001). Supranutritional Se-yeast dosages increased WB-Se concentrations in a dose-dependent manner (563 ng/mL, 14.7 mg of Se/wk; 748 ng/mL, 24.5 mg of Se/wk; P < 0.001), whereas WB-Se concentrations were not different for the Na-selenite groups (350 ng/mL, 14.7 mg of Se/wk; 363 ng/mL, 24.5 mg of Se/wk) or the 4.9 mg of Se/wk Se-yeast group (364 ng/mL). In summary, the dose range whereby Se supplementation increased blood Se concentrations was more limited for inorganic Na-selenite than for organic Se-yeast. The smallest rate (FDA-recommended quantity) of organic Se supplementation was equally effective as supranutritional rates of Na-selenite supplementation in increasing WB-Se concentrations, demonstrating the greater oral bioavailability of organic Se.

Serum cytokine concentrations, flavonol intake and colorectal adenoma recurrence in the Polyp Prevention Trial.

BACKGROUND: Serum cytokine concentrations may reflect inflammatory processes occurring during the development of colorectal neoplasms. Flavonols, bioactive compounds found in plant-based foods and beverages, may inhibit colorectal neoplasms partly by attenuating inflammation. METHODS: Using logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) to investigate the association between serum concentrations of interleukin (IL) ß, 2, 8, 10, 12p70, granulocyte macrophage colony stimulating factor, interferon-γ, and tumour necrosis factor-α, measured over time, flavonol intake, estimated from a flavonol database used in conjunction with a food frequency questionnaire, and adenoma recurrence in 872 participants from the intervention arm of the Polyp Prevention Trial. RESULTS: Decreased IL-2 concentration during the trial increased the risk of any adenoma recurrence (4th vs 1st quartile, OR=1.68, 95% CI=1.13-2.49), whereas decreased IL-1ß or IL-10 reduced the risk of advanced adenoma recurrence (OR=0.37, 95% CI=0.15-0.94; OR=0.39, 95% CI=0.15-0.98, respectively). Individuals with flavonol intake above the median (29.7 mg per day) and decreased cytokine concentrations had the lowest risk of advanced adenoma recurrence. CONCLUSION: Overall, no consistent associations were observed between serum cytokine profile and colorectal adenoma recurrence; however, decreased cytokine concentrations during high flavonol consumption may indicate prevention of colorectal neoplasms.

Chronic metabolic responses of postpartal dairy cows to subcutaneous glucagon injections, oral glycerol, or both.

We examined the long-term effects of daily subcutaneous injections of 15 mg of glucagon during the first 14 d postpartum with or without coadministration of 400 mL of pure glycerol orally on blood metabolites and hormones and liver composition of Holstein dairy cows during early lactation. Fourteen multiparous cows with body condition score of >or=3.5 points (1-5 point scale) were assigned randomly to one of 4 treatment groups-saline, glucagon, glycerol, or glucagon plus glycerol. Fatty liver syndrome was induced by feeding cows a dry-cow ration supplemented with 6 kg of cracked corn daily during the last 6 wk of the dry period. Compared with saline treatment (n=3), coadministration of glucagon and glycerol (n=4) increased plasma glucose and insulin and decreased plasma nonesterified fatty acid concentrations in both treatment weeks, whereas glucagon alone (n=3) produced similar changes plus a decrease in plasma beta-hydroxybutyrate in the second week only. No significant changes were observed for the glycerol alone treatment (n=4). We conclude that a single daily dose of glycerol for the first 14 d postpartum may potentiate the action of glucagon in the first treatment days to alleviate some symptoms of fatty liver syndrome, such as the increase in plasma nonesterified fatty acids and the decrease in plasma glucose and insulin, in Holstein dairy cows after parturition.