@article{maile_busby_gollahon_flowers_garbacik_garbacik_stewart_nichols_bellinger_patel_et al._2014, title={Blocking Ligand Occupancy of the alpha V beta 3 Integrin Inhibits the Development of Nephropathy in Diabetic Pigs}, volume={155}, ISSN={["1945-7170"]}, DOI={10.1210/en.2014-1318}, abstractNote={Hyperglycemia stimulates secretion of αVβ3 ligands from vascular cells, including endothelial cells, resulting in activation of the αVβ3 integrin. This study determined whether blocking ligand occupancy of αVβ3 would inhibit the development of diabetic nephropathy. Ten diabetic pigs received an F(ab)2 fragment of an antibody directed against the extracellular domain of the β3-subunit, and 10 received a control IgG F(ab)2 for 18 weeks. Nondiabetic pigs excreted 115 ± 50 μg of protein/mg creatinine compared with control F(ab)2-treated diabetic animals (218 ± 57 μg/mg), whereas diabetic animals treated with the anti-β3 F(ab)2 excreted 119 ± 55 μg/mg (P < .05). Mesangial volume/glomerular volume increased to 21 ± 2.4% in control-treated diabetic animals compared with 14 ± 2.8% (P < .01) in animals treated with active antibody. Diabetic animals treated with control F(ab)2 had significantly less glomerular podocin staining compared with nondiabetic animals, and this decrease was attenuated by treatment with anti-β3 F(ab)2. Glomerular basement membrane thickness was increased in the control, F(ab)2-treated diabetic animals (212 ± 14 nm) compared with nondiabetic animals (170 ± 8.8 nm), but it was unchanged (159.9 ± 16.4 nm) in animals receiving anti-β3 F(ab)2. Podocyte foot process width was greater in control, F(ab)2-treated, animals (502 ± 34 nm) compared with animals treated with the anti-β3 F(ab)2 (357 ± 47 nm, P < .05). Renal β3 tyrosine phosphorylation decreased from 13 934 ± 6437 to 6730 ± 1524 (P < .01) scanning units in the anti-β3-treated group. We conclude that administration of an antibody that inhibits activation of the β3-subunit of αVβ3 that is induced by hyperglycemia attenuates proteinuria and early histologic changes of diabetic nephropathy, suggesting that it may have utility in preventing the progression of this disease complication.}, number={12}, journal={ENDOCRINOLOGY}, author={Maile, Laura A. and Busby, Walker H. and Gollahon, Katherine A. and Flowers, William and Garbacik, Nikol and Garbacik, Stefani and Stewart, Kara and Nichols, Timothy and Bellinger, Dwight and Patel, Amit and et al.}, year={2014}, month={Dec}, pages={4665–4675} } @article{lovercamp_stewart_lin_flowers_2013, title={Effect of dietary selenium on boar sperm quality}, volume={138}, ISSN={0378-4320}, url={http://dx.doi.org/10.1016/j.anireprosci.2013.02.016}, DOI={10.1016/j.anireprosci.2013.02.016}, abstractNote={The primary objective of this research was to evaluate the effect of long-term dietary selenium supplementation of commercial swine diets on semen production and sperm quality. The dietary treatments were a non-supplemented basal diet or the basal diet supplemented with 0.3ppm selenium in either an organic or inorganic form. A secondary objective was to determine if there were any beneficial effects of dietary selenium supplementation on changes in sperm quality during storage of semen post collection. Boars were fed dietary treatments from weaning at 20.97±0.18 d of age until the study was terminated when they were 382.97±0.18 d of age. Boars (n=6 per treatment) were maintained on a 1 time per week collection frequency for 5 months. Immediately after this, boars were collected six times over a 4 day period. Ejaculates were extended in a commercially available, 5-day semen extender and evaluated on day 1 and 6 of storage post-collection. Boars fed the organic selenium had higher (P<0.01) plasma levels of selenium compared to control boars and similar levels to those supplemented with the inorganic form (P=0.18). Dietary treatment did not affect (P>0.2) volume, concentration, total sperm in the ejaculate, sperm motility, progressive motility, morphology, lipid peroxidation, or glutathione peroxidase activity. These results indicate that supplementing a basal diet with organic or inorganic selenium did not affect semen quantity or sperm quality in fresh ejaculates nor did it appear to have any beneficial latent effects in extended semen stored post collection.}, number={3-4}, journal={Animal Reproduction Science}, publisher={Elsevier BV}, author={Lovercamp, K.W. and Stewart, K.R. and Lin, X. and Flowers, W.L.}, year={2013}, month={May}, pages={268–275} } @article{fry_ashwell_lloyd_o'nan_flowers_stewart_spears_2012, title={Amount and source of dietary copper affects small intestine morphology, duodenal lipid peroxidation, hepatic oxidative stress, and mRNA expression of hepatic copper regulatory proteins in weanling pigs}, volume={90}, ISSN={["1525-3163"]}, DOI={10.2527/jas.2011-4403}, abstractNote={Thirty weanling, crossbred barrows (SUS SCROFA) were used to determine the effects of amount and source of dietary Cu on small intestinal morphology and lipid peroxidation, Cu metabolism, and mRNA expression of proteins involved in hepatic Cu homeostasis. At 21 d of age, pigs were stratified by BW (6.33 ± 0.23 kg) and allocated to 1 of the following dietary treatments: i) control (no supplemental Cu; 6.7 mg Cu/kg), ii) 225 mg supplemental Cu/kg diet from Cu sulfate (CuSO(4)), or iii) 225 mg supplemental Cu/kg diet from tribasic Cu chloride (TBCC). Pigs were housed 2 pigs per pen and were fed a 3-phase diet regimen until d 35 or 36 of the study. During harvest, bile and liver were obtained for mineral analysis, and liver samples were also obtained for analysis of liver glutathione (GSH) and mRNA expression of Cu regulatory proteins. Segments of duodenum, proximal jejunum, and ileum were obtained for mucosal morphology, and duodenal mucosal scrapings were collected from all pigs for analysis of malondialdehyde (MDA). Duodenal villus height was reduced in CuSO(4) pigs compared with control (P = 0.001) and TBCC (P = 0.03) pigs. Villus height in the proximal jejunum of CuSO(4) pigs was reduced (P = 0.03) compared with control pigs, but ileal villus height was not affected (P = 0.82) by treatment. Duodenal MDA concentrations were greater (P = 0.03) in CuSO(4) pigs and tended to be greater (P = 0.10) in pigs supplemented with TBCC compared with control pigs. Liver Cu was greater (P = 0.01) in CuSO(4) vs. control pigs, and tended (P = 0.07) to be greater in TBCC pigs than control pigs. Bile Cu concentrations were greater (P < 0.001) in CuSO(4) and TBCC pigs vs. controls and were also greater (P = 0.04) in TBCC vs. CuSO(4) pigs. Total liver GSH concentrations were less (P = 0.02) in pigs fed diets supplemented with CuSO(4) vs. pigs fed control diets but total liver GSH did not differ (P = 0.11) between control and TBCC pigs. Hepatic mRNA of cytochrome c oxidase assembly protein 17 was less (P = 0.01) in CuSO(4) and tended to be less (P = 0.08) in TBCC pigs vs. control pigs. Expression of antioxidant 1 mRNA was greater (P = 0.04) in TBCC pigs and tended to be greater (P = 0.06) in CuSO(4) pigs compared with control pigs. Results of this study indicated that, when fed at 225 mg Cu/kg diet, TBCC may cause less oxidative stress in the duodenum than CuSO(4). Feeding weanling pigs increased Cu resulted in modulation of certain Cu transporters and chaperones at the transcription level.}, number={9}, journal={JOURNAL OF ANIMAL SCIENCE}, author={Fry, R. S. and Ashwell, M. S. and Lloyd, K. E. and O'Nan, A. T. and Flowers, W. L. and Stewart, K. R. and Spears, J. W.}, year={2012}, month={Sep}, pages={3112–3119} } @article{stewart_flowers_rampacek_greger_swanson_hafs_2010, title={Endocrine, ovulatory and reproductive characteristics of sows treated with an intravaginal GnRH agonist}, volume={120}, ISSN={["1873-2232"]}, DOI={10.1016/j.anireprosci.2010.04.003}, abstractNote={The present study examined the effectiveness of intravaginal administration of a GnRH agonist, triptorelin, on the induction of the preovulatory LH surge; synchronization of time of ovulation; and reproductive characteristics in weaned sows. Sows were given 100 μg of triptorelin in 0.9, 1.2, or 1.5% methylcellulose gel intravaginally 96 h after weaning and then bred at 8 and 32 h post-treatment. Untreated sows inseminated once each day of estrus served as the positive controls, while females treated with only the methyl cellulose gel and also bred once each day of estrus were negative controls. Sows treated intravaginally with triptorelin exhibited preovulatory LH surges with magnitudes comparable to those that occurred spontaneously in the negative controls. Preovulatory LH surges were initiated over a narrow and well-defined time interval that occurred 4–12 h after treatment in sows receiving triptorelin in 1.2 or 1.5% methyl cellulose gel. As a result, the majority of the sows in these two treatments had ovulations within a 12 h time frame 36–48 h after treatment. In contrast, both the LH surge and ovulation occurred over extended periods of time after weaning in negative controls and sows given triptorelin in 0.9% methylcellulose gel. Farrowing rates and litter size were similar between untreated controls and triptorelin-treated sows that were bred with two fixed timed inseminations. Insemination of sows induced to have ovulations and bred at least once while not in estrus did not have any overt negative effects on reproductive characteristics. These results demonstrate that 100 μg of triptorelin administered intravaginally in a least 1.2% methyl cellulose gel induced a normal preovulatory LH surge and synchronized time of ovulation in weaned sows. Furthermore, there were no obvious changes in reproductive performance when these sows were bred with two fixed time inseminations regardless of whether they exhibited a standing reflex.}, number={1-4}, journal={ANIMAL REPRODUCTION SCIENCE}, author={Stewart, K. R. and Flowers, W. L. and Rampacek, G. B. and Greger, D. L. and Swanson, M. E. and Hafs, H. D.}, year={2010}, month={Jul}, pages={112–119} }