Excretion of major odor-causing and acidifying compounds in response to dietary supplementation of chicory inulin in growing pigs.
(17/95)
The excretion of major odor-causing and acidifying compounds in response to dietary supplementation of chicory inulin extract was investigated with six Yorkshire barrows, with an average initial BW of 30 kg, according to a balanced two-period cross-over design. The animals were fed a control diet containing no inulin extract and a treatment diet with 5% inulin extract (as-fed basis) at the expense of cornstarch. Each diet was formulated (as-fed basis) to contain 16% CP from corn (51%) and soybean meal (29%). Each experimental period lasted 14 d, with 10 d for dietary adaptation and 4 d for collection of fecal and urine samples. The fecal samples were analyzed for four major classes of odor-causing and acidifying compounds: 1) VFA; 2) N-containing compounds, including total N and ammonia; 3) volatile sulfides measured as hydrogen sulfide units; and 4) phenols and indoles, including p-cresol, indole, and skatole. Supplementation of chicory inulin at 5% had no effects on the fecal excretion of VFA (P = 0.29), ammonia (P = 0.96), total volatile sulfides (P = 0.56), p-cresol (P = 0.56), and indole (P = 0.75). Fecal excretion of total N (inulin = 6.13 vs. control = 5.10 g/kg DMI) was increased (P < 0.05), whereas urinary total N excretion (inulin = 15.1 vs. control = 16.4 g/[pig x d]) was not affected (P = 0.17) by the inulin supplementation compared with the control group. Furthermore, fecal excretion of skatole (inulin = 9.07 vs. control = 18.93 mg/kg DMI) was decreased (P < 0.05) by the inulin supplementation compared with the control group. In conclusion, dietary supplementation of 5% chicory inulin extract is effective in decreasing the fecal excretion of skatole in growing pigs fed corn and soybean meal diets. (+info)
Bayesian analysis of quantitative trait loci for boar taint in a Landrace outbred population.
(18/95)
The genetic basis of the main components of boar taint was investigated in intact male pigs in a commercial population. We analyzed fat androsten-one and skatole concentrations from 217 males of an outbred Landrace population. Records were normalized using a logarithm transformation and tested for normality using a Wilk-Shapiro test. Bayesian analysis was then used to map QTL in 10 candidate regions previously selected on chromosomes 1, 2, 3, 4, 6, 7, 8, 9, 10, and 13. The criterion for QTL detection was the Bayes factor (BF) between polygenic models with and without QTL effects. Both traits had considerable genetic determination, with posterior means of total heritabilities ranging from 0.59 to 0.73 for androstenone and from 0.74 to 0.89 for skatole. Positive evidence for a fat skatole QTL was detected on SSC6 (BF = 5.16); however, no QTL for androstenone were found in any of the 10 chromosomal regions analyzed. With the detection of a QTL for the fat skatole concentration segregating in this population, marker-assisted selection or even gene-assisted selection could be used once the causal mutation of the QTL was identified. (+info)
Insulin-like growth factor binding protein-2: contributions of the C-terminal domain to insulin-like growth factor-1 binding.
(19/95)
Signaling by the insulin-like growth factor (IGF)-1 receptor (IGF-1R) has been implicated in the promotion and aggressiveness of breast, prostate, colorectal, and lung cancers. The IGF binding proteins (IGFBPs) represent a class of natural IGF antagonists that bind to and sequester IGF-1/2 from the IGF-1R, making them attractive candidates as therapeutics for cancer prevention and control. Recombinant human IGFBP-2 significantly attenuated IGF-1-stimulated MCF-7 cell proliferation with coaddition of 20 or 100 nM IGFBP-2 (50 or 80% inhibition, respectively). We previously identified IGF-1 contact sites both upstream and downstream of the CWCV motif (residues 247-250) in human IGFBP-2 (J Biol Chem 276:2880-2889, 2001). To further test their contributions to IGFBP-2 function, the single tryptophan in human IGFBP-2, Trp-248, was selectively cleaved with 2-(2'nitrophenylsulfenyl)-3-methyl-3 bromoindolenine (BNPS-skatole) and the BNPS-skatole products IGFBP-2(1-248) and IGFBP-2(249-289) as well as IGFBP-2(1-190) were expressed as glutathione S-transferase-fusion proteins and purified. Based on competition binding analysis, deletion of residues 249 to 289 caused an approximately 20-fold decrease in IGF-1 binding affinity (IGFBP-2 EC50 = 0.35 nM and IGFBP-2(1-248) = 7 nM). Removal of the remainder of the C-terminal domain had no further effect on affinity (IGFBP-2(1-190) EC50 = 9.2 nM). In kinetic assays, IGFBP-2(1-248) and IGFBP-2(1-190) exhibited more rapid association and dissociation rates than full-length IGFBP-2. These results confirm that regions upstream and downstream of the CWCV motif participate in IGF-1 binding. They further support the development of full-length IGFBP-2 as a cancer therapeutic. (+info)
Importance of tensor asymmetry for the analysis of 2H NMR spectra from deuterated aromatic rings.
(20/95)
We have used ab initio calculations to compute all of the tensor elements of the electric field gradient for each carbon-deuterium bond in the ring of deuterated 3-methyl-indole. Previous analyses have ignored the smaller tensor elements perpendicular to principal component Vzz which is aligned with the C-2H bond (local bond z-axis). At each ring position, the smallest element Vxx is in the molecular plane and Vyy is normal to the plane of the ring. The asymmetry parameter = (Vyy - Vxx)/Vzz ranges from 0.07 at C4 to 0.11 at C2. We used the perpendicular (off-bond) tensor elements, in concert with an improved understanding of the indole ring geometry, to analyze prototype 2H NMR spectra from well-oriented, hydrated peptide/lipid samples. For each of the four tryptophans of membrane-spanning gramicidin A (gA) channels, the inclusion of the perpendicular elements changes the deduced ring tilt by nearly 10 and increases the ring principal order parameter Szz for overall "wobble" with respect to the membrane normal (molecular z-axis). With the improved analysis, the magnitude of Szz for the outermost indole rings of Trp13 and Trp15 is indistinguishable from that observed previously for backbone atoms (0.93 +/- 0.03). For the Trp9 and Trp11 rings, which are slightly more buried within the membrane, Szz is slightly lower (0.86 +/- 0.03). The results show that the perpendicular elements are important for the detailed analysis of 2H NMR spectra from aromatic ring systems. (+info)
The role of CYP2A and CYP2E1 in the metabolism of 3-methylindole in primary cultured porcine hepatocytes.
(21/95)
The accumulation of 3-methylindole (3MI) in uncastrated male pigs (boars) is a major cause of boar taint, which negatively affects the quality of meat from the animal. Previously, CYP2E1 and CYP2A have been identified as cytochrome P450 (P450) isoforms involved in the metabolism of 3MI using porcine liver microsomes. This study further examines the role of these isoforms in the metabolism of 3MI using a primary porcine hepatocyte model by examining metabolic profiles of 3MI after incubation with P450 inhibitors. Incubation of hepatocytes with 4-methylpyrazole resulted in a selective inhibition of CYP2E1 activity as determined by p-nitrophenol hydroxylase activity and an associated significant decrease in the production of the 3MI metabolites 3-hydroxy-3-methyloxindole and 3-methyloxindole. Furthermore, inhibition of CYP2A, as assayed by coumarin 7-hydroxylase activity, using 8-methoxypsoralen and diethyldithiocarbamate was not associated with any further significant inhibition of the production of 3MI metabolites. Treatment with general P450 inhibitors resulted in further decreases in CYP2E1 activity and a more dramatic decrease in the production of 3MI metabolites, suggesting that additional P450s may be involved in the phase 1 metabolism of 3-methylindole. In conclusion, CYP2E1 activity levels are more important than CYP2A activity levels for the metabolism of 3-methylindole in isolated pig hepatocytes. (+info)
Characterizing developmental changes in plasma and tissue skatole concentrations in the prepubescent intact male pig.
(22/95)
The accumulation of skatole in boars to concentrations resulting in carcass taint has been associated with elevated concentrations of steroid hormones in plasma. Studying boar taint in vivo has been challenging because steroid hormones are highly variable between individual boars. However, a peak in steroid hormones occurs between 2 and 4 wk postpartum; therefore, skatole production was investigated in the prepubescent pig. Plasma concentrations of estrone sulphate, dehydroepiandrosterone sulphate, and testosterone peaked between 2 and 4 wk postpartum in intact male pigs, whereas plasma concentrations of these steroid hormones remained low or undetectable in gilts and barrows. However, plasma skatole concentration peaked in all 3 groups of animals between 2 and 3 wk postweaning. The effects of weaning time, intestinal cell turnover, and diet on tissue skatole concentrations were then investigated. Intact male piglets were weaned at 14, 21, 28, or 35 d of age. Plasma skatole concentrations were measured weekly for a period of 63 d and peaked at 17 +/- 1, 14 +/- 1, 13 +/- 1, and 10 +/- 2 d postweaning, respectively. Intestinal cell turnover, as evaluated by villous height:crypt depth ratio, was not correlated with skatole concentrations in cecal contents, suggesting that cellular debris did not constitute a gross source of tryptophan for hindgut fermentation. The inclusion of 10% chicory inulin to piglet diets suppressed the postweaning increase in plasma skatole. Cecal skatole concentrations were also 3.3-fold lower in inulin-supplemented piglets compared with controls. The rise in plasma skatole in the prepubescent intact male pig was not associated with increased steroidogenesis but is likely due to the postweaning adaptation of the intestinal flora to an abrupt dietary change. (+info)
Effect of dietary melengestrol acetate on the incidence of acute interstitial pneumonia in feedlot heifers.
(23/95)
Over a 3-y period, 906,000 cattle were monitored in 23 feedlots in southern Alberta for symptoms of acute interstitial pneumonia (AIP). Plasma, urine, and lung tissue were collected at slaughter from 299 animals clinically diagnosed with AIP and from 156 healthy penmates and analyzed for 3-methylindole (3MI) derivatives and reduced glutathione concentration. From each animal, the left lung was subsampled for histologic examination. Concentrations of glutathione in lung tissue were reduced (P < 0.001) in animals showing clinical symptoms of AIP as compared with their asymptomatic penmates. Animals histologically confirmed as having AIP had higher levels of 3MI protein adducts in blood and lung tissue (P < 0.05) than did emergency-slaughtered animals without AIP. Within feedlots, where pens of heifers were fed either a standard dosage of melengestrol acetate (MGA) or none, the rate of death attributable to AIP was similar between treatment groups, but emergency slaughter after clinical diagnosis of AIP was done 3.2 times more often (P < 0.001) in the MGA-fed heifers than in the group not fed MGA. Use of MGA did not influence glutathione concentration. As growth performance of heifers given steroidal implants may not be improved by feeding MGA, the most cost-effective method of reducing the incidence of AIP-related emergency slaughter in feedlot heifers may be to eliminate MGA from the diet. (+info)
Olfactory performance of rats after selective deafferentation of the olfactory bulb by 3-methyl indole.
(24/95)
Rats trained to detect propyl acetate and valeric acid and to discriminate between propyl acetate and amyl acetate and between valeric acid and butyric acid were injected with a low dose of 3-methyl indole, a treatment that produces well-defined and selective deafferentation of the olfactory bulbs. Treatment completely deafferented most but not all bulbar loci for aliphatic acids and at least disrupted those for propyl and amyl acetate. In posttreatment tests, experimental rats performed somewhat but not significantly more poorly than controls and about as well on the acid detection and discrimination tasks as on the corresponding acetate tests. (+info)