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Responses to an intra-articular lipopolysaccharide challenge following dietary supplementation of Saccharomyces cerevisiae fermentation product in young horses.

ABSTRACT: Dietary intervention may be a valuable strategy to optimize the intra-articular environment in young horses to prolong their performance career. To test the hypothesis that dietary supplementation of a Saccharomyces cerevisiae fermentation product would reduce markers of joint inflammation and increase markers of cartilage metabolism following a single inflammatory insult, Quarter Horse yearlings (mean ± SD; 9 ± 1.0 mo) were balanced by age, sex, body weight (BW), and farm of origin and randomly assigned to: 1.25% BW/d (dry matter basis) custom-formulated concentrate only (CON; n = 9) or concentrate top dressed with 21 g/d Saccharomyces cerevisiae fermentation product (SCFP; n = 10) for 98 d. Horses had ad libitum access to Coastal bermudagrass hay. On d 84, one randomly selected radial carpal joint from each horse was injected with 0.5 ng lipopolysaccharide solution (LPS). The remaining carpal joint was injected with sterile lactated Ringer's solution as a contralateral control. Synovial fluid obtained before supplementation (d 0) and on d 84 at pre-injection h 0, and 6, 12, 24, 168, and 336 h post-injection was analyzed for prostaglandin E2 (PGE2), carboxypeptide of type II collagen (CPII), and collagenase cleavage neopeptide (C2C) by commercial assays. Rectal temperature, heart rate, respiration rate, carpal surface temperature, and carpal circumference (CC) were recorded prior to each sample collection and for 24 h post-injection. Data were analyzed using linear models with repeated measures. From d 0 to 84, synovial C2C declined (P ≤ 0.01) and the CPII:C2C ratio increased (P ≤ 0.01) in all horses with no effect of diet. In response to intra-articular LPS, synovial PGE2 increased by h 6 (P ≤ 0.01) and returned to baseline by h 336, CPII increased by h 12, remained elevated through h 168 (P ≤ 0.01), and returned to baseline by h 336, and C2C increased by h 6 (P ≤ 0.01) but did not return to baseline through h 336 (P ≤ 0.01). Post-intra-articular injection, PGE2 levels were lower in SCFP than CON horses (P = 0.01) regardless of injection type. Synovial CPII and the CPII:C2C ratio demonstrated stability during the LPS challenge in SCFP compared to CON horses (P ≤ 0.01). Clinical parameters were not influenced by diet but increased in response to repeated arthrocentesis (P ≤ 0.01). Dietary SCFP may favorably modulate intra-articular inflammation following an acute stressor and influence cartilage turnover in young horses.

SUBMITTER: Martinez RE

PROVIDER: S-EPMC8557629 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:This study was conducted to determine if feeding a Saccharomyces cerevisiae fermentation product (SCFP) to calves would alter the acute phase response to a lipopolysaccharide (LPS) challenge. Crossbred steer calves [n = 32; 274 ± 1.9 kg body weight (BW)] were randomly allotted to two treatment diets for 21 d: 1) control, fed RAMP (Cargill, Dalhart, TX) and 2) SCFP, fed the control ration supplemented with NaturSafe at 12 g/hd/d mixed into the TMR (NaturSafe, Diamond V, Cedar Rapids, IA). On day 22, steers were fitted with indwelling jugular catheters and rectal temperature monitoring devices and placed in individual bleeding stalls. On day 23, steers were challenged i.v. with 0.25 µg/kg BW LPS. Blood samples were collected at 0.5-h (serum) or 2-h (complete blood counts) intervals from -2 to 8 h and again at 24 h relative to the LPS challenge at 0 h. Sickness behavior scores (SBS) were recorded after the collection of each blood sample. Rectal temperatures were greater in SCFP steers from 6 to 11 h, at 13 h, from 15 to 20 h, and from 22 to 24 h following the LPS challenge compared to Control steers (treatment × time: P = 0.01). Additionally, SCFP-supplemented steers had reduced (P < 0.01) SBS compared to Control steers. Platelet concentrations remained greater in SCFP-supplemented steers compared to Control steers throughout the study (P = 0.05), while there was a tendency (P = 0.09) for SCFP steers to have greater white blood cells and eosinophils concentrations than Control steers. There was a treatment × time interaction for serum cortisol and glucose (P < 0.01). Specifically, cortisol was greater at 0.5 and 2 h postchallenge but was reduced at 3 h for SCFP steers compared to Control steers. Glucose was greater in SCFP steers at -0.5, 2, and 7.5 h compared to Control steers. Serum amyloid A was reduced in SCFP steers at 0.5 h, yet greater at 1 and 7.5 h postchallenge compared to Control steers (treatment × time: P < 0.01). Fibrinogen concentrations were greater (P < 0.01) in SCFP compared to Control steers. There was a treatment × time interaction (P < 0.01) for tumor necrosis factor-α (TNF-α) such that concentrations were reduced in SCFP steers from 1 to 2 h postchallenge compared to Control steers. Overall, these data suggest that supplementing calves with SCFP may have primed the innate immune response prior to the challenge, particularly platelets, which resulted in an attenuated sickness behavior and TNF-α response to LPS.

Project description:BackgroundIntra-articular corticosteroids, such as isoflupredone acetate, are commonly used in the treatment of joint inflammation, especially in performance horses. Following administration in a non-inflamed joints blood concentrations of isoflupredone were low and detectable for only a short period of time post-administration compared to synovial fluid concentrations. For some drugs, inflammation can affect pharmacokinetics, therefore, the goal of the current study was to describe the pharmacokinetics of isoflupredone acetate following intra-articular administration using a model of acute synovitis. Secondarily, pharmacodynamic effects, including effects on joint circumference, joint flexion, and lameness following intra-articular administration of isoflupredone acetate in the experimental model were described.MethodsSixteen horses received a single intra-articular dose of 8 mg of isoflupredone acetate or saline 12 h post-administration of lipopolysaccharide. Blood and urine samples were collected up to 72 h and synovial fluid for 28 days post-administration, drug concentrations determined by liquid chromatography- mass spectrometry and pharmacokinetic analysis performed. Joint circumference, maximum angle of pain free joint flexion and lameness were evaluated prior to and post-treatment.ResultsThe maximum isoflupredone plasma concentration was 2.45 ± 0.61 ng/mL at 2.5 ± 0.75 h and concentrations were less than the limit of quantitation by 72 h. Isoflupredone was below detectable concentrations in urine by 72 h post-administration in all horses and no longer detectable in synovial fluid by 96 h post-administration. Joint circumference was significantly decreased in the isoflupredone treatment group compared to the saline group at 24 and 48 h post drug administration. Pain free joint flexion was significantly different between the saline and isoflupredone treatment groups on day 4 post-treatment.ConclusionsSynovial fluid concentrations and maximum plasma concentrations of isoflupredone differed slightly between the current study and a previous one describing administration into a non-inflamed joint, however, the detection time of isoflupredone in blood was comparable. Effects of isoflupredone on joint circumference and degree of pain free joint flexion suggest a short duration of effect with respect to alleviation of lipopolysaccharide induced synovitis, however, results of this study support future studies of the anti-inflammatory effects of intra-articular isoflupredone acetate.

Project description:BackgroundWe aimed to characterize the protective effects and the molecular mechanisms of action of a Saccharomyces cerevisiae fermentation product (NTK) in response to a mastitis challenge. Eighteen mid-lactation multiparous Holstein cows (n = 9/group) were fed the control diet (CON) or CON supplemented with 19 g/d NTK for 45 d (phase 1, P1) and then infected in the right rear quarter with 2500 CFU of Streptococcus uberis (phase 2, P2). After 36-h, mammary gland and liver biopsies were collected and antibiotic treatment started until the end of P2 (9 d post challenge). Cows were then followed until day 75 (phase 3, P3). Milk yield (MY) and dry matter intake (DMI) were recorded daily. Milk samples for somatic cell score were collected, and rectal and udder temperature, heart and respiration rate were recorded during the challenge period (P2) together with blood samples for metabolite and immune function analyses. Data were analyzed by phase using the PROC MIXED procedure in SAS. Biopsies were used for transcriptomic analysis via RNA-sequencing, followed by pathway analysis.ResultsDMI and MY were not affected by diet in P1, but an interaction with time was recorded in P2 indicating a better recovery from the challenge in NTK compared with CON. NTK reduced rectal temperature, somatic cell score, and temperature of the infected quarter during the challenge. Transcriptome data supported these findings, as NTK supplementation upregulated mammary genes related to immune cell antibacterial function (e.g., CATHL4, NOS2), epithelial tissue protection (e.g. IL17C), and anti-inflammatory activity (e.g., ATF3, BAG3, IER3, G-CSF, GRO1, ZFAND2A). Pathway analysis indicated upregulation of tumor necrosis factor α, heat shock protein response, and p21 related pathways in the response to mastitis in NTK cows. Other pathways for detoxification and cytoprotection functions along with the tight junction pathway were also upregulated in NTK-fed cows.ConclusionsOverall, results highlighted molecular networks involved in the protective effect of NTK prophylactic supplementation on udder health during a subclinical mastitic event.

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Responses to an intra-articular lipopolysaccharide challenge following dietary supplementation of Saccharomyces cerevisiae fermentation product in young horses.

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