EFFECTS OF PITUITARY PARS INTERMEDIA DYSFUNCTION AND PRASCEND\u3csup\u3e®\u3c/sup\u3e TREATMENT ON ENDOCRINE AND IMMUNE FUNCTION IN SENIOR HORSES

Pituitary pars intermedia dysfunction (PPID) is one of the most common endocrine diseases affecting senior horses. PPID causes abnormally high concentrations of adrenocorticotropic hormone (ACTH) in the plasma and a very distinct, long, shaggy haircoat (hypertrichosis). At present, the recommended treatment for PPID is daily oral administration of pergolide mesylate. Due to the increased ACTH levels associated with PPID, it is commonly thought that these horses are immunosuppressed and at increased risk of opportunistic infections, although current research in this area is sparse. Additionally, it is not well-understood how treatment with Prascend® (pergolide tablets) affects endocrine measures other than ACTH and if it also impacts the immune response. To better understand how PPID influences endocrine and immune function in the horse, Non-PPID horses (n=10), untreated PPID horses (n=9), and PRASCEND-treated PPID horses (n=9) were followed over 15 months. Endocrine measures assessed included basal ACTH, ACTH responses to thyrotropin-releasing hormone (TRH) stimulation tests, basal insulin, insulin responses to oral sugar tests (OST), total cortisol, and free cortisol. Systemic immune function measures included basal and stimulated whole blood and peripheral blood mononuclear cell (PBMCs) cytokine and receptor expression, plasma myeloperoxidase levels, and complete blood counts. Localized immune function measures within the lung included cytokine and receptor expression after stimulation of cells obtained via bronchoalveolar lavage (BAL), myeloperoxidase levels in BAL fluid, and BAL fluid cytology. We hypothesized that PPID would affect immune function, but that any alterations would be corrected by treatment with PRASCEND. Results for the endocrine analyses showed that basal ACTH was reduced in the PRASCEND-treated horses to the levels of the Non-PPID horses, but ACTH in response to TRH stimulation was only reduced in the PRASCEND-treated horses at non-fall timepoints. PPID did not affect basal insulin, insulin responses to OSTs, total cortisol, or free cortisol, and PRASCEND treatment did not appear to have an impact on these measures either. These results suggest that PPID and hyperinsulinemia/insulin dysregulation are distinct endocrine conditions, and that the excess ACTH in horses with PPID is inactive, as it is unable to stimulate a normal cortisol response. In the immune function analyses, PPID horses had decreased expression of interferon gamma (IFNγ) from PBMCs stimulated with Rhodococcus equi and Escherichia coli and increased transforming growth factor beta (TGFβ) expression from the E. coli-stimulated PBMCs. TGFβ was also increased in PPID horses in the unstimulated whole blood samples. These results suggest that PPID horses are unable to mount an appropriate Th1 response, and that the regulatory subset of T-lymphocytes may be contributing to this decreased Th1 response. Results for the localized immune function analyses may indicate altered Th2 responses within the lung of PPID horses, although these results were severely limited by the sample size available for analyses. PRASCEND did not appear to affect immune function as measured in this study. In summary, PRASCEND successfully reduces basal ACTH in PPID horses and remains the best choice for veterinarians in monitoring dosage and response to PRASCEND treatment. Insulin, total cortisol, and free cortisol were not affected by PPID status or PRASCEND treatment in this study. Immune function was altered in horses with PPID, and it is likely that these horses are indeed at increased risk of opportunistic infection. PRASCEND treatment did not correct the differences in immune function in this study. Additional research is needed to further understand which mechanisms are driving the alterations in immune function for horses with PPID

Stepping Responses of Young and Old Adults to Postural Disturbances: Kinematics

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111171/1/j.1532-5415.1994.tb04972.x.pd

Do Neural Factors Underlie Age Differences in Rapid Ankle Torque Development?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111232/1/j.1532-5415.1996.tb03737.x.pd

Short-Term Transport Stress and Supplementation Alter Immune Function in Aged Horses

Long-distance transport is associated with stress-related changes in equine immune function, and shipping-associated illnesses are often reported. Horses are frequently transported short distances, yet the effects of short-term transport on immune function remain largely unknown. Twelve horses, aged 15–30 yr, were assigned to either the control (n = 6) or treatment (n = 6) groups; treatment horses received a daily antioxidant supplement 3 weeks before and after transport. All horses were transported for approximately 1.5–2 hr on Day 0. Blood was collected via jugular venipuncture at 15-min pre- and post-transport and on Days –21, 1, 3, 7, 14, and 21. Body temperature, heart rate, body weight, total cortisol, and gene expression of IFNγ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12α, IL-17α, SAA1, and TNFα in whole blood were measured. Peripheral blood mononuclear cells were isolated, stimulated with PMA/ionomycin, and stained for IFNγ and TNFα before analysis via flow cytometry. Statistical analyses were performed with significance set at P \u3c 0.05 (SAS 9.4). Transport and supplementation did not appear to affect body weight, heart rate, IL-4, IL-8, IL-12α, IL-17α, change (Δ) in the % and mean fluorescence intensity (MFI) of IFNγ+ lymphocytes after stimulation, or Δ in the % and MFI of TNFα+ lymphocytes after stimulation. Supplementation decreased IL-1β and SAA1 expression. Transport increased total cortisol concentration, body temperature, and IL-2, IL-6, and IL-10 expression but decreased IL-1β, TNFα, and IFNγ expression. Short-term transportation affected physiological, endocrine, and immune responses; supplementation may ameliorate inflammation in aged horses. Immune responses were most altered at 15-min post-transport and typically recovered by Day 1, suggesting that horses may be vulnerable to disease during and almost immediately after short-term transport

Effect of increased quadriceps tensile stiffness on peak anterior cruciate ligament strain during a simulated pivot landing

ACL injury prevention programs often involve strengthening the knee muscles. We posit that an unrecognized benefit of such training is the associated increase in the tensile stiffness of the hypertrophied muscle. We tested the hypothesis that an increased quadriceps tensile stiffness would reduce peak anteromedial bundle (AM‐)ACL relative strain in female knees. Twelve female cadaver knees were subjected to compound impulsive two‐times body weight loads in compression, flexion, and internal tibial torque beginning at 15° flexion. Knees were equipped with modifiable custom springs to represent the nonlinear rapid stretch behavior of a normal and increased stiffness female quadriceps (i.e., 33% greater stiffness). Peak AM‐ACL relative strain was measured using an in situ transducer while muscle forces and tibiofemoral kinematics and kinetics were recorded. A 3D ADAMS™ dynamic biomechanical knee model was used in silico to interpret the experimental results which were analyzed using a repeated‐measures Wilcoxon test. Female knees exhibited a 16% reduction in peak AM‐ACL relative strain and 21% reduction in change in flexion when quadriceps tensile stiffness was increased by 33% (mean (SD) difference: 0.97% (0.65%), p  = 0.003). We conclude that increased quadriceps tensile stiffness reduces peak ACL strain during a controlled study simulating a pivot landing. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:423–430, 2014.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102663/1/jor22531.pd

Poster 194: Biomechanical Analysis of a Novel Clinical Measure of Reaction Time

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147091/1/pmr2s188a.pd

Biomechanical analyses of rising from a chair

Quantification of the biomechanical factors that underlie the inability to rise from a chair can help explain why this disability occurs and can aid in the design of chairs and of therapeutic intervention programs. Experimental data collected earlier from 17 young adult and two groups of elderly subjects, 23 healthy and 11 impaired, rising from a standard chair under controlled conditions were analyzed using a planar biomechanical model. The joint torque strength requirements and the location of the floor reaction force at liftoff from the seat in the different groups and under several conditions were calculated. Analyses were also made of how body configurations and the use of hand force affect these joint torques and reaction locations.In all three groups, the required torques at liftoff were modest compared to literature data on voluntary strengths. Among the three groups rising with the use of hands, at the time of liftoff from the seat, the impaired old subjects, on an average, placed the reaction force the most anterior, the healthy old subjects placed it intermediately and the young subjects placed it the least anterior, within the foot support area. Moreover, the results suggest that, at liftoff, all subjects placed more importance on locating the floor reaction force to achieve acceptable postural stability than on diminishing the magnitudes of the needed joint muscle strengths.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29713/1/0000047.pd

Age effects on strategies used to avoid obstacles

Chen et al.1 found that the rates of success which 24 healthy younger and 24 healthy older adults achieved in not stepping on fixed and suddenly appearing virtual obstacles was adversely affected by reducing their available response time. This paper reports the gait strategies used by those 48 subjects in avoiding the obstacles and the factors associated with falls by four of the subjects. Differences among gait parameters were analysed with respect to age, gender, available response time, and avoidance strategy. Both short- and long-step strategies were used to avoid stepping on the obstacles, but age differences in strategy choice were not significant. The short-step strategy was used more often with shorter available response times. To avoid a fized obstacle gait was seldom adjusted more than two steps before reaching it; the older adults, however, adjusted their stepping pattern one step earlier than did the younger adults. As the available response time was shortened, the results suggest that older adults had more difficulty than did younger adults in employing the long-step strategy. Although the short-step strategy is easier to employ at short available response times, it becomes a highly risky strategy when combined with a fast walking speed and resulted in actual falls. The results show that in both young and old healthy adults, tripping does not necessarily originate from contacts with a physical obstacle; it can be self initiated.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31348/1/0000258.pd

Identification of dynamic myoelectric signal-to-force models during isometric lumbar muscle contractions

A 14-muscle myoelectric signal (MES)-driven muscle force prediction model of the L3-L4 cross section is developed which includes a dynamic MES-force relationship and allows for cocontraction. Model parameters are estimated from MES and moments data recorded during rapid exertions in trunk flexion, extension, lateral bending and axial twist. Nine young healthy males participated in the experimental testing. The model used in the parameter estimation is of the output error type. Consistent and physically feasible parameter estimates were obtained by normalizing the RMS MES to maximum exertion levels and using nonlinear constrained optimization to minimize a cost function consisting of the trace of the output error covariance matrix. Model performance was evaluated by comparing measured and MES-predicted moments over a series of slow and rapid exertions. Moment prediction errors were on the order of 25, 30 and 40% during attempted trunk flexion-extensions, lateral bends and axial twists, respectively. The model and parameter estimation methods developed provide a means to estimate lumbar muscle and spine loads, as well as to empirically investigate the use and effects of cocontraction during physical task performances.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31486/1/0000408.pd

On the Implications of a Sex Difference in the Reaction Times of Sprinters at the Beijing Olympics

Elite sprinters offer insights into the fastest whole body auditory reaction times. When, however, is a reaction so fast that it represents a false start? Currently, a false start is awarded if an athlete increases the force on their starting block above a given threshold before 100 ms has elapsed after the starting gun. To test the hypothesis that the fastest valid reaction times of sprinters really is 100 ms and that no sex difference exists in that time, we analyzed the fastest reaction times achieved by each of the 425 male and female sprinters who competed at the 2008 Beijing Olympics. After power transformation of the skewed data, a fixed effects ANOVA was used to analyze the effects of sex, race, round and lane position. The lower bounds of the 95, 99 and 99.9% confidence intervals were then calculated and back transformed. The mean fastest reaction time recorded by men was significantly faster than women (p<0.001). At the 99.9% confidence level, neither men nor women can react in 100 ms, but they can react in as little as 109 ms and 121 ms, respectively. However, that sex difference in reaction time is likely an artifact caused by using the same force threshold in women as men, and it permits a woman to false start by up to 21 ms without penalty. We estimate that female sprinters would have similar reaction times to male sprinters if the force threshold used at Beijing was lowered by 22% in order to account for their lesser muscle strength