Fecal microbiota composition, serum metabolomics, and markers of inflammation in dogs fed a raw meat-based diet compared to those on a kibble diet.

Introduction: Despite the potential health risks associated with feeding raw and non-traditional diets, the use of these diets in dogs is increasing, yet the health outcomes associated with these diets is not well understood. This study investigates the effect of feeding dogs a kibble or raw meat-based diets on fecal microbiota composition, serum metabolomics and inflammatory markers. Methods: Clinically healthy dogs with a history of consuming either kibble (KD, n = 27) or raw meat-based diets (RMBD, n = 28) for more than 1 year were enrolled. Dogs were fed a standardized diet of either a single brand of KD or RMBD for 28 days. Serum and fecal samples were collected for analysis of microbiota, metabolomics, and inflammatory markers. Multiple regression analysis was performed for each of the metabolites and inflammatory markers, with feed group, age and BCS included as independent variables. Results: The fecal microbiota composition differed between the KD and RMBD groups. Beta-diversity and some indices of alpha-diversity (i.e., Shannon and Simpson) were different between the two diet groups. Sixty- three serum metabolites differed between KD and RMBD-fed dogs with the majority reflecting the differences in macronutrient composition of the two diets.Fecal IAP, IgG and IgA were significantly higher in RMBD dogs compared to KD dogs, while systemic markers of inflammation, including serum c-reactive protein (CRP), galectin, secretory receptor of advanced glycation end-products (sRAGE), haptoglobin, and serum IgG were similar in dogs fed either diet. Discussion: Diet composition significantly affected fecal microbiota composition and metabolome. Although it had a potentially beneficial effect on local inflammatory markers, feeding RMBD had no impact on systemic inflammation. The influence of these changes on long term health outcomes provides an area for future study.

BEVA primary care clinical guidelines: Diagnosis and management of equine pituitary pars intermedia dysfunction.

BACKGROUND: Pituitary pars intermedia dysfunction (PPID) is a prevalent, age-related chronic disorder in equids. Diagnosis of PPID can be challenging because of its broad spectrum of clinical presentations and disparate published diagnostic criteria, and there are limited available treatment options. OBJECTIVES: To develop evidence-based primary care guidelines for the diagnosis and treatment of equine PPID based on the available literature. STUDY DESIGN: Evidence-based clinical guideline using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. METHODS: Research questions were proposed by a panel of veterinarians and developed into PICO or another structured format. VetSRev and Veterinary Evidence were searched for evidence summaries, and systematic searches of the NCBI PubMed and CAB Direct databases were conducted using keyword searches in July 2022 and updated in January 2023. The evidence was evaluated using the GRADE framework. RESULTS AND RECOMMENDATIONS: The research questions were categorised into four areas: (A) Case selection for diagnostic testing, pre-test probability and diagnostic test accuracy, (B) interpretation of test results, (C) pharmacological treatments and other treatment/management options and (D) monitoring treated cases. Relevant veterinary publications were identified and assessed using the GRADE criteria. The results were developed into recommendations: (A) Case selection for diagnostic testing and diagnostic test accuracy: (i) The prevalence of PPID in equids aged ≥15 years is between 21% and 27%; (ii) hypertrichosis or delayed/incomplete hair coat shedding provides a high index of clinical suspicion for PPID; (iii) the combination of clinical signs and age informs the index of clinical suspicion prior to diagnostic testing; (iv) estimated pre-test probability of PPID should be considered in interpretation of diagnostic test results; (v) pre-test probability of PPID is low in equids aged <10 years; (vi) both pre-test probability of disease and season of testing have strong influence on the ability to diagnose PPID using basal adrenocorticotropic hormone (ACTH) or ACTH after thyrotropin-releasing hormone (TRH) stimulation. The overall diagnostic accuracy of basal ACTH concentrations for diagnosing PPID ranged between 88% and 92% in the autumn and 70% and 86% in the non-autumn, depending on the pre-test probability. Based on a single study, the overall diagnostic accuracy of ACTH concentrations in response to TRH after 30 minutes for diagnosing PPID ranged between 92% and 98% in the autumn and 90% and 94% in the non-autumn, depending on the pre-test probability. Thus, it should be remembered that the risk of a false positive result increases in situations where there is a low pre-test probability, which could mean that treatment is initiated for PPID without checking for a more likely alternative diagnosis. This could compromise horse welfare due to the commencement of lifelong therapy and/or failing to identify and treat an alternative potentially life-threatening condition. (B) Interpretation of diagnostic tests: (i) There is a significant effect of breed on plasma ACTH concentration, particularly in the autumn with markedly higher ACTH concentrations in some but not all 'thrifty' breeds; (ii) basal and/or post-TRH ACTH concentrations may also be affected by latitude/location, diet/feeding, coat colour, critical illness and trailer transport; (iii) mild pain is unlikely to have a large effect on basal ACTH, but caution may be required for more severe pain; (iv) determining diagnostic thresholds that allow for all possible contributory factors is not practical; therefore, the use of equivocal ranges is supported; (v) dynamic insulin testing and TRH stimulation testing may be combined, but TRH stimulation testing should not immediately follow an oral sugar test; (vi) equids with PPID and hyperinsulinaemia appear to be at higher risk of laminitis, but ACTH is not an independent predictor of laminitis risk. (C) Pharmacologic treatments and other treatment/management options: (i) Pergolide improves most clinical signs associated with PPID in the majority of affected animals; (ii) Pergolide treatment lowers basal ACTH concentrations and improves the ACTH response to TRH in many animals, but measures of insulin dysregulation (ID) are not altered in most cases; (iii) chasteberry has no effect on ACTH concentrations and there is no benefit to adding chasteberry to pergolide therapy; (iv) combination of cyproheptadine with pergolide is not superior to pergolide alone; (v) there is no evidence that pergolide has adverse cardiac effects in horses; (vi) Pergolide does not affect insulin sensitivity. (D) Monitoring pergolide-treated cases: (i) Hormone assays provide a crude indication of pituitary control in response to pergolide therapy, however it is unknown whether monitoring of ACTH concentrations and titrating of pergolide doses accordingly is associated with improved endocrinological or clinical outcome; (ii) it is unknown whether monitoring the ACTH response to TRH or clinical signs is associated with an improved outcome; (iii) there is very weak evidence to suggest that increasing pergolide dose in autumn months may be beneficial; (iv) there is little advantage in waiting for more than a month to perform follow-up endocrine testing following initiation of pergolide therapy; there may be merit in performing repeat tests sooner; (v) timing of sampling in relation to pergolide dosing does not confound measurement of ACTH concentration; (vi) there is no evidence that making changes after interpretation of ACTH concentrations measured at certain times of the year is associated with improved outcomes; (vii) evidence is very limited, however, compliance with PPID treatment appears to be poor and it is unclear whether this influences clinical outcome; (viii) evidence is very limited, but horses with clinical signs of PPID are likely to shed more nematode eggs than horses without clinical signs of PPID; it is unclear whether this results in an increased risk of parasitic disease or whether there is a need for more frequent assessment of faecal worm egg counts. MAIN LIMITATIONS: Limited relevant publications in the veterinary scientific literature. CONCLUSIONS: These findings should be used to inform decision-making in equine primary care practice.

Adverse health events and recommended health research priorities in agility dogs as reported by dog owners.

Objective: To understand relative frequency of adverse health events, defined as injuries or infectious diseases, in dogs participating in agility and to determine health research priorities of agility dog owners. Procedures: An internet-based questionnaire distributed to agility dog owners included items related to experiences with infectious diseases and injuries in agility dogs, reasons for retirement of dogs from competition, and ranking of health research priorities. Frequencies of infectious diseases in US geographic regions were compared with Chi-square tests. Research priority rankings were determined as median and interquartile range (IQR) for each topic. Rank-based tests (Kruskal Wallis and Mann-Whitney) compared rankings between participants in different agility organizations, between veterinarian and non-veterinarian competitors, and between respondents who had competed in national championship events and other respondents. Results: There were 1,322 respondents who had competed in canine agility in the previous 6 months, with those respondents reporting a median time competing in the sport of 13 years (IQR = 8-20 years); 50% of respondents had competed in at least one national championship agility event in the preceding 5 years. Overall, 1,015 respondents (77%) indicated that one or more of their dogs had been injured and approximately one-third (n = 477, 36%) indicated that one or more dogs had likely acquired one or more infectious diseases as a result of agility activities. Specific types of infectious diseases acquired varied by geographic region in the US. Research priority rankings were similar regardless of preferred agility organization or respondent experience. The highest-ranking research topics were identification of risk factors for specific types of injuries, improvements in equipment and understanding of safe course design, and physical conditioning programs to prevent injury. Conclusions and clinical relevance: Agility competitors prioritize research in areas that advance understanding of injury prevention in their dogs. Research priorities are nearly uniform among competitors regardless of their preferred agility organization or level of experience, providing a strong rationale for agility organizations to collaborate in research initiatives that improve safety and well-being for dogs competing in the sport. There has been little published research focusing on the high-priority research areas identified by competitors.

Immunosenescence and inflammaging in the aged horse.

The equine population in the United States and worldwide now includes a higher percentage of geriatric horses than ever previously recorded, and as methods to treat and manage elderly equids are developed and refined, this aging population will likely continue to expand. A better understanding of how horses age and the effect of age on immunity and disease susceptibility is needed to enable targeted preventative healthcare strategies for aged horses. This review article outlines the current state of knowledge regarding the effect of aging on immunity, vaccine responsiveness, and disease risk in the horse, highlighting similarities and differences to what is observed in aged humans. Horses show similar but milder age-related alterations in immune function to those reported in people. Decreases in lymphocyte proliferation and antibody production and diminished response to vaccination have all been documented in elderly horses, however, increased risk of infectious disease is not commonly reported. Aged horses also show evidence of a proinflammatory state (inflammaging) yet appear less susceptible to the chronic diseases of people for which inflammation is a risk factor. Information is currently lacking as to why the horse does not experience the same risk of age-related disease (e.g., cancer, heart disease, neurodegeneration) as people, although a lack of negative lifestyle habits, differences in diet, exercise, genetics and physiology may all contribute to improved health outcomes in the older horse.

Thromboelastography in obese horses with insulin dysregulation compared to healthy controls.

BACKGROUND: Both obesity and metabolic syndrome are associated with hypercoagulability in people, increasing the risk of cardiovascular disease and thromboembolic events. Whether hypercoagulability exists in obese, insulin-dysregulated horses is unknown. HYPOTHESIS/OBJECTIVES: To determine if coagulation profiles differ between healthy horses and those with obesity and insulin dysregulation. ANIMALS: Fifteen healthy horses (CON) and 15 obese, insulin-dysregulated horses (OBID). Individuals were university or client owned. METHODS: Case-control study. Obesity was defined as a body condition score (BCS) ≥7.5/9 (modified Henneke scale). Insulin dysregulation status was assessed by an oral sugar test (OST). Kaolin-thromboelastography and traditional coagulation variables were compared between groups. The direction and strength of the association between coagulation variables and BCS and OST results were determined using Spearman's correlation. RESULTS: Thromboelastography variables MA (OBID: 69.5 ± 4.5 mm; CON: 64.8 ± 4.3 mm; P = .007) and G-value (OBID: 11749 ± 2536 dyn/m2 ; CON: 9319 ± 1650 dyn/m2 ; P = .004) were higher in OBID compared to CON. Positive correlations between MA and BCS (R = 0.45, P = .01) and serum insulin (T0 : R = 0.45, P = .01; T60 : R = 0.39, P = .03), and G-value and BCS (R = 0.46, P = .01), and serum insulin (T0 : R = 0.48, P = .007; T60 : R = 0.43, P = .02; T90 : R = 0.38, P = .04) were present. CONCLUSIONS AND CLINICAL IMPORTANCE: Obese, insulin-dysregulated horses are hypercoagulable compared to healthy controls.

Perioperative considerations for cancer patients with obesity: A narrative review.

Cancer in patients with obesity has become increasingly common throughout much of the world. Based on our experiences in a specialized cancer center, we have developed a set of standards and expectations that should streamline the surgical journey for this patient population. These recommendations should inform the perioperative management of oncology patients with obesity and help raise awareness of this critical and under-discussed topic.

Clinical health markers in dogs fed raw meat-based or commercial extruded kibble diets.

The interest and demand for healthy and less processed foods for human consumption have been mirrored in the pet industry, with an explosion of alternative diets available. Several nontraditional feeding methodologies including raw meat-based diets (RMBDs) are believed by many dog owners to be superior to traditional extruded commercial dog foods. Despite the strong opinions, limited data are available comparing objective health measures among healthy dogs fed using different methods of diet preparation. Therefore, we compared health markers in client-owned dogs fed an RMBD to markers in dogs fed a high-quality extruded kibble. We hypothesized that healthy adult dogs fed RMBD would show differences in biochemical and hematological parameters and improved clinical health scores (e.g., dental, external ear canal, and integument scores) compared with dogs fed a kibble diet. A cross-sectional observational study was performed comparing hematology, serum biochemistry, urinalysis management history, and clinical health scores in healthy client-owned dogs reported as fed RMBD (n = 28) or kibble (n = 27) for >1 yr. Dental, external ear canal, and integument health scores were assigned by a single veterinary evaluator blinded to feed group, using a scale where 0 was normal and 3 was most severely affected. Spearman correlation coefficient (rs) was calculated to assess the strength and direction of the relationship of biochemical outcomes with age and body condition score (BCS), while analysis of variance was used to determine if biochemical analytes differed by breed or gender. Biochemical data were analyzed using multiple linear regression models, adjusting for the covariates gender, breed, age, and BCS. A composite clinical health score, (CCS) = 9 - (dental score + otitis score + integument score), was compared between feeding groups using Mann-Whitney test. Serum alkaline phosphatase activity (P < 0.001) and globulin concentration (P < 0.001) were lower, while lymphocyte count (P < 0.05) was higher in dogs fed RMBD. No differences were found in urinalysis between diet groups. Dogs fed RMBD showed a slight improvement in CCS compared with kibble-fed dogs (CCS: P = 0.03). Owner management significantly differed with a greater likelihood of management interventions including dietary supplements and sporting activities in the RMBD group. Further work is needed to specifically determine the impact of diet processing and nutrient content on canine health.

Effects of Chronic Viral Infection on Lymphocyte Populations in Middle-aged Baboons (Papio anubis).

Aging of the immune system is characterized by the loss of naïve T-cells, increased inflammation, and immune function impairment. Chronic infection with cytomegalovirus is thought to play a role in age-related changes in immunity. Therefore, to assess the effect of pathogens such as cytomegalovirus on the immune system, we determined lymphocyte populations and inflammatory markers over a 3-y period in captive, middle-age baboons, with various exposure to pathogens and shedding pressure. Groups included SPF (i.e., pathogen-negative; n = 14); large-group, conventionally housed (CONV LG; pathogen- positive; n = 14), and small-group, conventionally housed (CONV SM; pathogen-positive; n = 7). All baboon groups showed a decrease in CD45RA+ CD28+ (i.e., naive) cells over time during middle age, but the rate of decline appeared faster in CONV LG baboons than in the other groups. In addition, the reduction in CD45RA+ CD28+ cells in the CONV LG baboons coincided with higher IgG levels against baboon cytomegalovirus, increased serum cortisol concentration, and a greater inflammatory phenotype. The results of this project support a role for cytomegalovirus infection in immune system alterations in middle-aged baboons.

Genome-Wide Association Analyses of Equine Metabolic Syndrome Phenotypes in Welsh Ponies and Morgan Horses.

Equine metabolic syndrome (EMS) is a complex trait for which few genetic studies have been published. Our study objectives were to perform within breed genome-wide association analyses (GWA) to identify associated loci in two high-risk breeds, coupled with meta-analysis to identify shared and unique loci between breeds. GWA for 12 EMS traits identified 303 and 142 associated genomic regions in 264 Welsh ponies and 286 Morgan horses, respectively. Meta-analysis demonstrated that 65 GWA regions were shared across breeds. Region boundaries were defined based on a fixed-size or the breakdown of linkage disequilibrium, and prioritized if they were: shared between breeds or across traits (high priority), identified in a single GWA cohort (medium priority), or shared across traits with no SNPs reaching genome-wide significance (low priority), resulting in 56 high, 26 medium, and seven low priority regions including 1853 candidate genes in the Welsh ponies; and 39 high, eight medium, and nine low priority regions including 1167 candidate genes in the Morgans. The prioritized regions contained protein-coding genes which were functionally enriched for pathways associated with inflammation, glucose metabolism, or lipid metabolism. These data demonstrate that EMS is a polygenic trait with breed-specific risk alleles as well as those shared across breeds.

Diagnostic Testing for Equine Endocrine Diseases: Confirmation Versus Confusion.

Despite there being only 2 common endocrine diseases in horses, pituitary pars intermedia dysfunction (PPID) and equine metabolic syndrome (EMS), diagnosis is still confusing. Failing to consider horse factors and treating based on laboratory results only have caused many animals to receive lifelong drug treatment unnecessarily. Increased plasma ACTH, baseline or TRH stimulated, supports a diagnosis of PPID; however, breed, age, thriftiness, illness, coat color, geography, diet, and season also affect ACTH concentration. Insulin dysregulation, the hallmark of EMS, can result from insulin resistance or excessive postprandial insulin release. Each requires a different diagnostic test to reach a diagnosis.

Characterization of Baboon Cytomegalovirus Infection in Healthy Adult Baboons (Papio anubis).

Cytomegalovirus (CMV) is a common chronic herpesvirus found in humans and numerous other mammalian species. In people, chronic viruses like CMV can alter overall health and immunity and pose a serious risk for those with an inadequate immune system. In addition, CMV plays an important role in animal health, and could affect the health of vulnerable populations, like endangered species. Previous studies found a high rate of CMV seropositivity among adult baboons (Papio anubis), and results from our laboratory revealed that baboon CMV (BaCMV) seropositivity was correlated with altered immune cell populations. In the current study, we further characterized BaCMV infection in normal, adult baboons. Analysis of blood samples from baboons (age, 6 to 26 y) revealed a low overall prevalence of detectable of BaCMV DNA, with a higher detection rate in aged baboons (older than 15 y). Furthermore, data suggest that individual baboons maintain similar rates of recurrence and levels of BaCMV shedding in saliva over time. Finally, we evaluated multiple commercially available assays for antihuman CMV IgG and IgM for use with baboon sera. Results of this study will improve our understanding of BaCMV and may be directly relevant to other closely related species.

Comparison of two methods for measurement of equine adrenocorticotropin.

Accurate measurement of equine adrenocorticotropin (ACTH) is important for the diagnosis of equine pituitary pars intermedia dysfunction (PPID). Several radioimmunoassays (RIAs) and chemiluminescent immunoassays (CIAs) are used for measurement of ACTH concentration in horses; whether these methods yield similar results across a range of concentrations is not determined. We evaluated agreement between a commercial RIA and CIA. Archived plasma samples ( n = 633) were measured with both assays. Correlation between the 2 methods was moderate ( r = 0.49, p < 0.001). Bland-Altman analysis revealed poor agreement, with a proportional bias and widening limits of agreement with increasing values. Poor agreement between assays was also observed when evaluating plasma samples with concentrations at or below the recommended diagnostic cutoff value for PPID testing. The lack of agreement suggests that measurements obtained should not be considered interchangeable between methods.

Efficacy of the early administration of valacyclovir hydrochloride for the treatment of neuropathogenic equine herpesvirus type-1 infection in horses.

OBJECTIVE To determine whether prophylactic administration of valacyclovir hydrochloride versus initiation of treatment at the onset of fever would differentially protect horses from viral replication and clinical disease attributable to equine herpesvirus type-1 (EHV-1) infection. ANIMALS 18 aged mares. PROCEDURES Horses were randomly assigned to receive an oral placebo (control), treatment at detection of fever, or prophylactic treatment (initiated 1 day prior to viral challenge) and then inoculated intranasally with a neuropathogenic strain of EHV-1. Placebo or valacyclovir was administered orally for 7 or 14 days after EHV-1 inoculation or detection of fever (3 horses/group). Effects of treatment on viral replication and clinical disease were evaluated. Plasma acyclovir concentrations and viremia were assessed to determine inhibitory concentrations of valacyclovir. RESULTS Valacyclovir administration decreased shedding of virus and viremia, compared with findings for control horses. Rectal temperatures and clinical disease scores in horses that received valacyclovir prophylactically for 2 weeks were lower than those in control horses. The severity of but not the risk for ataxia was decreased by valacyclovir administration. Viremia was decreased when steady-state trough plasma acyclovir concentrations were > 0.8 µg/mL, supporting the time-dependent activity of acyclovir. CONCLUSIONS AND CLINICAL RELEVANCE Valacyclovir treatment significantly decreased viral replication and signs of disease in EHV-1-infected horses; effects were greatest when treatment was initiated before viral inoculation, but treatment was also effective when initiated as late as 2 days after inoculation. During an outbreak of equine herpesvirus myeloencephalopathy, antiviral treatment may be initiated in horses at various stages of infection, including horses that have not yet developed signs of viral disease.

Relationship of skeletal muscle inflammation with obesity and obesity-associated hyperinsulinemia in horses.

Local (skeletal muscle and adipose) and systemic inflammation are implicated in the development of obesity-associated insulin resistance in humans. In horses, obesity is neither strongly nor consistently associated with systemic inflammation. The role of skeletal muscle inflammation in the development of insulin dysregulation (insulin resistance or hyperinsulinemia) remains to be determined. We hypothesized that skeletal muscle inflammation is related to obesity-associated hyperinsulinemia in horses. Thirty-five light-breed horses with body condition scores (BCSs) of 3/9 to 9/9 were studied, including 7 obese, normoinsulinemic (BCS ≥ 7, resting serum insulin < 30 µIU/mL) and 6 obese, hyperinsulinemic (resting serum insulin ≥ 30 µIU/mL) horses. Inflammatory biomarkers were evaluated in skeletal muscle biopsies and plasma. Relationships between markers of inflammation and BCS were evaluated. To assess the role of inflammation in obesity-associated hyperinsulinemia, markers of inflammation were compared among lean or ideal, normoinsulinemic (L-NI); obese, normoinsulinemic (O-NI); and obese, hyperinsulinemic (O-HI) horses. Skeletal muscle and plasma tumor necrosis factor alpha (TNFα) concentrations were negatively correlated with BCS. When comparing inflammatory markers among groups, skeletal muscle TNFα was lower in the O-HI group than in the O-NI or L-NI groups. In horses, neither skeletal muscle nor systemic inflammation appears to be positively related to obesity or obesity-associated hyperinsulinemia.

L'inflammation locale (muscle squelettique et tissu adipeux) et systémique sont impliquées dans le développement de la résistance à l'insuline associée à l'obésité chez l'humain. Chez les chevaux, l'obésité n'est pas fortement ou de manière constante associée avec l'inflammation systémique. Le rôle de l'inflammation des muscles squelettiques dans le développement de la dérégulation de l'insuline (résistance à l'insuline ou hyper-insulinémie) reste à être déterminé. Nous avons émis l'hypothèse que chez les chevaux l'inflammation des muscles squelettiques est reliée à l'hyper-insulinémie associée à l'obésité. Trente-cinq chevaux de race légère avec des pointages de condition corporelle (PCCs) variant de 3/9 à 9/9 ont été étudiés, incluant sept chevaux obèses, normo-insulinémique (PCC ≥ 7, insuline sérique au repos < 30 µUI/mL) et six chevaux obèses, hyper-insulinémique (insuline sérique au repos ≥ 30 µUI/mL). Les biomarqueurs de l'inflammation ont été évalués dans des biopsies de muscles squelettiques et le plasma. Les relations entre les marqueurs de l'inflammation et le PCC ont été évaluées. Pour apprécier le rôle de l'inflammation dans l'hyper-insulinémie associée à l'obésité, les marqueurs de l'inflammation ont été comparés parmi les chevaux élancés ou idéal, normo-insulinémique (L-NI); les chevaux obèses, normo-insulinémique (O-NI); et les chevaux obèses, hyperinsulinémique (O-HI). Les concentrations du facteur nécrosant des tumeurs alpha (TNFα) étaient corrélées négativement avec le PCC. Lors de la comparaison des marqueurs de l'inflammation entre les groupes, la concentration de TNFα dans les muscles squelettiques était plus basse dans le groupe O-HI que dans les groupes O-NI ou L-NI. Chez les chevaux, ni l'inflammation systémique ou celle des muscles squelettiques ne semblent reliées positivement à l'obésité ou à l'hyper-insulinémie associée à l'obésité.(Traduit par Docteur Serge Messier).

Immune Dysfunction in Aged Horses.

The aging process in people is associated with changes in adaptive and innate immune responses. Similar changes occur in aged horses. Age-related progressive impairment in the ability to respond to pathogen challenge and an increased inflammatory reactivity may predispose geriatric horses to many diseases of old age. Specific recommendations for immune modification of older horses, including an age-appropriate vaccination schedule, are not currently available. In addition, the effect of old age on risk of infectious disease is poorly documented. More work is needed to better understand the interactions of age on immunity, vaccine response, and disease risk in horses.

Relationship of oxidative stress in skeletal muscle with obesity and obesity-associated hyperinsulinemia in horses.

In horses, hyperinsulinemia and insulin resistance (insulin dysregulation) are associated with the development of laminitis. Although obesity is associated with insulin dysregulation, the mechanism of obesity-associated insulin dysregulation remains to be established. We hypothesized that oxidative stress in skeletal muscle is associated with obesity-associated hyperinsulinemia in horses. Thirty-five light breed horses with body condition scores (BCS) of 3/9 to 9/9 were studied, including 7 obese, normoinsulinemic (BCS ≥ 7, resting serum insulin < 30 µIU/mL) and 6 obese, hyperinsulinemic (resting serum insulin ≥ 30 µIU/mL) horses. Markers of oxidative stress (oxidative damage, mitochondrial function, and antioxidant capacity) were evaluated in skeletal muscle biopsies. A Spearman's rank correlation coefficient was used to determine relationships between markers of oxidative stress and BCS. Furthermore, to assess the role of oxidative stress in obesity-related hyperinsulinemia, markers of antioxidant capacity and oxidative damage were compared among lean, normoinsulinemic (L-NI); obese, normoinsulinemic (O-NI); and obese, hyperinsulinemic (O-HI) horses. Increasing BCS was associated with an increase in gene expression of a mitochondrial protein responsible for mitochondrial biogenesis (estrogen-related receptor alpha, ERRα) and with increased antioxidant enzyme total superoxide dismutase (TotSOD) activity. When groups (L-NI, O-NI, and O-HI) were compared, TotSOD activity was increased and protein carbonyls, a marker of oxidative damage, decreased in the O-HI compared to the L-NI horses. These findings suggest that a protective antioxidant response occurred in the muscle of obese animals and that obesity-associated oxidative damage in skeletal muscle is not central to the pathogenesis of equine hyperinsulinemia.

Chez les chevaux l'hyperinsulinémie et la résistance à l'insuline (dérèglement de l'insuline) sont associées avec le développement de fourbure. Bien que l'obésité soit associée avec le dérèglement de l'insuline, le mécanisme de l'obésité associée au dérèglement de l'insuline demeure à être établi. Nous émettons l'hypothèse que le stress oxydatif dans les muscles squelettiques est associé avec l'obésité associée à l'hyperinsulinémie chez les chevaux. Trente-cinq chevaux de races légères avec des pointages de conditions corporelles (PCC) de 3/9 à 9/9 ont été étudiés, incluant sept chevaux obèses, normo-insulinémique (PCC ≥ 7, insuline sérique au repos < 30 µIU/mL) et six chevaux obèses, hyperinsulinémique (insuline sérique au repos ≥ 30 µIU/mL). Les marqueurs de stress oxydatif (damage oxydatif, fonction mitochondriale, et capacité antioxydante) furent évalués dans des biopsies de muscles squelettiques. Un coefficient de corrélation de rang de Spearman a été utilisé pour déterminer la relation entre les marqueurs de stress oxydatif et le PCC. De plus, pour évaluer le rôle du stress oxydatif dans l'obésité reliée à l'hyperinsulinémie, les marqueurs de la capacité anti-oxydante et des dommages oxydatifs ont été comparés entre des chevaux minces, normo-insulinémiques (L-NI); des chevaux obèses, normo-insulinémique (O-NI); et des chevaux obèses, hyperinsulinémiques (O-HI). Une augmentation des PCCs était associée avec une augmentation de l'expression des gènes d'une protéine mitochondriale responsable de la biogénèse des mitochondries (récepteur alpha apparenté aux estrogènes, ERRα) et d'une augmentation de l'activité anti-oxydante totale de l'enzyme superoxyde dismutase (TotSOD). Lors de la comparaison des groupes (L-NI, O-NI, et O-HI), l'activité TotSOD était augmentée et les carbonyles protéiques, un marqueur des dommages oxydatifs, avaient diminué chez les chevaux O-HI comparativement aux chevaux L-NI. Ces données suggèrent qu'une réponse anti-oxydante protectrice s'est produite dans le muscle des chevaux obèses et que le dommage oxydatif associés à l'obésité dans les muscles squelettiques n'est pas central à la pathogénèse de l'hyperinsulinémie équine.(Traduit par Docteur Serge Messier).

Neutrophil function in healthy aged horses and horses with pituitary dysfunction.

Immunosuppression leading to opportunist bacterial infection is a well-recognized sequela of equine pituitary pars intermedia dysfunction (PPID). The mechanisms responsible for immune dysfunction in PPID however, are as of yet poorly characterized. Horses with PPID have high concentrations of hormones known to impact immune function including α-melanocyte stimulating hormone (α-MSH) and insulin. α-MSH and related melanocortins have been shown in rodents and people to impair neutrophil function by decreasing superoxide production (known as oxidative burst activity), migration and adhesion. The goal of this study was to determine if neutrophil function is impaired in horses with PPID and, if so, to determine if plasma α-MSH or insulin concentration correlated with the severity of neutrophil dysfunction. Specifically, neutrophil phagocytosis, oxidative burst activity, chemotaxis and adhesion were assessed. Results of this study indicate that horses with PPID have reduced neutrophil function, characterized by decreased oxidative burst activity and adhesion. In addition, chemotaxis was greater in healthy aged horses than in young horses or aged horses with PPID. Plasma insulin: α-MSH ratio, but not individual hormone concentration was correlated to neutrophil oxidative burst activity. In summary, neutrophil function is impaired in horses with PPID, likely due to altered hormone concentrations and may contribute to increased risk of opportunistic infections. Whether regulation of hormone concentration profiles in horses with PPID using therapeutic intervention improves neutrophil function and reduces infections needs to be explored.

The effects of age and cytomegalovirus on markers of inflammation and lymphocyte populations in captive baboons.

The human immune system undergoes age-related changes that can lead to increased disease susceptibility. Using the baboon as a model for human immune system aging, we examined age-related changes in relative and absolute numbers of T cell subpopulations, cytomegalovirus (CMV) titer and markers of inflammation. In addition, the effect of gender, social status and peer group on lymphocyte subpopulations was determined. Relative and absolute numbers of total lymphocytes (CD3+), T helper cells (CD4+), and cytotoxic T cells (CD8+) increased with age. The proportion of naïve T cells (CD45RA+) decreased, while the total number of cells negative for the co-stimulatory receptor, CD28 (CD28-) increased in an age-dependent manner. Furthermore, CMV titers were negatively correlated with the number of naive CD4+ cells. IL-6 and cortisol concentration were also negatively associated with T cell subpopulations. Additionally, socially dominant baboons exhibited decreases in naïve CD4+ and CD8+ cells (by 65% and 52%, respectively) compared to subordinate animals. These results suggest that factors such as CMV exposure and inflammation may contribute to the age-related decline in immune health and indicate that factors like social status should be considered when studying immunosenescence in animal models.

Comparison of two methods for measurement of equine insulin.

Diagnosis of equine hyperinsulinemia requires an accurate method for quantification of equine insulin concentrations. The objectives of the current study were to compare 2 commercially available techniques for measurement of equine insulin, the radioimmunoassay (RIA) and chemiluminescent immunoassay (CIA). Recovery was poor for both assays, but worse for the CIA. Serial dilution of a high endogenous insulin sample yielded better linearity for the RIA ( r2 = 0.99, P < 0.001) than the CIA ( r2 = 0.92, P = 0.009). Bland-Altman analysis indicated that the CIA was, on average, 91 pmol/l higher than the RIA, with wide limits of agreement (95% limits of agreement: -508 to 691 pmol/l). These findings suggest that results between the assays should not be considered interchangeable.