PPID
Peptidyl-prolyl cis-trans isomerase D (EC 5.2.1.8) (PPIase D) (40 kDa peptidyl-prolyl cis-trans isomerase) (Cyclophilin-40) (CYP-40) (Cyclophilin-related protein) (Rotamase D) [CYP40] [CYPD]
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Similarly to aged humans, senior horses (≥20 years) exhibit chronic low-grade inflammation systemically, known as inflamm-aging. Inflamm-aging in the senior horse has been characterized by increased circulating inflammatory cytokines as well as increased inflammatory cytokine production by lymphocytes and monocytes in response to a mitogen. Little is currently known regarding underlying causes of inflamm-aging. However, senior horses are also known to present with muscle wasting and often the endocrinopathy pituitary pars intermedia dysfunction (PPID). Despite the concurrence of these phenomena, the relationships inflamm-aging may have with measures of body composition and pituitary function in the horse remain unknown. Furthermore, nutrition has been a focus of research in an attempt to promote health span as well as life span in senior horses, with some nutrients, such as omega-3 fatty acids, having known anti-inflammatory effects. Thus, an exploratory study of a population of n = 42 similarly-managed senior horses was conducted to determine relationships between inflamm-aging and measures of circulating nutrients, body composition, age, and PPID. Serum was collected to determine vitamin, mineral, and fatty acid content. Peripheral blood mononuclear cells were also isolated to determine inflammatory cytokine production of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) following stimulation with a mitogen, as well as to determine gene expression of interleukin(IL)-1β, IL-6, IL-10, IFN-γ, and TNF-α. Serum IL-6 and C-reactive protein were determined by enzyme-linked immunosorbent assay. Whole blood was collected for hematological and biochemical analysis. Body composition was evaluated via ultrasound and muscle scoring for all 42 horses as well as by deuterium oxide dilution for a subset of n = 10 horses. Pituitary function was evaluated by measuring basal adrenocorticotropin hormone concentrations as well as by thyrotropin releasing hormone stimulation testing (to determine PPID status). Results showed various relationships between inflammatory markers and the other variables measured. Most notably, docosadienoic acid (C22:2n6c), docosapentaenoic acid (C22:5n3c), and folate were positively associated with numerous inflammatory parameters (P ≤ 0.05). Although no relationships were found between inflamm-aging and PPID, being positive for PPID was negatively associated with vitamin B12 (P ≤ 0.01). No relationships between inflammation and body composition were found. Even within this senior horse population, age was associated with multiple parameters, particularly with numerous inflammatory cytokines and fatty acids. In summary, inflamm-aging exhibited relationships with various other parameters examined, particularly with certain fatty acids. This exploratory study provides insights into physiological changes associated with inflamm-aging in the senior horse.
MeSH Terms
- Aging
- Animals
- Body Composition
- Cytokines
- Female
- Folic Acid
- Horse Diseases
- Horses
- Inflammation
- Male
- Nutrients
- Pituitary Diseases
- Pituitary Gland, Intermediate
Keywords
- Horse
- Inflamm-aging
- Muscle
- Nutrition
- Pituitary pars intermedia dysfunction
- Senior
Pituitary pars intermedia dysfunction (PPID) is caused by an age-related degenerative disease of dopaminergic neurones. Despite its importance in equine practice, available information regarding its epidemiology is limited. This systematic review aimed to assess published literature to evaluate available evidence regarding the clinical presentation, prevalence and risk factors for PPID in horses and ponies. Electronic database searches were undertaken using a range of terms, and English language publications published prior to August 2016 were included. Both authors independently reviewed screened papers for inclusion, extracted data, and assessed the quality of reporting using predefined criteria. Data were extracted using modified critically appraised topic data collection forms. Meta-analysis was not undertaken due to marked between-study variations. Following removal of duplicate records, of 358 published papers yielded by the search, 97 abstracts were screened for eligibility and 29 publications meeting inclusion criteria were included in the review. Most studies reviewed were case series or cross-sectional studies, with considerable variation in study populations and PPID case definition. Hypertrichosis and/or other hair coat abnormalities, laminitis and epaxial muscle wastage or muscle atrophy are the most frequently reported clinical signs, with prevalence of these signs increasing with increasing horse age. The most robust prevalence estimates for PPID were 21.2% in horses and ponies aged ≥15 years and 2.9% amongst the general equine population. Findings regarding breed and sex predispositions were equivocal and only increasing age has been identified as a significant risk factor for PPID.
MeSH Terms
- Aging
- Animals
- Female
- Horse Diseases
- Horses
- Male
- Neurodegenerative Diseases
- Pituitary Diseases
- Pituitary Gland, Intermediate
- Risk Factors
Keywords
- Cushing’s disease
- Geriatric
- Horse
- Hypertrichosis
- Laminitis
Increased free cortisol fraction is associated with insulin dysregulation (ID) in people with Metabolic Syndrome and Cushing's Disease. Free cortisol has not been investigated in equine endocrine disorders. (1) In healthy horses, sex, age, body condition score (BCS), and season impact free cortisol; (2) free cortisol is increased in horses with Pituitary Pars Intermedia Dysfunction (PPID) or Equine Metabolic Syndrome (EMS). Fifty-seven healthy horses; 40 horses and ponies with PPID (n = 20) or EMS (n = 20). Prospective study. Serum collected seasonally from healthy animals and archived serum from PPID and EMS animals was analyzed for insulin, total and free cortisol concentrations, and free cortisol fraction (FCF). Linear mixed models were used to determine effects of age, sex, season, and BCS on hormones in controls. Hormone measurements were compared between disease groups and age- and season-matched controls with t-tests. EMS and hyperinsulinemic PPID animals were combined in an ID (hyperinsulinemia) group. Free cortisol concentrations were increased in overweight/obese controls (0.3 ± 0.1 μg/dL) compared to lean controls (0.2 ± 0.1 μg/dL; P = .017). Mean FCF was significantly higher in animals with PPID (8.8 ± 5.8 μg/dL, P = .005) or ID (8.8 ± 10.2 μg/dL, P = .039) than controls (5.0 ± 0.9 μg/dL), but total cortisol concentrations were similar (P ≥ .350) (PPID: 4.2 ± 4.3 μg/dL; ID: 5.0 ± 4.5 μg/dL; controls: 4.6 ± 1.7 and 5.1 ± 2.1 μg/dL). Increased FCF is associated with obesity in healthy horses and with ID (hyperinsulinemia) in horses and ponies with endocrine disease. Decreased plasma cortisol-binding capacity could be a component of these endocrine disorders in horses.
MeSH Terms
- Aging
- Animals
- Body Composition
- Case-Control Studies
- Female
- Horse Diseases
- Horses
- Hydrocortisone
- Insulin
- Male
- Metabolic Syndrome
- Pituitary Diseases
- Seasons
Keywords
- Equine
- Equine Metabolic Syndrome
- Insulin resistance
- Obesity
- Pituitary pars intermedia dysfunction
- Steroid
The aim of this study was to characterize the age-related morphological changes in the equine pituitary and to identify features that allow distinction between pituitary pars intermedia dysfunction (PPID)-associated and non-functional/age-associated pars intermedia (PI) adenoma. Pituitary glands of all horses submitted for necropsy examination at the Institute of Veterinary Pathology, Ludwig Maximilians University Munich, between 2008 and 2012 were examined. The pituitary glands of 124 horses were weighed, cut into ∼2 mm slices and examined histologically. A slightly modified grading scheme (grades 1-5) was applied to evaluate histological alterations of the PI semiquantitatively. The volume fractions and total volumes of the three pituitary lobes, PI, pars distalis (PD) and pars nervosa (PN), as well as the total number and mean size of PI cells (PICs), were determined using state-of-the-art quantitative stereological methods. There were significant associations between histological grade, the appearance of PI adenomas, follicles and cysts in the PI, lipofuscin in the PN (P <0.001) and focal hyperplasia of chromophobes in the PD and age. In contrast, the appearance of follicles and cysts in the PD, invasion of basophil cells into the PN, haemorrhage and necrosis were not age dependent. PI adenomas were observed in 18% (22/124) of the animals, but only four horses were evidently suffering from PPID, therefore clinically overt/PPID-associated PI adenomas were found in 3% (4/124) of all horses. Most PI adenomas were incidental and considered non-functional. Pituitary weight, PI volume, total number and mean volume of PICs increased with age in all horses. The total PI volume and the number of PICs of horses exhibiting PPID-associated PI adenomas were significantly higher, while the mean size of PICs was smaller compared with that of horses showing non-PPID-associated adenoma, which suggests that different growth processes are responsible for adenoma formation. The present study demonstrated various age-associated lesions of the PD and PN and revealed a high frequency of incidental, non-PPID-associated PI adenomas in aged horses. Therefore, post-mortem diagnosis of PPID in horses is possible, by determination of pituitary weight and by demonstration of PIC hyperplasia, using quantitative stereological methods.
MeSH Terms
- Adenoma
- Aging
- Animals
- Horse Diseases
- Horses
- Pituitary Gland
- Pituitary Neoplasms
Keywords
- endocrine disease
- horse
- morphometry
- pituitary pars intermedia dysfunction
Postmortem findings in 241 equids admitted to a teaching hospital that were at least 15 years old at autopsy were reviewed (1) to determine disease prevalence, (2) to compare the cause of death (or euthanasia) in equids 15 to 19 years of age (n = 116) with that in equids ≥20 years of age (n = 125), and (3) to catalog coexisting lesions in equids with pituitary pars intermedia dysfunction (PPID). Breed and sex were evenly distributed between the age groups. Death or euthanasia was attributed to disease of the digestive system (41.5%), pituitary gland (12.9%), locomotor system (10.0%), nervous system (7.9%), cardiovascular system (4.6%), urinary system (4.6%), reproductive system (4.2%), respiratory system (4.2%), integumentary system (4.2%), lymphoid system (2.5%), liver (2.5%), or systemic neoplasia (1.2%). Nervous system disease was more common in the 15- to 19-year group; urinary tract disease was more common in the ≥20-year group. Neoplastic disease, regardless of systemic location, was the basis for death or euthanasia in 18.7% of all equids. Squamous cell carcinoma, lymphoma, and melanoma were the most common malignant neoplasms. PPID was the most common specific diagnosis, based on the postmortem presence of hyperplasia or adenoma, and was the reason for euthanasia in 47.7% of 65 equids with PPID. The most common nonpituitary causes for death or euthanasia in equids with PPID were colic, lameness, cancer, and spinal cord disease. Coexisting conditions in equids with PPID that were not considered the basis for euthanasia included neoplasms, infections, lameness, and recurrent airway obstruction.
MeSH Terms
- Age Factors
- Aging
- Animals
- Cause of Death
- Diagnosis
- Digestive System Diseases
- Endocrine System Diseases
- Female
- Geriatrics
- Horse Diseases
- Horses
- Lameness, Animal
- Male
- Nervous System Diseases
- Pituitary Diseases
- Pituitary Gland, Intermediate
- Pituitary Neoplasms
Keywords
- aging
- alimentary diseases
- cause of death
- endocrine diseases
- geriatrics
- horse diseases
- locomotor system diseases
- pituitary adenoma
- pituitary pars intermedia dysfunction
Equine pituitary pars intermedia dysfunction (PPID) has been associated with reduced insulin sensitivity in comparison with younger adult horses; however, the difference in insulin sensitivity between horses with PPID and aged-matched controls has not been well characterized. The objective of the study was to determine if aged horses with PPID had reduced insulin sensitivity and alterations in the insulin-mediated signaling pathways in the skeletal muscle when compared with healthy aged horses. Isoglycemic hyperinsulinemic clamp procedures were conducted in 12 horses that were classified as either PPID (n = 6; age: 25.0 ± 2.5 yr; mean ± standard deviation) or non-PPID, aged-matched controls (control) (n = 6; age: 25.7 ± 2.0 yr). Blood samples were taken before and during the clamp procedures to measure plasma glucose, insulin, and amino acid concentrations, and 2 muscle biopsies were collected from the gluteus medius muscle, one in the basal state and the second at the end of the clamp procedure (insulin-stimulated state). Plasma insulin concentrations increased ∼9-fold during the clamp compared with basal conditions (P < 0.001) in both groups. During the last 30 min of the clamp, the rate of glucose infusion required to maintain isoglycemia in horses with PPID was similar to that in the control horses (P = 0.67). The plasma concentrations of most indispensible amino acids were lower in the insulin-stimulated state than the basal state (P < 0.05). PPID status did not have an effect on the activation of factors associated with protein synthesis and breakdown; however, factors associated with protein synthesis had increased phosphorylation in the insulin-stimulated state, compared with basal. The results from this study provide evidence that PPID is not always associated with impairments in insulin sensitivity.
MeSH Terms
- Aging
- Animals
- Female
- Gene Expression Regulation
- Glucose Clamp Technique
- Horse Diseases
- Horses
- Insulin Resistance
- Male
- Muscle, Skeletal
- Pituitary Diseases
- Pituitary Gland, Intermediate
- Signal Transduction
Keywords
- Equine
- Insulin sensitivity
- Isoglycemic hyperinsulinemic clamp
- PPID
- Protein metabolism
To determine effects of age and pituitary pars intermedia dysfunction (PPID) on corneal sensitivity in horses. 20 adult horses allocated into 3 groups (PPID group, old [> 15 years old] horses with PPID [n = 5]; old group, old [> 15 years old] horses without PPID [9]; and young group, young [≤ 10 years old] horses without PPID [6]). All horses with PPID had hirsutism and abnormal fat deposition or laminitis; none of the old or young horses had hirsutism, abnormal fat deposition, or laminitis. A Cochet-Bonnet aesthesiometer was used to measure the corneal touch threshold (CTT) in both eyes of each horse. The nylon monofilament was applied at a maximum length of 60 mm to the central region of the cornea and length was decreased by 5-mm increments until a consistent blink response was elicited. Tear production was assessed in all eyes via the Shirmer tear test (STT). Mean ± SD CTT was significantly greater for young horses (47.50 ± 4.52 mm) than for horses in the old (28.06 ± 5.72 mm) and PPID (21.5 ± 3.37 mm) groups. Old horses had significantly higher CTT values than did horses with PPID. The STT values were within the reference range for all groups and did not differ significantly among groups. Corneal sensitivity decreased with both age and PPID. Because decreased corneal sensitivity is associated with impaired wound healing, increasing age and PPID may increase the risk for nonhealing or recurrent corneal ulcers in horses.
MeSH Terms
- Aging
- Animals
- Cornea
- Female
- Horse Diseases
- Horses
- Male
- Pituitary Diseases
- Pituitary Gland, Intermediate
Pituitary pars intermedia dysfunction (PPID) in older equids is commonly recognized by a long hair coat that fails to shed. The aim of this study was to compare hair follicle stages in PPID-affected horses with excessively long hair coats with the stages of normal aged horses (controls) and to compare hair follicle stages in PPID-affected horses after 6 months of treatment with pergolide mesylate with those of control horses. Eight PPID-affected horses and four normal, age-matched, control horses. Skin biopsies were collected from the neck and rump of PPID-affected and control horses. A diagnosis of PPID was established based on hair coat changes and supportive overnight dexamethasone suppression test results. Skin biopsies were repeated after 6 months of treatment with pergolide. The number of hair follicles in anagen (A) or telogen (T) was counted for each skin biopsy using transverse sections. Pretreatment biopsies had a greater percentage of A follicles (neck 96%, rump 95%) and a lower percentage of T follicles (neck 4%, rump 5%) in PPID-affected horses than in control horses (A, neck 15%, rump 25%; and T, neck 85%, rump 75%). After treatment with pergolide, all PPID-affected horses had improved shedding, and the percentages of A follicles (neck 69%, rump 70%) and T follicles (neck 31%, rump 30%) were not different from untreated control horses (A, neck 68%, rump 82%; and T, neck 32%, rump 18%). These findings document that excessive hair growth (hypertrichosis) in PPID-affected horses is due to persistence of hair follicles in A. Furthermore, treatment with pergolide improved shedding and reduced the percentage of A follicles in PPID-affected horses.
MeSH Terms
- Aging
- Animals
- Dopamine Agonists
- Female
- Hair
- Hair Follicle
- Horse Diseases
- Horses
- Male
- Pergolide
- Pituitary Diseases
- Pituitary Gland, Intermediate