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Biomedical subjects

P A Harris

Publications and source records attributed to P A Harris.

At least 19 recordsLinked to original sources

Insulin resistance and compensation in Thoroughbred weanlings adapted to high-glycemic meals.

Insulin resistance has been suggested to increase the risk of certain diseases, including osteochondrosis and laminitis. Our objective was to evaluate the effect of adaptation to high-glycemic meals on glucose-insulin regulation in healthy Thoroughbred weanlings. Twelve Thoroughbred foals were raised on pasture and supplemented twice daily with a feed high in either sugar and starch (SS; 49% nonstructural carbohydrates, 21% NDF, 3% crude fat on a DM basis) or fat and fiber (FF; 12% nonstructural carbohydrates, 44% NDF, 10% crude fat on a DM basis). As weanlings (age 199 +/- 5 d; BW 274 +/- 5 kg) the subjects underwent a modified frequently sampled i.v. glucose tolerance test. A series of 39 blood samples was collected from -60 to 360 min, with a glucose bolus of 300 mg/kg BW injected at 0 min and an insulin bolus of 1.5 mIU/kg BW at 20 min. All samples were analyzed for glucose and insulin, and basal samples also were analyzed for plasma cortisol, triglyceride, and IGF-I. The minimal model of glucose and insulin dynamics was used to determine insulin sensitivity (SI), glucose effectiveness, acute insulin response to glucose (AIRg), and disposition index (DI). Insulin sensitivity was 37% less (P = 0.007) in weanlings fed SS than in those fed FF; however, DI did not differ (P = 0.65) between diets because AIRg tended to be negatively correlated with SI (r = -0.55; P = 0.067). This finding indicates that the SI decrease was compensated by AIRg in the weanlings adapted to SS. This compensation was further demonstrated by greater insulin concentrations in SS-adapted weanlings compared with FF-adapted weanlings at 11 of 36 sample points (P < 0.055) and greater (P = 0.040) total area under the insulin curve in SS than in FF weanlings. Plasma cortisol and triglycerides did not differ between dietary groups, but IGF-I was greater (P = 0.001) in SS weanlings. Despite appearing healthy, horses adapted to high-glycemic feeds may exhibit changes in altered insulin sensitivity and compensation that increase the risk of diseases involving insulin resistance. These changes seem to be partially amenable to dietary management.

Animal Feed↗

Antioxidant and inflammatory responses of healthy horses and horses affected by recurrent airway obstruction to inhaled ozone.

REASONS FOR PERFORMING STUDY: Inhaled ozone can induce oxidative injury and airway inflammation. Horses affected by recurrent airway obstruction (RAO) have a decreased pulmonary antioxidant capacity, which may render them more susceptible to oxidative challenge. It is currently unknown whether RAO-affected horses are more susceptible to oxidative stress than those unaffected by RAO. OBJECTIVES: To determine whether ozone exposure induces greater oxidative stress and airway inflammation in RAO-affected horses in remission than in healthy horses. METHODS: Seven healthy control horses and 7 RAO-affected horses were exposed to 0.8 ppm ozone for 2 h at rest. RESULTS: At baseline, bronchoalveolar lavage fluid (BALF) ascorbic acid concentrations were lower in RAO-affected horses than healthy controls. Ozone appeared to preferentially oxidise glutathione rather than ascorbic acid 6 h after exposure. Individual healthy and RAO-affected horses demonstrated oxidation of BALF glutathione after ozone exposure. Overall, RAO-affected horses did not demonstrate increased oxidative stress following ozone exposure, compared with healthy horses. Ozone did not induce significant airway inflammation in either group. CONCLUSIONS: RAO-affected horses in remission are not more sensitive to ozone despite a decreased pulmonary antioxidant capacity. Sensitivity to ozone appears to be independent of initial pulmonary antioxidant status. POTENTIAL RELEVANCE: Horses with high susceptibility to oxidative stress may benefit from antioxidant supplementation.

Animals↗

Antioxidant supplementation and subsequent oxidative stress of horses during an 80-km endurance race.

This study tested the development of oxidative stress and the effects of antioxidant supplementation in an 80-km ride. A precompetition survey revealed that no competitor would participate without vitamin E supplementation; therefore, 46 horses were paired for past performances and randomly assigned to two groups of 23 each for 3 wk of supplementation before the ride. One group (E) was orally supplemented with 5,000 IU of vitamin E per day; the other group (E+C) received that dose of vitamin E plus 7 g/d of vitamin C. Blood samples, temperature, and heart rate were taken the day before the race, at 21 and 56 km during the ride, at completion, and after 20 min of recovery. Plasma was assayed for lipid hydroperoxides, alpha-tocopherol, total ascorbate, albumin, creatine kinase (CK), and aspartate aminotransferase (AST). Total glutathione and glutathione peroxidase activity were determined in red blood cells and white blood cells. Thirty-four horses completed the race, 12 horses (six in E and six in E+C) did not finish for reasons including lameness, metabolic problems, and rider option. Plasma ascorbate was higher (P = 0.045) in the E+C group than in the E group. Other than ascorbate, neither antioxidant status nor CK and AST activities were affected by supplementation with E+C vs. E. Red blood cell glutathione peroxidase, white blood cell total glutathione, lipid hydroperoxides, CK, and AST increased, and red blood cell total glutathione and white blood cell glutathione peroxidase activity decreased with distance (P < 0.001). Positive correlations were found for plasma lipid hydroperoxides on CK (r = 0.25; P = 0.001) and AST (r = 0.33; P < 0.001). These results establish an association between muscle leakage and a cumulative index of oxidative stress.

Animal Welfare↗

Growth rate consists of baseline and systematic deviation components in Thoroughbreds.

The objective of this study was to establish a procedure for differentiating a baseline curve from a systematic deviation in weight-age data, and hence to develop a physiological growth model for the Thoroughbred. A total of 2,698 records for 175 foals was obtained during a period of 8 yr (1994 to 2001). Weight-age data were fit with a sigmoid growth equation, W = A(1 + be(-kt))M, where W is BW at age t, A is the asymptotic value of W, b is a scaling parameter that defines the degree of maturity at t = 0, k is a rate constant, and M defines the point of inflection in the sigmoid curve in relation to age. Short-term systematic deviations in the weight-age data were identified by a goodness-of-fit procedure and illustrated in three-dimensional contour plots of the sigmoid equation parameters as they changed upon removal of selected subsets of the data. Based on features of the contour plots, a negative deviation between 210 and 420 d of age was set aside, with the remaining data establishing the baseline data set. The sigmoid growth equation was fit to the baseline data set using a nonlinear mixed model with repeated measures, and indicated a mature weight of 542 +/- 6.2 kg reached at 7 yr. The systematic deviation identified in this weight-age data set is present in other published Thoroughbred growth data and is likely to result in erroneous parameter estimates if not set aside before fitting sigmoid growth equations to the thus-modified weight-age data set. The techniques developed in this study enable identification of short-term systematic deviations in weight-age data and define a realistic baseline growth curve. Differentiation of these two components enables the development of a physiological model of growth that distinguishes between baseline growth and environmental influences, represented respectively, by the baseline curve and the systematic deviation.

Animals↗

Fat digestibility in Equus caballus follows increasing first-order kinetics.

The digestibility of ether extract varies greatly from forages to grains and further to added fats consisting mainly of triglycerides. This variation has been attributed to two main factors, the presence of nonhydrolyzable substances in the ether extract, especially in leafy foods, and the dilution of endogenous fecal fat. A compilation of results from 188 equine digestion balance observations on five basal feeds and 18 test feeds with added fats demonstrated a true digestibility of fat approaching 100% and an endogenous fecal fat of 0.22 g x d(-1) x kg BW(-1). The results revealed that nonhydrolyzable ether extract and endogenous fecal fat were insufficient to account for the difference between true digestibility and apparent digestibilities of ether extract in basal feeds and partial digestibilities of added fats in test feeds. A third possible contributing factor was demonstrated: an increasing first-order relationship between observed digestibilities (D, %) and the fat content of the feed (F, g/kg): D = 92.0 - 92.0e(-F/342). r2 = 0.81, P < 0.001. This equation indicates that 46% digestibility (half maximum) occurs at an ether extract or fat content of 24 g/kg, which is common in forages. It is consistent with fat digestibility or efficiency of absorption being a function of the rate of lipolysis, especially when residence time in the small intestine is limited. Consequently, we suggest that the kinetics of lipases, which are difficult to measure, may contribute to low digestibility when substrate concentration in the small intestine is low due to a low fat content in food. The status of vitamins A and E might be affected by low dietary fat contents and might be improved by fat supplementation.

Animal Feed↗

Weight prediction from linear measures of growing Thoroughbreds.

REASON FOR PERFORMING STUDY: Monitoring weight of foals is a useful management practice to aid in maximising athletic potential while minimising risks associated with deviations from normal growth. OBJECTIVE: To develop predictive equations for weight, based on linear measurements of growing Thoroughbreds (TBs). METHODS: Morphometric equations predicting weight from measurements of the trunk and legs were developed from data of 153 foals. The accuracy, precision and bias of the best fitting equation were compared to published equations using a naive data set of 22 foals. RESULTS: Accuracy and precision were maximised with a broken line relating calculated volumes (V(t + l)) to measured weights. Use of the broken line is a 2 step process. V(t + l) is calculated from linear measures (m) of girth (G), carpus circumference (C), and length of body (B) and left forelimb (F). V(t + I) = ([G2 x B] + 4[C2 x F]) 4pi. If V(t + l) < 0.27 m3, weight is estimated: Weight (kg) = V(t + l) x 1093. If V(t + l) > or = 0.27 m3: Weight (kg) = V(t + l) x 984 + 24. The broken line was more accurate and precise than 3 published equations predicting the weight of young TBs. CONCLUSIONS: Estimation of weight using morphometric equations requires attention to temporal changes in body shape and density; hence, a broken line is needed. Including calculated leg volume in the broken line model is another contributing factor to improvement in predictive capability. POTENTIAL RELEVANCE: The broken line maximises its value to equine professionals through its accuracy, precision and convenience.

Animal Nutritional Physiological Phenomena↗

In vitro and in vivo studies of homocysteine in equine tissues: implications for the pathophysiology of laminitis.

REASONS FOR PERFORMING STUDY: Elevated plasma homocysteine (HCy) concentration is a risk factor for cardiovascular diseases associated with endothelial dysfunction, including the human digital ischaemic disease, Raynaud's phenomenon. HYPOTHESIS: HCy causes dysfunction of equine vascular endothelium and elevated plasma concentrations predispose to laminitis. OBJECTIVES: To determine 1) the concentration of HCy in vitro, which inhibits equine vascular endothelial cell function and 2) any association between risk of laminitis and plasma HCy concentration. METHODS: Endothelial function was studied by measuring endothelium-dependent vasodilatory responses of the equine isolated perfused digit and basal nitric oxide (NO) production by cultured equine digital vein endothelial cells (EDVECs). Total plasma HCy (tHCy) concentrations were measured in samples collected in the winter and spring from normal ponies and ponies predisposed to laminitis. RESULTS: HCy (10 and 100 micromol/l) inhibited endothelial function and, at concentrations above 100 micromol/l, inhibited NO production by EDVECs. Plasma tHCy concentration ranged from 13 to 14.7 micromol/l. There was no effect of season or disease status on the concentration measured. CONCLUSIONS: In vitro, HCy was shown to interfere with endothelial cell function at physiologically relevant concentrations. No evidence was found for an association between risk of laminitis and high plasma concentrations of HCy. POTENTIAL RELEVANCE: Elevated plasma HCy concentrations could adversely affect endothelial cell function and mangement regimens that lead to increases in plasma HCy concentration should be avoided in ponies predisposed to laminitis.

Animals↗

A common beta1-adrenergic receptor polymorphism (Arg389Gly) affects blood pressure response to beta-blockade.

BACKGROUND: A common polymorphism of the beta(1)-adrenergic receptor Arg389Gly markedly affects function in vitro, but little is known about its in vivo significance. METHODS AND RESULTS: Resting and exercise hemodynamic responses were measured in subjects homozygous for Arg389 (n = 21) or Gly389 (n = 13) alleles before and 3 hours after administration of a beta-blocker, atenolol. Demographic characteristics and atenolol concentrations were similar in the two genotypic groups. Genotype had a marked effect on resting hemodynamic responses to atenolol, with Arg389-homozygous subjects having a larger decrease in resting systolic blood pressure (8.7 +/- 1.3 mm Hg versus 0.2 +/- 1.7 mm Hg, P < .001) and mean arterial blood pressure (7.2 +/- 1.0 mm Hg versus 2.0 +/- 1.7 mm Hg, P = .009). Attenuation of exercise-induced hemodynamic responses by atenolol was not affected by genotype. CONCLUSIONS: There is reduced sensitivity of Gly389 homozygotes to a beta-adrenergic receptor antagonist, and this polymorphism may be an important determinant of variability in response to beta-blockade.

Adrenergic beta-Antagonists↗

Identification of equine cecal bacteria producing amines in an in vitro model of carbohydrate overload.

Acute laminitis has been associated with the overgrowth of gram-positive bacteria within the equine hindgut, causing the release of factor(s) leading to ischemia-reperfusion of the digits. The products of fermentation which trigger acute laminitis are, as yet, unknown; however, vasoactive amines are possible candidates. The objectives of this study were to use an in vitro model of carbohydrate overload to study the change in populations of cecal streptococci and lactobacilli and to establish whether certain species of these bacteria were capable of producing vasoactive amines from amino acids. Cecal contents from 10 horses were divided into aliquots and incubated anaerobically with either corn starch or inulin (fructan; both at 1 g/100 ml). Samples were taken at 6-h intervals over a 24-h period for enumeration of streptococci, lactobacilli, and gram-negative anaerobes by a dilution method onto standard selective growth media. The effects of the antibiotic virginiamycin (1 mg/100 ml) and calcium hydrogen phosphate (CaHPO(4); 0.3 g/100 ml) were also examined. Fermentation of excess carbohydrate was associated with increases in numbers of streptococci and lactobacilli (2- to 3.5-log unit increases; inhibited by virginiamycin) but numbers of gram-negative anaerobes were not significantly affected. A screening agar technique followed by 16S rRNA gene sequence analysis enabled the identification of 26 different bacterial strains capable of producing one or more vasoactive amines. These included members of the species Streptococcus bovis and five different Lactobacillus spp. These data suggest that certain bacteria, whose overgrowth is associated with carbohydrate fermentation, are capable of producing vasoactive amines which may play a role in the pathogenesis of acute laminitis.

Acute Disease↗

Glucose clearance in grazing mares is affected by diet, pregnancy, and lactation.

The glucose tolerance test in the horse may be used to determine metabolic responses to diet, disease, or physiologic state. The objective of this study was to determine the effect of reproductive stage (gestation and lactation) and supplemental dietary energy source (sugar and starch [SS] or fiber and fat [FF]) on glucose metabolism in grazing mares using an oral glucose tolerance test. Twelve mares, six on each supplement, were examined on three occasions: one in the third trimester of pregnancy, the second in early lactation, and the third in late lactation. During each test, venous samples were taken at 30 and 1 min before, and 30, 60, 90, 120, 150, 180, 240, and 300 min after a nasogastric dose of glucose at 0.2 g/kg of BW. Plasma was assayed for glucose, insulin, and cortisol. Statistical analysis was a mixed model with repeated measures with horse, diet, and reproductive stage as fixed effects. The incremental glucose area under the curve (AUC) in response to oral glucose was lower in SS than in FF mares (P = 0.022). Mares tended to have a lower incremental glucose AUC in early lactation than in late gestation (P = 0.057), and insulin AUC was lower in early lactation than in late gestation (P = 0.002) and late lactation (P = 0.013). Glucose clearance was more rapid (P = 0.007) in SS than in FF mares. The glycemic response to the oral glucose tolerance test was consistent with adaptation to dietary sugar and starch as well as metabolic changes associated with pregnancy and lactation. Feeding twice-daily grain meals rich in SS influenced glucose metabolism in horses to an extent that the natural adaptation of glucose metabolism to pregnancy was moderated. Feeding a diet rich in FF more closely mimics the natural grazing state of pasture and allows for adaptation of glucose metabolism to pregnancy and lactation.

Adaptation, Physiological↗

Obesity and diet affect glucose dynamics and insulin sensitivity in Thoroughbred geldings.

Insulin resistance is considered a risk factor in obesity, laminitis, exertional rhabdomyolysis, and osteochondrosis. The objective was to use the minimal model to estimate glucose effectiveness (Sg) and insulin sensitivity (Si) in nonobese to obese horses initially adapted to forage only, then adapted to forage plus supplements rich in starch and sugar (SS) or fiber and fat (FF). Ten Thoroughbred geldings, with BCS of 5 (nonobese), 6 (moderately obese), and 7 to 8 (obese), were adapted to pasture and hay, allocated to two groups, and fed SS or FF in a switch-back design with 8 wk of adaptation. Modified frequent-sampling i.v. glucose tolerance tests were applied after adaptation to forage, SS, and FF. For the tolerance tests, horses were kept in stalls overnight and provided hay, and venous catheters were placed the next morning. Baseline samples were collected, 0.3 g of glucose/kg of BW was given i.v., and blood was sampled at 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14, 16, and 19 min. At 20 min, 30 mU of insulin/kg of BW was given, followed by sampling at 22, 23, 24, 25, 27, 30, 35, 40, 50, 60, 70, 80, 90, 100, 120, 150, and 180 min. Plasma was analyzed for glucose and insulin, and Si, Sg, acute insulin response to glucose, and the disposition index were calculated. Normality was tested using the Shapiro-Wilk statistic. Body condition effects were analyzed using a mixed model with repeated measures. Diet effects were analyzed using a Wilcoxon signed rank test. The Sg was higher in obese than nonobese (P = 0.003) and moderately obese (P = 0.007) horses; Si was lower in obese than nonobese (P = 0.008) horses, and acute insulin response to glucose was higher in obese than nonobese (P = 0.039) horses. Effects of diet were likely confounded by body condition, but horses had lower Si (P = 0.066) when fed SS compared with FF, especially when nonobese. In conclusion, the minimal model effectively estimated Sg, Si, acute insulin response to glucose, and disposition index in horses. Obese geldings were insulin-resistant and seemed to rely primarily on Sg for glucose disposal. Feeding a diet rich in sugar and starch decreased insulin sensitivity of horses. Maintenance of body condition and avoidance of grain-based meals rich in sugar and starch would be beneficial to decrease the risk of developing insulin resistance and associated metabolic syndromes in horses, especially for horses at risk for these syndromes.

Animal Feed↗

Study of crib-biting and gastric inflammation and ulceration in young horses.

Nineteen young horses that had recently started to perform the stereotypy of crib-biting were compared with 16 non-stereotypic horses for 14 weeks. After initial observations of their behaviour and an endoscopic examination of the condition of their stomachs, the horses were randomly allocated to a control or an antacid diet At the start of the trial, the stomachs of the crib-biting foals were significantly more ulcerated and inflamed than the stomachs of the normal foals. In addition, the faecal pH of the crib-biting foals (6.05) was significantly lower than that of the normal foals (6.58). The antacid diet resulted in a significant improvement in the condition of the horses' stomachs. The crib-biting behaviour declined in most of the foals, regardless of their diet, but tended to decline to a greater extent in the foals on the antacid diet.

Animal Husbandry↗

Surgical trial investigating nocturnal gastroesophageal reflux and sleep (STINGERS).

BACKGROUND: Nocturnal reflux is important in the pathogenesis of esophagitis. The relationship between reflux and sleep is poorly understood, although data support both paradigms of nocturnal reflux causing arousal and nocturnal arousal allowing reflux. Furthermore, the effect of fundoplication on sleep is unknown. METHODS: Seven volunteers and 11 patients with gastroesophageal reflux disease (GERD) and nocturnal symptoms were studied with esophageal pH and polysomnography at baseline and at 8 to 10 weeks follow-up evaluation, with patients undergoing interval fundoplication. Gastrointestinal and sleep questionnaires were completed before each study. RESULTS: Questionnaire data between the groups showed differences at baseline, which were eliminated by surgery. No objective differences in sleep were observed between the groups at baseline or at follow-up evaluation. However, the patient group significantly increased the fraction of the night spent in deeper sleep (49.6% vs 58.3%; p = 0.022). Reflux events were associated with arousals in sleep. CONCLUSIONS: Fundoplication improves both subjective and objective sleep quality in patients with nocturnal GERD symptoms.

Case-Control Studies↗

The role of arginine vasopressin in human labour: functional studies, fetal production and localisation of V1a receptor mRNA.

OBJECTIVE: To investigate labour-associated changes in: 1. the myometrial contractile response to arginine vasopressin compared with oxytocin in vitro 2. fetal production of arginine vasopressin and 3. myometrial vasopressin V1a receptor mRNA. DESIGN: The contractile response to vasopressin (compared with oxytocin) was investigated in paired myometrial strips in vitro. Blood was taken from the umbilical artery and vein at delivery and arginine vasopressin measured by radio-immunoassay. V1a receptor mRNA was determined by in situ hybridisation. RESULTS: Myometrium was more sensitive to arginine vasopressin than oxytocin (P<0.05 for frequency, amplitude and activity integral in paired strips) after, but not before labour. There was a marked umbilical arteriovenous difference in arginine vasopressin concentration at delivery suggesting fetal production which was not influenced by labour. Myometrial vasopressin V1a receptor mRNA was not increased after the onset of labour. CONCLUSIONS: The human uterus is extremely sensitive to arginine vasopressin in vitro. Arginine vasopressin is produced by the fetus but fetal formation is not increased during labour.

Adult↗

Effects of fat adaptation on glucose kinetics and substrate oxidation during low-intensity exercise.

This study was designed to determine the effects of fat adaptation on carbohydrate and fat oxidation in conditioned horses during low-intensity exercise. Five mature Arabians were studied. The study was conducted as a crossover design with 2 dietary periods, each of 10 week's duration: a) a control (CON) diet, and b) a fat-supplemented (FAT) diet. The total amount of digestible energy (DE) supplied by the fat in the CON and FAT diets was 7% and 29%, respectively. During each period, the horses completed exercise tests at the beginning of the period (Week 0) and after 5 and 10 weeks on the diet. Tests consisted of 90 min of exercise at a speed calculated to elicit 35% VO2max on a treadmill inclined to 3 degrees. Oxygen consumption (VO2), carbon dioxide production (VCO2), and respiratory exchange ratio (RER) were measured at 15-min intervals. For determination of glucose kinetics, a stable isotope ([6-6-d2] glucose) technique was used. Compared to the CON diet, FAT diet consumption for 5-10 weeks was associated with an altered metabolic response to low-intensity exercise, as evidenced by a more than 30% reduction in the production and utilisation of glucose; a decrease in RER; a decrease in the estimated rate of whole-body carbohydrate utilisation; and an increase in the whole-body rate of lipid oxidation during exercise.

Adaptation, Physiological↗