The potent carcinogen dibenzo[a,l]pyrene is metabolically activated to fjord-region 11,12-diol 13,14-epoxides in human mammary carcinoma MCF-7 cell cultures.

Dibenzo[a,l]pyrene (DB[a,l]P), an environmental hydrocarbon and very potent carcinogen in rodent bioassays, could be activated to DNA-binding intermediates in cells through formation of three different regioisomeric bay- or fjord-region diol-epoxides or other more highly oxidized metabolites. The mechanism of metabolic activation of DB[a,l]P in the human mammary carcinoma cell line MCF-7 was elucidated by analyzing the DB[a,l]P-DNA adducts formed by [35S]phosphorothioate postlabeling, immobilized boronate chromatography, and high-performance liquid chromatography. Six DB[a,l]P-DNA adducts were detected. Comparison with those formed in cells by DB[a,l]P-11,12-diol and by reaction of DNA with syn- and anti-(benzylic hydroxyl and epoxide oxygen cis and trans, respectively) DB[a,l]P-11,12-diol-13,14-epoxide (DB[a,l]PDE) demonstrated that all DB[a,l]P-DNA adducts in MCF-7 cells were formed by these diol-epoxide isomers. Cellular DNA contained large amounts of two syn- and one anti-DB[a,l]PDE-DNA adducts and small amounts of one syn- and two anti-DB[a,l]PDE-DNA adducts. The ability of human cells to activate DB-[a,l]P to its fjord-region 11,12-diol 13,14-epoxides suggests that environmental exposure to DB[a,l]P could pose a risk for humans.

Short- and long-term racing performance of Standardbred pacers and trotters after early surgical intervention for tarsal osteochondrosis.

REASONS FOR PERFORMING STUDY: Osteochondrosis (OC) is commonly diagnosed in young Standardbred racehorses but its effect on performance when surgically treated at a young age is still incompletely understood. This is especially true for Standardbred pacers, which are underrepresented in the existing literature. OBJECTIVE: To characterise the short- (2-year-old) and long-term (through 5-year-old) racing performance in Standardbred pacers and trotters after early surgical intervention (<17 months of age) for tarsal OC. STUDY DESIGN: Retrospective clinical study. METHODS: The study population consisted of related, age-matched Standardbred racehorses (n = 278; 151 pacers, 127 trotters) with (n = 133) or without (n = 145) one or more tarsal OC lesions. All OC-affected horses were treated surgically prior to being sold as yearlings. Data obtained from publicly available race records for each horse included starts, wins, finishes in the top 3 (win, place or show), earnings and fastest time. Comparisons between OC-affected and unaffected horses were made for the entire population and within gaits. A smaller related population (n = 94) had these performance measures evaluated for their 2-5-year-old racing seasons. RESULTS: Osteochondrosis status was associated with few performance measures. Trotters were at higher risk for lesions of the medial malleolus but lower risk for lesions of the distal intermediate ridge of the tibia than were pacers. Horses with bilateral OC lesions and lateral trochlear ridge (LTR) lesions started fewer races at 2 years of age than those with unilateral lesions or without LTR lesions. CONCLUSIONS: Osteochondrosis seemed to have minimal effect on racing performance in this cohort, although horses with bilateral and LTR lesions started fewer races at 2 years. There was evidence for different distribution of OC lesions among pacers and trotters, which should be explored further. Standardbreds undergoing early removal of tarsal OC lesions can be expected to perform equivalently to their unaffected counterparts.

Factors in the control of feed intake of horses and ponies.

Ponies are large nonruminant herbivores which are capable of utilizing the products of both enzymatic digestion in the small intestine and bacterial fermentation (volatile fatty acids, VFAs) in the cecum and large colon as sources of metabolizable energy. Recent studies have demonstrated that ponies utilize nutrient stimuli from both carbohydrate and fat digestion in the small intestine and VFAs in the cecum and large colon in the control of meal frequency. These animals, however, rely primarily upon oropharyngeal and external stimuli to control the size and duration of meals. This is perhaps an adaptation to a feeding pattern of small frequent meals and food sources which provide significant amounts of nutrients to the animal system only after microbial fermentation in the hind gut. Nutrient cues which are operant in controlling feed intake in omnivores, carnivores, and ruminants appear to be important primarily in the regulation of meal frequency and long-term energy balance in the equine animal. The emphasis on oropharyngeal stimuli in the immediate control of feed intake of ponies reflects the unusual digestive physiology of these animals relative to other species studied to date.

Effect of dental correction on feed digestibility in horses.

To test the hypothesis that routine dental correction (removal only of sharp hooks and points from molars and premolars) would improve digestion of a hay/grain ration whereas performance 'floats' (rounding and smoothing of the dental arcades) would adversely affect digestion, 8 mature horses free from dental correction for over a year were used. Five-day digestion trials were conducted before and 2 and 4 weeks after correction in all horses. Although all horses had sharp points and minor premolar hooks, none had severe dental abnormalities. There were no significant differences found in apparent digestion of dry matter, crude protein, neutral detergent fibre or acid detergent fibre relative to precorrection data or controls (uncorrected horses on same digestion trial). Apparent digestibility of crude protein and fibre, however, was reduced if the occlusal angle of premolar 307 was greater than 80 degrees relative to the vertical axis (flattened). It should be recommended that regular dental correction be continued. However, if only small points and hooks are present, correction will not significantly improve digestion. Performance floating does not adversely affect digestion 2-4 weeks after the procedure is performed. Alterations in molar occlusal surface angle may affect digestibility of protein and fibre.

Controls of feeding in horses.

Members of the genus Equus are large, nonruminant herbivores. These animals utilize the products of both enzymatic digestion in the small intestine and bacterial fermentation (volatile fatty acids) in the cecum and large colon as sources of metabolizable energy. Equine animals rely primarily upon oropharyngeal and external stimuli to control the size and duration of an isolated meal. Meal frequency, however, is regulated by stimuli generated by the presence and (or) absorption of nutrients (sugars, fatty acids, protein) in both the large and small intestine plus metabolic cues reflecting body energy stores. The control of feeding in this species reflects its evolutionary development in an environment which selected for consumption of small, frequent meals of a variety of forages.

Plasma glucose and insulin concentrations and feeding behavior in ponies.

The hypothesis that changes in blood glucose concentrations and(or) utilization rate affect feeding behavior in ponies was tested. Ponies (n = 4) were fasted for 4 h, then given iv injections of 50% glucose [.2 g glucose/BW.75 kg (low dose, LD) or 1.0 g glucose/BW.75 kg (high dose, HD)] or an equal volume of normal saline (HDS; LDS) 5 min before being allowed access to pelleted feed. Blood samples were drawn at regular intervals pre- and post-treatment and analyzed for plasma glucose (PG), immunoreactive insulin (IRI) and glucagon concentrations. All glucose-treated animals immediately ate meals of size (HD = .67 +/- .23 kg, LD = .62 +/- .30 kg) and duration (HD = 54 +/- 19 min; LD = 49 +/- 16 min) comparable to those observed after saline injections (HDS = .58 +/- .29 kg in 48 +/- 16 min. LDS = .58 +/- .10 g in 50 +/- 15 min). There was a tendency, however, to prolong the interval between the first and second meal (first intermeal interval) after glucose injections (LD = 62 +/- 16 min, P less than .10; HD = 65 +/- 12 min, P less than .05) relative to saline treatment (LDS = 44 +/- 15 min; HDS = 35 +/- 8 min). Glucose-treated ponies PG was elevated (P less than .01) at the time of refeeding (LD = 122 +/- 14 mg/100 ml; HD = 259 +/- 69 mg/100 ml) relative to controls (84 +/- 2 mg/100 ml) as was 11.2 ng/ml; control = 2.67 +/- 2.20 ng/ml). The concentration of glucagon did not change significantly with either feeding of glucose treatment. The animal's PG and IRI dropped to within or below control ranges by 35 (LD) or 65 min (HD) post-treatment. The results indicated that, in ponies, intravenous glucose loads can prolong the duration of satiety experienced after a meal. Exogenously-induced hyperglycemia and resultant hyperinsulinemia do not, however, affect the first meal size or duration of ponies after a 4 h fast.

Diurnal variation and age differences in the biochemical markers of bone turnover in horses.

Biochemical markers of bone turnover provide sensitive, rapid, and noninvasive monitoring of bone resorption and formation. Serum concentrations of osteocalcin (OC) reflect rates of bone formation, and urinary concentrations of the pyridinium crosslinks pyridinoline (Pyd) and deoxypyridinoline (Dpd) are specific and sensitive markers of bone resorption. These markers are age-dependent and are used to detect and monitor changes in the rates of bone turnover in a variety of orthopedic diseases in humans and may prove to have similar application in horses. This study examined age differences and diurnal variation in OC, Pyd, and Dpd in eight adult geldings and seven weanling colts. Blood and urine were collected at regular intervals over 24 h. Serum OC and cortisol, and urinary Pyd and Dpd were analyzed. Mean 24-h concentrations of cortisol and all three markers were higher (P<.003) in weanlings than adults. Significant 24-h variation was observed in adult gelding OC, Pyd, and Dpd concentrations (P< .02). Adult OC concentrations were highest between 2400 and 0900; Pyd and Dpd peaked between 0200 and 0800. Similar patterns of bone turnover were observed in weanling values, but they were not significant (P>.17) owing to greater variability between individuals. Cortisol secretion varied (P<.001) over 24 h in both adults and weanlings and, thus, did not seem to be responsible for greater variability in markers of bone turnover between weanlings. These data demonstrate that diurnal rhythms exist for serum OC and urinary Pyd and Dpd in adult horses, as reported in humans, and that sample timing is an important consideration in future equine studies using these markers.

Volatile fatty acids and the role of the large intestine in the control of feed intake in ponies.

The roles of volatile fatty acids (VFA) and of the large intestine in the control of feeding in ponies were investigated. Ponies with cecal fistulas were adapted to ad libitum access to pelleted feed. Treatment solutions were given as a bolus 15 min before the animals were allowed free access to feed after a 4-h fast. Each dose of VFA solution was tested in a crossover design with a water control. When the ponies were permitted to eat after the treatments, the latency to eat, first meal size, and duration and first intermeal interval were recorded. Feed intakes were measured at 3 and 18 h after the treatments were given. Intracecal infusions of .4 mmol propionate (Prop)/kg body weight (BW) increased (P less than .05) total feed intake 7.5% relative to control values. Higher doses of Prop (.75 mmol/kg BW) and acetate (1.00 and 1.25 mmol/kg BW) reduced (P less than .05) feed intake by prolonging the first intermeal interval 143% (Prop) and 71 to 74% (acetate), although 24-h intakes did not differ from controls. The highest dose of Prop tested (1.00 mmol/kg BW) reduced first meal size 22% (P less than .01) without affecting subsequent feeding behaviors. The results indicate that changes in cecal VFA concentration can generate cues that may contribute to the control of meal size and frequency in ponies.

Effects of transportation on early embryonic death in mares.

Incidence of early embryonic death (EED) and associated changes in serum cortisol, progesterone and plasma ascorbic acid (AA) in transported mares were investigated. Mares were transported for 472 km (9 h) during either d 16 to 22 (T-3 wk, n = 15) or d 32 to 38 (T-5 wk, n = 15) of gestation. Blood samples were drawn from control, nontransported mares (NT-3 wk, NT-5 wk, n = 24) and transported mares pre-trip, midtrip, and at 0, 12, 24, 48 and 72 h post-transport and daily for the next 2 wk. Incidence of EED between transported and nontransported mares was not different (P greater than .05). Serum cortisol in all transported mares increased (P less than .05) relative to pre-trip values at midtrip and 0 h post-transport. Relative to NT mares, serum cortisol was higher (P less than .05) at midtrip in T-3 wk mares and 0 h post-transport in T-5 wk mares. Serum progesterone in all T mares increased (P less than .05) at midtrip relative to pre-trip values and was higher (P less than .05) in T-3 wk mares than in NT-3 wk mares at midtrip and 0 h post-transport. Post-transport decreases (P less than .05) in concentrations of progesterone were observed in mares that aborted. Plasma AA in transported mares increased (P less than .05) at midtrip in T-5 wk mares and decreased (P less than .05) relative to pre-trip values at 24 and 48 h post-transport (T-3 wk and T-5 wk mares, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of transportation on the estrous cycle and concentrations of hormones in mares.

Effect of transportation on estrous behavior, duration of the estrous cycle, ovulation, pregnancy rates and concentrations of serum cortisol, plasma ascorbic acid (AA), LH, estradiol and progesterone in mares was investigated. Fifteen mares were transported for 792 km (12 h) during the preovulatory stage of estrus. Transported mares were bled immediately before transport (baseline), at midtrip and 0, 12, 24, 48 and 72 h post-transport and twice daily from d 1 before transport to d 1 (estrogen) or 3 (LH) post-ovulation. Blood samples also were taken for progesterone on d 0, 2, 6, 10, 15, 16, 17, 18, 19 and 20 post-ovulation. Nontransported control mares (n = 15) were bled on the same schedule as transported mares. There was no difference (P greater than .05) in number of mares ovulating, estrous behavior, duration of the estrous cycle or pregnancy rate between groups. Cortisol in transported mares increased to concentrations greater (P less than .05) than those in control mares at midtrip and 0 h post-transport. Concentrations of AA in transported mares also increased (P less than .05) at midtrip, then decreased (P less than .05) below baseline at 24 h post-transport. Concentrations of LH and estradiol increased (P less than .05) above baseline throughout the blood-sampling period. Increases apparently were due to preovulatory surges of these hormones. Increase in LH concentrations in transported mares, however, was greater (P less than .05) than that in control mares at 0 h post-transport.(ABSTRACT TRUNCATED AT 250 WORDS)

Digestion in horses after resection or ischemic insult of the large colon.

The effect of 60% resection of the large colon vs ischemic insult without resection on the ability of horses to digest grass hay was investigated. Digestion trials were performed on 9 horses before surgery (base line) and 3 weeks, 6 weeks, and 6 months after surgery. The percentage of apparent digestion of crude protein, crude fiber, nitrogen-free extract, calcium, phosphorus, magnesium, manganese, copper, and zinc was calculated. Horses that had resection (n = 5) had decreased apparent digestion of crude protein, crude fiber, and phosphorus 3 weeks after surgery, compared with those in horses with ischemic insults (n = 4) and with base-line values. Horses with ischemic insults also had a decrease in crude protein digestion 3 weeks after surgery, compared with base-line values. All horses returned to base-line values of digestion at the 6-month trials, although horses that had resection had higher fecal concentrations of phosphorus and nitrogen-free extract than did horses with ischemic insult. During the study, all horses had maintained good body condition.

Differences in diagnostic test results and hematologic data between aged and young horses.

Hematologic data and results of diagnostic tests were compared between aged (greater than or equal to 20 years old) and young (less than or equal to 5 years old) horses to identify hematologic and metabolic changes associated with aging. Initial data were obtained from 8 aged and 6 young mares (group 1). Similar data were collected from a second group of aged (3 mares and 3 geldings) and young (1 mare and 5 geldings) horses (group 2). Dexamethasone suppression tests (DST) and necropsies were performed on 6 additional mares and mare 8 from group 1 (group 3). Complete blood counts and serum biochemical profiles were compared between young and aged horses of groups 1 and 2. Mean corpuscular volume was higher (P less than 0.05) in aged horses. Oral glucose tolerance and insulin response to orally administered glucose were measured in 13 aged horses (groups 1 and 2) and 6 young mares of group 1. In group 1, plasma ascorbic acid values were lower (P less than 0.05) in aged horses than in young horses maintained under the same conditions and feeding regimens. An apparent age-related hyperinsulinemic response to orally administered glucose identified in group-1 mares was probably a result of a high occurrence of subclinical hypophyseal and/or thyroid adenomas. Of 13 aged horses necropsied (groups 2 and 3), 10 had hypophyseal and/or thyroid adenomas that, in group 2, were consistently associated (P less than 0.05) with hyperinsulinemic responses to orally administered glucose. All horses in groups 2 and 3 were given a 24-hour DST.(ABSTRACT TRUNCATED AT 250 WORDS)

Fiber digestion and voluntary intake in horses after adaptation to extensive large-colon resection.

Each of 3 digestion trials (3 forage diets) was performed on 2 groups of horses 6 to 12 months after sham operation (group 1; n = 3) or large-colon resection (group 2; n = 5). Diets were alfalfa pellets, alfalfa hay, and grass hay. Feed and fecal analyses were performed to determine apparent digestion of dry matter, organic matter, and crude protein and true digestion of dry matter, organic matter, crude protein, total plant cell wall, hemicellulose, cellulose, and lignin. Additional fecal and metabolic variables determined were percentage of fecal water, total fecal water, metabolic organic matter, metabolic crude protein, and metabolic nitrogen. Large-colon resection decreased the digestion of plant cell wall because of decreased digestion of cellulose in alfalfa pellet and grass hay diets, but not in alfalfa hay diet. Insufficient digestible energy and/or protein from grass hay was obtained by horses with colon resection, and significant (P less than 0.05) weight loss was observed. Voluntary intake was significantly (P less than 0.05) increased by horses with colon resection. Of the diets studied, alfalfa hay was the most appropriate forage diet, compared with average grass hay and alfalfa pellet diet, for horses after extensive large-colon resection. Additionally, horses with colon resection may have higher levels of feed intake than do horses without colon resection.

Large intestinal capacity, retention times, and turnover rates of particulate ingesta associated with extensive large-colon resection in horses.

Fecal excretion of a particulate marker, ytterbium (Yb), was evaluated in 9 horses before surgery and 3 weeks, 3 months, and 6 months (4 trials) after sham-operation (group 1; n = 3) or extensive large colon resection (group 2; n = 6). Fecal excretion curves of total Yb excretion, loge Yb excretion, % Yb excretion, loge % Yb excretion, and cumulative % Yb excretion were evaluated, and kinetic analysis was performed on the loge Yb excretion curves to detect mixing pools and to calculate the fractional rate of particulate passage, turnover rate, and pool size. Calculations were performed to determined transit time, mean overall retention time, adjusted mean retention time, peak time, and disappearance time. Values were statistically analyzed to determine differences between groups and among trials (P less than 0.05). Group-2 horses had significantly shorter transit, peak, and mean overall retention times, compared with preoperative values and with values for group-1 horses. Two mixing pools were identified: a slower emptying pool of 5.7% hour-1 (k1) and a faster emptying pool of 12.3% hour-1 (k2). The rate of passage from the first pool (k1) was not altered by colon resection, and was interpreted as being most influenced by the cecum. In further support of this interpretation, the capacity of the k1 pool approximated the capacity of the cecum (17 L). The capacity of the k1 pool significantly expanded by 6 months in the resected horses. the rate of passage from the second pool (k2) significantly increased initially after colon resection (3 weeks and 3 months), but returned to preoperative values by 6 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of extensive resection of the small intestine in the pony.

Small intestinal resection (SIR) is not uncommonly done in surgical treatment of equine colic, but little is known about the long-term effects of SIR on horses and ponies. Twelve ponies, fed maintenance amounts of pelleted feed, were divided randomly into 4 treatment groups. D-Xylose absorption curves were recorded for each pony before surgical treatments were performed. Treatments consisted of control (ileal bypass) and 40%, 60%, or 80% SIR. D-Xylose absorption, serum electrolyte, and enzyme profiles for each animal were recorded once every 30 days for 180 days after surgical treatment, and the ponies were weighed every 2 weeks. The ponies then were necropsied and the remaining small and large intestine were examined. D-Xylose absorption values were depressed (P less than 0.05) in the ponies subjected to 40%, 60%, and 80% SIR as compared with the absorption values of the controls. The ponies with the 60% and 80% SIR lost body weight throughout the experimental period, whereas the controls and the ponies with 40% SIR maintained their base-line (presurgical manipulation) weight. Serum alkaline phosphatase activity was increased (P less than 0.05) in the ponies subjected to 60% and 80% SIR and significant biliary hyperplasia was present in those with 80% SIR. Extensive (greater than or equal to 60%) SIR severely compromised the capability of ponies to absorb nutrients and to derive adequate nutrition from a maintenance diet, resulting in changes in hepatic parenchyma and elevations in serum alkaline phosphatase. These changes are consistent with those reported in other species following SIR.

Weight, water, and cation losses in horses competing in a three-day event.

Body weight of 48 horses competing in a 3-day event was measured the day before the event (baseline), following the dressage phase of the event (day 1), after the endurance phases of the event (day 2), and 18 to 24 hours after the endurance phases (day 3). Plasma sodium and potassium concentrations were measured the evening before, immediately after, and 10 minutes after the endurance phases. Total body water, water loss, and net exchangeable cation loss were then calculated. Body weight and total body water were significantly decreased, compared with baseline values, at all times during the event, and significant water loss was detected. The largest changes were recorded after the endurance phases of the event. Water deficits were still detected 18 to 24 hours after the endurance phases of the event. Mean plasma sodium concentration was significantly increased immediately after the endurance phases of the event, compared with concentration measured the evening before, and remained increased after the 10-minute recovery period, presumably because of dehydration. Mean plasma potassium concentration was significantly increased immediately after the endurance phases of the event, compared with concentration measured the evening before, but was not increased after the 10-minute recovery period.