A mechanism of excessive accumulation of abomasal gas in vagotomized cattle determined using fluoroscopy.

To better understand the mechanism of excessive gas accumulation in the abomasum in bovine abomasal displacement, we performed gastric fluoroscopy in vagotomized cattle. Fifteen 6-month-old Holstein steers were divided into three groups: a non-vagotomized control group (Group C; n=5), a ventral thoraco-vagotomized group (Group V; n=5), and a dorsal and ventral thoraco-vagotomized group (Group DV; n=5). These groups were examined by fluoroscopy before and during a 5-week observation period after surgery. In Group C, no change was observed throughout the observation period. In Group DV, immediately after surgery, reticuloruminal motility was completely absent and ruminal distention was seen. Two weeks after surgery, abnormal reticulum motility and increased gas accumulation in the abomasal body were noted. Abomasal dilatation was also observed. In Group V, 1 week after surgery, gas inflow into the abomasum and relatively normal reticulum motility were observed along with a rapid increase in abomasal gas. Abomasal dilatation was also observed. In addition, left-displaced abomasum occurred in one of the steers in this group. From these results, we concluded that one of the mechanisms of excessive gas accumulation in the abomasum is reticulum-mediated gas inflow from the rumen combined with vagotomy-induced hypomotility.

Pharmacokinetics of the gastroprokinetic agent mosapride citrate after single oral administration in horses.

The purpose of this study was to determine the pharmacokinetics and dose proportionality of mosapride citrate, a selective 5-HT4 agonist, after oral administration in horses. Seven healthy Thoroughbreds were dosed with distilled water and 0.5, 1.0, or 1.5 mg/kg mosapride citrate through a nasogastric tube. Serum mosapride concentrations were measured by a liquid chromatography/tandem mass spectrometry (LC/MS/MS) method. Mosapride showed the Cmaxs of 31, 60, and 104 ng/g and AUCs of 178, 357, and 566 ng.hr/g at doses of 0.5, 1.0, 1.5 mg/kg, respectively. The Cmaxs and AUCs increased in proportion to the dose, indicating linear pharmacokinetics of mosapride up to 1.5 mg/kg. The pharmacokinetic profiles of mosapride in horses are quite different from that in humans. The average t1/2 in horses was almost 2 fold longer than that reported in healthy adult humans. Therefore, it is thought that it is suitable to reduce the number of doses a day in horses compared to humans.

In vitro evaluation of allogeneic bone screws for use in internal fixation of transverse fractures created in proximal sesamoid bones obtained from equine cadavers.

OBJECTIVE: To evaluate effectiveness of allogeneic bone screws and pins for internal fixation of midbody transverse fractures of equine proximal sesamoid bones (PSBs) in vitro. SAMPLE POPULATION: 14 forelimbs from cadavers of 3-year-old Thoroughbreds. PROCEDURES: Allogeneic cortical bone fragments were collected from the limbs of a male Thoroughbred, and cortical bone screws were prepared from the tissue by use of a precision desktop microlathe programmed with the dimensions of a metal cortical bone screw. A midbody transverse osteotomy of each PSB was performed by use of a bone-shaping oscillating saw and repaired via 1 of 3 internal fixation techniques: 1 allogeneic bone screw with 1 allogeneic bone pin (type I; n = 6 PSBs), 2 allogeneic bone screws (type II; 8), or 1 stainless steel cortical bone screw (control repair; 6). Mechanical tension measurements were obtained by use of a commercially available materials testing system. RESULTS: Mean +/- SD tensile strength (TS) was 668.3 +/- 216.6 N for type I repairs, 854.4 +/- 253.2 N for type II repairs, and 1,150.0 +/- 451.7 N for control repairs. CONCLUSIONS AND CLINICAL RELEVANCE: Internal fixation of PSB fractures by the use of allogeneic bone screws and bone pins was successful. Although mean TS of control repairs with stainless steel cortical bone screws was greater than the mean TS of type I and type II repairs, the difference between type II and control repairs was not significant. Allogeneic screws may advance healing and result in fewer complications in a clinical setting.

Effects of mosapride citrate, metoclopramide hydrochloride, lidocaine hydrochloride, and cisapride citrate on equine gastric emptying, small intestinal and caecal motility.

OBJECTIVE: Although extensive work has been done to elucidate the beneficial and unfavorable effects of gastrointestinal prokinetic agents in humans, little is known on the effects of these agents in horses. In this study, we compared the effects of mosapride, metoclopramide, cisapride, and lidocaine on equine gastric emptying, jejunal and caecal motility and evaluated these agents' adverse drug reactions (ADRs). ANIMALS: Seven healthy adult Thoroughbreds. PROCEDURE: Mosapride 1.0mg/kg and 2.0mg/kg, metoclopramide 0.2mg/kg, and cisapride 1.0mg/kg were dissolved in 100mL distilled water for oral administration. Lidocaine 1.3mg/kg was mixed with 500 mL saline for a 30-min intravenous infusion. Oral administration of 100mL distilled water was used as control. Gastric emptying was evaluated using (13)CO(2) breath test, and jejunal and caecal motility was assessed by electrointestinography. RESULTS: The present study demonstrates that mosapride at doses of 1.0mg/kg and 2.0mg/kg facilitates gastric emptying in horses. Improved jejunal motility was observed following administration of mosapride (1.0mg/kg and 2.0mg/kg), metoclopramide (0.2mg/kg), and cisapride (1.0mg/kg). Similarly, improved caecal motility was observed following administration of mosapride (2.0mg/kg). CONCLUSIONS AND CLINICAL RELEVANCE: This study shows that among the prokinetic agents studied here, only mosapride (2.0mg/kg) promotes jejunal and caecal motility in horses. Considering mosapride ADRs profile, it is believed that this compound is useful in the treatment of diseases associated with decreased GI motility, including postoperative ileus.

Temporal changes in concentrations of branched-chain amino acids in plasma on healthy mares and foals from birth to 24 weeks of age.

The concentrations of branched-chain amino acids (BCAA; valine, leucine, isoleucine) were determined in plasma of 7 healthy thoroughbred mares and their foals from birth (0 week) to 24 weeks of age, using automated high-performance liquid chromatography. In foals, the concentrations of plasma valine were significantly high (p<0.05) at 16, 20 and 24 weeks. The concentrations of plasma leucine were significantly high (p<0.05) at 1 and 3 weeks. The concentrations of plasma isoleucine were significantly high (p<0.05) from 1 to 24 weeks. In mares, the concentrations of plasma valine were significantly high (p<0.05) at 16 and 24 weeks. The concentrations of plasma leucine and isoleucine were significantly high (p<0.05) at 16 weeks. It was clear that the concentrations of plasma BCAA in foals and mares were at different levels at various times after birth. Since mares and foals were kept in health during this study, we could get the base data of the concentrations of BCAA in plasma of healthy foals and mares from birth to 24 weeks.

A preliminary study of (13)c-phenylalanine and (13)c-dipeptide breath tests in horses.

This study aimed to establish a standard dose and sample collection time for (13)C phenylalanine and (13)C-Dipeptide breath test in horses. To evaluate dose-dependent effects, healthy horses received 2.5 mg/kg, 5 mg/kg, and 10 mg/kg (13)C phenylalanine dissolved in 1 ml/kg distilled water and 1.25 mg/kg, 2.5 mg/kg, and 5 mg/kg (13)C dipeptide dissolved in 2 ml/ kg distilled water. Tmax was observed during the sample collection time. For (13)C phenylalanine, the standard deviation of Cmax at 5 mg/kg was lower than that of 10 mg/kg. For (13)C dipeptide, the standard deviation of Tmax was the lowest at 5 mg/kg. This study revealed that an optimal dose for breath tests with (13)C phenylalanine and (13)C dipeptide may be 5 mg/kg in horses.

Evaluation of the cranial cruciate ligament repair system(®) in surgery for laryngeal hemiplegia in heavy draft horses.

The purpose of this study was to evaluate the effect of the canine cranial cruciate ligament repair system on laryngeal hemiplegia in heavy draft horses. Twenty-four heavy draft horses diagnosed with grade 4 laryngeal hemiplegia were allocated to either the prosthetic laryngoplasty (PL) group (n=14) or a canine cranial cruciate ligament repair system (CCCLRS) group (n=10). Right to left angle quotients (RLQs) of abductions of the arytenoid cartilages were endoscopically evaluated before and after surgery. Post-operative RLQs in the CCCLRS group were significantly lower than those of the PL group (P<0.01). The canine cranial cruciate ligament repair system was revealed to be a good surgical procedure for laryngeal hemiplegia in heavy draft horses.

Evaluation of equine cecal motility by ausculation, ultrasonography and electrointestinography after jejunocecostomy.

OBJECTIVE: Horses often suffer reduced intestinal motility after jejunocecostomy. Therefore, accurate evaluation of intestinal motility is important for the prevention, diagnosis and treatment of this condition. The purpose of this study was to evaluate intestinal motility in horses after jejunocecostomy using three different methods, i.e. auscultation, ultrasonography and electrointestinography. ANIMALS: Six healthy thoroughbreds were used in this study. They were subjected to jejunocecostomy. PROCEDURE: Bowel sounds in the right paralumbar fossa were assigned a score of 0-3 for intestinal motility evaluation by auscultation, and the number of cecal contractions during a 3-min period were counted by ultrasonography. Electrointestinography (EIG) was used to measure percutaneous potential of the cecum. RESULTS: We identified three specific postoperative periods: the period of reduced intestinal motility (postoperative day 1 to day 2), in which intestinal motility declined, the unstable period (day 3 to day 7), in which intestinal motility partially recovered, and the full recovery period (day 8 to day 31), in which intestinal motility returned to preoperative state. Careful management was found to be especially important during the period of reduced intestinal motility and the unstable period. We found that, in healthy horses that underwent jejunocecostomy, it takes approximately one month for the cecum to return to normal motility patterns observed before surgery. CONCLUSION: We have shown in this study that evaluation of intestinal motility after jejunocecostomy in horses by EIG is more objective and provides more details than evaluation by auscultation or ultrasonography.

The prokinetic effect of mosapride citrate on horse gastric emptying rates.

The prokinetic effect of the 5-HT4 receptor agonist mosapride was evaluated in seven healthy thoroughbreds. Mosapride was orally administered at doses of 0.5, 1.0 or 1.5 mg/kg. The breath 13CO2/12CO2 rate (Delta13CO2), an indirect indicator for the rate of gastric emptying, was measured at appropriate points for 4 hr after drug administration. There was a significant increase compared with the control value at 15, 20 and 165 min for 0.5 mg/kg, 30 min at 1.0 mg/kg and 165 min for 1.5 mg/kg. The results suggest that mosapride may facilitate the gastric emptying in horses.

In vivo effects of intra-articular injection of gelatin hydrogen microspheres containing basic fibroblast growth factor on experimentally induced defects in third metacarpal bones of horses.

OBJECTIVE: To evaluate the effect of intra-articular injection of gelatin hydrogel microspheres containing basic fibroblast growth factor (bFGF) on experimentally induced defects in third metacarpal bones (MC3s) of horses, in vivo. ANIMALS: 6 healthy adult Thoroughbreds. PROCEDURES: Horses were anesthetized, and a hole (diameter, 4.5 mm) was drilled into the medial condyle of both MC3s of each horse. One milliliter (100 microg) of a solution of gelatin hydrogel microspheres (2 mg) containing bFGF was injected into the joint capsule of the right metacarpophalangeal joint of each horse (bFGF joint). One milliliter of saline (0.9% NaCl) solution was injected into the left metacarpophalangeal joint (control joint). Radiography was performed 1 day and 4, 8, 12, and 16 weeks after surgery to evaluate bone defect refilling. Sixteen weeks after surgery, multidetector-row computed tomography (MDRCT) was performed to determine the degree of refilling at the bone defect site. RESULTS: Radiography revealed healing of bone defects at 4 to 12 weeks after surgery in bFGF joints and at 8 to 16 weeks after surgery in control joints. In addition, MDRCT revealed a higher degree of healing in bFGF versus control joints. Mean+/-SD MDRCT score for bFGF joints (411.7+/-135.6 Hounsfield units) was significantly higher than that for control joints (240.8+/-133.1 Hounsfield units). CONCLUSIONS AND CLINICAL RELEVANCE: Treatment of horses with gelatin hydrogel microspheres that contained bFGF enhanced bone regeneration and healing of experimentally induced defects. This treatment strategy may be useful for treating horses with fractures.

A case of equine motor neuron disease (EMND).

We report a case of EMND in a heavy horse that was bred and trained in Hokkaido, Japan. Clinical symptoms included severe ataxia of all four limbs, tilted head, lethargy, and flaccid lips. Numerous axonal degenerations and swellings were observed in nuclei, mostly in the cerebellar dentate nucleus and the nucleus of the hypoglossal nerve, and in the ventral horn of the spinal cord. In the ventral horn of the spinal cord, neuronal degeneration, swelling, and/or necrosis were observed sporadically. The case was diagnosed as EMND from the clinical symptoms and pathological findings.

Practical tips for modified dorsolumbar epidural anesthesia in cattle.

Segmental dorsolumbar epidural anesthesia has been considered difficult to perform. The purpose of this study was to determine whether or not it is difficult for beginners to learn how to do modified dorsolumbar epidural anesthesia of cattle. Thirty cattle were divided into two groups, young (n = 8) and adult (n = 22), according to their age and body weight, and 0.12% new methylene blue (NMB) was injected into the first interlumbar (L1.L2) epidural space by four fifth-year veterinary school students who had never performed this method. After a 1 hour lecture on the modified dorsolumbar epidural anesthesia procedure which included basic anatomy and skills, each student successfully performed the procedure. In the young group, the NMB solution was distributed between the periosteum and the epidural fat (BPF) in one half and between the epidural fat and the dura mater (BFD) in the other half of the cattle. In about 60% (13/22) of the adult group, the NMB solution distributed as BFD type. This study showed that the modified dorsolumbar epidural anesthesia procedure is easy for beginners to perform if they overcome their fear about the deeper insertion of the epidural needle with basic anatomical knowledge and a little experience.

Use of 13C-acetate breath test for assessment of gastric emptying in horses.

This study aimed to establish and standardize a breath test that uses 13C-acetate in a liquid diet for evaluation of gastric emptying in horses. Seven adult healthy thoroughbreds were used in this study. They were given 13C-acetate (125 mg, 250 mg, or 500 mg) in a test meal (2000 ml liquid diet) via an intranasal catheter. 13C concentrations in the exhaled CO2 were measured in samples taken before and after test meal administration using an infrared absorption spectroscope. In the 500 mg 13C-acetate group, Delta13CO2 showed a steep gradient immediately after meal administration compared to the 125 mg and 250 mg groups. Therefore, t(max) in the 500 mg group was easier to determine than in the 125 mg and 250 mg groups. In the 500 mg group, GEC, half-empty time (t1/2), calculated t(max) (t(lag)), and t(max) were 1.95 +/- 0.28 (mean +/- SD), 229.2 +/- 57.0 (min), 139.2 +/- 22.2 (min), and 124.0 +/- 28.4, respectively. Differences in CV observed in the 500 mg group were lower than those in the 125 mg and 250 mg groups. This study demonstrates that the 13C-acetate breath test is useful for evaluating gastric emptying in horses since it is non-invasive and does not require set up of special facilities or equipment. Optimum evaluation of gastric emptying in horses can be achieved with 500 mg of 13C-acetate given in a liquid diet.

Effects of mosapride, a 5-hydroxytryptamine 4 receptor agonist, on electrical activity of the small intestine and cecum in horses.

OBJECTIVE: To examine the effects of various doses of mosapride, a 5-hydroxytryptamine 4 receptor agonist, on motility of the small intestine and cecum in horses by use of electrical activity and to determine the dose that provides the optimal response. ANIMAL: 6 healthy adult Thoroughbreds. PROCEDURE: Electrical activity of the small intestine and cecum was recorded before and after mosapride administration by use of an electrogastrograph. Mosapride (0.5, 1, 1.5, and 2 mg/kg) was dissolved in 200 mL of water and administered orally to horses through a nasogastric tube. Three hours after drug administration, mean amplitude of electrical activity calculated for a period of 30 minutes was expressed as the percentage of the mean amplitude of electrical activity for a period of 30 minutes before drug administration. RESULTS: Mosapride administered orally increased the percentage of the mean amplitude of electrical activity in the small intestine and cecum in a dose-dependent manner. Mean +/- SD values differed significantly for 1, 1.5, and 2 mg/kg (127.0 +/- 12.5%, 137.7 +/- 22.2%, and 151.1 +/- 24.0%, respectively) in the small intestine and for 1.5 and 2 mg/kg (130.1 +/- 34.5% and 151.6 +/- 45.2%, respectively) in the cecum. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of results of this study clearly documents that mosapride promotes motility in the small intestine and cecum of horses and that the optimal orally administered dosage is 1.5 to 2 mg/kg. Therefore, mosapride may be useful for treatment of horses with gastrointestinal tract dysfunction.

Epidural administration of fixed volumes of xylazine and lidocaine for anesthesia of dairy cattle undergoing flank surgery.

A modified method for epidural anesthesia in standing cattle undergoing flank surgery in which fixed volumes of xylazine and lidocaine were injected is described, along with results in 18 cattle. A Tuohy needle was inserted into the L1-2 intervertebral space from a dorsal midline approach, positioning of the needle tip in the epidural space was confirmed by use of the hanging drop technique, the needle was slowly advanced 7 to 10 mm to penetrate the epidural fat, and the anesthetic solution was then administered. In the initial 8 cattle, the anesthetic solution consisted of 1 mL of 2% xylazine and 4 mL of 2% lidocaine. However, 1 of these cattle became recumbent prior to surgery. Therefore, the dose of lidocaine was decreased, and in the subsequent 10 cattle, the anesthetic solution consisted of 1 mL of 2% xylazine and 3 mL of 2% lidocaine. Surgery was begun 30 minutes after epidural administration of anesthetic; surgery time ranged from 27 to 276 minutes. Sedation and anesthesia were adequate, except in 1 cow that received the lower dose of lidocaine and became recumbent during suturing of the incision. The modified epidural anesthesia technique with injection of fixed volumes of xylazine and lidocaine appears to be an adequate method for anesthesia of standing cattle undergoing flank surgery.

Synthesis of di-branched heptasaccharide by one-pot glycosylation using seven independent building blocks.

[reaction: see text] We describe an efficient synthesis of di-branched heptasaccharide 1 having phytoalexin elicitor activity in soybeans by one-pot glycosylation. The synthesis involves chemo- and regioselective sequential six-step glycosylations using seven independent building blocks and sequential removal of acyl- and benzyl ether-type protecting groups. The coupling of seven building blocks requires only four chemoselective activitable leaving groups of glycosyl donors. Both the glycosylation and deprotection reactions can be achieved utilizing a parallel manual synthesizer.

Anti-hyperlipidemic action of a newly synthesized benzoic acid derivative, S-2E.

A newly synthesized benzoic acid derivative, (+)-(S)-p-[1-(p-tert-butylphenyl)-2-oxo-4-pyrrolidinyl]methoxybenzoic acid (S-2E), has the capacity to inhibit the biosynthesis of both sterol and fatty acids. Here, we report the mechanism by which S-2E lowers blood cholesterol and triglyceride levels. In the liver, S-2E was converted into its active metabolite, S-2E-CoA. S-2E-CoA noncompetitively inhibited the enzymatic activities of both 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase and acetyl-CoA carboxylase at K(i)=18.11 microM and K(i)=69.2 microM, respectively. Interestingly, pharmacokinetic experiments in rats showed that the concentration of S-2E-CoA in the liver was sufficient to inhibit the activities of HMG-CoA reductase and acetyl-CoA carboxylase, for example, when orally given to rats at 10 mg/kg. Indeed, S-2E (3-30 mg/kg) given orally suppressed the secretion rate of very-low-density lipoprotein (VLDL)-cholesterol and triglyceride in Triton WR-1339-injected rats. Furthermore, S-2E lowered the blood total cholesterol and triglyceride levels simultaneously in Zucker fatty rats. Collectively, S-2E may be useful in the treatment of familial hypercholesterolemia and mixed hyperlipidemia.

An immunohistochemical study of endocrine cells in the abomasum of vagotomized calf.

The effect of thoraco-vagotomy on the distribution and frequency of chromogranin-, serotonin-, somatostatin- and gastrin-immunoreactive cells in the abomasum of the calf were investigated by immunohistochemistry. Calves were vagotomized at 1 week old and sampled 2 and 4 weeks later. The endocrine cells generally decreased in number in vagotomized calves as compared to non-operated control calves. However, the detailed responses of endocrine cells to vagotomy varied depending on the endocrine cell type, region of gastric mucosa, and period after vagotomy. The present result suggests that the vagus nerve has an influence on the intrinsic regulatory system by endocrine cell control in the ruminant abomasum.

Multivariate regression analysis of epidural pressure in cattle.

OBJECTIVE: To evaluate the effects of growth, maturity, and pregnancy on epidural pressure in cattle. ANIMALS: 50 healthy Holstein cattle (18 heifers, 23 lactating cows, and 9 pregnant nonlactating cows). PROCEDURE: Each of the cattle was restrained in a standing position. Height of the second lumbar vertebra's transverse process (2LTP) and humeral tuberosity (HT) on the right side as well as abdominal girth (AG) were measured in each animal, and body condition score (BCS) was ascertained. Skin caudal to the first lumbar spinous process was aseptically prepared, and anesthetic was injected. After inserting a 16-gauge 120-mm Tuohy needle in the ligamentum flavum, a calibrated pressure transducer was connected to the needle. Then, the needle was introduced into the epidural space, and epidural pressure was recorded. RESULTS: Mean +/- SD residual epidural pressure of heifers (-9.3+/-3.3 mm Hg) was significantly higher than that of lactating (-174+/-5.5 mm Hg) or nonlactating (-14.5+/-2.4 mm Hg) cows. Stepwise regression of 5 variables revealed that only the difference in height between 2LTP and HT (2LTP - HT) in heifers and only BCS in lactating cows were significantly correlated with residual epidural pressure. For all cattle, the optimal equation (R2 = 0.47) describing the relationship was y = -12.7 + 6.3x, - 0.4x2 - 0.1x3, where y is epidural pressure, x1 is BCS, x2 is 2LTP - HT, and x3 is age. CONCLUSIONS AND CLINICAL RELEVANCE: Negative epidural pressure was detected in standing cattle. Growth, maturity, and pregnancy affect epidural pressure in cattle.