Effects of cimetidine and ranitidine on basal gastric pH, free and total acid contents in horses

The basal gastric pH, free and total acid contents from five adult horses were determined at two-hour intervals for six- to eight-hour periods. The basal gastric pH, free and total acid contents varied from 2.14 +/- 0.08 to 2.41 +/- 0.14, 28.63 +/- 8.27 to 17.89 +/- 2.86 mmol litre-1 and 41.38 +/- 9.72 to 37.38 +/- 3.70 mmol litre-1, respectively. Cimetidine (8.8 mg kg-1 orally) and ranitidine (2.2 mg kg-1 orally) increased the basal gastric pH to above 3.6 (P less than 0.05) with a concomitant reduction of 75 per cent and 75 to 100 per cent in the basal gastric free acid content, respectively, for an eight-hour period. Cimetidine (4.4 mg kg-1, intramuscularly) and ranitidine (1.4 mg kg-1, intramuscularly) increased the basal gastric pH to above 3.6 with a concomitant reduction of 54 to 93 per cent and 69 to 100 per cent in the basal gastric free acid content, respectively, for an eight-hour period. This study shows that the horse is a basal acid secretor, and that cimetidine and ranitidine, two widely used histaminergic-H2 type antagonists in human clinical practice are effective in horses with ranitidine being approximately four times more potent than cimetidine.     

Effects of misoprostol and omeprazole on basal gastric pH and free acid content in horses

The basal gastric pH and free acid contents from five young adult healthy horses were determined at one hour intervals for eight hours. The basal gastric pH and free acid contents varied from 1.63 +/- 0.06 to 1.97 +/- 0.11 and 26.42 +/- 4.14 to 17.92 +/- 5.28 mmol litre-1, respectively. Misoprostol, a methylester analogue of prostaglandin (5 micrograms kg-1, orally) produced a time-dependent increase in the basal gastric pH to above 3.5 (P less than 0.05) at three, four and five hours after administration with a concomitant reduction of 80 to 90 per cent in the basal gastric free acid contents throughout the eight hour period monitored. Omeprazole, a benzimidazole derivative (0.5 mg kg-1, intravenously) increased the basal gastric pH to above 3.5 at two and three hours after administration with a concomitant reduction of 65 to 90 per cent in the basal gastric free acid contents for seven of the eight hour periods monitored. These results confirm that the horse is a basal acid secretor, and both misoprostol and omeprazole are effective inhibitors of the basal gastric acid secretion, thus establishing that both prostaglandins and H+/K+-ATPase play an important role in controlling parietal cell function of the equine gastric mucosa.     

Isometamidium in pigs: disposition kinetics, tissue residues and adverse reactions

The disposition and adverse effects of the anti-trypanosomal drug isometamidium in pigs were evaluated. Following intramuscular administration of the drug at doses of 0.5, 15 and 35 mg kg-1, the drug was rapidly absorbed within 15 to 30 minutes to reach maximum plasma concentrations of 12 to 477 (n = 6), 302 to 655 (n = 4) and 1620 (n = 1) ng ml-1, respectively. No drug was detectable in plasma (less than 5 ng ml-1) 24 hours after drug administration at the three doses used. The half-lives of disappearance of the drug from plasma during the terminal phase were 7.12 h for the pigs given a dose of 15 mg kg-1, and 7.20 h for the pig which received a dose of 35 mg kg-1. At all the intramuscular injection sites, high drug concentrations were found six weeks after administration. The most dramatic adverse reactions observed were: one death after intramuscular administration at a dose of 35 mg kg-1 to two animals, and two deaths after intravenous administration at a dose of 2 mg kg-1 to two animals. For all these cases, the immediate cause of death was acute cardiovascular collapse. Biochemical analyses and gross and histological examinations showed that the animals that tolerated the high doses of 15 and 35 mg kg-1 given intramuscularly had extensive and severe tissue damage at the injection sites. Significant increases in plasma gamma-glutamyltransferase and alanine aminotransferase following drug administration suggested a degree of hepatobiliary damage.     

Effect of orally administered cimetidine and ranitidine on abomasal luminal pH in clinically normal milk-fed calves

OBJECTIVE: To characterize the change of pH in the abomasal lumen throughout a 24-hour period, to determine whether pH of the abomasal body differs from pH of the pyloric antrum, and to determine whether oral administration of cimetidine and ranitidine alters pH of the abomasal lumen in milk-fed calves. ANIMALS: 5 male dairy calves (4 Holsteins-Friesian, 1 Ayrshire), 5 to 15 days old. PROCEDURE: Cannulas were surgically positioned in the abomasal body and pyloric antrum of each calf. Calves received the following treatments in a randomized crossover design: milk replacer (60 ml/kg of body weight, q 12 h [untreated control calves]), milk replacer and cimetidine (50 or 100 mg/kg, q 8 h), or milk replacer and ranitidine (10 or 50 mg/kg, q 8 h). The pH of the abomasal body and pyloric antrum was measured for 24 hours, using miniature glass pH electrodes. RESULTS: Suckling of milk replacer immediately increased abomasal luminal pH from 1.4 to 6.0, followed by a gradual decrease to preprandial values by 6 hours. Preprandial and postprandial pH values were not significantly different between the abomasal body and pyloric antrum, indicating lack of pH compartmentalization in the abomasum of milk-fed calves. Administration of cimetidine and ranitidine caused a significant dose-dependent increase in mean 24-hour abomasal luminal pH. CONCLUSIONS AND CLINICAL RELEVANCE: Abomasal acid secretion in milk-fed calves is mediated in part by histamine type-2 receptors. Cimetidine and ranitidine may be efficacious in the treatment of abomasal ulcers in milk-fed calves.     

Effect of ranitidine on gastric acid secretion in young male horses

Gastric cannulas were placed surgically in 5 young male horses. After a 2-week recovery period, horses were studied once a week. Horses were fasted for 24 hours, and gastric fluid output was collected for 5 continuous hours. Volumes were recorded every 15 minutes, and pH and hydrogen ion concentration were determined in an aliquot from each period. In 10 basal experiments, using 5 horses, volume, pH, and hydrogen ion concentration were continuously variable. Mean acid output was 45.1 +/- 2.02 microEq/15 min/kg (mean +/- SEM). In 6 experiments, using 3 horses, 0.5 mg of ranitidine/kg of body weight, given as an IV bolus after a 1-hour basal collection, significantly (P less than 0.02) inhibited hourly total acid output for 4 hours, but did not significantly change pH. The cannulation technique was done without complications, and horses tolerated the cannula for several months. Seemingly, the horse has a continuously variable gastric acid secretion, and histamine type-2 receptors have a role in this process.     

Effect of cimetidine on abomasal pH and Haemonchus and Ostertagia species in sheep

Cimetidine, a histamine H2-receptor blocking agent which reduces gastric acid flow in simple stomach animals was administered directly into the abomasum of sheep at 100 mg kg-1 twice daily for five consecutive days and again on the eighth day. The drug caused a significant increase in the pH values of the abomasal contents and was highly effective in reducing the adult population of Haemonchus contortus (100 per cent) and Ostertagia circumcincta (70 per cent) in the abomasum of sheep. The possibility of using cimetidine as a method of treating abomasal nematode parasitism is discussed.     

Effects of low dosages of intravenous dexamethasone on serum cortisol concentrations in the normal cat

The suppressive effects of three different low dosages of dexamethasone (5, 10 and 15 micrograms kg-1) on serum cortisol concentrations were evaluated in 10 normal cats. On four different days, serum was collected before and at two, four, six and eight hours after the intravenous administration of saline or dexamethasone. Following the administration of saline, no significant difference in mean serum cortisol concentrations was noted between the basal or postinjection values. In contrast, mean serum cortisol concentrations decreased significantly (P less than 0.05) by two hours and remained significantly below mean basal values eight hours after injection of all three dosages of dexamethasone. The degree of cortisol suppression became progressively greater as the dosages of dexamethasone were increased. After administration of the highest dose of dexamethasone (15 micrograms kg-1), serum cortisol decreased to below 5 ng ml-1 by two to four hours and remained suppressed (under 5 ng ml-1) eight hours after injection in all cats. In contrast, two of the 10 cats showed a slight escape from cortisol suppression by eight hours after injection of dexamethasone at the dosage of 10 micrograms kg-1, whereas a dosage of 5 micrograms kg-1 failed to suppress cortisol concentrations below 10 ng ml-1 at any of the sampling times in one cat and was associated with increasing serum cortisol concentrations at eight hours after injection in three cats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Experimental 3-nitro-4-hydroxyphenylarsonic acid toxicosis in pigs

Five times the recommended dose of 3-nitro-4-hydroxyphenylarsonic acid (187.5 mg kg-1) induces a pathognomonic clinical syndrome in pigs. The main clinical features are not continually present but are inducible only by exercise. From day 11 on the experimental diet a nervous syndrome was inducible. This manifested as muscle tremors and clonic convulsive episodes. Paraparesis developed by day 22 and paraplegia by day 33. Liver arsenic levels plateaued at 5.4 +/- 1.3 mg kg-1. The experiment confirms field observations that 3-nitro produces a characteristic toxicological syndrome, which is distinct from that of arsanilic acid. It also confirms that 3-nitro has a higher absolute toxicity than arsanilic acid in pigs as well as a lower margin of safety.     

Effects of intravenously administrated omeprazole on gastric juice pH and gastric ulcer scores in adult horses

The study was performed to evaluate the efficacy of omeprazole powder in sterile water, administered intravenously, on gastric juice pH in adult horses with naturally occurring gastric ulcers. Omeprazole (0.5 mg/kg, IV) was administered once daily for 5 days to 6 adult horses with gastric ulcers. Gastric juice was aspirated through the biopsy channel of an endoscope and pH was measured before and 1 hour after administration of omeprazole on day 1, and then before and after administration of omeprazole on day 5. Gastric ulcer scores were recorded on day 1 before administration of omeprazole and on day 5, 23 hours after the 4th daily dose. Gastric juice pH and ulcer scores were compared between the times. When compared with the pre-injection value (2.01 +/- 0.42), mean +/- SD gastric juice pH was significantly higher when measured 1 hour after administration of the initial dose (4.35 +/- 2.31), and before (5.27 +/- 1.74) and 1 hour after (7.00 +/- 0.25) administration of omeprazole on day 5. Nonglandular gastric ulcer number score significantly decreased from a mean +/- SD of 3.2 +/- 0.80 to 2.0 +/- 1.1, but nonglandular gastric ulcer severity score remained the same. Few glandular ulcers were seen in the study, and scores did not change. Because of its potent and long duration of action on gastric juice pH, this intravenous formulation of omeprazole may show promise for treatment of equine gastric ulcer syndrome (EGUS) in horses with dysphagia, gastric reflux, or other conditions that restrict oral intake of omeprazole paste. Aspiration of gastric juice and measurement of pH can be of use to determine whether the desired pH > 4.0 has been reached after omeprazole treatment.     

Effect of flunixin meglumine and cimetidine hydrochloride on the pH in the third compartment of the stomach of llamas.

A Tigon fistula was surgically implanted into the third compartment of the stomach of 5 llamas to allow measurement of gastric pH. The llamas were allotted into 2 groups and given flunixin meglumine or cimetidine hydrochloride for 3 days. After 4 days without treatment, the drugs given to each group were reversed. Measurements of gastric pH were taken every 30 minutes for 6 hours, using an automated pH meter. The pH measurements after drug administration were compared with measurements obtained during a pretreatment control period. Gastric pH during pretreatment control periods had a mean of 1.43 +/- 0.063 (mean +/- SE). The use of flunixin did not significantly decrease gastric pH, compared with pretreatment controls. Gastric pH was significantly higher within the first 30 minutes after administering cimetidine, compared with pretreatment controls, but this difference disappeared at all later times.     

Evaluation of lansoprazole (an H+/K+-ATPase inhibitor) and azithromycin (an antibiotic) for control of gastric ulceration in swine during periods of feed deprivation.

Helicobacter-like organisms as well as fermentative bacteria have been implicated in gastric ulcer production in swine. Irregular feeding schedules are also considered a major risk factor. A research trial was conducted to determine whether medication with an acid secretion inhibitor (lansoprazole), either alone or in combination with an antibiotic (azithromycin), would protect pigs from gastric ulceration if the animals were subjected to a 48 h period of fasting. In a 2 x 3 factorial design, 48 pigs were fasted, while an equal number were fed ad libitum. Within these 2 study groups, pigs were randomly assigned to 1 of 3 treatments: control, 30 mg lansoprazole s.i.d. for 7 d, or lansoprazole (30 mg s.i.d. for 7 d) and azithromycin (500 mg s.i.d. for 3 d). Overall, fasted pigs were 1.9 times more likely to develop erosive or ulcerative lesions of the pars esophagea (chi2 = 9.89, P < 0.002). Treatment with an acid secretion inhibitor alone or in combination with an antibiotic did not protect pigs from developing gastric lesions. Helicobacter-like organisms were not detected in any of the stomachs. Possibly, the lansoprazole dose of 30 mg given once per day was insufficient to prevent pH levels from becoming low enough to cause damage to epithelial tissue. Alternatively other substances such as bile acids may have caused the ulcerative lesions, even though stomach acid production was suppressed.     

Effect of cimetidine on aspirin-induced gastric hemorrhage in dogs

Efficacy of cimetidine in the prevention of aspirin-induced gastric hemorrhage was evaluated, using 4 groups of 6 dogs given: Group 1--controls; group 2-7.5 mg of cimetidine/kg of body weight every 8 hours; group 3-7.5 mg of cimetidine/kg every 8 hours and 35 mg of nonbuffered aspirin/kg every 8 hours; and group 4-35 mg of nonbuffered aspirin/kg every 8 hours. All medication was given orally for 10 days at the time of feeding a commercial dry food. The gastric mucosa was evaluated endoscopically before treatment, on treatment day 5, and 36 hours after the final treatment. The dogs were given halothane inhalation anesthesia and were evaluated, using a grading system. Total 24-hour fecal hemoglobin (Hb) concentration was measured, using a quantitative fluorometric analysis for Hb-derived porphyrins. Control dogs and dogs given cimetidine only had no endoscopically visible gastric lesions and no increase in fecal Hb concentration. All dogs given aspirin or aspirin and cimetidine had a similar marked increase in endoscopically visible gastric hemorrhage and marked increases in fecal Hb concentration; however, there was no significant (P = 0.48) difference between the 2 groups. Seemingly, cimetidine given at an oral dosage of 7.5 mg/kg every 8 hours was not effective in preventing aspirin-induced gastric hemorrhage in clinically normal dogs.     

Effects of short-term sodium chlorate exposure on pigs

The present study evaluated the effects of exposure to different doses of sodium chlorate in 10-week-old pigs. Twenty pigs were divided into four equal groups and treated with different doses of sodium chlorate: 0, 125, 250 and 500 mg kg-1 body weight per day via the drinking water for 7 consecutive days. The results showed a significant decrease (P < 0.05) in red blood cell and white blood cell counts, packed cell volume, haemoglobin, blood urea nitrogen (P < 0.001) and creatinine levels, and an increase in aspartate aminotransferase and alanine aminotransferase (P < 0.05) activities in swine administered sodium chlorate at a dose of 500 mg kg-1 body weight per day. The histopathological study revealed increased numbers of vacuoles in the convoluted tubules, tubular necrosis and degeneration of the renal tubular epithelial cells, depletion of nuclei and lobular necrosis of the liver in all pigs treated with sodium chlorate at 500 mg kg-1 body weight per day. Thus, 7-day administration of sodium chlorate at 500 mg kg-1 body weight per day to pigs affects the liver and kidney tissues as well as the haematologic and serum biochemical parameters.     

巴马小型猪对高致病性猪繁殖与呼吸综合征病毒的敏感性评价

为评价巴马小型猪对高致病性猪繁殖与呼吸综合征病毒(HP-PRRSV)的敏感性,本研究选择PRRSV抗体阴性的16头巴马小型猪和17头本地二元杂交猪作为研究对象,分别分为低剂量接毒组、高剂量接毒组、对照组1和对照组2,低剂量、高剂量接毒组肌肉注射接种PRRSV NVDC-JXA1强毒株,对照组1和接毒组混合饲养,对照组2分开饲养作为空白对照。接毒后每天测量体温,观察精神、食欲、死亡等情况,死亡动物剖检病变,攻毒后每隔7d采血用RT-PCR法检测病原,连续观察21d。结果绝大部分猪体温升高到41℃以上,且有3个以上温次,所有接种及混养动物都死亡,巴马小型猪死亡时间在8d~17d,二元杂交猪在7d~13d,死亡动物出现肺充血、出血、实变,扁桃体、淋巴结、肝脏、肾脏、皮下有出血等症状,病原RTPCR检测为阳性,说明攻毒动物死于HP-PRRS,表明巴马小型猪对PRRSV NVDC-JXA1强毒株非常敏感,可用于PRRS活疫苗的检验。     

Stimulation of in vitro muscle cell proliferation by sera from swine injected with porcine growth hormone

The proliferation-promoting activity of sera obtained from pigs before and after porcine growth hormone injections was tested in a muscle cell culture bioassay. For 3 d, purified porcine growth hormone (pGH) was administered by intramuscular injection to crossbred barrows. Two levels of pGH were administered: 18 micrograms pGH X kg-1 body weight X d-1 (low dose) or 143 micrograms pGH X kg-1 body weight X d-1 (high dose). Multiple blood samples were withdrawn from jugular catheters for 3 d prior to the injection, during the injection period and for 6 d after the last injection. Although serum pGH levels in low-dose pigs were raised from two to three times pre-injection levels, there was no significant change in serum proliferation-promoting activity or somatomedin-C (SmC), insulin or cortisol levels during or after administration of pGH. In contrast, the proliferation-promoting activity of sera obtained during and after the high-dose pGH injections was higher (P less than .005) than the pre-injection levels. Serum pGH levels were increased approximately 30-fold by 4 h after each injection, and increases in SmC levels were observed 10 to 16 h after the pGH injection. During the injection period SmC levels increased from 1.7 to 4 times pre-injection levels. Insulin and cortisol levels did not change significantly during the 3-d treatment period. We believe that this muscle cell culture bioassay system will be a useful addition to traditional radioimmunoassays and whole animal studies in elucidating the mode of action of pGH in pituitary-intact swine.     

Cephalexin in ponies: a preliminary investigation

The administration of a single dose of the antibacterial agent cephalexin intramuscularly to six ponies at a dose rate of 7 mg/kg was well tolerated. No reactions at the injection site were apparent. It was absorbed rapidly and reached a mean peak plasma concentration of 6.77 micrograms/ml after a mean of 1.41 hours; plasma concentrations above 2.0 and 0.5 micrograms/ml were maintained for 3.8 and 9.8 hours, respectively.     

Disposition of the anti‐ulcer medications ranitidine,cimetidine, and omeprazole following administration of multiple doses to exercised Thoroughbred horses

The use of anti‐ulcer medications, such as cimetidine, ranitidine, and omeprazole, is common in performance horses. The use of these drugs is regulated in performance horses, and as such a withdrawal time is necessary prior to competition to avoid a medication violation. To the authors' knowledge, there are no reports in the literature describing repeated oral administrations of these drugs in the horse to determine a regulatory threshold and related withdrawal time recommendations. Therefore, the objective of the current study was to describe the disposition and elimination pharmacokinetics of these anti‐ulcer medications following oral administration to provide data upon which appropriate regulatory recommendations can be established. Nine exercised Thoroughbred horses were administered 20 mg/kg BID of cimetidine or 8 mg/kg BID of ranitidine, both for seven doses or 2.28 g of omeprazole SID for four doses. Blood samples were collected, serum drug concentrations were determined, and elimination pharmacokinetic parameters were calculated. The serum elimination half‐life was 7.05 ± 1.02, 7.43 ± 0.851 and 3.94 ± 1.04 h for cimetidine, ranitidine, and omeprazole, respectively. Serum cimetidine and ranitidine concentrations were above the LOQ and omeprazole and omeprazole sulfide below the LOQ in all horses studied upon termination of sample collection.     

Effect of pantothenic acid on disposition kinetics and tissue residues of sulphadimidine in chickens

Sulphadimidine was administered to chickens via the intracrop route to determine plasma concentrations of the unchanged sulphonamide and its acetylated derivatives, kinetic disposition, tissue residues and acetylation. The sulphadimidine was given alone (group 1) at a dose of 200 mg kg-1 bodyweight. Pantothenic acid was given via the intracrop route at a dose of 100 mg kg-1 bodyweight one hour before (group 2) and six hours after (group 3) sulphadimidine administration (200 mg kg-1 bodyweight intracrop). The highest plasma concentrations of sulphadimidine in groups 1, 2 and 3 were reached in 1.73, 1.62 and 1.71 hours, respectively, following intracrop administration. In birds of groups 1, 2 and 3 no sulphadimidine was detected at 72, 24 and 48 hours, respectively, following its administration. Estimation of sulphadimidine in most of the body tissues revealed that all tissues examined had lower concentrations than plasma. In chickens given pantothenic acid (groups 2 and 3) before and after sulphadimidine administration, an increase in the concentration of N4 acetylated derivatives of sulphadimidine was observed compared with birds given sulphadimidine alone (group 1).     

Anesthesia of growing pigs with tiletamine-zolazepam and reversal with flumazenil

The aim of the present study was to evaluate the anesthetic and cardiorespiratory effects of tiletamine/zolazepam and the effect of flumazenil on the recovery from tiletamine/zolazepam anesthesia in the pig. Six Landrace and Yorkshire cross-bred pigs (three females and three males, 3-4 months old) weighing 35.8 ± 1.7 kg were used in this study. Pigs were given tiletamine/zolazepam intramuscularly at a dose of 4.4 mg kg(-1) (2.2 mg kg(-1) tiletamine and 2.2 mg kg(-1) zolazepam) of body weight. Twenty minutes after the administration of tiletamine/zolazem, the pigs were given saline solution (control, Group TZ) or given flumazenil intravenously at a dose of 0.08 mg kg(-1) of body weight (Group TZF). Anesthesia and recovery times, scores of anesthetic effects and cardiorespiratory variables were recorded for each pig. There was a significant difference between the duration of tiletamine/zolazepam anesthesia with and without the antagonist. Flumazenil significantly shortened the recovery time. A significant difference in blood gas variables was observed between the two groups. The anesthetic effects induced by tiletamine/zolazepam could be reversed successfully and safely by flumazenil alone. Therefore, flumazenil administration could be considered in cases in which quick recovery is required in pigs.     

Prolonged interval between parturition of normal live pups in a bitch

On day 64 after artificial insemination, a six-year-old primiparous briard bitch whelped three live pups between 05.00 and 08.00. It was presented at 11.00 on the same day with failure to complete parturition. On ultrasound examination, a normal live fetus was observed and the bitch was treated with oxytocin three times during the day (1.0, 2.0 and 2.0 iu intramuscularly), with no effect. The following day, a higher dose of oxytocin (5.0 iu) was administered intramuscularly at 11.00, after a uterine ultrasound examination confirmed viability of the fetus. At 18.00 of the same day, the bitch whelped the fourth normal live pup, 37 hours after initiation of parturition and 34 hours after expulsion of the last fetus. Effectiveness of oxytocin and normal versus prolonged parturition due to uterine inertia are discussed.