Use of an isolated intestinal circuit to evaluate the effect of ischemia and reperfusion on mucosal permeability of the equine jejunum

OBJECTIVES: To evaluate the efficacy of an isolated perfusion circuit and the effect of ischemia-reperfusion on mucosal permeability of the jejunum. STUDY DESIGN: In vitro study of intestinal mucosal permeability. ANIMALS: Twelve healthy adult horses. METHODS: A control segment of jejunum was placed in an isolated perfusion circuit for 240 minutes and mucosal permeability was measured. After detecting no deleterious effects of the isolated system on the control intestine, low flow ischemia was created in experimental segments for 20, 40, 60 and 90 minutes followed by 60 minutes of reperfusion and mucosal permeability was evaluated. At the completion of the studies, histologic evaluation was used to determine mucosal grades, surface area, and volume. RESULTS: Control tissue was maintained in the isolated circuit for 240 minutes without effect on mucosal grade, surface area, or volume relative to intact tissue. After ischemia-reperfusion, mucosal grade increased, and volume and surface area decreased progressively with longer periods of ischemia. Mucosal clearance of albumin remained constant during 240 minutes of perfusion in control tissue and was elevated after ischemia-reperfusion. CONCLUSIONS: No deleterious changes were noted in jejunum perfused with this isolated circuit, whereas alterations in mucosal permeability were present after ischemia-reperfusion. CLINICAL RELEVANCE: The isolated perfusion circuit successfully maintained an isolated segment of jejunum within physiologic limits, and can be used to evaluate the effects of injury and the efficacy of pharmaceuticals to attenuate these changes.     

The effects of endoparasitism on the immune response to orally administered antigen in cats

The aim of the study was to assess whether infection with Toxocara cati (T. cati) facilitates the induction of immunoglobulin (Ig) E or other antibody responses to a specific antigen administered with food in kittens. Two groups of 10 cats each, either experimentally infected with T. cati or parasite-free, were dosed with human serum albumin (HSA) added daily to their food from day 7 to 28 inclusive. Levels of HSA-specific IgE, IgG, IgA and IgM were assessed in the serum by enzyme-linked immunosorbent assay (ELISA) in both groups of cats at weeks 0, 2, 4 and 8. Although weak, an IgE response was detected in most of the cats 1 week after exposure to HSA. However, HSA-specific IgG and IgA could only be detected from the third week after exposure to HSA. The group of parasitized cats had significantly higher levels of HSA-specific antibodies of the IgG and IgA at weeks 4 and 8 (p<0.05 by Mann-Whitney) and IgE isotypes at weeks 2 and 4 (p<0.05 by analysis of variance (ANOVA)) than did the group of parasite-free cats. Specific IgM antibody was not detected in the sera of any of the 20 cats. These findings are supportive of a role of T. cati infection in enhancing the IgE response to orally administered antigens, and hence possibly, in genetically susceptible individuals, in the development of food hypersensitivity.     

Effect of orally administered tramadol alone or with an intravenously administered opioid on minimum alveolar concentration of sevoflurane in cats

OBJECTIVE-To compare the effect of oral administration of tramadol alone and with IV administration of butorphanol or hydromorphone on the minimum alveolar concentration (MAC) of sevoflurane in cats. DESIGN-Crossover study. ANIMALS-8 Healthy 3-year-old cats. PROCEDURES-Cats were anesthetized with sevoflurane in 100% oxygen. A standard tail clamp method was used to determine the MAC of sevoflurane following administration of tramadol (8.6 to 11.6 mg/kg [3.6 to 5.3 mg/lb], PO, 5 minutes before induction of anesthesia), butorphanol (0.4 mg/kg [0.18 mg/lb], IV, 30 minutes after induction), hydromorphone (0.1 mg/kg [0.04 mg/lb], IV, 30 minutes after induction), saline (0.9% NaCl) solution (0.05 mL/kg [0.023 mL/lb], IV, 30 minutes after induction), or tramadol with butorphanol or with hydromorphone (same doses and routes of administration). Naloxone (0.02 mg/kg [0.009 mg/lb], IV) was used to reverse the effects of treatments, and MACs were redetermined. RESULTS-Mean +/- SEM MACs for sevoflurane after administration of tramadol (1.48 +/- 0.20%), butorphanol (1.20 +/- 0.16%), hydromorphone (1.76 +/- 0.15%), tramadol and butorphanol (1.48 +/- 0.20%), and tramadol and hydromorphone (1.85 +/- 0.20%) were significantly less than those after administration of saline solution (2.45 +/- 0.22%). Naloxone reversed the reductions in MACs. CONCLUSIONS AND CLINICAL RELEVANCE-Administration of tramadol, butorphanol, or hydromorphone reduced the MAC of sevoflurane in cats, compared with that in cats treated with saline solution. The reductions detected were likely mediated by effects of the drugs on opioid receptors. An additional reduction in MAC was not detected when tramadol was administered with butorphanol or hydromorphone.     

Serum glucose and insulin responses to an insulin-containing ophthalmic solution administered topically in clinically normal cats

Serum glucose and immunoreactive insulin concentrations were monitored after topical administration of an insulin-containing ophthalmic solution in 20 clinically normal cats. Three ophthalmic surface-acting agents, benzalkonium chloride, dimethyl sulfoxide, and proparacaine hydrochloride, were evaluated individually for their effectiveness in enhancing absorption of topically applied insulin. The ophthalmic effects of insulin-containing ophthalmic preparations were assessed by complete ophthalmic examination before and at the conclusion of each test period. Withholding of food overnight (12 hours) preceded each topical application of insulin-containing ophthalmic solution (12.25 to 26.4 U/cat), either alone or in combination with surface-acting agents, after which blood samples were drawn serially from an indwelling IV catheter over a period of 8 hours. Baseline serum insulin concentration, after food was withheld for 12 hours, in nonstressed cats was 6.0 microU/ml (geometric mean), and an exponentiation of the logarithmic quantity (mean +/- SD) yielded values of 1.5 to 23.0 microU/ml. All ophthalmic solutions tested failed to significantly lower serum glucose concentration or increase serum insulin concentration. Solutions used did not induce deleterious effect on ocular structures. Results indicate that topical administration of insulin-containing ophthalmic solution, either alone at the concentrations used or in combination with surface-acting agents, did not result in effective absorption of insulin across the conjunctival and lacrimal nasal mucosa in biologically relevant quantities. Thus, this route of insulin administration, under these specific conditions, is not an effective alternative or adjunct to SC administration of insulin for treatment of cats with insulin-dependent diabetes mellitus or severe noninsulin-dependent diabetes mellitus.     

Sedative and physiologic effects of orally administered alpha 2-adrenoceptor agonists and ketamine in cats

OBJECTIVE: To compare efficacy of 3 regimens of orally administered sedatives and determine physiologic effects of 1 of these regimens in healthy cats. DESIGN: Prospective randomized study. ANIMALS: 34 cats. PROCEDURE: Cats were assigned to 1 of 3 groups that were treated by oral administration of detomidine and ketamine, xylazine and ketamine, or medetomidine and ketamine. Cats were monitored for degree of sedation at 5-minute intervals for 60 minutes. Physiologic effects in cats treated with detomidine and ketamine were measured at 5-minute intervals for 30 minutes and compared with effects in cats treated i.m. with detomidine and ketamine or xylazine and ketamine. RESULTS: All cats treated orally with detomidine and ketamine became laterally recumbent; sedation was more variable in the other 2 groups treated orally. Vomiting and excessive salivation were the only adverse effects. Bradycardia (heart rate < 145 beats/min) was detected at each evaluation time in cats treated orally with detomidine and ketamine and in all cats treated i.m. Minimal differences among groups were detected for heart and respiratory rates, rectal temperature, and hemoglobin oxygen saturation. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of detomidine and ketamine is an effective method of sedating healthy cats and induces minimal physiologic effects that are similar to those resulting from i.m. administration of sedatives.     

Use of orally administered carfentanil prior to isoflurane-induced anesthesia in a Kodiak brown bear

A captive 590-kg (1,298-lb) 22-year-old castrated male Kodiak brown bear was evaluated because of a soft tissue mass in the right carpal and antebrachial regions. General anesthesia was deemed necessary on 3 occasions for various procedures including radiographic evaluation and biopsy, excision, and radiation treatment. The bear was given carfentanil orally to induce sedation, followed by i.m. administration of tiletamine-zolazepam (on 1 occasion) and atropine. Anesthesia was maintained by administration of isoflurane in oxygen. After each procedure, effects of carfentanil were reversed by administration of naltrexone. Although there was some variability, blood pressure, nasal temperature, heart rate, respiratory rate, oxygen saturation, PO2, and PCO2 remained within a clinically acceptable ranges.     

Use of thermal threshold response to evaluate the antinociceptive effects of butorphanol in cats

OBJECTIVE: To characterize the antinociceptive actions of several doses of butorphanol by use of a thermal threshold testing device specifically designed for cats. ANIMALS: 6 domestic shorthair cats. PROCEDURE: The study was a masked, randomized, crossover design. Thermal thresholds were measured by use of a thermal threshold-testing device specifically developed for cats. A small probe containing a heater element and temperature sensor was held with consistent contact against a shaved area of the cat's skin with an elasticized band. Skin temperature was recorded before each test, prior to activation of the heater. On detection of a response (eg, the cat flinched, turned, or jumped), the stimulus was terminated and the threshold temperature recorded. Three baseline measurements were recorded before IV injection of 0.1, 0.2, 0.4, or 0.8 mg of butorphanol/kg. Each cat received all doses in a randomized order at least 1 week apart. The investigator was unaware of the treatment received. Thermal thresholds were measured every 15 minutes for 6 hours. RESULTS: Mean+/-SD pretreatment threshold temperature for all cats was 40.8+/-2.2 degrees C. There were no dose-related differences among treatments. There was a significant increase in threshold values for all treatments from 15 to 90 minutes after injection. Mydriasis was detected in all cats after treatment with butorphanol and dysphoric behavior was frequently exhibited. CONCLUSIONS AND CLINICAL RELEVANCE: Results obtained by use of a thermal stimulus indicated that the duration of antinociceptive action of butorphanol was 90 minutes and there was no dose-response relationship in cats.     

Effects of nicarbazin on sugar intestinal absorption in rabbits.

Nicarbazin is an anticoccidial drug, used mainly in birds, which can also be used in rabbits. It has been shown to produce several effects, such as inhibition of growth and feed efficiency in poultry. The aim of the present work was to determine whether nicarbazin alters intestinal absorption of sugar. Results obtained show that nicarbazin decreases D-galactose accumulation in the jejunal tissue and increases mucosal to serosal transepithelial fluxes of this sugar, in both cases in a dose-dependent way. Furthermore, nicarbazin seems not to modify the sugar diffusion across the intestinal epithelium. The drug also stimulates the sugar uptake in brush border and basolateral membrane vesicles. The results suggest that in rabbits nicarbazin increases sugar intestinal absorption mediated by carriers.     

Comparison of an orally administered gastrointestinal lavage solution with traditional enema administration as preparation for colonoscopy in dogs

Forty dogs were randomly assigned to be given either multiple enemas (group A) or orally administered lavage solution (group B) before colonoscopy. Dogs of group A (n = 20) were given 3 large-volume warm-water enemas 6 hours apart, with the last enema given 9 to 15 hours before colonoscopy. Dogs of group B (n = 20) were given a total dose of 50 ml of the lavage solution/kg of body weight through an orogastric tube. The lavage solution was administered in 2 doses of 25 ml/kg given 1 hour apart, 12 to 18 hours before colonoscopy. Dogs were monitored for changes in body weight and in serum sodium, potassium, chloride, calcium, phosphate, urea nitrogen, creatinine, and total CO2 concentrations. Colonoscopy was performed on dogs under general anesthesia by an investigator blinded as to the method of preparation, and the quality of preparation was subjectively evaluated. The quality of colon preparation was significantly (P less than 0.005) better after administration of oral lavage solution, compared with that after multiple enemas. There were minimal changes in laboratory values, side-effects were minimal, and biopsy specimen artifacts were not seen. Because proper patient preparation is necessary for complete colonoscopic examination, results suggested that an orally administered polyethylene glycol-containing electrolyte solution is preferable to administration of multiple enemas in preparing dogs for colonoscopy.     

Pharmacokinetics of enrofloxacin administered intravenously and orally to foals

OBJECTIVE: To determine the pharmacokinetics of enrofloxacin administered IV and orally to foals. ANIMALS: 5 clinically normal foals. PROCEDURE: A 2-dose cross-over trial with IV and oral administration was performed. Enrofloxacin was administered once IV (5 mg/kg of body weight) to 1-week-old foals, followed by 1 oral administration (10 mg/kg) after a 7-day washout period. Blood samples were collected for 48 hours after the single dose IV and oral administrations and analyzed for plasma enrofloxacin and ciprofloxacin concentrations by use of high-performance liquid chromatography. RESULTS: For IV administration, mean +/- SD total area under the curve (AUC0-infinity) was 48.54 +/- 10.46 microg x h/ml, clearance was 103.72 +/- 0.06 ml/kg/h, half-life (t1/2beta) was 17.10 +/- 0.09 hours, and apparent volume of distribution was 2.49 +/- 0.43 L/kg. For oral administration, AUC0-infinity was 58.47 +/- 16.37 microg x h/ml, t1/2beta was 18.39 +/- 0.06 hours, maximum concentration (Cmax) was 2.12 +/- 00.51 microg/ml, time to Cmax was 2.20 +/- 2.17 hours, mean absorption time was 2.09 +/- 0.51 hours, and bioavailability was 42 +/- 0.42%. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with adult horses given 5 mg of enrofloxacin/kg IV, foals have higher AUC0-infinity, longer t1/2beta, and lower clearance. Concentration of ciprofloxacin was negligible. Using a target Cmax to minimum inhibitory concentration ratio of 1:8 to 1:10, computer modeling suggests that 2.5 to 10 mg of enrofloxacin/kg administered every 24 hours would be effective in foals, depending on minimum inhibitory concentration of the pathogen.     

Use of orally administered oxidised copper wire particles for copper therapy in cattle

Oxidised copper wire particles (OCWP) were given per os to cattle as an alternative to subcutaneous copper glycinate injections. OCWP were recovered from the stomachs of cattle slaughtered 3 months after treatment. OCWP (50g) treatment resulted in sustained higher plasma copper concentrations than subcutaneous injections of copper glycinate. OCWP given at high doses (300g) raised liver copper concentrations to 16 mmol/kg without clinical effects. It is concluded that OCWP could be a practical alternative to current injection methods of copper therapy.     

口服精胺激发血浆皮质醇促进哺乳仔猪肠道发育的机理

试验建立仔猪血浆皮质醇抑制模型初步探索精胺促进哺乳仔猪肠道发育的机制。选取6窝11日龄的哺乳仔猪进行试验,采用随机区组设计,以窝别为区组,每头仔猪为试验重复,每窝选取体重相近的4头仔猪(共24头)随机分配到4个处理组。处理组设计如下:处理组1,口服生理盐水和注射生理盐水;处理组2,口服0.4 mmol/(kg BW·d)精胺和注射生理盐水;处理组3,口服生理盐水和肌肉注射5 mg/(kg BW·d)甲双吡丙酮(metyrapone);处理组4,注射5 mg/(kg BW·d)甲双吡丙酮和口服0.4 mmol/(kg BW·d)精胺。结果显示:试验成功地建立血浆皮质醇模型。处理组1~4仔猪空肠黏膜麦芽糖酶比活力分别为118.5、195.3、88.3、144.2 U/g蛋白。处理组2麦芽糖酶比活力显著高于处理组1和处理组4(P0.05),且显著高于处理组3(P0.05);处理组1和处理组4麦芽糖酶比活力差异不显著,但显著高于处理组3(P0.05)。处理组1和处理组3空肠绒毛高度差异不显著(P0.05),且显著高于处理组2和处理组4(P0.05)。以上结果初步证明,口服精胺具有激发血浆皮质醇促进幼龄哺乳仔猪肠道发育的作用。     

Biokinetics and biliary excretion of radiotocopherol administered orally to sheep.

Four adult sheep were given .4 microCi/kg of BW of D-alpha[5-Me-3H]tocopherol orally. Plasma alpha-tocopherol specific activities were measured serially during a 72-h period, after which the sheep were killed. The disposition kinetics were best described by the use of a two-compartment model. The radiotocopherol had a slow distribution phase followed by a relatively slow elimination phase. During the 72-h period of serial monitoring the peak plasma specific activities were observed between 32 to 48 h. At slaughter (72 h after dosing) tissue radioactivity distribution indicated a high rate of accumulation in some glandular organs such as the liver and adrenals. Identification of radioactive components excreted in bile, using HPLC or thin-layer chromatography, showed that unchanged radiotocopherol was present only at very low concentrations (less than 3% of the total recovered radioactivity).     

Responses of horses to acepromazine maleate administered orally in a paste

The effects of acepromazine maleate (ACP), given orally in a paste form, were examined in six standard-bred geldings over a 12 hour period. Three dose rates, zero (placebo paste), 0.13 mg kg-1 and 0.26 mg kg-1, given before or after feeding, were investigated. The data were divided into two sampling periods for analysis, one from zero to 120 minutes and the other from four to 12 hours. Sedation was assessed by a score (TS score) based on general appearance, anal sphincter relaxation and penile protrusion. This TS score was significantly elevated 40 minutes after dosing with ACP, irrespective of whether the horses had been fed or not. Dose rate had no significant effect on TS in the zero to 120 minute sampling period, but the TS score was significantly (P less than 0.01) higher at the higher dose rate in the four to 12 hour period. At both dose rates, the TS scores were still significantly higher than their pretreatment values 12 hours after dosing. Systolic blood pressure (SBP), measured indirectly from the coccygeal artery, haematocrit (PCV) and total plasma protein concentration (TPP) were also examined. ACP caused significant falls in SBP and PCV, but the effect was complicated by feeding. ACP given after feeding had a reduced effect on SBP and PCV. Feeding appeared to cause a rise then a fall in PCV and TPP which was superimposed upon the fall caused by ACP. There was no difference between the two dose rates of ACP on SBP and PCV.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of an orally administered methylcellulose formulation of gallium maltolate in neonatal foals

Chaffin, M. K., Fajt, V., Martens, R. J., Arnold, C. E., Cohen, N. D., O’Conor, M., Taylor, R. J., Bernstein, L. R. Pharmacokinetics of an orally administered methylcellulose formulation of gallium maltolate in neonatal foals. J. vet. Pharmacol. Therap. doi: 10.1111/j.1365‐2885.2009.01150.x. Gallium is a trivalent semi‐metal with anti‐microbial effects because of its incorporation into crucial iron‐dependent reproductive enzyme systems. Gallium maltolate (GaM) provides significant gallium bioavailability to people and mice following oral administration and to neonatal foals following intragastric administration. To study the prophylactic and therapeutic effects of GaM against Rhodococcus equi pneumonia in foals, we developed a methylcellulose formulation of GaM (GaM‐MCF) for oral administration to neonatal foals. Normal neonatal foals were studied. Six foals received 20 mg/kg and another six foals received 40 mg/kg of GaM‐MCF orally. Serial serum samples were collected and serum gallium concentrations were determined using inductively coupled plasma mass spectroscopy. Gallium was rapidly absorbed (T_max of 4 h), and a mean C_max of 0.90 or 1.8 μg/mL was achieved in foals receiving 20 or 40 mg/kg respectively. Marked variability existed in C_max among foals: only half of the foals receiving 20 mg/kg attained serum concentrations of >0.7 μg/mL, a level suggested to be therapeutic against R. equi by previous studies. Mean elimination half‐life was 32.8 or 32.4 h for foals receiving 20 or 40 mg/kg respectively. The results of this study suggest that at least 30 mg/kg orally every 24 h should be considered in future pharmacodynamic and efficacy studies.     

Pharmacokinetics of sulphamethoxazole and trimethoprim administered intravenously and orally to Japanese quails

The pharmacokinetic behaviour of sulphamethoxazole and trimethoprim was studied after combined intravenous (i.v.) administration at doses of 20 mg/kg and 4 mg/kg, respectively, and after oral administration at doses of 50 mg/kg and 10 mg/kg. The serum concentration versus time data after i.v. administration were best described by the biexponential equations C = 34.77.e^-2.655.t+ 39.03.e^-0.241.t for sulphamethoxazole and C = 3.29.e^-3.878.t+ 0.83.e^-0.306.t for trimethoprim. Mean biological half-lives of the drugs were 2.89 ± 0.11 and 2.38 ± 0.33 h, respectively. The distribution volumes (V_area) were 0.475 ± 0.026 l/kg (sulphamethoxazole) and 3.89 ± 0.61 I/kg (trimethoprirn). Orally administered sulphamethoxazole and trimethoprim were rapidly absorbed. The maximum serum concentrations were reached 0.5-1 h after administration. The bioavailability was 8 1% for sulphamethoxazole and 41% for trimethoprim.     

Oxytetracycline pharmacokinetics in rainbow trout during and after an orally administered medicated feed regimen

The pharmacokinetic-pharmacodynamic predictor of antimicrobial activity for tetracyclines is reported to be the area under the concentration-time curve at steady state (AUC(ss)) divided by the minimal inhibitory concentration of the targeted pathogen. Here, we estimate AUC(ss) values for oxytetracycline (OTC) in serum of rainbow trout Oncorhynchus mykiss by using a destructive sampling study design. Seventy-two rainbow trout were fed OTC-medicated feed at 74.7 +/- 1.5 mg/kg (mean +/- SD) body weight (BW) by oral gavage for 10 consecutive days. Serum was collected from nine fish at 1, 3, 6, 8, 10, 12, 15, and 22 d after dosing began. Serum OTC concentrations were measured by high-performance liquid chromatography with a 0.01-microg/mL limit of detection. The average OTC AUC(ss) was 29.2 microg x h/mL and was estimated using nonlinear mixed-effects modeling and bootstrap resampling techniques. The elimination half-life was estimated as 85.0 h, and the fraction of steady state achieved was estimated as 0.85. The calculated AUC(ss) (24.8 microg x h/mL) following 10 d of oral dosing with 75 mg OTC/kg BW was less than the estimated AUC(ss). Results suggest that the pharmacokinetics of OTC exposure, including the AUC(ss), is better evaluated by using multiday dosimetry than by using a standard single-dose protocol.