A study was conducted to investigate whether aspiration of amniotic fluid is associated with a deleterious effect on absorption of colostral immunoglobulins or on blood gas and acid-base values of healthy newborn calves. Fourteen calves purchased from commercial sources were transported to a research facility immediately after birth and fed colostrum with known concentrations of immunoglobulins. Blood samples for gas analyses were collected within 5 hours of birth, 24 hours later, and prior to euthanasia. Between 3 and 5 days of age, calves were euthanatized by an overdose of barbiturates. Eleven calves had evidence of bronchoaspiration of amniotic fluid, as determined by presence of meconium, squamous epithelium, or keratin in histologic sections of fixed lung or by cytologic analysis of bronchoalveolar lavage fluid. Blood gas tensions and pH were within reference ranges in 11 of 14 calves. Aspiration of amniotic fluid could not be linked to any specific changes in blood gas tensions, acid-base status, or absorption of colostral immunoglobulins. Presence of keratin and meconium in the lungs often was accompanied by mild exudative alveolitis and focal atelectasis. It was concluded that aspiration of small amounts of amniotic fluid with or without meconium is common in calves and is not associated with hypoxemia, respiratory acidosis, or failure of passive transfer.

Newborn pups from 4 large litters were allotted to 6 groups to determine effect of time and route of administration on absorption of an alternate source of immunoglobulin. Selective absorption of specific classes of immunoglobulins was also investigated. The alternate source of immunoglobulin consisted of pooled serum that was administered either PO or SC. Control groups were either left with the dam (group C1) or fed milk replacer (group C2). Blood samples were collected from pups at birth and 24 hours. Immunoglobulin (IgA, IgG, IgM) concentrations were determined by use of radial immunodiffusion on samples of pooled serum, colostrum, and pups' serum (birth and 24 hours). Serum IgA concentration was less than the sensitivity of the procedure and was not included in the statistical analysis. Pups fed 8 ml of pooled serum at birth and 12 hours later (group T1) absorbed more (P < 0.05) IgG and IgM than did group-C2 pups, but less (P < 0.05) than did group-C1 pups. Pups fed 8 ml of pooled serum at 12 hours only had significant (P < 0.05) increase of IgG concentration, but no absorption of IgM (P > 0.05) at 24 hours, compared with control pups (group C2). Pups administered 8 ml of pooled serum SC at birth (group SC1) had similar (P > 0.05) absorption of IgG and higher (P < 0.05) absorption of IgM than did pups of group T1. Pups administered 16 ml of pooled serum SC at birth had the highest increase of IgG and IgM concentrations of all treatment groups, but immunoglobulin concentrations were lower (P < 0.05) than those for group-C1 pups. Absorption of IgG was favored, compared with IgM, when pooled serum was fed. Results indicate clearly that intestinal absorption of immunoglobulins is minimal after 12 hours and thus, another route of administration should be used. Pups in groups SC1 and T1 had similar absorption of IgG, despite lower IgM absorption in pups of group T1. This lower IgM concentration in group-T1 pups may have been the result of selective intestinal absorption or the consequence of low number of pups per group. Subcutaneous administration of 16 ml of pooled serum was the most successful alternative to colostrum, with minimal pain to pups if serum was administered slowly. Serum IgG concentration in C1 pups was higher than expected and probably was attributable to the amount of colostrum available to the pups.

Absorption rate and plasma and fat disposition of lindane after various lindane percutaneous treatments in shorn and unshorn sheep were investigated. To analyze data with a deconvolution method, IV administration was performed to determine the basic pharmacokinetic values of lindane in sheep. After IV administration, the steady state volume of distribution was very high (8.07 +/- 3.60 L/kg of body weight), and the mean residence time was long (28.1 +/- 11.7 hours). Deconvolution analysis indicated that lindane absorption was continuous until 33 to 41 days after spraying with a 0.025% lindane solution. Total amount of absorbed lindane in shorn (15,171 +/- 4,463 microgram/kg) sheep was about twice that in unshorn (7,615 +/- 3,128 microgram/kg) sheep; from deconvolution analysis, it was calculated that the time required for 50% of the available dose to be absorbed was between 115 and 179 hours. After percutaneous lindane administration, the fat concentration was compared with the available lindane dose. The apparent half-life of lindane elimination in fat was 225 +/- 47.4 hours, which is similar to the value calculated for the absorption rate constant. By comparing fat and plasma concentrations, it was calculated that for a mean plasma concentration of 5 ng/ml, the fat lindane concentration was 1.65 +/- 0.87 microgram/g (ie, lower than the generally accepted tolerance level of 2 microgram/g).

Mobile phones (MP) and other electronic and communication devices that are used daily expose users to electromagnetic fields (EMF) and contribute to an increasing incidence of neurological disorders. Brain tissue is the closest organ to the MP as it operates, thus the influence of MP radiation on brain tissue is of particular concern, although research is still inconclusive. The present study investigated the possible effect of an EMF (1,350–1,375 megahertz (MHz)) from an MP on morphological and histopathological profiles in the mouse brain. Healthy BALB/c mice were assigned to three equal groups (a control and two experimental groups, n = 10 each). Experimental mice were exposed to EMFs continuously for 72 h, those of experimental group I to a 1,350 MHz field at a specific absorption rate (SAR) of 4.0 W/kg, and group II to a 1,375 MHz field EMF at an SAR of 4.0 W/kg. Brain segmentation and histopathological analysis were applied to detect changes in the morphometric parameters of the brain lobes and identify pathological lesions, respectively. Histopathology results revealed shrinkage of pyramidal neurons, presence of mild perivascular and perineural oedema, and some vacuolation of neurons and glial cells derived from mouse great hemispheres. The lesions also included reduction of Purkinje cells, vacuolisation of neurons and glial cells, and interstitial oedema in the cerebellum. MP distance of 3 cm from the cage may induce appreciable morphological changes in mouse brain structures; therefore, more comprehensive research is essential for assessment of safe distance. These pronounced effects may interfere with the results of laboratory tests on murine experimental models in veterinary or biomedical research.

OBJECTIVE To determine the pharmacokinetics of florfenicol, terbinafine, and betamethasone acetate after topical application to canine auricular skin and the influence of synthetic canine cerumen on pharmacokinetics. SAMPLE Auricular skin from 6 euthanized shelter dogs (3 females and 3 neutered males with no visible signs of otitis externa). PROCEDURES Skin adjacent to the external opening of the ear canal was collected and prepared for use in a 2-compartment flow-through diffusion cell system to evaluate penetration of an otic gel containing florfenicol, terbinafine, and betamethasone acetate over a 24-hour period. Radiolabeled 14C-terbinafine hydrochloride and 3H-betamethasone acetate were added to the gel to determine dermal penetration and distribution. Florfenicol absorption was determined by use of high-performance liquid chromatography–UV detection. Additionally, the effect of synthetic canine cerumen on the pharmacokinetics of all compounds was evaluated. RESULTS During the 24-hour experiment, mean ± SD percentage absorption without the presence of synthetic canine cerumen was 0.28 ± 0.09% for 3H-betamethasone acetate, 0.06 ± 0.06% for florfenicol, and 0.06 ± 0.02% for 14C-terbinafine hydrochloride. Absorption profiles revealed no impact of synthetic canine cerumen on skin absorption for all 3 active compounds in the gel or on skin distribution of 3H-betamethasone acetate and 14C-terbinafine hydrochloride. CONCLUSIONS AND CLINICAL RELEVANCE 3H-betamethasone acetate, 14C-terbinafine hydrochloride, and florfenicol were all absorbed in vitro through healthy auricular skin specimens within the first 24 hours after topical application. Synthetic canine cerumen had no impact on dermal absorption in vitro, but it may serve as a temporary reservoir that prolongs the release of topical drugs.

OBJECTIVE To determine the pharmacokinetics of detomidine hydrochloride administered IV (as an injectable formulation) or by the oral-transmucosal (OTM) route (as a gel) and assess sedative effects of the OTM treatment in healthy dogs. ANIMALS 12 healthy adult dogs.PROCEDURES In phase 1, detomidine was administered by IV (0.5 mg/m2) or OTM (1 mg/m2) routes to 6 dogs. After a 24-hour washout period, each dog received the alternate treatment. Blood samples were collected for quantification via liquid chromatography with mass spectrometry and pharmacokinetic analysis. In phase 2, 6 dogs received dexmedetomidine IV (0.125 mg/m2) or detomidine gel by OTM administration (0.5 mg/m2), and sedation was measured by a blinded observer using 2 standardized sedation scales while dogs underwent jugular catheter placement. After a l-week washout period, each dog received the alternate treatment. RESULTS Median maximum concentration, time to maximum concentration, and bioavailability for detomidine gel following OTM administration were 7.03 ng/mL, 1.00 hour, and 34.52%, respectively; harmonic mean elimination half-life was 0.63 hours. All dogs were sedated and became laterally recumbent with phase 1 treatments. In phase 2, median global sedation score following OTM administration of detomidine gel was significantly lower (indicating a lesser degree of sedation) than that following IV dexmedetomidine treatment; however, total sedation score during jugular vein catheterization did not differ between treatments. The gel was subjectively easy to administer, and systemic absorption was sufficient for sedation. CONCLUSIONS AND CLINICAL RELEVANCE Detomidine gel administered by the OTM route provided sedation suitable for a short, minimally invasive procedure in healthy dogs.

OBJECTIVES To determine, following oral administration of famciclovir, pharmacokinetic (PK) parameters for 2 of its metabolites (penciclovir and BRL42359) in plasma and tears of healthy cats so that famciclovir dosage recommendations for the treatment of herpetic disease can be optimized. ANIMALS 7 male domestic shorthair cats. PROCEDURES In a crossover study, each of 3 doses of famciclovir (30, 40, or 90 mg/kg) was administered every 8 or 12 hours for 3 days. Six cats were randomly assigned to each dosage regimen. Plasma and tear samples were obtained at predetermined times after famciclovir administration. Pharmacokinetic parameters were determined for BRL42359 and penciclovir by compartmental and noncompartmental methods. Pharmacokinetic-pharmacodynamic (PK-PD) indices were determined for penciclovir and compared among all dosage regimens. RESULTS Compared with penciclovir concentrations, BRL42359 concentrations were 5- to 11-fold greater in plasma and 4- to 7-fold greater in tears. Pharmacokinetic parameters and PK-PD indices for the 90 mg/kg regimens were superior to those for the 30 and 40 mg/kg regimens, regardless of dosing frequency. Penciclovir concentrations in tears ranged from 18% to 25% of those in plasma. Administration of 30 or 40 mg/kg every 8 hours achieved penciclovir concentrations likely to be therapeutic in plasma but not in tears. Penciclovir concentrations likely to be therapeutic in tears were achieved only with the two 90 mg/kg regimens. CONCLUSIONS AND CLINICAL RELEVANCE In cats, famciclovir absorption is variable and its metabolism saturable. Conversion of BRL42359 to penciclovir is rate limiting. The recommended dosage of famciclovir is 90 mg/kg every 12 hours for cats infected with feline herpesvirus.

Objective—To assess the suitability of the modified acetaminophen absorption test for evaluation of abomasal emptying rate in ruminating cattle. Animals—7 Holstein-Friesian heifers. Procedures—In a crossover study design, heifers consecutively underwent an IV infusion of 1 L of saline (0.9% NaCl) solution (control treatment), 1 L of saline solution containing metoclopramide (0.1 mg/kg), and 1 L of saline solution containing atropine (0.1 mg/kg), with an interval of 15 days between treatments. Immediately after each treatment, acetaminophen diluted in ethanol (50 mg/kg) was infused transcutaneously into the abomasum. Blood samples were obtained repeatedly for measurement of plasma acetaminophen concentration, and pharmacokinetic data were obtained. Results—Maximum plasma acetaminophen concentration was significantly lower after atropine treatment than after control or metoclopramide treatment, whereas no difference was identified between control and metoclopramide treatments. The interval to maximum plasma acetaminophen concentration was significantly longer in atropine-treated versus metoclopramide-treated heifers. The interval to maximum acetaminophen concentration obtained from a pharmacokinetic model was significantly longer for atropine than for control and metoclopramide treatment. Similarly, areas under the plasma acetaminophen concentration-time curves for the first 60, 90, 120, and 240 minutes after administration were significantly lower for atropine versus metoclopramide or control treatment, whereas differences between metoclopramide and control treatments were not identified. Conclusions and Clinical Relevance—The modified acetaminophen absorption test was a practical, minimally invasive, and reliable method to assess abomasal emptying in cattle. Metoclopramide administered at a dose of 0.1 mg/kg did not increase the abomasal emptying rate.