Cerebral lateralization of haptic perception: interaction of responses to Braille and music reveals a functional basis.

Normally, haptic perception of the left hand surpasses that of the right. But simultaneously playing music into the left (but not the right) ear reverses this superiority. This suggests that the left cerebral hemisphere has full haptic perceptual capability, which is subject to right hemisphere interference unless the latter's attentional mechanisms are engaged by contralateral peripheral stimulation.

Effects of 25-hydroxycholecalciferol and soy isoflavones supplementation on bone mineralisation of quail.

1. The effects of 25-hydroxycholecalciferol (25-OH-D(3)) and soy isoflavones supplementation on performance, carcase recovery, bone mineral density, and tibia ash, Ca, P, and serum vitamin D concentrations and alkaline phosphatase activity in the Japanese quail (Coturnix coturnix japonica) exposed to high ambient temperature were evaluated. 2. A total of 270 ten-d-old Japanese quail were randomly assigned to 9 treatment groups, 6 replicates of 5 birds each in a 2 x 3 x 3 factorial arrangement of treatments. Birds were kept in a temperature-controlled room at either 22 degrees C (thermo-neutral) or 34 degrees C (heat stress) for 8 h/d (09:00-17:00 h) and given a basal (control) diet or the basal diet supplemented with one of three levels of 25-OH-D(3) (0, 250 and 500 IU/kg of diet) combined with one of three levels of soy isoflavones (0, 400 and 800 mg/kg of diet). 3. Birds kept at 34 degrees C consumed less feed and gained less weight than control birds. An increase in body weight, feed intake (and improvement in feed efficiency and carcase recovery were found in soy isoflavones and 25-OH-D(3)-supplemented quail reared under heat stress conditions. Bone mineral density, tibia ash, Ca, and P were linearly improved by 25-OH-D(3) and soy isoflavones supplementation in both thermoneutral and heat stress groups. Serum vitamin D levels and alkaline phosphatase activity were improved by 25-OH-D(3) and soy isoflavones supplementation in both thermoneutral and heat stress groups in quail. 4. In conclusion, a combination of 25-OH-D(3) and soy isoflavones supplementation to basal diet significantly improved bone mineralisation in quail.

Supplementation of zinc from organic or inorganic source improves performance and antioxidant status of heat-distressed quail.

Two sources of zinc [ZnSO4.H2O or ZnPicolinate (ZnPic)] supplementation were evaluated for their effects on performance, carcass weight, levels of malondialdehyde, and vitamins C, E, A in Japanese quail (Coturnix coturnix Japonica) exposed to high ambient temperature of 34 degrees C. The birds (n = 360; 10-d-old) were randomly assigned to 12 treatment groups consisting of 3 replicates of 10 birds each in a 2 x 2 x 3 factorial arrangement of treatments (temperatures, zinc sources, zinc levels). Birds were kept in wire cages in a temperature-controlled room at either 22 degrees C (thermoneutral) or 34 degrees C (heat stress) for 8 h/d (0900 to 1700 h) until the end of study, and fed a basal (control) diet or the basal diet supplemented with either 30 or 60 mg of Zn as ZnSO4 H2O or ZnPic/kg of diet. Heat exposure decreased (P = 0.001) live weight gain, feed intake, feed efficiency, and carcass weight when the basal diet was fed. A linear increase in feed intake (P = 0.01) and BW (P = 0.01), and improvement in feed efficiency (P = 0.01) and carcass weight (P < or = 0.05) were found in zinc-supplemented quail reared under heat-stress conditions. Serum vitamin C (P = 0.04), E (P = 0.05), and cholesterol (P = 0.01) concentrations increased linearly, whereas malondialdehyde concentrations decreased linearly (P = 0.02) as dietary zinc sulfate and ZnPic supplementation increased. An interaction between dietary zinc sources, temperature, and levels of supplementation (P < or = 0.05) for these parameters was detected. Serum vitamins C, E, and A concentrations were not different in supplemented birds reared at thermoneutral temperature. Supplementation with zinc improved carcass weight and antioxidant status of birds, and the effects of ZnPic were relatively greater than those of ZnSO4.H2O in heat-stressed quail. Results of the present study suggest that supplementation with ZnPic could be considered to be more protective than ZnSO4.H2O by reducing the negative effects of oxidative stress induced by heat stress in quail.

Bisphosphonates induce apoptosis in mouse macrophage-like cells in vitro by a nitric oxide-independent mechanism.

Bisphosphonates (BPs) are an important class of antiresorptive drugs used in the treatment of bone diseases, including osteoporosis. Although their mechanism of action has not been identified at the molecular level, there is substantial evidence that BPs can have a direct effect on osteoclasts by mechanisms that may lead to osteoclast cell death by apoptosis. BPs can also inhibit proliferation and cause cell death in macrophages in vitro. We have now shown that the toxic effect of BPs on macrophages is also due to the induction of apoptotic, rather than necrotic, cell death. Morphological and biochemical features that are definitive of apoptosis (chromatin condensation, nuclear fragmentation, and endonuclease-mediated internucleosomal cleavage of DNA) could be identified in mouse macrophage-like J774 and RAW264 cells, following treatment with 100 microM pamidronate, alendronate, and ibandronate for 24 h or more. Clodronate was much less potent, even at 2000 microM, while 2000 microM etidronate did not cause apoptosis. Apoptosis was not due to increased synthesis of nitric oxide and could not be prevented by inhibitors of nitric oxide synthases. Since macrophages, like osteoclasts, are particularly susceptible to BPs, these observations support the recent suggestion that the mechanism by which BPs inhibit bone resorption may involve osteoclast apoptosis. Furthermore, the macrophage-like cell lines used in this study may be a convenient model with which to identify the molecular mechanisms by which BPs promote apoptosis in osteoclasts. Induction of macrophage apoptosis by BPs in vivo may also account, at least in part, for the anti-inflammatory properties of BPs as well as the ability of BPs to cause an acute phase response.

Intrathecal synthesis of IgG in simian immunodeficiency virus (SIV)-infected rhesus macaques (Macaca mulatta).

We examined cerebrospinal fluid (CSF) and serum from 25 simian immunodeficiency (SIV)-infected rhesus macaques for the presence of SIV-specific immunoglobulin G (IgG) and for intrathecal synthesis of IgG. SIV-specific IgG was present in CSF from almost 50% of the macaques. In approximately half of these animals the SIV-specific IgG appeared to be derived from serum by leakage across a disrupted blood-brain barrier, whereas in the remaining animals there was evidence of intrathecal IgG synthesis. There were no significant associations between CSF SIV-specific IgG, intrathecal IgG synthesis and isolation of virus from CSF, clinical status, or neuropathological findings. However, SIV-specific IgG was absent from CSF in all four of the macaques with SIV encephalitis. The presence of SIV-specific IgG in CSF may have a modulating effect on the development of SIV-associated neurological disease.

Use of volatile fatty acids from an acid-phase digester for denitrification.

This study investigates the ability of naturally-produced volatile fatty acids (VFAs) to act as a carbon source for the removal of nitrate-Nitrogen concentrations in the range of 20 to 200 mg/L. The VFAs were generated from an anaerobic digester treating a 1:1 mixture of starch-rich industrial and municipal wastewater. The experiments were carried out at an ambient temperature of 22+/-2 degrees C using 600 mL batch reactors containing VFA-rich effluent from the digester and prepared primary sludge. Nitrates added in the form of a 1 M potassium nitrate solution were observed to completely disappear in conjunction with significant recovery of pH and alkalinity (i.e. biological denitrification). In all cases, denitrification followed zero-order kinetics with an average rate constant of 2.67 mg/[Lh] and a mean specific denitrification rate of 0.0111 g NOx-N/g volatile suspended solids (VSS) per day. The denitrifier population had a preference for acetic acid which occurred in the largest quantity and was exhausted the most rapidly. The next two most abundant VFAs were butyric acid and propionic acid, which were consumed only after acetate concentrations began to decline. The third "choice" of the denitrifiers was valeric acid, thus it appears that denitrifying bacteria have a sequential preference for VFAs. In addition, they prefer VFAs over other more complex soluble organic carbon forms.

Deficiency of fucosidase results in acrosomal dysgenesis and impaired sperm maturation.

Although a variety of glycosyltransferases and glycosidases have been implicated in spermatogenesis and posttesticular sperm maturation, the biological role of these enzymes in these processes is largely unknown. We describe reproductive sequelae in a cohort of male dogs suffering from fucosidosis, a heritable lysosomal storage disorder caused by a severe deficiency of alpha-L-fucosidase. There was a reduction in the total number of sperm in the ejaculate. Only 3-5% of sperm were motile. None of the sperm were found to be morphologically normal. The predominant morphological defects observed were malformed acrosomes (56%) and retained proximal cytoplasmic droplets (92%), indicating that spermiogenesis and sperm maturation were impaired. The cytoplasm of all cellular components of the testis and excurrent ducts were vacuolated. The vacuolation resulted from enlargement of lysosomes caused by accumulation of compounds that are otherwise cleaved/degraded when lysosomal hydrolases are present normally. It is possible that impairment in spermatogenesis, particularly morphogenesis of the acrosome, is due to physical damage caused by anomalous enlargement of lysosomes. Although an unambiguous causal relationship could not be established, it is evident from the available information that the derangement in events associated with epididymal sperm maturation, namely acquisition of motility and shedding of the cytoplasmic droplet, is likely due to lack of fucosidase leading to impaired sperm membrane modification. This heritable condition in dogs may serve as a spontaneously occurring knock-out model for further elucidating the role of alpha-L-fucosidase in spermatogenesis and sperm maturation.

MPTP-induced Parkinson-like disease in sheep: clinical and pathologic findings.

Eight ewes, divided into two groups based on age, with group 1 7-8 and group 2 1-3 years old, respectively, were administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intravenously (IV) at cumulative doses of 2.0 to 34.6 mg/kg body weight. Two group 1 sheep, given cumulative doses of 2 and 8.5 mg/kg, developed persistent severe neurologic signs of body stiffness and rigidity, paucity of movement, intention body tremors, and abnormal body posture and stance similar to those signs in MPTP-induced disease in people and primates. After their acute onset, these persistent signs were nonprogressive up to the observation period of 32 days post infusion. None of the younger ewes had persistent neurologic symptoms at equivalent cumulative doses (9.0 mg/kg). The only pathologic changes were microscopic lesions in the central nervous system, consisting of bilaterally symmetrical neuronal chromatolysis and necrosis limited to the substantia nigra and locus ceruleus. These lesions were found in two persistently affected and two younger sheep, suggesting age-based differences in dose response and the threshold of clinical expression of disease. Serum MPTP half-life was 11 days. Thus sheep exposed to MPTP could be an alternative model to the primate for the comparative study of clinical, pathologic, and biochemical mechanisms in MPTP neurotoxicity and Parkinson's disease in people.

Exogenous growth hormone levels predict attentional performance: a preliminary report.

The imminent commercial availability of synthetic growth hormone (GH) and the potential for large scale and possibly indiscriminant use mandate a critical examination of possible adverse effects. This double-blind study examined the effects of human GH on attention. Treatment of eight GH-deficient children, aged 8.7 to 14.1 years, was suspended to establish base lines. Injections with GH (0.1 units/kg) and placebo followed in counterbalanced 2-week periods. At the end of each period, GH levels were assayed, and attention was tested. Scores earned under the GH condition did not differ from base line and placebo values. However, patients displaying high levels (14 +/- 2.12 ng/ml) of exogenous GH 12 hours after injection generally surpassed norms and patients with low levels (3.5 +/- 1.12 ng/ml) of GH under all conditions of the experiment. If 12-hour levels in this study are indicative of the fate of GH received during therapy, prolonged use of GH may bring benefits to attention that vary directly with half-life.

Isolation of cholinergic active ingredients in aqueous extracts of Mareya micrantha using the longitudinal muscle of isolated guinea-pig ileum as a pharmacological activity marker.

In our attempt to isolate the pharmacologically active ingredients in the aqueous extracts of Mareya micrantha, we have selected the contractions of the longitudinal muscle of the isolated guinea-pig ileum preparation as a pharmacological marker to monitor retention of pharmacological activity during the chromatographic separation. The aqueous extracts of Mareya micrantha elicited concentration-dependent contractions of the preparation. The maximum response elicited by the aqueous extracts was 50% of the maximum response elicited by the maximum dose of acetylcholine (ACh), 10(-7) M. Mepenzolate (10(-8)-10(-5) M), a specific muscarinic receptor antagonist, similarly antagonized contractions elicited by the aqueous extracts suggesting that the cholinergic ingredient(s) in the extract are acting at the muscarinic receptors of the preparation. Fraction 2-4, which was separated from the aqueous extracts by Sephadex gel chromatography, dose-dependently elicited contractions of the preparation. The maximum response was 80% of the maximum response elicited by the maximum dose of ACh suggesting that separation has enhanced the cholinergic activity of the content in the extract.

The use of isolated functional heart to pharmacologically characterize active ingredients in the aqueous extracts of Mareya micrantha.

Aqueous extracts of Mareya micrantha are used as folk medicine in West Africa. However, no systemic investigation directed to the identification of the active ingredients in M. micrantha has been done. Therefore, this study investigated the effects of M. micrantha on the cardiac contractility of the isolated frog heart. Also, two sequential fractions from M. micrantha were separated and their effects on cardiac contractility investigated. M. micrantha concentration-dependently suppressed cardiac contractility. Separation of the cardioactive components in series by column chromatography (Sephadex G-50, Column 2.5 x 30 cm and 1 x 20 cm) produced two fractions which facilitated a leftward shift of the dose-response curve of the cardiodepressant effects suggesting that column chromatograph is effective in the isolation of the cardioactive ingredients in M. micrantha. The data suggest that M. micrantha contains cardioactive components and that contractions of the isolated functional frog heart can be used as a pharmacological activity marker during the process of isolation of cardioactive ingredients in M. micrantha.

Juvenile-onset distal myopathy in Rottweiler dogs.

Two juvenile Rottweiler siblings were presented with the complaint of decreased activity and various postural abnormalities, including plantigrade and palmigrade stance and splayed forepaw digits. The neurologic examinations were otherwise normal. Electromyography revealed rare fibrillation potentials and positive sharp waves. Motor nerve conduction velocities were normal, whereas compound muscle action potentials from the interosseous muscles were decreased. These findings were consistent with a primary myopathy. A 3rd pup from a different litter and a 4th pup from a litter with 3 of 8 affected dogs had similar clinical presentations. Histopathologic changes in fresh-frozen muscle biopsy samples were similar in all pups and consisted of myofiber atrophy with mild myonecrosis, endomysial fibrosis and replacement of muscle with fatty tissue. These changes were more severe in distal muscles than in proximal muscles. Plasma carnitine concentrations (total and free) were decreased in all pups. Muscle carnitine concentrations (total and free) were decreased in 3 of 4 pups and the least affected pup had a borderline low free muscle carnitine concentration. Abnormalities involving major metabolic pathways were not found on quantification of organic and amino acids. Dystrophin immunocytochemistry was normal in 2 dogs tested. Distal myopathies in humans are classified under the dystrophic group of muscle disorders. These 4 cases represent a form of muscular dystrophy apparently not previously reported in dogs.

Muscular dystrophy in female dogs.

The most common form of muscular dystrophy in dogs and humans is caused by mutations in the dystrophin gene. The dystrophin gene is located on the X chromosome, and, therefore, disease-causing mutations in dystrophin occur most often in males. Therefore, females with dystrophin deficiency or other forms of muscular dystrophy may be undiagnosed or misdiagnosed. Immunohistochemistry was used to analyze dystrophin and a number of other muscle proteins associated with muscular dystrophy in humans, including sarcoglycans and laminin alpha2, in muscle biopsy specimens from 5 female dogs with pathologic changes consistent with muscular dystrophy. The female dogs were presented with a variety of clinical signs including generalized weakness, muscle wasting, tremors, exercise intolerance, gait abnormalities, and limb deformity. Serum creatine kinase activity was variably high. One dog had no detectable dystrophin in the muscle; another was mosaic, with some fibers normal and others partly dystrophin-deficient. A 3rd dog had normal dystrophin but no detectable laminin alpha2. Two dogs could not be classified. This study demonstrates the occurrence of dystrophin- and laminin alpha2-associated muscular dystrophy and the difficulty in clinical diagnosis of these disorders in female dogs.

Effects of sex, age, puncture site, and blood contamination on the clinical chemistry of cerebrospinal fluid in rhesus macaques (Macaca mulatta).

Paired CSF and serum samples were obtained from 109 rhesus macaques aged 1 to 18 years. The CSF and serum IgG and albumin concentrations were determined, using radial immunodiffusion; CSF total protein and glucose were determined, using colorimetric methods; and Na, K, and Cl concentrations were determined, using ion-specific electrodes. The CSF protein values were lower than those reported for non-human primates, and this finding was confirmed by results of agar gel electrophoresis. Animal age and sex had no significant effects on CSF composition, but serum IgG concentration increased with age. Concentrations of total protein, albumin, and IgG were greater, and concentrations of glucose and potassium were lower in CSF obtained from the lumbar rather than the cisternal site. Composition of CSF was not significantly altered by contamination with blood at values up to 10,000 RBC/microliters. The CSF albumin quotient, IgG quotient, and IgG index were determined and differed markedly from values reported for human beings, indicating that the properties and specificity of the blood-brain barrier may be species-specific.

Clinical evaluation of cimetidine, sucralfate, and misoprostol for prevention of gastrointestinal tract bleeding in dogs undergoing spinal surgery.

OBJECTIVE: To determine the incidence of gastrointestinal (GI) tract bleeding in dogs undergoing spinal surgery with adjunct corticosteroid treatment, and to determine the protective efficacy of cimetidine, sucralfate, and misoprostol against such bleeding in these dogs. ANIMALS: 40 dogs that underwent spinal surgery. PROCEDURES: Myelography and surgery were performed on the first or second day of hospitalization. Methylprednisolone sodium succinate was given at a dosage of 30 mg/kg of body weight prior to myelography, followed by a second full or half dose 2 to 4 hours later at clinician discretion. Spinal surgery was performed in conventional manner, postoperative administration of analgesics was done, and dogs were fed a diet lacking red meat. Dogs were assigned at random to 1 of the 3 treatment groups or to the control group. Dogs of the treatment groups received cimetidine, sucralfate, or misoprostol. Physical examination and determination of PCV and serum total protein values were performed daily. A fecal sample was examined daily for gross and occult blood. RESULTS: 36 of 40 dogs had GI tract bleeding during a hospitalization period of 3 to 6 days. There was no significant difference in development of bleeding between the control group and any of the treatment groups. CONCLUSIONS: Gastrointestinal tract bleeding occurred in 90% of dogs undergoing spinal surgery combined with administration of methylprednisilone sodium succinate, a higher rate than that found in previous studies. This bleeding was not life-threatening. Prophylactic benefit from any of the GI protectants tested was not found.

Genomic screening for fucosidosis in English Springer Spaniels.

OBJECTIVE: To develop a robust molecular genetic test for alpha-L-fucosidosis in English Springer Spaniels and to screen dogs from the United Kingdom and United States for the mutant allele. ANIMALS: 35 English-bred English Springer Spaniels, 60 American-bred English Springer Spaniels, and 1 affected dog and its parents from a family of English Springer Spaniels in Colorado. PROCEDURE: Polymerase chain reaction analysis was used to amplify the mutated region in the gene encoding alpha-L-fucosidase. High guanine-cytosine (GC) content of the region required use of an amplification buffer with high pH. Mutant and normal alleles were separated by polyacrylamide gel electrophoresis. Molecular genetic test results were compared with enzyme data. RESULTS: A 262-bp PCR product was amplified from normal dogs and compared with a 248-bp product from affected dogs. Carriers had 1 copy of each allele, distinguishable by the 14-bp size difference. Two carriers among the English-bred dogs were identified by use of enzyme and genomic DNA analyses. The molecular defect in dogs from Colorado was proven to be the same as that in British and Australian dogs. None of the other 60 American-bred dogs carried the mutant allele. CONCLUSIONS AND CLINICAL RELEVANCE: A PCR method that can be used to identify dogs affected with or carriers of the autosomal recessive disease fucosidosis was established. Amplification was achieved within a GC-rich region, using a method that may be useful in overcoming amplification problems in GC-rich areas within other genes. Using this test, fucosidosis can be controlled and ultimately eradicated from the English Springer Spaniel population.

Effects of iatrogenic blood contamination on results of cerebrospinal fluid analysis in clinically normal dogs and dogs with neurologic disease.

OBJECTIVE: To examine the effects that iatrogenic blood contamination would have on total protein concentration and nucleated cell count in CSF from clinically normal dogs and dogs with neurologic disease. DESIGN: Case-control study. STUDY POPULATION: 53 dogs confirmed to have neurologic disease and 21 clinically normal dogs. PROCEDURE: CSF samples were obtained from the cerebellomedullary cistern or the lumbar portion of the subarachnoid space. Red blood and nucleated cell counts were determined, and protein concentration was measured. RESULTS: RBC count was not significantly correlated with nucleated cell count or protein concentration in clinically normal dogs or dogs with neurologic disease. CLINICAL IMPLICATIONS: High CSF nucleated cell counts and protein concentrations are indicative of neurologic disease, even if samples contain moderate amounts of blood contamination.

Fucosidosis in a family of American-bred English Springer Spaniels.

Fucosidosis was detected in a family of English Springer Spaniels in the United States. To our knowledge, these are the first reported cases of this disease in American-bred dogs. Affected and carrier status of dogs were determined by measuring the activity of the enzyme alpha-L-fucosidase in plasma and in leukocytes. Fucosidosis results in neurologic signs, particularly changes in behavior, in adolescent and adult dogs. Late onset of signs may result in misdiagnosis as a primary behavior problem or acquired neurologic disease. Fucosidosis is inherited in an autosomal recessive manner, and carrier dogs are clinically normal. Thus, the abnormal gene can become widespread in a population before homozygous-affected dogs are produced.

Neurologic abnormalities as the predominant signs of neoplasia of the nasal cavity in dogs and cats: seven cases (1973-1986).

Neurologic abnormalities were the predominant historic and physical findings in 5 dogs and 2 cats with primary nasal cavity tumors that had invaded the cranial vault. Seizures, behavior changes, and obtundation were the most common signs. Other neurologic signs included paresis, ataxia, circling, visual deficit, and proprioceptive deficit. Although 1 dog and 2 cats had historic findings of mild respiratory disease, no physical abnormalities related to the respiratory tract were found in any of the 7 animals. Nasal cavity neoplasia was suggested by radiographic and computed tomographic studies and was confirmed histopathologically in each case. The nasal tumor types in the 5 dogs were epidermoid carcinoma (n = 1), adenocarcinoma (n = 2), solid carcinoma (n = 1), and anaplastic chondrosarcoma (n = 1). An esthesioneuroblastoma was found in each cat. Radiation therapy was effective for 3 months in palliating the clinical signs in the 2 dogs in which it was used. Neoplasia of the nasal cavity should be considered in the differential diagnosis for animals with neurologic signs suggestive of cerebral disorders.

Effects of diet on pharmacokinetics of phenobarbital in healthy dogs.

OBJECTIVE: To determine effects of various diets on the pharmacokinetics of phenobarbital and the interactive effects of changes in body composition and metabolic rate. DESIGN: Prospective study. ANIMALS: 27 healthy sexually intact adult female Beagles. PROCEDURE: Pharmacokinetic studies of phenobarbital were performed before and 2 months after dogs were fed 1 of 3 diets (group 1, maintenance diet; group 2, protein-restricted diet; group 3, fat- and protein-restricted diet) and treated with phenobarbital (approx 3 mg/kg [1.4 mg/lb] of body weight, p.o., q 12 h). Pharmacokinetic studies involved administering phenobarbital (15 mg/kg [6.8 mg/lb], i.v.) and collecting blood samples at specific intervals for 240 hours. Effects of diet and time were determined by repeated-measures ANOVA. RESULTS: Volume of distribution, mean residence time, and half-life (t1/2) of phenobarbital significantly decreased, whereas clearance rate and elimination rate significantly increased with time in all groups. Dietary protein or fat restriction induced significantly greater changes: t1/2 (hours) was lower in groups 2 (mean +/- SD; 25.9 +/- 6.10 hours) and 3 (24.0 +/- 4.70) than in group 1 (32.9 +/- 5.20). Phenobarbital clearance rate (ml/kg/min) was significantly higher in group 3 (0.22 +/- 0.05 ml/kg/min) than in groups 1 (0.17 +/- 0.03) or 2 (0.18 +/- 0.03). Induction of serum alkaline phosphatase activity (U/L) was greater in groups 2 (192.4 +/- 47.5 U/L) and 3 (202.0 +/- 98.2) than in group 1 (125.0 +/- 47.5). CONCLUSIONS AND CLINICAL RELEVANCE: Clinically important differences between diet groups were observed regarding pharmacokinetics of phenobarbital, changes in CBC and serum biochemical variables, and body composition. Drug dosage must be reevaluated if a dog's diet, body weight, or body composition changes during treatment. Changes in blood variables that may indicate liver toxicosis caused by phenobarbital may be amplified by diet-drug interactions.