Fatal septicemia caused by the zoonotic bacterium Streptococcus iniae during an outbreak in Caribbean reef fish.

An outbreak of Streptococcus iniae occurred in the early months of 2008 among wild reef fish in the waters of the Federation of St Kitts and Nevis, lasting almost 2 months. Moribund and dead fish were collected for gross, histological, bacteriological, and molecular analysis. Necropsy findings included diffuse fibrinous pericarditis, pale friable livers, and serosal petechiation. Cytological and histological analysis revealed granulocytic and granulomatous inflammation with abundant coccoid bacterial organisms forming long chains. Necrosis, inflammation, and vasculitis were most severe in the pericardium, meninges, liver, kidneys, and gills. Bacterial isolates revealed ß-hemolytic, Gram-positive coccoid bacteria identified as S. iniae by amplification and 16S ribosomal RNA gene sequencing. Results from biochemical and antimicrobial susceptibility analysis, together with repetitive element palindromic polymerase chain reaction fingerprinting, suggest that a single strain was responsible for the outbreak. The inciting cause for this S. iniae-associated cluster of mortalities is unknown.

Trichomonosis in free-ranging Eurasian collared doves (Streptopelia decaocto) and African collared dove hybrids (Streptopelia risoria) in the Caribbean and description of ITS-1 region genotypes.

We report the first documented occurrence of an outbreak of trichomonosis in a free-ranging small flock of Eurasian collared doves (Streptopelia decaocto) and African collared dove hybrids (Streptopelia risoria) in the Caribbean. In total, 18 birds were examined, including six African collared dove x Eurasian collared dove hybrids and 12 Eurasian collared doves. The affected age class consisted of adults. Sex distribution was equal. With a flock population size of 200 birds, mortality rate for the outbreak was estimated at 15-20%. Living birds were weak, showing evidence of mucus-stained beaks and open-mouth breathing. Caseous ulcerative yellow lesions were restricted to the upper gastrointestinal tract, with the exception of one bird, which had lesions in the upper gastrointestinal tract and in the liver. Ninety-four percent (17/18) of the affected birds had multiple extensive lesions. Lesions located on the roof of the oral cavity extended in 33% (6/18) into the orbit and in 11% (2/18) into the braincase. Using wet-mount microscopy, we were able to confirm Trichomonas gallinae in 22% (4/18) of the sampled animals. Fifteen samples submitted for PCR analysis tested positive. Sequence analysis of the internal transcribed spacer 1 (ITS-1) region of the ribosomal RNA (rRNA) revealed two distinct genotypes of Trichomonas. One sequence had 100% identity to the prototype T. gallinae isolate, whereas the other sequences had 98-100% identity to recently described Trichomonas-like parabasalid. On the basis of gross and histologic findings, along with the sequence results from the columbids in this report, it is likely that this Trichomonas-like parabasalid is pathogenic.

Prognostic markers for myeloid neoplasms: a comparative review of the literature and goals for future investigation.

Myeloid neoplasms include cancers associated with both rapid (acute myeloid leukemias) and gradual (myelodysplastic syndromes and myeloproliferative neoplasms) disease progression. Percentage of blast cells in marrow is used to separate acute (rapid) from chronic (gradual) and is the most consistently applied prognostic marker in veterinary medicine. However, since there is marked variation in tumor progression within groups, there is a need for more complex schemes to stratify animals into specific risk groups. In people with acute myeloid leukemia (AML), pretreatment karyotyping and molecular genetic analysis have greater utility as prognostic markers than morphologic and immunologic phenotypes. Karyotyping is not available as a prognostic marker for AML in dogs and cats, but progress in molecular genetics has created optimism about the eventual ability of veterinarians to discern conditions potentially responsive to medical intervention. In people with myelodysplastic syndromes (MDS), detailed prognostic scoring systems have been devised that use various combinations of blast cell percentage, hematocrit, platelet counts, unilineal versus multilineal cytopenias and dysplasia, karyotype, gender, age, immunophenotype, transfusion dependence, and colony-forming assays. Predictors of outcome for animals with MDS have been limited to blast cell percentage, anemia versus multilineal cytopenias, and morphologic phenotype. Prognostic markers for myeloproliferative neoplasms (eg, polycythemia vera, essential thrombocythemia) include clinical and hematological factors and in people also include cytogenetics and molecular genetics. Validation of prognostic markers for myeloid neoplasms in animals has been thwarted by the lack of a large case series that requires cooperation across institutions and veterinary specialties. Future progress requires overcoming these barriers.

Critical role for glycosphingolipids in Niemann-Pick disease type C.

Niemann-Pick type C (NPC) disease is a cholesterol lipidosis caused by mutations in NPC1 and NPC2 gene loci. Most human cases are caused by defects in NPC1, as are the spontaneously occurring NPC diseases in mice and cats. NPC1 protein possesses a sterol-sensing domain and has been localized to vesicles that are believed to facilitate the recycling of unesterified cholesterol from late endosomes/lysosomes to the ER and Golgi. In addition to accumulating cholesterol, NPC1-deficient cells also accumulate gangliosides and other glycosphingolipids (GSLs), and neuropathological abnormalities in NPC disease closely resemble those seen in primary gangliosidoses. These findings led us to hypothesize that NPC1 may also function in GSL homeostasis. To evaluate this possibility, we treated murine and feline NPC models with N-butyldeoxynojirimycin (NB-DNJ), an inhibitor of glucosylceramide synthase, a pivotal enzyme in the early GSL synthetic pathway. Treated animals showed delayed onset of neurological dysfunction, increased average life span (in mice), and reduced ganglioside accumulation and accompanying neuropathological changes. These results are consistent with our hypothesis and with GSLs being centrally involved in the pathogenesis of NPC disease, and they suggest that drugs inhibiting GSL synthesis could have a similar ameliorating effect on the human disorder.

Neutrophil function in normal and Chediak-Higashi syndrome cats following administration of recombinant canine granulocyte colony-stimulating factor.

The effects of recombinant canine granulocyte colony-stimulating factor (rcG-CSF) on leukocyte counts and neutrophil function in clinically normal cats and in cats heterozygotic and homozygotic for Chediak-Higashi syndrome (CHS) were examined. CHS is a genetic disease characterized by neutropenic episodes and defects in a variety of phagocyte functions. Short-term administration of rcG-CSF at 10 micrograms/kg body weight resulted in a five- to tenfold increase in circulating granulocytes by day 10 of administration and normalizes CHS neutrophil counts by day 3. The drug was specific for neutrophils as determined by differential cell counts. Neutrophil chemotaxis under agarose and phagocytosis of Escherichia coli were characterized following administration of rcG-CSF in vivo. Granulocytes elicited by rcG-CSF show enhanced chemotactic abilities toward activated serum, increased spontaneous migration, and an enhanced ability to ingest opsonized E. coli. At a concentration of 1 nM rcG-CSF in vitro, chemotaxis and spontaneous migration were increased, with no effect on phagocytosis. CHS neutrophil function was improved by administration of rcG-CSF in all parameters studied, although the defect in chemotaxis was present throughout the treatment period. We conclude from this study that neutrophils elicited by rcG-CSF are functionally enhanced and that rcG-CSF may be a viable therapy for CHS and other related disorders.

Characterization of osteopenia in feline mucopolysaccharidosis VI and evaluation of bone marrow transplantation therapy.

Studies on a feline model of MPS VI demonstrated a marked osteopenia in iliac crest bone samples from young adult animals with fewer, finer trabeculae. In the absence of significant differences in bone remodeling, this was considered due to defects in endochondral ossification and the formation of fewer trabeculae. Cell-level bone formation was normal despite the presence of vacuolated osteoblasts. Affected animals had vacuolated osteocytes in larger lacunae. Cats of the same age who had received a bone marrow transplant 12 months prior as young kittens, had significantly more trabecular bone with thicker trabeculae. The presence of smaller osteocyte lacunae in these animals as compared to their untreated MPS VI cats appeared to be a direct effect of bone marrow transplantation and a useful parameter to monitor its efficacy.

Bone changes in mucopolysaccharidosis VI in cats and the effects of bone marrow transplantation: mechanical testing of long bones.

Mucopolysaccharidosis VI (MPS VI) is a genetic lysosomal storage disease in which a defect in aryl sulfatase B leads to accumulation of the glycosaminoglycan dermatan sulfate and abnormalities in the development of cartilage and bone. A feline model of this disease was used to evaluate the efficacy of bone marrow transplant (BMT) therapy. Long bones from MPS VI cats (N = 6) and MPS VI + BMT cats (N = 7) were compared with control cats (N = 11) and control + BMT cats (N = 5) in mechanical tests. Dissected femurs and tibias were subjected to three-point bending and a subgroup of tibias were tested with the mechanical response tissue analyzer (MRTA) in which vibration is used to measure tissue impedance. Cats with MPS VI had markedly decreased stiffness and strength in both bone (p < 0.01). There was no significant difference in the MPS VI + BMT group. In the tibias, there was also decreased stiffness and strength in the control + BMT group as compared to controls (p < 0.05). However, when cross-sectional area was used to normalize for bone size there was good correlation with strength in both femurs (r = 0.907, p < 0.01) and tibias (r = 0.915, p < 0.1), and there were no significant differences between groups in the modulus of elasticity. In the tibias, in which stiffness was measured by MRTA, there was significant correlation with three-point bending stiffness. These results indicate that, in cats with MPS VI, the decreases in stiffness and strength of long bones can be largely accounted for by the decrease in bone size (osteopenia) that is present.

Restoration of neutrophil and platelet function in feline Chediak-Higashi syndrome by bone marrow transplantation.

Allogeneic bone marrow transplantation (BMT) was successfully performed in four Chediak-Higashi (CHS) syndrome affected cats. Preparatory regimens included selective intestinal flora decontamination, fractionated total body irradiation for myeloablation, and prophylactic treatment for graft-versus-host disease with cyclosporin A. Neutrophil chemotaxis under-agarose and whole-blood platelet aggregation/secretion were characterized prior to BMT and after engraftment of donor-origin marrow cells. Liver and kidney biopsies were obtained and evaluated by light and electron microscopy before, and at 6 months post-BMT to determine what effect BMT might have on abnormal lysosome fusion in hepatocytes and renal tubule cells. The platelet storage pool defect was resolved by day 40 post-BMT. In vitro neutrophil migration in all cats appeared to improve with time after BMT and complete restoration was evident by day 175 post-BMT. No apparent differences were evident in either the liver or the kidney at 6 months post-BMT. One cat developed seizures and one developed posterior paresis 5 months post-BMT; neurologic impairment ultimately resulted in death of two cats at 6 and 8 months post-BMT, respectively. Neurologic lesions in both cats were characterized by non-suppurative encephalitis. Allogeneic BMT successfully corrected the neutrophil migration defect and platelet storage pool deficiency but had no effect on lysosome distribution in liver and kidney cells of CHS cats.

Urine glycosaminoglycan concentrations in mucopolysaccharidosis VI-affected cats following bone marrow transplantation or leukocyte infusion.

Urinary glycosaminoglycan (GAG) concentrations were determined in nineteen normal cats (eleven kittens and eight adult cats), eighteen mucopolysaccharidosis VI (MPS VI)-affected untreated cats (ten kittens and eight adult cats), thirteen cats MPS VI-affected cats following bone marrow transplants (BMT), and two MPS VI-affected cats following intravenous infusion of leukocytes from normal cats. Mucopolysaccharidosis VI-affected cats treated with BMT had a precipitous decrease in urinary GAG by day 7 post-BMT, then a transient increase just prior to engraftment, followed by a sustained decrease to within, or near, the range of urinary GAG concentration established for normal cats. The pre-engraftment changes in urinary GAG excretion were reproduced by leukocyte infusion. After infusion of comparable members of normal peripheral blood leukocytes, a significant decrease in urinary GAG concentrations, specifically dermatan sulfate (DS), was seen with a nadir at day 5 post-infusion, followed by a return by day 9 to pre-infusion values. Post-engraftment, a continued low urinary GAG concentration with a specific decrease in DS can be utilized to document successful autologous engraftment in MPS VI-affected cats.

Comparison of the effects of ethanol and 4-methylpyrazole on the pharmacokinetics and toxicity of ethylene glycol in the dog.

The purpose of this investigation was to compare the effects of ethanol and 4-methylpyrazole (4MP) on the toxicity and pharmacokinetics of ethylene glycol (EG) in the dog. All dogs received 173 mmol/kg EG, p.o. Dogs were randomly assigned to 3 groups: EG-treated only, EG + ethanol (19.3 mmol/kg, i.v. 3, 7, 14 and 24 h after EG) and EG + 4MP (0.24 mmol/kg, i.v. 3 h after EG, 0.18 mmol/kg at 24 h and 0.06 mmol/kg at 36 h). EG produced a rapid onset of metabolic acidosis (within 3 h) and acute oliguric renal failure (after 48 h), whereas administration of ethanol or 4MP greatly attenuated acidosis and prevented renal toxicity. The administration of ethanol, however, severely increased the central nervous system (CNS) depression that existed after ingestion of EG. The half-life of FG in serum was 10.8 +/- 0.7 h in the EG-only treatment group, 6.8 +/- 0.7 (P less than 0.05) in the EG + ethanol group and 9.8 +/- 0.9 h in the EG + 4MP group. Approx. 10% and 48% of the dose of EG was excreted unchanged in the urine at the 0-3 and 3-72 h periods, respectively. Treatment with 4MP increased the amount of EG excreted in the urine (71% from 3-72 h), whereas ethanol did not (51%). However, both ethanol and 4MP increased the rate constant of EG excretion into urine approx. 70%. These data demonstrate the utility of 4MP over ethanol for the treatment of EG-induced toxicity in dogs and indicate that ethanol and 4MP cause an increase in the rate constant of EG excretion in the urine and not a prolongation in EG half-life.

Defective in vitro motility of polymorphonuclear leukocytes of homozygote and heterozygote Chediak-Higashi cats.

The in vitro migratory responses of neutrophils of homozygote and heterozygote Chediak-Higashi cats were defective in an under-agarose assay when compared to the behavior of phagocytes of control cats. The linear distances traversed by the leading front of migrating Chediak-Higashi neutrophils toward streptococcal culture supernatant, zymosan-activated serum or buffer were reduced and smaller numbers of Chediak-Higashi phagocytes populated the resulting migration areas than did cells of control animals. The relative migration parameters of the Chediak-Higashi phagocytes, however, did not differ from the corresponding parameters of control neutrophils in the presence of streptococcal culture supernatant. Therefore, phagocytes of homozygote and heterozygote Chediak-Higashi cats recognized and responded equally well to the bacterial stimuli as did cells of control animals but traveled shorter distances primarily because of a reduced inherent motility. Similar results were also obtained when the feline phagocytes were attracted by zymosan-activated serum. In addition the relative migration parameters of the neutrophils of homozygote Chediak-Higashi cats were reduced and the normalized spatial distributions of their migrating cells were significantly different in the presence of 100% and 20% zymosan-activated serum when compared to the corresponding migration parameters of carrier and control animals. Defective recognition or responses to the higher concentrations of these host-derived attractants complicated, therefore, the already reduced inherent motility of the phagocytes of homozygote Chediak-Higashi cats.

Regional seroprevalence of Cryptosporidium parvum-specific IgG of cats in the United States.

The objective of this study was to determine the regional prevalence of Cryptosporidium parvum-specific IgG in the sera of cats in the United States. The continental United States was partitioned into eight regional areas. Serum samples from 75 cats from each region were assayed for C. parvum-specific IgG using an indirect enzyme-linked immunosorbent assay (ELISA). Age, sex, breed, and indoor/outdoor status were examined as possible risk factors for developing a positive C. parvum-specific IgG antibody titer. The presence of gastro-intestinal signs and Toxoplasma gondii-specific IgG in the serum were also evaluated for association with C. parvum seropositivity. Of the 600 samples assayed, 50 (8.3%) were positive for C. parvum-specific IgG. Regional seroprevalence ranged from 1.3% in the mid-Atlantic states to 14.7% in the south-eastern states. The oldest group of cats (>10 years) had the highest seroprevalence (15.3%). The prevalence of C. parvum-specific IgG was higher among male (10.1%) than among female cats (6.9%), although, the difference was not statistically significant (p = 0.17). Seropositivity was not associated with pure-bred status. C. parvum-specific IgG antibodies was detected most frequently in T. gondii-specific IgG seropositive cats, outdoor cats, and cats with gastro-intestinal signs. These results suggest that cats in the United States are commonly exposed to C. parvum.

Enzyme-linked immunosorbent assay for the detection of Cryptosporidium parvum IgG in the serum of cats.

The objective was to develop an enzyme-linked immunosorbent assay (ELISA) for the detection of Cryptosporidium parvum IgG in the serum of cats. The ELISA was an indirect ELISA using soluble C. parvum oocyst antigens and a peroxidase-labeled anti-feline IgG secondary antibody. Sera from cats with Toxocara felis, Giardia spp., Aelurostrongylus abstrusus, Isospora felis, Isospora rivolta, Toxoplasma gondii, or Taenia spp. infections were assayed in specificity studies. Following optimization, the ELISA and fecal examination for oocysts were performed on samples from 170 client-owned or humane society source cats and 1 cat inoculated orally with C. parvum oocysts. Cryptosporidium parvum oocysts were detected in feces (4/170; 2.4%), and C. parvum IgG was detected in serum (26/170; 15.3%) from naturally exposed cats. The seroprevalence data suggest that some cats in the geographical area studied were exposed to C. parvum, but persistent oocyst shedding was less common. The ELISA is not useful for predicting oocyst shedding in individual cats.

Neurological manifestations of Niemann-Pick disease type C in cats.

Seven Domestic shorthair cats with a lysosomal storage disorder analogous to human Niemann-Pick disease type C, from a breeding colony were studied to characterize the neurological manifestations of this disorder. Affected cats were identified by means of liver biopsies at 4 to 6 weeks of age. Neurological examinations were performed at 2 week intervals from the onset of clinical signs. All cats displayed signs referrable to the cerebellum, with a subtle intention tremor noticed initially at 8 to 12 weeks of age; the disease was rapidly progressive. The tremor became more pronounced, menace response was lost, and severe dysmetria and ataxia developed. Three cats also had signs referrable to other areas of the central nervous system. Cats died or were euthanized between 12 and 43 weeks of age. Pathological findings included accumulation of substrate within neurons throughout the central nervous system, and axonal spheroid formation. The clinical and pathological findings in these cats are comparable to those in the human form of the disease.

Bone marrow cytological findings in 4 dogs and a cat with hemophagocytic syndrome.

Hemophagocytic syndrome or hemophagic histiocytosis was diagnosed in 4 dogs and 1 cat by evaluation of bone marrow aspirate smears. One of the dogs had a suspected infection with canine parvovirus and a confirmed infection with Salmonella spp, 2 dogs had presumptive diagnoses of myeloproliferative and lymphoproliferative disease, respectively, and 1 dog died without a diagnosis. The cat had hepatic lipidosis and lesions compatible with feline calicivirus infection. All animals had cytopenias involving 2 or more cell lines, and fragmented erythrocytes in the blood, along with mild to moderate increases in the number of macrophages in the bone marrow. Numerous marrow macrophages contained phagocytized hematopoietic cells. Other cytological features of the bone marrow were variable in each patient, but the degree of response in the blood was inadequate, even in those with bone marrow hyperplasia. The phagocytosis of hematopoietic elements did not appear to be caused by a primary immune disorder, but rather by the inappropriate activation of normal macrophages secondary to infectious, neoplastic, or metabolic diseases. These findings suggest that hemophagocytic syndrome may be an important factor in the development of cytopenias; the data also support the cytological evaluation of bone marrow aspirates as an aid in the diagnosis of hemophagocytic syndrome.

Inhibition of canine and feline alcohol dehydrogenase activity by fomepizole.

OBJECTIVE: To determine and compare substrate specificity and kinetic rate constants of feline and canine alcohol dehydrogenase (ADH) with ethanol (EtOH) and ethylene glycol (EG) as substrates in vitro, with and without fomepizole. SAMPLE POPULATION: Livers from 3 dogs and 3 cats. PROCEDURE: Canine and feline ADH activity, in cytosolic fractions of homogenized liver, was determined by use of various concentrations of nicotinamide adenine dinucleotide (NAD), EtOH, or EG as substrates. Initial reaction velocities were calculated, and kinetic inhibition rate constants (Ki) for fomepizole were determined. RESULTS: Substrate specificity of canine and feline ADH for EtOH or EG was not significantly different. A 2-fold difference was detected in the maximal velocity of canine, compared with feline, ADH, using either substrate. Fomepizole Ki in feline hepatic homogenates was significantly greater than Ki in canine hepatic homogenates when either EtOH or EG was used as substrate (10- and 30-fold, respectively). A 6-fold increase in the concentration of fomepizole was required to achieve ADH inhibition, with feline homogenates equivalent to those of canine homogenates. CONCLUSIONS AND CLINICAL RELEVANCE: Feline ADH has lower enzymatic capacity for turnover or is less concentrated in liver than canine ADH with regard to EtOH and EG catalysis. Canine ADH was more effectively inhibited by fomepizole than feline ADH. Results suggest that higher dosages of fomepizole may be more effective to treat cats with EG intoxication than dosages reported to treat dogs.

Efficacy of 4-methylpyrazole for treatment of ethylene glycol intoxication in dogs.

4-Methylpyrazole (4-MP), an alcohol dehydrogenase inhibitor, was administered to dogs to treat ethylene glycol (EG) intoxication. Eleven dogs were given 10.6 g of EG/kg of body weight; 5 dogs were treated with 4-MP 5 hours after EG ingestion and 6 dogs were treated with 4-MP 8 hours after EG ingestion. 4-Methylpyrazole was administered IV as a 50-mg/ml [corrected] solution in 50% polyethylene glycol: initial dose, 20 mg/kg; at 12 hours after initial dose, 15 mg/kg; at 24 hours after initial dose, 10 mg/kg; and at 30 hours after initial dose, 5 mg/kg. Physical, biochemical, hematologic, blood gas, serum and urine EG concentrations, and urinalysis findings were evaluated at 0, 1, 3, 6, 9, 12, 24, 48, 72 hours, and at 1 week and 2 weeks after EG ingestion. Dogs of both groups developed clinicopathologic signs associated with EG intoxication, including CNS depression, hyperosmolality, high anion gap metabolic acidosis, polydipsia, polyuria, calcium oxalate monohydrate and dihydrate crystalluria, and isosthenuria. Fractional excretion of sodium was increased in all dogs between 1 and 9 hours after EG ingestion, but remained increased beyond 24 hours only in the 2 dogs treated at 8 hours after EG ingestion that developed acute renal failure. All dogs treated 5 hours after EG ingestion recovered without morphologic, biochemical, or clinical evidence of renal impairment. Of the 6 dogs treated 8 hours after EG ingestion, 2 developed acute renal failure. One of the dogs treated 8 hours after EG ingestion remained isosthenuric for 2 months, but did not manifest any other signs of renal impairment.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of ethanol and 4-methylpyrazole as treatments for ethylene glycol intoxication in cats.

The efficacy of 4-methylpyrazole (4-MP) and ethanol as treatment for ethylene glycol (EG) intoxication in cats was compared. Twenty-two cats were assigned at random to 6 experimental groups. Cats of 1 experimental group were given only 4-MP; those of another experimental group were given only EG. Cats of 3 experimental groups were intoxicated with EG and given 4-MP at 0 hour or 2 or 3 hours after EG ingestion, and those of 1 experimental group were given EG and treated with ethanol 3 hours after EG ingestion. Physical, biochemical, hematologic, blood gas, serum and urine EG concentrations, and urinalysis findings were evaluated at 0, 1, 3, 6, 9, 12, 24, 48, and 72 hours, 1 weeks, and 2 weeks after EG ingestion or 4-MP treatment in cats of the 4-MP only group. The half-life of EG and percentage of ingested EG excreted unchanged were determined for each group. 4-Methylpyrazole treatment at 0 hour was most effective at preventing metabolism of EG. 4-Methylpyrazole was not effective in preventing development of renal failure when given 2 or 3 hours after EG ingestion. Ethanol given 3 hours after EG ingestion was successful in preventing development of renal dysfunction in 2 of the 6 cats treated 3 hours after EG ingestion. Of the remaining 4 cats treated with ethanol, 2 developed transient renal dysfunction and 2 developed acute oliguric renal failure and were euthanatized. 4-Methylpyrazole given 2 or 3 hours after EG ingestion was less effective in preventing EG metabolism than was ethanol given 3 hours after EG ingestion. Therefore 4-MP, at the dose found to be effective in dogs, cannot be recommended as an alternative to ethanol for treatment of EG intoxication in cats.

Effects of low-dose aspirin and specific thromboxane synthetase inhibition on whole blood platelet aggregation and adenosine triphosphate secretion in healthy dogs.

Platelet aggregation and adenosine triphosphate (ATP) secretion in response to arachidonic acid (10 microM) or collagen (5 micrograms/ml) were compared in healthy, adult female Beagles treated with low-dosage aspirin (3.5 mg/kg of body weight, PO, q 12 h for 7 treatments) or with CGS 12970, a specific thromboxane synthetase inhibitor (10 mg/kg, PO, q 8 h for 10 treatments). Platelet aggregation was assessed in whole blood by use of an electrical impedance method. Baseline values obtained prior to treatment served as controls. Addition of arachidonic acid to blood from nontreated dogs resulted in significantly (P less than 0.001) increased impedance, but had no effect in blood from dogs treated with either aspirin or CGS 12970. Treatment with CGS 12970 or aspirin significantly (P less than 0.001) decreased platelet ATP secretion in response to arachidonic acid, compared with baseline values; however ATP secretion in aspirin-treated dogs was significantly (P less than 0.01) less than ATP secretion in CGS 12970-treated dogs. Differences in platelet aggregation were not observed between control dogs and aspirin- or CGS 12970-treated dogs in response to collagen as an aggregant, however, collagen-induced platelet ATP secretion was significantly (P less than 0.001) decreased in dogs treated with aspirin, compared with control values and values from dogs treated with CGS 12970. In dogs treated orally with 0.1, 0.2, 1.0, or 10 mg of CGS 12970/kg, dose-dependent inhibition of arachidonic acid-induced platelet aggregation was observed, with impedance changes not observed at the 10-mg/kg dosage and normal platelet aggregation associated with the 0.1-mg/kg dosage.(ABSTRACT TRUNCATED AT 250 WORDS)

Early clinicopathologic findings in dogs ingesting ethylene glycol.

Fifteen dogs were given 9.5 ml of ethylene glycol/kg of body weight, orally. Physical examination and clinical laboratory findings were evaluated at 1 and 3 hours after ingestion. Three of these dogs were also evaluated at 6, 9, 12, 24, 48, and 72 hours after ingestion. At 1 and 3 hours, the dogs were depressed, ataxic, and polydipsic with increased urine output and serum osmolality. Plasma bicarbonate and urine osmolality were decreased. The osmolal and anion gaps were increased at 1 and 3 hours, respectively. Calcium oxalate crystalluria was first observed at 6 hours. Diminished renal excretory function was not evident until 48 hours. Depression, ataxia, metabolic acidosis, polydipsia, and polyuria in the presence of serum hyperosmolality were early (1 and 3 hour) findings that indicated ethylene glycol intoxication in dogs.