Immobilization of Japanese black bears (Ursus thibetanus japonicus) with tiletamine hydrochloride and zolazepam hydrochloride

The effect of anesthetizing with a 1:1 combination of tiletamine hydrochloride and zolazepam hydrochloride (TZ) was evaluated in 75 Japanese black bears. TZ was administered to 43 captive and 11 wild, 8 captives and 13 hibernating captive bears at the doses of approximately 9.0 mg/kg (usual dosage), 18.0 mg/kg (high dosage) and 5.0 mg/kg (low dosage), respectively. Sufficient anesthetic effects were achieved in all bears, and rectal temperatures, heart rates and respiratory rates did not change significantly during an hour handling. Complete blood cell examinations showed no abnormal data. A combination of TZ would be an efficient and safe drug for chemical immobilization of Japanese black bears.     

Prognostic value of magnetic resonance imaging in dogs with paraplegia caused by thoracolumbar intervertebral disk extrusion: 77 cases (2000-2003)

OBJECTIVE: To determine whether magnetic resonance imaging findings in dogs with paraplegia caused by thoracolumbar intervertebral disk extrusion were predictive of clinical outcome. DESIGN: Retrospective case series. ANIMALS: 77 dogs. PROCEDURE: Medical records and magnetic resonance images were reviewed; clinical outcome was classified as successful (regained ability to walk with no more than mild neurologic deficits) or unsuccessful (severe neurologic deficits persisted). The prognostic value of magnetic resonance imaging was compared with prognostic value of deep pain perception, duration of clinical signs, and rate of onset of clinical signs. RESULT: 33 (43%) dogs had areas of hyperintensity of the spinal cord greater than or equal to the length of the L2 vertebral body on T2-weighted magnetic resonance images. All 44 dogs without areas of hyperintensity on T2-weighted images had a successful outcome, but only 18 of the 33 (55%) dogs with an area of hyperintensity did. Only 5 of 16 dogs with an area of hyperintensity that had also lost deep pain perception had a successful outcome. The odds ratio for an unsuccessful outcome for a dog with an area of hyperintensity (29.87) was higher than the odds ratio for a dog that had lost deep pain perception (5.24). Duration and rate of onset of clinical signs were not associated with clinical outcome. CONCLUSIONS AND CLINICAL RELEVANCE: Findings suggest that results of magnetic resonance imaging can be used to predict clinical outcome in dogs with paraplegia caused by intervertebral disk extrusion.     

Concentrations of ketone body and antidiuretic hormone in cerebrospinal fluid in response to the intra‐ruminal administration of butyrate in suckling calves

The aim of the present study was to elucidate the mechanism by which ketone bodies increase antidiuretic hormone (ADH) secretion. Four male Holstein calves (5 weeks of age) were utilized. Four levels of butyrate (0 g, 11 g, 22 g and 44 g) were administrated intra‐ruminally in a 4 × 4 Latin square design and cerebrospinal fluid (CSF, six‐position lumbar puncture), blood plasma and urine were collected. The concentration of total plasma and CSF protein was 5.5–5.6 g/dL and 27.5–28.3 mg/dL, respectively. CSF concentrations of a specific ketone body, 3‐hydroxybutyric acid, were significantly higher in the 22 g and 44 g butyrate groups than in the control group. CSF concentrations of ADH in the 11 g and 44 g butyrate groups were significantly higher than in the control group. Plasma concentration of 3‐hydroxybutyric acid was increased by intraruminal administration of butyrate within 15 min in a dose‐dependent manner, and it was higher in the 22 g and 44 g butyrate group than in the control group from 15 min to 4 h. With the exception of the 11 g butyrate group, plasma concentrations of ADH also increased in response to butyrate treatment, and it was higher in the 44 g butyrate group than in the 22 g butyrate group from 15 min to 1.5 h. The duration of the elevated plasma concentrations of ADH was shorter than that of the plasma concentration of 3‐hydroxybutyric acid. The relationship between the plasma concentrations of ADH and 3‐hydroxybutyric acid was statistically significant but the correlation between the two concentrations was not high. Butyrate treatment elevated the plasma concentration of ADH and also resulted in reduced urine volume and increased urine osmolality. Haematocrit (Ht) values, and the osmolality of CSF and plasma were not different among the groups. Our results suggested that the increased ADH secretion observed in suckling calves fed dry feeds was caused by butyrate‐derived ketone body that crossed the blood‐brain barrier rapidly.     

IgG antibody subclass response against equine herpesvirus type 4 in horses

In this study, IgG subclass responses against equine herpesvirus type 4 (EHV-4) were examined by enzyme-linked immunosorbent assay (ELISA) using a type-specific region of EHV-4 glycoprotein G (gG). ELISA using sera collected from horses experimentally infected with EHV-4 revealed that IgGa and IgGb antibodies were detected at high level, but IgGc and IgG(T) antibody responses were detected at low level or were undetectable. The IgGa antibody response reached its peak on day 10 post-infection, and then dropped. The IgGb antibody response reached its maximum level on day 12 post-infection, and then the level was sustained during at least 28 days after infection. Forty healthy racehorses that had already been infected with EHV-4 possessed antibody against EHV-4. Although IgGa antibodies specific for EHV-4 were not detected in any horses, IgGb antibodies were detected and the levels correlated with total IgG antibodies against EHV-4 gG. The results suggest that EHV-4-specific IgGa and IgGb antibodies are induced in EHV-4-infected horses, and that IgGb antibody, but not IgGa, is long lasting.     

Clinical and molecular analysis of GM2 gangliosidosis in two apparent littermate kittens of the Japanese domestic cat

This case report documents clinical and molecular findings in two littermate kittens of the Japanese domestic cat with GM2 gangliosidosis variant 0. Analysis included detailed physical, magnetic resonance imaging, biochemical, pathological and genetic examinations. At first, these littermate kittens showed typical cerebellar signs at approximately 2 months of age. About 2 months later, they progressively showed other neurological signs and subsequently died at about 7 months of age. Magnetic resonance imaging just before the death showed an enlarged ventricular system, T1 hyperintensity in the internal capsule, and T2 hyperintensity in the white matter of the whole brain. Histological findings suggested a type of lysosomal storage disease. Biochemical studies demonstrated that the kittens were affected with GM2 gangliosidosis variant 0, and a DNA assay finally demonstrated that these animals were homozygous for the mutation, which the authors had identified in a different family of the Japanese domestic cat. The findings in the present cases provide useful information about GM2 gangliosidosis variant 0 in Japanese domestic cats.     

Effect of multiple oral dosing of fluconazole on the pharmacokinetics of cyclosporine in healthy beagles

Fluconazole (Fcz) is successfully used in human organ transplant patients as an antifungal therapy. However, Fcz can increase the cyclosporine (CsA) trough level and lead to CsA nephrotoxicity. In canine renal transplantation, CsA has been used as a major immunosuppressant, and it is important to control its trough level. However, the interaction of Fcz with CsA has not yet been reported in dogs. In this study, the effect of Fcz treatment on the pharmacokinetics of CsA in four healthy beagles was investigated using a four-period crossover design. The treatments included CsA alone (A), CsA + multiple-dose Fcz 50 mg (B), CsA + multiple-dose Fcz 25 mg (C) and CsA + single-dose Fcz 50 mg (D). Blood CsA concentrations were measured at 0.5, 1, 2, 4, 6, 8, 10, 12 and 24 hr after CsA administration. The AUC(0-12) and C(max) values for treatment B were significantly higher than those for the other treatments. In particular, the AUC(0-12) of treatment B was about two times higher than that of treatment A. Fcz administration did not significantly prolong the half-life or mean residence time of CsA. The results of our study show that administration of multiple therapeutic doses of Fcz can significantly increase the CsA blood concentration, which might partially depend upon the Fcz blood concentration. When Fcz is used in CsA-based canine renal transplantation, it may be necessary to adjust the CsA trough level by decreasing the dose.     

A new ENU-induced mutant mouse with defective spermatogenesis caused by a nonsense mutation of the syntaxin 2/epimorphin (Stx2/Epim) gene

Repro34 is an N-ethyl-N-nitrosourea (ENU)-induced mutation in mice showing male-specific infertility caused by defective spermatogenesis. In the present study, we investigated pathogenesis and molecular lesions in relation to spermatogenesis in the repro34/repro34 homozygous mouse. Histological examination of the testis showed that the seminiferous epithelium of the repro34/repro34 mouse contained spermatogonia and spermatocytes but no round and elongating spermatids. Instead of these haploid cells, multinucleated giant cells occupied the niche of the seminiferous tubules. Immunohistochemical staining for Hsc70t, an elongating spermatid specific protein, confirmed the absence of elongating spermatids. Furthermore, RT-PCR showed that there were significantly reduced expressions of the marker genes specifically expressed in the spermatid and that there was no difference in the expressions of the spermatocyte specific marker genes. These findings indicated interruption of the spermatogenesis during transition from the spermatocyte to spermatid in the repro34/repro34 mouse. The repro34 locus has been mapped on a 7.0-Mb region of mouse chromosome 5 containing the Syntaxin 2/Epimorphin (Stx2/Epim) gene, and targeted disruption of this gene has been reported to cause defective spermatogenesis. We therefore sequenced the entire coding region of the Stx2/Epim gene and found a nucleotide substitution that results in a nonsense mutation of this gene. The expression pattern of the Stx2/Epim gene during the first wave of spermatogenesis, increased expression at later stages of spermatogenesis, was in agreement with the affected phase of spermatogenesis in the adult repro34/repro34 testis. We therefore concluded that the male infertility of the repro34/repro34 mouse is caused by the interruption of spermatogenesis during transition from the spermatocyte to spermatid and that the nonsense mutation of the Stx2/Epim gene is responsible for the interruption of spermatogenesis.     

Frequencies of bovine PrP gene polymorphisms in Holstein and Japanese Black bulls in Japan

We screened for Japanese Black and Holstein bull sire samples to detect single nucleotide polymorphisms (SNPs) involving animo‐acid substitutions in the bovine prion gene in the entire coding region of the PRNP gene. Although three silent SNPs were found, we could not detect any SNP with animo‐acid substitution. We also examined the polymorphism of the octapeptide repeat number in these samples. There was no homozygous bull with repeat number 5. The frequency of heterozygous (6/5) bulls was 8% in the Japanese Black bull and 4% in the Holstein bull, respectively. The bull samples used in this study contain popular elite sires, so it appears that the polymorphisms of prion protein (PrP) are rather difficult to find in these two breeds in Japan, except for polymorphism of the octapeptide repeat number.