Doxorubicin affects the cardiac muscarinic system in the rat.

During the study on the mechanism of doxorubicin-induced cardiotoxicity, we observed that a long incubation (4 hr) with doxorubicin reduced the maximal negative inotropic effects of a muscarinic receptor agonist, carbachol. The mechanism responsible for this doxorubicin-induced reduction of the efficacy of carbachol was examined in isolated guinea pig hearts. In isolated left atrial muscle preparations, 1 hr incubation with 100 microM doxorubicin caused a parallel right-ward shift of the concentration-response curves for carbachol, but a longer (4 hr) incubation with this agent (30, 100 or 200 microM), caused a significant reduction of the magnitude of the negative inotropic effect of carbachol in addition to the concentration-dependent parallel right-ward shift. The 4-hr incubation with these concentrations of doxorubicin also reduced the maximal negative inotropic effect of an adenosine A1 receptor agonist, R-phenylisopropyl adenosine (R-PIA), without affecting the potency of this agonist. Doxorubicin (1 to 100 microM) reduced [3H]quinuclidinyl benzilate (QNB) binding in a concentration dependent manner, but failed to alter [3HIR-PIA binding. The decrease in the magnitude of the maximal negative inotropic effect by doxorubicin was caused by changes in the muscarinic system at steps common to the transduction of muscarinic and adenosine A1 receptor mechanisms.     

Direct and indirect markers of cartilage metabolism in synovial fluid obtained from dogs with hip dysplasia and correlation with clinical and radiographic variables

OBJECTIVE: To compare activities of interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)-alpha, and matrix metalloproteinase (MMP)-3 and contents of sulfated glycosaminoglycan (S-GAG) in joint fluid obtained from dogs with hip dysplasia (HD) and clinically normal dogs, evaluate correlations among these markers in joint fluid obtained from dogs with HD, and evaluate correlations between each marker and clinical and radiographic variables. Animals-26 dogs with HD (clinical group) and 43 clinically normal Beagles (control group). PROCEDURE: Joint fluid was aseptically collected from the hip joints of all dogs. For each dog in the clinical group, age, duration of lameness, radiographic osteoarthritis (OA) score, and Norberg angle in each affected joint were recorded. Activities of IL-1beta, IL-6, TNF-alpha, and MMP-3 and S-GAG contents were measured. Values were compared between groups by use of Mann-Whitney U tests, and the Spearman rank correlation test was used to evaluate correlations among markers and between each marker and clinical or radiographic variables. RESULTS: Values of all markers were significantly higher for the clinical group, compared with values for the control group. There was a moderate positive correlation between lameness duration and IL-6 activity and a strong negative correlation between the Norberg angle and IL-1beta activity. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of our results indicated that there was a significant increase in markers of OA in dogs with HD. Activities of IL-1beta and IL-6 in joint fluid of dogs with HD may be influenced by the severity of laxity in the hip joint and lameness duration, respectively.     

Characterization of the cathelicidin cluster in the Japanese quail (Coturnix japonica)

The Japanese quail has several advantages as a low‐fat meat bird with high immunity against diseases. Cathelicidins (CATHs) are antimicrobial peptides that play an important role in innate immunity. The aim of this study was to characterize the CATH cluster in the Japanese quail (Coturnix japonica). The Japanese quail CATH (CjCATH) cluster, contains four CATH genes, as in the chicken. The coding sequences of CjCATHs exhibited >85.3% identity to chicken CATHs. The predicted amino acid sequences of the four CjCATH genes contained the cathelin‐like domain characteristic of CATH proteins. Polymorphisms were detected in the open reading frames (ORFs) of all CjCATH sequences. Two amino acid substitutions were observed in the antimicrobial region of the mature peptide of CjCATH2, and predicted to influence peptide function. CjCATH1 is expressed in lung, heart, bone marrow and bursa of Fabricius (BF). CjCATH2 is expressed in bone marrow. CjCATH3 is expressed in lung, heart, bone marrow, BF, tongue and duodenum. CjCATHB1 is expressed in bone marrow and BF. This study is the first to characterize CATH genes in the Japanese quail, and identifies novel antimicrobial peptide sequences belonging to the cathelicidin family, which may play a role in immunity in this species.     

FCV-VBS isolated from cats with typical symptoms caused VSD in experimental cats

Commercially available vaccines have been used widely to prevent feline calicivirus infection (FCI). However, with their widespread use, field strains, which are weakly cross-reactive with the live-virus vaccine strain F9, have posed the problem of vaccine breakdown. Recently the existence of FCV—associated virulent systemic disease (VSD) has been published. But their molecular diversity, antigenic mutations and physicochemical property have not been sufficiently clarified. Thus, we experimentally gave the vaccine breakdown strain (VBS) H10 to cats that had been inoculated with an F9 live vaccine. After the administration of strain H10, vaccinated cats (1 through 4) had no respiratory symptoms, whereas the non-vaccinated cat 5 showed clinical symptoms such as a fever of over 40°C, loss of vitality, decreased appetite, diarrhea, and nasal discharge after receiving strain H10, and died. Lethal FCV is rare, and may be a virulent systemic disease (VSD)—inducing strain. This is the initial report on VSD in Japan. It has been reported that symptoms of VSD were similar in vaccinated and nonvaccinated cats on experimental infection. However, no VSD-like symptoms developed, and the incidence of the disease varied depending on the presence or absence of vaccination, suggesting that there are two mechanisms of vaccine breakdown: one is associated with the vaccine immunity level, and the other is not. The characteristics of the VBS revealed were: (1) the duration of virus excretion was short when the originally carried antibody titer before virus challenge was high, (2) the excreted viral molecular species varied daily, not being limited to a specific species with time, and (3) the acquired physicochemical properties did not persist, and altered daily. FCV-VBS alters the molecular species and physicochemical properties daily due to the reduction of host immunity, which may lead to VSD.     

Presettlement and modern disturbance regimes in coast redwood forests: Implications for the conservation of old-growth stands

Coast redwood (Sequoia sempervirens), a western North American conifer of ancient lineage, has a paradoxical combination of late-successional characteristics and strong adaptations to disturbance. Despite its shade tolerance and heavy dominance of the canopy on many sites, redwood saplings are uncommon in upland old-growth stands. Information needed to ensure the conservation of old-growth redwood forests has been limited. In this review paper, we integrate evidence on redwood biology with data on the historic and modern disturbance regimes to help clarify the degree to which key attributes of redwood forests may have been dependent upon periodic disturbance. Available evidence suggests that episodes of fire, flooding, and slope failure prior to European settlement were frequent but predominantly of low to moderate severity and extent, resulting in broadly uneven-aged forests. The majority of fires prior to European settlement were apparently of human origin. Frequency and severity of the major disturbance agents have been radically changed in modern times. Fires have been largely excluded, and flooding has been altered in ways that have often been detrimental to old-growth redwoods on alluvial terraces. However, because of the apparent anthropogenic origin of most presettlement fires, the long-term evolutionary role of fire for coast redwood is ecologically ambiguous. With fire exclusion, redwood possibly could be displaced to some extent on upland sites by increasing abundance of fire-sensitive competitors. Alternatively, redwood may be able to maintain dominance by vegetative sprouting and new seedling establishment on root-wad mounds, fallen logs, and on soil exposed by slope failure. Future research priorities are suggested that will help resolve some of the current ambiguities.     

Surgical treatment of middle ear cholesteatoma using an oral approach in 2 dogs

Middle ear cholesteatoma is caused by the formation of epidermoid cysts that result in distention and enlargement of the tympanic bulla with subsequent destruction of surrounding tissues. We report treatment of middle ear cholesteatoma in 2 dogs, via an oral surgical approach. Abnormal tympanic bulla contents and the wall compressing the pharynx were successfully removed in both cases. Computed tomography imaging, surgical findings, and histopathology results were consistent with middle ear cholesteatoma in both cases. The outcomes in both cases suggest that an oral surgical approach may be an alternative treatment for middle ear cholesteatoma in dogs.Key clinical message:Despite the limited number of cases described herein, our report indicates that the direct oral approach for canine cholesteatoma may be and alternative approach.     

Secondary chronic respiratory acidosis in a dog following the cervical cord compression by an intradural glioma

An intradural tumor in the upper cervical region was found in a dog with quadriparesis and chronic respiratory acidosis. Surgical removal of the tumor in the atlas and intraoperative radiotherapy were attempted. The tumor was histologically diagnosed as a neural glioma. A preoperative acid-base disturbance was dramatically improved after surgery. The clinical changes appeared in this case suggest that compression of the spinal cord at this region may cause paralysis of the respiratory muscles and secondarily result in chronic respiratory acidosis following the respiratory insufficiency.     

Ki-67 and minichromosome maintenance-7 (MCM7) expression in canine pituitary corticotroph adenomas

Pituitary-dependent hyperadrenocorticism (PDH) caused by pituitary corticotroph adenoma is a common endocrine disorder in dogs. The ratio between pituitary height and the area of the brain (P/B) has been used to evaluate the pituitary size. A P/B ratio > 0.31 indicates an enlarged pituitary, whereas a P/B ratio ≤ 0.31 indicates a nonenlarged pituitary. The aim of this study was to investigate the expression of proliferation markers Ki-67 and minichromosome maintenance-7 (MCM7) in canine corticotroph adenomas in enlarged and in nonenlarged pituitaries and to evaluate their relation with the size of canine pituitary corticotroph adenomas. Ki-67 and MCM7 expression in ACTH-positive tumor cells was determined by dual-labeling immunohistochemistry in resected corticotroph adenomas from 15 dogs with PDH. The mean ± SD Ki-67 labeling index (LI) was 0.55% ± 0.59% in corticotroph adenomas with nonenlarged pituitaries and 1.6% ± 0.6% in adenomas with enlarged pituitaries. The MCM7 LI in corticotroph adenomas with nonenlarged pituitaries and in adenomas with enlarged pituitaries was 2.9% ± 2.2% and 10.9% ± 3.7%, respectively. The Ki-67 LI and MCM7 LI were significantly greater in the adenomas with enlarged pituitaries than in the adenomas with nonenlarged pituitaries (P < 0.01 and P < 0.01, respectively). The MCM7 LI was significantly greater than the Ki-67 LI in adenomas (P < 0.01). The Ki-67 LI was positively correlated with the MCM7 LI (r = 0.820, P < 0.01), and the P/B ratio was positively correlated with the Ki-67 LI (r = 0.560, P = 0.03) and the MCM7 LI (r = 0.854, P < 0.01). In conclusion, canine corticotroph adenomas in enlarged pituitaries show greater proliferation potential than do adenomas in nonenlarged pituitaries. MCM7 expression was significantly greater than Ki-67 expression in canine pituitary corticotroph adenomas. Thus, MCM7 may be superior to Ki-67 as a proliferation marker in pituitary tumors.     

Oocyte growth in temperate basses: multiple forms of vitellogenin and their receptor

A full-length cDNA encoding a vitellogenin (Vg) receptor (VgR) was isolated and sequenced from a white perch, Morone americana, ovarian cDNA library. The perch expresses a single VgR that is structurally classified as an LR8 type (without an 0-linked sugar domain) and appears to be the only species observed to possess no splice variant of the receptor. We proposed a hypothetical model for ovarian lipid transfer in Morone species, one in which the `single VgR' transports Vg and other lipoproteins via a selective endocytotic pathway based on ligand affinity, in conjunction with a lipase-mediated pathway of fatty acid transport.