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Tissues of dogs treated with ivermectin were examined microscopically to learn the fate of microfilariae of canine heartworm that disappear from the peripheral circulation within a few days of treatment. Medicated dogs were killed 18 hours, 3 days, and 6 days after treatment with 0.5 mg of ivermectin/kg of body weight subcutaneously. Ivermectin was dissolved in 60% propylene glycol and 40% glycerol formal. In dogs killed at posttreatment hour 18, the peripheral microfilaremia had decreased by an average of 89%. At this time, a dense mass of RBC, WBC, and macrophages plus many microfilariae was found in pulmonary alveolar septae. Similar reactions were seen in liver, kidney, and spleen. Phagocytosis of microfilarial fragments was evident. In dogs killed at posttreatment day 3, many microfilariae were fragmented and phagocytosis of the fragments was common. In dogs killed at posttreatment day 6, microgranulomas were common, particularly in such vascular organs as lungs, kidney, and liver. Microgranulomas containing microfilariae were also seen in spleen, skeletal and cardiac muscles, diaphragm, lymph nodes, gastrointestinal tract, and pancreas. Small glial nodules were seen in the CNS. Denudation of the atrial epicardium was associated with fragments of microfilariae and granulomatous inflammatory cells. Renal epithelial crescents were observed in treated and nontreated dogs. Plasma cells were conspicuous in treated and nontreated dogs, especially in some livers and kidneys. Before treatment, all dogs were severely microfilaremic. At the end of the experiment, the peripheral microfilaremia was reduced by 98%.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

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Introduction:  Aberrant expression of the proto‐oncogene c‐Met has been noted in a variety of human cancers. In dogs, inappropriate Met expression has been identified in canine osteosarcoma (OSA) tumor samples. To better define the potential role of Met dysregulation in canine cancer, we cloned canine Met, HGF, and HGF activator and evaluated their expression patterns in a variety of canine tumor cell lines.
Methods:  Canine Met, HGF, and HGF activator were cloned from normal canine liver and canine OSA cell lines using primers based on regions of homology between mouse and human sequences as well as 5' and 3' RACE.
Results:  Inappropriate expression of Met was found in canine cell lines derived from OSAs, mast cell tumors, histiocytic sarcomas, hemangiosarcoma, and melanomas. Both HGF and HGF activator were found to be expressed in several of these tumor cell lines, providing evidence of a possible autocrine loop of Met stimulation. Incubation of canine tumor cell lines with rhHGF resulted in Met autophosphorylation and activation of the downstream signaling elements Gab1, Akt and Erk1/2. Scattering of tumor cells in response to HGF occurred under conditions of cell stress, such as serum starvation. Lastly, the Met inhibitor PHA‐665752 blocked HGF induced phosphorylation of canine Met and Gab1.
Conclusions:  These studies provide evidence that similar to the case in human tumors, aberrant Met expression may play an important role in the biology of canine cancer. As such, inhibition of Met function may represent a potentially useful novel therapeutic approach.  相似文献   

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An avidin-biotin immunoperoxidase procedure was optimized for detection of canine adenoviral antigens in formalin-fixed, paraffin-embedded liver. Long-term stability of viral antigen was shown by successful demonstration of virus in liver tissue preserved up to six years from dogs with infectious canine hepatitis. This immunohistochemical stain was applied to sections from livers with a wide range of inflammatory lesions. Examination of sections from 53 dogs yielded five livers with small amounts of adenovirus. An additional virus-positive liver was identified from a dog with no hepatic inflammation. Although a cause and effect relationship remains to be determined, these findings suggest a possible connection between canine adenovirus and spontaneous chronic hepatitis.  相似文献   

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探讨同源异体骨髓间充质干细胞(BMMSCs)移植对犬急性肝功能损伤的治疗作用,为犬干细胞治疗相关疾病提供理论基础和技术支持。对患急性肝损伤的10只病犬经超声引导腹腔内肝门附近移植BMMSCs,移植后检测血常规、肝功能和肝脏B超,观察同期的症状体征和不良反应情况。结果显示,干细胞移植7天后可使患犬各项肝功能指标明显改善,10d后B超结果显示肝组织回声均匀,无明显异常,14d后患犬的精神、体力、食欲明显好转,干细胞移植21d后血常规各项指标恢复正常,患犬基本康复,移植干细胞的患犬均未发现有不良反应。说明相对于常规治疗,犬BMMSCs同源异体移植治疗急性肝损伤可明显缩短治疗时间,显著提高患犬生活质量。  相似文献   

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Activities of enzymes related to glucose metabolism were measured in canine and feline liver. There were no significant differences in plasma glucose and immunoreactive insulin concentrations between dogs and cats. Glucokinase activities were absent in feline liver, however, activities of other glycolytic enzymes such as hexokinase, phosphofructokinase and pyruvate kinase, were significantly higher than those in canine livers. Activities of rate limiting enzymes of gluconeogenesis such as pyruvate carboxylase, fructose-1, 6-bisphosphatase and glucose-6-phosphatase in feline livers were significantly higher than those in canine livers.  相似文献   

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Signaling lymphocyte activation molecule (SLAM) or CD150 can function as a receptor for the canine distemper virus (CDV) in vitro. The expression of SLAM was studied using immunohistochemistry in order to evaluate the presence and distribution of the receptor in dogs in vivo. Additionally, receptor expression was assessed after experimental infection of dogs with CDV. In 7 control dogs without distemper virus, the receptor was found in various tissues, mostly on cells morphologically identified as lymphocytes and macrophages. In 7 dogs with early distemper lesions characterized by presence of the virus, higher numbers of SLAM-expressing cells were found in multiple tissues recognized as targets of CDV compared with those in control dogs. These findings suggest that SLAM, a putative distemper receptor, is expressed in dogs in vivo. Additionally, virus infection is associated with up-regulation of SLAM, potentially causing an amplification of virus in the host.  相似文献   

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Objective: To determine the effect of storage on ammonia concentration in canine packed red blood cell (pRBC) units.
Design: In vitro and in vivo study.
Setting: University Veterinary Teaching Hospital.
Interventions: Ammonia concentration was measured in 7 units of canine pRBC prepared in citrate-phosphate-dextrose (CPD) and Adsola on Days 1 and 35 of storage. Ammonia was measured in 4 additional units of canine pRBC on Days 0, 7, 14, 21, 28, and 35. Plasma ammonia was also determined in 5 anemic dogs receiving pRBC.
Measurements and Main Results: Ammonia concentration increased from 73 ± 15 mmol/L (mean ± SD) on Day 1 to 800 ± 275 mmpl/L on Day (p<0.001). When measured every 7 days in 4 units of canine pRBC, ammonia concentration increased from 23 ± 8 mmol/L on Day 0 to 179 ± 13 mmol/L (Day 7), 276 ± 56 mmol/L (Day 14). 383 ± 47 mmol/L (Day21), 466 ± 30 mmol/L (Day 28), and 562 ± 27 mmol/L (Day 35) (p<0.05 for all comparisons). In a preliminary study, plasma ammonia concentration measured in blood samples from 5 anemic dogs without primary liver disease immediately before and after transfusion with 5–10 ml/kg of stored pRBC remained in the normal reference range.
Conclusions: The ammonia concentration in stored canine pRBC increased markedly with time. In this preliminary study, ammonia concentrations in dogs without primary liver disease did not increase above the reference range after transfusion with pRBC.  相似文献   

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Tetracyclines have been shown to have anti-inflammatory effects in addition to their antimicrobial action. We investigated the effects of in vivo administration of chlortetracycline (CTC) on ex vivo perfused pig livers. The retention and clearance of Salmonella choleraesuis, production of acute phase proteins C-reactive protein (CRP), and haptoglobin (HPG) by whole livers were studied. The in vitro modulation by CTC of TNF-alpha secretion by pig Kupffer cells (KC) was also studied. Pigs were dosed orally with CTC for three days, and given injections of Salmonella LPS 24 h before removal of the liver. Salmonella retention and clearance by livers of pigs given CTC was lower than by control livers (p < 0.01 and p < 0.05, respectively). We demonstrated an increase of CRP and HPG by livers from control pigs after a three-hour perfusion while pigs from CTC pretreated pigs varied in this response. Further, CTC decreased the secretion of TNF-alpha by cultured KC incubated in vitro with LPS. Modulation of TNF-alpha production by CTC suggests a potential for attenuating the inflammatory response. However, this possible beneficial action of CTC was accompanied by a significant decline in the antimicrobial effect of the liver.  相似文献   

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Hemangiosarcoma (HSA) is a highly malignant tumour with aggressive biological behaviour. HSAs are more common in dogs than other domestic animals. The median survival time of dogs with HSA remains short, even with chemotherapy and surgery. Therefore, there is a critical need to improve the adjuvant chemotherapeutic regimens to improve clinical outcomes in dogs with HSA. Resveratrol has been shown to possess strong anti‐proliferative and/or pro‐apoptotic properties in human cancer cell lines. Nevertheless, the potential anticancer effects of resveratrol have not been reported in canine HSAs. The objective of this study is to determine the growth inhibitory effects of resveratrol in HSA cells when used alone or in combination with doxorubicin, a commonly used chemotherapeutic agent. Frog and DD‐1 canine HSA cell lines were treated with varying concentrations of resveratrol with and without doxorubicin. Cell viability was measured by the MTT assay. The expression of apoptotic proteins, activation of p38 mitogen‐activated protein kinase (MAPK), AMP‐activated protein kinase (AMPK) and extracellular signal‐regulated kinase 1/2 (ERK1/2) were assessed by western blotting. Similar to human cancer cell lines, resveratrol markedly inhibited the growth and induced apoptosis in both HSA cell lines. Mechanistically, resveratrol activated p38 MAPK, but did not affect the AMPK or the ERK1/2 pathways. Additional experiments showed that resveratrol augmented the growth‐inhibitory and apoptotic effects of doxorubicin in both HSA cell lines. These findings suggest that resveratrol has pro‐apoptotic effects in canine HSA cells; therefore, its use as a potential adjunct therapy in canine HSA patients warrants further investigation.  相似文献   

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BACKGROUND: Survivin, a member of the inhibitor of apoptosis protein family, has a dual role in tumor cell proliferative and antiapoptotic pathways. Survivin expression has been shown to be a negative prognostic factor in several cancers of humans, including B-cell non-Hodgkin's lymphoma. HYPOTHESES: High survivin expression will be a negative prognostic factor in dogs with lymphoma (LSA) treated with chemotherapy. In addition, survivin expression will be upregulated in relapsed canine LSA when compared with patient-matched, pretreatment biopsies. ANIMALS: Thirty-one client-owned dogs with stage IIIa or IVa LSA. METHODS: Retrospective evaluation of survivin immunoreactivity was performed on pretreatment lymph node biopsies and patient-matched samples obtained from dogs at relapse after being treated with an abbreviated CHOP-based protocol. RESULTS: In this population of dogs presenting with stage IIIa or IVa B-cell LSA, those dogs that had high survivin immunoreactivity scores had a significantly (P < .01, hazard ratio = 0.30) shorter median disease-free interval than did dogs with low survivin immunoreactivity scores (171 days versus 321 days, respectively). Survivin immunoreactivity was not significantly different in relapsed canine LSA when compared with patient-matched, pretreatment biopsies. CONCLUSIONS AND CLINICAL IMPORTANCE: Survivin expression is a negative prognostic factor that can predict early treatment failure of dogs that present with stage IIIa or IVa, B-cell LSA when treated with a CHOP-based protocol.  相似文献   

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Degenerative Myelopathy (DM) is a progressive neurological disorder of the spinal cord preferentially occurring in German shepherd dogs. The pathogenesis of the disease is unknown. However, there are indications that vitamin E deficiency may be involved in the pathogenesis of DM. Therefore, we analyzed the expression and the nucleotide sequence of the canine alpha-tocopherol transfer protein (alpha Ttp) of German shepherd dogs with DM in order to determine whether a deficiency or a defect of the alpha Ttp could be a primary factor in the pathogenesis of DM, as found in human patients with Ataxia with vitamin E deficiency (AVED). The cDNA of the coding region of the canine alpha Ttp-mRNA was generated from total liver RNA using RT-PCR and 5' RACE technique. We determined the sequence of 707 out of 834 base pairs or 84.8% of the canine alpha Ttp coding region. Sequence comparison of canine alpha Ttp between affected and control dogs revealed no differences in either nucleotide or predicted amino acid sequence. Using Northern blot analysis alpha Ttp-mRNA expression was solely found in the liver of the dogs, rats and humans, while various other organs showed no alpha Ttp-mRNA expression. No significant differences in expression levels of canine alpha Ttp mRNA were found between DM and control dogs. Our data suggest that the canine alpha Ttp gene is unlikely to be involved in the pathogenesis of DM in German shepherd dogs.  相似文献   

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Toll-like receptor 7 (TLR7) is activated by single strand RNA and imidazoquinoline compounds, and induces interferon production. In this study, canine TLR7 cDNA was cloned and sequenced. The full-length cDNA of canine TLR7 gene was 3419bp, encoding 1032 amino acids. The similarities of canine TLR7 with human and mouse TLR7 were 84 and 80% at the nucleotide sequence level, and 86 and 79% at amino acid sequence level, respectively. Further, the expression of TLR7 mRNA was investigated in canine normal tissues by semiquantitative RT-PCR analysis. The common expression level of TLR7 mRNA in tissues from three dogs examined was in large intestine, lung, pancreas, small intestine and skin, though the expression level in each tissue was varied among these healthy dogs. In other tissues (kidney, liver, lymph node, spleen, adrenal gland, and PBMCs), the level of TLR7 mRNA expression was different in individuals.  相似文献   

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Effects of oral prednisolone (OP) on the development of immune responses of Beagle pups to canine distemper virus (CDV) were studied. Dogs were treated with OP for 21 days, twice a day for the first 7 days, once a day for the next 7 days, and on alternate days for the last 7 days. Dogs given dosages of OP (1 mg/kg and 10 mg/kg) showed a normal in vivo immunogenic response after CDV vaccination and survived a virulent CDV challenge exposure, whereas non-treated, nonvaccinated dogs became ill or died after challenge exposure. The most marked effect of corticosteroid treatment on the immune system was the graded phytoimmunosuppressive effect upon the lymphocyte blast transformation test.  相似文献   

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Real-time PCR was optimized for the quantification of canine CD56 mRNA expression. This study was conducted to easily quantify canine CD56 expression and to identify its expression in normal tissues, peripheral blood mononuclear cells and activated lymphocytes in dogs. This assay revealed the highest level of CD56 mRNA expression in the normal canine brain, followed by the lung, kidney and liver. CD56 mRNA expression level in peripheral blood mononuclear cells was considerably lower; among activated lymphocytes in vitro, CD56 mRNA expression was increased.  相似文献   

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The enzyme 11β-hydroxysteroid dehydrogenase 1 (11β-HSD-1) is expressed in a number of tissues in rodents and humans and is responsible for the reactivation of inert cortisone into cortisol. Its gene expression and activity are increased in white adipose tissue (WAT) from obese humans and may contribute to the adverse metabolic consequences of obesity and the metabolic syndrome. The extent to which 11β-HSD-1 contributes to adipose tissue function in dogs is unknown; the aim of the present study was to examine 11β-HSD-1 gene expression and its regulation by proinflammatory and anti-inflammatory agents in canine adipocytes. Real-time PCR was used to examine the expression of 11β-HSD-1 in canine adipose tissue and canine adipocytes differentiated in culture. The mRNA encoding 11β-HSD-1 was identified in all the major WAT depots in dogs and also in liver, kidney, and spleen. Quantification by real-time PCR showed that 11β-HSD-1 mRNA was least in perirenal and falciform depots and greatest in subcutaneous, omental, and gonadal depots. Greater expression was seen in the omental depot in female than in male dogs (P = 0.05). Gene expression for 11β-HSD-1 was also seen in adipocytes, from both subcutaneous and visceral depots, differentiated in culture; expression was evident throughout differentiation but was generally greatest in preadipocytes and during early differentiation, declining as cells progressed to maturity. The inflammatory mediators lipopolysaccharide and tumor necrosis factor α had a main stimulatory effect on 11β-HSD-1 gene expression in canine subcutaneous adipocytes, but IL-6 had no significant effect. Treatment with dexamethasone resulted in a significant time- and dose-dependent increase in 11β-HSD-1 gene expression, with greatest effects seen at 24 h (2nM: approximately 4-fold; 20nM: approximately 14-fold; P = 0.010 for both). When subcutaneous adipocytes were treated with the peroxisome proliferator activated receptor γ agonist rosiglitazone, similar dose- and time-dependent effects were noted. However, no effects were seen when adipocytes from the gonadal WAT depot were treated with rosiglitazone. The induction of 11β-HSD-1 expression, by the pro-inflammatory cytokine tumor necrosis factor α and by lipopolysaccharide may have implications for the pathogenesis of obesity and its associated diseases in the dog.  相似文献   

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