RESUMO
BACKGROUND: Iron toxicosis is rarely reported in horses and chronic excessive oral iron intake has not been reported to cause clinical symptoms in equids. OBJECTIVES: This case series describes 21 genetically unrelated horses and one donkey with chronic iron overload causing haemochromatosis and hepatopathy. STUDY DESIGN: Case series. METHODS: All equids showing clinical signs compatible with chronic liver disease presented to Utrecht University and diagnosed with iron overload and haemochromatosis based on histopathological evaluation of liver tissue and/or blood transferrin saturation levels of >80% and proof of excess dietary iron intake due to excess iron content in drinking water were included. RESULTS: This study included 22 equids. All tested animals (n = 19) had transferrin saturation >80% and 21 of 22 had increased gamma-glutamyltransferase (γGT). Ultrasonography revealed rounded liver margins in five out of six horses and increased echogenicity in 4/6. Histological examination of liver tissue of 12 animals showed hepatitis, fibrosis and haemosiderin accumulation in macrophages and hepatocytes. Post-mortem examination also revealed haemosiderin accumulation in other organs in all seven examined animals. High iron content in drinking water was identified as the source of iron overload in all cases. All animals were housed under the same conditions for a minimum of 9 years prior to diagnosis of haemochromatosis. Of 22 animals, 13 survived until 1 January 2018, ranging from 17 to 79 months post diagnosis. MAIN LIMITATIONS: Histology of liver tissue was not available for 10 of 22 cases. CONCLUSIONS: Chronic iron overload can lead to haemochromatosis and hepatopathy in equids. Development of disease is slow and clinical signs are nonspecific. Long-term excessive iron intake in equids should be avoided. If animals drink from natural water sources, it is important to test the water for iron content. The Summary is available in Spanish - see Supporting Information.
Assuntos
Equidae , Doenças dos Cavalos/patologia , Sobrecarga de Ferro/veterinária , Hepatopatias/veterinária , Animais , Feminino , Doenças dos Cavalos/diagnóstico , Cavalos , Sobrecarga de Ferro/diagnóstico , Sobrecarga de Ferro/patologia , Hepatopatias/diagnóstico , Hepatopatias/etiologia , Hepatopatias/patologia , MasculinoRESUMO
Major hallmarks of osteoarthritis (OA) are cartilage degeneration, inflammation and osteophyte formation. COX-2 inhibitors counteract inflammation-related pain, but their prolonged oral use entails the risk for side effects. Local and prolonged administration in biocompatible and degradable drug delivery biomaterials could offer an efficient and safe treatment for the long-term management of OA symptoms. Therefore, we evaluated the disease-modifying effects and the optimal dose of polyesteramide microspheres delivering the COX-2 inhibitor celecoxib in a rat OA model. Four weeks after OA induction by anterior cruciate ligament transection and partial medial meniscectomy, 8-week-old female rats (n = 6/group) were injected intra-articular with celecoxib-loaded microspheres at three dosages (0.03, 0.23 or 0.39 mg). Unloaded microspheres served as control. During the 16-week follow-up, static weight bearing and plasma celecoxib concentrations were monitored. Post-mortem, micro-computed tomography and knee joint histology determined progression of synovitis, osteophyte formation, subchondral bone changes, and cartilage integrity. Systemic celecoxib levels were below the detection limit 6 days upon delivery. Systemic and local adverse effects were absent. Local delivery of celecoxib reduced the formation of osteophytes, subchondral sclerosis, bone cysts and calcified loose bodies, and reduced synovial inflammation, while cartilage histology was unaffected. Even though the effects on pain could not be evualated directly in the current model, our results suggest the application of celecoxib-loaded microspheres holds promise as novel, safe and effective treatment for inflammation and pain in OA.
Assuntos
Osso e Ossos/diagnóstico por imagem , Celecoxib/farmacologia , Cistos/tratamento farmacológico , Preparações de Ação Retardada/farmacologia , Inflamação/tratamento farmacológico , Osteoartrite/tratamento farmacológico , Animais , Ligamento Cruzado Anterior/efeitos dos fármacos , Materiais Biocompatíveis/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Modelos Animais de Doenças , Feminino , Osteófito/tratamento farmacológico , RatosRESUMO
A 12-year-old male Yorkshire Terrier was presented because of decreased appetite. Physical examination revealed mammary gland swelling and galactorrhea. Contrast-enhanced computed tomographic scanning of the skull indicated an enlarged pituitary gland, compatible with a pituitary tumor. The serum prolactin concentration was markedly elevated. One week after the start of treatment with the dopamine agonist cabergoline, the serum prolactin concentration normalized and the galactorrhea resolved. Cabergoline was administered for approximately 4 months and then discontinued. Subsequently, serum prolactin concentration increased again, and mammary gland swelling and galactorrhea reappeared. The dog was euthanized 10 months after the first detection of the galactorrhea because of problems not directly related to pituitary disease. Postmortem examination revealed an infiltrative adenoma of the pituitary gland with immunolabeling for prolactin. The clinical and histopathologic findings indicated the diagnosis of a functional prolactinoma in a male dog.
Assuntos
Adenoma/veterinária , Agonistas de Dopamina/uso terapêutico , Ergolinas/uso terapêutico , Neoplasias Hipofisárias/veterinária , Prolactinoma/veterinária , Adenoma/diagnóstico por imagem , Adenoma/tratamento farmacológico , Adenoma/patologia , Animais , Cabergolina , Cães , Evolução Fatal , Masculino , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/patologia , Prolactina/sangue , Prolactinoma/diagnóstico por imagem , Prolactinoma/tratamento farmacológico , Prolactinoma/patologia , Tomógrafos ComputadorizadosRESUMO
Hepatic progenitor cells (HPCs) are an adult stem cell compartment in the liver that contributes to liver regeneration when replication of mature hepatocytes is insufficient. In this study, laser microdissection was used to isolate HPC niches from the livers of healthy dogs and dogs with lobular dissecting hepatitis (LDH), in which HPCs are massively activated. Gene expression of HPC, hepatocyte and biliary markers was determined by quantitative reverse transcriptase PCR. Expression and localisation of selected markers were further studied at the protein level by immunohistochemistry and immunofluorescent double staining in samples of normal liver and liver from dogs with LDH, acute and chronic hepatitis, and extrahepatic cholestasis. Activated HPC niches had higher gene expression of the hepatic progenitor markers OPN, FN14, CD29, CD44, CD133, LIF, LIFR and BMI1 compared to HPCs from normal liver. There was lower expression of albumin, but activated HPC niches were positive for the biliary markers SOX9, HNF1ß and keratin 19 by immunohistochemistry and immunofluorescence. Laminin, activated stellate cells and macrophages are abundant extracellular matrix and cellular components of the canine HPC niche. This study demonstrates that the molecular and cellular characteristics of canine HPCs are similar to rodent and human HPCs, and that canine HPCs are distinctively activated in different types of liver disease.
Assuntos
Doenças do Cão/terapia , Regulação da Expressão Gênica , Hepatite Animal/terapia , Fígado/citologia , Transplante de Células-Tronco/veterinária , Células-Tronco/fisiologia , Animais , Biomarcadores/metabolismo , Doenças do Cão/genética , Cães , Imuno-Histoquímica/veterinária , Microdissecção/veterinária , Reação em Cadeia da Polimerase Via Transcriptase Reversa/veterináriaRESUMO
Normal sexual differentiation depends on completion of chromosomal sex determination, gonadal differentiation, and development of the phenotypic sex. An irregularity in any of these three steps can lead to a disorder in sexual development (DSD). We examined nine dogs with DSD by abdominal ultrasonography, laparotomy, histologic examination of the gonads, and reproductive tract, cytogenetic analysis, and mRNA expression of the SRY gene. We also determined the plasma concentrations of luteinizing hormone (LH), estradiol-17ß, and testosterone before and after administration of gonadotropin-releasing hormone (GnRH) and compared these results with those obtained in anestrous bitches and male control dogs. The gonads of three dogs with DSD contained both testicular and ovarian tissue, while in the other six only testicular tissue was found. Each of the dogs had a uterus. Based on gynecologic examination, cytogenetic analysis, and the histology of the gonads, seven of the nine dogs appeared to be XX sex reversals. Three of these were XX true hermaphrodites and four were XX males; the other two dogs had incomplete XY gonadal dysgenesis. All seven XX sex-reversed dogs were found to be negative for the SRY gene by polymerase chain reaction. The basal plasma luteinizing hormone (LH) concentration was significantly higher in dogs with DSD than in anestrous bitches but not significantly different from that in male dogs. The basal plasma LH concentration increased significantly after GnRH administration in all dogs with DSD. The basal plasma estradiol concentration was significantly higher in dogs with DSD than in anestrous bitches but not significantly different from that in male dogs. The basal plasma testosterone concentration was lower in dogs with DSD than in male dogs. In all dogs with DSD both the basal and GnRH-induced plasma testosterone concentrations were above the upper limit of their respective ranges in the anestrous bitches. In conclusion, the secretion of LH and estradiol in these dogs with DSD, all of which had testicular tissue in their gonads, was similar to that in male control dogs. These results indicate that the basal and/or GnRH-stimulated plasma testosterone concentration might be used to detect the presence of testicular tissue in dogs with DSD.
Assuntos
Transtornos do Desenvolvimento Sexual/veterinária , Doenças do Cão/fisiopatologia , Ovário/fisiopatologia , Hipófise/fisiopatologia , Testículo/fisiopatologia , Animais , Transtornos do Desenvolvimento Sexual/patologia , Transtornos do Desenvolvimento Sexual/fisiopatologia , Cães , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Genes sry/genética , Disgenesia Gonadal/veterinária , Hormônio Liberador de Gonadotropina , Hormônio Luteinizante/sangue , Masculino , Ovário/patologia , Transtornos Ovotesticulares do Desenvolvimento Sexual/veterinária , Progesterona/sangue , RNA Mensageiro/análise , Testículo/patologia , Testosterona/sangueRESUMO
An 8-year-old male German longhaired pointer was referred for diabetes insipidus responsive to treatment with desmopressin. The dog had polyuria and polydipsia, exercise intolerance and a dull hair coat. Plasma concentrations of thyroid-stimulating hormone, thyroxine, growth hormone (GH) and insulin-like growth factor-1 were decreased; plasma adrenocorticotropic hormone (ACTH) was slightly elevated and plasma α-melanocyte-stimulating hormone (MSH) was within the reference range. Computed tomography revealed a heterogeneously contrast-enhancing pituitary mass compressing the hypothalamus. Transsphenoidal hypophysectomy was performed and microscopical examination of the surgical biopsy samples revealed hypophysitis without evidence of pituitary adenoma. The hypophysitis was characterized by marked lymphocytic infiltration of the adenohypophysis that contained a mixed population of neuroendocrine cells expressing GH, ACTH or α-MSH. The lymphocytes were identified as T cells, resulting in a final diagnosis of lymphocytic hypophysitis strongly resembling human primary lymphocytic hypophysitis.
Assuntos
Diabetes Insípido/veterinária , Hipopituitarismo/veterinária , Linfócitos/patologia , Adeno-Hipófise/patologia , Hormônio Adrenocorticotrópico/metabolismo , Animais , Antidiuréticos/uso terapêutico , Desamino Arginina Vasopressina/uso terapêutico , Diabetes Insípido/patologia , Diabetes Insípido/terapia , Doenças do Cão , Cães , Eutanásia Animal , Evolução Fatal , Hormônio do Crescimento/metabolismo , Hipopituitarismo/metabolismo , Hipopituitarismo/patologia , Hipopituitarismo/terapia , Masculino , Células Neuroendócrinas/metabolismo , Células Neuroendócrinas/patologia , Adeno-Hipófise/metabolismo , alfa-MSH/metabolismoRESUMO
Pituitary-dependent hypercortisolism (PDH), which is caused by adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas, is a common endocrinopathy in dogs. Dogs with non-enlarged pituitaries harboring a microadenoma have a better prognosis than those with enlarged pituitaries. The aim of this study was to investigate the expression of the proliferation markers Ki-67 and proliferating cell nuclear antigen (PCNA) and the cell-cycle inhibitor p27kip1 in corticotroph adenomas in enlarged and non-enlarged pituitaries. The expression of Ki-67, PCNA, and p27kip1 was analyzed by immunohistochemical staining of 17 pituitary adenoma samples harvested during pituitary surgery in dogs with PDH. The labeling index was calculated by counting the number of immunopositive cells per 1,000 cells. The mean (+/- standard deviation) labeling index for Ki-67 was 8.4%+/-14.2% for the group with enlarged pituitaries, and 8.8%+/-5.5% for the group with non-enlarged pituitaries; that for PCNA was 35.5%+/-12.2% and 37.0%+/-15.5%; and that for p27kip1 was 29.3%+/-22.6% and 42.5%+/-27.9%, respectively. No significant differences in Ki-67, PCNA, and p27kip1 labeling indices were found between enlarged and non-enlarged pituitaries. However, a trend toward significance was observed when comparing the expression of p27kip1 in enlarged pituitaries versus normal pituitary tissue. It is concluded that Ki-67 and PCNA are not useful as proliferative markers for studying the pathobiology of pituitary corticotroph adenomas in dogs.
Assuntos
Adenoma Hipofisário Secretor de ACT/veterinária , Inibidor de Quinase Dependente de Ciclina p27/análise , Doenças do Cão/metabolismo , Antígeno Ki-67/análise , Neoplasias Hipofisárias/veterinária , Antígeno Nuclear de Célula em Proliferação/análise , Adenoma Hipofisário Secretor de ACT/química , Adenoma Hipofisário Secretor de ACT/patologia , Hormônio Adrenocorticotrópico/análise , Animais , Cães , Feminino , Imuno-Histoquímica , Masculino , Neoplasias Hipofisárias/química , Neoplasias Hipofisárias/patologia , alfa-MSH/análiseRESUMO
A proliferative disorder of lymphocytes was observed in a macroscopically normal young adult wild-type zebrafish (Danio rerio) during routine histological screening in a two-generation toxicity study. Proliferating lymphocytes were observed to invade the gill arches, infiltrate the cranial skeletal muscle and inner ear, and accumulate at distant sites in the frontal epidermis. The test compound, tetrabromobisphenol A (TBBPA, a flame retardant), is not known as a carcinogen and no tumours were detected in any of the 53 other fish in the study, including tank mates. Although neoplastic lymphoid proliferation in the thymus region is occasionally observed, we have never seen epitheliotropism in zebrafish during other similar exposure studies or brood stock. Our findings indicate that epitheliotropic lymphoma can occur spontaneously in zebrafish but at a low incidence.
Assuntos
Doenças dos Peixes/diagnóstico , Linfoma Cutâneo de Células T/veterinária , Neoplasias Cutâneas/veterinária , Linfócitos T/patologia , Peixe-Zebra , Animais , Feminino , Doenças dos Peixes/epidemiologia , Incidência , Linfoma Cutâneo de Células T/diagnóstico , Linfoma Cutâneo de Células T/epidemiologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/epidemiologiaRESUMO
Gallium scintigraphy was used to evaluate therapeutic response in a 10-year-old, male, Dutch sheepdog, suffering from an oral melanoma. Treatment was performed with a combination of carboplatin and hypofractionated radiation. Nineteen weeks after radiation therapy, the left submandibular lymph node was surgically removed because of metastatic disease. Thirty weeks after radiation therapy, 67Gallium scintigraphy was performed to assess for residual disease and metastasis. Increased uptake in the right submandibular lymph node area was noted and identified as a melanoma metastasis on cytology. Surgical excision was performed. Twenty-one weeks later, the dog was euthanased because of advanced pulmonary metastases. This report of a case of oral melanoma illustrates the advantages of 67Gallium scintigraphy in monitoring for the presence of metastatic disease and effectiveness of therapy.
Assuntos
Citratos , Doenças do Cão/diagnóstico por imagem , Radioisótopos de Gálio , Gálio , Melanoma/veterinária , Neoplasias Bucais/veterinária , Compostos Radiofarmacêuticos , Animais , Antineoplásicos/uso terapêutico , Carboplatina/uso terapêutico , Terapia Combinada , Doenças do Cão/patologia , Doenças do Cão/terapia , Cães , Eutanásia Animal , Excisão de Linfonodo/veterinária , Metástase Linfática , Masculino , Melanoma/diagnóstico por imagem , Melanoma/terapia , Neoplasias Bucais/diagnóstico por imagem , Neoplasias Bucais/terapia , Cintilografia , Neoplasias da Glândula Submandibular/secundário , Neoplasias da Glândula Submandibular/cirurgia , Neoplasias da Glândula Submandibular/veterináriaRESUMO
Two littermates, a young male and female boxer, were admitted to the Utrecht University's Department of Clinical Sciences of Companion Animals within a three month period. Both dogs suffered from anaemia caused by chronic intestinal blood loss, vomiting and weight loss. In both cases, there was no response to conservative medical management. Eventually, the dogs suffered significant gastrointestinal haemorrhage that resulted in collapse. Gastroduodenoscopy and exploratory surgery showed a duodenal diverticulum in both dogs. This is the first report that describes this congenital anomaly in two siblings.
Assuntos
Divertículo/veterinária , Doenças do Cão/diagnóstico , Duodenopatias/veterinária , Hemorragia Gastrointestinal/veterinária , Animais , Diagnóstico Diferencial , Divertículo/complicações , Divertículo/congênito , Divertículo/diagnóstico , Cães , Duodenopatias/complicações , Duodenopatias/congênito , Duodenopatias/diagnóstico , Evolução Fatal , Feminino , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , MasculinoRESUMO
Telomerase is a ribonucleoprotein enzyme complex that synthesizes telomere DNA. It is detected in 85-90% of malignant tumours in humans, but not in most somatic cells. Because telomerase plays a critical role in cell immortality, it represents an important target for anticancer therapies. We have previously shown that the dog is a potentially useful model for evaluating telomerase-based therapeutics. In this present study we analysed 93 canine brain tumours for telomerase reverse transcriptase (TERT) expression by immunohistochemistry. TERT immunoreactivity was detected in 16 of 50 grade 1 (32%) and 29 of 43 grade 2 tumours (67.4%), demonstrating a statistically significant association with histological grade (P = 0.00012). A subset of 51 tumours was also assessed for MIB-1 expression. The MIB-1 labelling index (LI) was found to correlate significantly with tumour grade, with a mean MIB-1 LI of 1.5% for grade 1 tumours, as compared with a mean MIB-1 LI of 21.7% for grade 2 tumours (P << 0.001). The MIB-1 LI was also significantly associated with TERT expression in all brain tumours (P << 0.001). These data further support the dog as a model for the preclinical development of telomerase-based therapeutics in brain tumours.
Assuntos
Neoplasias Encefálicas/metabolismo , Proliferação de Células , Modelos Animais de Doenças , Cães , Telomerase/biossíntese , Animais , Imuno-Histoquímica , Telomerase/imunologiaRESUMO
This paper briefly reviews the application of histopathology as aninstrument or endpoint in toxicity studies in fish. For long this has been applied rather occasionally in (regulatory) toxicology, and was mainly of interest in fundamental studies and limited carcinogenicity experiments. However, nowadays there are various incentives that ask for the application of pathology, such as field monitoring of pollution effects, the wish for optimal use and lower species of laboratory animals, the availability of modern histology techniques, and insight and interest in mechanistic data. This is timely illustrated by the current broad interest in endocrine disrupting pollutants-a threat mainly in the aquatic environment-where histopathological organ and tissue changes in intact sentinel fish species provide pivotal diagnostic and mechanistic features.