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1.
Viruses ; 13(4)2021 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-33918079

RESUMO

Vascular changes represent a characteristic feature of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection leading to a breakdown of the vascular barrier and subsequent edema formation. The aim of this study was to provide a detailed characterization of the vascular alterations during SARS-CoV-2 infection and to evaluate the impaired vascular integrity. Groups of ten golden Syrian hamsters were infected intranasally with SARS-CoV-2 or phosphate-buffered saline (mock infection). Necropsies were performed at 1, 3, 6, and 14 days post-infection (dpi). Lung samples were investigated using hematoxylin and eosin, alcian blue, immunohistochemistry targeting aquaporin 1, CD3, CD204, CD31, laminin, myeloperoxidase, SARS-CoV-2 nucleoprotein, and transmission electron microscopy. SARS-CoV-2 infected animals showed endothelial hypertrophy, endothelialitis, and vasculitis. Inflammation mainly consisted of macrophages and lower numbers of T-lymphocytes and neutrophils/heterophils infiltrating the vascular walls as well as the perivascular region at 3 and 6 dpi. Affected vessels showed edema formation in association with loss of aquaporin 1 on endothelial cells. In addition, an ultrastructural investigation revealed disruption of the endothelium. Summarized, the presented findings indicate that loss of aquaporin 1 entails the loss of intercellular junctions resulting in paracellular leakage of edema as a key pathogenic mechanism in SARS-CoV-2 triggered pulmonary lesions.


Assuntos
Aquaporina 1/metabolismo , COVID-19/patologia , Células Endoteliais/metabolismo , Células Endoteliais/ultraestrutura , Inflamação/patologia , Animais , Vasos Sanguíneos/ultraestrutura , Modelos Animais de Doenças , Imuno-Histoquímica , Pulmão/irrigação sanguínea , Pulmão/ultraestrutura , Pulmão/virologia , Mesocricetus , SARS-CoV-2 , Vasculite/patologia , Vasculite/virologia
3.
J Zoo Wildl Med ; 50(2): 470-473, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31260217

RESUMO

Two nonrelated Goeldi's monkeys (Callimico goeldii) from the same enclosure developed multifocal alopecia with hyperkeratotic to ulcerative skin lesions on the lower abdomen and inner thighs. Necropsy samples of the first animal showed hyperplastic dermatitis together with in situ carcinoma and intralesional Demodex organisms. The second monkey developed similar lesions 2.5 yr later. Skin scrapings and biopsies also revealed Demodex mites within hyperplastic dermatitis. Long-term treatment with ivermectin, imidacloprid-moxidectin, and sarolaner resolved the demodicosis but skin lesions progressed to actinic keratosis and carcinoma. Both cutaneous neoplasia and demodicosis are rarely described in New World monkeys and these are the first reported cases in Goeldi's monkeys. Since the animals had access to ultraviolet (UV) light, as recommended for indoor-housed callitrichids, the skin tumors were likely UV-induced and the mites have settled particularly within impaired regions. Thus, apparent demodicosis can indicate cutaneous immunosuppression and might alert caretakers to adjust the UV regime.


Assuntos
Callimico , Carcinoma de Células Escamosas/veterinária , Infestações por Ácaros/veterinária , Doenças dos Macacos/etiologia , Neoplasias Cutâneas/veterinária , Raios Ultravioleta/efeitos adversos , Animais , Animais de Zoológico , Antibacterianos/uso terapêutico , Antiparasitários/administração & dosagem , Antiparasitários/uso terapêutico , Azetidinas/administração & dosagem , Azetidinas/uso terapêutico , Carcinoma de Células Escamosas/patologia , Combinação de Medicamentos , Feminino , Fluoroquinolonas/uso terapêutico , Inseticidas/administração & dosagem , Inseticidas/uso terapêutico , Ivermectina/uso terapêutico , Macrolídeos/administração & dosagem , Macrolídeos/uso terapêutico , Masculino , Infestações por Ácaros/tratamento farmacológico , Infestações por Ácaros/parasitologia , Doenças dos Macacos/parasitologia , Doenças dos Macacos/patologia , Neonicotinoides/administração & dosagem , Neonicotinoides/uso terapêutico , Nitrocompostos/administração & dosagem , Nitrocompostos/uso terapêutico , Neoplasias Cutâneas/etiologia , Compostos de Espiro/administração & dosagem , Compostos de Espiro/uso terapêutico
5.
Mol Psychiatry ; 24(10): 1489-1501, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-29426955

RESUMO

Autoantibodies of the IgG class against N-methyl-D-aspartate-receptor subunit-NR1 (NMDAR1-AB) were considered pathognomonic for anti-NMDAR encephalitis. This view has been challenged by the age-dependent seroprevalence (up to >20%) of functional NMDAR1-AB of all immunoglobulin classes found in >5000 individuals, healthy or affected by different diseases. These findings question a merely encephalitogenic role of NMDAR1-AB. Here, we show that NMDAR1-AB belong to the normal autoimmune repertoire of dogs, cats, rats, mice, baboons, and rhesus macaques, and are functional in the NMDAR1 internalization assay based on human IPSC-derived cortical neurons. The age dependence of seroprevalence is lost in nonhuman primates in captivity and in human migrants, raising the intriguing possibility that chronic life stress may be related to NMDAR1-AB formation, predominantly of the IgA class. Active immunization of ApoE-/- and ApoE+/+ mice against four peptides of the extracellular NMDAR1 domain or ovalbumin (control) leads to high circulating levels of specific AB. After 4 weeks, the endogenously formed NMDAR1-AB (IgG) induce psychosis-like symptoms upon MK-801 challenge in ApoE-/- mice, characterized by an open blood-brain barrier, but not in their ApoE+/+ littermates, which are indistinguishable from ovalbumin controls. Importantly, NMDAR1-AB do not induce any sign of inflammation in the brain. Immunohistochemical staining for microglial activation markers and T lymphocytes in the hippocampus yields comparable results in ApoE-/- and ApoE+/+ mice, irrespective of immunization against NMDAR1 or ovalbumin. These data suggest that NMDAR1-AB of the IgG class shape behavioral phenotypes upon access to the brain but do not cause brain inflammation on their own.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato/imunologia , Transtornos Mentais/imunologia , Receptores de N-Metil-D-Aspartato/imunologia , Adulto , Animais , Autoanticorpos/imunologia , Barreira Hematoencefálica , Encéfalo/imunologia , Gatos , Cães , Feminino , Humanos , Imunoglobulina G/genética , Imunoglobulina G/imunologia , Masculino , Camundongos , Proteínas do Tecido Nervoso/imunologia , Proteínas do Tecido Nervoso/metabolismo , Neurônios/imunologia , Primatas , Ratos , Receptores de N-Metil-D-Aspartato/metabolismo , Estudos Soroepidemiológicos
6.
Nature ; 564(7736): 430-433, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30518863

RESUMO

Heart transplantation is the only cure for patients with terminal cardiac failure, but the supply of allogeneic donor organs falls far short of the clinical need1-3. Xenotransplantation of genetically modified pig hearts has been discussed as a potential alternative4. Genetically multi-modified pig hearts that lack galactose-α1,3-galactose epitopes (α1,3-galactosyltransferase knockout) and express a human membrane cofactor protein (CD46) and human thrombomodulin have survived for up to 945 days after heterotopic abdominal transplantation in baboons5. This model demonstrated long-term acceptance of discordant xenografts with safe immunosuppression but did not predict their life-supporting function. Despite 25 years of extensive research, the maximum survival of a baboon after heart replacement with a porcine xenograft was only 57 days and this was achieved, to our knowledge, only once6. Here we show that α1,3-galactosyltransferase-knockout pig hearts that express human CD46 and thrombomodulin require non-ischaemic preservation with continuous perfusion and control of post-transplantation growth to ensure long-term orthotopic function of the xenograft in baboons, the most stringent preclinical xenotransplantation model. Consistent life-supporting function of xenografted hearts for up to 195 days is a milestone on the way to clinical cardiac xenotransplantation7.


Assuntos
Transplante de Coração , Xenoenxertos/transplante , Papio , Suínos , Transplante Heterólogo , Animais , Anticorpos/análise , Anticorpos/sangue , Proteínas do Sistema Complemento/análise , Enzimas/sangue , Fibrina/análise , Galactosiltransferases/deficiência , Galactosiltransferases/genética , Xenoenxertos/patologia , Humanos , Fígado/enzimologia , Masculino , Proteína Cofatora de Membrana/genética , Proteína Cofatora de Membrana/metabolismo , Miocárdio/enzimologia , Necrose , Perfusão , Contagem de Plaquetas , Tempo de Protrombina , Trombomodulina/genética , Trombomodulina/metabolismo , Fatores de Tempo
7.
J Zoo Wildl Med ; 49(2): 501-504, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29900783

RESUMO

A captive-born adult female Nilgiri langur ( Semnopithecus johnii) developed an edematous swelling of the left thigh and a firm mass around the right ankle joint. The animal also suffered from lethargy and anorexia and was euthanized because of poor general condition. Necropsy revealed that the skeletal muscle of the left thigh had been replaced by a multilocular cystic mass containing numerous sand-grain-sized whitish structures. Small cysts were also present in the lung and the myocardium. The mass of the right ankle joint was histologically consistent with a myxosarcoma. In contrast, the cystic masses from the left thigh, the lung, and the myocardium represented metacestode tissue with evidence of numerous larval cestodes consistent with cysticerci. Cysticerci showed morphological characteristics of Cysticercus longicollis, the larval form of Taenia crassiceps, which was confirmed by genetic analysis. This is the first documented case of a Taenia crassiceps cysticercosis in an Old World monkey species.


Assuntos
Colobinae , Cisticercose/veterinária , Cysticercus/isolamento & purificação , Doenças dos Macacos/diagnóstico , Animais , Animais de Zoológico , Cisticercose/diagnóstico , Cisticercose/parasitologia , Feminino , Alemanha , Doenças dos Macacos/parasitologia
8.
Can J Vet Res ; 82(2): 115-123, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29755191

RESUMO

Studies in humans have shown that the ubiquitin-proteasome pathway and the insulin-like growth factor axis are involved in carcinogenesis, thus, components of these systems might be useful as prognostic markers and constitute potential therapeutic targets. In veterinary medicine, only a few studies exist on this topic. Here, serum concentrations of 26S proteasome (26SP) and insulin-like growth factor-1 (IGF-1) were measured by canine enzyme-linked immunosorbent assay (ELISA) in 43 dogs suffering from malignant tumors and 21 clinically normal dogs (control group). Relationships with tumor size, survival time, body condition score (BCS), and tumor entity were assessed. The median 26SP concentration in the tumor group was non-significantly higher than in the control group. However, dogs with mammary carcinomas displayed significantly increased 26SP levels compared to the control group and dogs with tumor size less than 5 cm showed significantly increased 26SP concentrations compared to dogs with larger tumors and control dogs. 26SP concentrations were not correlated to survival time or BCS. No significant difference in IGF-1 levels was found between the tumor group and the control group; however, IGF-1 concentrations displayed a larger range of values in the tumor group. Dogs with tumors greater than 5 cm showed significantly higher IGF-1 levels than dogs with smaller tumors. The IGF-1 concentrations were positively correlated to survival time, but no correlation with BCS was found. Consequently, serum 26SP concentrations seem to be increased in some dogs suffering from malignant tumors, especially in dogs with mammary carcinoma and smaller tumors. Increased serum IGF-1 concentrations could be an indication of large tumors and a poor prognosis.


Des études chez l'humain ont démontré que la voie ubiquitine-protéasome et l'axe du facteur de croissance apparenté à l'insuline sont impliqués dans la carcinogénèse, et ainsi, des composantes de ces systèmes pourraient être utiles en tant que marqueurs du pronostic et constituer des cibles thérapeutiques potentielles. En médecine vétérinaire, seules quelques études existent sur ce sujet. Dans cette étude, les concentrations sériques de protéasome 26S (26SP) et du facteur de croissance 1 apparenté à l'insuline (IGF-1) ont été mesurés par réaction immunoenzymatique (ELISA) chez 43 chiens souffrant de tumeurs malignes et 21 chiens cliniquement normaux (groupe témoin). Les associations entre la taille des tumeurs, le temps de survie, le pointage de la condition corporelle (PCC) et le type de tumeurs ont été évaluées. La concentration médiane de 26SP dans le groupe avec tumeur était plus élevée que celle du groupe témoin mais de manière non-significative. Toutefois, les chiens avec des carcinomes mammaires montraient des quantités significativement augmentées de 26SP comparativement au groupe témoin et les chiens avec des tumeurs dont la taille était de moins de 5 cm avaient des concentrations de 26SP significativement augmentées comparativement aux chiens avec des tumeurs plus grosses et aux chiens du groupe témoin. Les concentrations de 26SP n'étaient pas corrélées au temps de survie ou au PCC. Aucune différence significative dans les niveaux d'IGF-1 ne fut trouvée entre le groupe avec tumeur et le groupe témoin; toutefois, les concentrations d'IGF-1 s'étendaient sur un plus large spectre dans le groupe avec tumeur. Les chiens avec des tumeurs plus large que 5 cm avaient des concentrations d'IGF-1 significativement plus élevées que les chiens avec des tumeurs plus petites. Les concentrations d'IGF-1 étaient corrélées positivement avec le temps de survie, mais aucune corrélation avec le PCC ne fut trouvée. Conséquemment, les concentrations de 26SP semblent être augmentées chez quelques chiens souffrant de tumeurs malignes, et plus spécialement les chiens avec des carcinomes mammaires et des plus petites tumeurs. Des concentrations augmentées d'IGF-1 pourraient être une indication d'une grosse tumeur et d'un pronostic sombre.(Traduit par Docteur Serge Messier).


Assuntos
Carcinoma/veterinária , Doenças do Cão/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Linfoma/veterinária , Complexo de Endopeptidases do Proteassoma/sangue , Animais , Carcinoma/sangue , Carcinoma/metabolismo , Estudos de Casos e Controles , Doenças do Cão/sangue , Cães , Feminino , Linfoma/sangue , Linfoma/metabolismo , Masculino , Estudos Prospectivos
9.
Res Vet Sci ; 118: 484-490, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29751280

RESUMO

In patients suffering from chronic diseases, the objective assessment of metabolic states could be of interest for disease prognosis and therapeutic options. Therefore, the aim of this study was to assess insulin-like growth factor-1 (IGF-1) and 26S proteasome (26SP) in healthy dogs and dogs suffering from chronic diseases depending on their body condition score (BCS) and to examine their potential for objective assessment of anabolic and catabolic states. Serum concentrations of IGF-1, an anabolic hormone, and 26SP, a multiprotein complex which is part of the ubiquitin-proteasome pathway, by which the majority of endogenous proteins including the muscle proteins are degraded, were measured in 21 healthy dogs and 20 dogs with chronic diseases by canine ELISA. The concentrations of IGF-1, 26SP and their ratio (IGF-1/26SP) were set in relationship to the BCS of the dogs. When examining healthy and chronically diseased dogs separately, a positive correlation between IGF-1 and the BCS was observed in the healthy group and a negative correlation between 26SP and the BCS was noted in dogs with chronic diseases. Further, dogs suffering from chronic diseases showed higher 26SP concentrations and lower values for IGF-1/26SP than the healthy dogs. Overall, we detected a negative correlation between 26SP and the BCS and a positive correlation between IGF-1/26SP and the BCS. The results of our study indicate usability of IGF-1 for description of anabolic states, while 26SP could be useful for detection and description of catabolic states. Finally, the ratio IGF-1/26SP seems to be promising for assessment of metabolic states.


Assuntos
Doenças do Cão/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Complexo de Endopeptidases do Proteassoma/sangue , Animais , Estudos de Casos e Controles , Doença Crônica , Doenças do Cão/metabolismo , Cães/sangue
10.
Viruses ; 9(12)2017 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-29182537

RESUMO

Experimental intranasal infection of marmosets (Callithrix jacchus) with calpox virus results in fatal disease. Route and dose used for viral inoculation of the test animals mimics the natural transmission of smallpox, thus representing a suitable model to study pathogenesis and to evaluate new vaccines against orthopoxvirus infection. However, the pathogenic mechanisms leading to death are still unclear. Therefore, our study aimed at investigating the kinetics of pathological alterations to clarify the pathogenesis in calpox virus infection. Following intranasal inoculation with two different viral doses, common marmosets were sacrificed on days 3, 5, 7, 10 and 12 post inoculation. Collected tissue was screened using histopathology, immunohistochemistry, transmission electron microscopy, and virological assays. Our data suggest that primary replication took place in nasal and bronchial epithelia followed by secondary replication in submandibular lymph nodes and spleen. Parallel to viremia at day 7, virus was detectable in many organs, mainly located in epithelial cells and macrophages, as well as in endothelial cells. Based on the onset of clinical signs, the histological and ultrastructural lesions and the immunohistochemical distribution pattern of the virus, the incubation period was defined to last 11 days, which resembles human smallpox. In conclusion, the data indicate that the calpox model is highly suitable for studying orthopoxvirus-induced disease.


Assuntos
Callithrix , Modelos Animais de Doenças , Orthopoxvirus/patogenicidade , Infecções por Poxviridae/patologia , Administração Intranasal , Animais , Brônquios/virologia , Feminino , Imuno-Histoquímica , Masculino , Microscopia Eletrônica de Transmissão , Mucosa Nasal/virologia , Orthopoxvirus/genética , Orthopoxvirus/fisiologia , Infecções por Poxviridae/transmissão , Infecções por Poxviridae/virologia , Varíola/patologia , Varíola/transmissão , Varíola/virologia , Baço/patologia , Baço/virologia , Vírus da Varíola/genética , Vírus da Varíola/patogenicidade , Vírus da Varíola/fisiologia , Carga Viral , Tropismo Viral , Viremia/virologia , Replicação Viral
11.
Proc Natl Acad Sci U S A ; 114(44): 11745-11750, 2017 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-29078330

RESUMO

Transplantation of pancreatic islets for treating type 1 diabetes is restricted to patients with critical metabolic lability resulting from the need for immunosuppression and the shortage of donor organs. To overcome these barriers, we developed a strategy to macroencapsulate islets from different sources that allow their survival and function without immunosuppression. Here we report successful and safe transplantation of porcine islets with a bioartificial pancreas device in diabetic primates without any immune suppression. This strategy should lead to pioneering clinical trials with xenotransplantation for treatment of diabetes and, thereby, represents a previously unidentified approach to efficient cell replacement for a broad spectrum of endocrine disorders and other organ dysfunctions.


Assuntos
Diabetes Mellitus Experimental/cirurgia , Diabetes Mellitus Tipo 1/cirurgia , Diabetes Mellitus Tipo 1/terapia , Ilhotas Pancreáticas/cirurgia , Animais , Feminino , Terapia de Imunossupressão/métodos , Transplante das Ilhotas Pancreáticas/métodos , Primatas , Suínos , Transplante Heterólogo/métodos
12.
J Med Primatol ; 46(4): 144-148, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28748664

RESUMO

Hallmarks of SIV infection are early depletion of gut CD4 T cells and diminished intestinal integrity. Comprehensive studies on colon biopsies of SIV-infected macaques efficiently controlling infection revealed that in contrast to viremic and failing controllers, elite controllers show preserved CD4 T cells, and low viral load, apoptosis, and inflammation.


Assuntos
Colo/imunologia , Macaca mulatta , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Animais , Apoptose , Contagem de Linfócito CD4 , Colo/anatomia & histologia , Colo/virologia , Índia , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/fisiologia
13.
J Med Primatol ; 46(5): 211-217, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28444886

RESUMO

BACKGROUND: Due to a sporadic occurrence of Mycobacterium avium subsp. paratuberculosis (MAP) in non-human primates (NHP), the susceptibility of different NHP to MAP should be investigated. METHODS: Fecal and tissue samples (ileum, ileocecal lymph node, bone marrow) of 20 animals (seven species) were analyzed by IS900-based PCRs and sequenced. Samples of MAP PCR positive NHP were further cultivated. RESULTS: MAP DNA was detectable in two animals; the ileum of a cottontop tamarin and the bone marrow of a common marmoset. Cultivation of MAP failed. Sequence analysis revealed 100% homology to the MAP-K10 sequence. Pathohistological examinations offered no direct correlation to a MAP infection. CONCLUSIONS: MAP was detected for the first time in a common marmoset. But as both NHP suffered from other diseases, an asymptomatic infection with MAP was assumed. The detection of MAP in the bone marrow might play a role in establishing latent paratuberculosis, as known from tuberculosis.


Assuntos
Callitrichinae , Colobus , Macaca , Doenças dos Macacos/epidemiologia , Mycobacterium avium subsp. paratuberculosis/isolamento & purificação , Paratuberculose/epidemiologia , Animais , Animais de Zoológico , DNA Bacteriano/análise , Fezes/microbiologia , Feminino , Alemanha/epidemiologia , Incidência , Masculino , Doenças dos Macacos/microbiologia , Paratuberculose/microbiologia , Reação em Cadeia da Polimerase
14.
Res Vet Sci ; 110: 16-21, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28159231

RESUMO

Because of the limited number of tumor markers in veterinary medicine, there is need for identifying new markers. Ki-67 has been investigated as a tissue marker of malignant alterations. We hypothesized that Ki-67 would also be measurable in serum and should therefore be elevated in cases of malignancy. The purpose of this prospective study was to measure Ki-67 in clinically healthy dogs, dogs with nonmalignant diseases, and dogs with malignant tumors. Samples from 8 healthy dogs, 13 dogs with nonmalignant diseases, and 20 dogs with malignant tumors were collected. Ki-67 was measured using the commercially available canine-specific ELISA. Results demonstrated undetectable Ki-67 serum concentrations in healthy dogs. Dogs with nonmalignant diseases displayed low Ki-67 serum concentrations. In contrast, dogs with malignancies showed significantly increased serum Ki-67 concentrations compared with the healthy (p<0.001) or nonmalignant diseased dogs (p<0.001). The degree of malignancy had a positive influence on serum Ki-67 levels. In contrast, no influence of tumor size on Ki-67 serum concentration was observed (p>0.05). Comparing healthy dogs and tumor bearing dogs a sensitivity of 0.75 and a specificity of 1.0 can be calculated using a Ki-67 cut-off value of 5.5pg/mL. When dogs with a low degree of malignancy were compared with dogs of moderate-to-severe degree malignant tumors a sensitivity of 1.0 and a specificity of 1.0 can be observed at a Ki-67 cut-off value of 19.25pg/mL. In conclusion, our results demonstrate an association of malignancies with elevated Ki-67 serum concentrations in dogs.


Assuntos
Biomarcadores Tumorais/sangue , Doenças do Cão/diagnóstico , Ensaio de Imunoadsorção Enzimática/veterinária , Antígeno Ki-67/sangue , Neoplasias/veterinária , Animais , Doenças do Cão/etiologia , Cães , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Masculino , Neoplasias/etiologia , Estudos Prospectivos , Sensibilidade e Especificidade , Células Tumorais Cultivadas
15.
J Zoo Wildl Med ; 48(4): 1086-1094, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29297824

RESUMO

Mycobacterium avium subspecies paratuberculosis (MAP) causes chronic, progressive, and consecutively fatal enteritis, especially in ruminants. MAP distribution among wildlife is not yet clear. In this study, three wild-born rock hyraxes ( Procavia capensis) had been imported from South Africa to a German zoological garden. During the quarantine period, four young animals were born. The wild-born animals showed symptoms of mild diarrhea shortly after their arrival in the zoological garden, but all routine parasitological and bacteriologic tests performed were negative. Therefore, the animals were additionally tested for MAP infection. MAP DNA was detected by seminested PCR (snPCR) in a pooled fecal sample of the seven animals. Subsequent PCR analysis of the individual feces samples confirmed the excretion of MAP in two rock hyraxes (one wild-born and one born in captivity). Sequence analysis of the corresponding 278-bp amplicons revealed 100% homology to the reference MAP-K10 IS900 sequence. No antibody response against MAP was detected in the individual serum samples. MAP-specific postmortem lesions were not observed by gross pathology and histology, neither after death nor after euthanization of the animals. Nevertheless, MAP was detected by snPCR and culture in the gastrointestinal tract, urogenital tract, cardiovascular system, and/or respiratory system of three other animals of the group (one wild-born and two born in captivity). This study is the first report confirming MAP occurrence in rock hyraxes. Therefore, it is recommended that veterinarians and zoo employees consider rock hyraxes as a possible source of MAP infection for domestic livestock in South Africa and the valuable animal stock of zoological facilities.


Assuntos
Procaviídeos/microbiologia , Mycobacterium avium subsp. paratuberculosis , Paratuberculose/microbiologia , Animais , Animais Selvagens , Animais de Zoológico , DNA Bacteriano/isolamento & purificação , Fezes/microbiologia , Alemanha , Paratuberculose/epidemiologia , Paratuberculose/mortalidade , África do Sul
16.
Exp Toxicol Pathol ; 68(6): 335-43, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27165445

RESUMO

Common marmosets (Callithrix jacchus) are frequently used as translational animal models for human diseases. However, a comparative study of cytological and histochemical detection methods as well as morphometric and ultrastructural characterization of neutrophils and eosinophils in this species is lacking. Blood samples of house dust mite sensitized and allergen challenged as well as lipopolysaccharide (LPS) challenged marmosets were analyzed with different cytological and histological staining methods. Furthermore, cell size and number of nuclear segments were compared between neutrophils and eosinophils. Electron microscopy was performed to characterize the ultrastructure of granulocytes. Of all applied cytological stains, three allowed differentiation of eosinophils and neutrophils and, thus, reliable quantification in blood smears: May-Grünwald-Giemsa stain, Congo Red and Naphthol AS-D Chloroacetate-Esterase. For histology, Hematoxylin-Eosin (H&E) could not demonstrate clear differences, whereas Sirius Red, Congo Red, and Naphthol AS-D Chloroacetate Esterase showed capable results for identification of eosinophils or neutrophils in lung tissue. Morphometry revealed that marmoset neutrophils have more nuclear segments and are slightly larger than eosinophils. Ultrastructurally, eosinophils presented with large homogeneous electron-dense granules without crystalloid cores, while neutrophils were characterized by heterogeneous granules of different size and density. Additionally, sombrero-like vesicles were detected in tissue eosinophils of atopic marmosets, indicative for hypersensitivity-related piecemeal degranulation. In conclusion, we provide a detailed overview of marmoset eosinophils and neutrophils, important for phenotypic characterization of marmoset models for human airway diseases.


Assuntos
Callithrix/imunologia , Eosinófilos/ultraestrutura , Neutrófilos/ultraestrutura , Animais , Callithrix/sangue , Granulócitos/ultraestrutura , Imuno-Histoquímica , Masculino , Microscopia Eletrônica de Transmissão , Coloração e Rotulagem
17.
J Vet Med Sci ; 78(3): 375-81, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26522810

RESUMO

Interleukin-8 (IL-8 or CXCL8) is a highly selective pro-inflammatory chemokine, that is elevated in sera of humans and animals with various inflammatory diseases. CXCL8 is possibly involved in uncontrolled inflammation and the development of a systemic inflammatory response syndrome (SIRS) and sepsis. Nevertheless, its behavior and precise properties in the course of inflammation are not fully understood. Thus, we used naturally occurring canine pyometra as a model of inflammation, in order to examine the behavior of serum CXCL8 in relation to the disease intensity and commonly analyzed inflammatory mediators. Using a commercially available canine ELISA kit, a significant increase of CXCL8 was determined in the serum of 23 dogs with pyometra compared with 35 healthy dogs. Interestingly, serum CXCL8 did not increase in severely diseased patients and behaved contrary to white blood cells (WBC), neutrophils and C-reactive protein (CRP). The measurement of serum CXCL8 may provide valuable information about the extent of ongoing lesions and could be a useful complement for existing laboratory tests.


Assuntos
Doenças do Cão/sangue , Inflamação/veterinária , Interleucina-8/sangue , Piometra/veterinária , Animais , Cães , Feminino , Inflamação/sangue , Piometra/sangue
18.
PLoS One ; 10(7): e0131280, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26132936

RESUMO

BACKGROUND: A somatic deletion at the proximal end of canine chromosome 27 (CFA27) was recently reported in 50% of malignant mammary tumors. This region harbours the tumor suppressor gene prefoldin subunit 5 (PFDN5) and the deletion correlated with a higher Ki-67 score. PFDN5 has been described to repress c-MYC and is, therefore, a candidate tumor-suppressor and cancer-driver gene in canine mammary cancer. Aim of this study was to confirm the recurrent deletion in a larger number of tumors. METHODS: Droplet digital PCR for PFDN5 was performed in DNA from 102 malignant, 40 benign mammary tumors/dysplasias, 11 non-neoplastic mammary tissues and each corresponding genomic DNA from leukocytes. The copy number of PFDN5 was normalized to a reference amplicon on canine chromosome 32 (CFA32). Z-scores were calculated, based on Gaussian distributed normalized PFDN5 copy numbers of the leukocyte DNA. Z-scores ≤ -3.0 in tissue were considered as being indicative of the PFDN5 deletion and called as such. The Ki-67 proliferation index was assessed in a subset of 79 tissue samples by immunohistochemistry. RESULTS: The deletion was confirmed in 24% of all malignant tumors, detected in only 7.5% of the benign tumors and was not present in any normal mammary tissue sample. The subgroup of solid carcinomas (n = 9) showed the highest frequency of the deletion (67%) and those malignomas without microscopical high fraction of benign tissue (n = 71) had a 32% frequency (p<0.01 vs. benign samples). The Ki-67 score was found to be significantly higher (p<0.05) in the PFDN5-deleted group compared to malignant tumors without the deletion. CONCLUSIONS: A somatic deletion of the PFDN5 gene is recurrently present in canine mammary cancer, supporting a potential role in carcinogenesis. The association of this deletion with higher Ki-67 indicates an increased proliferation rate and thus a link to tumor aggressiveness can be hypothesized. The confirmation of earlier results warrants further studies on PFDN5 as cancer-driver gene.


Assuntos
Deleção de Genes , Neoplasias Mamárias Animais/genética , Chaperonas Moleculares/genética , Animais , Cães , Feminino , Subunidades Proteicas/genética
19.
Res Vet Sci ; 97(2): 257-62, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25241388

RESUMO

Splenic haemangiosarcomas are frequently seen in dogs. Because of their bad prognosis differentiation from other benign splenic lesions are of prognostic importance. However, because haemangiosarcoma is a tumour of the vascular system, it was hypothesised that vascular endothelial growth factor (VEGF) might play a major role in tumour growth and might thus be increased in the blood of affected dogs. The aim of this study was to investigate the clinical relevance of differences in serum VEGF concentrations between dogs with splenic haemangiosarcomas and those with non-malignant splenic lesions (haematomas) and healthy subjects using a canine ELISA. Serum VEGF levels were significantly higher in dogs with splenic masses compared with healthy dogs, but did not differ significantly between dogs with haemangiosarcomas and haematomas. VEGF has a potential clinical utility as a diagnostic marker for dogs with splenic lesions but may not be useful to differentiate among the various splenic lesions.


Assuntos
Biomarcadores Tumorais/sangue , Doenças do Cão/diagnóstico , Hemangiossarcoma/veterinária , Hematoma/veterinária , Esplenopatias/veterinária , Neoplasias Esplênicas/veterinária , Fator A de Crescimento do Endotélio Vascular/sangue , Animais , Biomarcadores/sangue , Estudos de Casos e Controles , Diagnóstico Diferencial , Doenças do Cão/sangue , Cães , Ensaio de Imunoadsorção Enzimática/veterinária , Feminino , Hemangiossarcoma/sangue , Hemangiossarcoma/diagnóstico , Hematoma/sangue , Hematoma/diagnóstico , Masculino , Prognóstico , Estudos Prospectivos , Esplenopatias/sangue , Esplenopatias/diagnóstico , Neoplasias Esplênicas/sangue , Neoplasias Esplênicas/diagnóstico
20.
J Med Primatol ; 43(1): 55-8, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24536099

RESUMO

BACKGROUND: The distribution of ciliated cells in the tracheal epithelium of common marmosets was evaluated. METHODS: Light and scanning electron microscopy of tracheal epithelium was performed. RESULTS: Ciliated cells were concentrated in cartilage-free areas and virtually absent in cartilage-supported epithelial regions. CONCLUSIONS: Heterogeneous distribution of ciliated cells in the trachea has to be considered when using animal models for translational respiratory research approaches.


Assuntos
Callithrix/anatomia & histologia , Cílios/ultraestrutura , Células Epiteliais/citologia , Traqueia/citologia , Animais , Células Epiteliais/ultraestrutura , Feminino , Masculino , Microscopia Eletrônica de Varredura , Traqueia/ultraestrutura
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