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1.
Artículo en Alemán | MEDLINE | ID: mdl-38412953

RESUMEN

OBJECTIVE: In this retrospective study, patient records of dogs suffering from poisoning with coumarin derivatives were evaluated to characterize the clinical appearance more precisely. MATERIAL UND METHODS: Retrospective data analysis included 52 dogs with hemostaseologically proven anticoagulant rodenticide poisoning which were treated as inpatients at the Clinic for Small Animals between September 2011 and October 2018. RESULTS: In only 2 dogs (4%) the intake of poison could be observed with certainty. The most common clinical signs observed were reduced general behavior (79%), pallor of the mucosa (79%), anorexia (60%), and dyspnea/tachypnea (60%). In contrast, macroscopically visible internal and external bleedings occurred less frequently. Initially, all cases showed a highly altered prothrombin time and most patients a considerably prolonged activated partial thromboplastin time. Anemia was present in 75% of patients. All dogs included in the study received initially an intravenous treatment with 10 mg/kg vitamin K1. Pretreatment with 1 mg/kg prednisolone was given for prophylaxis of possible incompatibility reactions. No patient showed signs of anaphylactic reaction. Transfusions of whole blood or concentrated red cells were given to only 10 of the 52 animals; only one received 2 transfusions of erythrocytes. 94% of the animals could be discharged home for outpatient therapy after a median length of hospitalization of 3 days (1-9 days) with physiological or almost physiological coagulation test results. CONCLUSION: Anticoagulant rodenticide poisoning is often associated with non-specific symptoms and good prognosis if treated adequately. CLINICAL RELEVANCE: Coagulation diagnostics is always indicated in cases with unclear disorders. In life-threatening emergencies, immediate intravenous infusion of high-dose vitamin K1 is a very effective treatment and results in a rapid increase in coagulation factor activity.


Asunto(s)
Enfermedades de los Perros , Intoxicación , Rodenticidas , Humanos , Perros , Animales , Anticoagulantes , Estudios Retrospectivos , Enfermedades de los Perros/inducido químicamente , Enfermedades de los Perros/diagnóstico , Vitamina K 1 , Intoxicación/veterinaria
2.
Artículo en Alemán | MEDLINE | ID: mdl-37956663

RESUMEN

The autoimmune polyendocrine syndrome (APS) refers to a combination of autoimmune endocrine disorders. It is rarely described in dogs. The most common combinations are hypoadrenocorticism and hypothyroidism, followed by diabetes mellitus, and less often hypoparathyroidism and orchitis. The diagnosis of the APS is based on the diagnosis of each endocrinopathy, as is the therapy, which involves the substitution of deficient hormones. If a patient was previously stable under treatment and is showing further signs (e.g. polyuria, polydipsia, or weight loss), the development of additional endocrinopathies like hypoadrenocorticism or diabetes mellitus should be considered. The diagnosis of the initially diagnosed endocrinopathy should also be critically questioned. This article summarizes some cases of our own animal hospital and selected cases published in the available literature.


Asunto(s)
Diabetes Mellitus Tipo 1 , Enfermedades de los Perros , Hipoparatiroidismo , Poliendocrinopatías Autoinmunes , Masculino , Perros , Animales , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 1/veterinaria , Poliendocrinopatías Autoinmunes/diagnóstico , Poliendocrinopatías Autoinmunes/terapia , Poliendocrinopatías Autoinmunes/veterinaria , Síndrome , Hipoparatiroidismo/diagnóstico , Hipoparatiroidismo/terapia , Hipoparatiroidismo/veterinaria , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/terapia
3.
Res Vet Sci ; 161: 77-79, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37327691

RESUMEN

This study aimed to determine a pharmacokinetic profile for a single dosage of cyclosporine A (CsA) clinically used for immunosuppression in cats. Blood-CsA-concentrations were measured before and 1, 2, 4, 6, 8, 12 and 24 h after oral administration of 7 mg/kg body weight (BW) CsA (Atopica® oral solution) to 8 healthy adult cats using high-performance liquid chromatography coupled to mass spectrometry. Pharmacokinetic parameters were calculated using WinNonLin software based on a 1-compartment-model. The median maximum plasma-concentration of 1466 ng/ml (530-2235 ng/ml; minimum-maximum) was reached after 2.0 h (1.0-4.7 h). The area under the curve was 12,568 h x ng/ml (5732-20,820 h x ng/ml) and the apparent total clearance of the drug from plasma was 557 ml/h/kg (336-1221 ml/h/kg). Half-life of absorption into the central compartment was 0.6 h (0.4-2.6 h), half-life of elimination from the central compartment was 4.6 h (1.4-7.5 h).


Asunto(s)
Ciclosporina , Gatos , Animales , Ciclosporina/farmacocinética , Área Bajo la Curva , Cromatografía Líquida de Alta Presión/veterinaria , Administración Oral , Semivida
4.
Ticks Tick Borne Dis ; 14(6): 102220, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37356181

RESUMEN

Tick-borne encephalitis virus (TBEV) is a tick-transmitted flavivirus, which can infect humans and animals, sometimes even with a fatal outcome. Since many decades, TBEV is endemic in southern Germany, while only sporadic occurrence has been noted in northern parts of the country so far. Nevertheless, autochthonous human clinical cases are increasing in the federal state of Lower Saxony in north-western Germany, and several natural foci of TBEV transmission have recently been detected in this federal state. In order to shed more light on the current distribution of TBEV in Lower Saxony, the present study examined blood samples from wild and domestic animals for antibodies against TBEV. Overall, samples from 4,085 animals were tested by ELISA, including wild boar (N = 1,208), roe deer (N = 149), red deer (N = 61), fallow deer (N = 18), red foxes (N = 9), nutria (N = 9), raccoon dogs (N = 3), raccoons (N = 3), badgers (N = 1), European pine martens (N = 1), horses (N = 574), sheep (N = 266), goats (N = 67), dogs (N = 1,317) and cats (N = 399). Samples with an ELISA result of ≥60 Vienna units (VIEU)/ml were subjected to confirmatory serum neutralization tests (SNT). In total, 343 of 4,085 (8.4%) animals tested positive for anti-TBEV-IgG by ELISA, of which 60 samples were confirmed by SNT. Samples of 89 animals showed a cytotoxic effect in the SNT and were excluded from seroprevalence calculation, resulting in an overall seroprevalence of 1.5% (60/3,996). Seroprevalence was higher among wild animals (wild boar: 2.9% [34/1,190], roe deer: 2.7% [4/149], red deer: 1.7% [1/60], fallow deer: 5.6% [1/18]) than among domestic animals (dogs: 1.1% [15/1,317], horses: 0.8% [4/505], sheep: 0.4% [1/266]). No anti-TBEV-antibodies were detected in the other wild animal species as well as goats and cats. A notable clustering of positive samples was observed in districts where TBEV transmission foci have been described. Further clusters in other districts suggest the existence of so far undetected transmission foci, underlining the fact that both wild and domestic animals are useful sentinels for monitoring the spread of TBEV.


Asunto(s)
Ciervos , Virus de la Encefalitis Transmitidos por Garrapatas , Encefalitis Transmitida por Garrapatas , Porcinos , Animales , Humanos , Gatos , Caballos , Ovinos , Animales Domésticos , Encefalitis Transmitida por Garrapatas/epidemiología , Encefalitis Transmitida por Garrapatas/veterinaria , Estudios Seroepidemiológicos , Animales Salvajes , Sus scrofa , Cabras , Anticuerpos Antivirales , Alemania/epidemiología , Zorros
5.
Drug Test Anal ; 14(6): 1149-1154, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34997698

RESUMEN

Since rodenticides represent a substance group relevant in toxicological analyses, the aim of this work was the development of a complex multi-target screening strategy for the identification with liquid chromatography-tandem mass spectrometry. A simple protein precipitation was used as the sample preparation strategy. Further, a Luna 5 µm C18 (2) 100 Å, 150 × 2 mm analytical column was applied for the separation of relevant analytes with a Shimadzu HPLC. Signal detection was performed with a SCIEX API 5500 QTrap MS/MS system. The rodenticides investigated (α-chloralose, brodifacoum, bromadiolone, coumatetralyl, difenacoum, and warfarin) could be incorporated effectively into a multi-target screening strategy covering about 250 substances representing different groups with a limit of detection appropriate for substance identification. The strategy can easily be modified to perform semi-quantitative measurements for this substance group and could be supplemented by quantification based on standard addition.


Asunto(s)
Rodenticidas , Anticoagulantes/análisis , Cromatografía Líquida de Alta Presión/métodos , Cromatografía Liquida/métodos , Toxicología Forense , Rodenticidas/análisis , Rodenticidas/química , Espectrometría de Masas en Tándem/métodos
6.
Artículo en Inglés | MEDLINE | ID: mdl-34638155

RESUMEN

A 9-year-old female, neutered European shorthair cat was presented with acute vomiting, obvious jaundice and painful enlargement of the abdomen. Icteric skin and mucous membranes in addition to severe bilirubinaemia (mainly direct bilirubin) and a large increase in liver enzyme activities were the main findings at the initial examination. Radio- and ultrasonographic evaluation revealed a massive fluid-filled structure caudal to the liver displacing abdominal organs, in particular the stomach. As this structure with a diameter of 8-10 cm occupied considerable space in the cranioventral abdomen, a detailed ultrasonographic examination of the liver and the gallbladder, and determination of the structure's association with a particular abdominal organ was initially impossible. Via ultrasound-assisted puncture under general anaesthesia 300 ml of an almost clear fluid could be aspirated. Cytological examination revealed a cyst content-like fluid with cell detritus.Further ultrasonographic and computed tomographic diagnostics followed by abdominal laparotomy finally enabled diagnosis of a cystic dilatation of the entire common bile duct and accumulation of white bile. Histopathological examination after euthanasia (requested by the owner) identified lymphoplasmacytic cholangitis and necrosis of the duodenal papilla. The massive dilatation of the common bile duct complicated its definite diagnosis by diagnostic imaging methods. It was most likely caused by a longer-standing obstruction of the bile flow by lymphoplasmacytic cholangitis with necrosis and granulation tissue formation in the area of the duodenal papilla. An interesting but initially misleading feature was the presence of white bile. The etiology of this extremely rare condition remains obscure but in the described case a manifestation of impaired hepatocyte function secondary to biliary stasis is suspected to be the cause.


Asunto(s)
Enfermedades de los Gatos , Colangitis , Abdomen , Animales , Enfermedades de los Gatos/diagnóstico por imagen , Gatos , Colangitis/veterinaria , Femenino , Tomografía Computarizada por Rayos X , Ultrasonografía/veterinaria
7.
Artículo en Alemán | MEDLINE | ID: mdl-34670314

RESUMEN

A 4-year-old, neutered male Husky-mix dog weighing 29.4 kg that reportedly ingested a mushroom most likely of the genus Amanita one day prior to presentation exhibited signs of diarrhea, vomitus, inappetence and progressively worsening lethargy. Clinical chemistry revealed hypoglycemia, hyperbilirubinemia, decreased prothrombin and thromboplastin time, as well as increased liver enzyme activities. Despite hospitalization and supportive therapy over a period of 3 days the dog's general condition worsened leading to euthanasia. The pathomorphological findings were characterized by hemorrhage in several organs, hemorrhagic ingesta, icterus, and marked hepatic cellular necrosis.


Asunto(s)
Enfermedades de los Perros , Fallo Hepático Agudo , Intoxicación por Setas , Amanita , Animales , Diarrea/veterinaria , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/etiología , Perros , Fallo Hepático Agudo/diagnóstico , Fallo Hepático Agudo/etiología , Fallo Hepático Agudo/terapia , Fallo Hepático Agudo/veterinaria , Masculino , Intoxicación por Setas/complicaciones , Intoxicación por Setas/diagnóstico , Intoxicación por Setas/terapia , Intoxicación por Setas/veterinaria
8.
Genes (Basel) ; 12(7)2021 07 13.
Artículo en Inglés | MEDLINE | ID: mdl-34356081

RESUMEN

Congenital fibrinogen disorders are very rare in dogs. Cases of afibrinogenemia have been reported in Bernese Mountain, Bichon Frise, Cocker Spaniel, Collie, Lhasa Apso, Viszla, and St. Bernard dogs. In the present study, we examined four miniature wire-haired Dachshunds with afibrinogenemia and ascertained their pedigree. Homozygosity mapping and a genome-wide association study identified a candidate genomic region at 50,188,932-64,187,680 bp on CFA15 harboring FGB (fibrinogen beta chain), FGA (fibrinogen alpha chain), and FGG (fibrinogen gamma-B chain). Sanger sequencing of all three fibrinogen genes in two cases and validation of the FGA-associated mutation (FGA:g.6296delT, NC_006597.3:g.52240694delA, rs1152388481) in pedigree members showed a perfect co-segregation with afibrinogenemia-affected phenotypes, obligate carriers, and healthy animals. In addition, the rs1152388481 variant was validated in 393 Dachshunds and samples from 33 other dog breeds. The rs1152388481 variant is predicted to modify the protein sequence of both FGA transcripts (FGA201:p.Ile486Met and FGA-202:p.Ile555Met) leading to proteins truncated by 306 amino acids. The present data provide evidence for a novel FGA truncating frameshift mutation that is very likely to explain the cases of severe bleeding due to afibrinogenemia in a Dachshund family. This mutation has already been spread in Dachshunds through carriers before cases were ascertained. Genetic testing allows selective breeding to prevent afibrinogenemia-affected puppies in the future.


Asunto(s)
Afibrinogenemia/veterinaria , Enfermedades de los Perros/patología , Fibrinógeno/genética , Mutación del Sistema de Lectura , Afibrinogenemia/genética , Afibrinogenemia/patología , Animales , Enfermedades de los Perros/genética , Perros , Femenino , Estudio de Asociación del Genoma Completo , Masculino , Linaje
9.
Artículo en Alemán | MEDLINE | ID: mdl-34157761

RESUMEN

Hypothyroidism is one of the most common endocrinopathies in dogs. In rare cases, it may be associated with further endocrinopathies. The most common combination is the con-currence of hypothyroidism and hypoadrenocorticism. The diagnosis of hypothyroidism is based on the measurement of thyroid hormones (T4/fT4) and thyroid stimulating hormone (TSH). As thyroid hormone concentrations in the blood are influenced by various factors (e. g. systemic diseases or drugs), test results must be interpreted in conjunction with complaints demonstrated by the patient. In cases when diagnosis is not definite, stimulating tests or diagnostic imaging techniques (ultrasound, scintigraphy) are advisable. Dogs with hypothyroidism should be diagnosed and treated with thyroid hormones. When addiditional clinical signs are not consistent with hypothyroidism, co-existing additional endocrinopathies need to be considered. Furthermore, when treatment fails to result in the expected clinical response, the diagnosis of hypothyroidism must be subject to critical re-evaluation. This article provides an overview of the current diagnostic and treatment methods in canine hypothyroidism.


Asunto(s)
Enfermedades de los Perros , Hipotiroidismo , Animales , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/terapia , Perros , Hipotiroidismo/diagnóstico , Hipotiroidismo/veterinaria , Cintigrafía , Tirotropina , Tiroxina
10.
Res Vet Sci ; 135: 253-259, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33229057

RESUMEN

The aim of this study was to assess the "FreeStyle Libre" flash glucose monitoring system regarding its measurement accuracy and tolerability in cats. Results from 66 sensors applied to 34 predominantly diabetic cats are included. The behaviour during the attachment, wearing, and removal of the sensor and the skin site of attachment were assessed. Blood samples were regularly collected for comparative measurements (hexokinase method). Minimal signs of discomfort were noted, although the sensor was additionally fixed using individual skin stitches. Sensors, which stopped working in situ (70% [46/66]), had a median functional life of 8.3 (1.6-14) days. Skin reactions on the adhesive surface occurred after removal of 39% (23) of 59 sensors with assessable skin reaction (mild erythema: n = 21; superficial dermatitis: n = 2). Due to the upper limit of the measurement range of 27.8 mmol/l (500 mg/dl), the reading device displayed "Hi" in 62% (17/34) of cats repeatedly and/or for periods >1 h. Results were highly correlated with those of the reference method (rS = 0.90, n = 359). 67.7% (243/359) of the "FreeStyle Libre" measurement values had a maximum deviation of 15% from reference measurements and 99.4% (357/359) were within the zones A and B of Parkes Consensus error grid analysis. In conclusion, the device proved to be practicable, less stressful for the animals and generated in general acceptable results. Although the upper limit of the measurement range is a limiting factor, the device promises to significantly facilitate the management of diabetic cats.


Asunto(s)
Automonitorización de la Glucosa Sanguínea/veterinaria , Glucemia/análisis , Enfermedades de los Gatos/sangre , Diabetes Mellitus/veterinaria , Adhesivos , Animales , Automonitorización de la Glucosa Sanguínea/instrumentación , Gatos , Diabetes Mellitus/sangre , Femenino , Masculino
11.
J Proteomics ; 223: 103817, 2020 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-32416315

RESUMEN

Canine pyometra is a common inflammatory disease of uterus in sexually mature bitches caused by secondary bacterial infection, leading to change in plasma proteins associated with the innate immune system. Proteomic investigation is increasingly being applied to canine diseases in order to identify and quantify significant changes in the plasma proteome. The aim of the study was to assess and quantify changes in plasma proteome profiles of healthy dogs and pyometra affected bitches using a TMT-based high-resolution quantitative proteomic approach. As a result, 22 proteins were significantly down-regulated including transthyretin, antithrombin, retinol-binding protein, vitamin D binding protein, paraoxonase 1, and kallikrein, while 16 were significantly up-regulated including haptoglobin light chain, alpha-1-acid glycoprotein, C-reactive protein precursor, and lipopolysaccharide-binding protein in dogs with pyometra. Pathway analysis indicated that acute inflammatory response, regulation of body fluid levels, protein activation cascade, the humoral immune response, and phagocytosis were affected in pyometra. Validation of biological relevance of the proteomic study was evident with significant increases in the concentrations of haptoglobin, C-reactive protein, alpha-1-acid glycoprotein, and ceruloplasmin by immunoassay. Pyometra in bitches was shown to stimulate an increase in host defence system proteins in response to inflammatory disease including the acute phase proteins. SIGNIFICANCE: The label-based high-resolution quantitative proteomics analysis and bioinformatic approach used in this study provide insight into the complex pathophysiology of inflammation associated with pyometra revealing proteins with biomarker potential. Early diagnosis and therapeutic intervention may prevent severe complications associated with advancing sepsis in dogs with pyometra. Therefore the identification of diagnostic biomarkers that, after clinical validation may be used in veterinary practice and protein relevant to pathways responding to disease are important findings of the study. Data are available via ProteomeXchange with identifier PXD015951.


Asunto(s)
Enfermedades de los Perros , Piómetra , Reacción de Fase Aguda , Animales , Proteína C-Reactiva , Perros , Femenino , Humanos , Proteoma , Proteómica , Piómetra/veterinaria
12.
Res Vet Sci ; 130: 26-32, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32114247

RESUMEN

Aims of the present study were to define reference intervals for viscoelastic analyses of canine haemostasis using the ROTEM® delta analyser, and as a secondary aspect to determine the precision (repeatability) of this method. Blood samples from 125 clinically healthy dogs were included. Measurements were performed with commercially available activating reagents (ex-tem, in-tem and kaolin solution) as well as without activation. Additional fourfold measurements were done in 3 of the normal blood samples and in 3 samples with haemostatic alterations to evaluate the precision of the method. Coefficients of variation (CVs) for most of the ROTEM variables were < 10%. Clot formation time and maximum clot elasticity showed a wide inter-individual variation in comparison with alpha angle and maximum clot firmness. A multivariate analysis on various ROTEM parameters revealed particularly a significant influence of neuter status and a significant interrelationship between the factors sex and neuter status for measurements with different activating reagents. These results reflected the fact that significant differences occurred only between intact and neutered females, but not in males. No or only occasionally significant differences were found between groups of sex, age, and size. In conclusion, CVs demonstrated that the method delivers repeatable results in canine citrated whole blood. Established reference intervals should deliver valuable orientation for the evaluation of viscoelastic properties of clotting whole blood in dogs using the ROTEM delta analyser. Neuter status in females appeared to be the most relevant influencing factor and should be considered for the interpretation of ROTEM delta test results.


Asunto(s)
Coagulación Sanguínea , Tromboelastografía/veterinaria , Animales , Perros , Femenino , Masculino , Valores de Referencia , Factores Sexuales
13.
Res Vet Sci ; 129: 117-119, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31954882

RESUMEN

It was the aim of the study to assess the impact of a minor surgical intervention under general anaesthesia on results of a low-dose dexamethasone suppression test (LDDST) in dogs. Five clinically healthy dogs underwent a LDDST (standard protocol) prior and 1, 4, 7, 14 and 28 days after a dental restoration under general anaesthesia. All LDDSTs revealed negative results. On all test days after intervention some dogs had basal cortisol concentrations below the reference range. Accordingly, plasma cortisol concentrations 4 and 8 h after dexamethasone injection were noticeably lower than before surgery and often even below the lower detection limit of 2.0 ng/ml. The study results may indicate a suppressive effect of a minor surgery under general anaesthesia on cortisol measurements during LDDSTs. It may be speculated that this could possibly lead to false negative test results in the postsurgical period, although transfer of these results to clinical cases is subject to limitations.


Asunto(s)
Hiperfunción de las Glándulas Suprarrenales/veterinaria , Anestesia General/veterinaria , Reparación de Restauración Dental/veterinaria , Dexametasona/administración & dosificación , Enfermedades de los Perros/diagnóstico , Hiperfunción de las Glándulas Suprarrenales/sangre , Hiperfunción de las Glándulas Suprarrenales/diagnóstico , Animales , Enfermedades de los Perros/sangre , Perros , Relación Dosis-Respuesta a Droga , Femenino , Glucocorticoides/administración & dosificación , Hidrocortisona/sangre , Masculino
14.
Res Vet Sci ; 127: 113-121, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31693942

RESUMEN

The aim of this study was to establish a thrombin generation assay (calibrated automated thrombogram, CAT) in cats by determining the precision (repeatability), reference values, and the sensitivity to anticoagulant treatment with the factor Xa inhibitor apixaban. The CAT method was performed on citrated plasma with different commercial tissue factor (TF) reagents (PPP Reagent 1 pM [LOW], PPP Reagent 5 pM, PPP Reagent 20 pM [HIGH]) according to the manufacturers` test instruction. Measurements in triplicate were performed in platelet poor plasma (PPP) of 58 healthy cats and in 6 cats at different times following the oral administration of 2.5 mg apixaban. The median CVs in healthy cats usually were < 10% with the exception of thrombin peak height measured using PPP Reagent 1 pM (14.6%). Reference values of all parameters showed marked inter-individual variability and depended largely on the TF concentration of the used activating reagent. Thrombin generation was significantly influenced by apixaban and reacted more sensitively than other tests of haemostasis including the prothrombin time, aPTT, and rotational elastometry. In conclusion, thrombin generation measured by the CAT method using commercially available reagents seems suitable for the examination of feline PPP and may be a valuable method to establish effective anticoagulant therapies for the feline patient and monitoring of such therapies in cats.


Asunto(s)
Pruebas de Coagulación Sanguínea/veterinaria , Inhibidores del Factor Xa/farmacología , Pirazoles/farmacología , Piridonas/farmacología , Trombina/análisis , Tromboplastina/análisis , Animales , Pruebas de Coagulación Sanguínea/métodos , Gatos , Valores de Referencia
15.
Haematologica ; 104(11): 2307-2313, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-30846504

RESUMEN

Hemophilia B is a classical monogenic, X-chromosomal, recessively transmitted bleeding disorder caused by genetic variants within the coagulation factor IX gene (F9). Although hemophilia B has been described in dogs, it has not yet been reported in the Hovawart breed. Here we describe the identification of a Hovawart family transmitting typical signs of an X-linked bleeding disorder. Five males were reported to suffer from recurrent hemorrhagic episodes. A blood sample from one of these males with only 2% of the normal concentration of plasma factor IX together with samples from seven relatives were provided. Next-generation sequencing of the mother and grandmother revealed a single nucleotide deletion in the F9 promoter. Genotyping of the deletion in 1,298 dog specimens including 720 Hovawarts revealed that the mutant allele was only present in the aforementioned Hovawart family. The deletion is located 73 bp upstream of the F9 start codon in the conserved overlapping DNA binding sites of hepatocyte nuclear factor 4α (HNF-4α) and androgen receptor (AR). The deletion only abolished binding of HNF-4α, while AR binding was unaffected as demonstrated by electrophoretic mobility shift assay using human HNF-4α and AR with double-stranded DNA probes encompassing the mutant promoter region. Luciferase reporter assays using wildtype and mutated promoter fragment constructs transfected into Hep G2 cells showed a significant reduction in expression from the mutant promoter. The data provide evidence that the deletion in the Hovawart family caused a rare type of hemophilia B resembling human hemophilia B Leyden.


Asunto(s)
Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/genética , Factor IX/genética , Hemofilia B/veterinaria , Mutación Puntual , Regiones Promotoras Genéticas , Eliminación de Secuencia , Animales , Sitios de Unión , Perros , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Haplotipos , Linaje , Fenotipo , Unión Proteica , Factores de Transcripción/metabolismo
16.
Artículo en Inglés | MEDLINE | ID: mdl-30808038

RESUMEN

A 4-year-old, neutered male European shorthair was presented for evaluation of right hind limb lameness. Radiographs revealed bilateral femoral capital physeal fractures, widened vertebral growth plates and constipation. Physical findings included lethargy, mental dullness, mild hypothermia, retarded growth, pharyngeal stridor, moderate muscle atrophy of pelvic limbs, hair coat abnormalities, and lack of defecation and urination. A thyroid panel revealed thyroid hormone values below detection limits and high thyroid stimulation hormone values. A presumptive diagnosis of congenital primary hypothyroidism was made, however also an early onset acquired primary hypothyroidism could not be ruled out. Results of the insulin-like growth factor (IGF-1) and the parathyroid hormone as well as an adrenocorticotropic hormone stimulating test were normal. A bilateral femoral head and neck excision was performed. Levothyroxine supplementation was started at a dosage of 50 µg (11 µg/kg) BID and later adjusted to 100 µg (22 µg/kg) BID based on total thyroxine concentrations. The tomcat showed full clinical recovery and normal clinical behaviour. The case shows that primary hypothyroidism may be considered in cats presented with femoral capital physeal fractures.


Asunto(s)
Enfermedades de los Gatos/diagnóstico , Fracturas del Fémur/veterinaria , Hipotiroidismo/veterinaria , Animales , Enfermedades de los Gatos/tratamiento farmacológico , Gatos , Fracturas del Fémur/diagnóstico por imagen , Fracturas del Fémur/etiología , Hipotiroidismo/complicaciones , Hipotiroidismo/diagnóstico , Hipotiroidismo/tratamiento farmacológico , Cojera Animal/diagnóstico por imagen , Cojera Animal/etiología , Masculino , Tiroxina/uso terapéutico
17.
Mol Psychiatry ; 24(10): 1489-1501, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-29426955

RESUMEN

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.


Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato/inmunología , Trastornos Mentales/inmunología , Receptores de N-Metil-D-Aspartato/inmunología , Adulto , Animales , Autoanticuerpos/inmunología , Barrera Hematoencefálica , Encéfalo/inmunología , Gatos , Perros , Femenino , Humanos , Inmunoglobulina G/genética , Inmunoglobulina G/inmunología , Masculino , Ratones , Proteínas del Tejido Nervioso/inmunología , Proteínas del Tejido Nervioso/metabolismo , Neuronas/inmunología , Primates , Ratas , Receptores de N-Metil-D-Aspartato/metabolismo , Estudios Seroepidemiológicos
18.
Vet Immunol Immunopathol ; 206: 16-24, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30502908

RESUMEN

The intestinal mucosa is in contact with abundant luminal antigens and coordinates immune responses to differentiate commensals from pathogens. Intestinal epithelial cells (IECs) not only represent a physical barrier but also an immunologically important cell type that recognizes microbe-associated molecular patterns via Toll-like receptors (TLR). The importance of TLR expression has been elucidated for intestinal disorders in humans, mice and dogs. However, as knowledge about canine intestinal TLRs is mainly limited to the transcriptional level, the present study analyzed the protein expression of TLR2, TLR3, TLR4, TLR5 and TLR9 by primary canine IECs in the steady state and after stimulation with TLR ligands. This exhibited TLR5 and TLR9 to be predominantly expressed in canine IECs. TLR stimulation did not result in changes of the TLR expression pattern. Further studies are needed to elucidate whether this implicates hyporesponsiveness of canine IECs towards TLR stimulation under steady state conditions.


Asunto(s)
Colon/metabolismo , Perros/metabolismo , Mucosa Intestinal/metabolismo , Yeyuno/metabolismo , Receptor Toll-Like 5/metabolismo , Receptor Toll-Like 9/metabolismo , Animales , Células Cultivadas , Colon/citología , Perfilación de la Expresión Génica , Yeyuno/citología , Ligandos , Receptor Toll-Like 5/genética , Receptor Toll-Like 9/genética , Receptores Toll-Like/metabolismo
20.
Artículo en Alemán | MEDLINE | ID: mdl-29727898

RESUMEN

Veterinarians are regularly faced with the diagnosis and therapy of immune-mediated diseases. More frequently occurring immune-mediated diseases are immune-mediated hemolytic anemia, immunemediated thrombocytopenia and polyarthritis. Glucocorticoids are commonly used as first-line treatment because of their availability, efficacy and rapid action. Nevertheless, some patients do not respond to glucocorticoid therapy alone. Others require a rapid dose reduction because of severe side effects from glucocorticoid treatment. These patients benefit from adjuvant therapies. Ciclosporin preparations are licensed for use in veterinary medicine. The use of azathioprine, mycophenolate mofetil and human immunoglobulin therapy has also been documented. This article describes the mode of action of certain immunosuppressive agents and their use in selected diseases from recent literature.


Asunto(s)
Enfermedades de los Gatos/tratamiento farmacológico , Enfermedades de los Perros/tratamiento farmacológico , Enfermedades del Sistema Inmune/veterinaria , Inmunosupresores/uso terapéutico , Anemia Hemolítica Autoinmune/tratamiento farmacológico , Anemia Hemolítica Autoinmune/inmunología , Anemia Hemolítica Autoinmune/veterinaria , Animales , Enfermedades de los Gatos/inmunología , Gatos , Enfermedades de los Perros/inmunología , Perros , Enfermedades del Sistema Inmune/tratamiento farmacológico , Trombocitopenia/tratamiento farmacológico , Trombocitopenia/inmunología , Trombocitopenia/veterinaria
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