Tierärztl. Hochsch., Diss., 2004--Hannover.

Six different isoforms of Type IV collagen (colIVα1-6) have been identified. The individual isoforms of colIV are termed alpha chains and are translated from six different COLIV genes (COLIVA1-A6). Collagen Type IV gene products compose the structural framework of basement membranes. The glomerular basement membrane (GBM) is a specialized basement membrane involved in the ultrafiltration processes of the kidney. The colIVα1-α5 chains are expressed in the human GBM while the colIV α1-α6 chains are expressed in the canine GBM. Many inherited diseases of the kidney have been reported and mutations in genes regulating kidney function have been identified. Alport syndrome (AS) is the most common form of human hereditary nephritis (HN). AS is defined as an inherited progressive kidney disorder associated with sensoneural deafness and is characterized by extensive thickening and multilamminar splitting of the GBM when examined by electron microscopy. AS has both X-linked (XLAS) and autosomal (ARAS) modes of inheritance. Mutations in the COLIVA5 gene are responsible for XLAS. A form of HN with characteristic splitting of the GBM with X-linked inheritance has been described in Samoyed dogs. A specific mutation in the COLIVA5 gene has been identified in Samoyed dogs affected with HN. Mutations in the COLIVA3 and COLIVA4 genes are responsible for ARAS. A form of HN has been identified in English cocker spaniel dogs (ECS) that has been described as autosomal in inheritance and includes GBM abnormalities including extensive lammination characteristic of ARAS. Both ARAS and ECS-HN show loss of the colIVA3 and colIVA4 chains in the GBM when examined with monoclonal anitibodies. ECS-HN has been hypothesized to have the same molecular basis of disease as ARAS. As such, we have isolated and characterized canine COLIVA3 and COLIVA4 sequences from normal dogs and ECS dogs affected with HN and compared the coding regions of these candidate genes.

Six different isoforms of Type IV collagen (colIVα1-6) have been identified. The individual isoforms of colIV are termed alpha chains and are translated from six different COLIV genes (COLIVA1-A6). Collagen Type IV gene products compose the structural framework of basement membranes. The glomerular basement membrane (GBM) is a specialized basement membrane involved in the ultrafiltration processes of the kidney. The colIVα1-α5 chains are expressed in the human GBM while the colIV α1-α6 chains are expressed in the canine GBM. Many inherited diseases of the kidney have been reported and mutations in genes regulating kidney function have been identified. Alport syndrome (AS) is the most common form of human hereditary nephritis (HN). AS is defined as an inherited progressive kidney disorder associated with sensoneural deafness and is characterized by extensive thickening and multilamminar splitting of the GBM when examined by electron microscopy. AS has both X-linked (XLAS) and autosomal (ARAS) modes of inheritance. Mutations in the COLIVA5 gene are responsible for XLAS. A form of HN with characteristic splitting of the GBM with X-linked inheritance has been described in Samoyed dogs. A specific mutation in the COLIVA5 gene has been identified in Samoyed dogs affected with HN. Mutations in the COLIVA3 and COLIVA4 genes are responsible for ARAS. A form of HN has been identified in English cocker spaniel dogs (ECS) that has been described as autosomal in inheritance and includes GBM abnormalities including extensive lammination characteristic of ARAS. Both ARAS and ECS-HN show loss of the colIVA3 and colIVA4 chains in the GBM when examined with monoclonal anitibodies. ECS-HN has been hypothesized to have the same molecular basis of disease as ARAS. As such, we have isolated and characterized canine COLIVA3 and COLIVA4 sequences from normal dogs and ECS dogs affected with HN and compared the coding regions of these candidate genes.

Ecodopplercardiografia é o estudo do coração e grandes vasos por meio da ultra-sonografia, no qual são obtidas informações importantes de caráter qualitativo e quantitativo sobre o sistema cardiovascular. O objetivo deste trabalho foi estabelecer os parâmetros ecodopplercardiográficos de cães da raça Cocker Spaniel Inglês e correlacioná-los entre si e com medidas biométricas corpóreas. No total, foram utilizados 22 cães, da raça Cocker Spaniel Inglês, 7 machos e 15 fêmeas, com idades entre 1 e 7 anos (3,47 ± 1,7) e peso corpóreo entre 11,2 e 18 Kg (13,25 ± 1,68), sem alterações cardiovasculares (previamente verificadas através da anamnese, exame físico, radiografia do tórax, eletrocardiografia e mensuração da pressão arterial), correlacioná-los entre si e com medidas biométricas corpóreas. Após a obtenção dos valores de referência dos parâmetros em modo M e Doppler observou-se que as medidas biométricas corpóreas correlacionaram-se entre si, mas não se correlacionaram com os parâmetros ecodopplercardiográficos, à exceção do comprimento do animal. Não houve, também, influência do sexo sobre estes parâmetros. / Ecocardiography is the study of the heart and great vessels through ultrasounds that allows qualitative and quantitative cardiovascular evaluation. The objective of this work was to stablish Doppler echocardiographic parameters and to correlate it with themselves and with body size parameters of English Cocker Spaniel dogs. A total of 22 English Cocker Spaniels dogs, 7 males and 15 females, aged 1 to 7 (3,47 ± 1,7), weighted 11,2 to 18 Kg (13,25 ± 1,68), without cardiovascular alterations (previously verified by means of anamnese, physical exams, radiography, electrocardiography and arterial blood pressure measurement) were used. After Doppler echocardiographic examination and body size measurements, it was possible to obtain M mode and Doppler reference values. Body size measures correlated among themselves but there has not been noted significant correlation between Doppler echocardiographic parameters and body size, except body lenght. Sex did not influence any Doppler echocardiographic variables.

Ecodopplercardiografia é o estudo do coração e grandes vasos por meio da ultra-sonografia, no qual são obtidas informações importantes de caráter qualitativo e quantitativo sobre o sistema cardiovascular. O objetivo deste trabalho foi estabelecer os parâmetros ecodopplercardiográficos de cães da raça Cocker Spaniel Inglês e correlacioná-los entre si e com medidas biométricas corpóreas. No total, foram utilizados 22 cães, da raça Cocker Spaniel Inglês, 7 machos e 15 fêmeas, com idades entre 1 e 7 anos (3,47 ± 1,7) e peso corpóreo entre 11,2 e 18 Kg (13,25 ± 1,68), sem alterações cardiovasculares (previamente verificadas através da anamnese, exame físico, radiografia do tórax, eletrocardiografia e mensuração da pressão arterial), correlacioná-los entre si e com medidas biométricas corpóreas. Após a obtenção dos valores de referência dos parâmetros em modo M e Doppler observou-se que as medidas biométricas corpóreas correlacionaram-se entre si, mas não se correlacionaram com os parâmetros ecodopplercardiográficos, à exceção do comprimento do animal. Não houve, também, influência do sexo sobre estes parâmetros. / Ecocardiography is the study of the heart and great vessels through ultrasounds that allows qualitative and quantitative cardiovascular evaluation. The objective of this work was to stablish Doppler echocardiographic parameters and to correlate it with themselves and with body size parameters of English Cocker Spaniel dogs. A total of 22 English Cocker Spaniels dogs, 7 males and 15 females, aged 1 to 7 (3,47 ± 1,7), weighted 11,2 to 18 Kg (13,25 ± 1,68), without cardiovascular alterations (previously verified by means of anamnese, physical exams, radiography, electrocardiography and arterial blood pressure measurement) were used. After Doppler echocardiographic examination and body size measurements, it was possible to obtain M mode and Doppler reference values. Body size measures correlated among themselves but there has not been noted significant correlation between Doppler echocardiographic parameters and body size, except body lenght. Sex did not influence any Doppler echocardiographic variables.

Retinal dysplasia has been documented in many breeds of dogs. It has recently been hypothesized that Miniature Schnauzer dogs affected with retinal dysplasia and associated persistent hyperplastic primary vitreous have a decreased amount of Tfam and several mtDNA transcripts in the retina and RPE. Affected dogs were also hypothesized to have a decrease in leukocyte mtDNA compared to normal dogs. Additionally, using electron microscopy, these dogs were hypothesized to having decreased mitochondrial numbers and size with altered morphology in multiple tissues, including neutrophils. Due to these recent discoveries in this breed it has been proposed that retinal dysplasia could be the result of an altered energy supply to the retina and RPE. The objective of this study was to further investigate the pathogenesis of retinal dysplasia in the Miniature Schnauzer and English Springer Spaniel dog.<p> The hypothesis of an altered Tfam gene sequence in affected Miniature Schnauzer dogs leading to a decreased amount of Tfam transcript in the retina and RPE was tested by amplifying, cloning and sequencing the coding, 5 and 3non-coding regions, and intron 1 of the Tfam gene from affected and normal Miniature Schnauzer dogs. Using transmission electron microscopy, affected and normal lymphocyte mitochondria were also objectively measured and quantified in this breed along with mitochondrial morphology assessment. In the English Springer Spaniel dog, the hypothesis of a decreased amount of leukocyte mtDNA in affected dogs was tested using real-time PCR. In addition, using transmission electron microscopy, affected and normal lymphocyte mitochondria were objectively measured and quantified in this breed with mitochondrial morphology assessment.<p> Sequencing of the particular regions of the Miniature Schnauzer Tfam gene revealed no significant nucleotide changes between affected and normal dogs. Evaluation of lymphocyte mitochondrial size, number and morphology also revealed no significant differences between the two groups. In the English Springer Spaniel dog a relative decrease in leukocyte mtDNA did not exist in dogs affected with retinal dysplasia. Furthermore, evaluation of affected English Springer Spaniel dog lymphocyte mitochondria revealed no significant differences in mitochondrial number, surface area or morphology when compared to normal English Springer Spaniel dogs.<p> To conclude, we failed to demonstrate a mutation in the areas of the Tfam gene sequenced in Miniature Schnauzers affected with retinal dysplasia and associated persistent hyperplastic primary vitreous. In contrast to previous findings of decreased leukocyte mtDNA in the affected Miniature Schnauzer dog, no evidence was found to support a relative decrease in leukocyte mtDNA in English Springer Spaniel dogs affected with retinal dysplasia. Furthermore, the hypothesis of altered mitochondrial size, number and morphology in affected dogs is not supported by this study. Further evaluation of mitochondria, mtDNA and mitochondrial gene expression within age-matched retina and RPE of Miniature Schnauzer and English Springer Spaniel dogs is necessary to determine if mitochondria and altered energy supply play a role in the pathogenesis of retinal dysplasia in these breeds.

Retinal dysplasia has been documented in many breeds of dogs. It has recently been hypothesized that Miniature Schnauzer dogs affected with retinal dysplasia and associated persistent hyperplastic primary vitreous have a decreased amount of Tfam and several mtDNA transcripts in the retina and RPE. Affected dogs were also hypothesized to have a decrease in leukocyte mtDNA compared to normal dogs. Additionally, using electron microscopy, these dogs were hypothesized to having decreased mitochondrial numbers and size with altered morphology in multiple tissues, including neutrophils. Due to these recent discoveries in this breed it has been proposed that retinal dysplasia could be the result of an altered energy supply to the retina and RPE. The objective of this study was to further investigate the pathogenesis of retinal dysplasia in the Miniature Schnauzer and English Springer Spaniel dog.<p> The hypothesis of an altered Tfam gene sequence in affected Miniature Schnauzer dogs leading to a decreased amount of Tfam transcript in the retina and RPE was tested by amplifying, cloning and sequencing the coding, 5 and 3non-coding regions, and intron 1 of the Tfam gene from affected and normal Miniature Schnauzer dogs. Using transmission electron microscopy, affected and normal lymphocyte mitochondria were also objectively measured and quantified in this breed along with mitochondrial morphology assessment. In the English Springer Spaniel dog, the hypothesis of a decreased amount of leukocyte mtDNA in affected dogs was tested using real-time PCR. In addition, using transmission electron microscopy, affected and normal lymphocyte mitochondria were objectively measured and quantified in this breed with mitochondrial morphology assessment.<p> Sequencing of the particular regions of the Miniature Schnauzer Tfam gene revealed no significant nucleotide changes between affected and normal dogs. Evaluation of lymphocyte mitochondrial size, number and morphology also revealed no significant differences between the two groups. In the English Springer Spaniel dog a relative decrease in leukocyte mtDNA did not exist in dogs affected with retinal dysplasia. Furthermore, evaluation of affected English Springer Spaniel dog lymphocyte mitochondria revealed no significant differences in mitochondrial number, surface area or morphology when compared to normal English Springer Spaniel dogs.<p> To conclude, we failed to demonstrate a mutation in the areas of the Tfam gene sequenced in Miniature Schnauzers affected with retinal dysplasia and associated persistent hyperplastic primary vitreous. In contrast to previous findings of decreased leukocyte mtDNA in the affected Miniature Schnauzer dog, no evidence was found to support a relative decrease in leukocyte mtDNA in English Springer Spaniel dogs affected with retinal dysplasia. Furthermore, the hypothesis of altered mitochondrial size, number and morphology in affected dogs is not supported by this study. Further evaluation of mitochondria, mtDNA and mitochondrial gene expression within age-matched retina and RPE of Miniature Schnauzer and English Springer Spaniel dogs is necessary to determine if mitochondria and altered energy supply play a role in the pathogenesis of retinal dysplasia in these breeds.

A cardiomiopatia dilatada (CMD) é uma das cardiopatias mais frequentes em cães, sendo a redução da contratilidade miocárdica uma de suas principais características. Dentre as raças predispostas, destaca-se o Cocker Spaniel Inglês. O diagnóstico baseia-se nos achados da ecocardiografia convencional. Todavia, as recentes técnicas ecocardiográficas de Doppler tecidual, como a determinação das velocidades miocárdicas, o registro da deformação (Df) e da taxa de deformação (TDf) miocárdicas, podem identificar padrões característicos de disfunção, antes mesmo do surgimento de anormalidades na ecocardiografia convencional. Com o objetivo de investigar os padrões de disfunção miocárdica ventricular, por meio das técnicas retro-mencionadas, foram incluídos 32 cães da raça Cocker Spaniel Inglês, sendo 16 com diagnóstico de cardiomiopatia dilatada e 16 considerados hígidos, para fins de grupo controle. O estudo Doppler tecidual possibilitou a identificação de disfunção miocárdica ventricular sistólica e diastólica, em ambos os ventrículos dos cães com CMD. No ventrículo esquerdo encontrou-se disfunção miocárdica longitudinal e transversal, caracterizada por menor velocidade miocárdica sistólica, retardo eletromecânico, contrações pós-sistólicas longitudinais, redução na Df e TDf sistólicas, além de distúrbio no relaxamento miocárdico. Por sua vez, diminuição da Df miocárdica sistólica longitudinal e retardo no relaxamento miocárdico caracterizaram a disfunção ventricular direita. O presente estudo identificou, de maneira inédita, padrões de disfunção miocárdica, obtidos por meio de Doppler tecidual, em uma população de cães da raça Cocker Spaniel Inglês com CMD. / Dilated cardiomyopathy (DCM) is one of the most common heart diseases in dogs and its main feature is reduced contractility. English Cocker Spaniel is among predisposed breeds. Diagnosis is based on conventional echocardiographic findings. However, recent tissue Doppler echocardiographic techniques, such as myocardial velocities determination and recordings of myocardial strain (St) and strain rate (SR), can identify characteristic patterns of dysfunction, even before the onset of abnormalities in conventional echocardiography. In order to investigate the patterns of ventricular myocardial dysfunction by means of retro-mentioned techniques, 32 English Cocker Spaniels were studied, being 16 diagnosed with DCM and 16 considered healthy for control purpose. Tissue Doppler study allowed identification of systolic and diastolic ventricular myocardial dysfunction in both ventricles of dogs with DCM. Left ventricular findings included longitudinal and transversal myocardial dysfunction, characterized by lower systolic myocardial velocity, electromechanical delay, longitudinal post systolic contractions, reduced systolic St and SR, and myocardial relaxation disturbance. In turn, reduced longitudinal systolic myocardial St and delayed myocardial relaxation characterized right ventricular dysfunction. The present study identified, in an unprecedented way, patterns of dysfunction, obtained by tissue Doppler, in a dog population of English Cocker Spaniels with DCM.

A cardiomiopatia dilatada (CMD) é uma das cardiopatias mais frequentes em cães, sendo a redução da contratilidade miocárdica uma de suas principais características. Dentre as raças predispostas, destaca-se o Cocker Spaniel Inglês. O diagnóstico baseia-se nos achados da ecocardiografia convencional. Todavia, as recentes técnicas ecocardiográficas de Doppler tecidual, como a determinação das velocidades miocárdicas, o registro da deformação (Df) e da taxa de deformação (TDf) miocárdicas, podem identificar padrões característicos de disfunção, antes mesmo do surgimento de anormalidades na ecocardiografia convencional. Com o objetivo de investigar os padrões de disfunção miocárdica ventricular, por meio das técnicas retro-mencionadas, foram incluídos 32 cães da raça Cocker Spaniel Inglês, sendo 16 com diagnóstico de cardiomiopatia dilatada e 16 considerados hígidos, para fins de grupo controle. O estudo Doppler tecidual possibilitou a identificação de disfunção miocárdica ventricular sistólica e diastólica, em ambos os ventrículos dos cães com CMD. No ventrículo esquerdo encontrou-se disfunção miocárdica longitudinal e transversal, caracterizada por menor velocidade miocárdica sistólica, retardo eletromecânico, contrações pós-sistólicas longitudinais, redução na Df e TDf sistólicas, além de distúrbio no relaxamento miocárdico. Por sua vez, diminuição da Df miocárdica sistólica longitudinal e retardo no relaxamento miocárdico caracterizaram a disfunção ventricular direita. O presente estudo identificou, de maneira inédita, padrões de disfunção miocárdica, obtidos por meio de Doppler tecidual, em uma população de cães da raça Cocker Spaniel Inglês com CMD. / Dilated cardiomyopathy (DCM) is one of the most common heart diseases in dogs and its main feature is reduced contractility. English Cocker Spaniel is among predisposed breeds. Diagnosis is based on conventional echocardiographic findings. However, recent tissue Doppler echocardiographic techniques, such as myocardial velocities determination and recordings of myocardial strain (St) and strain rate (SR), can identify characteristic patterns of dysfunction, even before the onset of abnormalities in conventional echocardiography. In order to investigate the patterns of ventricular myocardial dysfunction by means of retro-mentioned techniques, 32 English Cocker Spaniels were studied, being 16 diagnosed with DCM and 16 considered healthy for control purpose. Tissue Doppler study allowed identification of systolic and diastolic ventricular myocardial dysfunction in both ventricles of dogs with DCM. Left ventricular findings included longitudinal and transversal myocardial dysfunction, characterized by lower systolic myocardial velocity, electromechanical delay, longitudinal post systolic contractions, reduced systolic St and SR, and myocardial relaxation disturbance. In turn, reduced longitudinal systolic myocardial St and delayed myocardial relaxation characterized right ventricular dysfunction. The present study identified, in an unprecedented way, patterns of dysfunction, obtained by tissue Doppler, in a dog population of English Cocker Spaniels with DCM.

O crescimento e as dimensões das estruturas oculares em cães de diversas raças têm sido objeto de estudo. Sabe-se que quanto mais longilíneo o crânio, maior o comprimento axial do bulbo ocular. O objetivo deste trabalho foi acompanhar o desenvolvimento das dimensões dos componentes oculares (comprimento axial, espessura da lente, profundidade da câmara anterior e da câmara vítrea) e relacionar as medidas com o sexo, a idade, tamanho, medidas do crânio e peso de cães da raça Cavalier King Charles Spaniel, uma raça braquicéfala. Foram realizadas 117 medidas biométricas oculares em cães variando entre 15 dias e 36 meses de idade, não sedados, sentados ou deitados em posição esternal, utilizando-se ultrassonografia modo-B com transdutor microconvexo de 8 MHz. No momento de cada medida ocular os cães foram pesados e as medidas de comprimento, altura, distâncias fronto-occipital, fronto-nasal, bizigomática e circunferência do crânio foram registradas. As estruturas oculares mostraram uma curva de rápido crescimento entre 15 dias e 4 meses de idade e uma curva suave de crescimento até os 12 meses, idade em que cessou o crescimento do cão (altura e comprimento). Os machos apresentaram medidas maiores de altura, comprimento e crânio do que fêmeas, porém não houve diferença significativa entre os parâmetros de biometria ocular de machos e fêmeas. O valor médio de comprimento axial do bulbo para cães adultos (acima de 12 meses) foi de 18,10 ± 0,48 mm, para a espessura da lente, de 7,15 ± 0,16 mm, para profundidade da câmara anterior, de 2,05 ± 0,37 mm e para a profundidade da câmara vítrea, de 8,91 ± 0,30 mm. Não houve diferença entre as medidas dos olhos direito e esquerdo. Os resultados sugerem que a curva de crescimento ocular acompanha a curva de crescimento do cão, fato semelhante ao que ocorre em diferentes espécies estudadas por outros autores. Em cães adultos, não foi observada relação entre as medidas dos componentes oculares e as medidas de altura, comprimento, peso e tamanho do crânio. Foi estabelecida uma tabela de crescimento correlacionando comprimento axial do bulbo e idade do cão com a finalidade de padronizar esses dados para a raça. / Ocular biometry and ocular growth has been studied in dogs of different breeds. It\'s already known that dogs with longer skulls have longer axial length of the eye. This study aimed to evaluate the development of ocular dimensions (axial length of the bulbus, lens thickness, anterior and vitreous chamber depth) in Cavalier King Charles Spaniels, a braquicephalic breed, and its relationship to age, gender, weight, height and lenght of the dog and dimensions of the head. Ocular dimensions were obtained from 117 measurements between 15 days and 3 years old, in standing nonsedated animals using B-mode ultrasound with an 8 MHz curvilinear probe. At the same time the dogs were weighted and height, length and head dimensions (head circumference, fronto-occipital, fronto-nasal distance and bizigomatic distances) were recorded. The ocular parameters showed a rapid growth curve from 15 days to 4 months and then a slow curve until 12 months, same age that the height and length ceased its growth. Males showed significant higher measurements of height, length and head parameters than females, but no difference in ocular biometry was found between males and females. The mean value for axial lenght for adults (over 12 months) was 18,10 ± 0,48 mm, for lens thickness was 7,15 ± 0,16 mm, for anterior chamber depth was 2,05 ± 0,37 mm and for vitreous chamber depth was 8,91 ± 0,30 mm. There was no significant difference between left and right eyes. Results suggest that eye growth curves accompanies dogs height, length, head size growth curves, what is similar to the data found in different species studied by other authors. There was no relation between eye parameters and dog\'s height, length, head size or weight in adult individuals. A table was established correlating axial length of the bulbus and age to be used as a reference for the breed.