RESUMO
In this study, we determined the expression of key signalling pathway proteins TP53, MDM2, P21, AKT, PTEN, RB1, P16, MTOR and MAPK in canine gliomas using western blotting. Protein expression was defined in three canine astrocytic glioma cell lines treated with CCNU, temozolamide or CPT-11 and was further evaluated in 22 spontaneous gliomas including high and low grade astrocytomas, high grade oligodendrogliomas and mixed oligoastrocytomas. Response to chemotherapeutic agents and cell survival were similar to that reported in human glioma cell lines. Alterations in expression of key human gliomagenesis pathway proteins were common in canine glioma tumour samples and segregated between oligodendroglial and astrocytic tumour types for some pathways. Both similarities and differences in protein expression were defined for canine gliomas compared to those reported in human tumour counterparts. The findings may inform more defined assessment of specific signalling pathways for targeted therapy of canine gliomas.
Assuntos
Neoplasias Encefálicas/veterinária , Doenças do Cão/genética , Glioma/veterinária , Transdução de Sinais/genética , Animais , Antineoplásicos , Western Blotting/veterinária , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , California , Linhagem Celular Tumoral , Doenças do Cão/patologia , Cães , Feminino , Genes Supressores de Tumor , Glioma/genética , Glioma/patologia , Masculino , PTEN Fosfo-Hidrolase/genética , Proteínas Proto-Oncogênicas c-mdm2/genética , Serina-Treonina Quinases TOR/genética , Proteína Supressora de Tumor p53/genéticaRESUMO
BACKGROUND: Previous study of the diagnostic validity of electroencephalography (EEG) to detect abnormalities in equine cerebral cortical function relied on the administration of various drugs for sedation, induction, and maintenance of general anesthesia but used identical criteria to interpret recordings. OBJECTIVES: To determine the effects of 2 inhalation anesthetics on the EEG of healthy horses. ANIMALS: Six healthy horses. METHODS: Prospective study. After the sole administration of one of either isoflurane or halothane at 1.2, 1.4, and 1.6 times the minimum alveolar concentration, EEG was recorded during controlled ventilation, spontaneous ventilation, and nerve stimulation. RESULTS: Burst suppression was observed with isoflurane, along with EEG events that resembled epileptiform discharges. Halothane results were variable between horses, with epileptiform-like discharges and bursts of theta, alpha, and beta recorded intermittently. One horse died and 2 were euthanized as the result of anesthesia-related complications. CONCLUSIONS AND CLINICAL IMPORTANCE: The results of this study indicate that the effects of halothane and isoflurane on EEG activity in the normal horse can be quite variable, even when used in the absence of other drugs. It is recommended that equine EEG be performed without the use of these inhalation anesthetics and that general anesthesia be induced and maintained by other contemporary means.
Assuntos
Anestesia por Inalação/veterinária , Eletroencefalografia/veterinária , Halotano/farmacologia , Cavalos/cirurgia , Isoflurano/farmacologia , Anestésicos Inalatórios/farmacologia , Animais , Estudos Cross-Over , Eletroencefalografia/efeitos dos fármacos , Reprodutibilidade dos TestesRESUMO
BACKGROUND: The effects of anesthesia on the equine electroencephalogram (EEG) after administration of various drugs for sedation, induction, and maintenance are known, but not that the effect of inhaled anesthetics alone for EEG recording. OBJECTIVE: To determine the effects of isoflurane and halothane, administered as single agents at multiple levels, on the EEG and quantitative EEG (qEEG) of normal horses. ANIMALS: Six healthy horses. METHODS: Prospective study. Digital EEG with video and quantitative EEG (qEEG) were recorded after the administration of one of the 2 anesthetics, isoflurane or halothane, at 3 alveolar doses (1.2, 1.4 and 1.6 MAC). Segments of EEG during controlled ventilation (CV), spontaneous ventilation (SV), and with peroneal nerve stimulation (ST) at each MAC multiple for each anesthetic were selected, analyzed, and compared. Multiple non-EEG measurements were also recorded. RESULTS: Specific raw EEG findings were indicative of changes in the depth of anesthesia. However, there was considerable variability in EEG between horses at identical MAC multiples/conditions and within individual horses over segments of a given epoch. Statistical significance for qEEG variables differed between anesthetics with bispectral index (BIS) CV MAC and 95% spectral edge frequency (SEF95) SV MAC differences in isoflurane only and median frequency (MED) differences in SV MAC with halothane only. CONCLUSIONS AND CLINICAL IMPORTANCE: Unprocessed EEG features (background and transients) appear to be beneficial for monitoring the depth of a particular anesthetic, but offer little advantage over the use of changes in mean arterial pressure for this purpose.
Assuntos
Anestesia por Inalação/veterinária , Eletroencefalografia/veterinária , Halotano/farmacologia , Cavalos/cirurgia , Isoflurano/farmacologia , Anestésicos Inalatórios/farmacologia , Animais , Estudos Cross-Over , Eletroencefalografia/efeitos dos fármacosRESUMO
BACKGROUND: Reports of motor polyneuropathies in young cats are scarce. Further, in-depth electrophysiologic evaluation to confirm a motor polyneuropathy in young cats of various breeds other than 2 Bengal cats is lacking. HYPOTHESIS/OBJECTIVES: To confirm a motor polyneuropathy in young cats of various breeds. ANIMALS: Five young cats with heterogenous chronic or relapsing episodes of weakness. METHODS: Retrospective case series. Cats were presented for evaluation of generalized neuromuscular disease and underwent electrophysiologic examination including electromyography, nerve conduction, and repetitive nerve stimulation. Minimum database and muscle and nerve biopsy analyses were carried out. Descriptive statistics were performed. RESULTS: Disease onset was at 3 months to 1 year of age and in 5 breeds. The most common clinical sign (5 of 5 cats) was weakness. Additional neurologic deficits consisted of palmigrade and plantigrade posture (4/4), low carriage of the head and tail (4/4), and variable segmental reflex deficits (5/5). Motor nerve conduction studies were abnormal for the ulnar (4/4), peroneal (5/5), and tibial (2/2) nerves (increased latencies, reduced amplitudes, slow velocities). A marked decrement was observed on repetitive nerve stimulation of the peroneal nerve in 3 cats for which autoimmune myasthenia gravis was ruled out. All sensory nerve conduction studies were normal. Histologic evaluation of muscle and nerve biopsies supported heterogenous alterations consistent with motor polyneuropathy with distal nerve fiber loss. CONCLUSIONS AND CLINICAL IMPORTANCE: Heterogenous motor polyneuropathies should be considered in young cats of any breed and sex that are presented with relapsing or progressive generalized neuromuscular disease.
Assuntos
Doenças do Gato/diagnóstico , Polineuropatias/veterinária , Animais , Doenças do Gato/patologia , Doenças do Gato/fisiopatologia , Gatos , Eletromiografia/veterinária , Feminino , Masculino , Neurônios Motores/patologia , Músculo Esquelético/patologia , Condução Nervosa , Polineuropatias/diagnóstico , Polineuropatias/patologia , Polineuropatias/fisiopatologia , Estudos Retrospectivos , Estimulação Elétrica Nervosa Transcutânea/veterináriaRESUMO
BACKGROUND: Idiopathic headshaking (HSK) in horses is a distressing disorder in which the etiology and pathophysiology are unknown. HYPOTHESIS: Differences in sensory function of the trigeminal nerve exist between healthy and affected horses. ANIMALS: Six healthy mature geldings and 6 mature geldings with idiopathic HSK. METHODS: Prospective study. Sensory nerve action and somatosensory evoked potentials studies were performed. The stimulus site comprised the gingival mucosa dorsal to the maxillary canine. A pair of recording electrodes was placed along the sensory pathway of the trigeminal complex at the infraorbital nerve (R1), maxillary nerve (R2), spinal tract of trigeminal (R3), and somatosensory cortex (R4). Sensory nerve action potential latency (ms), amplitude (µV), duration (ms), area under the curve (µVms), and conduction velocity (m/s) were calculated. RESULTS: Threshold for activation of the infraorbital branch of the trigeminal nerve was significantly different between 5 affected (≤ 5 mA) and 6 control horses (≥ 10 mA). After initiation of an action potential, there were no differences in all parameters measured and no differences between left and right sides. A horse with seasonal HSK tested during a time of no clinical manifestations showed a threshold for activation similar to control horses. CONCLUSIONS AND CLINICAL IMPORTANCE: This study confirms involvement of the trigeminal nerve hyperexcitability in the pathophysiology of disease. Further, results might support a functional rather than a structural alteration in the sensory pathway of the trigeminal complex that can be seasonal. The horse could serve as a natural animal model for humans with idiopathic trigeminal neuralgia.
Assuntos
Potenciais Somatossensoriais Evocados/fisiologia , Cabeça/fisiopatologia , Doenças dos Cavalos/fisiopatologia , Condução Nervosa/fisiologia , Nervo Trigêmeo/fisiopatologia , Animais , Área Sob a Curva , Estimulação Elétrica , Cabeça/inervação , Cavalos , Masculino , Estudos Prospectivos , Estações do AnoRESUMO
BACKGROUND: The administration of certain sedatives has been shown to promote sleep in humans. Related agents induce sleep-like behavior when administered to horses. Interpretation of electroencephalograms (EEGs) obtained from sedated horses should take into account background activity, presence of sleep-related EEG events, and the animal's behavior. HYPOTHESIS: Sedatives induce states of vigilance that are indistinguishable on EEGs from those that occur naturally. ANIMALS: Six healthy horses. METHODS: Digital EEG with video was recorded after administration of 1 of 4 sedatives (acepromazine, butorphanol, xylazine, or detomidine). Serum drug concentrations were measured. Recordings were reviewed, states were identified, and representative EEG samples were analysed. These data were compared with data previously obtained during a study of natural sleep. RESULTS: Butorphanol was associated with brief episodes resembling slow wave sleep in 1 horse. Acepromazine led to SWS in 3 horses, including 1 that also exhibited rapid eye movement sleep. Periods of SWS were observed in all horses afer xylazine or detomidine administration. Normal sleep-related EEG events and heart block, occurred in association with SWS regardless of which sedative was used. Spectral data varied primarily by state, but some differences were observed between sedative and natural data. CONCLUSIONS AND CLINICAL IMPORTANCE: Qualitatively, EEG findings appeared identical whether sedation-induced or naturally occurring. The startle response and heart block associated with some sedatives may be related to sleep. Alpha(2) agonists can be used to obtain high quality EEGs in horses, but acepromazine does not promote a relaxed state in all animals.
Assuntos
Eletroencefalografia/veterinária , Cavalos/fisiologia , Hipnóticos e Sedativos/farmacologia , Sono/fisiologia , Acepromazina/sangue , Acepromazina/farmacologia , Animais , Butorfanol/sangue , Butorfanol/farmacologia , Feminino , Hipnóticos e Sedativos/sangue , Imidazóis/sangue , Imidazóis/farmacologia , Masculino , Distribuição Aleatória , Gravação em Vídeo , Xilazina/sangue , Xilazina/farmacologiaRESUMO
The p53 tumor suppressor gene (TP53) is the most frequently altered gene in human cancer. Mutation of the gene has been shown to be an important mechanism of p53 pathway inactivation in a variety of human brain tumors, particularly those of astrocytic origin. Genomic DNA from a series of 37 glial and 51 nonglial canine brain tumors was sequenced to determine the frequency of TP53 gene mutations involving exons 3-9. Exonic mutations were found in 3 of 88 tumors (3.4%) and specifically in 1 of 18 astrocytic tumors (5.5%). This is markedly lower than that reported in comparable human tumors, suggesting that alternative mechanisms of p53 inactivation are likely to be present if p53 function contributes significantly to oncogenesis in canine brain tumors.
Assuntos
Astrocitoma/veterinária , Neoplasias Encefálicas/veterinária , Doenças do Cão/genética , Genes p53/genética , Mutação , Animais , Astrocitoma/genética , Neoplasias Encefálicas/genética , DNA Complementar/genética , DNA de Neoplasias/química , DNA de Neoplasias/genética , Cães , Éxons/genética , Feminino , Frequência do Gene , Masculino , RNA Neoplásico/genética , Análise de Sequência de DNARESUMO
BACKGROUND: Botulism is a potentially fatal paralytic disorder for which definitive diagnosis is difficult. OBJECTIVES: To determine if repetitive stimulation of the common peroneal nerve will aid in the diagnosis of botulism in foals. ANIMALS: Four control and 3 affected foals. METHODS: Validation of the test in healthy foals for its comparison in foals with suspected botulism. Controls were anesthetized and affected foals were sedated to avoid risks of anesthesia. The common peroneal nerve was chosen for its superficial location and easy access. Stimulating electrodes were placed along the common peroneal nerve. For recording, the active and reference electrodes were positioned over the midpoint and distal end of the extensor digitorum longus muscle, respectively. Repeated supramaximal stimulation of the nerve was performed utilizing a range of frequencies (1-50 Hz). Data analysis consisted of measuring the amplitude and area under the curve for each M wave and converting these values into percentages of decrement or increment based on the comparison of subsequent potentials to the initial one (baseline) within each set. RESULTS: A decremental response was seen at all frequencies in control foals. Decremental responses also were observed in affected foals at low frequencies. An incremental response was seen in all affected foals at 50 Hz. CONCLUSIONS AND CLINICAL IMPORTANCE: Decreased baseline M wave amplitudes with incremental responses at high rates are supportive of botulism. Repetitive nerve stimulation is a safe, simple, fast, and noninvasive technique that can aid in the diagnosis of suspected botulism in foals.
Assuntos
Botulismo/veterinária , Eletrodiagnóstico/veterinária , Doenças dos Cavalos/diagnóstico , Condução Nervosa/fisiologia , Nervo Fibular/fisiologia , Animais , Animais Recém-Nascidos , Área Sob a Curva , Botulismo/diagnóstico , Eletrodiagnóstico/métodos , Feminino , Cavalos , MasculinoRESUMO
Meningiomas are common primary brain tumors in dogs; however, little is known about the molecular genetic mechanisms involved in their tumorigenesis. Several tumor suppressor genes have been implicated in meningioma pathogenesis in humans, including the neurofibromatosis 2 (NF2), protein 4.1B (4.1 B), and tumor suppressor in lung cancer-1 (TSLC1) genes. We investigated the expression of these tumor suppressor genes in a series of spontaneous canine meningiomas using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) (NF2; n = 25) and western blotting (NF2/merlin, 4.1B, TSLC1; n = 30). Decreased expression of 4.1B and TSLC1 expression on western blotting was seen in 6/30 (20%) and in 15/30 (50%) tumors, respectively, with 18/30 (60%) of meningiomas having decreased or absent expression of one or both proteins. NF2 gene expression assessed by western blotting and RT-PCR varied considerably between individual tumors. Complete loss of NF2 protein on western blotting was not seen, unlike 4.1B and TSLC1. Incidence of TSLC1 abnormalities was similar to that seen in human meningiomas, while perturbation of NF2 and 4.1B appeared to be less common than reported for human tumors. No association was observed between tumor grade, subtype, or location and tumor suppressor gene expression based on western blot or RT-PCR. These results suggest that loss of these tumor suppressor genes is a frequent occurrence in canine meningiomas and may be an early event in tumorigenesis in some cases. In addition, it is likely that other, as yet unidentified, genes play an important role in canine meningioma formation and growth.
Assuntos
Doenças do Cão/patologia , Regulação Neoplásica da Expressão Gênica/fisiologia , Neoplasias Meníngeas/veterinária , Meningioma/veterinária , Neurofibromatose 2/metabolismo , Neurofibromina 2/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Animais , Western Blotting/veterinária , Doenças do Cão/genética , Doenças do Cão/metabolismo , Cães , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/metabolismo , Neoplasias Meníngeas/patologia , Meningioma/genética , Meningioma/metabolismo , Meningioma/patologia , Neurofibromatose 2/genética , Neurofibromina 2/genética , RNA Neoplásico/química , RNA Neoplásico/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/veterinária , Proteínas Supressoras de Tumor/genéticaRESUMO
BACKGROUND: Choroid plexus tumors (CPTs) comprise approximately 10% of all primary brain tumors in dogs. The clinical utility of magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, or both in the presumptive diagnosis of CPTs has not been determined. OBJECTIVES: To report MRI and CSF findings in dogs with CPT and determine if there are distinguishing features that allow clinical discrimination between the tumor grades. ANIMALS: Fifty-six client-owned dogs with naturally occurring CPT. METHODS: Retrospective case series. The inclusion criterion was histologically confirmed CPT. Blinded review of cranial MRI and cisternal CSF analysis was performed. RESULTS: Thirty-six of 56 dogs had a choroid plexus carcinoma (CPC) and 20 had a choroid plexus papilloma (CPP). Golden Retrievers were overrepresented compared with the hospital population (frequency 3.7 times that expected, confidence interval 95%= 2.0-6.7, P< .0002). Median CSF protein concentration in CPCs (108 mg/dL, range 27-380 mg/dL) was significantly higher than in CPPs (34 mg/dL, range 32-80 mg/dL) (P= .002). Only dogs with CPCs had a CSF protein concentration >80 mg/dL. Cytological evidence of malignancy in CSF was seen in 7 of 15 CPCs. Only CPCs had evidence of intraventricular or subarachnoid metastases on MRI. CONCLUSIONS AND CLINICAL IMPORTANCE: MRI, CSF analysis or both can help to differentiate between CPPs and CPCs, and may provide valuable prognostic and pretreatment information.
Assuntos
Neoplasias do Plexo Corióideo/veterinária , Doenças do Cão/patologia , Animais , Carcinoma/patologia , Carcinoma/veterinária , Neoplasias do Plexo Corióideo/patologia , Cães , Feminino , Masculino , Papiloma/patologia , Papiloma/veterinária , Estudos RetrospectivosRESUMO
An acute to chronic idiopathic necrotizing meningoencephalitis was diagnosed in 5 Chihuahua dogs aged between 1.5 and 10 years. Presenting neurologic signs included seizures, blindness, mentation changes, and postural deficits occurring from 5 days to 5.5 months prior to presentation. Cerebrospinal fluid analyses from 2 of 3 dogs sampled were consistent with an inflammatory disease. Magnetic resonance imaging of the brain of 2 dogs demonstrated multifocal loss or collapse of cortical gray/white matter demarcation hypointense on T1-weighted images, with T2-weighted hyperintensity and slight postcontrast enhancement. Multifocal asymmetrical areas of necrosis or collapse in both gray and white matter of the cerebral hemispheres was seen grossly in 4 brains. Microscopically in all dogs, there was a severe, asymmetrical, intensely cellular, nonsuppurative meningoencephalitis usually with cystic necrosis in subcortical white matter. There were no lesions in the mesencephalon or metencephalon except in 1 dog. Immunophenotyping defined populations of CD3, CD11d, CD18, CD20, CD45, CD45 RA, and CD79a immunoreactive inflammatory cells varying in density and location but common to acute and chronic lesions. In fresh frozen lesions, both CD1b,c and CD11c immunoreactive dendritic antigen-presenting cells were also identified. Immunoreactivity for canine distemper viral (CDV) antigen was negative in all dogs. The clinical signs, distribution pattern, and histologic type of lesions bear close similarities to necrotizing meningoencephalitis as described in series of both Pug and Maltese breed dogs and less commonly in other breeds.
Assuntos
Encéfalo/patologia , Doenças do Cão/patologia , Meningoencefalite/veterinária , Animais , Comportamento Animal , Cães , Feminino , Masculino , Meningoencefalite/patologia , Lobo Parietal/patologia , Convulsões/etiologia , Convulsões/veterináriaRESUMO
BACKGROUND: The influence of sleep on the equine electroencephalogram (EEG) has not been well documented. HYPOTHESIS: The objectives were to develop a noninvasive method of electrode placement for recording the EEG in horses and to establish normal EEG parameters for the various states of vigilance. Findings are compared with previously published reports on equine sleep based on electrocorticography (ECoG). ANIMALS: Five neurologically normal horses. METHODS: Overnight EEGs were recorded digitally in association with simultaneous videotaping of the horses' behavior. Data were analyzed by visual inspection, states of vigilance were identified, and representative segments were quantitatively processed. Transient EEG events were examined. RESULTS: Slow wave sleep (SWS) was significantly different (P < .05) in frequency and power from drowsiness and rapid eye movement (REM) sleep. Second-degree heart block was associated with SWS as were transient events commonly recognized in EEGs of humans. Drowsiness and REM sleep were similar. In both, background activity was low-amplitude beta activity admixed with prominent activity of approximately 4 Hz. Standing REM sleep was associated with numerous partial collapses in 1 horse. CONCLUSIONS AND CLINICAL IMPORTANCE: Normative data for several states were described and probable benign variants identified. This information will serve as control data for sedative and anesthetic studies in this species. The sleep patterns observed during this study are those of horses removed from their usual surroundings, and thus may represent those encountered in a clinical environment.
Assuntos
Eletroencefalografia/veterinária , Cavalos/fisiologia , Sono/fisiologia , Animais , Feminino , Masculino , Fases do Sono/fisiologia , Sono REM/fisiologia , Vigília/fisiologiaRESUMO
BACKGROUND: Intracranial meningiomas are the most common primary brain tumors in dogs. Classification of meningiomas by tumor grade and subtype has not been reported, and the value of magnetic resonance imaging (MRI) characteristics for predicting tumor subtype and grade has not been investigated. HYPOTHESIS: Canine intracranial meningiomas are a heterogenous group of tumors with differing histological subtypes and grades. Prediction of histopathological classification is possible based on MRI characteristics. ANIMALS: One hundred and twelve dogs with a histological diagnosis of intracranial meningioma. METHODS: Retrospective observational study. RESULTS: Meningiomas were overrepresented in the Golden Retriever and Boxer breeds with no sex predilection. The incidence of specific tumor grades was 56% benign (Grade I), 43% atypical (Grade II), and 1% malignant (Grade III). Grade I histological subtypes included meningothelial (43%), transitional (40%), microcystic (8%), psammomatous (6%), and angiomatous (3%). No statistically significant (P < .05) associations were found among tumor subtype or grade and any of the MRI features studied. CONCLUSIONS AND CLINICAL IMPORTANCE: Meningiomas in dogs differ from their counterparts in humans mainly in their higher incidence of atypical (Grade II) tumors observed. MRI characteristics do not allow for prediction of meningioma subtype or grade, emphasizing the necessity of histopathology for antemortem diagnosis. The higher incidence of atypical tumors in dogs may contribute to the poorer therapeutic response in dogs with meningiomas as compared with the response in humans with meningiomas.
Assuntos
Doenças do Cão/classificação , Técnicas Histológicas/veterinária , Imageamento por Ressonância Magnética/veterinária , Neoplasias Meníngeas/veterinária , Meningioma/veterinária , Animais , Doenças do Cão/patologia , Cães , Feminino , Masculino , Neoplasias Meníngeas/classificação , Neoplasias Meníngeas/patologia , Meningioma/classificação , Meningioma/patologiaRESUMO
BACKGROUND: Meningioma is the most common primary intraspinal nervous system tumor in dogs. Clinical findings, clinicopathologic data, and treatment of these tumors have been reported sporadically, but little information is available regarding cerebrospinal fluid (CSF) analysis, histologic tumor grade, or efficacy of radiation therapy as an adjunct to cytoreductive surgery. ANIMALS: Dogs with histologically confirmed intraspinal meningiomas (n = 34). METHODS: A retrospective study of dogs with intraspinal meningiomas between 1984 and 2006 was carried out. Signalment, historical information, physical examination, clinicopathologic data, radiation therapy protocols, surgery reports, and all available images were reviewed. All tumors were histologically classified and graded as defined by the international World Health Organization classification scheme for central nervous system tumors. RESULTS: Intraspinal mengiomas in dogs are most common in the cervical spinal cord but can be found throughout the neuraxis. Location is correlated with histologic grade, with grade I tumors more likely to be in the cervical region than grade II tumors. Myelography generally shows an intradural extramedullary compressive lesion. On magnetic resonance imaging, the masses are strongly and uniformly contrast enhancing and a dural tail often is present. CSF analysis usually shows increased protein concentration with mild to moderate mixed pleocytosis. Surgical resection is an effective means of improving neurologic status, and adjunctive radiation therapy may lead to an improved outcome. CONCLUSIONS AND CLINICAL IMPORTANCE: Biopsy is necessary for definitive diagnosis, but imaging and CSF analysis can suggest a diagnosis of meningioma. Treatment of meningiomas with surgery and radiation therapy can result in a fair to excellent prognosis.
Assuntos
Doenças do Cão/patologia , Meningioma/veterinária , Animais , Doenças do Cão/classificação , Cães , Feminino , Imageamento por Ressonância Magnética/veterinária , Masculino , Meningioma/classificação , Meningioma/patologia , Radiografia/veterinária , Estudos RetrospectivosRESUMO
Vascular endothelial growth factor (VEGF) is an important regulator of tumor angiogenesis and vascular permeability, and has been implicated both in progression of central nervous system (CNS) tumors and development of vasogenic peritumoral edema. A retrospective study was done to characterize the levels of expression of the 3 major canine VEGF isoforms (VEGF(120), VEGF(164), VEGF(188)) in a variety of spontaneous canine CNS tumors using quantitative TaqMan reverse transcription real-time polymerase chain reaction. Presence and degree of peritumoral edema also were determined in sampled tumors using magnetic resonance imaging (MRI). Increased expression of VEGF relative to normal cerebral cortex tissue was seen predominantly in high grade astrocytic (grade IV) and oligodendroglial (grade III) tumors, with lower expression in low grade astrocytomas (grade II) and meningiomas (grade I). All 3 major VEGF isoforms were present; VEGF(164) was the predominant isoform, particularly in the tumors with the highest VEGF expression. Peritumoral edema was present in all tumor types; however, a significant association between the extent of peritumoral edema and the level of VEGF expression was not apparent.
Assuntos
Edema Encefálico/metabolismo , Edema Encefálico/veterinária , Neoplasias do Sistema Nervoso Central/veterinária , Doenças do Cão/metabolismo , RNA Mensageiro/biossíntese , Fator A de Crescimento do Endotélio Vascular/biossíntese , Animais , Astrocitoma/genética , Astrocitoma/metabolismo , Astrocitoma/patologia , Astrocitoma/veterinária , Edema Encefálico/genética , Edema Encefálico/patologia , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/metabolismo , Neoplasias do Sistema Nervoso Central/patologia , Doenças do Cão/genética , Doenças do Cão/patologia , Cães , Meningioma/genética , Meningioma/metabolismo , Meningioma/patologia , Meningioma/veterinária , Oligodendroglioma/genética , Oligodendroglioma/metabolismo , Oligodendroglioma/patologia , Oligodendroglioma/veterinária , Reação em Cadeia da Polimerase/veterinária , Isoformas de Proteínas , RNA Mensageiro/genética , Estudos Retrospectivos , Estatísticas não Paramétricas , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
Fifteen horses with pituitary pars intermedia dysfunction were studied. The horses were of various breeds and between 15 and 28 years of age. Control horses matched for breed and age were studied for comparison. Evaluations included complete blood cell count and serum biochemical analysis, electromyography, and gluteus medius muscle biopsies for histochemical, morphometric, and ultrastructural analysis. No differences were found between groups of horses on routine laboratory analysis or electromyography. We demonstrated that muscle wasting in diseased horses was the result of atrophy of types 2A and 2B muscle fibers and loss of type 2B myofibers. Mild non-specific non-inflammatory myopathic alterations such as myofiber size variation, internal nuclei, perimysial, endomysial and sarcoplasmic fat accumulation were observed. At the ultrastructural level, subsarcolemmal mitochondrial accumulation and increased lipid droplets were evident. Similar to other species, this study confirmed atrophy of type 2 fibers as the cause of muscle mass loss in horses with Cushing's disease.
Assuntos
Doenças dos Cavalos/etiologia , Doenças Musculares/veterinária , Hipersecreção Hipofisária de ACTH/veterinária , Adeno-Hipófise Parte Intermédia/fisiopatologia , Animais , Eletromiografia , Feminino , Doenças dos Cavalos/patologia , Cavalos , Masculino , Mitocôndrias Musculares/patologia , Mitocôndrias Musculares/ultraestrutura , Fibras Musculares Esqueléticas/patologia , Fibras Musculares Esqueléticas/ultraestrutura , Debilidade Muscular/etiologia , Debilidade Muscular/fisiopatologia , Debilidade Muscular/veterinária , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Músculo Esquelético/ultraestrutura , Doenças Musculares/etiologia , Doenças Musculares/patologia , Hipersecreção Hipofisária de ACTH/complicações , Hipersecreção Hipofisária de ACTH/patologia , Adeno-Hipófise Parte Intermédia/patologiaRESUMO
A 6-year-old castrated German Shepherd Dog was presented with a 6-month history of progressive, nonpainful, left pelvic limb paresis. Magnetic resonance imaging revealed atrophy of left-sided epaxial and hypaxial muscles from L5-L7 and an enlarged L5 spinal nerve. Exploratory hemi-laminectomy revealed focally and cylindrically thickened L5 and L6 nerve roots. Histologic evaluation of a surgical biopsy specimen from the L6 dorsal nerve root, and the L5 nerve roots after later amputation revealed distended hypercellular fascicles. This distension was due to widely separated axons surrounded by concentric lamellations formed by neoplastic perineurial cells and their processes. These pseudo-onion bulbs were separated from each other by a basophilic myxoid stroma. The perineurioma cell processes were immunonegative for S-100 (alpha and beta chains) and collagen IV, but were immunoreactive for laminin. The central axons were also immunoreactive for NF-200 and S-100. The proliferative index of the perineurioma cells, as determined by MIB-1 immunoreactivity, was about 3%. Ultrastructurally, the widely separated, interdigitating perineurioma cell processes were connected by desmosomal-like junctional complexes to form continuous circles. Their processes were covered by a discontinuous basal lamina. Each centrally placed axon was normally, thinly, or completely unmyelinated and was surrounded by a normal Schwann cell. These morphologic and immunologic features distinguish this lesion from hypertrophic neuropathy and were consistent with intraneural perineurioma.
Assuntos
Doenças do Cão/patologia , Neoplasias de Bainha Neural/veterinária , Neoplasias do Sistema Nervoso Periférico/veterinária , Raízes Nervosas Espinhais/ultraestrutura , Animais , Cães , Imuno-Histoquímica/veterinária , Laminectomia/veterinária , Imageamento por Ressonância Magnética/veterinária , Masculino , Microscopia Eletrônica/veterinária , Neoplasias de Bainha Neural/patologia , Neoplasias do Sistema Nervoso Periférico/patologiaRESUMO
Inhibition of tumour growth and angiogenesis by targeting key growth factor receptors is a promising therapeutic strategy for central nervous system tumours. Characterization of these growth factor receptors in canine primary brain tumours has not been done. Using quantitative real-time TaqMan polymerase chain reaction (PCR), we evaluated the expression of messenger RNA (mRNA) for five tyrosine kinase growth factor receptors (vascular endothelial growth factor receptor [VEGFR]-1, VEGFR-2, endothelial growth factor receptor [EGFR]-1, platelet-derived growth factor receptor a [PDGFRa], and c-Met) relative to normal cerebral cortex in 66 spontaneous canine primary brain tumours. Increased expression of VEGFR-1 and VEGFR-2 mRNA was greatest in grade IV astrocytomas (glioblastoma multiforme) and grade III (anaplastic) oligodendrogliomas. EGFR-1 mRNA expression was more consistently increased than the other receptors in all tumour types, while increased PDGFRa mRNA expression was mostly restricted to oligodendrogliomas. The similarities in increased expression of these tyrosine kinase growth factor receptors in these canine tumours, as compared to data from their human counterparts, suggest that common molecular mechanisms may be present.
RESUMO
Sarcoplasmic masses in humans have been associated with various myopathies, although the significance remains elusive. Similar structures have also been observed in equine muscle. The aim of this study was to determine the frequency of such structures in normal and abnormal equine muscle, and to characterize these structures using histological, histochemical, immunohistochemical, ultrastructural, and morphometric analyses. The histological and histochemical appearance was similar to that of human sarcoplasmic masses with a central or subsarcolemmal distribution. Of interest was a predilection for the gluteus medius muscle in younger horses and type 2B fibers. Ultrastructurally they contained disorganized myofibrils and other cellular components that were not membrane bound and were present in both normal and abnormal equine muscle without a specific disease association, suggesting they are a non-pathological degenerative structure. The relatively frequent occurrence of sarcoplasmic masses in horses may make this species a good model for studying the pathogenesis of these structures.
Assuntos
Doenças dos Cavalos/patologia , Fibras Musculares Esqueléticas/patologia , Músculo Esquelético/patologia , Doenças Musculares/veterinária , Fatores Etários , Animais , Biomarcadores , Citoplasma/patologia , Citoplasma/ultraestrutura , Doenças dos Cavalos/fisiopatologia , Cavalos , Imuno-Histoquímica , Microscopia Eletrônica de Transmissão , Fibras Musculares Esqueléticas/ultraestrutura , Proteínas Musculares/metabolismo , Músculo Esquelético/fisiopatologia , Músculo Esquelético/ultraestrutura , Atrofia Muscular/patologia , Atrofia Muscular/fisiopatologia , Doenças Musculares/patologia , Doenças Musculares/fisiopatologia , Miofibrilas/patologia , Miofibrilas/ultraestrutura , Estudos Prospectivos , Estudos RetrospectivosRESUMO
Two geriatric domestic shorthaired cats (DSH) were treated surgically with a ventral bulla osteotomy and craniectomy for middle ear tumours that invaded the calvarium. Both cats had a history of vestibular disease. One cat had a normal neurological examination. Both cats underwent computed tomographic imaging of the head. After intravenous injection of an iodinated contrast material, one cat had a ring-enhancing intracranial lesion and the other had a uniform contrast-enhancing intracranial lesion, which either communicated with the bulla or was associated with bulla osseous lysis/production. One cat had a papillary adenoma and the other had an adenocarcinoma. Both cats had prolonged survivals (630 days; alive and lost to follow-up at 840 days), which is longer than reported in cats with middle ear neoplasia. Craniectomy, in addition to ventral bulla osteotomy, may be part of the treatment plan for middle ear tumours that invade the calvarium.