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1.
FASEB J ; 38(7): e23609, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38593345

RESUMO

PTPRD, a well-established tumor suppressor gene, encodes the protein tyrosine phosphatase-type D. This protein consists of three immunoglobulin-like (Ig) domains, four to eight fibronectin type 3 (FN) domains, a single transmembrane segment, and two cytoplasmic tandem tyrosine phosphatase domains. PTPRD is known to harbor various cancer-associated point mutations. While it is assumed that PTPRD regulates cellular functions as a tumor suppressor through the tyrosine phosphatase activity in the intracellular region, the function of its extracellular domain (ECD) in cancer is not well understood. In this study, we systematically examined the impact of 92 cancer-associated point mutations within the ECD. We found that 69.6% (64 out of 92) of these mutations suppressed total protein expression and/or plasma membrane localization. Notably, almost all mutations (20 out of 21) within the region between the last FN domain and transmembrane segment affected protein expression and/or localization, highlighting the importance of this region for protein stability. We further found that some mutations within the Ig domains adjacent to the glycosaminoglycan-binding pocket enhanced PTPRD's binding ability to heparan sulfate proteoglycans (HSPGs). This interaction is proposed to suppress phosphatase activity. Our findings therefore suggest that HSPG-mediated attenuation of phosphatase activity may be involved in tumorigenic processes through PTPRD dysregulation.


Assuntos
Proteoglicanas de Heparan Sulfato , Neoplasias , Humanos , Proteoglicanas de Heparan Sulfato/metabolismo , Mutação Puntual , Proteínas da Matriz Extracelular/genética , Imunoglobulinas , Estabilidade Proteica , Tirosina/genética , Monoéster Fosfórico Hidrolases/genética , Heparitina Sulfato , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/genética , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/metabolismo
2.
Skeletal Radiol ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38647687

RESUMO

Osteoid osteoma (OO) is a common, benign bone tumor. However, there are no case reports of OO associated with osteogenesis imperfecta (OI), or pathological fractures in OO. A 3-year-old girl with OI sustained a complete right tibial diaphyseal fracture. Bony fusion was completed after 4 months of conservative therapy; nevertheless, 18 months later spontaneous pain appeared at the fracture site, without any cause. Plain radiographs showed a newly apparent, rounded area of translucency 1 cm in diameter, just overlapping the previous fracture. Images obtained using three-dimensional time-resolved contrast-enhanced magnetic resonance angiography showed strong central enhancement in the early phase, with an apparent nidus, suggesting the diagnosis of OO. Nineteen months after the first fracture, while skipping, the patient refractured her tibial diaphysis at the site of the previous fracture. This is a very rare case of OO, apparently co-existing with OI and leading to a bony fracture. In our case, the combination of bone fragility in OI and a recent fracture at the site of the OO may have caused the re-fracture.

3.
Mol Brain ; 17(1): 16, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38475840

RESUMO

Neuroligin (NLGN) 3 is a postsynaptic cell adhesion protein organizing synapse formation through two different types of transsynaptic interactions, canonical interaction with neurexins (NRXNs) and a recently identified noncanonical interaction with protein tyrosine phosphatase (PTP) δ. Although, NLGN3 gene is known as a risk gene for neurodevelopmental disorders such as autism spectrum disorder (ASD) and intellectual disability (ID), the pathogenic contribution of the canonical NLGN3-NRXN and noncanonical NLGN3-PTPδ pathways to these disorders remains elusive. In this study, we utilized Nlgn3 mutant mice selectively lacking the interaction with either NRXNs or PTPδ and investigated their social and memory performance. Neither Nlgn3 mutants showed any social cognitive deficiency in the social novelty recognition test. However, the Nlgn3 mutant mice lacking the PTPδ pathway exhibited significant decline in the social conditioned place preference (sCPP) at the juvenile stage, suggesting the involvement of the NLGN3-PTPδ pathway in the regulation of social motivation and reward. In terms of learning and memory, disrupting the canonical NRXN pathway attenuated contextual fear conditioning while disrupting the noncanonical NLGN3-PTPδ pathway enhanced it. Furthermore, disruption of the NLGN3-PTPδ pathway negatively affected the remote spatial reference memory in the Barnes maze test. These findings highlight the differential contributions of the canonical NLGN3-NRXN and noncanonical NLGN3-PTPδ synaptogenic pathways to the regulation of higher order brain functions associated with ASD and ID.


Assuntos
Transtorno do Espectro Autista , Moléculas de Adesão Celular Neuronais , Deficiência Intelectual , Proteínas de Membrana , Proteínas do Tecido Nervoso , Animais , Camundongos , Transtorno do Espectro Autista/genética , Moléculas de Adesão Celular , Moléculas de Adesão Celular Neuronais/genética , Moléculas de Adesão Celular Neuronais/metabolismo , Cognição , Aprendizagem em Labirinto , Mudança Social , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo
4.
Front Mol Neurosci ; 16: 1298238, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38098940

RESUMO

Environmental and genetic factors influence synapse formation. Numerous animal experiments have revealed that pesticides, including herbicides, can disturb normal intracellular signals, gene expression, and individual animal behaviors. However, the mechanism underlying the adverse outcomes of pesticide exposure remains elusive. Herein, we investigated the effect of maternal exposure to the herbicide glufosinate ammonium (GLA) on offspring neuronal synapse formation in vitro. Cultured cerebral cortical neurons prepared from mouse embryos with maternal GLA exposure demonstrated impaired synapse formation induced by synaptic organizer neuroligin 1 (NLGN1)-coated beads. Conversely, the direct administration of GLA to the neuronal cultures exhibited negligible effect on the NLGN1-induced synapse formation. The comparison of the transcriptomes of cultured neurons from embryos treated with maternal GLA or vehicle and a subsequent bioinformatics analysis of differentially expressed genes (DEGs) identified "nervous system development," including "synapse," as the top-ranking process for downregulated DEGs in the GLA group. In addition, we detected lower densities of parvalbumin (Pvalb)-positive neurons at the postnatal developmental stage in the medial prefrontal cortex (mPFC) of offspring born to GLA-exposed dams. These results suggest that maternal GLA exposure induces synapse pathology, with alterations in the expression of genes that regulate synaptic development via an indirect pathway distinct from the effect of direct GLA action on neurons.

5.
Radiol Case Rep ; 18(3): 840-843, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36589501

RESUMO

Cystitis cystica and glandularis is a hyperproliferative disease of the urothelium, and may form a papillary or polypoid mass. Clinically, these mass lesions are often difficult to distinguish from malignant tumors. We present a pediatric patient of cystitis cystica and glandularis with a bladder mass and discuss dynamic contrast-enhanced magnetic resonance imaging (MRI) findings and histopathological profiles, which have not been previously explored in the literature. Dynamic contrast-enhanced MRI showed unique, superficial, strong enhancement that resembles an inchworm in appearance. The term "inchworm sign" is a characteristic finding on diffusion-weighted MRI, proposed as a criterion for T-staging in non-muscle-invasive bladder cancer. We would like to propose another "inchworm sign" on dynamic contrast-enhanced MRI as a new hallmark of cystitis cystica and glandularis, which may differentiate it from a malignant tumor.

6.
Nat Commun ; 12(1): 1848, 2021 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-33758193

RESUMO

Neuroligin 3 (NLGN3) and neurexins (NRXNs) constitute a canonical transsynaptic cell-adhesion pair, which has been implicated in autism. In autism spectrum disorder (ASD) development of sociality can be impaired. However, the molecular mechanism underlying NLGN3-mediated social development is unclear. Here, we identify non-canonical interactions between NLGN3 and protein tyrosine phosphatase δ (PTPδ) splice variants, competing with NRXN binding. NLGN3-PTPδ complex structure revealed a splicing-dependent interaction mode and competition mechanism between PTPδ and NRXNs. Mice carrying a NLGN3 mutation that selectively impairs NLGN3-NRXN interaction show increased sociability, whereas mice where the NLGN3-PTPδ interaction is impaired exhibit impaired social behavior and enhanced motor learning, with imbalance in excitatory/inhibitory synaptic protein expressions, as reported in the Nlgn3 R451C autism model. At neuronal level, the autism-related Nlgn3 R451C mutation causes selective impairment in the non-canonical pathway. Our findings suggest that canonical and non-canonical NLGN3 pathways compete and regulate the development of sociality.


Assuntos
Transtorno do Espectro Autista/genética , Proteínas de Ligação ao Cálcio/metabolismo , Moléculas de Adesão Celular Neuronais/metabolismo , Proteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Moléculas de Adesão de Célula Nervosa/metabolismo , Neurônios/metabolismo , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/metabolismo , Sequência de Aminoácidos , Animais , Transtorno do Espectro Autista/metabolismo , Escala de Avaliação Comportamental , Proteínas de Ligação ao Cálcio/química , Proteínas de Ligação ao Cálcio/genética , Moléculas de Adesão Celular Neuronais/química , Moléculas de Adesão Celular Neuronais/genética , Modelos Animais de Doenças , Feminino , Células HEK293 , Humanos , Masculino , Proteínas de Membrana/química , Proteínas de Membrana/genética , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Mutação , Proteínas do Tecido Nervoso/química , Proteínas do Tecido Nervoso/genética , Moléculas de Adesão de Célula Nervosa/química , Moléculas de Adesão de Célula Nervosa/genética , Domínios Proteicos , Processamento de Proteína , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/química , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/genética , Proteínas Recombinantes , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Comportamento Social , Sinapses/genética
7.
J Neurodev Disord ; 12(1): 25, 2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32942984

RESUMO

BACKGROUND: Rare genetic variants contribute to the etiology of both autism spectrum disorder (ASD) and schizophrenia (SCZ). Most genetic studies limit their focus to likely gene-disrupting mutations because they are relatively easier to interpret their effects on the gene product. Interpretation of missense variants is also informative to some pathophysiological mechanisms of these neurodevelopmental disorders; however, their contribution has not been elucidated because of relatively small effects. Therefore, we characterized missense variants detected in NRXN1, a well-known neurodevelopmental disease-causing gene, from individuals with ASD and SCZ. METHODS: To discover rare variants with large effect size and to evaluate their role in the shared etiopathophysiology of ASD and SCZ, we sequenced NRXN1 coding exons with a sample comprising 562 Japanese ASD and SCZ patients, followed by a genetic association analysis in 4273 unrelated individuals. Impact of each missense variant detected here on cell surface expression, interaction with NLGN1, and synaptogenic activity was analyzed using an in vitro functional assay and in silico three-dimensional (3D) structural modeling. RESULTS: Through mutation screening, we regarded three ultra-rare missense variants (T737M, D772G, and R856W), all of which affected the LNS4 domain of NRXN1α isoform, as disease-associated variants. Diagnosis of individuals with T737M, D772G, and R856W was 1ASD and 1SCZ, 1ASD, and 1SCZ, respectively. We observed the following phenotypic and functional burden caused by each variant. (i) D772G and R856W carriers had more serious social disabilities than T737M carriers. (ii) In vitro assay showed reduced cell surface expression of NRXN1α by D772G and R856W mutations. In vitro functional analysis showed decreased NRXN1α-NLGN1 interaction of T737M and D772G mutants. (iii) In silico 3D structural modeling indicated that T737M and D772G mutations could destabilize the rod-shaped structure of LNS2-LNS5 domains, and D772G and R856W could disturb N-glycan conformations for the transport signal. CONCLUSIONS: The combined data suggest that missense variants in NRXN1 could be associated with phenotypes of neurodevelopmental disorders beyond the diagnosis of ASD and/or SCZ.


Assuntos
Transtorno do Espectro Autista , Proteínas de Ligação ao Cálcio/genética , Moléculas de Adesão de Célula Nervosa/genética , Esquizofrenia , Transtorno do Espectro Autista/genética , Éxons , Heterozigoto , Humanos , Mutação , Esquizofrenia/genética
8.
Nat Commun ; 11(1): 649, 2020 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-32005855

RESUMO

Synapse formation is induced by transsynaptic interaction of neuronal cell-adhesion molecules termed synaptic organizers. Type IIa receptor protein tyrosine phosphatases (IIa RPTPs) function as presynaptic organizers. The cytoplasmic domain of IIa RPTPs consists of two phosphatase domains, and the membrane-distal one (D2) is essential for synapse formation. Liprin-α, which is an active zone protein critical for synapse formation, interacts with D2 via its C-terminal domain composed of three tandem sterile alpha motifs (tSAM). Structural mechanisms of this critical interaction for synapse formation remain elusive. Here, we report the crystal structure of the complex between mouse PTPδ D2 and Liprin-α3 tSAM at 1.91 Å resolution. PTPδ D2 interacts with the N-terminal helix and the first and second SAMs (SAM1 and SAM2, respectively) of Liprin-α3. Structure-based mutational analyses in vitro and in cellulo demonstrate that the interactions with Liprin-α SAM1 and SAM2 are essential for the binding and synaptogenic activity.


Assuntos
Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/química , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/metabolismo , Proteínas de Transporte Vesicular/química , Proteínas de Transporte Vesicular/metabolismo , Animais , Cristalização , Camundongos , Modelos Moleculares , Ligação Proteica , Domínios Proteicos , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/genética , Sinapses/genética , Sinapses/metabolismo , Proteínas de Transporte Vesicular/genética
9.
Nat Commun ; 9(1): 269, 2018 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-29348429

RESUMO

Synapse formation is triggered by trans-synaptic interactions of cell adhesion molecules, termed synaptic organizers. Three members of type-II receptor protein tyrosine phosphatases (classified as type-IIa RPTPs; PTPδ, PTPσ and LAR) are known as presynaptic organizers. Synaptic adhesion-like molecules (SALMs) have recently emerged as a family of postsynaptic organizers. Although all five SALM isoforms can bind to the type-IIa RPTPs, only SALM3 and SALM5 reportedly have synaptogenic activities depending on their binding. Here, we report the crystal structures of apo-SALM5, and PTPδ-SALM2 and PTPδ-SALM5 complexes. The leucine-rich repeat (LRR) domains of SALMs interact with the second immunoglobulin-like (Ig) domain of PTPδ, whereas the Ig domains of SALMs interact with both the second and third Ig domains of PTPδ. Unexpectedly, the structures exhibit the LRR-mediated 2:2 complex. Our synaptogenic co-culture assay using site-directed SALM5 mutants demonstrates that presynaptic differentiation induced by PTPδ-SALM5 requires the dimeric property of SALM5.


Assuntos
Moléculas de Adesão Celular Neuronais/química , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/química , Sinapses/metabolismo , Transmissão Sináptica , Animais , Moléculas de Adesão Celular Neuronais/genética , Moléculas de Adesão Celular Neuronais/metabolismo , Cristalografia por Raios X , Células HEK293 , Humanos , Modelos Moleculares , Mutação , Ligação Proteica , Domínios Proteicos , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Multimerização Proteica , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/genética , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/metabolismo
10.
Vet Anaesth Analg ; 44(3): 461-472, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28579007

RESUMO

OBJECTIVE: To explore the major risk factors linking preoperative characteristics and anaesthesia-related death in dogs in referral hospitals in Japan. STUDY DESIGN: Observational cohort study. ANIMALS: From April 1, 2010 to March 31, 2011, 4323 dogs anaesthetized in 18 referral hospitals in Japan. METHODS: Questionnaire forms were collated anonymously. Death occurring within 48 hours after extubation was considered as an anaesthesia-related death. Patient outcome (alive or dead) was set as the outcome variable. Preoperative general physical characteristics, complete blood cell counts, serum biochemical examinations and intraoperative complications were set as explanatory variables. The risk factors for anaesthesia-related death were evaluated using chi-square test or Fisher's exact test, followed by multivariable logistic regression analysis of the data. Significance was set at p < 0.05. RESULTS: Thirteen dogs that died from surgical error or euthanasia were excluded from statistical analysis. The total mortality rate in this study was 0.65% [28/4310 dogs; 95% confidence interval (CI), 0.41-0.89]. Furthermore, 75% (95% CI, 55.1-89.3) of anaesthesia-related deaths occurred in dogs with pre-existing diseases. Most of the deaths occurred postoperatively (23/28; 82.1%; 95% CI, 63.1-93.9). Preoperative serum glucose concentration <77 mg dL-1 (6/46; 13.0%; 95% CI, 4.9-26.3), disturbance of consciousness (6/50; 12.0%; 95% CI, 4.5-24.3), white cell count >15,200 µL-1 (16/499; 3.4%; 95% CI, 1.9-5.5) and American Society of Anesthesiologists grade III-V (19/1092; 1.7%; 95% CI, 1.1-2.7) were identified as risk factors for anaesthesia-related death. Intraoperative hypoxaemia (8/34; 23.5%; 95% CI, 10.7-41.2) and tachycardia (4/148; 2.7%; 95% CI, 0.7-6.8) were also risk factors for anaesthesia-related death. CONCLUSIONS AND CLINICAL RELEVANCE: The results revealed that certain preoperative characteristics were associated with increased odds of anaesthesia-related death, specifically low serum glucose concentration and disturbances of consciousness. Greater attention to correcting preanaesthetic patient abnormalities may reduce the risk of anaesthesia-related death.


Assuntos
Anestesia/veterinária , Anestesia/mortalidade , Animais , Glicemia , Causas de Morte , Distribuição de Qui-Quadrado , Estudos de Coortes , Intervalos de Confiança , Transtornos da Consciência/mortalidade , Doenças do Cão/mortalidade , Cães , Hospitais Veterinários , Japão , Contagem de Leucócitos , Período Pré-Operatório , Encaminhamento e Consulta , Fatores de Risco , Fatores de Tempo
11.
Intractable Rare Dis Res ; 5(3): 214-7, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27672545

RESUMO

Allan-Herndon-Dudley syndrome (AHDS) is an X-linked disorder caused by impaired thyroid hormone transporter. Patients with AHDS usually exhibit severe motor developmental delay, delayed myelination of the brain white matter, and elevated T3 levels in thyroid tests. Neurological examination of two patients with neurodevelopmental delay revealed generalized hypotonia, and not paresis, as the main neurological finding. Nystagmus and dyskinesia were not observed. Brain magnetic resonance imaging demonstrated delayed myelination in early childhood in both patients. Nevertheless, matured myelination was observed at 6 years of age in one patient. Although the key finding for AHDS is elevated free T3, one of the patients showed a normal T3 level in childhood, misleading the diagnosis of AHDS. Genetic analysis revealed two novel SLC16A2 mutations, p.(Gly122Val) and p.(Gly221Ser), confirming the AHDS diagnosis. These results indicate that AHDS diagnosis is sometimes challenging owing to clinical variability among patients.

12.
PLoS One ; 10(3): e0120636, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25746668

RESUMO

Prenatal sex hormones can induce abnormalities in the reproductive system and adversely impact on genital development. We investigated whether sex hormones in cord blood influenced the ratio of the second to fourth digit lengths (2D/4D) in school-aged children. Of the 514 children who participated in a prospective cohort study on birth in Sapporo between 2002 and 2005, the following sex hormone levels were measured in 294 stored cord blood samples (135 boys and 159 girls); testosterone (T), estradiol (E), progesterone, LH, FSH, inhibin B, and insulin-like factor 3 (INSL3). A total of 350 children, who were of school age and could be contacted for this survey, were then requested via mail to send black-and-white photocopies of the palms of both the left and right hands. 2D/4D was calculated in 190 children (88 boys and 102 girls) using photocopies and derived from participants with the characteristics of older mothers, a higher annual household income, higher educational level, and fewer smokers among family members. 2D/4D was significantly lower in males than in females (p<0.01). In the 294 stored cord blood samples, T, T/E, LH, FSH, Inhibin B, and INSL3 levels were significantly higher in samples collected from males than those from females. A multivariate regression model revealed that 2D/4D negatively correlated with INSL3 in males and was significantly higher in males with <0.32 ng/mL of INSL3 (p<0.01). No correlations were observed between other hormones and 2D/4D. In conclusion, 2D/4D in school-aged children, which was significantly lower in males than in females, was affected by prenatal Leydig cell function.


Assuntos
Sangue Fetal , Dedos/crescimento & desenvolvimento , Hormônios Esteroides Gonadais/sangue , Células Intersticiais do Testículo/metabolismo , Modelos Biológicos , Adulto , Criança , Feminino , Dedos/anatomia & histologia , Humanos , Recém-Nascido , Masculino , Tamanho do Órgão/fisiologia , Gravidez , Estudos Prospectivos
13.
PLoS One ; 9(8): e105282, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25133605

RESUMO

D-Serine, an endogenous coagonist of the N-methyl-D-aspartate receptor (NMDAR), is widely distributed in the central nervous system and is synthesized from L-serine by serine racemase (SR). NMDAR plays an important role in pain processing including central sensitization that eventually causes hyperalgesia. To elucidate the roles of D-serine and SR in pain transmission, we evaluated the behavioral changes and spinal nociceptive processing induced by formalin using SR knock-out (KO) mice. We found that SR is mainly distributed in lamina II of the dorsal horn of the spinal cord in wild-type (WT) mice. Although the formalin injected subcutaneously induced the biphasic pain response of licking in SR-KO and WT mice, the time spent on licking was significantly longer in the SR-KO mice during the second phase of the formalin test. The number of neurons immunopositive for c-Fos and phosphorylated extracellular signal-regulated kinase (p-ERK), which are molecular pain markers, in laminae I-II of the ipsilateral dorsal horn was significantly larger in the SR-KO mice. Immunohistochemical staining revealed that the distribution of SR changed from being broad to being concentrated in cell bodies after the formalin injection. On the other hand, the expression level of the cytosolic SR in the ipsilateral dorsal horn significantly decreased. Oral administration of 10 mM D-serine in drinking water for one week cancelled the difference in pain behaviors between WT and SR-KO mice in phase 2 of the formalin test. These findings demonstrate that the SR-KO mice showed increased sensitivity to inflammatory pain and the WT mice showed translocation of SR and decreased SR expression levels after the formalin injection, which suggest a novel antinociceptive mechanism via SR indicating an important role of D-serine in pain transmission.


Assuntos
Formaldeído/toxicidade , Inflamação/fisiopatologia , Dor/fisiopatologia , Racemases e Epimerases/metabolismo , Animais , Western Blotting , Formaldeído/administração & dosagem , Imuno-Histoquímica , Injeções Subcutâneas , Masculino , Camundongos , Camundongos Knockout , Dor/induzido quimicamente , Racemases e Epimerases/genética , Medula Espinal/metabolismo , Corno Dorsal da Medula Espinal/metabolismo , Substância Gelatinosa/metabolismo
14.
J Clin Microbiol ; 48(4): 1176-81, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20107103

RESUMO

Canine herpesvirus (CHV; Canid herpesvirus 1) is principally a perinatal pathogen of pregnant bitches and newborn pups and secondarily a respiratory tract pathogen of older pups and dogs. Infectious disease of the canine respiratory tract frequently occurs among dogs in groups, in which it is called " infectious tracheobronchitis" (ITB). Mortality from ITB is generally negligible, and the clinical importance of CHV as an ITB pathogen is considered to be low. The present report describes a novel ITB outbreak accompanied by death among aged dogs in an animal medical center. Most inpatient dogs had received medications that could induce immunosuppression. CHV was the only pathogen identified, and several CHV isolates were recovered in cell culture. No other viral pathogens or significant bacterial pathogens were found. Molecular and serological analyses revealed that the causative CHV isolates were from a single source but that none was a peculiar strain when the strains were compared with previous CHV strains. The virus had presumably spread among the dogs predisposed to infection in the center. The present results serve as a warning to canine clinics that, under the specific set of circumstances described, such serious CHV outbreaks may be expected wherever canine ITB occurs.


Assuntos
Infecção Hospitalar/veterinária , Surtos de Doenças , Doenças do Cão/epidemiologia , Doenças do Cão/virologia , Infecções por Herpesviridae/veterinária , Herpesvirus Canídeo 1/isolamento & purificação , Doenças Respiratórias/veterinária , Animais , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/virologia , Impressões Digitais de DNA , DNA Viral/genética , Cães , Genótipo , Infecções por Herpesviridae/epidemiologia , Infecções por Herpesviridae/virologia , Herpesvirus Canídeo 1/classificação , Herpesvirus Canídeo 1/genética , Epidemiologia Molecular , Doenças Respiratórias/epidemiologia , Doenças Respiratórias/virologia
15.
Vet Surg ; 38(8): 927-33, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20017849

RESUMO

OBJECTIVE: To characterize the behavior of horses recovering in the Anderson Sling Suspension System after 4 hours of desflurane anesthesia and postdesflurane intravenous (IV) administration of propofol and xylazine. STUDY DESIGN: Experimental study. ANIMALS: Healthy horses (n=6), mean+/-SEM age 12.3+/-1.8 years; mean weight 556+/-27 kg. METHODS: Each horse was anesthetized with xylazine, diazepam, and ketamine IV and anesthesia was maintained with desflurane in O(2). At the end of 4 hours of desflurane, each horse was positioned in the sling suspension system and administered propofol-xylazine IV. Recovery events were quantitatively and qualitatively assessed. Venous blood was obtained before and after anesthesia for biochemical and propofol analyses. RESULTS: Anesthetic induction and maintenance were without incident. Apnea commonly accompanied propofol administration. All horses had consistent recovery behavior characterized by a smooth, careful, atraumatic return to a standing posture. CONCLUSIONS: Results of this study support careful, selective clinical use of desflurane, propofol-xylazine, and the Anderson Sling Suspension System to atraumatically transition horses with high anesthetic recovery risk to a wakeful standing posture. CLINICAL RELEVANCE: Technique choices to facilitate individualized, atraumatic recovery of horses from general anesthesia are desirable. Use of IV propofol and xylazine to transition horses from desflurane anesthesia during sling recovery to standing posture may facilitate improved recovery management of high-injury risk equine patients requiring general anesthesia.


Assuntos
Anestesia por Inalação/veterinária , Anestésicos Inalatórios , Anestésicos Intravenosos , Cavalos , Imobilização/veterinária , Isoflurano/análogos & derivados , Propofol , Xilazina , Período de Recuperação da Anestesia , Animais , Desflurano , Feminino , Cavalos/cirurgia , Masculino , Monitorização Fisiológica/veterinária , Propofol/sangue
16.
Am J Vet Res ; 70(8): 956-63, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19645576

RESUMO

OBJECTIVE: To compare characteristics of horses recovering from 4 hours of desflurane anesthesia with and without immediate postanesthetic IV administration of propofol and xylazine. Animals-8 healthy horses (mean +/- SEM age, 6.6 +/- 1.0 years; mean body weight, 551 +/- 50 kg). PROCEDURES: Horses were anesthetized twice. Both times, anesthesia was induced with a combination of xylazine hydrochloride, diazepam, and ketamine hydrochloride and then maintained for 4 hours with desflurane in oxygen. Choice of postanesthetic treatment was randomly assigned via a crossover design such that each horse received an IV injection of propofol and xylazine or saline (0.9% NaCl) solution after the anesthetic episode. Recovery events were quantitatively and qualitatively assessed. Venous blood samples were obtained before and after anesthesia for determination of serum creatine kinase activity and plasma propofol concentration. RESULTS: Anesthetic induction and maintenance were unremarkable in all horses. Compared with administration of saline solution, postanesthetic administration of propofol and xylazine resulted in an increased interval to emergence from anesthesia but improved quality of recovery-related transition to standing. Compared with administration of saline solution, administration of propofol also delayed the rate of decrease of end-tidal concentrations of desflurane and carbon dioxide and added to conditions promoting hypoxemia and hypoventilation. CONCLUSIONS AND CLINICAL RELEVANCE: Propofol and xylazine administered IV to horses after 4 hours of desflurane anesthesia improved the quality of transition from lateral recumbency to standing but added potential for harmful respiratory depression during the postanesthetic period.


Assuntos
Agonistas alfa-Adrenérgicos/farmacologia , Período de Recuperação da Anestesia , Anestésicos Intravenosos/farmacologia , Cavalos/fisiologia , Isoflurano/análogos & derivados , Propofol/farmacologia , Xilazina/farmacologia , Agonistas alfa-Adrenérgicos/administração & dosagem , Anestésicos Inalatórios/administração & dosagem , Anestésicos Intravenosos/administração & dosagem , Animais , Dióxido de Carbono/metabolismo , Estudos Cross-Over , Desflurano , Injeções Intravenosas/veterinária , Isoflurano/administração & dosagem , Propofol/administração & dosagem , Propofol/sangue , Fatores de Tempo , Xilazina/administração & dosagem
17.
Phys Rev Lett ; 102(9): 096805, 2009 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-19392551

RESUMO

The polarization vector of the Rashba spin, which must be parallel to the two-dimensional (2D) plane in an ideal system, is found to change abruptly and definitely to the direction perpendicular to the surface at the K point of the Brillouin zone of a real hexagonal system, the Tl/Si(111)-(1x1) surface. This finding obtained experimentally by angle-resolved and spin-resolved photoemission measurements is fully confirmed by a first-principles theoretical calculation. We found that the abrupt rotation of the Rashba spin is simply understood by the 2D symmetry of the hexagonal structure.

19.
Am J Vet Res ; 65(8): 1042-6, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15334836

RESUMO

OBJECTIVE: To determine whether high intracranial pressure (ICP) during spontaneous ventilation (SV) in anesthetized horses coincides with an increase in intracranial elastance (ie, change in ICP per unit change of intracranial volume). ANIMALS: 6 adult horses. PROCEDURE: Anesthesia was induced and maintained in each horse for 5 hours with isoflurane at a constant dose equal to 1.2 times the minimum alveolar concentration. Direct ICP measurements were obtained by use of a strain gauge transducer inserted in the subarachnoid space, and arterial blood pressure was measured from a carotid artery. Physiologic responses were recorded after 15 minutes of normocapnic controlled ventilation (CV) and then after 10 minutes of SV. Aliquots (3 mL) of CSF were removed from each horse during SV until ICP returned to CV values. Slopes of pressure-volume curves yielded intracranial elastance. RESULTS: Intracranial elastance ranged from 0.2 to 3.7 mm Hg/mL after removal of the first aliquot of CSF Slopes of pressure-volume curves were largest following removal of the initial CSF aliquot, but shallow portions of curves were detected at relatively high ICPs (25 to 35 mm Hg). A second-order relationship between SV ICP and initial intracranial elastance was found. CONCLUSIONS AND CLINICAL RELEVANCE: In horses anesthetized with isoflurane, small changes in intracranial volume can cause large changes in ICP Increased intracranial elastance could further exacerbate preexisting intracranial hypertension. However, removal of small volumes of CSF may cause rapid compensatory replacement from other intracranial compartments, which suggests steady-state maintenance of an increase in intracranial volume during isoflurane anesthesia in horses.


Assuntos
Anestésicos Inalatórios/farmacologia , Cavalos/fisiologia , Pressão Intracraniana , Isoflurano/farmacologia , Análise de Variância , Animais , Pressão Sanguínea/efeitos dos fármacos , Dióxido de Carbono/sangue , Dióxido de Carbono/líquido cefalorraquidiano , Pressão do Líquido Cefalorraquidiano/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Oxigênio/sangue , Oxigênio/líquido cefalorraquidiano , Ventilação Pulmonar/efeitos dos fármacos
20.
Am J Vet Res ; 64(11): 1444-8, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14620783

RESUMO

OBJECTIVE: To test the hypothesis that isoflurane-anesthetized horses during controlled ventilation and spontaneous ventilation exhibit temporal changes in cerebral hemodynamics, as measured by intracranial pressure and cerebral perfusion pressure, that reflect temporal changes in systemic arterial pressure. ANIMALS: 6 healthy adult horses. PROCEDURE: Horses were anesthetized in left lateral recumbency with 1.57% isoflurane in O2 for 5 hours in 2 experiments by use of either controlled ventilation (with normocapnia) or spontaneous ventilation (with hypercapnia) in a randomized crossover design. Intracranial pressure was measured with a subarachnoid strain-gauge transducer. Carotid artery pressure, central venous pressure, airway pressures, blood gases, and minute ventilation also were measured. RESULTS: Intracranial pressure during controlled ventilation significantly increased during constant dose isoflurane anesthesia and thus contributed to decreasing cerebral perfusion pressure. Intracranial pressure was initially higher during spontaneous ventilation than during controlled ventilation, but this difference disappeared over time; no significant differences in cerebral perfusion pressures were observed between horses that had spontaneous or controlled ventilation. CONCLUSIONS AND CLINICAL RELEVANCE: Cerebral hemodynamics and their association with ventilation mode are altered over time in isoflurane-anesthetized horses and could contribute to decreased cerebral perfusion during prolonged anesthesia.


Assuntos
Circulação Cerebrovascular/fisiologia , Cavalos/fisiologia , Pressão Intracraniana/fisiologia , Isoflurano/farmacologia , Anestésicos Inalatórios/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Artérias Carótidas/efeitos dos fármacos , Artérias Carótidas/fisiologia , Feminino , Hemodinâmica/efeitos dos fármacos , Hemodinâmica/fisiologia , Masculino
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