RESUMO
OBJECTIVE: Pedicle screws placed into C2 necessitate a thorough understanding of this bone's unique anatomy. Although multiple landmarks and measurements have been used by surgeons, these are often varied in the literature with no consensus. Herein, we studied one recently proposed landmark using the nutrient foramina of the posterior aspect of C2 for pedicle screw placement. METHODS: On 19 (38 sides) C2 dry bone specimens, the presence, size, location, and distance from the midline of the nutrient foramina found at the junction between the isthmus and lamina were documented and measured. In addition, to discern the source of the artery entering such foramina, an injected adult cadaver was dissected. RESULTS: The number of foramina ranged from 0-5 with a mean of 1.84. On 3 sides, no foramina were identified. The mean diameter of the foramina was 0.57 mm. The location of the foramina was at position 1 on 9.5% of sides, position 2 on 66.4% of sides, and position 3 on 24.1% of sides. The mean horizontal distance from the midline of the spinous process of C2 to the foramina was 25.17 mm. In the cadaveric specimen, the source of the artery entering these C2 nutrient foramina was found to be distal branches of the deep cervical artery. CONCLUSIONS: We found the nutrient foramina of the C2 laminae are useful for pedicle screw placement. However, there are minor variations of the number and position of these structures. Lastly, on the basis of our study, 7.9% (n = 3) of sides will not have such foramina.
Assuntos
Pontos de Referência Anatômicos , Vértebra Cervical Áxis/cirurgia , Idoso , Antropometria , Vértebra Cervical Áxis/anatomia & histologia , Cadáver , Humanos , Masculino , Parafusos PedicularesRESUMO
Respiratory syncytial virus (RSV) belongs to the family Paramyxoviridae and is the single most important cause of serious lower respiratory tract infections in young children, yet no highly effective treatment or vaccine is available. Through a CX3C chemokine motif (182CWAIC186) in the G protein, RSV binds to the corresponding chemokine receptor, CX3CR1. Since RSV binding to CX3CR1 contributes to disease pathogenesis, we investigated whether a mutation in the CX3C motif by insertion of an alanine, A186, within the CX3C motif, mutating it to CX4C (182CWAIAC187), which is known to block binding to CX3CR1, might decrease disease. We studied the effect of the CX4C mutation in two strains of RSV (A2 and r19F) in a mouse challenge model. We included RSV r19F because it induces mucus production and airway resistance, two manifestations of RSV infection in humans, in mice. Compared to wild-type (wt) virus, mice infected with CX4C had a 0.7 to 1.2 log10-fold lower virus titer in the lung at 5 days postinfection (p.i.) and had markedly reduced weight loss, pulmonary inflammatory cell infiltration, mucus production, and airway resistance after challenge. This decrease in disease was not dependent on decrease in virus replication but did correspond to a decrease in pulmonary Th2 and inflammatory cytokines. Mice infected with CX4C viruses also had higher antibody titers and a Th1-biased T cell memory response at 75 days p.i. These results suggest that the CX4C mutation in the G protein could improve the safety and efficacy of a live attenuated RSV vaccine.IMPORTANCE RSV binds to the corresponding chemokine receptor, CX3CR1, through a CX3C chemokine motif (182CWAIC186) in the G protein. RSV binding to CX3CR1 contributes to disease pathogenesis; therefore, we investigated whether a mutation in the CX3C motif by insertion of an alanine, A186, within the CX3C motif, mutating it to CX4C (182CWAIAC187), known to block binding to CX3CR1, might decrease disease. The effect of this mutation and treatment with the F(ab')2 form of the anti-RSV G 131-2G monoclonal antibody (MAb) show that mutating the CX3C motif to CX4C blocks much of the disease and immune modulation associated with the G protein and should improve the safety and efficacy of a live attenuated RSV vaccine.
Assuntos
Quimiocinas CX3C/metabolismo , Proteínas de Ligação ao GTP/genética , Mutação , Infecções por Vírus Respiratório Sincicial/imunologia , Vacinas contra Vírus Sincicial Respiratório/efeitos adversos , Vacinas contra Vírus Sincicial Respiratório/imunologia , Vírus Sincicial Respiratório Humano/imunologia , Animais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Quimiocinas CX3C/genética , Quimiocinas CX3C/imunologia , Feminino , Proteínas de Ligação ao GTP/química , Proteínas de Ligação ao GTP/imunologia , Humanos , Memória Imunológica , Pulmão/virologia , Camundongos , Camundongos Endogâmicos BALB C , Domínios e Motivos de Interação entre Proteínas , Vacinas contra Vírus Sincicial Respiratório/química , Vacinas contra Vírus Sincicial Respiratório/genética , Vírus Sincicial Respiratório Humano/genética , Vírus Sincicial Respiratório Humano/fisiologia , Células Th1 , Células Th2 , Vacinas Atenuadas/química , Vacinas Atenuadas/genética , Vacinas Atenuadas/imunologia , Replicação ViralRESUMO
The immune system undergoes age-associated changes known as immunosenescence, resulting in increased susceptibility to infections, cancers and autoimmunity in the aged. The basis of our understanding of immunosenescence has been derived primarily from studies examining intrinsic defects within many of the cells of the immune system. While these studies have provided insight into the mechanisms of immunosenescence, a picture is now emerging that the stromal microenvironment within lymphoid organs also contributes significantly to the age-associated decline of immune function. These extrinsic defects appear to impact the functional activity of immune cells and may offer a potential target to recover immune activity. Indeed, rejuvenation studies which have targeted the stromal niche have restored immune function in aged successfully, highlighting the impact of the microenvironment towards the aetiology of immunosenescence.
Assuntos
Envelhecimento/imunologia , Microambiente Celular/imunologia , Sistema Imunitário , Imunossenescência , Células Estromais/imunologia , Animais , Humanos , Regeneração/imunologiaRESUMO
Heterozygous germline mutations in PHOX2B, a transcriptional regulator of sympathetic neuronal differentiation, predispose to diseases of the sympathetic nervous system, including neuroblastoma and congenital central hypoventilation syndrome (CCHS). Although the PHOX2B variants in CCHS largely involve expansions of the second polyalanine repeat within the C-terminus of the protein, those associated with neuroblastic tumors are nearly always frameshift and truncation mutations. To test the hypothesis that the neuroblastoma-associated variants exert their effects through loss or gain of protein-protein interactions, we performed a large-scale yeast two-hybrid screen using both wild-type (WT) and six different mutant PHOX2B proteins against over 10 000 human genes. The neuronal calcium sensor protein HPCAL1 (VILIP-3) exhibited strong binding to WT PHOX2B and a CCHS-associated polyalanine expansion mutant but only weakly or not at all to neuroblastoma-associated frameshift and truncation variants. We demonstrate that both WT PHOX2B and the neuroblastoma-associated R100L missense and the CCHS-associated alanine expansion variants induce nuclear translocation of HPCAL1 in a Ca(2+)-independent manner, while the neuroblastoma-associated 676delG frameshift and K155X truncation mutants impair subcellular localization of HPCAL1, causing it to remain in the cytoplasm. HPCAL1 did not appreciably influence the ability of WT PHOX2B to transactivate the DBH promoter, nor did it alter the decreased transactivation potential of PHOX2B variants in 293T cells. Abrogation of the PHOX2B-HPCAL1 interaction by shRNA knockdown of HPCAL1 in neuroblastoma cells expressing PHOX2B led to impaired neurite outgrowth with transcriptional profiles indicative of inhibited sympathetic neuronal differentiation. Our results suggest that certain PHOX2B variants associated with neuroblastoma pathogenesis, because of their inability to bind to key interacting proteins such as HPCAL1, may predispose to this malignancy by impeding the differentiation of immature sympathetic neurons.
Assuntos
Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Mutação , Neuroblastoma/genética , Neuroblastoma/metabolismo , Neurocalcina/genética , Neurocalcina/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Cálcio/metabolismo , Diferenciação Celular/genética , Linhagem Celular , Linhagem Celular Tumoral , Núcleo Celular/genética , Núcleo Celular/metabolismo , Citoplasma/genética , Citoplasma/metabolismo , Células HEK293 , Humanos , Neuroblastoma/patologia , Peptídeos/genética , Peptídeos/metabolismo , Regiões Promotoras Genéticas , Ligação Proteica , Mapas de Interação de Proteínas , Ativação TranscricionalRESUMO
INTRODUCTION: Hematopoietic stem cell transplantation, which requires accurate enumeration of stem cells, is routinely used in clinical settings. Flow cytometry provides a qualitative and quantitative assessment of CD34⺠cells. Precision, linearity, and stability of the novel BD™ Stem Cell Enumeration (SCE) Kit were evaluated on two flow cytometry platforms using a modified ISHAGE gating strategy and including a viability dye for data acquisition and analysis. METHODS: Precision and linearity were evaluated on BD FACSCanto™ II and BD FACSCalibur™ systems. Stability was evaluated on the BD FACSCanto II system. Precision was tested using both high and low controls. Linearity was evaluated using dilutions from CD34⺠cell pools, while stability was evaluated using fresh leukapheresis specimens. RESULTS: Both systems showed precision with limited variability in absolute counts and percentages of viable CD34⺠cells. The linearity range of viable CD34⺠cells in both systems was established at 0-1000 cells/µL, showing a linear relationship (R² = 0.99). Stability of CD34⺠cells in mobilized leukapheresis samples was confirmed up to 24 h after collection and up to 60 min after the end of stain/lyse procedures. CONCLUSION: The BD SCE Kit on both flow cytometry systems shows consistent and reproducible results.
Assuntos
Citometria de Fluxo/normas , Células-Tronco Hematopoéticas/citologia , Kit de Reagentes para Diagnóstico/normas , Antígenos CD34/metabolismo , Biomarcadores/metabolismo , Calibragem , Contagem de Células/normas , Sobrevivência Celular , Células-Tronco Hematopoéticas/metabolismo , Humanos , Leucaférese , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Elevated concentrations of 25-hydroxyvitamin D (25(OH)-D) were diagnosed in captive short-beaked echidnas (Tachyglossus aculeatus) from three different zoological facilities within Australia. RESULTS: The mean serum 25(OH)-D concentration in the wild echidnas was 24.7 nmol/L and was significantly higher in captive echidnas from all three facilities: Facility 1, mean 335.5 nmol/L (P < 0.001); Facility 2, mean 187.2 nmol/L (P = 0.003); Facility 3, mean 194 nmol/L (P = 0.005). Animals did not appear to have clinical manifestations of vitamin D toxicosis. The increased serum 25(OH)-D concentration was attributed to excessive dietary intake and a reduction in the amount of vitamin D(3) in the diet of echidnas from Facility 1 resulted in a marked decrease in the serum 25(OH)-D concentrations (mean 33 nmol/L). The reduction in serum 25(OH)-D concentration was statistically significant (P = 0.002) and the resulting concentrations were similar to those of wild echidnas (P = 0.212). CONCLUSION: It is not known what effect an elevated serum 25(OH)-D concentration has on echidnas.
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Fenômenos Fisiológicos da Nutrição Animal/fisiologia , Dieta/veterinária , Tachyglossidae/sangue , Vitamina D/análogos & derivados , Animais , Animais Selvagens , Animais de Zoológico , Feminino , Masculino , Necessidades Nutricionais , Valores de Referência , Vitamina D/sangueRESUMO
BACKGROUND: There is good evidence from studies conducted in a single-centre research setting for the efficacy of graded motor imagery (GMI) treatment, a complex physiotherapy intervention, to reduce pain in long-standing complex regional pain syndrome (CRPS). However, whether GMI is effective in clinical practice is not established. AIM: To establish whether GMI is effective in clinical practice. METHODS: We undertook a prospective audit of GMI treatment at two UK centres with a special interest in the management of patients with CRPS. All patients received GMI, in conjunction with a range of other 'best practice' physical and psychological interventions. RESULTS: The patients' average pain intensities did not improve with treatment [centre 1: n = 20, pre-post numeric rating scale (NRS) difference 0.6 [confidence interval (CI) -0.3 to 1.5]; centre 2: n = 12, pre-post NRS difference 0.2 (CI: -0.9 to 1.2)]. Patients at centre 1 reported significant functional improvement. Improved performance on left/right judgement replicated in both centres seen in the clinical trials. CONCLUSIONS: The failure of our real-world implementation of GMI suggests that better understanding of both the GMI methodology and its interaction with other treatment methods is required to ensure that GMI research results can be translated into clinical practice. Our results highlight challenges with the translation of complex interventions for chronic pain conditions into clinical practice.
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Síndromes da Dor Regional Complexa/terapia , Imagens, Psicoterapia/métodos , Manejo da Dor/métodos , Adulto , Afeto , Causalgia/diagnóstico , Causalgia/psicologia , Causalgia/terapia , Síndromes da Dor Regional Complexa/diagnóstico , Síndromes da Dor Regional Complexa/psicologia , Intervalos de Confiança , Avaliação da Deficiência , Determinação de Ponto Final , Feminino , Lateralidade Funcional/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Prospectivos , Desempenho Psicomotor , Tempo de Reação , Distrofia Simpática Reflexa/diagnóstico , Distrofia Simpática Reflexa/psicologia , Distrofia Simpática Reflexa/terapia , Falha de Tratamento , Adulto JovemRESUMO
Influenza virus infection is considered a major worldwide public health problem. Seasonal infections with the most common influenza virus strains (e.g., H1N1) can usually be resolved, but they still cause a high rate of mortality. The factors that influence the outcome of the infection remain unclear. Here, we show that deficiency of interleukin (IL)-6 or IL-6 receptor is sufficient for normally sublethal doses of H1N1 influenza A virus to cause death in mice. IL-6 is necessary for resolution of influenza infection by protecting neutrophils from virus-induced death in the lung and by promoting neutrophil-mediated viral clearance. Loss of IL-6 results in persistence of the influenza virus in the lung leading to pronounced lung damage and, ultimately, death. Thus, we demonstrate that IL-6 is a vital innate immune cytokine in providing protection against influenza A infection. Genetic or environmental factors that impair IL-6 production or signaling could increase mortality to influenza virus infection.
Assuntos
Vírus da Influenza A Subtipo H1N1/imunologia , Interleucina-6/metabolismo , Pulmão/imunologia , Neutrófilos/imunologia , Infecções por Orthomyxoviridae/imunologia , Animais , Morte Celular/genética , Morte Celular/imunologia , Células Cultivadas , Citoproteção/genética , Humanos , Vírus da Influenza A Subtipo H1N1/patogenicidade , Interleucina-6/genética , Interleucina-6/imunologia , Pulmão/patologia , Pulmão/virologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Animais , Ativação de Neutrófilo/genética , Neutrófilos/patologia , Neutrófilos/virologia , Receptores de Interleucina-6/genética , Receptores de Interleucina-6/imunologia , Receptores de Interleucina-6/metabolismo , Carga Viral/genéticaRESUMO
To investigate the role of donor-specific indirect pathway T cells in renal transplant tolerance, we analyzed responses in peripheral blood of 45 patients using the trans-vivo delayed-type hypersensitivity assay. Subjects were enrolled into five groups-identical twin, clinically tolerant (TOL), steroid monotherapy (MONO), standard immunosuppression (SI) and chronic rejection (CR)-based on transplant type, posttransplant immunosuppression and graft function. The indirect pathway was active in all groups except twins but distinct intergroup differences were evident, corresponding to clinical status. The antidonor indirect pathway T effector response increased across patient groups (TOL < MONO < SI < CR; p < 0.0001) whereas antidonor indirect pathway T regulatory response decreased (TOL > MONO = SI > CR; p < 0.005). This pattern differed from that seen in circulating naïve B-cell numbers and in a cross-platform biomarker analysis, where patients on monotherapy were not ranked closest to TOL patients, but rather were indistinguishable from chronically rejecting patients. Cross-sectional analysis of the indirect pathway revealed a spectrum in T-regulatory:T-effector balance, ranging from TOL patients having predominantly regulatory responses to CR patients having predominantly effector responses. Therefore, the indirect pathway measurements reflect a distinct aspect of tolerance from the recently reported elevation of circulating naïve B cells, which was apparent only in recipients off immunosuppression.
Assuntos
Linfócitos B/imunologia , Rejeição de Enxerto/imunologia , Tolerância Imunológica/imunologia , Transplante de Rim/imunologia , Linfócitos T/imunologia , Doadores de Tecidos , Humanos , Terapia de Imunossupressão , Prognóstico , Transdução de SinaisRESUMO
This is a report of a study day held in London on 3 March 2010 to discuss measures with which to meet the nutritional requirements of patients with epidermolysis bullosa (EB). Members of national and international multidisciplinary teams (MDTs) caring for patients with EB attended this event. The study day focused on four challenging aspects of management intimately associated with nutritional status in EB, necessitating close cooperation between MDT members: iron-deficiency anaemia, gastrostomy placement and feeding, muscle mass and mobility, and dental health. The study day provided a unique forum for dietitians, doctors, nurses, physiotherapists, psychologists, psychotherapists, dentists, dental hygienists and occupational therapists to share knowledge and debate problems common to all who strive to promote best practice in this rare and complex group of conditions.
Assuntos
Epidermólise Bolhosa/dietoterapia , Apoio Nutricional/métodos , Adolescente , Adulto , Anemia Ferropriva/prevenção & controle , Criança , Prestação Integrada de Cuidados de Saúde/organização & administração , Serviços de Saúde Bucal , Epidermólise Bolhosa/complicações , Epidermólise Bolhosa/fisiopatologia , Exercício Físico , Feminino , Gastrostomia/métodos , Humanos , Comunicação Interdisciplinar , Masculino , Necessidades Nutricionais , Estado Nutricional , Adulto JovemRESUMO
The Substance Abuse Mental Health Services Administration has promoted HIV testing and counseling as an evidence-based practice. Nevertheless, adoption of HIV testing in substance abuse treatment programs has been slow. This article describes the experience of a substance abuse treatment agency where, following participation in a clinical trial, the agency implemented an HIV testing and counseling program. During the trial, a post-trial pilot, and early implementation the agency identified challenges and developed strategies to overcome barriers to adoption of the intervention. Their experience may be instructive for other treatment providers seeking to implement an HIV testing program. Lessons learned encompassed the observed acceptability of testing and counseling to clients, the importance of a "champion" and staff buy-in, the necessity of multiple levels of community and agency support and collaboration, the ability to streamline staff training, the need for a clear chain of command, the need to develop program specific strategies, and the requirement for sufficient funding. An examination of costs indicated that some staff time may not be adequately reimbursed by funding sources for activities such as adapting the intervention, start-up training, ongoing supervision and quality assurance, and overhead costs.
Assuntos
Aconselhamento , Medicina Baseada em Evidências/métodos , Infecções por HIV/diagnóstico , Centros de Tratamento de Abuso de Substâncias/estatística & dados numéricos , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Feminino , Humanos , Masculino , Projetos Piloto , Desenvolvimento de Programas/métodos , Avaliação de Programas e Projetos de Saúde , South Carolina , Fatores de Tempo , Estados Unidos , United States Substance Abuse and Mental Health Services AdministrationRESUMO
Hippocalcin is a Ca(2+)-binding protein that belongs to a family of neuronal Ca(2+)sensors and is a key mediator of many cellular functions including synaptic plasticity and learning. However, the molecular mechanisms involved in hippocalcin signalling remain illusive. Here we studied whether glutamate receptor activation induced by locally applied or synaptically released glutamate can be decoded by hippocalcin translocation. Local AMPA receptor activation resulted in fast hippocalcin-YFP translocation to specific sites within a dendritic tree mainly due to AMPA receptor-dependent depolarization and following Ca(2+)influx via voltage-operated calcium channels. Short local NMDA receptor activation induced fast hippocalcin-YFP translocation in a dendritic shaft at the application site due to direct Ca(2+)influx via NMDA receptor channels. Intrinsic network bursting produced hippocalcin-YFP translocation to a set of dendritic spines when they were subjected to several successive synaptic vesicle releases during a given burst whereas no translocation to spines was observed in response to a single synaptic vesicle release and to back-propagating action potentials. The translocation to spines required Ca(2+)influx via synaptic NMDA receptors in which Mg(2+) block is relieved by postsynaptic depolarization. This synaptic translocation was restricted to spine heads and even closely (within 1-2 microm) located spines on the same dendritic branch signalled independently. Thus, we conclude that hippocalcin may differentially decode various spatiotemporal patterns of glutamate receptor activation into site- and time-specific translocation to its targets. Hippocalcin also possesses an ability to produce local signalling at the single synaptic level providing a molecular mechanism for homosynaptic plasticity.
Assuntos
Hipocalcina/metabolismo , Hipocampo/metabolismo , Neurônios/metabolismo , Receptores de Glutamato/metabolismo , Sinapses/metabolismo , Animais , Cálcio/metabolismo , Canais de Cálcio/metabolismo , Espinhas Dendríticas/efeitos dos fármacos , Espinhas Dendríticas/metabolismo , Ácido Glutâmico/farmacologia , Hipocampo/efeitos dos fármacos , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Neurônios/efeitos dos fármacos , Ratos , Sinapses/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Transmissão Sináptica/fisiologiaRESUMO
AIMS: Increasing evidence suggests a role for oxidative damage to DNA in brain ageing and in neurodegenerative disorders, including Alzheimer's disease. Most studies have focussed on the reduced capacity for DNA repair by neurones, and have not taken into account the effect of oxidative stress on astrocytes, and their contribution to pathology. METHODS: We examined levels of oxidative stress, DNA damage and DNA repair mechanisms in astrocytes in a population-based sample derived from the Medical Research Council Cognitive Function and Ageing Neuropathology Study. RESULTS: We demonstrate wide variation in parameters for oxidative stress and DNA damage in astrocytes in the ageing population. We show that there is a significant reduction (P = 0.002) in the lipid peroxidation marker malondialdehyde with increasing Braak stage in Alzheimer's disease. Furthermore, we demonstrate that expression of the DNA damage-associated molecules H2AX and DNA-dependent protein kinase do not increase with increasing Braak stage, rather there is evidence of a nonsignificant reduction in DNA-dependent protein kinase expression by neurones and astrocytes, and in H2AX by neurones with increasing levels of Alzheimer's type pathology. CONCLUSIONS: These findings suggest that the changes in oxidative stress and the astrocyte DNA damage response are not accounted for as an accumulating effect due to established Alzheimer-type pathology. We hypothesize that astrocyte damage, leading to impaired function, may contribute to the development of ageing brain pathology in some individuals.
Assuntos
Envelhecimento/patologia , Astrócitos/patologia , Encéfalo/patologia , Dano ao DNA/fisiologia , Estresse Oxidativo/fisiologia , 8-Hidroxi-2'-Desoxiguanosina , Idoso , Doença de Alzheimer/patologia , Astrócitos/metabolismo , Western Blotting , Proteína Quinase Ativada por DNA/biossíntese , Desoxiguanosina/análogos & derivados , Desoxiguanosina/biossíntese , Histonas/biossíntese , Humanos , Imuno-Histoquímica , Neurônios/metabolismo , Neurônios/patologiaRESUMO
OBJECTIVE: To identify and gain an understanding of the influenza viruses circulating in wild birds in Australia. DESIGN: A total of 16,303 swabs and 3782 blood samples were collected and analysed for avian influenza (AI) viruses from 16,420 wild birds in Australia between July 2005 and June 2007. Anseriformes and Charadriiformes were primarily targeted. PROCEDURES: Cloacal, oropharyngeal and faecal (environmental) swabs were tested using polymerase chain reaction (PCR) for the AI type A matrix gene. Positive samples underwent virus culture and subtyping. Serum samples were analysed using a blocking enzyme-linked immunosorbent assay for influenza A virus nucleoprotein. RESULTS: No highly pathogenic AI viruses were identified. However, 164 PCR tests were positive for the AI type A matrix gene, 46 of which were identified to subtype. A total of five viruses were isolated, three of which had a corresponding positive PCR and subtype identification (H3N8, H4N6, H7N6). Low pathogenic AI H5 and/or H7 was present in wild birds in New South Wales, Tasmania, Victoria and Western Australia. Antibodies to influenza A were also detected in 15.0% of the birds sampled. CONCLUSIONS: Although low pathogenic AI virus subtypes are currently circulating in Australia, their prevalence is low (1.0% positive PCR). Surveillance activities for AI in wild birds should be continued to provide further epidemiological information about circulating viruses and to identify any changes in subtype prevalence.
Assuntos
Anseriformes , Doenças das Aves/virologia , Charadriiformes , Vírus da Influenza A/isolamento & purificação , Influenza Aviária/virologia , Animais , Anticorpos Antivirais/sangue , Austrália/epidemiologia , Doenças das Aves/epidemiologia , DNA Viral/química , DNA Viral/genética , Ensaio de Imunoadsorção Enzimática/veterinária , Vírus da Influenza A/genética , Influenza Aviária/sangue , Influenza Aviária/epidemiologia , Reação em Cadeia da Polimerase/veterinária , Prevalência , Proteínas da Matriz Viral/química , Proteínas da Matriz Viral/genéticaRESUMO
Developmental exposure to noninherited maternal antigens (NIMA) exerts a tolerizing or sensitizing influence on clinical transplantation in humans and experimental animals. The aim of this study was to determine if strain and gender differences influence the NIMA effect. Six different mouse strain backcross matings of F(1) females with homozygous males ('NIMA backcross') and corresponding control breedings of F1 males with homozygous females were performed. H-2 homozygous offspring underwent heterotopic heart transplantation from fully allogeneic donors expressing noninherited H-2 antigens. A NIMA tolerizing effect on heart allograft outcome was found in three of six breeding models. In all three cases, the tolerizing antigens were from an H-2(d+) strain. The tolerogenic effect was greatest in male as compared with female recipients. Offspring from the three breeding models in which no tolerance was seen, appeared to be sensitized based on poorer graft survival, or enhanced T- or B-cell responses to the noninherited H-2(b or k) antigens. Significantly higher percentages of maternal antigen(+) cells were found in the peripheral blood of tolerant versus nontolerant strains of backcross mice prior to transplant. Our findings imply that transplants are predisposed to tolerance or rejection due to recipient developmental history and immunogenetic background.
Assuntos
Antígenos/metabolismo , Transplante de Coração/métodos , Linfócitos T Reguladores/imunologia , Transplante Homólogo/métodos , Animais , Linfócitos B/imunologia , Linfócitos B/metabolismo , Cruzamentos Genéticos , Feminino , Antígenos H-2/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Linfócitos T/imunologia , Linfócitos T/metabolismo , Tolerância ao TransplanteRESUMO
BACKGROUND: Epidermolysis bullosa (EB) is a group of inherited disorders characterized by skin and mucous membrane fragility. Gastrointestinal (GI) complications have been described in many types of EB and are responsible for significant morbidity. OBJECTIVES: To delineate the nature and frequency of GI complications in a large cohort of paediatric patients with EB and to postulate why some complications occur more commonly in some specific subtypes. METHODS: The case notes of 223 children with EB seen at a national referral centre were examined retrospectively for the presence of GI symptoms, investigations and interventions. RESULTS: GI complications were present in 130/223 (58%) of all patients. In EB simplex, constipation and gastro-oesophageal reflux (GOR) were frequently observed. In junctional EB, failure to thrive and protein-losing enteropathy (PLE) were the prominent GI manifestations. Constipation was common in patients with dystrophic EB (DEB) requiring laxatives and in some cases fibre supplementation. GOR affected three-quarters of those with recessive DEB, two-thirds also having significant oesophageal strictures. Over half of patients with recessive DEB required gastrostomy insertion. Diarrhoea affected a small but significant proportion of children with recessive DEB with macroscopic and/or microscopic changes of colitis in the majority. CONCLUSION: GI problems in EB are very common with subtype specificity for some of these complications. The occurrence of diarrhoea, PLE and colitis in the context of EB has not been highlighted previously, and may arise secondarily to antigenic exposure in the gut lumen as a result of mucosal fragility.
Assuntos
Epidermólise Bolhosa Distrófica/complicações , Epidermólise Bolhosa Simples/complicações , Epidermólise Bolhosa Juncional/complicações , Gastroenteropatias/etiologia , Adolescente , Criança , Pré-Escolar , Colite/etiologia , Constipação Intestinal/etiologia , Progressão da Doença , Feminino , Humanos , Lactente , Masculino , FenótipoRESUMO
RATIONALE: Functional magnetic resonance imaging (fMRI) in rats can non-invasively identify brain regions activated by physiological stimuli and the effects of pharmacological intervention on these responses. OBJECTIVES: This study was conducted to investigate the effects of systemic administration of the mu-opioid receptor agonist morphine on whole brain functional signal intensity in anaesthetised rats; to investigate whether pre-treatment with the opioid receptor antagonist naloxone blocks the effects of morphine; to determine whether pre-treatment with morphine attenuates noxious-evoked changes in whole brain functional signal intensity. METHODS: Continuous whole brain fMRI scanning was used to study brain signal intensity prior to, and following, systemic administration of morphine (5 mg/kg, n=7), systemic administration of naloxone (1 mg/kg) and morphine (n=8). Effects of pre-treatment with saline (n=5) or morphine (5 mg/kg, n=5) on formalin (5%, intraplantar)-evoked changes in signal intensity were determined. Data were processed using SMP99 with fixed-effects analysis (p<0.05). RESULTS: Morphine produced significant positive bilateral increases in signal intensity in the cingulate cortex, amygdala, thalamus, hypothalamus and PAG (p<0.05), and these effects were blocked by naloxone. Intraplantar injection of formalin produced a significant positive increase in signal intensity in the cingulate cortex, somatosensory cortex, amygdala, thalamus, hypothalamus and PAG (p<0.05). Morphine attenuated formalin-evoked increases in signal intensity in the PAG, amygdala, hypothalamus and cingulate cortex. CONCLUSION: Our data demonstrate that morphine modulates noxious-evoked changes in signal intensity in discrete brain regions. fMRI studies in rats are able to identify specific brain regions involved in the pharmacological modification of physiologically evoked changes in regional brain activation.
Assuntos
Mapeamento Encefálico , Encéfalo/irrigação sanguínea , Encéfalo/fisiologia , Imageamento por Ressonância Magnética , Dor/fisiopatologia , Receptores Opioides/fisiologia , Analgésicos Opioides/farmacologia , Análise de Variância , Animais , Encéfalo/efeitos dos fármacos , Interações Medicamentosas , Formaldeído/efeitos adversos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Morfina/farmacologia , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Dor/induzido quimicamente , Medição da Dor/métodos , Ratos , Ratos Sprague-Dawley , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/fisiologiaRESUMO
Abnormal corticosteroid release is extensively associated with mood disorders. This association may result from the toxic actions of endogenous corticosteroids which can induce apoptosis of hippocampal neurons. Similarly, dexamethasone, a synthetic corticosteroid, can induce lethal and sublethal damage to rat hippocampal and striatal neurons and can result in steroid-induced psychoses in humans. The experiments reported here tested the hypothesis that pre-treatment with oestrogen would also attenuate dexamethasone-induced neuronal damage as oestrogens have neuroprotective actions against a variety of insults and falling levels of oestrogen are associated with increased vulnerability to mood disorders. Male Sprague-Dawley rats received three systemic injections which were a combination of vehicle, 17-beta-oestradiol (0.2 mg/kg, s.c.), the oestrogen receptor antagonist tamoxifen (10 mg/kg, s.c.) and dexamethasone (0.7 mg/kg, i.p.) and were killed 24 h after the final injection. Injections of dexamethasone (when preceded by vehicle injections) resulted in elevated levels of apoptosis and sub-lethal damage, as demonstrated by reduced levels of microtubule-associated protein-2-immunopositive neurons, in the striatum and hippocampus. This damage was regional with the dorsomedial caudate putamen and the dentate gyrus and CA1 and CA3 hippocampal sub-fields being particularly affected. Pretreatment with oestrogen substantially attenuated the dexamethasone-induced neuronal damage. This oestrogen-induced neuronal protection was in turn virtually eliminated by giving an initial injection of tamoxifen. These results suggest, therefore, that oestrogens can protect from corticosteroid-induced neuronal damage via an oestrogen receptor-mediated process.
Assuntos
Corpo Estriado/efeitos dos fármacos , Estradiol/metabolismo , Hipocampo/efeitos dos fármacos , Degeneração Neural/prevenção & controle , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/metabolismo , Animais , Apoptose/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Corpo Estriado/metabolismo , Dexametasona , Estradiol/administração & dosagem , Antagonistas de Estrogênios/farmacologia , Glucocorticoides , Hipocampo/metabolismo , Técnicas Histológicas , Masculino , Proteínas Associadas aos Microtúbulos/efeitos dos fármacos , Proteínas Associadas aos Microtúbulos/metabolismo , Degeneração Neural/induzido quimicamente , Degeneração Neural/tratamento farmacológico , Neurônios/metabolismo , Fármacos Neuroprotetores/administração & dosagem , Ratos , Ratos Sprague-Dawley , Tamoxifeno/farmacologiaRESUMO
The mammalian Toll-like receptor 4, TLR4, is an important component in the innate immune response to gram-negative bacterial infection. The role of TLR4 in antiviral immunity has been largely unexplored. In this study, the in vivo immune responses to respiratory syncytial virus (RSV) and influenza virus infection were examined in TLR4-deficient (C57BL/10ScNCr) and TLR4-expressing (C57BL/10Sn) mice. TLR4-deficient mice challenged with RSV, but not influenza virus, exhibited impaired natural killer (NK) cell and CD14(+) cell pulmonary trafficking, deficient NK cell function, impaired interleukin-12 expression, and impaired virus clearance compared to mice expressing TLR4. These findings suggest that Toll signaling pathways have an important role in innate immunity to RSV.