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1.
J Clin Exp Dent ; 12(9): e888-e891, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32994880

RESUMO

Benign nerve sheath tumours include perineuriomas, schwannomas and neurofibromas. Hybrid schwannoma-perineurioma represents a cutaneous, subcutaneous or occasionally intra-osseous tumour with schwannian cytomorphology and perineurioma-like architecture consisting of a mixture of both types of cells. These tumours can develop at any age and there is no gender-predilection. Tongue is the most frequently affected site, followed by palate, mouth floor, jugal mucosa, lips and, more rarely, mandible. We present a case of hybrid tumour with schwannoma-perineurioma morphology located on the right mandibular body (intra-osseous) of a 54-year-old female patient. The tumour was symptomatic and evolving for six months. Microscopically, it was encapsulated and highly cellularised, presenting fascicular aspect and exhibiting scant mitotic activity. The tumour consisted of distinct cellular populations involving fusiform cells, cells with wavy and hyperchromatic nucleus or even epithelioid cells. Positive immunostaining for S-100 and epithelial membrane antigen (EMA) was observed. The lesion was completely removed under general anaesthesia, with the patient showing no clinical or radiographic sign of relapse after two-year follow-up. Despite the limited knowledge on the pathogenesis of Hybrid Schwannoma-Perineurioma, these tumours seem to present a non-aggressive biological behaviour. Conservative surgery provides adequate solution without recurrence, even after a long-term follow-up. Key words:Nerve sheath tumours, Schwannoma, Perineurioma, Immunohistochemistry.

2.
Rev. Fac. Med. (Bogotá) ; 68(3): 446-452, July-Sept. 2020. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1143734

RESUMO

Abstract Introduction: Medicinal plants have been traditionally used to cure or alleviate infectious and non-infectious diseases. They are widely accepted due to their low cost and low toxicity indexes. These plants are frequently used in cases involving skin irritation, superficial wounds, insect bites, and snake bites. Objective: To compile available evidence on the main therapeutic uses and phytochemical components of Cnidoscolus aconitifolius (popularly known as chaya), a plant that grows in tropical regions of Mexico and Central America. Materials and methods: A literature review of studies on C. aconitifolius published until 2017 was conducted in the BIREME, PubMed/Medline, Elsevier and SciELO databases. Descriptors "Cnidoscolus" and "aconitifolius" were used for the literature search, and no language restrictions were applied. Results: 82 articles were retrieved after completing the initial search. Once the studies were filtered by title (descriptors in the title) and duplicates were removed, 18 articles were reviewed. Based on the information found, it was possible to confirm that this plant has multiple health benefits. Conclusions: The traditional therapeutic use of Cnidoscolus aconitifolius is backed by scientific evidence. Therefore, further research aimed at identifying new phytochemical properties of this plant should be conducted to establish alternative therapies for treating different conditions.


Resumen Introducción. El uso tradicional de plantas medicinales para tratar diferentes enfermedades, ya sean infecciosas o no, es ampliamente aceptado debido a su bajo costo y sus bajos índices de toxicidad. Estas plantas son frecuentemente usadas en casos que involucran irritaciones de la piel, heridas superficiales, picaduras de insectos y mordeduras de víboras. Objetivo. Recopilar la información disponible sobre los principales usos terapéuticos y los componentes fitoquímicos de Cnidoscolus aconitifolius, una planta conocida popularmente como chaya y que crece en regiones tropicales de México y Centroamérica. Materiales y métodos. Se realizó una revisión de la literatura sobre C. aconitifolius publicada hasta 2017 en las bases de datos BIREME, PubMed/Medline, Elsevier y SciELO. Para la búsqueda se emplearon los descriptores "Cnidoscolus" y "aconitifolius", y no se aplicaron filtros de idioma. Resultados. Se identificaron 82 artículos luego de completar la búsqueda inicial. Después de filtrar los estudios por título (presencia de descriptores de búsqueda en el título) y remover duplicados, se incluyeron 18 artículos en la revisión. De acuerdo a la información encontrada, fue posible confirmar que esta planta ofrece diversos beneficios para la salud. Conclusiones. El uso terapéutico tradicional de la chaya está sustentado por evidencia científica, por lo que se sugiere realizar más investigaciones centradas en la identificación de nuevas propiedades fitoquímicas de esta planta y, así, establecer alternativas terapéuticas para distintas afecciones.

3.
Acta neurol. colomb ; 36(3): 150-167, jul.-set. 2020. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1130709

RESUMO

SUMMARY INTRODUCTION: Chronic daily headache is a high impact entity in the general population. Although chronic migraine and tension-type headache are the most frequent conditions, it is necessary to consider hemicrania continua and new daily persistent headache as part of the differential diagnoses to perform a correct therapeutic approach. OBJECTIVE: To make recommendations for the treatment of chronic daily headache of primary origin METHODOLOGY: The Colombian Association of Neurology, by consensus and Grade methodology (Grading of recommendations, assessment, development and evaluation), presents the recommendations for the preventive treatment of each of the entities of the daily chronic headache of primary origin group. RESULTS: For the treatment of chronic migraine, the Colombian Association of Neurology recommends onabotulinum toxin A, erenumab, topiramate, flunarizine, amitriptyline, and naratriptan. In chronic tension-type headache the recommended therapeutic options are amitriptyline, imipramine, venlafaxine and mirtazapine. Topiramate, melatonin, and celecoxib for the treatment of hemicrania continua. Options for new daily persistent headache include gabapentin and doxycycline. The recommendations for inpatient treatment of patients with chronic daily headache and the justifications for performing neural blockades as a therapeutic complement are also presented. CONCLUSION: The therapeutic recommendations for the treatment of chronic daily headache based on consensus methodology and Grade System are presented.


RESUMEN INTRODUCCIÓN: La cefalea crónica diaria es una entidad de alto impacto en la población general. Aunque la migraña crónica y la cefalea tipo tensión son las condiciones más frecuentes, es necesario considerar la hemicránea continua y la cefalea diaria persistente de novo como parte de los diagnósticos diferenciales para realizar un enfoque terapéutico correcto. OBJETIVO: Hacer recomendaciones para el tratamiento de la cefalea crónica diaria de origen primario METODOLOGÍA: La Asociación Colombiana de Neurología, mediante consenso y metodología GRADE (Grading of Reccomendations, Assesment, Development and Evaluation), presenta las recomendaciones para el tratamiento preventivo de cada una de las entidades del grupo de la cefalea crónica diaria de origen primario. RESULTADOS: Para el tratamiento de la migraña crónica, la Asociación Colombiana de Neurología recomienda onabotulinum toxina A, erenumab, galcanezumab, fremanezumab, topiramato, flunarizina, amitriptilina y naratriptan. En cefalea tipo tensional crónica las opciones terapéuticas recomendadas son amitriptilina, imipramina, venlafaxina y mirtazapina. Para el tratamiento de la hemicránea continua topiramato, melatonina y celecoxib. Las opciones para cefalea diaria persistente de novo incluyen gabapentin y doxiciclina. Se presentan adicionalmente las recomendaciones para el tratamiento intrahospitalario de los pacientes con cefalea crónica diaria y las justificaciones para la realización de bloqueos neurales como complemento terapéutico. CONCLUSIÓN: se presentan las recomendaciones terapéuticas para el tratamiento de la cefalea crónica diaria basado en metodología de consenso y sistema GRADE.

4.
Genes Immun ; 21(2): 136-141, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31591503

RESUMO

The transcription factor STAT5 is critical for peripheral NK-cell survival, proliferation, and cytotoxic function. STAT5 refers to two highly related proteins, STAT5A and STAT5B. In this study, we verified the importance of STAT5A isoform for NK cells. We characterized an incidental chemically induced W484G mutation in the Stat5a gene and found that this mutation was associated with a reduction of STAT5A protein expression. Closer examination of NK-cell subsets from Stat5a mutant mice showed marked reductions in NK-cell number and maturation. IL-15 treatment of Stat5a mutant NK cells exhibited defective induction of both STAT5 and mTOR signaling pathways and reduced expression of granzyme B and IFN-γ. Finally, we observed that Stat5a mutant mice revealed more tumor growth upon injection of RMA-S tumor cell line. Overall, our results demonstrate that the W484G mutation in the linker domain of STAT5A is sufficient to compromise STAT5A function in NK-cell homeostasis, responsiveness, and tumoricidal function.

5.
PLoS One ; 14(4): e0215002, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30958846

RESUMO

In homes, problems in daily functioning of older people often occur in the bathroom, especially in the transfers to the toilet and/or shower/bath. Assistive products have the potential to maximise functional independence (i.e. performance without assistance from another person) in everyday activities; however, more research is needed to better understand the impact of this technology on independence in the transfers in the bathroom. Additionally, little is known about the role of the environmental factors in the process of implementing bathroom adaptations. Therefore, this cross-sectional study aimed to examine the relationship between the use of assistive products and independence in the transfers in the bathroom. The secondary objective was to determine the role of the environmental factors in predicting the implementation of bathroom adaptations. 193 community-dwelling older adults with disabilities in the basic activities of daily life, who requested public long-term care services in Spain, were included. Data was collected in the participant´s homes using a standardised assessment procedure. There was no significant association between the number of categories of assistive products used in the toilet transfer and the independent performance of this task. In a multivariate model, the number of categories of assistive products used in the transfer to shower/bath was positively associated with the independent performance of this transfer (OR = 2.59, 95%CI = 1.48-4.53; p = 0.001). A multivariate analysis revealed that social functioning was significantly associated with the implementation of a bathroom adaptation; social risk was lower in participants who made an adaptation (OR = 0.76, 95%CI = 0.63-0.93; p = 0.006). Assistive products may play an important role in promoting independence in the bathroom. Assistive product needs should be addressed when planning community-based interventions aimed at improving daily life. Moreover, social functioning had a strong influence on the installation of bathroom adaptations, suggesting the importance of paying special attention to social factors in the home adaptations planning process.


Assuntos
Atividades Cotidianas , Pessoas com Deficiência , Autocuidado , Equipamentos de Autoajuda , Toaletes , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Espanha
6.
J Immunol ; 202(5): 1479-1493, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30683700

RESUMO

Herpes simplex encephalitis (HSE), caused by HSV type 1 (HSV-1) infection, is an acute neuroinflammatory condition of the CNS and remains the most common type of sporadic viral encephalitis worldwide. Studies in humans have shown that susceptibility to HSE depends in part on the genetic make-up of the host, with deleterious mutations in the TLR3/type I IFN axis underlying some cases of childhood HSE. Using an in vivo chemical mutagenesis screen for HSV-1 susceptibility in mice, we identified a susceptible pedigree carrying a causal truncating mutation in the Rel gene (RelC307X ), encoding for the NF-κB transcription factor subunit c-Rel. Like Myd88-/- and Irf3-/- mice, RelC307X mice were susceptible to intranasal HSV-1 infection. Reciprocal bone marrow transfers into lethally irradiated hosts suggested that defects in both hematopoietic and CNS-resident cellular compartments contributed together to HSE susceptibility in RelC307X mice. Although the RelC307X mutation maintained cell-intrinsic antiviral control, it drove increased apoptotic cell death in infected fibroblasts. Moreover, reduced numbers of CD4+CD25+Foxp3+ T regulatory cells, and dysregulated NK cell and CD4+ effector T cell responses in infected RelC307X animals, indicated that protective immunity was also compromised in these mice. In the CNS, moribund RelC307X mice failed to control HSV-1 viral replication in the brainstem and cerebellum, triggering cell death and elevated expression of Ccl2, Il6, and Mmp8 characteristic of HSE neuroinflammation and pathology. In summary, our work implicates c-Rel in both CNS-resident cell survival and lymphocyte responses to HSV-1 infection and as a novel cause of HSE disease susceptibility in mice.


Assuntos
Sistema Nervoso Central/imunologia , Encefalite por Herpes Simples/imunologia , Inflamação/imunologia , Replicação Viral/imunologia , Animais , Chlorocebus aethiops , Encefalite por Herpes Simples/virologia , Inflamação/virologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células Vero
7.
Artigo em Inglês | MEDLINE | ID: mdl-29998539

RESUMO

Nonpharmacologic therapies such as occupational therapy (OT) are promising for people with Alzheimer's disease (AD). However, more research is needed to better understand the effectiveness of home-based OT programs. This pilot study aimed to assess the effects of a home-based, high-intensity and multicomponent OT intervention on the activities of daily living of people with AD in Spain. The secondary objective was to examine its impact on the cognitive functions. A multiple-baseline intrasubject design was used. Twenty-one community-dwelling older adults with mild AD (mean age 78.6 years) and their primary caregivers participated in a 12-week home-based OT program. This intervention was replicated for 8 weeks after a 1.5-month intervention withdrawal period. The intervention followed a holistic, biopsychosocial and client-centred approach and consisted of the following components: meaningful activities/tasks, cognitive stimulation, activation of psychomotor and sensory skills, home modification, caregiver counselling and training in daily living skills. Functional independence was the primary outcome (Barthel Index). The cognitive functions were assessed by the Loewenstein Occupational Therapy Cognitive Assessment-Geriatric (LOTCA-G). Data were analysed using nonparametric tests. Main results showed that after completing the OT program, 6.5 months after the moment of inclusion, the level of functional independence improved significantly and the effect size was large. Moreover, there was a significant moderate-to-substantial improvement in several cognitive functions after each of the two intervention periods: place orientation, time orientation and attention/concentration. In summary, the findings give a great deal of information as a basis for further research. This study provides evidence that an intensive home-based OT intervention has a positive influence on daily activities and some cognitive functions, suggesting that this program may be beneficial as a nonpharmacological supplementary tool in health and social care for people with AD living in the community.

8.
Sci Rep ; 8(1): 8446, 2018 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-29855523

RESUMO

Activation of the inflammasome pathway is crucial for effective intracellular host defense. The mitochondrial network plays an important role in inflammasome regulation but the mechanisms linking mitochondrial homeostasis to attenuation of inflammasome activation are not fully understood. Here, we report that the Parkinson's disease-associated mitochondrial serine protease HtrA2 restricts the activation of ASC-dependent NLRP3 and AIM2 inflammasomes, in a protease activity-dependent manner. Consistently, disruption of the protease activity of HtrA2 results in exacerbated NLRP3 and AIM2 inflammasome responses in macrophages ex vivo and systemically in vivo. Mechanistically, we show that the HtrA2 protease activity regulates autophagy and controls the magnitude and duration of inflammasome signaling by preventing prolonged accumulation of the inflammasome adaptor ASC. Our findings identify HtrA2 as a non-redundant mitochondrial quality control effector that keeps NLRP3 and AIM2 inflammasomes in check.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Serina Peptidase 2 de Requerimento de Alta Temperatura A/metabolismo , Inflamassomos/metabolismo , Mitocôndrias/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Animais , Autofagia , Células da Medula Óssea/citologia , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Caspase 1/deficiência , Caspase 1/genética , Caspase 1/metabolismo , Proteínas de Ligação a DNA/antagonistas & inibidores , Serina Peptidase 2 de Requerimento de Alta Temperatura A/deficiência , Serina Peptidase 2 de Requerimento de Alta Temperatura A/genética , Proteínas Inibidoras de Apoptose/metabolismo , Interleucina-1beta/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores
9.
Methods Mol Biol ; 1656: 209-227, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28808973

RESUMO

The clinical course of any viral infection greatly differs in individuals. This variation results from various viral, host, and environmental factors. The identification of host genetic factors influencing inter-individual variation in susceptibility to several pathogenic viruses has tremendously increased our understanding of the mechanisms and pathways required for immunity. Next-generation sequencing of whole exomes represents a powerful tool in biomedical research. In this chapter, we briefly introduce whole-exome sequencing in the context of genetic approaches to identify host susceptibility genes to viral infections. We then describe general aspects of the workflow for whole-exome sequence analysis together with the tools and online resources that can be used to identify and annotate variant calls, and then prioritize them for their potential association to phenotypes of interest.


Assuntos
Exoma , Predisposição Genética para Doença , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Viroses/genética , Linhagem Celular , Humanos , Viroses/imunologia , Vírus/genética , Vírus/imunologia
10.
Nat Immunol ; 18(1): 54-63, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27721430

RESUMO

Genes and pathways in which inactivation dampens tissue inflammation present new opportunities for understanding the pathogenesis of common human inflammatory diseases, including inflammatory bowel disease, rheumatoid arthritis and multiple sclerosis. We identified a mutation in the gene encoding the deubiquitination enzyme USP15 (Usp15L749R) that protected mice against both experimental cerebral malaria (ECM) induced by Plasmodium berghei and experimental autoimmune encephalomyelitis (EAE). Combining immunophenotyping and RNA sequencing in brain (ECM) and spinal cord (EAE) revealed that Usp15L749R-associated resistance to neuroinflammation was linked to dampened type I interferon responses in situ. In hematopoietic cells and in resident brain cells, USP15 was coexpressed with, and functionally acted together with the E3 ubiquitin ligase TRIM25 to positively regulate type I interferon responses and to promote pathogenesis during neuroinflammation. The USP15-TRIM25 dyad might be a potential target for intervention in acute or chronic states of neuroinflammation.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Encefalomielite Autoimune Experimental/imunologia , Malária Cerebral/imunologia , Inflamação Neurogênica/imunologia , Fatores de Transcrição/metabolismo , Proteases Específicas de Ubiquitina/metabolismo , Animais , Proteínas de Ligação a DNA/genética , Encefalomielite Autoimune Experimental/tratamento farmacológico , Células HEK293 , Humanos , Imunidade Inata , Interferon Tipo I/metabolismo , Malária Cerebral/tratamento farmacológico , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Terapia de Alvo Molecular , Glicoproteína Mielina-Oligodendrócito/imunologia , Inflamação Neurogênica/tratamento farmacológico , Fragmentos de Peptídeos/imunologia , Plasmodium berghei/imunologia , Fatores de Transcrição/genética , Proteases Específicas de Ubiquitina/genética
12.
Crit Care ; 20(1): 323, 2016 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-27724931

RESUMO

BACKGROUND: The disproportion between the large organ demand and the low number of transplantations performed represents a serious public health problem worldwide. Reducing the loss of transplantable organs from deceased potential donors as a function of cardiac arrest (CA) may contribute to an increase in organ donations. Our purpose was to test the hypothesis that a goal-directed protocol to guide the management of deceased donors may reduce the losses of potential brain-dead donors (PBDDs) due to CA. METHODS: The quality improvement project included 27 hospitals that reported deceased donors prospectively to the Transplant Center of the State of Santa Catarina, Brazil. All deceased donors reported prospectively between May 2012 and April 2014 were analyzed. Hospitals were encouraged to use the VIP approach checklist during the management of PBDDs. The checklist was composed of the following goals: protocol duration 12-24 hours, temperature > 35 °C, mean arterial pressure ≥ 65 mmHg, diuresis 1-4 ml/kg/h, corticosteroids, vasopressin, tidal volume 6-8 ml/kg, positive end-expiratory pressure 8-10 cmH2O, sodium < 150 mEq/L, and glycemia < 180 mg/dl. A logistic regression model was used to identify predictors of CA. RESULTS: There were 726 PBDD notifications, of which 324 (44.6) were actual donors, 141 (19.4 %) CAs, 226 (31.1 %) family refusals, and 35 (4.8 %) contraindications. Factors associated with CA reduction included use of the checklist (odds ratio (OR) 0.43, p < 0.001), maintenance performed inside the ICU (OR 0.49, p = 0.013), and vasopressin administration (OR 0.56, p = 0.04). More than three interventions had association with less CAs (OR 0.19, p < 0.001). After 24 months, CAs decreased from 27.3 % to 14.6 % (p = 0.002), reaching 12.1 % in the following two 4-month periods (p < 0.001). Simultaneous increases in organ recovered per donor and in actual donors were observed. CONCLUSIONS: A quality improvement program based on education and the use of a goal checklist for the management of potential donors inside the ICU is strongly associated with a decrease in donor losses and an increase in organs recovered per donor.


Assuntos
Morte Encefálica , Tomada de Decisão Clínica/métodos , Objetivos , Parada Cardíaca/prevenção & controle , Doadores de Tecidos , Obtenção de Tecidos e Órgãos/normas , Adolescente , Adulto , Morte Encefálica/diagnóstico , Protocolos Clínicos , Parada Cardíaca/diagnóstico , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Melhoria de Qualidade/normas , Obtenção de Tecidos e Órgãos/métodos , Adulto Jovem
13.
PLoS One ; 10(10): e0139192, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26447794

RESUMO

Historical discourses about the Caribbean often chronicle West African and European influence to the general neglect of indigenous people's contributions to the contemporary region. Consequently, demographic histories of Caribbean people prior to and after European contact are not well understood. Although archeological evidence suggests that the Lesser Antilles were populated in a series of northward and eastern migratory waves, many questions remain regarding the relationship of the Caribbean migrants to other indigenous people of South and Central America and changes to the demography of indigenous communities post-European contact. To explore these issues, we analyzed mitochondrial DNA and Y-chromosome diversity in 12 unrelated individuals from the First Peoples Community in Arima, Trinidad, and 43 unrelated Garifuna individuals residing in St. Vincent. In this community-sanctioned research, we detected maternal indigenous ancestry in 42% of the participants, with the remainder having haplotypes indicative of African and South Asian maternal ancestry. Analysis of Y-chromosome variation revealed paternal indigenous American ancestry indicated by the presence of haplogroup Q-M3 in 28% of the male participants from both communities, with the remainder possessing either African or European haplogroups. This finding is the first report of indigenous American paternal ancestry among indigenous populations in this region of the Caribbean. Overall, this study illustrates the role of the region's first peoples in shaping the genetic diversity seen in contemporary Caribbean populations.


Assuntos
Cromossomos Humanos Y , DNA Mitocondrial/genética , Variação Genética , Grupo com Ancestrais do Continente Africano/genética , Grupo com Ancestrais do Continente Asiático/genética , Região do Caribe , Hibridização Genômica Comparativa , DNA Mitocondrial/análise , DNA Mitocondrial/classificação , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Genética Populacional , Haplótipos , Humanos , Masculino , Filogenia , Polimorfismo de Nucleotídeo Único , São Vicente e Granadinas , Trinidad e Tobago
14.
Occup Ther Int ; 22(1): 1-9, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25308069

RESUMO

The main aim of this paper is to assess the effects of an occupational therapy home programme in Spain on 23 people who had had stroke (mean age 61.17 years). The programme was made up of a set of activities and techniques of physical, cognitive, social and functional nature aimed at preventing, maintaining and/or rehabilitating the abilities affected of people who had had stroke. A multiple-baseline intrasubject design and replication with a treatment withdrawal period to check whether the effects of the programme remained was applied. The results show a significant statistical improvement, concerning not only the participants' cognitive skills through Loewenstein Occupational Therapy Cognitive Assessment Battery - Second Edition but also their functional independence as assessed by the Barthel Index. Despite the low number of participants, being one of the limitations of our study, the results support the need to carry out research about the effectiveness of rehabilitation treatments in the home with the goal to plan how public healthcare systems should tackle them and how to improve those already being used.


Assuntos
Serviços de Assistência Domiciliar , Terapia Ocupacional , Reabilitação do Acidente Vascular Cerebral , Atividades Cotidianas , Idoso , Cognição , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Programas e Projetos de Saúde , Espanha , Acidente Vascular Cerebral/psicologia , Resultado do Tratamento
15.
PLoS Pathog ; 9(9): e1003637, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24068938

RESUMO

Herpes simplex encephalitis (HSE) is a lethal neurological disease resulting from infection with Herpes Simplex Virus 1 (HSV-1). Loss-of-function mutations in the UNC93B1, TLR3, TRIF, TRAF3, and TBK1 genes have been associated with a human genetic predisposition to HSE, demonstrating the UNC93B-TLR3-type I IFN pathway as critical in protective immunity to HSV-1. However, the TLR3, UNC93B1, and TRIF mutations exhibit incomplete penetrance and represent only a minority of HSE cases, perhaps reflecting the effects of additional host genetic factors. In order to identify new host genes, proteins and signaling pathways involved in HSV-1 and HSE susceptibility, we have implemented the first genome-wide mutagenesis screen in an in vivo HSV-1 infectious model. One pedigree (named P43) segregated a susceptible trait with a fully penetrant phenotype. Genetic mapping and whole exome sequencing led to the identification of the causative nonsense mutation L3X in the Receptor-type tyrosine-protein phosphatase C gene (Ptprc(L3X)), which encodes for the tyrosine phosphatase CD45. Expression of MCP1, IL-6, MMP3, MMP8, and the ICP4 viral gene were significantly increased in the brain stems of infected Ptprc(L3X) mice accounting for hyper-inflammation and pathological damages caused by viral replication. Ptprc(L3X) mutation drastically affects the early stages of thymocytes development but also the final stage of B cell maturation. Transfer of total splenocytes from heterozygous littermates into Ptprc(L3X) mice resulted in a complete HSV-1 protective effect. Furthermore, T cells were the only cell population to fully restore resistance to HSV-1 in the mutants, an effect that required both the CD4⁺ and CD8⁺ T cells and could be attributed to function of CD4⁺ T helper 1 (Th1) cells in CD8⁺ T cell recruitment to the site of infection. Altogether, these results revealed the CD45-mediated T cell function as potentially critical for infection and viral spread to the brain, and also for subsequent HSE development.


Assuntos
Códon sem Sentido , Encefalite por Herpes Simples/genética , Herpes Simples/imunologia , Herpesvirus Humano 1/imunologia , Imunidade Celular , Antígenos Comuns de Leucócito/metabolismo , Células Th1/imunologia , Animais , Tronco Encefálico/imunologia , Tronco Encefálico/metabolismo , Tronco Encefálico/patologia , Tronco Encefálico/virologia , Células Cultivadas , Cruzamentos Genéticos , Suscetibilidade a Doenças , Encefalite por Herpes Simples/etiologia , Feminino , Estudo de Associação Genômica Ampla , Herpes Simples/patologia , Herpes Simples/fisiopatologia , Herpes Simples/virologia , Antígenos Comuns de Leucócito/genética , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Mutagênese , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Neurônios/imunologia , Neurônios/metabolismo , Neurônios/patologia , Neurônios/virologia , Análise de Sobrevida , Células Th1/metabolismo , Células Th1/patologia , Células Th1/virologia
16.
PLoS One ; 7(2): e31012, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22363534

RESUMO

Cerebral malaria (CM) is a lethal neurological complication of malaria. We implemented a genome-wide screen in mutagenized mice to identify host proteins involved in CM pathogenesis and whose inhibition may be of therapeutic value. One pedigree (P48) segregated a resistance trait whose CM-protective effect was fully penetrant, mapped to chromosome 8, and identified by genome sequencing as homozygosity for a mis-sense mutation (W81R) in the FERM domain of Janus-associated kinase 3 (Jak3). The causative effect of Jak3(W81R) was verified by complementation testing in Jak3(W81R/-) double heterozygotes that were fully protected against CM. Jak3(W81R) homozygotes showed defects in thymic development with depletion of CD8(+) T cell, B cell, and NK cell compartments, and defective T cell-dependent production of IFN-γ. Adoptive transfer of normal splenocytes abrogates CM resistance in Jak3(W81R) homozygotes, an effect attributed to the CD8(+) T cells. Jak3(W81R) behaves as a dominant negative variant, with significant CM resistance of Jak3(W81R/+) heterozygotes, compared to CM-susceptible Jak3(+/+) and Jak3(+/-) controls. CM resistance in Jak3(W81R/+) heterozygotes occurs in presence of normal T, B and NK cell numbers. These findings highlight the pathological role of CD8(+) T cells and Jak3-dependent IFN-γ-mediated Th1 responses in CM pathogenesis.


Assuntos
Genes Dominantes/genética , Janus Quinase 3/genética , Malária Cerebral/enzimologia , Malária Cerebral/prevenção & controle , Mutação/genética , Transferência Adotiva , Sequência de Aminoácidos , Animais , Cromossomos de Mamíferos/genética , Citrobacter/fisiologia , Etilnitrosoureia , Feminino , Predisposição Genética para Doença , Heterozigoto , Homozigoto , Imunofenotipagem , Janus Quinase 3/química , Malária Cerebral/genética , Malária Cerebral/imunologia , Masculino , Camundongos , Camundongos Mutantes Neurológicos , Dados de Sequência Molecular , Mycobacterium/fisiologia , Linhagem , Fenótipo , Plasmodium berghei/fisiologia , Estrutura Terciária de Proteína , Baço/patologia
17.
Arq Neuropsiquiatr ; 70(1): 40-4, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22218472

RESUMO

OBJECTIVE: To devise and test the reliability and validity of a brief headache diary in a series of Colombian patients with chronic daily headache. METHODS: The study was designed in five stages: selection of domains (group of patients and experts); initial devising of the items (writing group); identification of non-understandable items (n=20); assessment of internal consistency (n=100); assessment of validity and assessment of sensitivity to change during seven consecutive days (n=25, 175 observations). RESULTS: Five domains were selected: headache presence, severity and length of pain, analgesics intake, and missing workdays. The headache diary is internally consistent (≈75% of rotated variance), correlates with the medical interview (Spearman's rho and Kendall's tau over 0.8 for each domain) and it has an adequate and stable sensitivity and specificity (82 to 96%). CONCLUSIONS: This headache diary is a reliable and valid instrument and represents the most important features affecting Colombian patients with chronic daily headache.


Assuntos
Transtornos da Cefaleia/diagnóstico , Registros Médicos/normas , Cefaleia do Tipo Tensional/diagnóstico , Adolescente , Adulto , Analgésicos/uso terapêutico , Colômbia , Feminino , Transtornos da Cefaleia/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Inquéritos e Questionários , Cefaleia do Tipo Tensional/tratamento farmacológico , Fatores de Tempo , Adulto Jovem
18.
Arq. neuropsiquiatr ; 70(1): 40-44, Jan. 2012. graf, tab
Artigo em Inglês | LILACS | ID: lil-612662

RESUMO

OBJECTIVE: To devise and test the reliability and validity of a brief headache diary in a series of Colombian patients with chronic daily headache. METHODS: The study was designed in five stages: selection of domains (group of patients and experts); initial devising of the items (writing group); identification of non-understandable items (n=20); assessment of internal consistency (n=100); assessment of validity and assessment of sensitivity to change during seven consecutive days (n=25, 175 observations). RESULTS: Five domains were selected: headache presence, severity and length of pain, analgesics intake, and missing workdays. The headache diary is internally consistent (≈75 percent of rotated variance), correlates with the medical interview (Spearman's rho and Kendall's tau over 0.8 for each domain) and it has an adequate and stable sensitivity and specificity (82 to 96 percent). CONCLUSIONS: This headache diary is a reliable and valid instrument and represents the most important features affecting Colombian patients with chronic daily headache.


OBJETIVO: Diseñar y testar la validez y reproducibilidad de un diario de cefalea en una serie de pacientes Colombianos con cefalea crónica diaria. MÉTODOS: El estudio fue diseñado en cinco fases: selección de los dominios (grupo de pacientes y expertos); diseño inicial de los ítems (grupo redactor); identificación de ítems no comprensibles (n=20); determinación de la consistencia interna (n=100); determinación de la validez y la sensibilidad al cambio durante siete días consecutivos (n=25, 175 observaciones). RESULTADOS: Fueron seleccionados cinco dominios: presencia, severidad y duración del dolor, ingesta de analgésicos y días laborales perdidos. El diario tiene una adecuada consistencia interna (≈75 por ciento de la varianza), se correlaciona con la entrevista médica (rho de Spearman y tau de Kendall >0.8 para cada dominio) y tiene sensibilidad y especificidad estables y satisfactorias (82 a 96 por ciento). CONCLUSIONES: Este diario de cefalea es un instrumento confiable y registra las principales características de las cefaleas en pacientes con cefalea crónica diaria.


Assuntos
Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Transtornos da Cefaleia/diagnóstico , Registros Médicos/normas , Cefaleia do Tipo Tensional/diagnóstico , Analgésicos/uso terapêutico , Colômbia , Transtornos da Cefaleia/tratamento farmacológico , Medição da Dor , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Inquéritos e Questionários , Fatores de Tempo , Cefaleia do Tipo Tensional/tratamento farmacológico
19.
J Immunol ; 186(11): 6398-405, 2011 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-21525387

RESUMO

Coxsackievirus B3 (CVB3) infection is the most common cause of viral myocarditis. The pathogenesis of viral myocarditis is strongly controlled by host genetic factors. Although certain indispensable components of immunity have been identified, the genes and pathways underlying natural variation between individuals remain unclear. Previously, we isolated the viral myocarditis susceptibility 1 (Vms1) locus on chromosome 3, which influences pathogenesis. We hypothesized that confirmation and further study of Vms1 controlling CVB3-mediated pathology, combined with pathway analysis and consomic mapping approaches, would elucidate both pathological and protective mechanisms accounting for natural variation in response to CVB3 infection. Vms1 was originally mapped to chromosome 3 using a segregating cross between susceptible A/J and resistant B10.A mice. To validate Vms1, C57BL/6J-Chr 3(A)/NaJ (a chromosome substitution strain that carries a diploid A/J chromosome 3) were used to replicate susceptibility compared with resistant C57BL/6J (B6). A second segregating F2 cross was generated between these, confirming both the localization and effects of Vms1. Microarray analysis of the four strains (A/J, B10.A, C57BL/6J, and C57BL/6J-Chr 3(A)/NaJ) illuminated a core program of response to CVB3 in all strains that is comprised mainly of IFN-stimulated genes. Microarray analysis also revealed strain-specific differential expression programs and genes that may be prognostic or diagnostic of susceptibility to CVB3 infection. A combination of analyses revealed very strong evidence for the existence and location of Vms1. Differentially expressed pathways were identified by microarray, and candidate gene analysis revealed Fpgt, H28, and Tnni3k as likely candidates for Vms1.


Assuntos
Infecções por Coxsackievirus/genética , Predisposição Genética para Doença/genética , Miocardite/genética , Locos de Características Quantitativas/genética , Animais , Mapeamento Cromossômico/métodos , Infecções por Coxsackievirus/imunologia , Enterovirus Humano B/imunologia , Enterovirus Humano B/fisiologia , Feminino , Perfilação da Expressão Gênica , Variação Genética , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Masculino , Camundongos , Camundongos Endogâmicos A , Camundongos Endogâmicos C57BL , Antígenos de Histocompatibilidade Menor/genética , Miocardite/imunologia , Miocárdio/metabolismo , Miocárdio/patologia , Nucleotidiltransferases/genética , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas Quinases/genética , Proteínas Serina-Treonina Quinases , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/genética , Fatores de Tempo
20.
Rev. cient. (Maracaibo) ; 20(4): 430-435, jul. 2010. ilus, graf, tab
Artigo em Espanhol | LILACS-Express | LILACS | ID: lil-631090

RESUMO

El consumo de alimentos con residuos de oxitetraciclina (OTC) puede causar diversos efectos tóxicos en el humano. Con la finalidad de extraer y cuantificar dichos residuos en matrices biológicas, como carne de pollo, se han desarrollado diversos métodos. Dentro de los métodos propuestos el más empleado es la extracción líquido-líquido por ser sencillo, rápido y económico. Este tipo de extracción fue aplicada por Furusawa para OTC en pollo, empleando acetonitrilo/hexano en una proporción 5:4 obteniendo una recuperación del 88%. Este trabajo tuvo como objetivo estudiar la recuperación de OTC en carne de pollo ensayada por Furusawa, aumentando la proporción del solvente polar con respecto al hexano (2:1), para su posterior cuantificación mediante cromatografía líquida de alta resolución (HPLC). Para ello se utilizaron 24 porciones de 1 g de tejido muscular perteneciente al muslo de 3 pollos libres de antibióticos, las cuales se fortificaron con soluciones estándares de OTC de 0,1; 0,2; 0,5 y 1 µg/g, obteniendo 6 muestras fortificadas con cada concentración, las cuales fueron almacenadas por 12 horas a 4°C. La extracción del antibiótico se llevó a cabo con acetonitrilo/hexano en proporciones 5:4 y 2:1. En cada caso se evaluó la recuperación, precisión y sensibilidad. Tanto para la proporción 5:4 como 2:1, la concentración de 0,2 µg/g presentó la mayor recuperación, siendo 91,5 y 92,5%, respectivamente; sin embargo, al aumentar la concentración de OTC disminuyó la recuperación. La precisión se incrementó a la concentración de 0,5 µg/g, sin embargo, al duplicar la concentración a 1 µg/g disminuyó dicho parámetro. El límite de detección obtenido para la extracción de OTC con acetonitrilo/hexano en proporción 2:1 fue de 0,09 µg/g. Se recomienda realizar una desproteinización de la muestra previo al proceso de extracción.


Consumption of food that contains oxytetracycline (OTC) residues may produce several toxic effects in human beings. In order to extract and quantify such residues in biological matrices, like chicken meat, several methods have been developed. Among these methods, liquid-liquid extraction is the mostly used, because is quick, simple and inexpensive. This extraction method was applied by Furusawa for OTC in chicken, using acetonitrile/hexanes in a 5:4 proportion, obtaining an 88% recovery. The objective of this research was to study extraction of OTC in chicken meat assayed by Furusawa, raising polar solvent proportion in relation to hexanes (2:1), and further quantifying by means of high performance liquid chromatography (HPLC). Twenty four portions of 1 g from 3 OTC free chickens were fortified with OTC standard solutions: 0.1, 0.2, 0.5 and 1 µg/g, obtaining 6 fortified samples for each concentration, stored for 12 hours at 4°C. Antibiotic extraction was performed using acetonitrile/hexanes in 5:4 and 2:1 proportions. Recovery, precision and sensitivity were analyzed in all samples. Either 5:4 or 2:1 proportions, 0.2 µg/g concentration obtained the higher recovery, 91.5 and 92.5%, respectively; however when OTC concentrations raised, recovery became lower. Precision increased at 0.5 µg/g concentration, but, fell down when concentration duplicated: 1 µg/mL. Detection limit obtained for OTC extraction using acetonitrile/hexanes in 2:1 proportion were 0.09 µg/g. Deproteinization is recommended previously to extraction process.

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