ABSTRACT
BACKGROUND Calpains are proteins belonging to the multi-gene family of calcium-dependent cysteine peptidases that undergo tight on/off regulation, and uncontrolled proteolysis of calpains is associated with severe human pathologies. Calpain orthologues are expanded and diversified in the trypanosomatids genome. OBJECTIVES Here, we characterised calpains in Leishmania braziliensis, the main causative agent of cutaneous leishmaniasis in Brazil. METHODS/FINDINGS In total, 34 predicted calpain-like genes were identified. After domain structure evaluation, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) during in vitro metacyclogenesis revealed (i) five genes with enhanced expression in the procyclic stage, (ii) one augmented gene in the metacyclic stage, and (iii) one procyclic-exclusive transcript. Western blot analysis revealed that an antibody against a consensus-conserved peptide reacted with multiple calpain-like proteins, which is consistent with the multi-gene family characteristic. Flow cytometry and immunocytochemistry analyses revealed the presence of calpain-like molecules mainly in the cytoplasm, to a lesser extent in the plasma membrane, and negligible levels in the nucleus, which are all consistent with calpain localisation. Eventually, the calpain inhibitor MDL28170 was used for functional studies revealing (i) a leishmaniostatic effect, (ii) a reduction in the association index in mouse macrophages, (iii) ultra-structural alterations conceivable with autophagy, and (iv) an enhanced expression of the virulence factor GP63. CONCLUSION This report adds novel insights into the domain structure, expression, and localisation of L. braziliensis calpain-like molecules.
Subject(s)
Animals , Mice , Leishmania braziliensis/chemistry , Calpain/genetics , Macrophages, Peritoneal/metabolism , Genome, Protozoan/genetics , Leishmania braziliensis/genetics , Leishmania braziliensis/metabolism , Leishmania braziliensis/ultrastructure , Immunohistochemistry , Calpain/drug effects , Calpain/metabolism , Calpain/ultrastructure , Cysteine Proteinase Inhibitors/pharmacology , Gene Expression Regulation , Blotting, Western , Reverse Transcriptase Polymerase Chain Reaction , Virulence Factors , Microscopy, Electron, Transmission , Dipeptides/pharmacology , Flow Cytometry , Mice, Inbred BALB CABSTRACT
Objetivo. Comparar la salud, uso de servicios sanitarios y necesidad insatisfecha de atención médica (NIAM) entre inmigrantes y nativos del sureste español. Material y métodos. Estudio transversal de dos muestras representativas de población: inmigrante (n=1150) y nativa (n=1303; Encuesta Nacional de Salud). Se creó una única base de datos con ponderación específica para cada muestra y se estimaron razones de prevalencia (RP) mediante regresión multivariante. Resultados. Marroquíes, ecuatorianos y europeos del este (EE) declararon peor salud que los nativos (RPs [IC95%]: 2.45 [1.91-3.15]; 1.51 [1.28-1.79] y 1.44 [1.08-1.93], respectivamente). Los inmigrantes hicieron mayor uso de las urgencias (excepto EE) y consumieron menos fármacos. Los marroquíes mostraron la mayor diferencia en la frecuencia de NIAM (RP [IC95%]: 12.20 [5.25-28.37]), principalmente por razones laborales (46%). Conclusiones. La salud y el uso de servicios sanitarios difirieron significativamente entre inmigrantes y nativos. Destaca la NIAM alta en marroquíes por causa laboral.
Objective. To compare the self-perceived health, use of health services and unmet need for health care (UNHC) among immigrants and native populations of Southeast Spain. Materials and methods. Cross-sectional study of two representative samples of 1150 immigrants, and 1303 native participants from the National Health Survey. A single database was created with specific weights for each sample, and prevalence ratios (PR) were estimated by multivariate regression. Results. Moroccans, Ecuadorians and Eastern Europeans (EE) reported poorer health than the native population (PRs [CI95%]: 2.45 [1.91-3.15]; 1.51 [1.28-1.79] and 1.44 [1.08-1.93], respectively). Immigrants made greater use of emergencies that natives (except for EE) and had lower use of medication. Moroccan showed the greatest difference in the frequency of UNHC (PR [CI95%]:12.20 [5.25 - 28.37]), mainly because of working limitations (46%). Conclusions. The health status and use of health services among immigrants differ significantly from those of natives. Results highlight the higher frequency of UNHC among immigrants, especially high in Moroccans.
Subject(s)
Animals , Humans , Cysteine Endopeptidases/isolation & purification , Taenia solium/enzymology , Chromatography, Gel , Chromatography, Ion Exchange , Collagen/metabolism , Cysteine Endopeptidases/chemistry , Cysteine Endopeptidases/metabolism , Cysteine Proteinase Inhibitors/pharmacology , Immunoglobulin G/metabolism , Iodoacetic Acid/pharmacology , Leucine/analogs & derivatives , Leucine/pharmacology , Serum Albumin, Bovine/metabolismABSTRACT
O objetivo deste trabalho foi analisar os motivos das faltas às consultas odontológicas em Unidades de Saúde da Família (USF) e implementar estratégias para sua redução por meio da pesquisa-ação. O estudo foi realizado em 12 USF de Piracicaba/SP, de 01 de janeiro a 31 de dezembro de 2010. A amostra se consistiu de 385 usuários, entrevistados por telefone, sobre os motivos das faltas, além de 12 cirurgiões-dentistas e 12 enfermeiras. Realizaram-se duas oficinas com os profissionais: uma para problematização dos dados coletados nas entrevistas e elaboração de estratégias; e outra após 4 meses, para avaliação. O maior motivo de faltas foi a coincidência do horário de funcionamento das unidades com o de trabalho dos usuários. Dentre as estratégias ressaltou-se a realização de palestras sobre saúde bucal, educação permanente nas reuniões de equipe, capacitação dos Agentes Comunitários de Saúde, participação em grupos terapêuticos e parcerias entre Equipe de Saúde Bucal e equipamentos sociais da comunidade. A adoção de prontuário único foi a estratégia desafiadora encontrada pelos profissionais. Concluiu-se que as estratégias implementadas levaram à diminuição das faltas em 66,6% e o caráter motivador das oficinas possibilitou a reflexão crítica para o redirecionamento da prática em saúde.
The aim of this study was to analyze the reasons for missed appointments in dental Family Health Units (FHU) and implement strategies to reduce same through action research. This is a study conducted in 12 FHUs in Piracicaba in the State of São Paulo from January, 1 to December, 31 2010. The sample was composed of 385 users of these health units who were interviewed over the phone and asked about the reasons for missing dental appointments, as well as 12 dentists and 12 nurses. Two workshops were staged with professionals: the first to assess the data collected in interviews and develop strategy, and the second for evaluation after 4 months. The primary cause for missed appointments was the opening hours of the units coinciding with the work schedule of the users. Among the strategies suggested were lectures on oral health, ongoing education in team meetings, training of Community Health Agents, participation in therapeutic groups and partnerships between Oral Health Teams and the social infrastructure of the community. The adoption of the single medical record was the strategy proposed by professionals. The strategies implemented led to a 66.6% reduction in missed appointments by the units and the motivating nature of the workshops elicited critical reflection to redirect health practices.
Subject(s)
Cysteine Endopeptidases/metabolism , Enzyme Precursors/metabolism , Plant Proteins/metabolism , Amino Acid Sequence , Biocatalysis , Computer Simulation , Cysteine Endopeptidases/chemistry , Cysteine Endopeptidases/genetics , Cysteine Proteinase Inhibitors/chemistry , Cysteine Proteinase Inhibitors/metabolism , Cysteine Proteinase Inhibitors/pharmacology , Enzyme Activation , Enzyme Precursors/antagonists & inhibitors , Enzyme Precursors/chemistry , Enzyme Precursors/genetics , Hot Temperature , Hydrogen-Ion Concentration , Hydrolysis , Isoenzymes/antagonists & inhibitors , Isoenzymes/chemistry , Isoenzymes/genetics , Isoenzymes/metabolism , Kinetics , Leucine/analogs & derivatives , Leucine/chemistry , Leucine/metabolism , Leucine/pharmacology , Models, Molecular , Molecular Sequence Data , Plant Proteins/antagonists & inhibitors , Plant Proteins/chemistry , Plant Proteins/genetics , Protein Conformation , Protein Folding , Protein Stability , Recombinant Proteins/chemistry , Recombinant Proteins/metabolismABSTRACT
O presente artigo tem por objetivo avaliar associação entre fatores de risco cardiovascular (FRCV) e indicadores antropométricos em amostra de base populacional de universitários de São Luís/MA. Estudo transversal com 968 universitários, mediana de 22 anos. Glicemia, triglicerídeos (TGL), HDL-c, tabagismo, consumo de álcool, sedentarismo, síndrome metabólica (SM–critérios do Joint Interim Statement) e resistência insulínica (RI), foram associados e correlacionados com os indicadores antropométricos Índice de Massa Corporal (IMC), Circunferência da Cintura (CC), Relação Cintura Quadril (RCQ) e Relação Cintura Altura (RCA). Encontraram-se associações entre TGL, HAS, SM e maiores valores de todas as variáveis antropométricas. RI associou-se a maiores valores IMC e RCA em homens e mulheres. Baixo HDL-c foi associado a maiores valores de todas as variáveis antropométricas em mulheres. Consumo de álcool associou-se a valores mais elevados de IMC e CC em mulheres e RCQ e RCA em homens. Fumo associou-se a maiores valores de RCA em ambos os sexos. Sedentarismo foi associado a maiores valores de RCQ apenas em homens. As correlações mais altas foram estabelecidas para mulheres entre TGL e IMC, CC, RCQ e RCA. Os indicadores que mais se associaram aos FRCV foram IMC, CC e RCA em mulheres e RCQ e RCA em homens.
The article aims to evaluate the relation between cardiovascular risk factors (CVRF) and anthropometric indicators in a sample of university students from São Luís-MA, Brazil. It is a cross-sectional study conducted with 968 university students, with median age of 22. Glycemia, triglycerides, HDL-c, smoking, alcohol consumption, physical inactivity, metabolic syndrome (Joint Interim Statement criteria) and insulin resistance (IR), were associated and correlated with anthropometric indicators such as BMI, WC, WHR and WHtR. Associations were found between TGL, SH, SM and higher values of all anthropometric variables. The RI was associated with higher BMI values and WHtR in men and women. The low HDL-c was associated with higher values of all anthropometric variables in women. Consumption of alcohol was associated with higher values of BMI and WC in women and WHR in men and WHtR. Smoking was associated with higher values of WHtR in both sexes. Physical inactivity was associated with higher values of WHR in men only. The highest correlations were established for women between TGL and BMI CC, WHR and WHtR. The indicators most associated with CVRF were BMI, WC and WHtR in females and WHR and WHtR in men.
Subject(s)
Cysteine Proteases/metabolism , Cysteine Proteinase Inhibitors/chemical synthesis , Cysteine Proteinase Inhibitors/pharmacology , Drug Design , Norwalk virus/enzymology , Chemistry Techniques, Synthetic , Crystallography, X-Ray , Cysteine Proteinase Inhibitors/chemistry , Dose-Response Relationship, Drug , Models, Molecular , Molecular Conformation , Stereoisomerism , Structure-Activity RelationshipABSTRACT
O objetivo foi conhecer fatores facilitadores e dificultadores e estratégias utilizadas por 28 municípios brasileiros de grande porte na realização de Educação Permanente em alimentação e nutrição, na Estratégia Saúde da Família. Método qualitativo de múltiplos casos. A técnica de coleta de dados foi a entrevista com coordenadores municipais das ações de alimentação e nutrição, das cinco regiões do país. O estudo foi realizado entre 2009 e 2010. Utilizou-se o software NVivo e a análise de conteúdo foi orientada por categorias temáticas. Foram entrevistados 44 profissionais, sendo 19 nutricionistas. A maioria dos municípios era do Nordeste e Sudeste, 14 eram capitais, 7 metrópoles e 14 tinham Núcleo de Apoio à Saúde da Família. Os fatores facilitadores para Educação Permanente em nutrição mais citados foram as parcerias e a disponibilidade de recursos. Os dificultadores mais frequentes foram a indisponibilidade de agendas e a falta de profissionais na gestão das ações de nutrição. As estratégias mais utilizadas foram a realização de ações educativas no nível local, por grupos e o planejamento e programação. Concluiu-se que são necessários maiores investimentos para que a Educação Permanente em alimentação e nutrição se concretize.
This study sought to ascertain the facilitating and inhibiting factors and strategies used by 28 major Brazilian cities in conducting ongoing food and nutrition education within the Family Health Strategy. It involved a qualitative study of multiple cases. The data collection technique was conducted in interviews with municipal coordinators of food and nutrition campaigns from the five regions of the country. The study was conducted between 2009 and 2010. NVivo 10 software was used and content analysis was divided up into thematic categories. Forty-four professionals were interviewed, 19 of which were nutritionists. Most cities were from the Northeast and Southeast; 14 were capitals, 7 were metropolises and 14 had Family Health Suppor Units. The most frequently mentioned facilitating factors for Ongoing Education in Nutrition were partnerships and the availability of funds. The most frequent inhibiting factors were difficulty in scheduling and a lack of professionals in management of nutrition actions. The strategies most commonly used were conducting training at the local level, in groups and planning and programming. The conclusion drawn is that more investment is needed for Ongoing Education in Feeding and Nutrition to be effectively implemented.
Subject(s)
Animals , Babesia bovis/drug effects , Cysteine Proteinase Inhibitors/pharmacology , Babesia bovis/enzymology , Babesia bovis/growth & development , Cysteine Endopeptidases/physiology , Erythrocytes/parasitology , Leucine/analogs & derivatives , Leucine/pharmacology , Leupeptins/pharmacologyABSTRACT
La listeriosis es una enfermedad transmitida por alimentos (ETA) y ocasionada por Listeria monocytogenes. La importancia de ésta se debe a su impacto clínico, la alta tasa de mortalidad y el efecto económico derivado de los brotes asociados con el consumo de alimentos. En México, las fallas en los sistemas de vigilancia epidemiológicos son causa de información imprecisa sobre la incidencia de la listeriosis y sobre su caracterización como ETA. En este trabajo se presentan datos referentes a la presencia de la bacteria en alimentos, reportes de casos de la enfermedad y patologías relacionadas con infección por L. monocytogenes. La falta de datos exactos sobre la importancia de esta bacteria plantea la necesidad de concientizar a las instancias correspondientes para definir estrategias de búsqueda intencionada de L. monocytogenes en alimentos y de la recopilación de información clínica precisa que permita conocer la importancia clínica y epidemiológica de la listeriosis en México.
Listeriosis is caused by Listeria monocytogenes, an important food-borne disease due to its clinical forms, high mortality rate, and the economic impact in both clinical and food production industries. In Mexico, the lack of epidemiological surveillance systems leads to the need of accurate data on the incidence of listeriosis and its association with food-borne disease. In this paper, we present data about the presence of this bacterium in food, reports related to clinical cases of listeriosis, and information of diseases in which L. monocytogenes may be involved. However, in most of these cases the etiology was not established. Given this, there's a need to inform and warn the appropriate entities, to define strategies for the mandatory search of L. monocytogenes through the whole food production chain and clinical suspects, for the epidemiological importance and control of listeriosis in Mexico.
Subject(s)
Animals , Cysteine Endopeptidases/isolation & purification , Egg Proteins/metabolism , Enzyme Precursors/isolation & purification , Antimalarials/pharmacology , Chromatography, Gel , Cysteine Endopeptidases/metabolism , Cysteine Proteinase Inhibitors/pharmacology , Egg Yolk/chemistry , Electrophoresis, Polyacrylamide Gel , Enzyme Activation , Enzyme Precursors/metabolism , Hydrogen-Ion Concentration , Leucine/analogs & derivatives , Leucine/metabolism , Molecular Weight , OrthopteraABSTRACT
Sarcocystis neurona is the major agent of equine protozoal myeloencephalitis. It infects several mammalian species in the Americas, where the definitive hosts, marsupials of the genus Didelphis (D. virginiana and D. albiventris) are found. Domestic cats are one of the confirmed intermediate hosts of the parasite; however, antibodies against S. neurona had never before been demonstrated in Brazilian cats. The aim of this study was to determine whether cats in Bahia, Brazil, are exposed to the parasite. A total of 272 feline serum samples (134 from feral and 138 from house cats) were subjected to an indirect fluorescent antibody test using cultured merozoites of S. neurona as antigen. Positivity was detected in 4.0% (11/272) of the tested samples, with titers ranging from 25 to 800. The feline sera were also tested for antibodies against the protozoan Neospora caninum, with an observed antibody frequency of 2.9%. To the author's knowledge, this is the first study to report antibodies against S. neurona in Brazilian cats. We conclude that cats are exposed to the parasite in the region of this study. Further investigations are needed to confirm the role of cats in the transmission cycle of S. neurona in Brazil.
Sarcocystis neurona é o principal agente da mieloencefalite protozoária equina. Esse parasito infecta várias espécies de mamíferos nas Américas, onde são encontrados os hospedeiros definitivos, os marsupiais do gênero Didelphis (D. virginiana and D. albiventris). O gato doméstico é um dos hospedeiros intermediários do parasito. Contudo, anticorpos contra S. neurona ainda não tinham sido demonstrados em gatos brasileiros. O objetivo deste trabalho foi determinar se gatos da Bahia, Brasil, são expostos ao parasito. Amostras séricas de 272 felinos (134 de gatos errantes e 138 de gatos domiciliados) foram testadas pelo teste de imunofluorescência indireta, utilizando-se como antígeno, merozoítos produzidos em cultura celular. Entre as amostras testadas, 4,0% (11/272) foram positivas com títulos entre 25 e 800. Os soros dos felinos foram também testados para anticorpos contra o protozoário Neospora caninum, cuja frequência de anticorpos foi de 2,9%. Esse é o primeiro relato de anticorpos contra S. neurona em gatos brasileiros. Conclui-se que os gatos da região estudada são expostos a S. neurona. Estudos futuros são necessários, a fim de se confirmar o papel dos gatos no ciclo de transmissão de S. neurona no Brasil.
Subject(s)
Animals , Antimalarials/pharmacology , Cysteine Proteinase Inhibitors/pharmacology , Leucine/analogs & derivatives , Plasmodium falciparum/drug effects , Plasmodium falciparum/enzymology , Cysteine Endopeptidases/biosynthesis , Cysteine Endopeptidases/pharmacology , Electrophoresis, Polyacrylamide Gel , Erythrocytes/parasitology , Gene Expression Regulation, Developmental , Hydrolysis , Hemoglobins/metabolism , Leucine/pharmacology , Leupeptins/pharmacology , Plasmodium falciparum/growth & development , Time FactorsABSTRACT
Entre 1916 e 1923, o Distrito Federal e 11 estados brasileiros estabeleceram acordos de cooperação com a divisão internacional de saúde – International Health Board – da Fundação Rockefeller para combater uma endemia rural, a ancilostomíase. Este breve texto apresenta o diário de Alan Gregg, um dos médicos norte-americanos que trabalharam no Brasil entre 1919-1922. Fonte interessante para discutir questões relativas à história da saúde pública no Brasil, o diário do médico, além das informações sobre as atividades de combate à ancilostomíase desenvolvidas pela Fundação Rockefeller no país, apresenta suas impressões relativas à natureza, à cultura, à política e à sociedade brasileiras. Na seleção de trechos do diário ora apresentado, priorizamos, porém, aspectos relativos às atividades profissionais realizadas por Gregg.
Between 1916 and 1923, the Federal District and 11 Brazilian states entered into cooperation agreements with the International Health Board of the Rockefeller Foundation to combat a rural endemic disease, namely ancylostomiasis. This paper presents the diary of Alan Gregg, one of the American physicians who worked in Brazil from 1919 to 1922. An interesting source to discuss issues relating to the history of public health in Brazil, in addition to information about the activities to combat ancylostomiasis developed by the Rockefeller Foundation in the country, the diary of the physician presents his impressions concerning nature, culture, politics and society in Brazil. In the diary excerpts presented here, however, aspects related to the professional activities performed by Gregg are prioritized.
Subject(s)
Animals , Rats , Calpain/antagonists & inhibitors , Cysteine Proteinase Inhibitors/pharmacology , Glutamic Acid/toxicity , Hippocampus/physiology , Neurons/drug effects , Neuroprotective Agents/pharmacology , Neurotoxins/toxicity , Cells, Cultured , Dipeptides/pharmacology , Glycoproteins/pharmacology , Hippocampus/cytology , Leucine/analogs & derivatives , Leucine/pharmacology , Neurons/cytology , Neurons/physiology , Neurotoxins/antagonists & inhibitorsABSTRACT
OBJECTIVE: to interpret the meanings patients with type 2 diabetes mellitus assign to health education groups. METHOD: ethnographic study conducted with Hyperdia groups of a healthcare unit with 26 informants, with type 2 diabetes mellitus, and having participated in the groups for at least three years. Participant observation, social characterization, discussion groups and semi-structured interviews were used to collect data. Data were analyzed through the thematic coding technique. RESULTS: four thematic categories emerged: ease of access to the service and healthcare workers; guidance on diabetes; participation in groups and the experience of diabetes; and sharing knowledge and experiences. The most relevant aspect of this study is the social use the informants in relation to the Hyperdia groups under study. CONCLUSION: the studied groups are agents producing senses and meanings concerning the process of becoming ill and the means of social navigation within the official health system. We expect this study to contribute to the actions of healthcare workers coordinating these groups given the observation of the cultural universe of these individuals seeking professional care in the various public health care services. .
OBJETIVO: interpretar os significados atribuídos por pacientes portadores de diabetes mellitus tipo 2 a grupos de educação em saúde. MÉTODO: estudo etnográfico em cinco grupos Hiperdia de um centro de saúde, com 26 informantes portadores de diabetes mellitus tipo 2 que participavam dos grupos há, no mínimo, três anos. Para coligir as informações, utilizaram-se observação participante, caracterização social, grupos de discussão e entrevistas semiestruturadas. Os dados foram analisados por meio da técnica de codificação temática. RESULTADOS: emergiram quatro categorias temáticas - facilidades de acesso ao serviço e profissionais de saúde, orientações sobre o diabetes, participação nos grupos e experiência com o diabetes e compartilhamento de saberes e experiências. O aspecto mais relevante deste estudo diz respeito aos usos sociais que os informantes conferiam aos grupos Hiperdia pesquisados. CONCLUSÃO: os grupos estudados mostraram-se como instâncias produtoras de sentidos e de significados, concernentes ao processo de adoecimento e aos modos de navegação social no interior do sistema oficial de saúde. Almeja-se que este estudo possa contribuir para as ações dos profissionais de saúde que atuam nesses grupos, tendo em vista a observação do universo cultural dos indivíduos que procuram por cuidado profissional, nos diversos serviços públicos de saúde. .
OBJETIVO: interpretar los significados atribuidos por pacientes con diabetes mellitus tipo 2 a los grupos de educación para la salud. MÉTODO: estudio etnográfico en cinco grupos Hiperdia de un centro de salud, con 26 informantes con diabetes mellitus tipo 2 que participaban de los grupos hace, por lo menos, tres años. Para recolectar las informaciones se utilizaron la observación participante, la caracterización social, los grupos de discusión y las entrevistas semiestructuradas. Los datos fueron analizados por medio de la técnica de codificación temática. RESULTADOS: surgieron cuatro categorías temáticas: facilidades de acceso al servicio y profesionales de la salud; orientaciones sobre la diabetes; participación en los grupos y experiencia con la diabetes; y, compartir conocimientos y experiencias. El aspecto más relevante de este estudio se refiere a los usos sociales que los informantes daban a los grupos Hiperdia investigados. CONCLUSIÓN: los grupos estudiados se mostraron capaces de producir sentidos y significados concernientes al proceso de enfermarse y a los modos de navegación social en el interior del sistema oficial de salud. El objetivo de este estudio es que pueda contribuir para las acciones de los profesionales de la salud que actúan en esos grupos, considerando la observación del universo cultural de los individuos que buscan cuidados profesionales en los diversos servicios públicos de salud. .
Subject(s)
Animals , Calcium/pharmacology , Muscles/drug effects , Antipain/pharmacology , Cysteine Proteinase Inhibitors/pharmacology , Dose-Response Relationship, Drug , Electrophoresis, Polyacrylamide Gel , Hydrogen-Ion Concentration , Iodoacetic Acid , Iodoacetates/pharmacology , Leucine/analogs & derivatives , Leucine/pharmacology , Leupeptins/pharmacology , Microscopy, Electron , Muscle Contraction/drug effects , Muscle Contraction/physiology , Muscles/physiopathology , Muscles/ultrastructure , Rana catesbeiana , TemperatureABSTRACT
Este estudo objetivou compreender as práticas de cuidado dos profissionais de saúde que assistem os idosos Kaingang. Estudo qualitativo, apoiado na etnografia, realizado com dez profissionais à que atuam na atenção primária saúde da Terra Indígena Faxinal, Paraná, Brasil. Os dados foram coletados no período de novembro de 2010 a fevereiro de 2012 por meio da observação participante e entrevistas, e, analisados à luz da Teoria Transcultural do Cuidado. Identificaram-se como práticas de cuidado a medicação e imunização, bem como, cuidados da medicina tradicional. Para realização destes cuidados, os profissionais dispunham de estratégias que proporcionavam manutenção dos idosos na assistência. Conclui-se que valores culturais e científicos necessitam integrar a assistência para melhoria da saúde dos idosos indígenas.
This research aims to understand the care practices of health professionals who assist the elderly Kaingang. It is a qualitative study, supported in ethnography, conducted by ten professionals working in primary health care in the indigenous land of Faxinal, Paraná, Brazil. The data was collected from November 2010 to February 2012 by participant observation and interviews, and analyzed based on the Transcultural Care Theory. Was identified the preoccupation of the carers practices with the medication and immunization, as well as traditional medical care. To achieve these, care professionals had strategies that implemented maintenance of older people in care. We conclude that cultural values and integrate scientific need assistance to improve the health of elderly indigenous.
Este estudio tuvo como objetivo entender las prácticas de cuidado de los profesionales de la salud que asisten a los ancianos Kaingang. Estudio cualitativo, apoyado en la etnografía, llevado a cabo con diez profesionales que trabajan en la atención primaria de la salud de la tierra indígena de Faxinal, Paraná, Brasil. Los datos fueron recogidos a partir de noviembre 2010 a febrero 2012 a través de la observación participante y las entrevistas, y analizado con base en la Teoría del Cuidado Transcultural. Se identificaron las prácticas de atención médica y imunizacion,el cuidado de la medicina, así tradicional. Para lograrlo, los profesionales tenían estrategias que proporcionaban el mantenimiento de las personas mayores en su atención. Se concluye que los valores culturales y científicos necesitan ayuda para mejorar la salud de los ancianos indígenas.
Subject(s)
Animals , Rats , Liver/enzymology , Lysosomes/enzymology , Phospholipases A/metabolism , Phospholipases/metabolism , Protease Inhibitors/pharmacology , Cells, Cultured , Chymotrypsin/antagonists & inhibitors , Cysteine Proteinase Inhibitors/pharmacology , Leucine/analogs & derivatives , Leucine/pharmacology , Leupeptins/pharmacology , Oligopeptides/pharmacology , Pepstatins/pharmacology , Phospholipases A1 , Time FactorsABSTRACT
OBJECTIVES: to identify adaptation problems under Roy's Model in patients undergoing hemodialysis and to correlate them with the socioeconomic and clinical aspects. METHOD: a transversal study, undertaken using a questionnaire. The sample was made up of 178 individuals. The Chi-squared and Mann-Whitney U tests were undertaken. RESULTS: the adaptation problems and the socioeconomic and clinical aspects which presented statistical associations were: Hyperkalemia and age; Edema and income; Impairment of a primary sense: touch and income; Role failure and age; Sexual dysfunction and marital status and sex; Impairment of a primary sense: vision and years of education; Intolerance to activity and years of education; Chronic pain and sex and years of education; Impaired skin integrity and age: Hypocalcemia and access; Potential for injury and age and years of education; Nutrition below the organism's requirements and age; Impairment of a primary sense: hearing and sex and kinetic evaluation of urea; Mobility in gait and/or coordination restricted, and months of hemodialysis; and, Loss of ability for self-care, and months of hemodialysis and months of illness. CONCLUSION: adaptation problems in the clientele undergoing hemodialysis can be influenced by socioeconomic/clinical data. These findings contribute to the development of the profession, fostering the nurse's reflection regarding the care. .
OBJETIVOS: identificar os problemas adaptativos de Roy em pacientes submetidos a hemodiálise e correlacioná-los aos aspectos socioeconômicos e clínicos. MÉTODO: estudo transversal, realizado através de um formulário. A amostra foi de 178 indivíduos. Efetuaram-se os testes qui-quadrado e U de Mann-Whitney. RESULTADOS: os problemas adaptativos e os aspectos socioeconômicos e clínicos que apresentaram associações estatísticas foram: hipercalemia e idade; edema e renda; deficiência de um sentido primário: tátil e renda; falha no papel e idade; disfunção sexual e estado civil e sexo; deficiência de um sentido primário: visão e anos de estudo; intolerância à atividade e anos de estudo; dor crônica e sexo e anos de estudo; integridade da pele prejudicada e idade; hipocalcemia e acesso; potencial para lesão e idade e anos de estudo; nutrição menor que as necessidades do organismo e idade; deficiência de um sentido primário: audição e sexo e avaliação cinética da ureia; mobilidade andar e/ou coordenação restritas e meses de hemodiálise e perda de habilidade de autocuidado e meses de hemodiálise e meses de doença. CONCLUSÃO: problemas adaptativos da clientela hemodialítica podem sofrer influências de dados socioeconômicos/clínicos. Tais achados contribuem para o desenvolvimento da profissão, proporcionando reflexão por parte do enfermeiro acerca do cuidado. .
OBJETIVOS: identificar los problemas adaptativos de Roy en pacientes sometidos a hemodiálisis y correlacionarlos a los aspectos socioeconómicos y clínicos. MÉTODO: estudio transversal, realizado a través de un formulario. La muestra fue de 178 individuos. Se efectuaron las pruebas Chi-cuadrado y U de Mann-Whitney. RESULTADOS: los problemas adaptativos y los aspectos socioeconómicos y clínicos que presentaron asociaciones estadísticas fueron: Hiperkalemia y edad; Edema y renta; Deficiencia de un sentido primario: táctil y renta; Fracaso en el papel y edad; Disfunción sexual y estado civil y sexo; Deficiencia de un sentido primario: visión y años de estudio; Intolerancia a la actividad y años de estudio; Dolor crónico y sexo y años de estudio; Integridad de la piel perjudicada y edad; Hipocalcemia y acceso; Potencial para lesión y edad y años de estudio; Nutrición menor que las necesidades del organismo y edad; Deficiencia de un sentido primario: audición y sexo y evaluación cinética de la urea; Movilidad andar y/o coordinación restringidas y meses de hemodiálisis; y, Pérdida de habilidad de autocuidado y meses de hemodiálisis y meses de enfermedad. CONCLUSIÓN: los problemas adaptativos de la clientela hemodialítica pueden sufrir influencias de datos socioeconómicos/clínicos. Esos hallazgos contribuyen para el desarrollo de la profesión, permitiendo la reflexión del enfermero acerca del cuidado. .
Subject(s)
Humans , Lysosomes/metabolism , Proteins/metabolism , Ubiquitins/physiology , Cell Compartmentation , Cysteine Proteinase Inhibitors/pharmacology , Intermediate Filaments/physiology , Leucine/analogs & derivatives , Leucine/pharmacology , Metabolism, Inborn Errors/metabolism , Organelles/ultrastructureABSTRACT
Neuroblastoma is a solid tumor that occurs mainly in children. Malignant neuroblastomas have a poor prognosis because conventional chemotherapeutic agents are not very effective. Survivin, a member of the inhibitor of the apoptosis protein family, plays a significant role in cell division, inhibition of apoptosis, and promotion of cell proliferation and invasion. Previous studies found that survivin is highly expressed in some malignant neuroblastomas and is correlated with poor prognosis. The aim of this study was to investigate whether survivin could serve as a potential therapeutic target of human neuroblastoma. We employed RNA interference to reduce survivin expression in the human neuroblastoma SH-SY5Y cell line and analyzed the effect of RNA interference on cell proliferation and invasion in vitro and in vivo. RNA interference of survivin led to a significant decrease in invasiveness and proliferation and increased apoptosis in SH-SY5Y cells in vitro. RNA interference of survivin inhibited tumor growth in vivo by 68±13% (P=0.002) and increased the number of apoptotic cells by 9.8±1.2% (P=0.001) compared with negative small interfering RNA (siRNA) treatment controls. Moreover, RNA interference of survivin inhibited the formation of lung metastases by 92% (P=0.002) and reduced microvascular density by 60% (P=0.0003). Survivin siRNA resulted in significant downregulation of survivin mRNA and protein expression both in vitro and in vivo compared with negative siRNA treatment controls. RNA interference of survivin was found to be a potent inhibitor of SH-SY5Y tumor growth and metastasis formation. These results support further clinical development of RNA interference of survivin as a treatment of neuroblastoma and other cancer types.
Subject(s)
Animals , Humans , Apoptosis/drug effects , Cysteine Proteinase Inhibitors/pharmacology , Inhibitor of Apoptosis Proteins/drug effects , Lung Neoplasms/secondary , Neuroblastoma/pathology , RNA, Small Interfering/pharmacology , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Down-Regulation/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Immunohistochemistry , In Situ Nick-End Labeling , Inhibitor of Apoptosis Proteins/genetics , Inhibitor of Apoptosis Proteins/metabolism , Mice, Nude , Neoplasm Invasiveness , Neuroblastoma/secondary , Reverse Transcriptase Polymerase Chain Reaction , RNA, Neoplasm/drug effects , RNA, Neoplasm/metabolism , Xenograft Model Antitumor AssaysABSTRACT
The quest for new antiparasitic alternatives has led researchers to base their studies on insights into biology, host-parasite interactions and pathogenesis. In this context, proteases and their inhibitors are focused, respectively, as druggable targets and new therapy alternatives. Herein, we proposed to evaluate the in vitro effect of the cysteine protease inhibitor E-64 on Giardia trophozoites growth, adherence and viability. Trophozoites (105) were exposed to E-64 at different final concentrations, for 24, 48 and 72 h at 37 °C. In the growth and adherence assays, the number of trophozoites was estimated microscopically in a haemocytometer, whereas cell viability was evaluated by a dye-reduction assay using MTT. The E-64 inhibitor showed effect on growth, adherence and viability of trophozoites, however, its better performance was detected in the 100 µM-treated cultures. Although metronidazole was more effective, the E-64 was shown to be able to inhibit growth, adherence and viability rates by ≥ 50%. These results reveal that E-64 can interfere in some crucial processes to the parasite survival and they open perspectives for future investigations in order to confirm the real antigiardial potential of the protease inhibitors.
As cisteína-proteases estão entre os alvos mais promissores para o desenvolvimento de novos agentes terapêuticos, visto que participam de eventos fundamentais do ciclo de vida de muitos microorganismos, inclusive Giardia. Como a atividade das proteases pode ser controlada por inibidores específicos, essas substâncias têm sido avaliadas quanto ao potencial antiparasitário. Diante disso, o presente estudo teve por objetivo avaliar o efeito in vitro do inibidor de cisteína-proteases E-64 sobre o crescimento, a aderência e a viabilidade de trofozoítos de cepa de Giardia isolada em Botucatu. Nos ensaios de crescimento e aderência, o número de trofozoítos foi estimado microscopicamente em hemocitômetro, enquanto que a viabilidade celular foi avaliada pelo método do MTT. No presente estudo, embora o metronidazol tenha se apresentado bastante efetivo, o E-64 mostrou ser capaz de inibir o crescimento, a aderência e a viabilidade em taxas superiores a 50%, especialmente nos cultivos expostos à concentração de 100 µM. A despeito de preliminares, esses resultados demonstram que o inibidor E-64 pode interferir em processos primordiais para a sobrevivência do parasita, além do que, abrem novas perspectivas para investigações futuras a fim de se avaliar o real potencial giardicida dos inibidores de proteases.
Subject(s)
Animals , Antiprotozoal Agents/pharmacology , Cysteine Proteinase Inhibitors/pharmacology , Giardia/drug effects , Leucine/analogs & derivatives , Trophozoites/drug effects , Cell Adhesion/drug effects , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Leucine/pharmacology , Time Factors , Trophozoites/growth & developmentABSTRACT
Following infection with Leishmania major, T cell activation and apoptosis can be detected in draining lymph nodes of C57BL/6-infected mice. We investigated the mechanisms involved in apoptosis and cytokine expression following Tcellactivation. After two weeks of infection, apoptotic T cells were not detected in draining lymph nodes but activation with anti-CD3 induced apoptosis in both CD4 and CD8 T cells. Treatment with anti-FasLigand, caspase-8 or caspase- 9 inhibitors did not block activation-induced T-cell death. We also investigated whether the blockade of caspase-8 activity would affect the expression of type-1 or type-2 cytokines. At early stages of infection, both CD4 and CD8 T cells expressed IFN-gamma upon activation. Treatment with the caspase-8 inhibitor zIETD-fmk (benzyl-oxycarbonyl-Ile- Glu(OMe)-Thr-Asp(OMe)-fluoromethyl ketone) reduced the proportion of CD8 T cells and IFN-gamma expression in both CD4 and CD8T cells. We conclude that a non apoptotic role of caspase-8 activity may be required for T cell-mediated type-1 responses during L. major infection.
A ativação e a morte por apoptose de linfócitos T foram observadas em linfonodos drenantes de camundongos C57BL/6 infectados com Leishmania major. Investigamos os mecanismos envolvidos na apoptose e na expressão de citocinas após a ativação de linfócitos T. Após duas semanas de infecção, embora as células apoptóticas ainda não sejam detectadas em linfonodos drenantes, células T CD4 e CD8 sofrem apoptose após ativação com anti-CD3. O tratamento com anticorpo antagonista anti-Ligante de Fas, ou com inibidores das caspases-8 e 9, não bloqueou a morte induzida por ativação das células T. Investigamos também se a inibição da atividade da caspase-8 poderia afetar a expressão de citocinas tipo-1 ou tipo-2. Nos estágios iniciais da infecção, células T CD4 e CD8 de animais infectados com L. major expressaram IFN-gama após ativação. O tratamento com o inibidor de caspase-8 zIETD (benzoil-oxicarbonil-Ile-Glu(OMe)-Thr-Asp(OMe)-fluorometilcetona) durante a estimulação de células T reduziu a proporção de células T CD8 e a expressão de IFN-gama por células T CD4 e CD8. Concluimos que a atividade não apoptótica de caspase-8 pode ser necessária para o estabelecimento da imunidade mediada por células T durante a infecção por L. major.
Subject(s)
Animals , Female , Mice , Apoptosis/immunology , /immunology , /immunology , /antagonists & inhibitors , Interferon-gamma/immunology , Leishmania major/immunology , Leishmaniasis, Cutaneous/immunology , Amino Acid Chloromethyl Ketones/pharmacology , /enzymology , /enzymology , Cysteine Proteinase Inhibitors/pharmacology , Immunity, Cellular , Leishmaniasis, Cutaneous/parasitology , Lymph Nodes/parasitologyABSTRACT
BACKGROUND: Human telomerase reverse transcriptase (hTERT) is a catalytic enzyme that is required for telomerase activity (TA) and cancer progression. Telomerase inhibition or inactivation increases cellular sensitivity to UV irradiation, DNA-damaging agents, the tyrosine kinase inhibitor, imatinib, and pharmacological inhibitors, such as BIBR1532. hTERT is associated with apoptosis. Some patients show drug-resistance during anti-cancer drug treatment and the cancer cell acquire anti-apoptotic mechanism. Therefore, we attempted to study correlation between hTERT and drug-resistance. METHODS: To study the correlation between protein level and activity of hTERT and drug-resistance, Western blotting and telomerase repeat amplification protocol (TRAP) assays were performed. To investigate whether hTERT contributes to drug resistance in tumor cells, we transiently decreased hTERT levels using small interfering RNA (siRNA) in T24/R2 cells. RESULTS: hTERT knockdown increased Bax translocation into the mitochondria and cytochrome C release into the cytosol. Caspase inhibitors, especially Z-VAD-FMK, rescued this phenomenon, suggesting that the stability or expression of hTERT might be regulated by caspase activity. CONCLUSIONS: These data suggest that hTERT might be a target molecule for drug-resistant tumor therapy.
Subject(s)
Humans , Amino Acid Chloromethyl Ketones/pharmacology , Antineoplastic Agents/pharmacology , Caspases/antagonists & inhibitors , Cell Line, Tumor , Cisplatin/pharmacology , Cysteine Proteinase Inhibitors/pharmacology , Cytochrome c Group/metabolism , Drug Resistance, Neoplasm/genetics , Neoplasms/therapy , RNA, Small Interfering , Telomerase/antagonists & inhibitors , bcl-2-Associated X Protein/metabolismABSTRACT
Selective neuronal loss following status epilepticus (SE) was first described just under 100 years ago. The acute pathology following SE was shown to be 'ischemic cell change' and was assumed to arise through hypoxia/ischemia. Recently, erythropoietin (Epo) has been shown to have potent anti-apoptosis activity in central nervous system neurons in animal models of ischaemic injury. AIMS: In this report, in order to determine Epo preconditioning on hippocampus neuronal apoptosis, we examined caspase-3 expression following SE caused by Li-pilocarpine in rats. SETTINGS AND DESIGN: Animals were classified into three groups: EP group (pilocarpine group), rhEpo-pilocarpine group and control group. Four hours after preconditioning with Epo intraperitoneally, pilocarpine hydrochloride was administered intraperitoneally and observed for behavioral manifestations of SE. The animals were sacrificed at one hour after SE onset. MATERIALS AND METHODS: At the above-mentioned time point, animals were deeply anesthetized and were perfused through the left ventricle. Detection of hippocampus neuronal apoptosis was performed with caspase-3 immunohistochemical technique on three groups. To further confirm which cell population upregulates caspase-3, brain sections were stained for NeuN (green) and caspase-3 (red). STATISTICAL ANALYSIS: ANOVA and Fisher's post hoc test was used. RESULTS: Quatification of hippocampus neurons revealed that the number of caspase-3-positive cells in the CA1/CA3 area and dentate gyrus(DG) of three groups had a significant difference. In comparison with control group, there was an increase by 74% and 534%, 42% and 272% in the CA1/CA3 area and DG of EP group and rhEpo-treated group respectively. There was a decrease by 18% and 26% in the CA1/CA3 area and DG of rhEpo-treated group compared with those in EP group. In addition, colocalization of caspase-3 with NeuN was shown. CONCLUSIONS: Systemic rhEpo therapy reduced caspase-3 expression in SE induced by Li-pilocarpine.
Subject(s)
Animals , Apoptosis/drug effects , Caspase 3 , Caspases/antagonists & inhibitors , Cysteine Proteinase Inhibitors/pharmacology , Disease Models, Animal , Erythropoietin/pharmacology , Hippocampus/drug effects , Male , Neurons/drug effects , Pilocarpine , Rats , Rats, Sprague-Dawley , Status Epilepticus/chemically inducedABSTRACT
Because of the complexity of the cathepsin B-like (CBL) family, an information on the biological and biochemical characteristics of individual CBL genes is lacking. In this study, we investigated the degradative effects of the recombinant HC58 protein isolated from Haemonchus contortus parasites on protein substrates over a broad pH range in vitro. This protein, which hydrolyzed the synthetic peptide substrates Z-FR-AMC and Z-RR-AMC, had characteristics of the cysteine protease class of proteins. In the acidic pH range, the isolated protein actively degraded hemoglobin (Hb), the heavy chain of goat immunoglobulin G, and azocasein. By contrast, it degraded fibrinogen in the alkaline pH range. These activities were strongly inhibited in the presence of the cysteine protease inhibitor E-64. While the protein digested Hb, it did not induce the agglutination of erythrocytes from its natural host. These results suggest that the HC58 protein may play a role in the nutrition of this parasite.
Subject(s)
Animals , Caseins/metabolism , Cathepsin B , Cysteine Proteinase Inhibitors/pharmacology , DNA, Complementary/genetics , Goat Diseases/parasitology , Goats , Haemonchiasis/parasitology , Haemonchus/enzymology , Hemagglutination Tests/veterinary , Hemoglobins/metabolism , Hydrogen-Ion Concentration , Immunoglobulin G/metabolism , Leucine/analogs & derivatives , RNA, Helminth/chemistry , Recombinant Proteins/genetics , Reverse Transcriptase Polymerase Chain Reaction/veterinaryABSTRACT
A 29 kDa cysteine protease of Taenia solium metacestodes was purified by Mono Q anion-exchanger and Superose 6 HR gel filtration chromatography. The enzyme was effectively inhibited by cysteine protease inhibitors, such as iodoacetic acid (IAA) and trans-epoxy-succinyl-L-leucyl-amido (4-guanidino) butane (E-64) while inhibitors acting on serine- or metallo-proteases did not affect the enzyme activity. The purified enzyme degraded human immunoglobulin G (IgG), collagen and bovine serum albumin (BSA), but human IgG was more susceptible for proteolysis by the enzyme. To define the precise biological roles of the enzyme, more detailed biochemical and functional studies would be required.
Subject(s)
Humans , Animals , Taenia solium/enzymology , Serum Albumin, Bovine/metabolism , Leucine/analogs & derivatives , Iodoacetic Acid/pharmacology , Immunoglobulin G/metabolism , Cysteine Proteinase Inhibitors/pharmacology , Cysteine Endopeptidases/chemistry , Collagen/metabolism , Chromatography, Ion Exchange , Chromatography, GelABSTRACT
Pseudolaric acid B was isolated from Pseudolarix kaempferi Gordon (Pinaceae) and was evaluated for the anti-cancer effect in HeLa cells. We observed that pseudolaric acid B inhibited cell proliferation and induced apoptosis in a time- and dose-dependent manner. HeLa cells treated with pseudolaric acid B showed typical characteristics of apoptosis including the morphological changes and DNA fragmentation. JNK inhibitor, SP600125, markedly inhibited pseudolaric acid B-induced cell death. In addition, Bcl-2 expression was down-regulated while Bax protein level was up-regulated. Caspase-3 inhibitor, z-DEVD-fmk, partially blocked pseudolaric acid B-induced cell death, and the expression of two classical caspase substrates, PARP and ICAD, were both decreased in a time- dependent manner, indicative of downstream caspase activation.
Subject(s)
Humans , Anthracenes/pharmacology , Apoptosis , Caspases/antagonists & inhibitors , Cell Proliferation/drug effects , Cysteine Proteinase Inhibitors/pharmacology , Diterpenes/pharmacology , Down-Regulation , Enzyme Activation , HeLa Cells , JNK Mitogen-Activated Protein Kinases/drug effects , Oligopeptides/pharmacology , Protein Kinase Inhibitors/pharmacology , Proto-Oncogene Proteins c-bcl-2/metabolism , Signal Transduction/drug effects , Up-RegulationABSTRACT
Tooth germ development is associated with morphological and biochemical changes of the dental papilla and enamel organ. Enzymes with gelatinolytic activities were studied by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and enzymography in tooth germ of newborn to 15-day-old rats. Three major bands with gelatinolytic activity were detected at all periods and characterized as the latent and active forms of MMP-2 using their molecular weight and activity dependent on Zn++ and Ca++ ions as criteria. Expression and activity of MMP-2 increased progressively from 0 to 15 days after birth. Mechanical separation of the tooth germ from 10-day-old rats showed that the gelatinolytic activity was localized mainly in the dental papilla and not the dental organ. These data indicate that the expression and activity of MMP-2 varies during the development and maturation of rat first molar tooth germ.