RESUMO
Tryptophan participates on several physiological mechanisms of the neuroendocrine-immune network and plays a critical role in macrophages and lymphocytes function. This study intended to evaluate the modulatory effects of dietary tryptophan on the European seabass (Dicentrarchus labrax) immune status, inflammatory response and disease resistance to Photobacterium damselae piscicida. A tryptophan deficient diet (NTRP); a control diet (CTRL); and two other diets supplemented with tryptophan at 0.13% (TRP13) and 0.17% (TRP17) of feed weight were formulated. Fish were sampled at 2 and 4 weeks of feeding and the remaining were i.p. injected with Phdp (3 × 106 cfu/fish) at 4 weeks and the inflammatory response (at 4, 24, 48 and 72 hours post-infection) as well as survival were evaluated. Results suggest that fish immune status was not altered in a tryptophan deficient scenario whereas in response to an inflammatory insult, plasma cortisol levels increased and the immune cell response was compromised, which translated in a lower disease resistance. When dietary tryptophan was offered 30% above its requirement level, plasma cortisol increased and, in response to bacterial infection, a decrease in lymphocytes, monocytes/macrophages and several immune-related genes was observed, also compromising at some degree fish disease resistance.
Assuntos
Bass/imunologia , Doenças dos Peixes/etiologia , Infecções por Bactérias Gram-Negativas/etiologia , Inflamação/imunologia , Triptofano/deficiência , Ração Animal , Animais , Bass/crescimento & desenvolvimento , Bass/microbiologia , Atividade Bactericida do Sangue , Contagem de Células Sanguíneas , Peso Corporal/efeitos dos fármacos , Via Alternativa do Complemento/efeitos dos fármacos , Resistência à Doença , Relação Dose-Resposta a Droga , Índices de Eritrócitos , Doenças dos Peixes/microbiologia , Perfilação da Expressão Gênica , Infecções por Bactérias Gram-Negativas/microbiologia , Hemoglobinas/análise , Hidrocortisona/sangue , Imunidade Humoral , Inflamação/sangue , Inflamação/genética , Muramidase/sangue , Neuroimunomodulação , Necessidades Nutricionais , Peroxidases/sangue , Photobacterium , Triptofano/administração & dosagem , Triptofano/fisiologia , Triptofano/uso terapêuticoRESUMO
This study aimed to evaluate the protective effects of four autochthonous bacteria isolated from juvenile sole (Solea senegalensis) intestine as dietary probiotic supplement against bacterial pathogen infection and handling/transport stressors. Growth performance and immune responses were evaluated after 85 days of feeding trial. Sole (IBWâ¯=â¯16.07⯱â¯0.11â¯g) were fed six experimental diets, a control diet (CTRL, without the dietary probiotic supplementation), and five diets supplemented with probiotic bacteria: PB1 (Shewanella hafniensis), PB2 (Enterococcus raffinosus), PB3 (Shewanella hafniensis + Arthrobacter soli), PB4 (Pseudomonas protegens + Arthrobacter soli) and PB5 (Shewanella hafniensis + Arthrobacter soli + Enterococcus raffinosus). All bacteria were selected based on their in vitro antimicrobial activity. After the growth trial, fish were submitted to a stress factor (transport) and then each dietary group was divided in two additional groups: non-infected (placebo) and infected with Photobacterium damselae subsp. piscicida. Immune and antioxidant responses were evaluated at day 10 post-infection. In infection trial A, fish were infected on the same day of transport, whereas in trial B fish were infected after a 7-day recovery from the transport stress. At the end of the feeding trial, fish fed with PB2 and PB4 showed lower final body weight when compared with the other dietary groups. Respiratory burst activity and nitric oxide production were not affected by probiotic supplementation. Fish fed with PB5 presented lower peroxidase activity compared to CTRL. Lysozyme and alternative complement pathway activity (ACH50) showed no significant differences between treatments. The innate immune responses were significantly affected after handling stress and bacterial infection. In trial A, the ACH50 levels of infected fish were significantly lower than the placebo groups. On the other hand, in trial B fish infected with Pdp demonstrated higher ACH50 levels when compared to placebos. Peroxidase levels were strongly modulated by bacterial infection and handling stress. In trials A and B, infection had a clear downgrade effect in peroxidase levels. Lipid peroxidation, catalase, glutathione S-transferase and glutathione reductase were altered by both bacterial infection and transport. Overall, dietary probiotic supplementation did not influence growth performance of sole. The immune and oxidative defenses of sole responded differently to infection depending on the probiotic and the synergy between pathogen infection and transport.
Assuntos
Doenças dos Peixes/imunologia , Linguados/imunologia , Infecções por Bactérias Gram-Negativas/imunologia , Photobacterium , Probióticos/farmacologia , Estresse Fisiológico/imunologia , Animais , Dieta/veterinária , Linguados/crescimento & desenvolvimento , Infecções por Bactérias Gram-Negativas/veterináriaRESUMO
The pathology of schistosomiasis is associated with the formation of granulomas, and this process is associated with liver fibrosis. Studies indicate that Th1 cytokines reduce fibrosis in schistosomiasis, while Th2 cytokines play a part in the progression of fibrosis, and IL-13 has a critical role in this process. The IL-13Rα2 receptor, known as a 'receptor antagonist' binds with high affinity to IL-13, and studies have identified that this plays a part in reducing fibrosis and the size of granulomas. The objective of this study was to evaluate the function of IL-13Rα2 and cellular immune response in hepatic fibrosis. A negative correlation between IL-13Rα2 and IL-13 was found, suggesting an increase in cytokine in early fibrosis. Initially, a negative correlation between IFN-γ and IL-13 was found in patients without fibrosis, and subsequently, this correlation was found to be positive in patients with severe fibrosis, thereby highlighting a new mechanism for regulating the progress of periportal fibrosis. There was a positive correlation between the profiles of Th1 and Th2 cytokines, suggesting the presence of both responses, thus regulating the disease. The results contribute to a better understanding of the immune mechanisms that control the process of hepatic fibrogenesis in schistosomiasis in humans.
Assuntos
Subunidade alfa2 de Receptor de Interleucina-13/imunologia , Interleucina-13/imunologia , Cirrose Hepática/imunologia , Fígado/imunologia , Esquistossomose mansoni/imunologia , Idoso , Animais , Brasil , Diagnóstico Precoce , Feminino , Regulação da Expressão Gênica , Humanos , Interferon gama/genética , Interferon gama/imunologia , Interleucina-13/genética , Subunidade alfa2 de Receptor de Interleucina-13/genética , Interleucina-2/genética , Interleucina-2/imunologia , Interleucina-4/genética , Interleucina-4/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Fígado/parasitologia , Fígado/patologia , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática/parasitologia , Masculino , Pessoa de Meia-Idade , Schistosoma mansoni/patogenicidade , Schistosoma mansoni/fisiologia , Esquistossomose mansoni/complicações , Esquistossomose mansoni/diagnóstico , Esquistossomose mansoni/parasitologia , Transdução de Sinais , Classe Social , Células Th1/imunologia , Células Th1/parasitologia , Células Th1/patologia , Equilíbrio Th1-Th2 , Células Th2/imunologia , Células Th2/parasitologia , Células Th2/patologia , Fatores de TempoRESUMO
O objetivo deste estudo foi detectar rotavírus em fezes de bezerros com diarreia em Uberaba, MG, e caracterizar os genes VP7 e VP4 por meio da genotipagem e da análise filogenética. Setenta e quatro amostras foram coletadas entre novembro de 2008 e setembro de 2009. A detecção do vírus foi feita por teste de aglutinação e as amostras positivas foram submetidas à transcrição reversa, seguida de reação em cadeia da polimerase (RT-PCR), tipagem por PCR e sequenciamento. A taxa de detecção de rotavírus foi de 6,8% e todas as amostras apresentaram o genótipo G6P[5]. A análise filogenética mostrou que as amostras do genótipo G6 pertencem à linhagem IV e que, para ambos os genes (VP7 e VP4), as amostras deste estudo compõem um sub-cluster à parte daquele das cepas referências e das amostras campo mais similares. O alinhamento das sequências de aminoácidos deduzidas mostrou substituições em regiões antigênicas quando comparadas com as sequências das cepas bovinas UK e NCDV, presentes nas vacinas disponíveis no Brasil. Uma nova sublinhagem genética de G6P[5] foi evidenciada neste estudo. Substituições de aminoácidos nas regiões antigênicas dos rotavírus e a circulação de novas variantes podem representar desafios para as vacinas utilizadas atualmente. O presente estudo contribui para a compreensão da epidemiologia dos rotavírus bovinos no Brasil.(AU)
Assuntos
Animais , Bovinos , Técnicas de Genotipagem/veterinária , Rotavirus , Vacinas contra Rotavirus/genética , Testes de Fixação do Látex/veterináriaRESUMO
Allogeneic stem cell transplantation is potentially curative, but associated with post-transplantation complications, including cytomegalovirus (CMV) infections. An effective immune response requires T cells recognizing CMV epitopes via their T cell receptors (TCRs). Little is known about the TCR repertoire, in particular the TCR-α repertoire and its clinical relevance in patients following stem cell transplantation. Using next-generation sequencing we examined the TCR-α repertoire of CD8(+) T cells and CMV-specific CD8(+) T cells in four patients. Additionally, we performed single-cell TCR-αß sequencing of CMV-specific CD8(+) T cells. The TCR-α composition of human leucocyte antigen (HLA)-A*0201 CMVpp65- and CMVIE -specific T cells was oligoclonal and defined by few dominant clonotypes. Frequencies of single clonotypes reached up to 11% of all CD8(+) T cells and half of the total CD8(+) T cell repertoire was dominated by few CMV-reactive clonotypes. Some TCR-α clonotypes were shared between patients. Gene expression of the circulating CMV-specific CD8(+) T cells was consistent with chronically activated effector memory T cells. The CD8(+) T cell response to CMV reactivation resulted in an expansion of a few TCR-α clonotypes to dominate the CD8(+) repertoires. These results warrant further larger studies to define the ability of oligoclonally expanded T cell clones to achieve an effective anti-viral T cell response in this setting.
Assuntos
Antígenos Virais/imunologia , Linfócitos T CD8-Positivos/imunologia , Infecções por Citomegalovirus/imunologia , Citomegalovirus/imunologia , Epitopos/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Idoso , Sequência de Aminoácidos , Antígenos Virais/genética , Linfócitos T CD8-Positivos/patologia , Linfócitos T CD8-Positivos/virologia , Células Clonais , Citomegalovirus/crescimento & desenvolvimento , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/genética , Infecções por Citomegalovirus/virologia , Epitopos/genética , Feminino , Regulação da Expressão Gênica , Antígeno HLA-A2/genética , Antígeno HLA-A2/imunologia , Humanos , Memória Imunológica , Leucemia Linfocítica Crônica de Células B/imunologia , Leucemia Linfocítica Crônica de Células B/patologia , Leucemia Linfocítica Crônica de Células B/terapia , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Análise de Sequência de DNA , Transdução de Sinais , Análise de Célula Única , Transplante HomólogoRESUMO
To appreciate the Portuguese circumstances concerning situations of obstetric medico-legal conflicts and to evaluate the influence of the quality of files in expert conclusions, an analysis of all cases of obstetric medical responsibility from 2001-11 was carried out. File quality was evaluated by absence or insufficiency of clinical information supplied, by poor quality of document copies and by the registered incongruities among all the health professionals involved. Clinical files sent for forensic analysis were defective in most cases (89.5%). In about 11% of cases, expert opinion was inconclusive as a result of the poor quality of the clinical files sent for technical and scientific analysis. This situation is particularly serious in cases where the reason for the dispute was asphyxia, traumatic lesions of the newborn following instrumented delivery or shoulder dystocia and maternal sequelae, where the lack or absence of information, and poor quality copies were significantly associated with inconclusive opinions.
Assuntos
Documentação/normas , Responsabilidade Legal , Prontuários Médicos/normas , Obstetrícia/legislação & jurisprudência , Aborto Induzido/efeitos adversos , Traumatismos do Nascimento/etiologia , Prova Pericial , Feminino , Hipóxia Fetal/etiologia , Humanos , Prontuários Médicos/legislação & jurisprudência , Portugal , Gravidez , Complicações na Gravidez/etiologia , Diagnóstico Pré-NatalRESUMO
Rotaviruses are the main cause of infantile acute diarrhea, and a monovalent (G1P[8]) vaccine against the virus was introduced into the Brazilian National Immunization Program for all infants in March 2006. The objectives of this study were to determine the rate and genotype distribution of rotavirus causing infantile diarrhea in the Triângulo Mineiro region of Brazil during 2011-2012 and to assess the impact of local vaccination. Fecal specimens were analyzed for detection and characterization of rotavirus using polyacrylamide gel electrophoresis, reverse transcription followed by polymerase chain reaction (PCR), and PCR-genotyping assays. Overall, rotavirus was diagnosed in 1.7% (6/348) of cases. Rotavirus positivity rates decreased 88% [95% confidence intervals (CI)=15.2, 98.3%; P=0.026] in 2011 and 78% (95%CI=30.6, 93.0%; P=0.007) in 2012 when compared with available data for baseline years (2005/2006) in Uberaba. In Uberlândia, reductions of 95.3% (95%CI=66.0, 99.4%; P=0.002) in 2011, and 94.2% (95%CI=56.4, 99.2%; P=0.004) in 2012 were also observed compared with data for 2008. The circulation of rotavirus G2P[4] strains decreased during the period under study, and strains related to the P[8] genotype reemerged in the region. This study showed a marked and sustained reduction of rotavirus-related cases, with a lack of rotavirus in the 2011 and 2012 seasons, suggesting a positive impact of the vaccination program.
Assuntos
Criança , Pré-Escolar , Humanos , Lactente , Diarreia Infantil/virologia , Infecções por Rotavirus/epidemiologia , Rotavirus/genética , Brasil/epidemiologia , Diarreia Infantil/epidemiologia , Monitoramento Epidemiológico , Fezes/microbiologia , Genótipo , Técnicas de Genotipagem , Programas de Imunização/estatística & dados numéricos , Pacientes Ambulatoriais/estatística & dados numéricos , Infecções por Rotavirus/prevenção & controle , Rotavirus/classificação , Estações do AnoRESUMO
Rotaviruses are the main cause of infantile acute diarrhea, and a monovalent (G1P[8]) vaccine against the virus was introduced into the Brazilian National Immunization Program for all infants in March 2006. The objectives of this study were to determine the rate and genotype distribution of rotavirus causing infantile diarrhea in the Triângulo Mineiro region of Brazil during 2011-2012 and to assess the impact of local vaccination. Fecal specimens were analyzed for detection and characterization of rotavirus using polyacrylamide gel electrophoresis, reverse transcription followed by polymerase chain reaction (PCR), and PCR-genotyping assays. Overall, rotavirus was diagnosed in 1.7% (6/348) of cases. Rotavirus positivity rates decreased 88% [95% confidence intervals (CI)=15.2, 98.3%; P=0.026] in 2011 and 78% (95%CI=30.6, 93.0%; P=0.007) in 2012 when compared with available data for baseline years (2005/2006) in Uberaba. In Uberlândia, reductions of 95.3% (95%CI=66.0, 99.4%; P=0.002) in 2011, and 94.2% (95%CI=56.4, 99.2%; P=0.004) in 2012 were also observed compared with data for 2008. The circulation of rotavirus G2P[4] strains decreased during the period under study, and strains related to the P[8] genotype reemerged in the region. This study showed a marked and sustained reduction of rotavirus-related cases, with a lack of rotavirus in the 2011 and 2012 seasons, suggesting a positive impact of the vaccination program.
Assuntos
Diarreia Infantil/virologia , Infecções por Rotavirus/epidemiologia , Rotavirus/genética , Brasil/epidemiologia , Criança , Pré-Escolar , Diarreia Infantil/epidemiologia , Monitoramento Epidemiológico , Fezes/microbiologia , Genótipo , Técnicas de Genotipagem , Humanos , Programas de Imunização/estatística & dados numéricos , Lactente , Pacientes Ambulatoriais/estatística & dados numéricos , Rotavirus/classificação , Infecções por Rotavirus/prevenção & controle , Estações do AnoRESUMO
This study evaluates the usefulness of spatio-temporal statistical tools to detect outbreaks using routine surveillance data where limited epidemiological information is available. A dataset from 2002 to 2007 containing information regarding date, origin, source and serotype of 29,586 Salmonella isolates from Thailand was analysed. Data was grouped into human and non-human categories and the analysis was performed for the top five occurring serovars for each year of the study period. A total 91 human and 39 non-human significant spatio-temporal clusters were observed, accounting for 11% and 16% of the isolates, respectively. Serovar-specific associations between human and non-human clusters were also evaluated. Results show that these statistical tools can provide information for use in outbreak prevention and detection, in countries where only limited data is available. Moreover, it is suggested that monitoring non-human reservoirs can be relevant in predicting future Salmonella human cases.
Assuntos
Surtos de Doenças , Monitoramento Epidemiológico , Salmonelose Animal/epidemiologia , Infecções por Salmonella/epidemiologia , Animais , Análise por Conglomerados , Humanos , Análise Espaço-Temporal , Tailândia/epidemiologiaRESUMO
AIM: In children suffering from severe hepatosplenic schistosomiasis, the surgical protocol includes splenectomy and autoimplantation of spleen morsels in the major omentum, which has the potential of reducing the overwhelming postsplenectomy infection (OPSI). The purpose of the study was to evaluate the remaining splenosis, with the mean postoperative followup of 12.1 ± 5.6 years; to compare the efficacy of the 2 evaluation tools. MATERIALS AND METHODS: Nineteen patients underwent, when they were children, portal decompression and autoimplantation of spleen. After a mean age of 23.4 ± 5.3 years, they were investigated regarding the number of infections and OPSI. They had undergone hepatosplenic scintigraphy with labeled colloidal SnTc(99m) and abdominal ultrasound. It was considered efficient splenosis when the patients presented with 5 or more spleen nodules. The evaluation was performed by 3 observers. RESULTS: None of the patients had increased infection rate or developed OPSI. Sixteen (84.2%) presented efficient splenosis. CONCLUSIONS: The remaining postoperative splenosis was considered efficient in the majority of patients in the long-term followup; and nuclear medicine was considered the gold standard for splenosis evaluation.
RESUMO
BACKGROUND: Rotaviruses are the major cause of diarrhea in children for which a monovalent G1P[8] vaccine has been provided free for all Brazilian infants since March 2006. OBJECTIVES: To investigate prevalence and genotypes of rotavirus strains causing diarrhea in children in Triângulo Mineiro, Minas Gerais, during 2007-2010, and to assess local vaccine impact. STUDY DESIGN: Fecal specimens were analyzed for rotavirus detection and characterization by PAGE, RT-PCR and PCR-genotyping assays. RESULTS: Overall, rotavirus was diagnosed in 12.1% (76/630) cases, accounting for 35.8% of the hospitalizations and 6.5% of outpatient attendance due to diarrhea. A trend in rotavirus disease reduction occurred in both cities (71.8% and 83.4% in Uberaba; 95.3% in Uberlândia) up to 2009, but it reversed in 2010 with increased rotavirus cases in Uberlândia. Short pattern G2P[4] strains were detected in all but three (96%) cases of mixed/P[NT] infections with long electropherotypes. CONCLUSIONS: This 4-year follow-up study showed a reduction in rotavirus-related diarrhea and even skipped a rotavirus season, which is consistent with vaccine mediated protection. The 2007-2010 rotavirus epidemic curve reflected the natural cyclic fluctuation of the single G2P[4] genotype, with sharp reduction of cases in 2008 leading to lack of a rotavirus 2009 season (both cases and hospitalizations) followed by its come back in 2010. Diarrhea cases related to either vaccine serotype/genotype (G1 or P[8]) were not detected. Thus, a new scenario emerged with a single epidemic genotype replacing the cocirculation of great diversity of genotypes, thus far, a hallmark of the epidemiology of rotavirus in Brazil.
Assuntos
Infecções por Rotavirus/virologia , Vacinas contra Rotavirus/administração & dosagem , Rotavirus/genética , Brasil/epidemiologia , Criança , Pré-Escolar , Diarreia/virologia , Fezes/virologia , Seguimentos , Gastroenterite/virologia , Genótipo , Humanos , Lactente , Infecções por Rotavirus/epidemiologiaRESUMO
Campylobacter spp. is a widespread and important cause of human illness worldwide. Disease is frequently associated with foodborne transmission, but other routes of exposure, such as direct contact with live animals and person-to-person transmission, are also recognized. Identifying the most important sources of human disease is essential for prioritizing food safety interventions and setting public health goals. Numerous case-control studies of sporadic infections of campylobacteriosis have been published. These studies investigated a variety of potential risk factors for disease, often using different methodologies and settings. Systematic reviews (SRs) consist of a formal process for literature review focused on a specific research question, and include the identification of relevant literature, quality assessment of relevant studies, summarization or statistical analysis of data, and conclusions. With the objective of identifying the most important risk factors for human sporadic campylobacteriosis, we performed a SR of case-control studies of human sporadic cases and a meta-analysis of the obtained results. A combined SR focusing on Salmonella and Campylobacter studies was performed and the results analysed separately. From 1295 identified references, 131 passed the relevance screening, 73 passed the quality assessment stage, and data was extracted from 72 studies. Of these, 38 focused on campylobacteriosis. Information on exposures of cases and controls, and estimated odds ratios for investigated risk factors were collected and analysed. In the meta-analysis, heterogeneity between the studies and possible sources of bias were investigated, and pooled odds ratios for identified risk factors were estimated. Results suggest that travelling abroad, eating undercooked chicken, environmental sources, and direct contact with farm animals were significant risk factors for campylobacteriosis. Sub-analyses by geographical region, age group, and study period were performed, and differences were discussed.
Assuntos
Infecções por Campylobacter/epidemiologia , Animais , Meio Ambiente , Microbiologia de Alimentos , Humanos , Razão de Chances , Fatores de Risco , ViagemRESUMO
Wrist actigraphy is a well established procedure to monitor human activity. Among other areas, it has a special relevance in sleep studies where its lightweight and non-intrusive nature make it a valuable tool to access the circadian cycle. While there are several methods to extract information from the data, the differentiation between sleep and wakefulness states is still an open discussion. In this paper, the characteristics of the movements in the different states are assumed to be intrinsically different. These differences are not simply related with magnitude and movement counting, but due to real differences on the statistical distributions describing the actigraphy data. Thus it is possible to refine the discrimination level when detecting these states. The proposed methodology to characterize the actigraphy data is based on a mixture of three canonical distributions; i)Exponential, ii)Rayleigh and iii)Gaussian. It is shown that the weights and parameters estimated in each state are organized into almost separable clusters on the feature space. This suggests the ability of the method to discriminate these states based only on the movements recorded on actigraphy data.
Assuntos
Actigrafia/métodos , Algoritmos , Diagnóstico por Computador/métodos , Movimento/fisiologia , Polissonografia/métodos , Fases do Sono/fisiologia , Punho/fisiologia , Simulação por Computador , Humanos , Modelos EstatísticosRESUMO
Salmonella is an important cause of human illness. Disease is frequently associated with foodborne transmission, but other routes of exposure are recognized. Identifying sources of disease is essential for prioritizing public health interventions. Numerous case-control studies of sporadic salmonellosis have been published, often using different methodologies and settings. Systematic reviews consist of a formal process for literature review focused on a research question. With the objective of identifying the most important risk factors for salmonellosis, we performed a systematic review of case-control studies and a meta-analysis of obtained results. Thirty-five Salmonella case-control studies were identified. In the meta-analysis, heterogeneity between studies and possible sources of bias were investigated, and pooled odds ratios estimated. Results suggested that travel, predisposing factors, eating raw eggs, and eating in restaurants were the most important risk factors for salmonellosis. Sub-analyses by serotype were performed when enough studies were available.
Assuntos
Doenças Transmitidas por Alimentos/epidemiologia , Doenças Transmitidas por Alimentos/microbiologia , Infecções por Salmonella/epidemiologia , Microbiologia de Alimentos , Humanos , Restaurantes , Fatores de Risco , ViagemRESUMO
Schistosomiasis mansoni is a fibrogenic liver disease that constitutes a major health problem in north-eastern Brazil. Although one common manifestation of the disease, periportal fibrosis (PPF), can be assessed by ultrasonography by well-trained physicians, the necessary equipment and personnel are not always readily available. Serum markers, including hyaluronic acid (HA), have been used as alternative means of measuring fibrosis. Recently serum concentrations of HA have been evaluated in 77 Brazilians (61 cases of schistosomiasis mansoni and 16 healthy controls) and compared against the ultrasound-evaluated PPF in the same subjects. The HA was measured using a non-competitive fluorescence-based assay, while the PPF was explored using a portable ultrasound scanner (SSD-500; Aloka, Tokyo) and graded, as patterns A-F, according to the World Health Organization's 'Niamey protocol'. In general, the serum concentrations of HA were found to be positively correlated with the severity of the PPF. The mean concentration of HA in the sera of the 16 controls was significantly lower than that recorded in the schistosomiasis cases who showed PPF of patterns D or E (P<0·001 for each). The cases who showed pattern-C PPF also had significantly less HA in their sera than the cases with PPF of patterns D or E (P<0·001 for each), and the cases with pattern-D fibrosis had significantly lower HA concentrations in their sera than the cases with PPF of pattern E (P<0·001). In an analysis based on a receiver-operating-characteristic (ROC) curve, an HA concentration of 20·2 µg/litre of serum was identified as a threshold that could be used to distinguish moderate cases of PPF (i.e. patterns C or D) from the more advanced cases (i.e. patterns E or F), with a sensitivity of 60% and specificity of 65%. In conclusion, it appears that serum concentrations of hyaluronic acid could be used as markers for periportal fibrosis in patients with schistosomiasis mansoni.
Assuntos
Ácido Hialurônico/sangue , Cirrose Hepática/diagnóstico , Hepatopatias Parasitárias/diagnóstico , Esquistossomose mansoni/diagnóstico , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/parasitologia , Hepatopatias Parasitárias/sangue , Hepatopatias Parasitárias/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Esquistossomose mansoni/sangue , Esquistossomose mansoni/diagnóstico por imagem , Sensibilidade e Especificidade , Ultrassonografia , Adulto JovemRESUMO
Recent studies have revealed that endoplasmic reticulum (ER) disturbance is involved in the pathophysiology of neurodegenerative disorders, contributing to the activation of the ER stress-mediated apoptotic pathway. Therefore, we investigated here the molecular mechanisms underlying the ER-mitochondria axis, focusing on calcium as a potential mediator of cell death signals. Using NT2 cells treated with brefeldin A or tunicamycin, we observed that ER stress induces changes in the mitochondrial function, impairing mitochondrial membrane potential and distressing mitochondrial respiratory chain complex Moreover, stress stimuli at ER level evoked calcium fluxes between ER and mitochondria. Under these conditions, ER stress activated the unfolded protein response by an overexpression of GRP78, and also caspase-4 and-2, both involved upstream of caspase-9. Our findings show that ER and mitochondria interconnection plays a prominent role in the induction of neuronal cell death under particular stress circumstances.
Assuntos
Caspases/metabolismo , Retículo Endoplasmático/metabolismo , Mitocôndrias/enzimologia , Neurônios/enzimologia , Estresse Oxidativo , Western Blotting , Linhagem Celular Tumoral , Chaperona BiP do Retículo Endoplasmático , Ativação Enzimática , HumanosRESUMO
Between the April and July of 2007, patients undergoing treatment for schistosomal liver fibrosis, at a university hospital in north-eastern Brazil, were examined by transthoracic Doppler echocardiography (TTE). The main aim was to determine the prevalence of pulmonary hypertension in the patients. The thorax of each patient who had such hypertension, as indicated by an estimated pulmonary arterial systolic pressure (PASP) in excess of 35 mmHg, was then investigated by contrast-enhanced multidetector-row computed tomography (MDCT). The 84 patients (53 women and 31 men) enrolled in the study had a mean (S.D.) age of 50.06 (12.25) years. Nine (10.7%, with a 95% confidence interval of 5.0%-19.4%) of the patients were found to have pulmonary hypertension, with PASP ranging from 40-126 mmHg, and a median (S.D.) PASP of 58.78 (28.01) mmHg. The contrast-enhanced thoracic MDCT indicated that most of the patients with pulmonary hypertension had a pulmonary artery trunk that was unusually wide (67%) and more than 1.1-fold wider than the ascending aorta (56%), dilatation of the main pulmonary arteries (100%), a segmental artery that, in diameter, was more than 1.1-fold larger than the adjacent bronchi (89%), tapering of the peripheral pulmonary arteries (78%), and cardiac enlargement (78%). No patient suffered pulmonary embolism as a result of the investigations. The prevalence of pulmonary hypertension in the patients with schistosomal liver fibrosis (10.7%) justifies the screening of such patients by TTE.
Assuntos
Hipertensão Pulmonar/parasitologia , Cirrose Hepática/parasitologia , Hepatopatias Parasitárias/complicações , Esquistossomose mansoni/complicações , Adulto , Idoso , Ecocardiografia Doppler , Feminino , Volume Expiratório Forçado , Humanos , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/fisiopatologia , Cirrose Hepática/fisiopatologia , Hepatopatias Parasitárias/diagnóstico por imagem , Hepatopatias Parasitárias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/patologia , Esquistossomose mansoni/diagnóstico por imagem , Esquistossomose mansoni/fisiopatologia , Fumar/efeitos adversos , Tomografia Computadorizada por Raios X , Capacidade Vital , Adulto JovemRESUMO
INTRODUCTION: Merkel cell carcinoma (MCC) is a very rare and aggressive neoplasm. Due to its rarity, therapeutic guidelines are not well established, especially for regionally advanced disease. Hyperthermic isolated limb perfusion (HILP) with Melphalan and either with or without tumor necrosis factor-alpha (TNF-alpha) is becoming more common in clinical practice, yet the long-term response is not clear. Previous reports have established indications for treatment of unresectable MCC as well as the outcome of MCC patients receiving perfusion treatment in combination with other therapies (e.g., radiation). METHOD: A review was performed of the most important articles in MEDLINE from the last 20 years related to HILP and MCC. It was possible to collect all cases of HILP from the literature. Details of one case of MCC where HILP was administered was included in the literature review. RESULTS: A total of nine cases of MCC receiving ILP were identified in the literature; of these, seven achieved a complete response, one a partial response and one no response. All five patients treated without TNF-alpha had a complete response. Of the four patients treated with TNF-alpha, two had complete, one partial and one no response. CONCLUSION: Based on the cases described, isolated limb perfusion is an acceptable option to treat regional advanced cases of MCC, and the use of TNF-alpha does not impact the overall response.
Assuntos
Antineoplásicos/administração & dosagem , Carcinoma de Célula de Merkel/tratamento farmacológico , Melfalan/administração & dosagem , Neoplasias Cutâneas/tratamento farmacológico , Idoso de 80 Anos ou mais , Quimioterapia do Câncer por Perfusão Regional , Extremidades , Evolução Fatal , Feminino , Virilha , Humanos , Hipertermia Induzida , Excisão de Linfonodo , Metástase Linfática , Fator de Necrose Tumoral alfa/administração & dosagemRESUMO
BACKGROUND: Rotaviruses are major causes of diarrhea in children for which vaccines were developed and are currently in use. OBJECTIVES: To investigate the genotypes of rotavirus strains causing dehydrating diarrhea in children in Uberaba, Triângulo Mineiro region, Minas Gerais, during 2005-2006. METHODS: Rotavirus-associated diarrhea was investigated in fecal specimens by PAGE and strains were characterized for their genotype by RT-PCR and PCR-typing assays. RESULTS: Rotavirus was detected in 15% (39/260) of the fecal specimens by PAGE: 64% of the specimens presented short electrophoretic patterns and G2P[4] genotype; and 36% presented long electropherotypes and G1P[8], G9P[8], G4P[9] and two strains with sill undetermined G and P[8] genotype. A change in the dominant electrophoretic pattern was observed, shifting from long to short patterns and coinciding with the highest incidence of diarrheal cases. CONCLUSIONS: Those are the first data on rotavirus strains circulating in the Triângulo Mineiro region. They were obtained over a 16-month period that included the first 10 months after the launch of the national rotavirus immunization program that uses a monovalent G1P[8] attenuated vaccine strain. These results should further our understanding of the dynamics of rotavirus strains and help interpreting the significance of the program.