Pseudomonas Aeruginosa AmpR Transcriptional Regulatory Network

In Enterobacteriaceae, the transcriptional regulator AmpR, a member of the LysR family, regulates the expression of a chromosomal β-lactamase AmpC. The regulatory repertoire of AmpR is broader in Pseudomonas aeruginosa, an opportunistic pathogen responsible for numerous acute and chronic infections including cystic fibrosis. Previous studies showed that in addition to regulating ampC, P. aeruginosa AmpR regulates the sigma factor AlgT/U and production of some quorum sensing (QS)-regulated virulence factors. In order to better understand the ampR regulon, the transcriptional profiles generated using DNA microarrays and RNA-Seq of the prototypic P. aeruginosa PAO1 strain with its isogenic ampR deletion mutant, PAO∆ampR were analyzed. Transcriptome analysis demonstrates that the AmpR regulon is much more extensive than previously thought influencing the differential expression of over 500 genes. In addition to regulating resistance to β-lactam antibiotics via AmpC, AmpR also regulates non-β-lactam antibiotic resistance by modulating the MexEF-OprN efflux pump. Virulence mechanisms including biofilm formation, QS-regulated acute virulence, and diverse physiological processes such as oxidative stress response, heat-shock response and iron uptake are AmpR-regulated. Real-time PCR and phenotypic assays confirmed the transcriptome data. Further, Caenorhabditis elegans model demonstrates that a functional AmpR is required for full pathogenicity of P. aeruginosa. AmpR, a member of the core genome, also regulates genes in the regions of genome plasticity that are acquired by horizontal gene transfer. The extensive AmpR regulon included other transcriptional regulators and sigma factors, accounting for the extensive AmpR regulon. Gene expression studies demonstrate AmpR-dependent expression of the QS master regulator LasR that controls expression of many virulence factors. Using a chromosomally tagged AmpR, ChIP-Seq studies show direct AmpR binding to the lasR promoter. The data demonstrates that AmpR functions as a global regulator in P. aeruginosa and is a positive regulator of acute virulence while negatively regulating chronic infection phenotypes. In summary, my dissertation sheds light on the complex regulatory circuit in P. aeruginosa to provide a better understanding of the bacterial response to antibiotics and how the organism coordinately regulates a myriad of virulence factors.

The effects of prone position ventilation on experimental mild acute lung injury induced by intraperitoneal lipopolysaccharide injection in rats

The benefits of prone position ventilation are well demonstrated in the severe forms of acute respiratory distress syndrome, but not in the milder forms. We investigated the effects of prone position on arterial blood gases, lung inflammation, and histology in an experimental mild acute lung injury (ALI) model. ALI was induced in Wistar rats by intraperitoneal Escherichia coli lipopolysaccharide (LPS, 5 mg/kg). After 24 h, the animals with PaO2/FIO2 between 200 and 300 mmHg were randomized into 2 groups: prone position (n = 6) and supine position (n = 6). Both groups were compared with a control group (n = 5) that was ventilated in the supine position. All of the groups were ventilated for 1 h with volume-controlled ventilation mode (tidal volume = 6 ml/kg, respiratory rate = 80 breaths/min, positive end-expiratory pressure = 5 cmH2O, inspired oxygen fraction = 1). Significantly higher lung injury scores were observed in the LPS-supine group compared to the LPS-prone and control groups (0.32 ± 0.03; 0.17 ± 0.03 and 0.13 ± 0.04, respectively) (p < 0.001), mainly due to a higher neutrophil infiltration level in the interstitial space and more proteinaceous debris that filled the airspaces. Similar differences were observed when the gravity-dependent lung regions and non-dependent lung regions were analyzed separately (p < 0.05). The BAL neutrophil content was also higher in the LPS-supine group compared to the LPS-prone and control groups (p < 0.05). There were no significant differences in the wet/dry ratio and gas exchange levels. In this experimental extrapulmonary mild ALI model, prone position ventilation for 1 h, when compared with supine position ventilation, was associated with lower lung inflammation and injury.

¿Cómo maximizar la utilización de recursos en el proyecto salud para el buen vivir (869) en pro de la disminución de la mortalidad infantil, por causas asociadas a EDA, IRA y Neumonía? Análisis descriptivo del proyecto salud para el buen vivir 869

Éste estudio describe la dinámica del sistema complejo emergente de la salud pública ambiental y su aplicación en el distrito capital, mediante la medición, ajuste, análisis y comparación de actividades y resultados en salud, obtenidos por el componente territorios ambientalmente saludables, en el área de mortalidad infantil asociada a EDA, IRA y neumonía, del proyecto Salud para el Buen Vivir ejecutado en el año 2013. De igual manera realiza aportes, mediante los cuales se proponen alternativas de solución que, por medio de la focalización poblacional, buscan superar las restricciones del sistema en pro del mejoramiento y el avance en la utilización de los recursos públicos de la salud ambiental.

Factores asociados a desenlaces clínicos en pacientes hospitalizados con diagnóstico de infección respiratoria aguda grave en una institución de nivel IV en Bogotá, Colombia

OBJETIVOS: Identificar los factores asociados a los desenlaces clínicos (muerte y estancia hospitalaria) en pacientes hospitalizados con diagnóstico de Infección Respiratoria Aguda Grave (IRAG) por grupos etarios, en una institución de nivel IV de Bogotá en el año 2015. POBLACIÓN Y MÉTODO: Estudio de corte transversal que incluyó la totalidad de pacientes de todas la edades hospitalizados con diagnóstico final IRAG notificados al sistema de vigilancia epidemiológica. Se realizó descripción de las características sociodemográficas y clínicas. Se hizo un análisis bivariado y multivariado para identificar los factores asociados a los desenlaces clínicos relevantes como muerte y estancia hospitalaria. CONCLUSIONES: La mayor prevalencia de la IRAG se presenta en los grupos extremos de la vida siendo la población menor de 5 años la de mayor número de casos. La mortalidad fue baja, siendo exclusiva del adulto mayor de 75 años asociada a puntuación alta en la escala CURB65. Las causas de estancia clínica prolongada son multifactoriales y pueden estar asociadas a condiciones propias de la historia natural de la enfermedad, a complicaciones, a descompensación de patologías de base o a factores no clínicos.

Icatibant, An Inhibitor Of Bradykinin Receptor 2, For Hereditary Angioedema Attacks: Prospective Experimental Single-cohort Study.

Hereditary angioedema (HAE) with C1 inhibitor deficiency manifests as recurrent episodes of edema involving the skin, upper respiratory tract and gastrointestinal tract. It can be lethal due to asphyxia. The aim here was to evaluate the response to therapy for these attacks using icatibant, an inhibitor of the bradykinin receptor, which was recently introduced into Brazil. Prospective experimental single-cohort study on the efficacy and safety of icatibant for HAE patients. Patients with a confirmed HAE diagnosis were enrolled according to symptoms and regardless of the time since onset of the attack. Icatibant was administered in accordance with the protocol that has been approved in Brazil. Symptom severity was assessed continuously and adverse events were monitored. 24 attacks in 20 HAE patients were treated (female/male 19:1; 19-55 years; median 29 years of age). The symptoms were: subcutaneous edema (22/24); abdominal pain (15/24) and upper airway obstruction (10/24). The time taken until onset of relief was: 5-10 minutes (5/24; 20.8%); 10-20 (5/24; 20.8%); 20-30 (8/24; 33.4%); 30-60 (5/24; 20.8%); and 2 hours (1/24; 4.3%). The time taken for complete resolution of symptoms ranged from 4.3 to 33.4 hours. Adverse effects were only reported at injection sites. Mild to moderate erythema and/or feelings of burning were reported by 15/24 patients, itching by 3 and no adverse effects in 6. HAE type I patients who received icatibant responded promptly; most achieved improved symptom severity within 30 minutes. Local adverse events occurred in 75% of the patients.

Monitoramento de parâmetros imunológicos em atletas adolescentes de basquetebol durante e após a temporada esportiva= : Monitoring of immunological parameters in adolescent basketball athletes during and after a sports season

Universidade Estadual de Campinas . Faculdade de Educação Física

Poluição da queima de cana e sintomas respiratórios em escolares de Monte Aprazível, SP

OBJETIVO: Estimar a prevalência de sintomas respiratórios e analisar fatores associados, bem como medidas de pico de fluxo expiratório em escolares. MÉTODOS: Estudo descritivo transversal com escolares de dez a 14 anos de Monte Aprazível, SP. Foram aplicados questionários sobre sintomas de asma e de rinite do protocolo International Study of Asthma and Allergies in Childhood, questões sociodemográficas, fatores predisponentes e antecedentes pessoais e familiares. Foram realizadas medidas repetidas do pico de fluxo expiratório nas crianças e dos níveis de concentração de material particulado (MP2,5) e de black carbon. RESULTADOS: A prevalência de sintomas de asma foi de 11% e de 33,2% de rinite; 10,6% apresentaram mais de quatro crises de sibilos nos últimos 12 meses. Antecedentes familiares para bronquite e rinite associaram-se à presença de asma (p = 0,002 e p < 0,001) e de rinite atuais (p < 0,001 e p < 0,001, respectivamente). Para rinite, houve associação com presença de mofo ou rachadura na casa (p = 0,009). Houve maior freqüência de rinite nos meses de junho a outubro, período de safra da cana de açúcar. Prevalência diária de pico de fluxo expiratório abaixo de 20% da mediana de medidas na criança foi maior em dias com maior concentração de MP2,5. CONCLUSÕES: A prevalência de sintomas de asma está abaixo e a de rinite está acima da média nacional. Ainda que dentro dos níveis aceitáveis, a poluição nos períodos de queima da palha da cana-de-açúcar pode contribuir para a exacerbação de episódios de asma e de rinite.

Circulation of antibodies against yellow fever virus in a simian population in the area of Porto Primavera Hydroelectric Plant, São Paulo, Brazil

Yellow fever (YF) is an acute viral infectious disease transmitted by mosquitoes which occurs in two distinct epidemiological cycles: sylvatic and urban. In the sylvatic cycle, the virus is maintained by monkey's infection and transovarian transmission in vectors. Surveillance of non-human primates is required for the detection of viral circulation during epizootics, and for the identification of unaffected or transition areas. An ELISA (enzyme-linked immunosorbent assay) was standardized for estimation of the prevalence of IgG antibodies against yellow fever virus in monkey sera (Alouatta caraya) from the reservoir area of Porto Primavera Hydroelectric Plant, in the state of São Paulo, Brazil. A total of 570 monkey sera samples were tested and none was reactive to antibodies against yellow fever virus. The results corroborate the epidemiology of yellow fever in the area. Even though it is considered a transition area, there were no reports to date of epizootics or yellow fever outbreaks in humans. Also, entomological investigations did not detect the presence of vectors of this arbovirus infection. ELISA proved to be fast, sensitive, an adequate assay, and an instrument for active search in the epidemiological surveillance of yellow fever allowing the implementation of prevention actions, even before the occurrence of epizootics.

O uso da acupuntura no auxílio à terapia da doença idiopática do trato urinário inferior dos felinos

Diferentes afecções podem acometer o trato urinário inferior dos felinos, acarretando sinais clínicos inespecíficos como: hematúria, disúria, polaquiúria, estrangúria, periúria ou obstrução, caracterizando a doença do trato urinário inferior dos felinos (DTUIF). Entretanto, em até 65% dos felinos acometidos, a etiologia é indeterminada, denominada de doença idiopática do trato urinário inferior dos felinos (DTUIF idiopática), que tem se mostrado como um desafio ao clínico veterinário, uma vez que não há diagnóstico específico ou terapia efetiva. Atualmente, tem sido estudado o papel da inflamação neurogênica da bexiga urinária secundária ao estresse, como etiologia da DTUIF idiopática. Há evidências científicas de que a acupuntura restaure a homeostase, reduza o estresse e, pela estimulação neural periférica, ative mecanismos endógenos de antinocicepção, regulando a liberação de mediadores dos mecanismos da dor e do processo inflamatório, como a substância P. O objetivo desta revisão bibliográfica foi descrever como a acupuntura pode ser um recurso na terapia da DTUIF idiopática, tendo como base a modulação da inflamação neurogênica da bexiga urinária e o controle do estresse desses gatos.

Morbi-mortalidade por doenças do aparelho respiratório em idosos antes e após a introdução da vacina contra influenza: município de Cubatão, São Paulo, 1999-2005

Apresenta-se análise da morbi-mortalidade por Doenças do Aparelho Respiratório entre idosos de Cubatão e cobertura vacinal no período 1999-2005. Observa-se tendência de redução, acompanhada de aumento da cobertura de vacinação contra o vírus influenza

Queimadas de cana-de-açúcar no Brasil: efeitos à saúde respiratória

O artigo objetivou atualizar as informações sobre a produção científica referente aos efeitos da queima da cana-de-açúcar à saúde respiratória, em vista da expansão das plantações de cana no Brasil e no estado de São Paulo. São comentados estudos publicados no período de 1996-2006 que tratam de efeitos à saúde da queima da cana e/ou de poluentes atmosféricos produzidos pela queima. Os estudos sugerem que uma parcela da população - sobretudo de idosos, crianças e asmáticos - tem sua saúde agravada pela queima da cana-de-açúcar, demandando atendimento dos serviços de saúde e assim onerando os serviços de saúde e suas famílias

Circulation of antibodies against yellow fever virus in a simian population in the area of Porto Primavera hydroeletric plant, São Paulo, Brazil

A febre amarela (FA) é doença infecciosa aguda de origem viral transmitida por mosquitos. No ciclo silvestre, o vírus é mantido por meio da infecção de macacos e da transmissão transovariana nos vetores. A vigilância sobre populações de primatas não humanos torna-se necessária para detectar a circulação viral, quando ainda está restrito a epizootias, e para determinar sua presença em regiões indenes ou de transição para a doença. Padronizou-se a técnica ELISA (Enzyme Linked Immunosorbent Assay) para determinar a prevalência de anticorpos da classe IgG contra o vírus da FA em soros de bugios (Alouatta caraya) da região do reservatório da Usina Hidrelétrica de Porto Primavera, SP. Foram testados soros de 570 macacos sendo que nenhuma amostra mostrou-se reativa para a presença de anticorpos contra o vírus da FA. Os resultados são coerentes com a epidemiologia da FA na região. Mesmo sendo área de transição, não se conhece, até o momento, ocorrência de epizootia ou surto de FA em humanos e investigações entomológicas não apontaram a presença de vetores para esta arbovirose. A técnica mostrou-se sensível, rápida e útil à vigilância epidemiológica como instrumento de busca ativa permitindo desencadear ações preventivas, como vacinação, antes mesmo do surgimento de epizootias

The impact of a 17-day training period for an international championship on mucosal immune parameters in top-level basketball players and staff members

This investigation examined the impact of a 17-d training period (that included basketball-specific training, sprints, intermittent running exercises, and weight training, prior to an international championship competition) on salivary immunoglobulin A (SIgA) levels in 10 subjects (athletes and staff members) from a national basketball team, as a biomarker for mucosal immune defence. Unstimulated saliva samples were collected at rest at the beginning of the preparation for the Pan American Games and 1 d before the first game. The recovery interval from the last bout of exercise was 4 h. The SIgA level was measured using enzyme-linked immunosorbent assay and expressed as absolute concentrations, secretion rate, and SIgA level relative to total protein. The decrease in SIgA levels following training was greater in athletes than in support staff; however, no significant differences between the two groups were detected. A decrease in SIgA level, regardless of the method used to express IgA results, was verified for athletes. Only one episode of upper respiratory tract illness symptoms was reported, and it was not associated with changes in SIgA levels. In summary, a situation of combined stress for an important championship was found to decrease the level of SIgA-mediated immune protection at the mucosal surface in team members, with greater changes observed in the athletes.

Salivary immunoglobulin a responses in professional top-level futsal players

Moreira, A, Arsati, F, de Oliveira Lima-Arsati, YB, de Freitas, CG, and de Araujo, VC. Salivary immunoglobulin a responses in professional top-level futsal players. J Strength Cond Res 25(7): 1932-1936, 2011-The purpose of this study was to investigate the responses of salivary immunoglobulin A (SIgA) in 10 professional top-level Brazilian futsal players after 2 highly competitive games separated by 7 days. Unstimulated saliva was collected over a 5-minute period at PRE- and POST-match. The SIgA was measured by an enzyme-linked immunosorbent assay and expressed as the absolute concentration (SIgAabs) and secretion rate of IgA (SIgArate). Rate of perceived exertion and heart rate were used to monitor the exercise intensity. A 2-way analysis of variance with repeated measures showed nonsignificant differences between matches to SIgAabs, SIgArate, and saliva flow rate (p > 0.05). However, significant time differences were observed for all these parameters. In summary, we showed that a competitive training match induced a decrease in SIgA levels in top-level futsal players, which suggests an increment of the vulnerability to infections meditated by the training stimulus. This decrease suggests that the athletes were at an increased risk of developing an upper respiratory tract infection, and therefore, it could be necessary to take protective actions to minimize contact with cold viruses or even reduce the training load for athletes.

Equine laminitis: loss of hemidesmosomes in hoof secondary epidermal lamellae correlates to dose in an oligofructose induction model: an ultrastructural study

Reasons for performing study: Light microscopical studies show that the key lesion of laminitis is separation at the hoof lamellar dermal-epidermal interface. More precise knowledge of the damage occurring in the lamellar basement membrane zone may result if laminitis affected tissue is examined with the transmission electron microscope. This could lead to better understanding of the pathogenesis of lesions and the means of treatment or prevention. Objectives: To investigate the ultrastructure of acute laminitis as disease of greater severity is induced by increasing oligofructose (OF) dosage. Methods: Three pairs of normal horses, dosed with OF at 7.5, 10 and 12.5 g/kg bwt via nasogastric intubation, developed laminitis 48 h later. Following euthanasia, their forefeet were processed for transmission electron microscopy. Lamellar basal cell hemidesmosome (HD) numbers and the distance between the basal cell plasmalemma and the lamina densa of the basement membrane were estimated and compared to control tissue. Results: Increasing OF dosage caused greater HD loss and more severe laminitis. The characteristic separation of the basement membrane, cytoskeleton failure and rounded basal cell nuclei results from combined HD dysassembly and anchoring filament failure. Conclusions: Without properly assembled HDs, dysadhesion between the lamina densa of the basement membrane (BM) and epidermal basal cells occurs, emphasising the fundamental importance of HDs in maintaining attachment at the lamellar interface. Medical conditions that trigger lamellar matrix metalloproteinase (MMP) activation and/or compromise entry of glucose into lamellar basal cells appear to promote loss and failure of HDs and, therefore, laminitis development. Potential relevance: A correlation between lameness severity and escalating loss of lamellar HDs now exists. Therapy aimed at protecting the lamellar environment from haematogenous delivery of MMP activators or from glucose deprivation may control laminitis development.