Clearance of immune complexes: role of complement and polymorphonuclear neutrophils

O sistema complemento desempenha um papel importante no transporte e eliminação de imunocomplexos (IC) circulantes. No entanto, existem circunstâncias em que os mecanismos envolvidos não são eficientes, favorecendo a deposição dos IC em órgãos específicos. Tais complexos depositados estimulam a fagocitose pelos polimorfonucleares neutrófilos, com conseqüente produção de radicais de oxigênio e liberação de enzimas lisossomais, e contribuem para a lesão tecidual local. Nesta revisão, damos ênfase ao papel do complemento, bem como dos neutrófilos, na patogênese das doenças por imunocomplexos.The complement system plays an important role in the transport and elimination of circulating immune complexes (IC). However, there are circunstances where the envolved mechanisms fail, leading to deposition of IC at specific organs. The deposited complexes stimulate phagocytosis by polymorphonuclear neutrophils, with production of oxygen radicals and release of lysossomal enzymes, thus contributing to tissular injury. In this review, we discuss the role of complement and neutrophils in pathogenesis of immune complexes diseases

Receptors for immunoglobulin G (FcyR)

Os receptores para IgG fazem uma importante ligação entre as respostas imunes humoral e celular. Estes receptores medeiam várias respostas biológicas tais como: fagocitose, endocitose, captura e clearance de imunocomplexos, citotoxicidade e liberação de mediadores inflamatórios. Os FcyR humanos pertencem à superfamília das imunoglobulinas e três classes principais destes receptores são descritas, as quais apresentam várias isoformas. Estas moléculas diferem quanto à afinidade e especificidade para os isotipos de IgG, distribuição celular, sinalização intracelular e pesos moleculares. Além disso, o polimorfismo genético é responsável por variações entre os indivíduos. A diversidade estrutural e funcional dos FcyR faz destas moléculas importantes alvos para a imunoterapia. A ativação e desativação de células efetoras via FcyR pode ser explorada para o desenvolvimento de novas terapias para o câncer, doenças infecciosas e desordens auto-imunes. Esta revisão descreve detalhes estruturais e funcionais, relevância clínica e alguns usos terapêuticos dos FcyR.Receptors for immunoglobulin G (FcyR) provide an important link between the humoral and cellular branches of the immune response. These receptors can trigger a variety of biological responses such as phagocytosis, endocytosis, capture and clearance of immune complexes, antibody-dependent cell citotoxicity and release of inflammatory mediators. Human FcyR belong to the Ig superfamily and three classes of these receptors are distinguished specifying many receptor isoforms. These molecules differ in affinity and specificity for IgG isotypes, cell distribution patterns, intracellular signal delivery and molecular weights. Moreover, the genetic polymorphism introduces variations among individuals. The structural and functional diversity makes these receptors potential targets for immunotherapy. Activation and deactivation of effector cells via FcyR can be exploited to develop novel therapies for cancer, infectious diseases and autoimmune disorders. This review describes structural and functional details, clinical relevance and some therapeutic use of the FcyR molecules.  &nbsp

Concentração e atividade de lisozima em tambaquis Colossoma macropomum vacinados contra Aeromonas hydrophila e suplementados com ß-Glucano.

Este estudo teve por objetivo avaliar o efeito da suplementação de ß-Glucano sobre a concentração e atividade de lisozima em tambaquis vacinados e desafiados com Aeromonas hydrophila

Early sedation and clinical outcomes of mechanically ventilated patients: a prospective multicenter cohort study

Introduction: Sedation overuse is frequent and possibly associated with poor outcomes in the intensive care unit (ICU) patients. However, the association of early oversedation with clinical outcomes has not been thoroughly evaluated. the aim of this study was to assess the association of early sedation strategies with outcomes of critically ill adult patients under mechanical ventilation (MV).Methods: A secondary analysis of a multicenter prospective cohort conducted in 45 Brazilian ICUs, including adult patients requiring ventilatory support and sedation in the first 48 hours of ICU admissions, was performed. Sedation depth was evaluated after 48 hours of MV. Multivariate analysis was used to identify variables associated with hospital mortality.Results: A total of 322 patients were evaluated. Overall, ICU and hospital mortality rates were 30.4% and 38.8%, respectively. Deep sedation was observed in 113 patients (35.1%). Longer duration of ventilatory support was observed (7 (4 to 10) versus 5 (3 to 9) days, P = 0.041) and more tracheostomies were performed in the deep sedation group (38.9% versus 22%, P=0.001) despite similar PaO2/FiO(2) ratios and acute respiratory distress syndrome (ARDS) severity. in a multivariate analysis, age (Odds Ratio (OR) 1.02; 95% confidence interval (CI) 1.00 to 1.03), Charlson Comorbidity Index >2 (OR 2.06; 95% Cl, 1.44 to 2.94), Simplified Acute Physiology Score 3 (SAPS 3) score (OR 1.02; Cl 95%, 1.00 to 1.04), severe ARDS (OR 1.44; Cl 95%, 1.09 to 1.91) and deep sedation (OR 2.36; Cl 9596, 1.31 to 4.25) were independently associated with increased hospital mortality.Conclusions: Early deep sedation is associated with adverse outcomes and constitutes an independent predictor of hospital mortality in mechanically ventilated patients.Research and Education Institute from Hospital Sirio-Libanes, São PauloD'Or Institute for Research and Education, Rio de Janeiro, BrazilBrazilian Research in Intensive Care NetworkHosp Copa DOr, BR-22031010 Rio de Janeiro, BrazilHosp Sirio Libanes, Res & Educ Inst, BR-01308060 São Paulo, BrazilUniv São Paulo, Fac Med, Hosp Clin, ICU,Emergency Med Dept, BR-05403000 São Paulo, BrazilHosp Sao Camilo Pompeia, ICU, BR-05022000 São Paulo, BrazilCEPETI, BR-82530200 Curitiba, Parana, BrazilHosp Canc I, Inst Nacl Canc, ICU, BR-20230130 Rio de Janeiro, BrazilPasteur Hosp, ICU, BR-20735040 Rio de Janeiro, BrazilIrmandade Santa Casa Misericordia Porto Alegre, RIPIMI, BR-90020090 Porto Alegre, RS, BrazilVitoria Apart Hosp, ICU, BR-29161900 Serra, ES, BrazilHosp Mater Dei, ICU, BR-30140093 Belo Horizonte, MG, BrazilHosp Santa Luzia, ICU, BR-70390902 Brasilia, DF, BrazilHosp Sao Luiz, ICU, BR-04544000 São Paulo, BrazilUniversidade Federal de São Paulo, Anesthesiol Pain & Intens Care Dept, ICU, BR-04024900 São Paulo, BrazilHosp Sao Jose Criciuma, ICU, BR-88801250 Criciuma, BrazilUDI Hosp, ICU, BR-65076820 Sao Luis, BrazilUniv São Paulo, Univ Hosp, ICU, BR-05508000 São Paulo, BrazilUniv São Paulo, Fac Med, Hosp Clin, ICU,Surg Emergency Dept, BR-05403000 São Paulo, BrazilIDOR DOr Inst Res & Educ, BR-22281100 Rio de Janeiro, BrazilInst Nacl Canc, Postgrad Program, BR-20230130 Rio de Janeiro, BrazilUniversidade Federal de São Paulo, Anesthesiol Pain & Intens Care Dept, ICU, BR-04024900 São Paulo, BrazilWeb of Scienc

Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Background: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42\ub74% vs 44\ub72%; absolute difference \u20131\ub769 [\u20139\ub758 to 6\ub711] p=0\ub767; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5\u20138] vs 6 [5\u20138] cm H2O; p=0\ub70011). ICU mortality was higher in MICs than in HICs (30\ub75% vs 19\ub79%; p=0\ub70004; adjusted effect 16\ub741% [95% CI 9\ub752\u201323\ub752]; p<0\ub70001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0\ub780 [95% CI 0\ub775\u20130\ub786]; p<0\ub70001). Interpretation: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status. Funding: No funding

Leukocytes respiratory burst and lysozyme level in pacu (Piaractus mesopotamicus Holmberg, 1887)

Respostas imunológicas inatas são úteis para determinar o estado de saúde de peixes e avaliar o efeito de substâncias imunomoduladoras no cultivo destes animais. A atividade respiratória de leucócitos foi medida em pacu (Piaractus mesopotamicus) através de ensaio de quimioluminescência e ensaio de redução do nitroblue tetrazolium (NBT). O ensaio de redução do nitroblue tetrazolium pareceu mais adequado que o ensaio de quimioluminescência para determinação da atividade respiratória de leucócitos, uma vez que foi difícil isolar com êxito os leucócitos do sangue para o ensaio de quimioluminescência. Lisozima sérica e plasmática foram medidas por meio de ensaio turbidimétrico. Com o objetivo de inativar as proteínas do sistema complemento, as amostras de soro e plasma foram aquecidas (56 ºC por 30 minutos). Porém, este procedimento provocou a turvação das amostras de plasma e interferiu nos resultados. A atividade de lisozima no soro foi maior que no plasma, sugerindo que amostras de soro são mais apropriadas para esta análise. Este estudo estabeleceu protocolos que podem ser utilizados como ferramentas no estudo de mecanismos imunológicos do peixe tropical pacu.Innate immune responses are useful to determine the health status of fish and to evaluate the effect of immunomodulatory substances in fish farming. Leukocytes respiratory burst was measured in pacu (Piaractus mesopotamicus) using chemiluminescence assay and nitroblue tetrazolium (NBT) reduction assay. The nitroblue tetrazolium reduction seemed more adequate than chemiluminescence assay for leukocytes oxidative burst determination, since it was difficult to isolate the blood leucocytes for chemiluminescence assay. Plasma and serum lysozyme were measured using a turbidimetric assay. The heating of serum and plasma samples (56 ºC for 30 minutes) for complement system inactivation darkened the plasma samples and interfered in the results. The lysozyme activity in serum was higher than in plasma, suggesting that serum samples are more appropriate for the analysis. This study established protocols that can be useful tools in the study of immune mechanisms of the tropical fish pacu.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Leukocytes respiratory burst and lysozyme level in pacu (Piaractus mesopotamicus Holmberg, 1887)

Innate immune responses are useful to determine the health status of fish and to evaluate the effect of immunomodulatory substances in fish farming. Leukocytes respiratory burst was measured in pacu (Piaractus mesopotamicus) using chemiluminescence assay and nitroblue tetrazolium (NBT) reduction assay. The nitroblue tetrazolium reduction seemed more adequate than chemiluminescence assay for leukocytes oxidative burst determination, since it was difficult to isolate the blood leucocytes for chemiluminescence assay. Plasma and serum lysozyme were measured using a turbidimetric assay. The heating of serum and plasma samples (56 ºC for 30 minutes) for complement system inactivation darkened the plasma samples and interfered in the results. The lysozyme activity in serum was higher than in plasma, suggesting that serum samples are more appropriate for the analysis. This study established protocols that can be useful tools in the study of immune mechanisms of the tropical fish pacu