Epidemiology of acute kidney injury in the clinical emergency: A prospective cohort study at a high-complexity public university hospital in São Paulo, Brazil.

INTRODUCTION: Southern Hemisphere countries have been underrepresented in epidemiological studies on acute kidney injury (AKI). The objectives of this study were to determine the frequency, risk factors, and outcomes of AKI in adult hospitalized patients from the emergency department of a public high-complexity teaching hospital in the city of São Paulo, Brazil. METHODS: Observational and prospective study. AKI was defined by the KDIGO guidelines (Kidney Disease: Improving Global Outcomes) using only serum creatinine. RESULTS: Among the 731 patients studied (age: median 61 years, IQR 47-72 years; 55% male), 48% had hypertension and 28% had diabetes as comorbidities. The frequency of AKI was 52.1% (25.9% community-based AKI [C-AKI] and 26.3% hospital-acquired AKI [H-AKI]). Dehydration, hypotension, and edema were found in 29%, 15%, and 15% of participants, respectively, at hospital admission. The in-hospital and 12-month mortality rates of patients with vs. without AKI were 25.2% vs. 11.1% (p<0.001) and 36.7% vs. 12.9% (p<0.001), respectively. The independent risk factors for C-AKI were chronic kidney disease (CKD), chronic liver disease, age, and hospitalization for cardiovascular disease. Those for H-AKI were CKD, heart failure as comorbidities, hypotension, and edema at hospital admission. H-AKI was an independent risk factor for death in the hospital, but not at 12 months. C-AKI was not a risk factor for death. CONCLUSIONS: AKI occurred in more than half of the admissions to the clinical emergency department of the hospital and was equally distributed between C-AKI and H-AKI. Many patients had correctable risk factors for AKI, such as dehydration and arterial hypotension (44%) at admission. The only independent risk factor for both C-AKI and H-AKI was CKD as comorbidity.

The growing impact of older patients in the emergency department: a 5-year retrospective analysis in Brazil.

BACKGROUND: The average age of the global population is rising at an increasing rate. There is a disproportional increase in Emergency Department (ED) visits by older people worldwide. In the Brazilian health system, complex and severely ill patients and those requiring specialized urgent procedures are referred to tertiary level care. As far as we know, no other study in Latin America has analyzed the impact of demographic changes in tertiary ED attendance. AIM: To describe the sociodemographic characteristics and outcomes of tertiary Brazilian ED users. METHODS: Design: Observational cross-sectional analytic study. SETTING: Emergency Department, tertiary university hospital, São Paulo, Brazil. PARTICIPANTS: patients aged 18 years or older attending a tertiary ED (2009-2013). The primary outcomes were hospitalization and mortality; the secondary outcome was ICU admission. Age was categorized as 'young adults' (18-39y), 'adults' (40-59y), 'young-older adults' (60-79y), and 'old-older adults' (80-109y). Other variables included sex, reason for attendance, time of ED visit, mode of presentation, type of hospitalization, main procedure, length of hospital stay (LOS) and length of ICU stay (ICU-LOS). We calculated descriptive statistics, built generalized linear mixed models for each outcome and estimated Odds Ratios (95% CI) for the independent categorical variables. The significance level was 5% with Bonferroni correction. RESULTS: Older age-groups represented 26.6% of 333,028 ED visits, 40.7% of admissions, 42.7% of ICU admissions and 58% of all deaths. Old-older patients accounted for 5.1% of ED visits, 9.5% of admissions and 10.1% of ICU admissions. Hospitalization, ICU admission and mortality rates increased with older age in both sexes. LOS and ICU-LOS were similar across age-groups. The proportions of visits and admissions attributed to young adults decreased annually, while those of people aged 60 or over increased. The ORs for hospitalization, ICU admission and mortality associated with the old-older group were 3.49 (95% CI = 3.15-3.87), 1.27 (1.15-1.39) and 5.93 (5.29-6.66) respectively, with young adults as the reference. CONCLUSIONS: In tertiary ED, age is an important risk factor for hospitalization and mortality, but not for ICU admission. Old-older people are at the greatest risk and demand further subgroup stratification.

A decision-aid tool for ICU admission triage is associated with a reduction in potentially inappropriate intensive care unit admissions.

PURPOSE: Intensive care unit (ICU) admission triage occurs frequently and often involves highly subjective decisions that may lead to potentially inappropriate ICU admissions. In this study, we evaluated the effect of implementing a decision-aid tool for ICU triage on ICU admission decisions. METHODS: This was a prospective, before-after study. Urgent ICU referrals to ten ICUs in a tertiary hospital in Brazil were assessed before and after the implementation of the decision-aid tool. Our primary outcome was the proportion of potentially inappropriate ICU referrals (defined as priority 4B or 5 referrals, accordingly to the Society of Critical Care Medicine guidelines of 1999 and 2016, respectively) admitted to the ICU within 48 h. We conducted multivariate analyses to adjust for potential confounders and evaluated the interaction between phase and triage priority. RESULTS: Of the 2201 patients analyzed, 1184 (53.8%) patients were admitted to the ICU. After adjustment for confounders, implementation of the decision-aid tool was associated with a reduction in potentially inappropriate ICU admissions using either the 1999 [adjOR (95% CI) = 0.36 (0.13-0.97)] or 2016 [adjOR (95%CI) = 0.35 (0.13-0.96)] definitions. CONCLUSION: Implementation of a decision-aid tool for ICU triage was associated with a reduction in potentially inappropriate ICU admissions.

Comparison of the effects of volemic reposition with 7. 5 % NaCl or blood in an experimental model of muscular compression and hemorrhagic shock / Comparação dos efeitos da reposição volêmica com NaCl 7, 5 % ou sangue em um modelo experimental de compressão muscular e choque hemorrágico

ABSTRACT Objective: Crush syndrome is characterized by traumatic muscular injuries with severe systemic clinical repercussions. The systemic inflammatory reaction characterized acutely by infiltration of neutrophils in the lungs has been studied as part of the spectrum of crush syndrome. Experimental research may demonstrate alternative treatments for crush syndrome. The authors studied the hypothesis that hypertonic saline solution (7.5% NaCl) could minimize the local and systemic effects in a model of muscular compression and hemorrhagic shock. Methods: Rabbits were submitted to a new model of muscle compression associated with hemorrhagic shock. Compression was applied through an Esmarch bandage, used for 1 h on the entire right lower limb. Hemorrhagic shock was induced for 1 h by dissection and catheterization of the carotid artery. Blood replacement or hypertonic saline solution was used to treat the shock. Biochemical analysis of plasma, quantification of muscular edema, and infiltration of inflammatory cells in the lungs were carried out. Results: Animals treated with hypertonic solution presented the same hemodynamic response as the blood treated patients, less water in the compressed muscles and less infiltration of inflammatory cells in the lungs. The blood group presented hypocalcemia, a facet of crush syndrome. Conclusions: The proposed model was effective for the study of crush syndrome associated with hemorrhagic shock. The treatment with hypertonic solution showed benefits when compared with blood volume replacement.

RESUMO Objetivo: A síndrome de esmagamento é caracterizada por lesões musculares traumáticas com graves repercussões clínicas sistêmicas. A reação inflamatória sistêmica, caracterizada agudamente por infiltração de neutrófilos nos pulmões, tem sido estudada como parte do espectro da síndrome de esmagamento. A pesquisa experimental pode demonstrar opções de tratamento para a síndrome de esmagamento. Os autores estudaram a hipótese de que solução salina hipertônica (NaCl 7,5%) pudesse minimizar os efeitos locais e sistêmicos da síndrome de esmagamento em um modelo de compressão muscular e choque hemorrágico. Métodos: Coelhos foram submetidos a um novo modelo de compressão muscular associado ao choque hemorrágico. A compressão foi feita por uma faixa de Esmarch aplicada por uma hora em todo membro inferior direito. O choque hemorrágico foi induzido durante uma hora por dissecção e cateterização da artéria carótida. O choque foi tratado com reposição de sangue ou solução salina hipertônica. Foram feitas análises bioquímicas do plasma, quantificação do edema muscular e infiltração de células inflamatórias nos pulmões. Resultados: Os animais tratados com solução hipertônica apresentaram a mesma resposta hemodinâmica observada naqueles tratados com sangue, menor quantidade de água nos músculos comprimidos e menor infiltração de células inflamatórias nos pulmões. O grupo tratado com sangue apresentou hipocalcemia, característica da síndrome de esmagamento. Conclusões: O modelo proposto mostrou-se efetivo para o estudo da síndrome de esmagamento associada ao choque hemorrágico. O tratamento com solução hipertônica apresentou benefícios quando comparado com a reposição volêmica com sangue.

Comparison of the effects of volemic reposition with 7.5% NaCl or blood in an experimental model of muscular compression and hemorrhagic shock.

OBJECTIVE: Crush syndrome is characterized by traumatic muscular injuries with severe systemic clinical repercussions. The systemic inflammatory reaction characterized acutely by infiltration of neutrophils in the lungs has been studied as part of the spectrum of crush syndrome. Experimental research may demonstrate alternative treatments for crush syndrome. The authors studied the hypothesis that hypertonic saline solution (7.5% NaCl) could minimize the local and systemic effects in a model of muscular compression and hemorrhagic shock. METHODS: Rabbits were submitted to a new model of muscle compression associated with hemorrhagic shock. Compression was applied through an Esmarch bandage, used for 1 h on the entire right lower limb. Hemorrhagic shock was induced for 1 h by dissection and catheterization of the carotid artery. Blood replacement or hypertonic saline solution was used to treat the shock. Biochemical analysis of plasma, quantification of muscular edema, and infiltration of inflammatory cells in the lungs were carried out. RESULTS: Animals treated with hypertonic solution presented the same hemodynamic response as the blood treated patients, less water in the compressed muscles and less infiltration of inflammatory cells in the lungs. The blood group presented hypocalcemia, a facet of crush syndrome. CONCLUSIONS: The proposed model was effective for the study of crush syndrome associated with hemorrhagic shock. The treatment with hypertonic solution showed benefits when compared with blood volume replacement.

OBJETIVO: A síndrome de esmagamento é caracterizada por lesões musculares traumáticas com graves repercussões clínicas sistêmicas. A reação inflamatória sistêmica, caracterizada agudamente por infiltração de neutrófilos nos pulmões, tem sido estudada como parte do espectro da síndrome de esmagamento. A pesquisa experimental pode demonstrar opções de tratamento para a síndrome de esmagamento. Os autores estudaram a hipótese de que solução salina hipertônica (NaCl 7,5%) pudesse minimizar os efeitos locais e sistêmicos da síndrome de esmagamento em um modelo de compressão muscular e choque hemorrágico. MÉTODOS: Coelhos foram submetidos a um novo modelo de compressão muscular associado ao choque hemorrágico. A compressão foi feita por uma faixa de Esmarch aplicada por uma hora em todo membro inferior direito. O choque hemorrágico foi induzido durante uma hora por dissecção e cateterização da artéria carótida. O choque foi tratado com reposição de sangue ou solução salina hipertônica. Foram feitas análises bioquímicas do plasma, quantificação do edema muscular e infiltração de células inflamatórias nos pulmões. RESULTADOS: Os animais tratados com solução hipertônica apresentaram a mesma resposta hemodinâmica observada naqueles tratados com sangue, menor quantidade de água nos músculos comprimidos e menor infiltração de células inflamatórias nos pulmões. O grupo tratado com sangue apresentou hipocalcemia, característica da síndrome de esmagamento. CONCLUSÕES: O modelo proposto mostrou-se efetivo para o estudo da síndrome de esmagamento associada ao choque hemorrágico. O tratamento com solução hipertônica apresentou benefícios quando comparado com a reposição volêmica com sangue.

Antimicrobial peptide LL-37 participates in the transcriptional regulation of melanoma cells.

Antimicrobial peptides are an ancient family of molecules that emerged millions of years ago and have been strongly conserved during the evolutionary process of living organisms. Recently, our group described that the human antimicrobial peptide LL-37 migrates to the nucleus, raising the possibility that LL-37 could directly modulate transcription under certain conditions. Here, we showed evidence that LL-37 binds to gene promoter regions, and LL-37 gene silencing changed the transcriptional program of melanoma A375 cells genes associated with histone, metabolism, cellular stress, ubiquitination and mitochondria.

Negative regulation of bacterial killing and inflammation by two novel CD16 ligands.

Sepsis, a leading cause of death worldwide, involves exacerbated proinflammatory responses and inefficient bacterial clearance. Phagocytic cells play a crucial part in the prevention of sepsis by clearing bacteria through host innate receptors. Here, we used a phage display library to identify two peptides in Escherichia coli that interact with host innate receptors. One of these peptides, encoded by the wzxE gene of E. coli K-12, was involved in the transbilayer movement of a trisaccharide-lipid intermediate in the assembly of enterobacterial common antigen. Peptide-receptor interactions induced CD16-mediated inhibitory immunoreceptor tyrosine-based activating motif signaling, blocking the production of ROS and bacterial killing. This CD16-mediated inhibitory signaling was abrogated in a WzxE(-/-) mutant of E. coli K-12, restoring the production of ROS and bacterial killing. Taken together, the two novel CD16 ligands identified negatively regulate bacterial killing and inflammation. Our findings may contribute toward the development of new immunotherapies for E. coli-mediated infectious diseases and inflammation.

Development of an algorithm to aid triage decisions for intensive care unit admission: a clinical vignette and retrospective cohort study.

BACKGROUND: Intensive care unit (ICU) admission triage is performed routinely and is often based solely on clinical judgment, which could mask biases. A computerized algorithm to aid ICU triage decisions was developed to classify patients into the Society of Critical Care Medicine's prioritization system. In this study, we sought to evaluate the reliability and validity of this algorithm. METHODS: Nine senior physicians evaluated forty clinical vignettes based on real patients. The reference standard was defined as the priorities ascribed by two investigators with full access to patients' records. Agreement of algorithm-based priorities with the reference standard and with intuitive priorities provided by the physicians were evaluated. Correlations between algorithm prioritization and physicians' judgment of the appropriateness of ICU admissions in scarcity and nonscarcity settings were also evaluated. Validity was further assessed by retrospectively applying this algorithm to 603 patients with requests for ICU admission for association with clinical outcomes. RESULTS: Agreement between algorithm-based priorities and the reference standard was substantial, with a median κ of 0.72 (interquartile range [IQR] 0.52-0.77). Algorithm-based priorities demonstrated higher interrater reliability (overall κ 0.61, 95% confidence interval [CI] 0.57-0.65; median percentage agreement 0.64, IQR 0.59-0.70) than physicians' intuitive prioritization (overall κ 0.51, 95% CI 0.47-0.55; median percentage agreement 0.49, IQR 0.44-0.56) (p = 0.001). Algorithm-based priorities were also associated with physicians' judgment of appropriateness of ICU admission (priorities 1, 2, 3, and 4 vignettes would be admitted to the last ICU bed in 83.7%, 61.2%, 45.2%, and 16.8% of the scenarios, respectively; p < 0.001) and with actual ICU admission, palliative care consultation, and hospital mortality in the retrospective cohort. CONCLUSIONS: This ICU admission triage algorithm demonstrated good reliability and validity. However, more studies are needed to evaluate a difference in benefit of ICU admission justifying the admission of one priority stratum over the others.

Fc Gamma Receptor IIA (CD32A) R131 Polymorphism as a Marker of Genetic Susceptibility to Sepsis.

Sepsis is a devastating disease that can affect humans at any time between neonates and the elderly and is associated with mortality rates that range from 30 to 80%. Despite intensive efforts, its treatment has remained the same over the last few decades. Fc receptors regulate multiple immune responses and have been investigated in diverse complex diseases. FcγRIIA (CD32A) is an immunoreceptor, tyrosine-based activation motif-bearing receptor that binds immunoglobulin G and C-reactive protein, important opsonins in host defense. We conducted a study of 702 patients (184 healthy individuals, 171 non-infected critically ill patients, and 347 sepsis patients) to investigate if genetic polymorphisms in the CD32A coding region affect the risk of septic shock. All individuals were genotyped for a variant at position 131 of the FcγRIIA gene. We found that allele G, associated with the R131 genotype, was significantly more frequent in septic patients than in the other groups (p = 0.05). Our data indicate that FcγRIIA genotyping can be used as a marker of genetic susceptibility to sepsis.

Impact of Time on Fluid Resuscitation with Hypertonic Saline (NaCl 7.5%) in Rats with LPS-Induced Acute Lung Injury.

Acute lung injury (ALI) is a common complication associated with septic shock that directly influences the prognosis of sepsis patients. Currently, one of the main supportive treatment modalities for septic shock is fluid resuscitation. The use of hypertonic saline (HS: 7.5% NaCl) for fluid resuscitation has been described as a promising therapy in experimental models of sepsis-induced ALI, but it has failed to produce similar results in clinical practice. Thus, we compared experimental timing versus clinical timing effectiveness (i.e., early vs. late fluid resuscitation) after the inflammatory scenario was established in a rat model of bacterial lipopolysaccharide-induced ALI. We found that late fluid resuscitation with hypertonic saline (NaCl 7.5%) did not reduce the mortality rates of animals compared with the mortality late associated with early treatment. Late fluid resuscitation with both hypertonic and normal saline increased pulmonary inflammation, decreased pulmonary function, and induced pulmonary injury by elevating metalloproteinase-2 and metalloproteinase-9 activity and collagen deposition in the animals, unlike early treatment. The animals with lipopolysaccharide-induced ALI that received late resuscitation with any kind of fluids demonstrated aggravated pulmonary injury and respiratory function. Moreover, we showed that the therapeutic window for a beneficial effect of fluid resuscitation with hypertonic saline is very narrow.

Plasma cytokine expression after lower-limb compression in rats.

OBJECTIVES: Muscle injury due to crushing (muscle compression injury) is associated with systemic manifestations known as crush syndrome. A systemic inflammatory reaction may also be triggered by isolated muscle injury. The aim of this study was to investigate the plasma levels of interleukins (IL) 1, 6 and 10 and tumor necrosis factor alpha (TNF-α), which are markers for possible systemic inflammatory reactions, after isolated muscle injury resulting from lower-limb compression in rats. METHODS: Male Wistar rats were subjected to 1 h of compression of their lower limbs by means of a rubber band. The plasma levels of IL 1, 6 and 10 and TNF-α were measured 1, 2 and 4 h after the rats were released from compression. RESULTS: The plasma levels of IL 10 decreased in relation to those of the other groups, with a statistically significant difference (p < 0.05). The method used did not detect the presence of IL 1, IL 6 or TNF-α. CONCLUSION: Our results demonstrated that the changes in plasma levels of IL 10 that were found may have been a sign of the presence of circulating interleukins in this model of lower-limb compression in rats.

OBJETIVOS: A lesão muscular por esmagamento (lesão por compressão muscular) está associada a manifestações sistêmicas conhecidas como síndrome do esmagamento. A reação inflamatória sistêmica pode também ser desencadeada pela lesão muscular isolada. O objetivo deste estudo foi investigar os níveis plasmáticos de interleucinas (IL) 1, 6, 10 e TNF-α, marcadores de uma possível reação inflamatória sistêmica, após a lesão muscular isolada resultante da compressão de membros inferiores de ratos. MÉTODOS: Ratos Wistar machos foram submetidos a uma hora de compressão dos membros inferiores por uma faixa de borracha. Os níveis plasmáticos de IL 1, 6, 10 e TNF-α foram medidos uma, duas e quatro horas após a liberação da compressão. RESULTADOS: Os níveis plasmáticos de IL 10 diminuíram quando comparados com outros grupos com diferença estatisticamente significante (p < 0,05). Não houve detecção, pelo método, da presença de IL 1, 6 e TNF-α. CONCLUSÃO: Nossos resultados demonstraram que as alterações dos níveis plasmáticos de IL 10 encontradas podem ser um sinal da presença de interleucinas circulantes nesse modelo de compressão de membros inferiores de ratos.

Auditory brainstem response in gerbils submitted to ischemia and sepsis.

INTRODUCTION: An ischemic stroke is a clinical condition that affects thousands of people worldwide. As a result of this injury, neuronal death can be observed, and in the natural course of recovery, the individual may develop sepsis. Sepsis is a systemic inflammatory response that can lead the patient to death. To assess the clinical condition of a patient with this condition, the Auditory Brainstem Response (ABR) can be useful, since it is not an invasive procedure, it is a fast technique and it can be done at the bedside. PURPOSE: To assess auditory brainstem response (ABR) latency values in gerbils subjected to ischemia and sepsis. METHODS: ABR values were collected from 72 adult male gerbils, which were divided into six groups: control, sepsis, ischemia, sham, ischemia with sepsis, and sham with sepsis. For the induction of sepsis, lipopolysaccharide (LPS) was applied intraperitoneally in gerbils. The animals were anesthetized with a ketamine/xylazine combination before collection; their ABR were collected before any procedure (base collection), after ischemia, and 24 hours after the application of LPS. The absolute latency of wave IV was evaluated, and the values were compared between groups. RESULTS: There were significant differences in the groups submitted to sepsis in the latency value of wave IV in relation with the other groups. CONCLUSION: ABR was sensitive to sepsis with the increase in latency of wave IV during the development of the disease in the experimental model used.

Hypertonic Saline (NaCl 7.5%) Reduces LPS-Induced Acute Lung Injury in Rats.

Acute respiratory distress syndrome (ARDS) is the most severe lung inflammatory manifestation and has no effective therapy nowadays. Sepsis is one of the main illnesses among ARDS causes. The use of fluid resuscitation is an important treatment for sepsis, but positive fluid balance may induce pulmonary injury. As an alternative, fluid resuscitation with hypertonic saline ((HS) NaCl 7.5%) has been described as a promising therapeutical agent in sepsis-induced ARDS by the diminished amount of fluid necessary. Thus, we evaluated the effect of hypertonic saline in the treatment of LPS-induced ARDS. We found that hypertonic saline (NaCl 7.5%) treatment in rat model of LPS-induced ARDS avoided pulmonary function worsening and inhibited type I collagen deposition. In addition, hypertonic saline prevented pulmonary injury by decreasing metalloproteinase 9 (MMP-9) activity in tissue. Focal adhesion kinase (FAK) activation was reduced in HS group as well as neutrophil infiltration, NOS2 expression and NO content. Our study shows that fluid resuscitation with hypertonic saline decreases the progression of LPS-induced ARDS due to inhibition of pulmonary remodeling that is observed when regular saline is used.

Auditory brainstem response in gerbils submitted to ischemia and sepsis / Potencial evocado auditivo de tronco encefálico em gerbils submetidos à isquemia e sepse

Introduction: An ischemic stroke is a clinical condition that affects thousands of people worldwide. As a result of this injury, neuronal death can be observed, and in the natural course of recovery, the individual may develop sepsis. Sepsis is a systemic inflammatory response that can lead the patient to death. To assess the clinical condition of a patient with this condition, the Auditory Brainstem Response (ABR) can be useful, since it is not an invasive procedure, it is a fast technique and it can be done at the bedside. Purpose: To assess auditory brainstem response (ABR) latency values in gerbils subjected to ischemia and sepsis. Methods: ABR values were collected from 72 adult male gerbils, which were divided into six groups: control, sepsis, ischemia, sham, ischemia with sepsis, and sham with sepsis. For the induction of sepsis, lipopolysaccharide (LPS) was applied intraperitoneally in gerbils. The animals were anesthetized with a ketamine/xylazine combination before collection; their ABR were collected before any procedure (base collection), after ischemia, and 24 hours after the application of LPS. The absolute latency of wave IV was evaluated, and the values were compared between groups. Results: There were significant differences in the groups submitted to sepsis in the latency value of wave IV in relation with the other groups. Conclusion: ABR was sensitive to sepsis with the increase in latency of wave IV during the development of the disease in the experimental model used. .

Introdução: O acidente vascular cerebral do tipo isquêmico é um quadro clínico que afeta milhares de pessoas no mundo. Como resultado dessa injúria observamos morte neuronal, e no decorrer natural de recuperação o indivíduo pode desenvolver a sepse. A sepse é uma resposta inflamatória sistêmica que pode levar o indivíduo à morte. Para avaliar as condições clínicas de um paciente com esse quadro, o potencial evocado auditivo de tronco encefálico (PEATE) pode ser útil, uma vez que ele não é um procedimento invasivo, sua técnica é rápida e pode ser feita à beira do leito. Objetivo: Verificar os valores de latência do PEATE em gerbils submetidos à isquemia e sepse. Métodos: Foram coletados os PEATEs de 72 gerbils machos adultos que foram distribuídos em 6 grupos: controle, sepse, isquemia, sham, isquemia com sepse e sham com sepse. Para a indução de sepse, foi aplicado lipopolissacarídeo (LPS) intraperitoneal nos gerbils. Os animais foram anestesiados antes das coletas com ketamina associada à xilazina, seus PEATEs foram coletados antes de qualquer procedimento (coleta base), após isquemia e 24 horas após a aplicação de LPS. Foi avaliada a latência absoluta da onda IV, e os valores foram comparados intergrupos. Resultados: Houve diferença significativa nos grupos submetidos à sepse no valor da latência da onda IV em relação aos demais grupos. Conclusão: O PEATE se mostrou sensível à sepse com aumento de latência da onda IV no desenvolver da doença no modelo experimental utilizado. .

Plasma cytokine expression after lower-limb compression in rats / Expressão de citoquinas plasmáticas após compressão de membros inferiores de ratos

Muscle injury due to crushing (muscle compression injury) is associated with systemic manifestations known as crush syndrome. A systemic inflammatory reaction may also be triggered by isolated muscle injury. The aim of this study was to investigate the plasma levels of interleukins (IL) 1, 6 and 10 and tumor necrosis factor alpha (TNF-α), which are markers for possible systemic inflammatory reactions, after isolated muscle injury resulting from lower-limb compression in rats. METHODS: Male Wistar rats were subjected to 1 h of compression of their lower limbs by means of a rubber band. The plasma levels of IL 1, 6 and 10 and TNF-α were measured 1, 2 and 4 h after the rats were released from compression. RESULTS: The plasma levels of IL 10 decreased in relation to those of the other groups, with a statistically significant difference (p < 0.05). The method used did not detect the presence of IL 1, IL 6 or TNF-α. CONCLUSION: Our results demonstrated that the changes in plasma levels of IL 10 that were found may have been a sign of the presence of circulating interleukins in this model of lower-limb compression in rats...

A lesão muscular por esmagamento (lesão por compressão muscular) está associada a manifestações sistêmicas conhecidas como síndrome do esmagamento. A reação inflamatória sistêmica pode também ser desencadeada pela lesão muscular isolada. O objetivo deste estudo foi investigar os níveis plasmáticos de interleucinas (IL) 1, 6, 10 e TNF-α, marcadores de uma possível reação inflamatória sistêmica, após a lesão muscular isolada resultante da compressão de membros inferiores de ratos. MÉTODOS: ratos Wistar machos foram submetidos a uma hora de compressão dos membros inferiores por uma faixa de borracha. Os níveis plasmáticos de IL 1, 6, 10 e TNF-α foram medidos uma, duas e quatro horas após a liberação da compressão. RESULTADOS: os níveis plasmáticos de IL 10 diminuíram quando comparados com outros grupos com diferença estatisticamente significante (p < 0,05). Não houve detecção, pelo método, da presença de IL 1, 6 e TNF-α. CONCLUSÃO: nossos resultados demonstraram que as alterações dos níveis plasmáticos de IL 10 encontradas podem ser um sinal da presença de interleucinas circulantes nesse modelo de compressão de membros inferiores de ratos...

The impact of hypertonic and normal saline in gut reperfusion after ischemia in rats.

OBJECTIVE: We investigated the effect of two different saline solutions on the mechanisms of injury after intestinal ischemia: oxidative stress and inflammatory responses. METHODS: Wistar rats underwent transient superior mesenteric artery occlusion and were studied for 6 hours after reperfusion. After randomization, the animals were divided into four groups: Sham; Hypertonic Saline, in which they received infusion of 4 mL/kg body weight of 7.5% hypertonic saline; Saline, in which they received infusion of 33 mL/kg body weight of 0.9% saline; and Non Treatment. The infusion was performed immediately prior to the reperfusion. The plasma concentrations of interleukin 6 and interleukin 10 were measured. Tissue samples (lung, liver, and intestine) were collected for malondialdehyde, myeloperoxidase, and interleukin measurements. RESULTS: The animals that received infusions (Hypertonic Saline and Saline) showed lower levels of tissue malondialdehyde, myeloperoxidase, interleukin 6, and interleukin 10 compared with the Non Treatment group. The plasma concentrations of interleukin 6 and interleukin 10 were higher in the animals treated with 7.5% hypertonic saline compared with Saline and Non Treatment groups. CONCLUSION: In this model of transient intestinal ischemia, the adequate maintenance of intravascular volume decreased oxidative stress and the synthesis of inflammatory markers. Both 7.5% Hypertonic Saline and Saline attenuated the deleterious effects observed after intestinal ischemia.

O impacto das soluções hipertônica e salina fisiológica na reperfusão do trato gastrintestinal pós-isquemia em ratos / The impact of hypertonic and normal saline in gut reperfusion after ischemia in rats

Objetivo: Investigar o papel de duas diferentes soluções salinas nos mecanismos de lesão após isquemia intestinal: estresse oxidativo e respostas inflamatórias. Métodos: Ratos Wistar foram submetidos a oclusão transitória da artéria mesentérica superior e estudados durante as 6 horas seguintes à reperfusão. Após randomização, os animais foram divididos em quatro grupos: Falso; Solução Hipertônica, os quais receberam infusão de solução salina hipertônica a 7,5% (4mL/kg de peso corpóreo); Solução Fisiológica, os quais receberam infusão de solução salina a 0,9% (33mL/kg); e Sem Tratamento. A infusão foi realizada imediatamente antes da reperfusão. Foram realizadas dosagens sequenciais de interleucina 6 e interleucina 10 no plasma. Foram coletadas amostras de tecidos (pulmão, fígado e intestino) para medir malondialdeído, mieloperoxidase e interleucina. Resultados: Em comparação ao Grupo Sem Tratamento, os animais que receberam volume (Grupos Solução Hipertônica e Solução Fisiológica) mostraram níveis tissulares mais baixos de malondialdeído, mieloperoxidase, interleucina 6 e interleucina 10. As concentrações plasmáticas de interleucina 6 e interleucina 10 foram mais altas nos animais tratados com solução hipertônica do que nos tratados com solução fisiológica e nos sem tratamento. Conclusão: Neste modelo de isquemia intestinal transitória, a manutenção adequada de volume intravascular diminuiu o estresse oxidativo e a síntese de marcadores de inflamação. Tanto a solução hipertônica quanto a fisiológica atenuaram os efeitos deletérios observados após isquemia intestinal. .

Objective: We investigated the effect of two different saline solutions on the mechanisms of injury after intestinal ischemia: oxidative stress and inflammatory responses. Methods: Wistar rats underwent transient superior mesenteric artery occlusion and were studied for 6 hours after reperfusion. After randomization, the animals were divided into four groups: Sham; Hypertonic Saline, in which they received infusion of 4mL/kg body weight of 7.5% hypertonic saline; Saline, in which they received infusion of 33mL/kg body weight of 0.9% saline; and Non Treatment. The infusion was performed immediately prior to the reperfusion. The plasma concentrations of interleukin 6 and interleukin 10 were measured. Tissue samples (lung, liver, and intestine) were collected for malondialdehyde, myeloperoxidase, and interleukin measurements. Results: The animals that received infusions (Hypertonic Saline and Saline) showed lower levels of tissue malondialdehyde, myeloperoxidase, interleukin 6, and interleukin 10 compared with the Non Treatment group. The plasma concentrations of interleukin 6 and interleukin 10 were higher in the animals treated with 7.5% hypertonic saline compared with Saline and Non Treatment groups. Conclusion: In this model of transient intestinal ischemia, the adequate maintenance of intravascular volume decreased oxidative stress and the synthesis of inflammatory markers. Both 7.5% Hypertonic Saline and Saline attenuated the deleterious effects observed after intestinal ischemia. .

Phagocytic activity of LPS tolerant macrophages.

Endotoxin tolerance is defined as a reduced capacity of the host to respond to LPS activation following a first exposure to this stimulus. It affects all leukocytes and regarding macrophages, most studies focus on the reduced ability of these cells to secrete pro-inflammatory cytokines. Therefore, we evaluated other macrophages functions (fungicidal capacity, reactive oxygen species production and antigen presentation) in cells from tolerant mice. We have performed a tolerance model in our laboratory that does not stimulate directly the place from where the cells will be removed (peritoneal cavity). Mouse received subcutaneous injections of LPS in the scruff for 5 days and we analyze the capacity of peritoneal macrophages to phagocyte using three different receptors: Fc, C3b and mannose receptors. We found a reduction in the phagocytosis of erythrocytes and Candida albicans related to the Fc and mannose receptors. These differences can be due to a macrophage reprogramming, as demonstrated by altered expression of cytokines and chemokines. Despite this reduction in phagocytosis capacity, macrophages from tolerant animals exhibited enhanced hydrogen peroxide production and expression of antigen presentation molecules, suggesting that their ability to combat an infection is improved. In summary, our data indicates that LPS tolerance drives macrophages from a predominant release of proinflammatory mediators that amplify inflammation and host damage toward a better killing and antigen presentation state.

Endotoxin tolerance drives neutrophil to infectious site.

The objective of this randomized animal study and laboratory investigation was to investigate whether lipopolysaccharide tolerance redirects neutrophil migration between organs. Male BALB/c mice received subcutaneous injections of lipopolysaccharide (1 mg/kg) for 5 days, followed by cecal ligation and puncture (CLP). Cytokines and adhesion molecules were measured after tolerance and CLP challenge. Increased numbers of neutrophils were observed in the peritoneal cavity of tolerant mice, which was associated with increased levels of adhesion molecules and chemokines. In contrast, nontolerant mice accumulated higher numbers of neutrophils in the lungs compared with those in the peritoneal cavity. Neutrophil function accessed by hydrogen peroxide production from neutrophils recovered from peritoneal cavity showed that tolerance increased the capacity to produce hydrogen peroxide. Mortality was reduced in tolerant animals. This study demonstrated that tolerance reduces leukocyte accumulation in the lung after CLP by redirecting neutrophils to the site of infection.