Does fasting protect liver from ischemia and reperfusion injury?

PURPOSE: To evaluate local and systemic effects of 24-hour fasting in liver ischemia and reperfusion injury. METHODS: Twenty-one adult male Wistar rats (330-390 g) were submitted to 60 minutes of hepatic ischemia followed by 24 hours of reperfusion. Before the day of the experiment, the animals fasted, but free access to water was allowed. Two groups were constituted: Control: non-fasted, that is, feeding ad libitum before surgical procedure; Fasting: rats underwent previous fasting of 24 hours. Hepatic ischemia was performed using vascular clamp in hepatic pedicle. At 24 hours after liver reperfusion, blood and tissue samples were collected. To analysis, liver lobes submitted to ischemia was identified as ischemic liver and paracaval non-ischemic lobes as non-ischemic liver. We evaluated: malondialdehyde levels, hepatocellular function (alanine aminotransferase, aspartate aminotransferase activities, and both ratio), cytokines (interleukins-6, -10, and tumor necrosis factor-alpha), hepatic ischemia and reperfusion injury (histology). RESULTS: Malondialdehyde measured in non-ischemic and ischemic liver samples, hepatocellular function and cytokines were comparable between groups. Histological findings were distinct in three regions evaluated. Microvesicular steatosis was comparable between 24-hour fasting and non-fasted control groups in periportal region of hepatic lobe. In contrast, steatosis was more pronounced in zones 2 and 3 of ischemic liver samples of fasting compared to control groups. CONCLUSIONS: These data indicates that fasting does not protect, but it can be also detrimental to liver submitted to ischemia/reperfusion damage. At that time, using long fasting before liver surgery in the real world may be contraindicated.

Chronic Low or High Nutrient Intake and Myokine Levels.

Inadequate nutrient availability has been demonstrated to be one of the main factors related to endocrine and metabolic dysfunction. We investigated the role of inadequate nutrient intakes in the myokine levels of runners. Sixty-one amateur runners participated in this study. The myokine levels were determined using the Human Magnetic Bead Panel from plasma samples collected before and after the marathon. Dietary intake was determined using a prospective method of three food records. The runners with lower carbohydrate and calcium intakes had higher percentages of fat mass (p < 0.01). The runners with a sucrose intake comprising above 10% of their energy intake and an adequate sodium intake had higher levels of BDNF (p = 0.027 and p = 0.031). After the race and in the recovery period, the runners with adequate carbohydrate intakes (g/kg) (>5 g/kg/day) had higher levels of myostatin and musclin (p < 0.05). The runners with less than 45% of carbohydrate of EI had lower levels of IL-15 (p = 0.015) and BNDF (p = 0.013). The runners with higher cholesterol intakes had lower levels of irisin (p = 0.011) and apelin (p = 0.020), and those with a low fiber intake had lower levels of irisin (p = 0.005) and BDNF (p = 0.049). The inadequate intake influenced myokine levels, which promoted cardiometabolic tissue repair and adaptations to exercise.

Use and misuse of biomarkers and the role of D-dimer and C-reactive protein in the management of COVID-19: A post-hoc analysis of a prospective cohort study.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is associated with high mortality among hospitalized patients and incurs high costs. Severe acute respiratory syndrome coronavirus 2 infection can trigger both inflammatory and thrombotic processes, and these complications can lead to a poorer prognosis. This study aimed to evaluate the association and temporal trends of D-dimer and C-reactive protein (CRP) levels with the incidence of venous thromboembolism (VTE), hospital mortality, and costs among inpatients with COVID-19. METHODS: Data were extracted from electronic patient records and laboratory databases. Crude and adjusted associations for age, sex, number of comorbidities, Sequential Organ Failure Assessment score at admission, and D-dimer or CRP logistic regression models were used to evaluate associations. RESULTS: Between March and June 2020, COVID-19 was documented in 3,254 inpatients. The D-dimer level ≥4,000 ng/mL fibrinogen equivalent unit (FEU) mortality odds ratio (OR) was 4.48 (adjusted OR: 1.97). The CRP level ≥220 mg/dL OR for death was 7.73 (adjusted OR: 3.93). The D-dimer level ≥4,000 ng/mL FEU VTE OR was 3.96 (adjusted OR: 3.26). The CRP level ≥220 mg/dL OR for VTE was 2.71 (adjusted OR: 1.92). All these analyses were statistically significant (p<0.001). Stratified hospital costs demonstrated a dose-response pattern. Adjusted D-dimer and CRP levels were associated with higher mortality and doubled hospital costs. In the first week, elevated D-dimer levels predicted VTE occurrence and systemic inflammatory harm, while CRP was a hospital mortality predictor. CONCLUSION: D-dimer and CRP levels were associated with higher hospital mortality and a higher incidence of VTE. D-dimer was more strongly associated with VTE, although its discriminative ability was poor, while CRP was a stronger predictor of hospital mortality. Their use outside the usual indications should not be modified and should be discouraged.

Effectiveness of the Mobile Emergency Medical Services (SAMU): use of interrupted time series.

OBJECTIVE: To evaluate the performance of the Mobile Emergency Medical Services (SAMU) in the ABC Region, using myocardial infarction as tracer condition. METHODS: The analysis of interrupted time series was the approach chosen to test immediate and gradual effects of the intervention on the study population. The research comprised adjusted monthly time series of the hospital mortality rate by myocardial infarction in the period between 2000 and 2011. Data were extracted from the Mortality Information System (SIM), using segmented regression analysis to evaluate the level and trend of the intervention before and after its implementation. To strengthen the internal validity of the study, a control region was included. RESULTS: The analysis of interrupted time series showed a reduction of 0.04 deaths per 100,000 inhabitants in the mortality rate compared to the underlying trend since the implementation of the Emergency Medical Services (p = 0.0040; 95%CI: -0.0816 - -0.0162) and a reduction in the level of 2.89 deaths per 100,000 inhabitants (p = 0.0001; 95%CI: -4.3293 - -1.4623), both with statistical significance. Regarding the control region, Baixada Santista, the difference in the result trend between intervention outcome and post-intervention control of -0.0639 deaths per 100,000 inhabitants was statistically significant (p = 0.0031; 95%CI: -0.1060 - -0.0219). We cannot exclude confounders, but we limited their presence in the study by including control region series. CONCLUSIONS: Although the analysis of interrupted time series has limitations, this modeling can be useful for analyzing the performance of policies and programs. Even though the intervention studied is not a condition that in itself implies effectiveness, the latter would not be present without the former, which, integrated with other conditions, generates a positive result. SAMU is a strategy that must be expanded when formulating and consolidating policies focusing on emergency care.

Analysis of inflammatory and metabolic biomarkers in patients submitted to abdominoplasty after bariatric surgery.

PURPOSE: To evaluate the serum variations of Interleukins (Il) and CPR of abdominoplasties in post-bariatric patients and, to equate the homeostasis (HOMA) from the variations of glycemia and insulin to evolute the metabolic modifications. METHODS: Fourteen women were submitted to abdominoplasties with weight loss after a gastroplasty. Levels of IL4, IL6, IL10, CRP, glycemia and insulin were obtained during the pre-operative, trans-operative, 24 hours post, 7th and 14th postoperative days. RESULTS: The IL4 was higher at 24 hours post-surgery, and after a moderate decrease, it remained high until the 14th day. The IL6 and CRP had an expressive increase during the trans-operative period. The CRP remained high, and the IL6 decreased on the 7th and 14th days. The IL10 increased during the transoperative period, and it posteriorly decreased to lower levels in comparison to the pre-operative period. The already increased glycemia during the pre-operative period was even higher during the trans-operative and then, returned to preliminary values on the 7th and 14th days after surgery. The HOMA accompanied the insulin. CONCLUSION: The inflammatory and glycemic serum levels decrease after abdominiplasty in obese post-bariatric patients.

Does fasting protect liver from ischemia and reperfusion injury?

Purpose: To evaluate local and systemic effects of 24-hour fasting in liver ischemia and reperfusion injury. Methods: Twenty-one adult male Wistar rats (330-390 g) were submitted to 60 minutes of hepatic ischemia followed by 24 hours of reperfusion. Before the day of the experiment, the animals fasted, but free access to water was allowed. Two groups were constituted: Control: non-fasted, that is, feeding ad libitum before surgical procedure; Fasting: rats underwent previous fasting of 24 hours. Hepatic ischemia was performed using vascular clamp in hepatic pedicle. At 24 hours after liver reperfusion, blood and tissue samples were collected. To analysis, liver lobes submitted to ischemia was identified as ischemic liver and paracaval non-ischemic lobes as non-ischemic liver. We evaluated: malondialdehyde levels, hepatocellular function (alanine aminotransferase, aspartate aminotransferase activities, and both ratio), cytokines (interleukins-6, -10, and tumor necrosis factor-alpha), hepatic ischemia and reperfusion injury (histology). Results: Malondialdehyde measured in non-ischemic and ischemic liver samples, hepatocellular function and cytokines were comparable between groups. Histological findings were distinct in three regions evaluated. Microvesicular steatosis was comparable between 24-hour fasting and non-fasted control groups in periportal region of hepatic lobe. In contrast, steatosis was more pronounced in zones 2 and 3 of ischemic liver samples of fasting compared to control groups. Conclusions: These data indicates that fasting does not protect, but it can be also detrimental to liver submitted to ischemia/reperfusion damage. At that time, using long fasting before liver surgery in the real world may be contraindicated.

Use and misuse of biomarkers and the role of D-dimer and C-reactive protein in the management of COVID-19: A post-hoc analysis of a prospective cohort study

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is associated with high mortality among hospitalized patients and incurs high costs. Severe acute respiratory syndrome coronavirus 2 infection can trigger both inflammatory and thrombotic processes, and these complications can lead to a poorer prognosis. This study aimed to evaluate the association and temporal trends of D-dimer and C-reactive protein (CRP) levels with the incidence of venous thromboembolism (VTE), hospital mortality, and costs among inpatients with COVID-19. METHODS: Data were extracted from electronic patient records and laboratory databases. Crude and adjusted associations for age, sex, number of comorbidities, Sequential Organ Failure Assessment score at admission, and D-dimer or CRP logistic regression models were used to evaluate associations. RESULTS: Between March and June 2020, COVID-19 was documented in 3,254 inpatients. The D-dimer level ≥4,000 ng/mL fibrinogen equivalent unit (FEU) mortality odds ratio (OR) was 4.48 (adjusted OR: 1.97). The CRP level ≥220 mg/dL OR for death was 7.73 (adjusted OR: 3.93). The D-dimer level ≥4,000 ng/mL FEU VTE OR was 3.96 (adjusted OR: 3.26). The CRP level ≥220 mg/dL OR for VTE was 2.71 (adjusted OR: 1.92). All these analyses were statistically significant (p<0.001). Stratified hospital costs demonstrated a dose-response pattern. Adjusted D-dimer and CRP levels were associated with higher mortality and doubled hospital costs. In the first week, elevated D-dimer levels predicted VTE occurrence and systemic inflammatory harm, while CRP was a hospital mortality predictor. CONCLUSION: D-dimer and CRP levels were associated with higher hospital mortality and a higher incidence of VTE. D-dimer was more strongly associated with VTE, although its discriminative ability was poor, while CRP was a stronger predictor of hospital mortality. Their use outside the usual indications should not be modified and should be discouraged.

Analysis of inflammatory and metabolic biomarkers in patients submitted to abdominoplasty after bariatric surgery

Abstract Purpose: To evaluate the serum variations of Interleukins (Il) and CPR of abdominoplasties in post-bariatric patients and, to equate the homeostasis (HOMA) from the variations of glycemia and insulin to evolute the metabolic modifications. Methods: Fourteen women were submitted to abdominoplasties with weight loss after a gastroplasty. Levels of IL4, IL6, IL10, CRP, glycemia and insulin were obtained during the pre-operative, trans-operative, 24 hours post, 7th and 14th postoperative days. Results: The IL4 was higher at 24 hours post-surgery, and after a moderate decrease, it remained high until the 14th day. The IL6 and CRP had an expressive increase during the trans-operative period. The CRP remained high, and the IL6 decreased on the 7th and 14th days. The IL10 increased during the transoperative period, and it posteriorly decreased to lower levels in comparison to the pre-operative period. The already increased glycemia during the pre-operative period was even higher during the trans-operative and then, returned to preliminary values on the 7th and 14th days after surgery. The HOMA accompanied the insulin. Conclusion: The inflammatory and glycemic serum levels decrease after abdominiplasty in obese post-bariatric patients.

Volume replacement with saline solutions during pancreatitis in rats and the hepatic profiles of apoptotic proteins and heat-shock proteins.

OBJECTIVE: Liver failure can occur as a consequence of the systemic inflammation after acute pancreatitis. We assessed the effect of volume repositioning with hypertonic saline solution or normal saline on hepatic cytokine production and the expression of heat-shock proteins and apoptotic proteins after acute pancreatitis. METHODS: Wistar rats were divided in four groups: C - control animals that were not subjected to insult or treatment; NT - animals that were subjected to acute pancreatitis and received no treatment; normal saline - animals that were subjected to acute pancreatitis and received normal saline (NaCl 0.9%); and HS - animals that were subjected to acute pancreatitis and received hypertonic saline solution (NaCl 7.5%). Acute pancreatitis was induced by retrograde transduodenal infusion of 2.5% sodium taurocholate into the pancreatic duct. At 4, 12 and 24 h following acute pancreatitis induction, TNF-alpha, IL-1-beta, IL-6 and IL-10, caspase-2 and -7, Apaf-1, AIF and HSP60 and 90 were analyzed in the liver. RESULTS: Casp2 decreased in the normal saline and hypertonic saline groups (p<0.05 versus. C) at 12 h. Apaf-1, AIF and HSP90 remained unchanged. At 4 h, Casp7 increased in the NT group (p<0.01 versus C), although it remained at the baseline levels in the reperfused groups. HSP60 increased in all of the groups at 4 h (p< 0.001 vs. C). However, the hypertonic saline group showed lower expression of HSP60 than the normal saline group (p<0.05). Hypertonic saline solution maintained the production of cytokines at normal levels. Volume reperfusion with normal or hypertonic saline significantly modulated the expression of Casp7. CONCLUSION: Volume replacement with hypertonic or normal saline was effective in reducing caspase 7. However, only hypertonic solution was capable of regulating cytokine production and HSP60 expression at all time points.

Hypertonic saline and reduced peroxynitrite formation in experimental pancreatitis.

OBJECTIVES: In this study, we tested the hypothesis that hypertonic saline exerts anti-inflammatory effects by modulating hepatic oxidative stress in pancreatitis. INTRODUCTION: The incidence of hepatic injury is related to severe pancreatitis, and hypertonic saline reduces pancreatic injury and mortality in pancreatitis. METHODS: Wistar rats were divided into four groups: control (not subjected to treatment), untreated pancreatitis (NT, pancreatitis induced by a retrograde transduodenal infusion of 2.5% sodium taurocholate into the pancreatic duct with no further treatment administered), pancreatitis with normal saline (NS, pancreatitis induced as described above and followed by resuscitation with 0.9% NaCl), and pancreatitis with hypertonic saline (HS, pancreatitis induced as described above and followed by resuscitation with 7.5% NaCl). At 4, 12, and 24 h after pancreatitis induction, liver levels of inducible nitric oxide synthase (iNOS), heat-shock protein 70, nitrotyrosine (formation of peroxynitrite), nitrite/nitrate production, lipid peroxidation, and alanine aminotransferase (ALT) release were determined. RESULTS: Twelve hours after pancreatitis induction, animals in the HS group presented significantly lower iNOS expression (P<0.01 vs. NS), nitrite/nitrate levels (P<0.01 vs. NS), lipid peroxidation (P<0.05 vs. NT), and ALT release (P<0.01 vs. NS). Twenty-four hours after pancreatitis induction, nitrotyrosine expression was significantly lower in the HS group than in the NS group (P<0.05). DISCUSSION: The protective effect of hypertonic saline was related to the establishment of a superoxide-NO balance that was unfavorable to nitrotyrosine formation. CONCLUSIONS: Hypertonic saline decreases hepatic oxidative stress and thereby minimizes liver damage in pancreatitis.

sRAGE no choque séptico: um potencial biomarcador de mortalidade / sRAGE in septic shock: a potential biomarker of mortality

Objetivo: Avaliar e compreender as implicações clínicas dos níveis plasmáticos de uma isoforma solúvel de um receptor de produtos finais de glicação avançada (do inglês receptor for advanced glycation end products - sRAGE) em diferentes fases da sepse. Métodos: Os valores do sRAGE sérico em pacientes divididos nos grupos controle na unidade de terapia intensiva, sepse grave, choque séptico e recuperação de choque séptico foram analisados do ponto de vista estatístico para avaliar a quantidade (Kruskal-Wallis), variabilidade (teste de Levine) e correlação (teste Spearman rank) em relação a certos mediadores inflamatórios (IL-1 α, IL-6, IL-8, IL-10, IP-10, G-CSF, MCP-1, IFN-γ e TNF-α). Resultados: Não se observaram modificações nos níveis de sRAGE entre os grupos; contudo o grupo com choque séptico demonstrou diferenças na variabilidade do sRAGE em comparação aos demais grupos. Foi relatada, no grupo com choque séptico, uma correlação positiva com todos os mediadores inflamatórios. Conclusão: Os níveis de sRAGE se associaram com desfechos piores nos pacientes com choque séptico. Entretanto, uma análise de correlação estatística com outras citocinas pró-inflamatórias indicou que as vias que levam a esses desfechos são diferentes, dependendo dos níveis de sRAGE. ...

Objective: To evaluate and understand the clinical implications of the plasma levels of a soluble isoform of a receptor for advanced glycation end products (sRAGE) in different stages of sepsis. Methods: Serum sRAGE values in patients who were divided into intensive care unit control, severe sepsis, septic shock and recovery from septic shock groups were statistically analyzed to assess quantity (Kruskal-Wallis), variability (Levine test) and correlation (Spearman rank test) with certain inflammatory mediators (IL-1 α, IL-6, IL-8, IL-10, IP-10, G-CSF, MCP-1, IFN-γ and TNF-α). Results: No changes in sRAGE levels were observed among the groups; however, the septic shock group showed differences in the variability of sRAGE compared to the other groups. A positive correlation with all the inflammatory mediators was reported in the septic shock group. Conclusion: sRAGE levels are associated with worse outcomes in patients with septic shock. However, a statistical correlation analysis with other proinflammatory cytokines indicated that the pathways leading to those outcomes are different depending on the sRAGE levels. Future studies to elucidate the pathophysiological mechanisms involving sRAGE in models of sepsis are of great clinical importance for the safe handling of this biomarker. .

Ânion gap corrigido para albumina, fosfato e lactato é um bom preditor de íon gap forte em pacientes enfermos graves: estudo de coorte em nicho / Anion gap corrected for albumin, phosphate and lactate is a good predictor of strong ion gap in critically ill patients: a nested cohort study

OBJETIVO: Ânion gap corrigido e íon gap forte são usados comumente para estimar os ânions não medidos. Avaliamos o desempenho do ânion gap corrigido para albumina, fosfato e lactato na predição do íon gap forte em uma população mista de pacientes enfermos graves. Formulamos a hipótese de que o ânion gap corrigido para albumina, fosfato e lactato seria um bom preditor do íon gap forte, independentemente da presença de acidose metabólica. Além disso, avaliamos o impacto do íon gap forte por ocasião da admissão na mortalidade hospitalar. MÉTODOS: Incluímos 84 pacientes gravemente enfermos. A correlação e a concordância entre o ânion gap corrigido para albumina, fosfato e lactato e o íon gap forte foi avaliada utilizando-se os testes de correlação de Pearson, regressão linear, plot de Bland-Altman e pelo cálculo do coeficiente de correlação interclasse. Foram realizadas duas análises de subgrupos: uma para pacientes com excesso de base <-2mEq/L (grupo com baixo excesso de base) e outro grupo de pacientes com excesso de base >-2mEq/L (grupo com alto excesso de base). Foi realizada uma regressão logística para avaliar a associação entre os níveis de íon gap forte na admissão e a mortalidade hospitalar. RESULTADOS: Houve correlação muito forte e uma boa concordância entre o ânion gap corrigido para albumina, fosfato e lactato e o íon gap forte na população geral (r2=0,94; bias 1,40; limites de concordância de -0,75 a 3,57). A correlação foi também elevada nos grupos com baixo excesso de base (r2=0,94) e alto excesso de base (r2=0,92). Estavam presentes níveis elevados de íon gap forte em 66% da população total e 42% dos casos do grupo alto excesso de. ...

OBJECTIVE: Corrected anion gap and strong ion gap are commonly used to estimate unmeasured anions. We evaluated the performance of the anion gap corrected for albumin, phosphate and lactate in predicting strong ion gap in a mixed population of critically ill patients. We hypothesized that anion gap corrected for albumin, phosphate and lactate would be a good predictor of strong ion gap, independent of the presence of metabolic acidosis. In addition, we evaluated the impact of strong ion gap at admission on hospital mortality. METHODS: We included 84 critically ill patients. Correlation and agreement between the anion gap corrected for albumin, phosphate and lactate and strong ion gap was evaluated by the Pearson correlation test, linear regression, a Bland-Altman plot and calculating interclass correlation coefficient. Two subgroup analyses were performed: one in patients with base-excess <-2mEq/L (low BE group - lBE) and the other in patients with base-excess >-2mEq/L (high BE group - hBE). A logistic regression was performed to evaluate the association between admission strong ion gap levels and hospital mortality. RESULTS: There was a very strong correlation and a good agreement between anion gap corrected for albumin, phosphate and lactate and strong ion gap in the general population (r2=0.94; bias 1.40; limits of agreement -0.75 to 3.57). Correlation was also high in the lBE group (r2=0.94) and in the hBE group (r2=0.92). High levels of strong ion gap were present in 66% of the whole population and 42% of the cases in the hBE group. Strong ion gap was not associated with hospital mortality by logistic regression. CONCLUSION: Anion gap corrected for albumin, phosphate and lactate and strong ion gap have an excellent correlation. Unmeasured anions are frequently elevated in critically ill patients with normal base-excess. However, there was no association between unmeasured anions and hospital mortality. .

HLA-A*31 como marcador de suscetibilidade genetica em sepse / HLA-A*31 as a marker of genetic susceptibility to sepsis

Objetivo: Haplótipos do HLA têm sido associados a muitas doenças autoimunes, mas não foi descrita qualquer associação na sepse. O objetivo desse estudo é investigar o sistema HLA como um possível marcador de suscetibilidade genética à sepse. Métodos: Estudo prospectivo de coorte, incluindo pacientes admitidos em unidade de terapia intensiva e controles-saudáveis obtidos em lista de doadores de transplante renal. Foram excluídos pacientes abaixo dos 18 anos de idade, gestantes ou HIV positivos, pacientes com doença maligna metastática ou sob quimioterapia, pacientes com hepatopatia avançada, com condições de fim de vida. O DNA foi extraído de sangue total, e a haplotipagem de HLA foi realizada com a tecnologia MiliPlex®. Resultados: Foram incluídos 1.121 pacientes (1.078 doadores de rim, 20 pacientes com sepse grave e 23 pacientes admitidos por choque séptico) entre outubro de 2010 e outubro de 2012. Os participantes positivos para HLA-A*31 tiveram risco aumentado de desenvolver sepse (OR: 2,36 IC95%: 1,26-5,35). Não foi identificada outra associação significativa, quando considerado como nível de significância o valor de p<0,01. Conclusão: A expressão de HLA-A*31 está associada ao risco de desenvolvimento de sepse. .

Objective: The HLA haplotype has been associated with many autoimmune diseases, but no associations have been described in sepsis. This study aims to investigate the HLA system as a possible marker of genetic sepsis susceptibility. Methods: This is a prospective cohort study including patients admitted to an intensive care unit and healthy controls from a list of renal transplant donors. Patients with less 18 years of age; pregnant or HIV positive patients; those with metastatic malignancies or receiving chemotherapy; or with advanced liver disease; or with end-of-life conditions were excluded. The DNA was extracted from the whole blood and HLA haplotypes determined using MiliPlex® technology. Results: From October 2010 to October 2012, 1,121 patients were included (1,078 kidney donors, 20 patients admitted with severe sepsis and 23 with septic shock). HLA-A*31 positive subjects had increased risk of developing sepsis (OR 2.36, 95%CI 1.26-5.35). Considering a p value <0.01, no other significant association was identified. Conclusion: HLA-A*31 expression is associated to risk of developing sepsis. .

Reposição volêmica com soluções salinas em pancreatite e perfil hepático de proteínas apoptóticas e de choque térmico / Volume replacement with saline solutions during pancreatitis in rats and the hepatic profiles of apoptotic proteins and heat-shock proteins

OBJETIVO: A falência hepática é uma consequência da inflamação sistêmica após pancreatite aguda. Avaliou-se o efeito da reposição volêmica com soluções salinas fisiológicas ou hipertônica na produção hepática de citocinas e na expressão de proteínas ativadas por choque térmico e proteínas ligadas à apoptose durante a pancreatite aguda. MÉTODOS: Ratos Wistar foram divididos em quatro grupos: C - animais controles não submetidos à lesão e nem ao tratamento; NT - animais submetidos à indução de pancreatite aguda e não tratados; SN - animais submetidos à indução de pancreatite aguda e tratados com solução salina normal (NaCl 0,9%); SH - animais submetidos à pancreatite aguda e tratados com solução salina hipertônica (NaCl 7,5%). A pancreatite aguda foi induzida por infusão retrógrada transduodenal de taurocolato de sódio 2,5% no ducto pancreático. Após 4, 12 e 24 horas da indução da pancreatite aguda, analisaram-se, no fígado, TNF-α, IL-1β, IL-6 e IL-10, caspase-2, caspase-7, APAF-1, AIF, HSP60 e HSP90. RESULTADOS: A caspase-2 diminuiu nos grupos SN e SH (p<0,05 versus C) após 12 horas. APAF-1, AIF e HSP90 permaneceram inalterados. Após 4 horas da indução, a capsase-7 aumentou no grupo NT (p<0,01 versus C), embora se mantendo em níveis basais nos grupos reperfundidos. A HSP60 aumentou em todos os grupos após 4 horas (p<0,001 versus C). No entanto, o grupo SH mostrou menor expressão de HSP60 que o grupo SN (p<0,05). A solução salina hipertônica manteve a produção de citocinas em níveis normais. A reperfusão com volume com solução salina normal ou hipertônica, modulou significativamente a expressão de caspase-7. CONCLUSÃO: A reposição volêmica com solução salina normal ou hipertônica foi efetiva em reduzir a caspase-7. Entretanto, somente a solução salina hipertônica foi capaz de regular a produção de citocinas e a expressão de HSP60 em todos os momentos analisados.

OBJECTIVE: Liver failure can occur as a consequence of the systemic inflammation after acute pancreatitis. We assessed the effect of volume repositioning with hypertonic saline solution or normal saline on hepatic cytokine production and the expression of heat-shock proteins and apoptotic proteins after acute pancreatitis. METHODS: Wistar rats were divided in four groups: C - control animals that were not subjected to insult or treatment; NT - animals that were subjected to acute pancreatitis and received no treatment; normal saline - animals that were subjected to acute pancreatitis and received normal saline (NaCl 0.9%); and HS - animals that were subjected to acute pancreatitis and received hypertonic saline solution (NaCl 7.5%). Acute pancreatitis was induced by retrograde transduodenal infusion of 2.5% sodium taurocholate into the pancreatic duct. At 4, 12 and 24 h following acute pancreatitis induction, TNF-alpha, IL-1-beta, IL-6 and IL-10, caspase-2 and -7, Apaf-1, AIF and HSP60 and 90 were analyzed in the liver. RESULTS: Casp2 decreased in the normal saline and hypertonic saline groups (p<0.05 versus. C) at 12 h. Apaf-1, AIF and HSP90 remained unchanged. At 4 h, Casp7 increased in the NT group (p<0.01 versus C), although it remained at the baseline levels in the reperfused groups. HSP60 increased in all of the groups at 4 h (p< 0.001 vs. C). However, the hypertonic saline group showed lower expression of HSP60 than the normal saline group (p<0.05). Hypertonic saline solution maintained the production of cytokines at normal levels. Volume reperfusion with normal or hypertonic saline significantly modulated the expression of Casp7. CONCLUSION: Volume replacement with hypertonic or normal saline was effective in reducing caspase 7. However, only hypertonic solution was capable of regulating cytokine production and HSP60 expression at all time points.

Hypertonic saline and reduced peroxynitrite formation in experimental pancreatitis

OBJECTIVES: In this study, we tested the hypothesis that hypertonic saline exerts anti-inflammatory effects by modulating hepatic oxidative stress in pancreatitis. INTRODUCTION: The incidence of hepatic injury is related to severe pancreatitis, and hypertonic saline reduces pancreatic injury and mortality in pancreatitis. METHODS: Wistar rats were divided into four groups: control (not subjected to treatment), untreated pancreatitis (NT, pancreatitis induced by a retrograde transduodenal infusion of 2.5 percent sodium taurocholate into the pancreatic duct with no further treatment administered), pancreatitis with normal saline (NS, pancreatitis induced as described above and followed by resuscitation with 0.9 percent NaCl), and pancreatitis with hypertonic saline (HS, pancreatitis induced as described above and followed by resuscitation with 7.5 percent NaCl). At 4, 12, and 24 h after pancreatitis induction, liver levels of inducible nitric oxide synthase (iNOS), heat-shock protein 70, nitrotyrosine (formation of peroxynitrite), nitrite/nitrate production, lipid peroxidation, and alanine aminotransferase (ALT) release were determined. RESULTS: Twelve hours after pancreatitis induction, animals in the HS group presented significantly lower iNOS expression (P<0.01 vs. NS), nitrite/nitrate levels (P<0.01 vs. NS), lipid peroxidation (P<0.05 vs. NT), and ALT release (P<0.01 vs. NS). Twenty-four hours after pancreatitis induction, nitrotyrosine expression was significantly lower in the HS group than in the NS group (P<0.05). DISCUSSION: The protective effect of hypertonic saline was related to the establishment of a superoxide-NO balance that was unfavorable to nitrotyrosine formation. CONCLUSIONS: Hypertonic saline decreases hepatic oxidative stress and thereby minimizes liver damage in pancreatitis.

Efeito da solução hipertônica de NaCI 7, 5 por cento na resposta inflamatória em modelo de choque hipovolêmico / Effects of hypertonic solution (NaCI 7, 5 per cent) on the inflammatory response in an experimental model of hemorrhagic shock

A solução hipertônica de cloreto de sódio 7,5 por cento (SSH) é eficaz em restaurar os parâmetros hemodinâmicos e reduzir a inflamação em modelos experimentais de choque hemorrágico. Assim, foi nosso objetivo investigar a ação da SSH sobre os mecanismos envolvidos na lesão de isquemia e reperfusão (I/R) em um modelo de choque hemorrágico controlado. Ratos Wistar (280-350 g) foram submetidos à hemorragia controlada, mantendo-se a pressão arterial média em 40 mmHg por 1 h / Hypertonic saline solution (HSS - NaCI 7,5 per cent) was shown to restore hemodynamic parameters in hemorrhagic shock and to decrease the inflammation triggered by ischemia-reperfusion injury (I/R). Therefore, our objective was to investigate the effects of HSS on the mechanisms involved in I/R, in an experimental model of controled hemorrhagic shock. Wistar rats (2`80-350 g) were submitted to the controled bleeding, keeping the mean arterial pressure around 40 mmHg, for 1 hour...