Dilênia de Oliveira Cipriano Torres

Effect of diethylcarbamazine on chronic hepatic inflammation induced by alcohol in C57BL/6 mice.

Some pharmacological studies showed that diethylcarbamazine (DEC) interferes with the arachidonic acid metabolism, acting as an anti-inflammatory drug. The chronic alcohol consumption activates the hepatic inflammatory response associated to T-cell activation and overproduction of pro-inflammatory cytokines. The present work analyzed the anti-inflammatory effect of DEC on hepatic cells of alcoholic mice. Thirty-two male C57BL/6 mice were equally divided in the following groups: (a) control group (C), which received only water, (b) DEC-treated group, which received 50 mg/kg for 12 day (DEC50), (c) the alcoholic group (EtOH), submitted to only alcohol and (d) the alcohol-DEC treated group (EtOH50), submitted to alcohol plus DEC treatment after the induction of chronic alcoholism for 5 weeks. Biochemical analyses were performed and liver fragments were processed for light microscopy, transmission electron microscopy, immunohistochemical and western blot. The level of AST increased significantly in alcoholic group whereas a significant reduction of serum AST was detected in the EtOH50 group. Histological and ultrastructural analysis of alcoholic group showed evident hepatocellular damage, which was strikingly reduced in the alcoholic DEC-treated group. Immunohistochemistry results revealed highly expression of inflammatory markers as MDA, NF-κB, TNF-α, IL-6, VCAM and ICAM by the hepatic cells of the EtOH group; however no immunoreactivity for any of these cytokines was detected after DEC treatment. Western blot analyses showed increased MCP-1 and iNOS expression in EtOH group, which was significantly inhibited by DEC treatment. According to the present results, DEC can be a potential drug for the treatment of chronic inflammation induced by chronic alcoholism.

Association Between Nutritional Status, Inflammatory Condition, and Prognostic Indexes with Postoperative Complications and Clinical Outcome of Patients with Gastrointestinal Neoplasia

ABSTRACT The aim of this study is to describe and relate nutritional and inflammatory status and prognostic indexes with postoperative complications and clinical outcome of patients with gastrointestinal malignancies. Twenty-nine patients were evaluated; nutritional assessment was carried out by subjective and objective parameters; albumin, pre-albumin, C-reactive protein (CRP), and alpha-1-acid glycoprotein (AGP) were determined. To assess prognosis, the Glasgow scale, the Prognostic Inflammatory Nutritional Index (PINI), and CRP/albumin ratio were used; the clinical outcomes considered were hospital discharge and death. A high Subjective Global Assessment (SGA) score was associated with the occurrence of postoperative complications: 73% of the patients with postoperative complications had the highest SGA score, but only 6% of those without postoperative complications had the highest SGA score (P < 0.001). Greater occurrence of death was observed in patients with a high SGA score, low serum albumin, increased CRP, PINI > 1, and Glasgow score 2. There was a positive correlation between weight loss percentage with serum CRP levels (P = 0.002), CRP/albumin (P = 0.002), PINI (P = 0.002), and Glasgow score (P = 0.000). This study provides evidence that the assessment of the nutritional status and the use of prognostic indexes are good tools for predicting postoperative complications and clinical outcome in patients with gastrointestinal neoplasia.

LPSF/GQ-02 Inhibits the Development of Hepatic Steatosis and Inflammation in a Mouse Model of Non-Alcoholic Fatty Liver Disease (NAFLD)

Non-alcoholic fatty liver disease (NAFLD) defines a wide spectrum of liver diseases that extends from simple steatosis to non-alcoholic steatohepatitis. Although the pathogenesis of NAFLD remains undefined, it is recognized that insulin resistance is present in almost all patients who develop this disease. Thiazolidinediones (TZDs) act as an insulin sensitizer and have been used in the treatment of patients with type 2 diabetes and other insulin-resistant conditions, including NAFLD. Hence, therapy of NAFLD with insulin-sensitizing drugs should ideally improve the key hepatic histological changes, while also reducing cardiometabolic and cancer risks. Controversially, TZDs are associated with the development of cardiovascular events and liver problems. Therefore, there is a need for the development of new therapeutic strategies to improve liver function in patients with chronic liver diseases. The aim of the present study was to assess the therapeutic effects of LPSF/GQ-02 on the liver of LDLR-/- mice after a high-fat diet. Eighty male mice were divided into 4 groups and two different experiments: 1-received a standard diet; 2-fed with a high-fat diet (HFD); 3–HFD+pioglitazone; 4–HFD+LPSF/GQ-02. The experiments were conducted for 10 or 12 weeks and in the last two or four weeks respectively, the drugs were administered daily by gavage. The results obtained with an NAFLD murine model indicated that LPSF/GQ-02 was effective in improving the hepatic architecture, decreasing fat accumulation, reducing the amount of collagen, decreasing inflammation by reducing IL-6, iNOS, COX-2 and F4 / 80, and increasing the protein expression of IκBα, cytoplasmic NFκB-65, eNOS and IRS-1 in mice LDLR -/-. These results suggest a direct action by LPSF/GQ-02 on the factors that affect inflammation, insulin resistance and fat accumulation in the liver of these animals. Further studies are being conducted in our laboratory to investigate the possible mechanism of action of LPSF/GQ-02 on hepatic lipid metabolism.

Nucleated Red Blood Cells as Predictors of All-Cause Mortality in Cardiac Intensive Care Unit Patients: A Prospective Cohort Study

Background The presence of nucleated red blood cells (NRBCs) in the peripheral blood of critically ill patients is associated with a poorer prognosis, though data on cardiovascular critical care patients is lacking. The aim of the present study was to assess the role of NRBCs as a predictor of intensive care unit (ICU) and in hospital all-cause mortality among cardiologic patients. Methods NRBCs were measured daily in consecutive cardiac ICU patients, including individuals with both coronary and non-coronary acute cardiac care. We excluded patients younger than 18 years, with cancer or hematological disease, on glucocorticoid therapy, those that were readmitted after hospital discharge and patients who died in the first 24 hours after admission. We performed a multiple logistic analysis to identify independent predictors of mortality. Results We included 152 patients (60.6 ± 16.8 years, 51.8% female, median ICU stay of 7 [4–11] days). The prevalence of NRBCs was 54.6% (83/152). The presence of NRBC was associated with a higher ICU mortality (49.4% vs 21.7%, P<0.001) as well as in-hospital mortality (61.4% vs 33.3%, p = 0.001). NRBC were equally associated with mortality among coronary disease (64.71% vs 32.5% [OR 3.80; 95%CI: 1.45–10.0; p = 0.007]) and non-coronary disease patients (61.45% vs 33.3% [OR 3.19; 95%CI: 1.63–6.21; p<0.001]). In a multivariable model, the inclusion of NRBC to the APACHE II score resulted in a significant improvement in the discrimination (p = 0.01). Conclusions NRBC are predictors of all-cause in-hospital mortality in patients admitted to a cardiac ICU. This predictive value is independent and complementary to the well validated APACHE II score.

Waist circumference and menopausal status are independent predictors of endothelial low-grade inflammation.

Abstract Background: The high-sensitivity C-reactive protein (hs-CRP) seems to be associated with the presence of atherosclerosis. The association between menopause-related changes in endogenous sex hormones and hs-CRP levels remains controversial. Objective: To compare the levels of hs-CRP in pre- and postmenopausal women and to evaluate the association of endogenous sex hormones, waist circumference (WC) and insulin resistance with the levels of hs-CRP. Methods: This cross-sectional study included 145 women (age range: 45–65 years), 56 premenopausal and 89 postmenopausal. Patients were evaluated for hormonal and lipid profile, HOMA-IR, hs-CRP and WC. Each variable was first assessed for correlation with log hs-CRP using a univariate model, and significant variables were then added to the multivariate regression model. A p value <0.05 was considered statistically significant. Results: The hs-CRP is higher in postmenopausal patients (3.6 ± 4.9 versus 2.6 ± 3.7, p = 0.004). The log hs-CRP was positively correlated with WC (r = 0.13, p = 0.005), HOMA-IR (r = 0.29, p = 0.001), and triglycerides (r = 0.50, p = 0.01). The menopausal status (p = 0.02) and WC (p = 0.00003) behaved as independent predictors of hs-CRP levels. No correlation was found between hs-CRP and the time since menopause (r = −0.1, p = 0.58). Conclusions: The hs-CRP is higher in postmenopausal patients. The menopausal status and WC were independently associated with hs-CRP levels in this sample of pre and postmenopausal women.

Implementation, validation and review of a critical values list in a cardiac emergency room

Introduction: Laboratory critical values (CV) can indicate threatening conditions that require rapid clinical intervention. The aim of this study was to implement, validate and review a critical values list (CVL) at Pronto-Socorro Cardiologico de Pernambuco - Universidade de Pernambuco (PROCAPE-UPE). Method: This study was conducted between 2011 and 2013. To formulate the CVL, laboratory tests performed at PROCAPE were analyzed and compared with those of the Journal of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and the College of American Pathologists (CAP). A draft CVL was validated by physicians; staff training and the standard operating procedure were developed covering the entire clinical analysis laboratory, in order to formalize the procedure of critical result reporting. The CVL was updated every six months. Results: Changes were made in CV intervals for the measurement of total serum calcium, serum sodium, serum potassium, the international normalized ratio (INR) and total leukocyte count. Thyroid-stimulating hormone (TSH) was also included in the CVL. In the pediatric CVL, dosages of serum sodium and INR were included, and a change in the value of serum potassium was made. Thus, periodic reviews of CVL allowed greater adequacy to the needs of the study population and avoided overloading the notification process. Conclusion: Clinical laboratories must be responsible for the implementation, validation and review of their CVL to ensure patients’ health.

Prognostic value of hematological parameters in patients with acute myocardial infarction: Intrahospital outcomes

Background The intensity of the inflammatory response and hemodynamic repercussion in acute myocardial infarction causing the presence in the peripheral circulation of nucleated red blood cells (NRBCs), increases in mean platelet volume (MPV) and neutrophil to lymphocyte ratio (NLR) are associated with a poorer prognosis. The aim of this study was to assess the role of these hematological biomarkers as predictors of all causes of mortality during the hospitalization of patients with acute myocardial infarction. Methods Nucleated red blood cells, mean platelet volume and neutrophil to lymphocyte ratio were measured daily during the hospitalization of the patients with acute myocardial infarction. We excluded patients younger than 18 years, on glucocorticoid therapy, with cancer or hematological diseases and those that were readmitted after hospital discharge. We performed a multiple logistic analysis to identify independent predictors of mortality. Results We included 466 patients (mean age 64.2 ± 12.8 years, 61.6% male). The prevalence of NRBCs in the sample was 9.1% (42 patients), with levels > 200/μL in 27 patients (5.8%). The mean MPV value was 10.9 ±0,9 and the mean NLR value was 3.71 (2,38; 5,72). In a multivariate analysis of serum NRBCs (HR 2.42, 95% CI: 1.35–4.36, p = 0.003), MPV (HR 2.97, 95% CI: 1.15–7.67, p = 0.024) and NLR (HR 5.02, 95% CI: 1.68–15.0, p = 0.004). The presence in the peripheral blood of NRBCs, increased in mean platelet volume and neutrophil to lymphocyte ratio were associated with higher mortality. Conclusions Nucleated red blood cells, mean platelet volume and neutrophil to lymphocyte ratio are independent predictors of intrahospital mortality. Therefore, an important tool in intrahospital clinical surveillance.