Chitosan and Chitooligosaccharides: Antifungal Potential and Structural Insights.

Chitosan is a cationic polysaccharide derived from chitin deacetylation. This polysaccharide and its oligosaccharides have many biological activities and can be used in several fields due to their favorable characteristics, such as biodegradability, biocompatibility, and nontoxicity. This review aims to explore the antifungal potential of chitosan and chitooligosaccharides along with the conditions used for the activity and mechanisms of action they use to kill fungal cells. The sources, chemical properties, and applications of chitosan and chitooligosaccharides are discussed in this review. It also addresses the threat fungi pose to human health and crop production and how these saccharides have proven to be effective against these microorganisms. The cellular processes triggered by chitosan and chitooligosaccharides in fungal cells, and prospects for their use as potential antifungal agents are also examined.

Hematological Changes during Seven Days of Hospitalization in Patients with Acute Myocardial Infarction. / Alterações Hematológicas durante um Período de Sete Dias de Internação em Pacientes com Infarto Agudo do Miocárdio.

BACKGROUND: Acute myocardial infarction is a major cause of mortality worldwide, and atherosclerotic plaque formation is the main pathophysiological mechanism, which results in chronic inflammation that induces erythrocyte maturation and may cause an increase in the red cell distribution width (RDW) index. OBJECTIVE: Evaluate the role of the anisocytosis index in patients with acute myocardial infarction in both types of infarctions as a predictor of severity. METHODS: Patients were included in the study according to the inclusion/exclusion criteria, following the hospital routine based on their clinical and laboratory history. Statistical analyzes were performed according to each variable. All conclusions were drawn considering the significance level of 5%. RESULTS: During the follow-up period, in the 349 patients analyzed, the mortality rate was associated with the variables RDW (CV) and RDW (SD), in those patients who died, an increase was noted, as demonstrated in the multivariate model, for the effects of an acute ST elevation myocardial infarction and the RDW, adjusted for confounding factors (p-value = 0.03 and 0.04). In contrast, the total number of erythrocytes (p-value = 0.00) and hemoglobin (p-value = 0.03) showed a decrease during severe patients' hospitalization. CONCLUSION: The anisocytosis index was a predictive factor of mortality and can be used as an indicator of worse prognosis in patients with acute myocardial infarction.

FUNDAMENTO: O infarto agudo do miocárdio é uma das principais causas de mortalidade em todo o mundo e a formação de placa aterosclerótica é o principal mecanismo fisiopatológico, que resulta em inflamação crônica e induz a maturação eritrocitária, podendo causar aumento no índice de amplitude de distribuição dos glóbulos vermelhos (RDW). OBJETIVO: Avaliar o papel do índice de anisocitose em pacientes com infarto agudo do miocárdio em ambos os tipos de infarto como preditor de gravidade. MÉTODOS: Os pacientes foram incluídos no estudo de acordo com os critérios de inclusão e exclusão, seguindo a rotina hospitalar baseada na história clínica e laboratorial. As análises estatísticas foram realizadas de acordo com cada variável. Chegou-se a todas as conclusões considerando o nível de significância de 5%. RESULTADOS: Durante o período de acompanhamento, nos 349 pacientes analisados, a taxa de mortalidade esteve associada às variáveis RDW (CV) e RDW (SD). Nos pacientes que foram a óbito, notou-se aumento, conforme demonstrado no modelo multivariado, nos efeitos de um infarto agudo do miocárdio com supradesnivelamento do segmento ST e RDW, ajustado para fatores de confusão (valor-p = 0,03 e 0,04). Em contrapartida, o número total de eritrócitos (valor-p = 0,00) e hemoglobina (valor-p = 0,03) apresentou diminuição durante a internação de pacientes graves. CONCLUSÃO: O índice de anisocitose foi fator preditivo de mortalidade e pode ser utilizado como indicador de pior prognóstico em pacientes com infarto agudo do miocárdio.

Alterações Hematológicas durante um Período de Sete Dias de Internação em Pacientes com Infarto Agudo do Miocárdio / Hematological Changes during Seven Days of Hospitalization in Patients with Acute Myocardial Infarction

Resumo Fundamento O infarto agudo do miocárdio é uma das principais causas de mortalidade em todo o mundo e a formação de placa aterosclerótica é o principal mecanismo fisiopatológico, que resulta em inflamação crônica e induz a maturação eritrocitária, podendo causar aumento no índice de amplitude de distribuição dos glóbulos vermelhos (RDW). Objetivo Avaliar o papel do índice de anisocitose em pacientes com infarto agudo do miocárdio em ambos os tipos de infarto como preditor de gravidade. Métodos Os pacientes foram incluídos no estudo de acordo com os critérios de inclusão e exclusão, seguindo a rotina hospitalar baseada na história clínica e laboratorial. As análises estatísticas foram realizadas de acordo com cada variável. Chegou-se a todas as conclusões considerando o nível de significância de 5%. Resultados Durante o período de acompanhamento, nos 349 pacientes analisados, a taxa de mortalidade esteve associada às variáveis RDW (CV) e RDW (SD). Nos pacientes que foram a óbito, notou-se aumento, conforme demonstrado no modelo multivariado, nos efeitos de um infarto agudo do miocárdio com supradesnivelamento do segmento ST e RDW, ajustado para fatores de confusão (valor-p = 0,03 e 0,04). Em contrapartida, o número total de eritrócitos (valor-p = 0,00) e hemoglobina (valor-p = 0,03) apresentou diminuição durante a internação de pacientes graves. Conclusão O índice de anisocitose foi fator preditivo de mortalidade e pode ser utilizado como indicador de pior prognóstico em pacientes com infarto agudo do miocárdio.

Abstract Background Acute myocardial infarction is a major cause of mortality worldwide, and atherosclerotic plaque formation is the main pathophysiological mechanism, which results in chronic inflammation that induces erythrocyte maturation and may cause an increase in the red cell distribution width (RDW) index. Objective Evaluate the role of the anisocytosis index in patients with acute myocardial infarction in both types of infarctions as a predictor of severity. Methods Patients were included in the study according to the inclusion/exclusion criteria, following the hospital routine based on their clinical and laboratory history. Statistical analyzes were performed according to each variable. All conclusions were drawn considering the significance level of 5%. Results During the follow-up period, in the 349 patients analyzed, the mortality rate was associated with the variables RDW (CV) and RDW (SD), in those patients who died, an increase was noted, as demonstrated in the multivariate model, for the effects of an acute ST elevation myocardial infarction and the RDW, adjusted for confounding factors (p-value = 0.03 and 0.04). In contrast, the total number of erythrocytes (p-value = 0.00) and hemoglobin (p-value = 0.03) showed a decrease during severe patients' hospitalization. Conclusion The anisocytosis index was a predictive factor of mortality and can be used as an indicator of worse prognosis in patients with acute myocardial infarction.

Structural and functional features of a class VI chitinase from cashew (Anacardium occidentale L.) with antifungal properties.

A partial cDNA sequence from Anacardium occidentale CCP 76 was obtained, encoding a GH19 chitinase (AoChi) belonging to class VI. AoChi exhibits distinct structural features in relation to previously characterized plant GH19 chitinases from classes I, II, IV and VII. For example, a conserved Glu residue at the catalytic center of typical GH19 chitinases, which acts as the proton donor during catalysis, is replaced by a Lys residue in AoChi. To verify if AoChi is a genuine chitinase or is a chitinase-like protein that has lost its ability to degrade chitin and inhibit the growth of fungal pathogens, the recombinant protein was expressed in Pichia pastoris, purified and biochemically characterized. Purified AoChi (45 kDa apparent molecular mass) was able to degrade colloidal chitin, with optimum activity at pH 6.0 and at temperatures from 30 °C to 50 °C. AoChi activity was completely lost when the protein was heated at 70 °C for 1 h or incubated at pH values of 2.0 or 10.0. Several cation ions (Al3+, Cd2+, Ca2+, Pb2+, Cu2+, Fe3+, Mn2+, Rb+, Zn2+ and Hg2+), chelating (EDTA) and reducing agents (DTT, ß-mercaptoethanol) and the denaturant SDS, drastically reduced AoChi enzymatic activity. AoChi chitinase activity fitted the classical Michaelis-Menten kinetics, although turnover number and catalytic efficiency were much lower in comparison to typical GH19 plant chitinases. Moreover, AoChi inhibited in vitro the mycelial growth of Lasiodiplodia theobromae, causing several alterations in hyphae morphology. Molecular docking of a chito-oligosaccharide in the substrate-binding cleft of AoChi revealed that the Lys residue (theoretical pKa = 6.01) that replaces the catalytic Glu could act as the proton donor during catalysis.

Secretory production in Escherichia coli of a GH46 chitosanase from Chromobacterium violaceum, suitable to generate antifungal chitooligosaccharides.

A chitosanase (CvCsn46) from Chromobacterium violaceum ATCC 12472 was produced in Escherichia coli, purified, and partially characterized. When subjected to denaturing polyacrylamide gel electrophoresis, the enzyme migrated as two protein bands (38 and 36 kDa apparent molecular masses), which were both identified as CvCsn46 by mass spectrometry. The enzyme hydrolyzed colloidal chitosan, with optimum catalytic activity at 50 °C, and two optimum pH values (at pH 6.0 and pH 11.0). The chitosanolytic activity of CvCsn46 was enhanced by some ions (Ca2+, Co2+, Cu2+, Sr2+, Mn2+) and DTT, whereas Fe2+, SDS and ß-mercaptoethanol completely inhibited its activity. CvCsn46 showed a non-Michaelis-Menten kinetics, characterized by a sigmoidal velocity curve (R2 = 0.9927) and a Hill coefficient of 3.95. ESI-MS analysis revealed that the hydrolytic action of CvCsn46 on colloidal chitosan generated a mixture of low molecular mass chitooligosaccharides, containing from 2 to 7 hexose residues, as well as D-glucosamine. The chitosan oligomers generated by CvCsn46 inhibited in vitro the mycelial growth of Lasiodiplodia theobromae, significantly reducing mycelium extension and inducing hyphal morphological alterations, as observed by scanning electron microscopy. CvCsn46 was characterized as a versatile biocatalyst that produces well-defined chitooligosaccharides, which have potential to control fungi that cause important crop diseases.

Performance of a Hematological Scoring System in Predicting All-Cause Mortality in Patients with Acute Myocardial Infarction

Abstract Background: The presence of nucleated red blood cells (NRBCs) and increases in mean platelet volume (MPV) and neutrophil to lymphocyte ratio (NLR) in peripheral circulation are associated with poorer prognosis in patients with acute coronary disease. Objective: We developed a scoring system for in-hospital surveillance of all-cause mortality using hematological laboratory parameters in patients with acute myocardial infarction (AMI). Methods: Patients admitted for AMI were recruited in this prospective study. Exclusion criteria were age younger than 18 years, glucocorticoid therapy, cancer or hematological diseases and readmissions. NRBCs, MPV and NLR were measured during hospitalization. The scoring system was developed in three steps: first, the magnitude of the association of clinical and laboratory parameters with in-hospital mortality was measured by odds ratio (OR), second, a multivariate logistic regression model was conducted with all variables significantly (p < 0.05) associated with the outcome, and third, a β-coefficient was estimated by multivariate logistic regression with hematological parameters with a p < 0.05. Results: A total of 466 patients (mean age were 64.2 ± 12.8 years, 61.6% male) were included in this study. A hematological scoring system ranging from 0 to 49, where higher values were associated with higher risk of in-hospital death. The best performance was registered for a cut-off value of 26 with sensitivity of 89.1% and specificity of 67.2%, positive predictive value of 26.8% (95% CI: 0.204 - 0.332) and negative predictive value of 97.9% (95% CI: 0.962 - 0.996). The area under the curve for the scoring system was 0.868 (95% CI: 0.818 - 0.918). Conclusions: Here we propose a hematological scoring system for surveillance tool during hospitalization of patients with acute myocardial infarction. Based on total blood count parameters, the instrument can evaluate inflammation and hypoxemia due to in-hospital complications and, consequently, predict in-hospital mortality.

Mo-CBP3, a 2S albumin from Moringa oleifera, is a complex mixture of isoforms that arise from different post-translational modifications.

Mo-CBP3 is a chitin-binding 2S albumin from Moringa oleifera. This seed storage protein is resistant to thermal denaturation and shows biological activities that might be of practical use, such as antifungal properties against Candida sp., a pathogen that causes candidiasis, and against Fusarium solani, a soil fungus that can cause diseases in plants and humans. Previous work has demonstrated that Mo-CBP3 is a mixture of isoforms encoded by members of a small multigene family. Mature Mo-CBP3 is a small protein (∼14 kDa), constituted by a small chain of approximately 4 kDa and a large chain of 8 kDa, which are held together by disulfide bridges. However, a more comprehensive picture on the spectrum of Mo-CBP3 isoforms which are found in mature seeds, is still lacking. In this work, genomic DNA fragments were obtained from M. oleifera leaves, cloned and completely sequenced, thus revealing new genes encoding Mo-CBP3. Moreover, mass spectrometry analysis showed that the mature protein is a complex mixture of isoforms with a remarkable number of molecular mass variants. Using computational predictions and calculations, most (∼86%) of the experimentally determined masses were assigned to amino acid sequences deduced from DNA fragments. The results suggested that the complex mixture of Mo-CBP3 isoforms originates from proteins encoded by closely related genes, whose products undergo different combinations of distinct post-translational modifications, including cleavage at the N- and C-terminal ends of both subunits, cyclization of N-terminal Gln, as well as Pro hydroxylation, Ser/Thr phosphorylation, and Met oxidation.

Hematological Parameters as Prognostic Biomarkers in Patients with Cardiovascular Diseases.

Cardiovascular diseases are the major causes of preventable health loss from disease in the world and lead to functional disturbances including hematological parameters. The inflammatory and hypoxemic nature of cardiovascular diseases causes a stimulus in the bone marrow and, depending on the intensity of this stimulus, there is a release of immature cells or increase of other cells in the bloodstream. Therefore, their presence in the circulation is an important variable used to diagnose, stratify and predict diseases. In the last five decades, with the advent of automated counting of immature cells in the peripheral blood, the hemogram was transformed into a clinical tool of great importance in hospital surveillance for demonstrating this daily variability in the hematopoietic response according to the existing injury in the patient. Studies have shown that the presence of nucleated red blood cells and increases in mean platelet volume, immature granulocytes and neutrophil to lymphocyte ratio in the systemic circulation are independent prognostic biomarkers. This review article has as main objective to demonstrate the association of these hematological parameters to cardiovascular diseases, emphasizing their importance in clinical decision making.

Cloning of cDNA sequences encoding cowpea (Vigna unguiculata) vicilins: Computational simulations suggest a binding mode of cowpea vicilins to chitin oligomers.

Vicilins are 7S globulins which constitute the major seed storage proteins in leguminous species. Variant vicilins showing differential binding affinities for chitin have been implicated in the resistance and susceptibility of cowpea to the bruchid Callosobruchus maculatus. These proteins are members of the cupin superfamily, which includes a wide variety of enzymes and non-catalytic seed storage proteins. The cupin fold does not share similarity with any known chitin-biding domain. Therefore, it is poorly understood how these storage proteins bind to chitin. In this work, partial cDNA sequences encoding ß-vignin, the major component of cowpea vicilins, were obtained from developing seeds. Three-dimensional molecular models of ß-vignin showed the characteristic cupin fold and computational simulations revealed that each vicilin trimer contained 3 chitin-binding sites. Interaction models showed that chito-oligosaccharides bound to ß-vignin were stabilized mainly by hydrogen bonds, a common structural feature of typical carbohydrate-binding proteins. Furthermore, many of the residues involved in the chitin-binding sites of ß-vignin are conserved in other 7S globulins. These results support previous experimental evidences on the ability of vicilin-like proteins from cowpea and other leguminous species to bind in vitro to chitin as well as in vivo to chitinous structures of larval C. maculatus midgut.

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.

Diabetes mellitus e a doença de Alzheimer / Diabetes Mellitus and Alzheimer's disease

A associação entre a Diabete Mellitus e a demência está sendo alvo de forte interesse devido a alta incidência com o aumento da expectativa de vida. A diabete, assim como doenças vasculares, apresenta forte fator de risco para o desenvolvimento de demências. Muitos fatores afetam adversamente a saúde do cérebro de indivíduos com Diabetes, incluindo a desregulação energética, inflamação, diminuição da perfusão, aumento do estresse oxidativo e deposição proteica. A diabete é uma doença metabólica complexa que pode ter efeitos devastadores sobre múltiplos sistemas orgânicos. É proposto que na fisiopatologia do déficit cognitivo no diabético sejam pela hipoglicemia crônica, efeitos acumulativos de eventos hipoglicêmicos e possíveis efeitos diretos da insulina no sistema nervoso central. Ainda não está claro se esses fatores, isoladamente, ou, em conjunto, conduzem ao desenvolvimento do déficit cognitivo. Fortes evidências demonstram que a Doença de Alzheimer, juntamente com as doenças cardiovasculares e diabetes possam ter uma mesma origem. Tendo em vista a discussão que o metabolismo energético seja enfatizado devido à hipoperfusão, não é difícil especular que a Diabetes possa ser um componente importante na patogênese da Doença de Alzheimer por reflexo da vasculopatia associada, resultando em danos ao ambiente microvascular. Com base nesta revisão foi possível perceber a forte a fluência da Diabetes sobre o quadro de declínio cognitivo o que sugere uma forte influência da Diabetes no desenvolvimento da Doença de Alzheimer e a existência de um potencial link etiológico entre as Doenças Vasculares, Diabetes e a Doença de Alzheimer.

The association between diabetes mellitus and dementia is target of strong interest due to high incidence with increasing life expectancy.Diabetes, as well as vascular diseases, presents a strong risk factor for the development of dementia. Many factors adversely affect the health of the brain in individuals with diabetes, including energy dysregulation, inflammation, decreased perfusion, increased oxidative stress and protein deposition. Diabetes is a complex metabolic disease that can have devastating effects in multiple organ systems. It is proposed that in the pathophysiology of cognitive deficit in diabetic patients is the chronic hypoglycemia, cumulative effects of hypoglycemic events and possible direct effects of insulin on the central nervous system. It is unclear whether these factors singly or together, lead to the development of cognitive deficit. Strong evidence shows that Alzheimer's disease together with cardiovascular disease and diabetes can have the same origin.In view of the discussion that energy metabolism is emphasized due to hypoperfusion, it is not difficult to speculate that diabetes may be an important component in the pathogenesis of Alzheimer's disease by reflecting the associated vasculopathy, resulting in damage to the microvascular environment. Based on this review it was revealed the strong influence of diabetes on cognitive decline framework and our conclusion supports the hypothesis of a strong influence of diabetes on the development of Alzheimer's disease and the existence of a potential etiological link between the Vascular Diseases, diabetes and Alzheimer's disease.

cDNA cloning, molecular modeling and docking calculations of L-type lectins from Swartzia simplex var. grandiflora (Leguminosae, Papilionoideae), a member of the tribe Swartzieae.

The genus Swartzia is a member of the tribe Swartzieae, whose genera constitute the living descendants of one of the early branches of the papilionoid legumes. Legume lectins comprise one of the main families of structurally and evolutionarily related carbohydrate-binding proteins of plant origin. However, these proteins have been poorly investigated in Swartzia and to date, only the lectin from S. laevicarpa seeds (SLL) has been purified. Moreover, no sequence information is known from lectins of any member of the tribe Swartzieae. In the present study, partial cDNA sequences encoding L-type lectins were obtained from developing seeds of S. simplex var. grandiflora. The amino acid sequences of the S. simplex grandiflora lectins (SSGLs) were only averagely related to the known primary structures of legume lectins, with sequence identities not greater than 50-52%. The SSGL sequences were more related to amino acid sequences of papilionoid lectins from members of the tribes Sophoreae and Dalbergieae and from the Cladratis and Vataireoid clades, which constitute with other taxa, the first branching lineages of the subfamily Papilionoideae. The three-dimensional structures of 2 representative SSGLs (SSGL-A and SSGL-E) were predicted by homology modeling using templates that exhibit the characteristic ß-sandwich fold of the L-type lectins. Molecular docking calculations predicted that SSGL-A is able to interact with D-galactose, N-acetyl-D-galactosamine and α-lactose, whereas SSGL-E is probably a non-functional lectin due to 2 mutations in the carbohydrate-binding site. Using molecular dynamics simulations followed by density functional theory calculations, the binding free energies of the interaction of SSGL-A with GalNAc and α-lactose were estimated as -31.7 and -47.5 kcal/mol, respectively. These findings gave insights about the carbohydrate-binding specificity of SLL, which binds to immobilized lactose but is not retained in a matrix containing D-GalNAc as ligand.

Expression in Escherichia coli of cysteine protease inhibitors from cowpea (Vigna unguiculata): The crystal structure of a single-domain cystatin gives insights on its thermal and pH stability.

Two cysteine proteinase inhibitors from cowpea, VuCys1 and VuCys2, were produced in E. coli ArcticExpress (DE3). The recombinant products strongly inhibited papain and chymopapain as well as the midgut proteases from Callosobruchus maculatus larvae, a bruchid that uses cysteine proteases as major digestive enzymes. Heat treatment at 100°C for up to 60min or incubation at various pH values caused little reduction in the papain inhibitory activity of both inhibitors. Moreover, minor conformational variations, as probed by circular dichroism spectroscopy, were observed after VuCys1 and VuCys2 were subjected to these treatments. The crystal structure of VuCys1 was determined at a resolution of 1.95Å, revealing a domain-swapped dimer in the asymmetric unit. However, the two lobes of the domain-swapped dimer are positioned closer to each other in VuCys1 in comparison to other similar cystatin structures. Moreover, some polar residues from opposite lobes recruit water molecules, forming a hydrogen bond network that mediates contacts between the lobes, thus generating an extended open interface. Due to the closer distance between the lobes, a small hydrophobic core is also formed, further stabilizing the folded domain-swapped dimer. These structural features might account for the extraordinary thermal and pH stability of VuCys1.

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.

Ángulo de fase como indicador del estado nutricional y pronóstico en pacientes críticos / Phase angle as an indicator of nutritional status and prognosis in critically ill patients

Introducción: El ángulo de fase (AF) viene siendo considerado una herramienta sensible para evaluar el estado nutricional y la efectividad de las intervenciones dietoterápicas. Objetivo: Evaluar el AF como indicador del estado nutricional y pronóstico en pacientes críticos. Métodos: Estudio prospectivo observacional con pacientes admitidos en Unidades de Cuidado Intensivo Coronarias, entre Mayo y Octubre de 2013. El AF se determinó por medio del análisis por Bioimpedancia Eléctrica, considerándose bajo AF valores inferiores a 5º para los hombres y 4,6º para las mujeres. Los valores obtenidos se relacionaron con otros parámetros de evaluación del estado nutricional: antropométricos (circunferencia del brazo - CB, pliegue cutáneo triciptal - PCT, área muscular del brazo corregida - AMBc circunferencia de pantorrilla - CP) y bioquímico (recuento total de linfocitos, hemoglobina, hematocrito), además de los pronósticos clínicos APACHE II (Acute Physiology and Chronic Health Disease Classification System II) y albúmina sérica. La tabulación y análisis de los datos se realizaron a través del paquete estadístico SPSS versión 13.0. Resultados: La muestra se compuso por 110 pacientes, en la cual se verificó asociación entre bajo AF e insuficiencia renal en diálisis (p<0,001), % de adecuación de CB (p=0,028), % de adecuación de PCT (p=0,043), hipoalbuminemia (p=0,042), anemia (p=0,040) y puntuación APACHE II (p=0,012). El AF se correlacionó positivamente con la CP e inversamente con el tiempo de internación (p=0,006). Conclusiones: El AF en UCI parece ser útil para identificar a pacientes desnutridos precozmente y como indicador pronóstico (AU)

Introduction: The phase angle (PA) has been considered a sensitive tool to assess nutritional status and effectiveness of interventions dietetics. Objective: To evaluate the PA as an indicator of nutritional status and prognosis in critically ill patients. Methods: Prospective observational study of patients admitted to the Coronary Intensive Care Unit between May and October 2013. The PA was determined by bioelectrical impedance analysis, PA was considered low below 5º values for men and 4.6º for women. The values obtained were related to other evaluation parameters of nutritional status: anthropometric (arm circumference- AC , triceps skinfold thickness - TST , corrected armmuscle area - AMAc and calf circumference - CC) and biochemical (total lymphocyte count, hemoglobin, hematocrit),in addition to clinical prognostic APACHE II(Acute Physiology and Chronic Health Disease Classification System II) and serum albumin. The tabulation and analysis were performed using SPSS version 13.0.Results: The sample consisted of 110 patients, in which an association was found between low AF and renal failure on dialysis (p < 0.001), % adequacy AC (p =0.028), % adequacy of TST (p = 0.043), albumin level (p= 0.042), anemia (p = 0.040) and APACHE II (p = 0.012)scores. The AF was positively correlated with CC (p=0.043) and inversely with the length of hospitalization(p = 0.006).Conclusions: PA in the ICU may be useful to identify early and malnourished patients as a prognostic indicator (AU)

Bioethical conflicts of gene therapy: a brief critical review / Conflitos bioéticos da terapia gênica: uma breve opinião crítica

Methods and techniques employed in gene therapy are reviewed in parallel with pertinent ethical conflicts. Clinical interventions based on gene therapy techniques preferentially use vectors for the transportation of therapeutic genes, however little is known about the potential risks and damages to the patient. Thus, attending carefully to the clinical complications arising as well as to security is essential. Despite the scientific and technological advances, there are still many uncertainties about the side effects of gene therapy. Moreover, there is a need, above all, to understand the principles of bioethics as both science and ethics, in accordance with its socioecological responsibility, in order to prioritize the health and welfare of man and nature, using properly natural resources and technology. Therefore, it is hard to determine objective results and to which extent the insertion of genes can affect the organism, as well as the ethical implication.

Métodos e técnicas empregadas na terapia gênica são revisados em paralelo a conflitos éticos pertinentes. Intervenções clínicas com base em técnicas de terapia gênica são usadas preferencialmente em vetores para o transporte de genes terapêuticos; porém, pouco se sabe sobre os possíveis riscos e danos para o paciente, sendo necessário atender cuidadosamente às complicações clínicas resultantes, bem como à segurança. Apesar dos avanços científicos e tecnológicos relacionados à terapia gênica, ainda há muitas incertezas sobre os efeitos colaterais do uso dessa terapia. Além disso, é necessário, acima de tudo, compreender os princípios da bioética como uma ética da ciência para com a responsabilidade socioecológica, a fim de priorizar a saúde e o bem-estar do homem e da natureza, utilizando adequadamente recursos naturais e tecnologia. Portanto, é difícil afirmar qual é o rendimento real, bem como os resultados do aumento da genética inserida no organismo e as implicações éticas.

Implementation, validation and review of a critical values list in a cardiac emergency room / Implantação, validação e revisão da lista de valores críticos em um pronto-socorro cardiológico

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 Cardiológico 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. .

Introdução: Valores críticos (VC) laboratoriais podem ser indicativos de condições de risco de morte que requerem intervenção clínica rápida. O objetivo deste estudo foi implantar, validar e revisar uma lista de valores críticos (LVC) no Pronto-Socorro Cardiológico Universitário de Pernambuco-Universidade de Pernambuco (PROCAPE-UPE). Método: Este trabalho foi realizado no período de 2011 a 2013. Para elaborar a LVC, os testes laboratoriais realizados no PROCAPE foram analisados e comparados com os dos jornais da Federação Internacional de Química Clínica e Medicina Laboratorial (IFCC) e do Colégio Americano de Patologistas (CAP). Após a elaboração da LVC, ela foi validada por médicos; treinamentos e procedimento operacional padrão foram desenvolvidos abrangendo todo o laboratório de análises clínicas, com o intuito de formalizar o procedimento de comunicação de resultados críticos. A LVC foi revisada a cada seis meses. Resultados: Foram realizadas modificações nos intervalos de VC na dosagem de cálcio sérico total, sódio sérico, potássio sérico, no índice internacional normalizado (INR) e na contagem total de leucócitos. Também foi incluído na LVC o hormônio estimulante de tireoide (TSH). Na LVC exclusiva da pediatria, foi incluída a dosagem de sódio sérico e o INR, e uma alteração no valor do potássio sérico foi realizada. Assim, uma avaliação periódica da LVC possibilitou maior adequação às necessidades da população de estudo e evitou sobrecarga no processo de notificação. Conclusão: Faz-se necessário que os laboratórios de análises clínicas sejam responsáveis pela implantação, validação ...