Erythrocyte and platelet phospholipid fatty acids as markers of advanced non-small cell lung cancer: comparison with serum levels of sialic acid, TPS and Cyfra 21-1

The phospholipid fatty acid profiles of erythrocytes and platelets from fifty patients with advanced non-small cell lung cancer were investigated using gas chromatography/mass spectrometry, followed by “ROC” curves analysis to gain novel biomarker information. Sialic acid and cytokeratins were also examined. Potentially useful fatty acid markers: Erythrocytes: phosphatidylcholine, 18:2n6 and 20:4n6; phosphatidylethanolamine, 22:4n6 and 22:6n3 + 24:1n9. Platelets: phosphatidylcholine, 22.0; phosphatidylethanolamine, 22:5n3 + 24:0. At the cut-off value to obtain maximum accuracy, the best biomarkers were found in platelets: phosphatidylserine + phosphatidylinositol (PS + PI), 21:0; sphyngomyelin: 20:1n9 and 22:1n9. All these fatty acids showed similar/higher diagnostic yields than the commonly used markers sialic acid or cytokeratins.     

Indicadores contextuales para evaluar los determinantes sociales de la salud y la crisis económica española

Objective

To provide indicators to assess the impact on health, its social determinants and health inequalities from a social context and the recent economic recession in Spain and its autonomous regions.

Proteomics for discovery of candidate colorectal cancer biomarkers

Colorectal cancer(CRC)is the second most common cause of cancer-related deaths in Europe and other Western countries,mainly due to the lack of wellvalidated clinically useful biomarkers with enough sensitivity and specificity to detect this disease at early stages.Although it is well known that the pathogenesis of CRC is a progressive accumulation of mutations in multiple genes,much less is known at the proteome level.Therefore,in the last years many proteomic studies have been conducted to find new candidate protein biomarkers for diagnosis,prognosis and as therapeutic targets for this malignancy,as well as to elucidate the molecular mechanisms of colorectal carcinogenesis.An important advantage of the proteomic approaches is the capacity to look for multiple differentially expressed proteins in a single study.This review provides an overview of the recent reports describing the different proteomic tools used for the discovery of new protein markers for CRC such as two-dimensional electrophoresis methods,quantitative mass spectrometry-based techniques or protein microarrays.Additionally,we will also focus on the diverse biological samples used for CRC biomarker discovery such as tissue,serum and faeces,besides cell lines and murine models,discussing their advantages and disadvantages,and summarize the most frequently identified candidate CRC markers.     

Platelet linoleic acid is a potential biomarker of advanced non-small cell lung cancer

New parameters that could be used as tumor markers for lung cancer would be valuable. Our aim was to analyze the fatty acid profiles of total lipids from erythrocytes and platelets from patients with advanced non-small cell lung cancer (NSCLC), chronic obstructive pulmonary disease (COPD) and asthma to reveal the fatty acids that could be used as NSCLC biomarkers. In our study, 50, 15 and 15 patients with advanced NSCLC, COPD and asthma and 50 healthy subjects were enrolled. Fatty acid profiles were investigated using gas chromatography/mass spectrometry followed by ROC (receiver operating characteristics) curves analysis to gain information about biomarkers. Sialic acid (SA) and cytokeratins were measured by the thiobarbituric acid and immunoradiometric methods respectively. Useful fatty acid markers were as follows: erythrocytes, 22:0 and linoleic acid (LA, 18:2n6); platelets, 16:0, 18:0, and LA. At the cutoff value to obtain maximum accuracy, the best biomarker was platelet LA, with higher diagnostic yields than the commonly used markers SA or cytokeratins (100%, 76%, 75% and 86% sensitivity, specificity, positive predictive value and accuracy, respectively). These findings suggest that platelet LA might be used as a biomarker of NSCLC in relation to different aspects of the disease process that now needs to be explored.     

Continuous electrocorticogram epileptiform discharges due to brain gliosis.

Cortical dysplasia is known to produce continuous epileptiform discharges (CEDs) on electrocorticogram (EcoG) and EEG recordings. The authors studied the incidence of CEDs on ECoGs and correlated this data with pathologic findings. Thirty ECoGs were reviewed that were performed on patients with parietal or occipital lobe epilepsy operated on since 1960. CED was classified as: (1) continuous or semicontinuous rhythmic spikes or sharp waves at frequencies ranging from 2 to 8 Hz, and (2) repetitive bursts of rhythmic polyspike activity lasting 2 to 10 s. All nontumoral pathologic specimens were reviewed. Epileptiform activity was classified using the following criteria: focal (one gyrus), regional (two gyri), lobar (three gyri), bilobar, or multilobar. Pathologic examination showed gliosis in eight specimens, focal cortical dysplasia in five specimens, tumoral lesions in eight specimens, and other pathology in nine specimens. CED was found in 11 ECoGs. In seven pathology specimens, significant gliosis was shown, and in the remaining four specimens, a dysplastic lesion was diagnosed. Epileptiform activity was widespread (lobar, bilobar, or multilobar) when gliosis or focal cortical dysplasia was present. Absence of epileptiform activity or a focal/regional distribution was found in tumors and other lesions. These data suggest that extensive gliotic lesions are highly epileptogenic and produce CEDs, which are morphologically undistinguishable from those produced by focal cortical dysplasia.     

Stress in a changing society

The objective of this study is to describe the job stress models and non-work stressors, their influence on health and magnitude in Spain. Data come from scientific publications, reports and official statistics, primarily of the last decade. Moreover, original data are provided from the analysis of the 5th Spanish Working Conditions Survey. Job stress analysis is based on two complementary models, that based on psychological demands, control and social support (Karaseks model) and another based on the effort-reward unbalance (Siegrists model). In Spain 15% of men and 22% of women have had an excessive workload that have made them feel tired in the last three months. A quarter of workers have low autonomy and 48% of men and 32% of women work in occupations that do not require special abilities, just experience. Moreover, Spain has the highest unemployment and temporary contracts rates in the 15-European Union. The entrance of women into the labour market implies difficulties in reconciling job and family life. Moreover, paid work provides women with power and economic autonomy, therefore making possible the divorce that has significantly increased in Spain as well as the lonely parents families, these being difficult and stressing situations. Additionally the higher economic autonomy and power among women is considered as one of the causes of the gender violence as well. Response to stress-related problems derived from the globalisation, the increasing importance of the tertiary sector and other social changes is insufficient either because health professionals ignore the causes of the problem and treat pharmacologically the consequences or because health consequences of these new social and economic tendencies are not taken into account in other sectors.     

Injuries from domestic violence in the Autonomous Community of Valencia (Spain)

The lack of homogeneous and reliable epidemiological data on domestic violence greatly limits public decision making on the help that should be provided to victims of this form of abuse. Health professionals are obliged to report cases of domestic violence in adults to the judicial authorities and a unified, easily completed model for reporting injuries from domestic violence has been established in the Autonomous Community of Valencia. From June to October 2005, 500 cases of domestic violence were received and processed, most of which were reported by primary care physicians (68%). Cases of domestic violence occurred mainly in young women (aged, 20-39 years), either married or cohabiting, and with primary or secondary level education. The most frequent findings were physical injury or psychological damage (62%). Eighty-three percent of victims had at least one antecedent of abuse.     

Metabolism and toxicity of arsenic in human urothelial cells expressing rat arsenic (+3 oxidation state)-methyltransferase

The enzymatic methylation of inorganic As (iAs) is catalyzed by As(+3 oxidation state)-methyltransferase (AS3MT). AS3MT is expressed in rat liver and in human hepatocytes. However, AS3MT is not expressed in UROtsa, human urothelial cells that do not methylate iAs. Thus, UROtsa cells are an ideal null background in which the role of iAs methylation in modulation of toxic and cancer-promoting effects of this metalloid can be examined. A retroviral gene delivery system was used in this study to create a clonal UROtsa cell line (UROtsa/F35) that expresses rat AS3MT. Here, we characterize the metabolism and cytotoxicity of arsenite (iAs(III)) and methylated trivalent arsenicals in parental cells and clonal cells expressing AS3MT. In contrast to parental cells, UROtsa/F35 cells effectively methylated iAs(III), yielding methylarsenic (MAs) and dimethylarsenic (DMAs) containing either As(III) or As(V). When exposed to MAs(III), UROtsa/F35 cells produced DMAs(III) and DMAs(V). MAs(III) and DMAs(III) were more cytotoxic than iAs(III) in UROtsa and UROtsa/F35 cells. The greater cytotoxicity of MAs(III) or DMAs(III) than of iAs(III) was associated with greater cellular uptake and retention of each methylated trivalent arsenical. Notably, UROtsa/F35 cells were more sensitive than parental cells to the cytotoxic effects of iAs(III) but were more resistant to cytotoxicity of MAs(III). The increased sensitivity of UROtsa/F35 cells to iAs(III) was associated with inhibition of DMAs production and intracellular accumulation of MAs. The resistance of UROtsa/F35 cells to moderate concentrations of MAs(III) was linked to its rapid conversion to DMAs and efflux of DMAs. However, concentrations of MAs(III) that inhibited DMAs production by UROtsa/F35 cells were equally toxic for parental and clonal cell lines. Thus, the production and accumulation of MAs(III) is a key factor contributing to the toxicity of acute iAs exposures in methylating cells.     

High-frequency jet ventilation in interventional bronchoscopy: factors with predictive value on high-frequency jet ventilation complications

STUDY OBJECTIVE: To evaluate the incidence and impact on clinical outcome of complications observed during high-frequency jet ventilation (HFJV) at interventional bronchoscopy and to identify the perioperative factors that may be associated to an increased incidence of such complications. DESIGN: Observational retrospective, study with an observational prospective validation of the statistically significant associations. SETTING: University hospital. PATIENTS: The retrospective study involved 276 patients who underwent an interventional rigid bronchoscopy during general anesthesia and HFJV. Forty consecutive patients were accrued for the prospective validation group. INTERVENTIONS/MEASUREMENTS: Information recorded included patient medical history and perioperative complications observed at HFJV-managed bronchoscopic procedures and their impact on clinical outcome until hospital discharge. MAIN RESULTS: At least one complication was detected in 38% of retrospective patients and 55% of prospective patients. Most frequent complications were hypercapnia, hypoxemia, and hemodynamic instability, but just one case of barotrauma in the retrospective group. Despite the high incidence, these complications were transient and did not increase hospital stay, whereas technical failure to widen airway lumen was associated with an adverse prognosis. Several clinical parameters showed a significant association with complications in the univariate analysis. However, the multivariate analysis only evidenced two independent predictive factors: the ASA physical status scale and baseline oxygen saturation. CONCLUSIONS: Classification in ASA physical status IV group and a baseline oxygen saturation of 95% or less independently predicted the development of complications during interventional rigid bronchoscopy with HFJV.     

Relationship Between Fibrinogen Protein and Fibrinogen Function in Postmyocardial Infarction Patients

The present study investigates the association between increases in the concentration and function of plasma fibrinogen in two groups of patients with chronic ischemic heart disease (11 with recurrent ischemic events and 19 free of these episodes) and in 34 healthy controls. The fibrinogen function index (fibrinogen function per unit of fibrinogen protein) (FgFI) was used as a measure of the fibrinogen clotting potential. The prothrombin fragment 1+2 (F1+2) and thrombin–antithrombin (TAT) were used as procoagulant markers. Plasma sialic acid (SA) was also evaluated as an inflammatory marker. No differences were found between FgFI (1.06±0.13 vs. 1.02±0.13), F1+2 (1.2±0.5 vs. 1.1±0.4 nmol/l) and TAT (2.5±1.3 vs. 2.5±0.7 μg/ml) in postinfarction patients without recurrent coronary ischemic events and the control group. However, postinfarction patients who suffered recurrent coronary ischemic events had significantly higher FgFI than patients without these symptoms (1.19±0.09 vs. 1.06±0.13), P<.01) and than the control group (1.19±0.09 vs. 1.02±0.13, P<.001). Moreover, the F1+2 (1.4±0.5 vs. 1.1±0.4 nmol/l, P<.05) and TAT (3.6±3.3 vs. 2.5±0.7 μg/ml, P<.05) were significantly higher in patients who suffered recurrent coronary ischemic events than in the control group. However, F1+2 and TAT were not different between patients with and without these symptoms. The fibrinogen protein (Fg-protein) concentration and high molecular weight fibrinogen (HMW-Fg) levels were significantly higher in both postinfarction patient groups than in the control group and in postinfarction patients with recurrent coronary ischemic events than in postinfarction patients without these symptoms. The plasma SA levels were significantly increased in postinfarction patients with and without recurrent coronary ischemia as compared with the control group. A positive correlation was found between fibrinogen and SA levels (r=.5, P<.01). In conclusion, our study indicates that the procoagulant factors, among which we include fibrinogen, F1+2 and TAT play a very active role in recurrent ischemic events in postmyocardial infarction patients. High plasma concentrations of both fibrinogen and SA suggests that fibrinogen becomes elevated as a consequence of inflammatory processes. The FgFI as an indicator of clotting potential of fibrinogen appears to be associated with ischemic events in chronic coronary artery disease.