DNA and RNA oxidative damage are associated to mortality in patients with cerebral infarction.

OBJECTIVE: Secondary injury due to oxidation may occur during ischemic stroke, possibly leading to oxidative damage to deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Higher blood concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG) (through the oxidation of guanosine from DNA) have been found in ischemic stroke patients than in healthy subjects, and in patients with versus without post-ischemic stroke depression. The present study was carried out to explore the possible association between serum DNA and RNA oxidative damage and mortality in patients with cerebral infarction. METHODS: A prospective, multicenter observational study was carried out in the Intensive Care Units of 6 Spanish hospitals. We included patients with severe malignant middle cerebral artery infarction (MMCAI) defined as ischemic changes evidenced by computed tomography in more than 50% of the middle cerebral artery territory and a Glasgow Coma Score (GCS)<9. Serum concentrations of the three oxidized guanine species (OGS) (8-hydroxyguanine from DNA or RNA, 8-hydroxyguanosine from RNA, and 8-OHdG from DNA) on the day of MMCAI diagnosis were determined. The study endpoint was 30-day mortality. RESULTS: We found higher serum OGS levels (p<0.001) in non-surviving (n=34) than in surviving patients (n=34). Logistic regression analyses showed serum OGS levels to be associated to 30-day mortality controlling for lactic acid, GCS and platelet count (OR=1.568; 95%CI=1.131-2.174; p=0.01). CONCLUSIONS: The novel observation in this study is the association between global serum OGS concentration and mortality in ischemic stroke patients.

Platelet-Derived Growth Factor C in Alcoholics.

AIMS: Platelet-derived growth factor (PDGF) promotes liver collagen deposition, acting on hepatic stellate cells. Despite this, low serum PDGF levels were reported in chronic hepatitis C or B infection, although some studies yield the opposite result. Since PDGF may be related not only to fibrosis but also with vascular, neuronal or muscle disease, it is important to analyze its behavior in alcoholics. METHODS: In total, 17 controls and 62 alcoholic patients consecutively admitted to the hospitalization unit of the Internal Medicine Service were included. We determined serum levels of PDGF C, routine laboratory evaluation, tumor necrosis factor-α, interleukin (IL)-6 and IL-8 and malondialdehyde (MDA) levels. We analyzed the relationships between PDGF and liver function, ethanol intake and inflammatory reaction by both univariate and multivariate analysis to discern which variables PDGF levels depend on. RESULTS: Serum PDGF levels were significantly lower among patients (675 ± 466 pg/ml) than among controls (1074 ± 337 pg/ml; Z = 3.70; P < 0.001), and even lower among cirrhotics (549 ± 412 among cirrhotics vs 778 ± 487 among non-cirrhotics; Z = 2.33; P = 0.02). PDGF levels showed a direct correlation with prothrombin activity (ρ = 0.50; P < 0.001), platelet count (ρ = 0.44; P < 0.001) and inverse ones with bilirubin (ρ = -0.39; P = 0.002), IL-6 (ρ = -0.33; P = 0.016), IL-8 (ρ = -0.47; P < 0.001), and MDA levels (ρ = -0.44; P < 0.001). By multivariate analysis, only prothrombin activity and platelet count were independently related to PDGF. CONCLUSION: PDGF-C levels are decreased in alcoholics, especially among cirrhotics. Multivariate analysis discloses that only prothrombin activity and platelet count are independently related to PDGF-C levels.

Changes in cytokine levels during admission and mortality in acute alcoholic hepatitis.

Cytokine levels are raised in acute alcoholic hepatitis. However, there are disparate results regarding the duration of altered plasma levels, and there are also discrepancies about the relation of changes during the first 15 days after admission with short-term (in-hospital) or long-term mortality. In 56 patients with acute alcoholic hepatitis we found that IL-8, IL-4, Interferon-γ (IFN-γ), malondialdehyde and C-reactive protein remained higher in patients than in 18 age- and sex-matched controls at admission, at the 7th day and at the 15th day after admission. Moreover, IL-4 levels (and to a lesser extent, IL-10 and IFN-γ ones) increased along the three determinations. However, comparing patients who died during the admission with those who did not, there were no statistically significant differences, but there was a nearly significant trend for MDA (Z=1.89; p=0.059), with higher levels among those who died. When changes between the first and the second determinations were compared with long-term survival, only IL-8 and IFN-γ showed a relation with mortality. IFN-γ values increased among those who survived and decreased among those who died (p=0.048). IFN-γ values at the first determination also showed a relation with long-term mortality, especially when patients with IFN-γ values in the first quartile were compared with those of the 4th one (log rank=5.64; p=0.018; Breslow=4.64; p=0.031). Besides Interferon-γ, only C-reactive protein showed differences between the first and the 4th quartile regarding mortality (Log rank=4.50; p=0.034; Breslow 4.33; p=0.038). In contrast with other studies, no relation was found between TNF-α or IL-6 and mortality.

[Female gender is an independent predictor of in-hospital mortality in patients with ST segment elevation acute myocardial infarction treated with primary angioplasty]. / El género femenino es un predictor independiente de la mortalidad intrahospitalaria en pacientes con infarto agudo de miocardio con elevación del segmento ST revascularizado mediante una angioplastia primaria.

OBJECTIVE: The aim of this study was to determine the influence of gender on in hospital outcome in patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary angioplasty (PA). DESIGN AND SCOPE: Prospective study of a cohort of patients consecutively admitted to the Coronary Unit of a tertiary hospital in the period of January to October 2004 with the diagnoses of IAMEST and treated with PA. PATIENTS: Consecutive sample of 86 patients with this diagnosis divided into two groups based on sex: 52 men and 34 women. MAIN VARIABLES OF INTEREST: In both groups, we analyzed the baseline clinical-demographic characteristics, extension of the coronary disease (ECD), success of the PA, appearance of heart failure (HF) and in-hospital mortality in the first 28 days after admission. We analyzed predictors of mortality in a multivariate model. RESULTS: The women were older (70+/-8 versus 65+/-11; p=0.02) and had greater prevalence of diabetes (37% versus 18%; p=0.002) and hypertension (58% versus 37%; p<0.001) than the men while the men had greater frequency of smoking (34% versus 22%; p=0.001). There were no differences in the presence of hyperlipidemia, ECD or the success of PA. Women had a higher incidence of HF on admission (22% versus 12%; p=0.01) and in-hospital mortality (17% versus 8%; p=0.002). In the multivariate analyses, female sex and HF on admission continued to be predictors of in-hospital mortality. CONCLUSIONS: In our study, female gender was an independent predictor of in-hospital mortality in patients with IAMEST treated with PA.

[Systemic inflammatory response syndrome: incidence and influence on outcome in acute myocardial infarction treated with primary angioplasty]. / Síndrome de respuesta inflamatoria sistémica: incidencia e influencia pronóstica en el infarto agudo de miocardio tratado con angioplastia primaria.

OBJECTIVE: To assess the incidence, clinical profile and influence on outcome of systemic inflammatory response syndrome (SIRS) in patients with acute myocardial infarction (AMI) treated with primary angioplasty (PA). DESIGN: Prospective observational study. SCOPE: A 12-beds coronary care unit at a university hospital. PATIENTS AND METHODS: Patients with AMI treated with PA, admitted in 2004 were studied. PRINCIPAL VARIABLES OF INTEREST: Age, gender, anterior localization of AMI, smoking, arterial hypertension, diabetes mellitus, troponin Ic levels, time delays until PA, heart failure, left ventricular ejection fraction (LVEF), in-hospital length of stay and mortality. RESULTS: Ninety patients were included. SIRS was diagnosed in 15 patients (16.6%), who were older (72 +/- 7 vs 66 +/- 9 years; p = 0,01). These patients had a greater frequency of diabetes mellitus (42% vs 17%; p = 0.01), higher troponin Ic levels (80 +/- 12 vs 68 +/- 19 ng/ml; p = 0.02), lower LVEF (41 +/- 8% vs 51 +/- 12%; p = 0.002), longer in-hospital length of stay (18 +/- 5 vs 7 +/- 3 days, p = 0.001), and higher in-hospital mortality (10 vs 3%, p = 0.03) compared with patients without SIRS. Diabetes mellitus (OR: 1.7; 95% CI: 1.2-1.9) and lower ejection fraction (OR: 2.3; 95% CI: 1.5-3.1) were the independent predictors of the presence of systemic inflammatory response syndrome. In multivariant analysis SIRS was an independent predictor of mortality in AMI patients treated with PA (OR: 3.3; 95% CI: 1.3-6). CONCLUSIONS: Systemic inflammatory response syndrome may be present in AMI patients treated with PA and its presence is associated to a worse outcome and longer in-hospital stay.

Protein deficiency and muscle damage in carbon tetrachloride induced liver cirrhosis.

Protein undernutrition, alterations of hormones such as IGF-1, testosterone and cortisol, and increased lipid peroxidation-which may be related with deranged metabolism of some elements such as iron (Fe), zinc (Zn), manganese (Mn), selenium (Se) or copper (Cu)-may contribute to muscle damage in non alcoholic cirrhosis. Here, we analyse the effect of protein deficiency on muscle Cu, Fe, Zn, Mn and Se in carbon-tetrachloride (CCl(4)) induced liver cirrhosis. We also study the association between protein undernutrition and these trace elements with the activity of glutathione peroxidase (GPX), superoxide dismutase (SOD) and lipid peroxidation products, and how all these are related with muscle morphological changes in 40 male adult Sprague-Dawley rats. Liver cirrhosis was induced by intraperitoneal injection of CCl(4) to 10 rats fed a 2% protein diet, and to another 10 fed a 18% protein control diet. Two further groups included rats without cirrhosis fed the 2% protein and the 18% protein diets. After sacrifice (6 weeks later), we found type IIa fibre atrophy in the cirrhotic animals, especially in the low-protein fed ones and this was due to protein deficiency. Muscle Fe increased in low protein fed cirrhotic rats. No relationship was found between muscle changes and any of the hormones, enzymes and trace elements analysed, or with liver fibrosis. These results suggest that muscle atrophy observed in CCl(4)-induced cirrhosis is related with protein deficiency, but not with cirrhosis itself.

Effects of protein deficiency on liver trace elements and antioxidant activity in carbon tetrachloride-induced liver cirrhosis.

In liver cirrhosis, liver tissue becomes progressively substituted by fibrosis, ultimately leading to architectural distortion, liver circulatory changes, and liver failure. Some data support the hypothesis that protein undernutrition may play a role in the development and progression of nonalcoholic liver cirrhosis and that this progression is at least partially mediated by changes in glutathione peroxidase (GPX), superoxide dismutase (SOD), and other antioxidative systems, leading to an increase in lipid peroxidation. We analyzed the effects of protein deficiency on liver Cu, Fe, Zn, Mn, and Se in carbon tetrachloride (CCl4)-induced liver cirrhosis, the relation of protein undernutrition and these trace elements with the activity of some hepatic antioxidative enzymatic mechanisms, and the relation of all of them with morphological and biochemical changes in 40 male adult Sprague-Dawley rats divided in four groups. Liver cirrhosis was induced by intraperitoneal injection of CCl4 to 10 rats fed a 2% protein diet and another 10 fed a 18% protein control diet; two further groups included rats without cirrhosis fed the 2% protein and the 18% protein diets. The study period lasted 6 wk. GPX, SOD, and lipid peroxidation products as well as Zn, Cu, Mn, Se, and Fe were determined in liver samples. We found that liver GPX and Se were reduced in the cirrhotic animals, especially in the low-protein-fed ones, protein deficiency, but not cirrhosis, exerting the main effects. A close correlation was found between liver GPX and serum albumin and weight loss and an inverse one among GPX and hepatocyte ballooning, liver fibrosis, and fat, histomorphometrically determined. These results suggest a pathogenetic role of decreased GPX in the progression of liver disease, which may become enhanced by concomitant protein undernutrition. In addition to iron, the levels of which were increased in the malnourished rats, no differences were found regarding the other trace elements, SOD activity, and lipid peroxidation products.