Antiproliferative effects of phenylaminonaphthoquinones are increased by ascorbate and associated with the appearance of a senescent phenotype in human bladder cancer cells.

Quinone-containing molecules have been developed against cancer mainly for their redox cycling ability leading to reactive oxygen species (ROS) formation. We have previously shown that donor-acceptor phenylaminonaphthoquinones are biologically active against a panel of cancer cells. In this report, we explored the mechanisms involved in cancer cell growth inhibition caused by two phenylaminonaphthoquinones, namely Q7 and Q9, with or without ascorbate (ASC). The results show that Q7 and Q9 are both redox cyclers able to form ROS, which strongly inhibit the proliferation of T24 cells. Q9 was a better redox cycler than Q7 because of marked stabilization of the semiquinone radical species arising from its reduction by ascorbate. Indeed, ASC dramatically enhances the inhibitory effect of Q9 on cell proliferation. Q9 plus ASC impairs the cell cycle, causing a decrease in the number of cells in the G2/M phase without involving other cell cycle regulating key proteins. Moreover, Q9 plus ASC influences the MAPK signaling pathways, provoking the appearance of a senescent cancer cell phenotype and ultimately leading to necrotic-like cell death. Because cellular senescence limits the replicative capacity of cells, our results suggest that induction of senescence may be exploited as a basis for new approaches to cancer therapy.

Inhibition of cell proliferation and migration by oxidative stress from ascorbate-driven juglone redox cycling in human bladder-derived T24 cells.

The effects of juglone on T24 cells were assessed in the presence and absence of ascorbate. The EC(50) value for juglone at 24 h decreased from 28.5 µM to 6.3 µM in the presence of ascorbate. In juglone-treated cells, ascorbate increased ROS formation (4-fold) and depleted GSH (65%). N-acetylcysteine or catalase restricted the juglone/ascorbate-mediated effects, highlighting the role of oxidative stress in juglone cytotoxicity. Juglone alone or associated with ascorbate did not cause caspase-3 activation or PARP cleavage, suggesting necrosis-like cell death. DNA damage and the mild ER stress caused by juglone were both enhanced by ascorbate. In cells treated with juglone (1-5 µM), a concentration-dependent decrease in cell proliferation was observed. Ascorbate did not impair cell proliferation but its association with juglone led to a clonogenic death state. The motility of ascorbate-treated cells was not affected. Juglone slightly restricted motility, but cells lost their ability to migrate most noticeably when treated with juglone plus ascorbate. We postulate that juglone kills cells by a necrosis-like mechanism inhibiting cell proliferation and the motility of T24 cells. These effects are enhanced in the presence of ascorbate.

Decrease phase angle one year after Roux-en-Y bypass and sleeve gastrectomy is related to risks to protein nutritional status.

BACKGROUND & AIMS: Phase angle (PhA) has been used as an indicator of nutritional status. However, the significance of PhA reduction after bariatric surgery is less known. This study evaluated PhA and its relation with biochemical parameters and prognostic inflammatory and nutritional indices at a one-year follow-up of patients subjected to Roux-en-Y bypass (RYGB) or sleeve gastrectomy (SG). METHODS: Our final sample consisted of 25 patients subjected to RYGB and 11 to SG. Body mass index, fat-free mass, fat mass, PhA, serum transthyretin (TTR), albumin, C-reactive protein, alpha-1-acid glycoprotein, and prognostic inflammatory and nutritional indices were evaluated at four time points: before and approximately two, six, and 12 months after RYGB or SG. One-way repeated measures ANOVA or the Friedman test with Tukey's post hoc test was used depending on data distribution. The correlation between PhA and biochemical parameters and indices were evaluated using Spearman's or Pearson's correlation coefficients. RESULTS: Except for serum albumin, all parameters significantly decreased over time (p < 0.001). Only the RYGB group showed transthyretinTR values below reference ones. Prognostic indices significantly decreased in both groups (p < 0.001). We found a significant positive correlation of PhA with TTR in both RYGB (r = 0.475; p < 0.001) and SG (r = 0.457; p < 0.001). CONCLUSIONS: Data suggest that at a one-year follow-up after bariatric surgery, lower PhA values might indicate a concomitant loss of visceral protein and a worsening of protein nutritional status.

[Cross-cultural adaptation to Spanish of the Signs of Depression Scale (SODS) to the early assessment of mood in patients admitted to a Stroke Unit]. / Adaptación transcultural al español de la Signs of Depression Scale (SODS) para la evaluación precoz del estado de ánimo en pacientes ingresados en una unidad de ictus.

INTRODUCTION: Stroke hospitalization negatively affects mood. Clinical guidelines recommend early evaluation of mood disorders. However, there is no consensus on the most appropriate scale in Spanish language. AIM: The objective of the study is the cross-cultural adaptation of the Signs of Depression Scale (SODS) in patients admitted to the stroke unit of the Hospital del Mar. MATERIALS AND METHODS: The work scheme for transcultural adaptation into Spanish was: a) direct translation; b) reconciliation and synthesis of translations; c) reverse translation into English; d) consensus of the back-translated version with original author; e) cognitive interrogation; f) revision and consensus version in Spanish; g) reading test, spelling, and grammar check; h) final version. Analysis and descriptive summary of the adaptation process was performed. RESULTS: There were no differences between direct translation versions. The back-translation version was accepted by the author of the original questionnaire. A convenience sample of patients with/without aphasia (n = 22) was included for cognitive interview from which no major problems were identified in the implementation of the questionnaire. Inclusive language was used in the final version. CONCLUSION: The transcultural adaptation of the scale allows in a simple and early way the evaluation mood in patients admitted to the stroke unit. The Spanish version is equivalent to the original instrument. This adaptation can be incorporated into care in the Stroke Unit and is extrapolated to other Spanish-speaking centres.

TITLE: Adaptación transcultural al español de la Signs of Depression Scale (SODS) para la evaluación precoz del estado de ánimo en pacientes ingresados en una unidad de ictus.Introducción. La hospitalización por ictus afecta negativamente al estado de ánimo. Las guías clínicas recomiendan evaluar precozmente el estado de ánimo. Sin embargo, no existe consenso sobre la escala más apropiada en idioma español. Objetivo. El objetivo del estudio es realizar una adaptación transcultural de la Signs of Depression Scale en pacientes ingresados en la unidad de ictus. Materiales y métodos. El esquema de trabajo de la adaptación transcultural al español fue: a) traducción directa; b) conciliación y síntesis de las traducciones; c) traducción inversa al inglés; d) consenso de la versión retrotraducida; e) interrogatorio cognitivo; f) revisión y versión consensuada en español; g) prueba de lectura, revisión ortográfica y gramatical, y h) versión final. Se realizó un análisis y un resumen descriptivo del proceso de adaptación transcultural. Resultados. Las versiones de traducción directa no presentaron diferencias. La versión de la traducción inversa fue aceptada por la autora del cuestionario original. Para el interrogatorio cognitivo se incluyó una muestra por conveniencia de 22 pacientes con/sin afasia a partir de la cual no se identificaron problemas en la aplicación del cuestionario. Se utilizó un lenguaje inclusivo en la versión final. Conclusiones. La versión española es equivalente al instrumento original. La adaptación transcultural de la escala permite, de forma sencilla y precoz, la evaluación del estado de ánimo en pacientes con ictus. Esta adaptación se puede incorporar en los cuidados en la unidad de ictus y es extrapolable a otros centros de habla hispana.

[Aneurysmal bone cyst of the temporal bone in a 8 year sold girl: case report]. / Quiste óseo aneurismático temporal en una niña de 8 años: descripción de un caso.

Aneurysmal bone cyst (ABC) is a very rare, benign, non-neoplastic lesion that typically occurs in the early life, usually before the 3rd decade, it's exceptional in younger than 10 years. We report the diagnosis and treatment of an 8 years old girl with an ABC in the left temporal bone, a very unusual location. Although the histologic characteristics have been well defined, its pathogenesis remains obscure and not totally explained. Total excision nowadays is the treatment of choice.

Cell-free DNA as an obesity biomarker.

Obesity is a disease that affects about 13 % of the world population (2016) (Who 2018). This condition generates a process of systemic inflammation that may contribute to the release of cell-free DNA (cfDNA) into the bloodstream. cfDNA has been considered a potential biomarker to monitor several physiological and pathological conditions, such as tumors, exercise intensity and obesity. Therefore, the objective of this study was to evaluate the association of cfDNA levels with the amount of weight and fat mass lost six months after bariatric surgery. Thirty-eight subjects classified as obese (BMI, 43.5+/-6.2; BFP, 46.6+/-4.8) were evaluated anthropometrically and underwent bariatric surgery. Weight, BMI, body fat percentage (BFP), waist circumference, C-Reactive Protein (CRP) and cfDNA levels were evaluated before and six months after surgery; furthermore, a correlation was performed between cfDNA levels and BFP and CRP. Decrease in total body weight and CRP were observed after bariatric surgery; however, the cfDNA levels remained unchanged. There was a weak correlation between cfDNA levels and BFP before the bariatric surgery, and a moderate correlation between cfDNA and CRP. Obese subjects who underwent bariatric surgery, the decrease in body fat percentage did not result in changes in cfDNA levels six months after surgery.

Changes in Left Ventricular Mechanics After Sleeve Gastrectomy.

OBJECTIVE: The aim of this study was to examine echocardiographic parameters of left ventricle (LV) mechanics in obese patients before and after sleeve gastrectomy (SG). DESIGN AND METHODS: Twenty-five obese individuals submitted to laparoscopic SG were enrolled in this study. Echocardiography was performed before and after the procedure, and left ventricle mechanics were evaluated by speckle tracking imaging. RESULTS: Before surgery, altered global longitudinal strain (GLS) values were present in 56% of the patients. In a mean follow-up of 3.6 ± 0.5 months after surgery, there was an increase in GLS values (from 17.4 ± 3.2 to 19.3 ± 2.7%, P = 0.01). There was an inverse correlation between the absolute values of GLS in the preoperative period and the variation in the GLS at follow-up (r = 0.577, P = 0.002). Measurements of global circumferential strain (GCS), global radial strain (GRS), and LV twist were normal preoperatively and did not change after surgery. CONCLUSIONS: Altered global longitudinal strain values were common in young obese patients. Sleeve gastrectomy increased global longitudinal strain even in the early postoperative phase without promoting changes in global radial strain, global circumferential strain, and left ventricle twist measurements.

In situ modulation of oxidative stress: a novel and efficient strategy to kill cancer cells.

Cancer cells show an up-regulation of glycolysis, they readily take up vitamin C, and they appear more susceptible to an oxidative stress than the surrounding normal cells. Here we compare, analyse and discuss these particular hallmarks by performing experiments in murine hepatomas (TLT cells) and freshly isolated mouse hepatocytes. The results show that rates of lactate formation are higher in TLT cells as compared to mouse hepatocytes, but their ATP content represents less than 25% of that in normal cells. The uptake of vitamin C is more important in hepatoma cells as compared to normal hepatocytes. This uptake mainly occurs through GLUT1 transporters. Hepatoma cells have less than 10% of antioxidant enzyme activities as compared to normal hepatocytes. This decrease includes not only the major antioxidant enzymes, namely catalase, superoxide dismutase and glutathione peroxidase, but also the GSH content. Moreover, catalase is almost not expressed in hepatoma cells as shown by western blot analysis. We explored therefore a selective exposure of cancer cells to an oxidative stress induced by pro-oxidant mixtures containing pharmacological doses of vitamin C and a redox active compound such as menadione (vitamin K(3)). Indeed, the combination of vitamin C (which accumulates in hepatoma cells) and a quinone undergoing a redox cycling (vitamin K(3)) leads to an oxidative stress that kills cancer cells in a selective manner. This differential sensitivity between cancer cells and normal cells may have important clinical applications, as it has been observed with other pro-oxidants like Arsenic trioxide, isothiocyanates, Adaphostin.

Apolipoprotein E polymorphism interacts with cigarette smoking in progression of multiple sclerosis.

BACKGROUND AND PURPOSE: The influence of apolipoprotein E (ApoE) polymorphism on clinical severity of multiple sclerosis (MS) is still controversial. Cigarette smoking has been suggested to influence the progression of disability in these patients. In this study, we aimed to investigate whether an interaction of smoking with the ApoE polymorphism influences the progression of disability in MS patients. METHODS: Smoking history from 205 female patients with MS was obtained. Clinical data collected include age at onset, disease duration, annual relapse rate, the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Severity Score (MSSS). ApoE polymorphism was examined in all patients and stratified according to smoking status and associations with the clinical data investigated. RESULTS: There were no significant associations between cigarette smoking and any of the clinical characteristics in the whole group of patients. In women carrying the ApoE E4 isoform, smokers had a lower EDSS (P = 0.033) and MSSS (P = 0.023) in comparison with non-smokers. CONCLUSION: Our data suggest that in women with MS carrying the ApoE E4 isoform, cigarette smoking may have a protective influence on disease progression and accumulation of disability. These findings need to be confirmed by future large longitudinal studies.

Use of coal mining waste for the removal of acidity and metal ions Al (III), Fe (III) and Mn (II) in acid mine drainage.

The coal industry may generate acid mine drainage (AMD) and mining wastes, which may adversely affect the quality of the environment. In this study we propose the use of this waste in the removal of acidity and metal ions, as well as in the reduction of the toxicity of AMD. A physico-chemical analysis of the waste shows the presence of mainly SiO2, Al2O3 and Fe2O3 and a superficial area of 4.316 m2 g(-1). The treatment of AMD with the waste resulted in an increase in pH from 2.6 to 7.8 and removed 100% of the Al (III), 100% of the Fe (III) and 89% of the Mn (II). We also observed that the high toxicity of the AMD towards Daphnia magna (LC50 = 3.68%) and Artemia sp. (LC50 = 4.97%) was completely eliminated after treatment with the waste. The data obtained allow us to propose that the waste can be used in the treatment of AMD, providing an economic use for the waste.

Adaptación transcultural al español de la Signs of Depression Scale (SODS) para la evaluación precoz del estado de ánimo en pacientes ingresados en una unidad de ictus / Cross-cultural adaptation to Spanish of the Signs of Depression Scale (SODS) to the early assessment of mood in patients admitted to a Stroke Unit

Introducción: La hospitalización por ictus afecta negativamente al estado de ánimo. Las guías clínicas recomiendan evaluar precozmente el estado de ánimo. Sin embargo, no existe consenso sobre la escala más apropiada en idioma español. Objetivo: El objetivo del estudio es realizar una adaptación transcultural de la Signs of Depression Scale en pacientes ingresados en la unidad de ictus. Materiales y métodos: El esquema de trabajo de la adaptación transcultural al español fue: a) traducción directa; b) conciliación y síntesis de las traducciones; c) traducción inversa al inglés; d) consenso de la versión retrotraducida; e) interrogatorio cognitivo; f) revisión y versión consensuada en español; g) prueba de lectura, revisión ortográfica y gramatical, y h) versión final. Se realizó un análisis y un resumen descriptivo del proceso de adaptación transcultural. Resultados: Las versiones de traducción directa no presentaron diferencias. La versión de la traducción inversa fue aceptada por la autora del cuestionario original. Para el interrogatorio cognitivo se incluyó una muestra por conveniencia de 22 pacientes con/sin afasia a partir de la cual no se identificaron problemas en la aplicación del cuestionario. Se utilizó un lenguaje inclusivo en la versión final. Conclusiones: La versión española es equivalente al instrumento original. La adaptación transcultural de la escala permite, de forma sencilla y precoz, la evaluación del estado de ánimo en pacientes con ictus. Esta adaptación se puede incorporar en los cuidados en la unidad de ictus y es extrapolable a otros centros de habla hispana.(AU)

Introduction: Stroke hospitalization negatively affects mood. Clinical guidelines recommend early evaluation of mood disorders. However, there is no consensus on the most appropriate scale in Spanish language. Aim: The objective of the study is the cross-cultural adaptation of the Signs of Depression Scale (SODS) in patients admitted to the stroke unit of the Hospital del Mar. Materials and methods: The work scheme for transcultural adaptation into Spanish was: a) direct translation; b) reconciliation and synthesis of translations; c) reverse translation into English; d) consensus of the back-translated version with original author; e) cognitive interrogation; f) revision and consensus version in Spanish; g) reading test, spelling, and grammar check; h) final version. Analysis and descriptive summary of the adaptation process was performed. Results:. There were no differences between direct translation versions. The back-translation version was accepted by the author of the original questionnaire. A convenience sample of patients with/without aphasia (n = 22) was included for cognitive interview from which no major problems were identified in the implementation of the questionnaire. Inclusive language was used in the final version. Conclusion: The transcultural adaptation of the scale allows in a simple and early way the evaluation mood in patients admitted to the stroke unit. The Spanish version is equivalent to the original instrument. This adaptation can be incorporated into care in the Stroke Unit and is extrapolated to other Spanish-speaking centres.(AU)

Albendazole as a promising molecule for tumor control.

This work evaluated the antitumor effects of albendazole (ABZ) and its relationship with modulation of oxidative stress and induction of DNA damage. The present results showed that ABZ causes oxidative cleavage on calf-thymus DNA suggesting that this compound can break DNA. ABZ treatment decreased MCF-7 cell viability (EC50=44.9 for 24h) and inhibited MCF-7 colony formation (~67.5% at 5µM). Intracellular ROS levels increased with ABZ treatment (~123%). The antioxidant NAC is able to revert the cytotoxic effects, ROS generation and loss of mitochondrial membrane potential of MCF-7 cells treated with ABZ. Ehrlich carcinoma growth was inhibited (~32%) and survival time was elongated (~50%) in animals treated with ABZ. Oxidative biomarkers (TBARS and protein carbonyl levels) and activity of antioxidant enzymes (CAT, SOD and GR) increased, and reduced glutathione (GSH) was depleted in animals treated with ABZ, indicating an oxidative stress condition, leading to a DNA damage causing phosphorylation of histone H2A variant, H2AX, and triggering apoptosis signaling, which was confirmed by increasing Bax/Bcl-xL rate, p53 and Bax expression. We propose that ABZ induces oxidative stress promoting DNA fragmentation and triggering apoptosis and inducing cell death, making this drug a promising leader molecule for development of new antitumor drugs.

Oxidative and non-oxidative mechanisms of neuronal cell death and apoptosis by L-3,4-dihydroxyphenylalanine (L-DOPA) and dopamine.

1. The present study was designed to evaluate the nature of intervening agents in L-DOPA- and dopamine-induced neurotoxicity in Neuro-2A cells. 2. In the absence of cells and in conditions of light protection, at 37 degrees C, L-DOPA or dopamine (1 mM) in culture medium degraded spontaneously in a time-dependent manner, this being prevented by ascorbic acid (200 microM) and other antioxidants, namely glutathione (1 mM), N-acetyl-L-cysteine (1 mM), sodium metabisulphite (200 microM), but not N-ter-butyl-alpha-phenylnitrone (1 mM) and deferoxamine (100 microM). 3. The viability of Neuro-2A cells declined following treatment with L-DOPA or dopamine in a concentration- and time-dependent manner. The decrease in cell viability by L-DOPA (10+/-4% of control) or dopamine (15+/-4% of control) was markedly attenuated by antioxidants (ascorbic acid, glutathione, N-acetyl-L-cysteine and sodium metabisulphite). Autoxidation of L-DOPA or dopamine was accompanied by the formation of H(2)O(2) in a time-dependent manner, this being completely prevented by ascorbic acid at 24 h or markedly reduced at 48 h. 4. Protective effects of 100 U ml(-1) catalase (40+/-1% of control) against L-DOPA-induced cell death were lower than those conferred by 200 microM ascorbic acid (70+/-3% of control). Catalase-induced protection (59+/-5% of control) against dopamine-induced cell death was similar to that conferred by 200 microM ascorbic acid (57+/-4% of control). L-DOPA-induced neuronal cell death was also accompanied by increases in caspase-3 activity, this being insensitive to ascorbic acid. Dopamine-induced increase in caspase-3 activity occurred only when autoxidation of the amine was prevented by ascorbic acid. 5. It is suggested that in addition to generation of H(2)O(2) and quinone formation, L-DOPA- and dopamine-induced cell death may result from induction of apoptosis, as evidenced by increases in caspase-3 activity. Dopamine per se induces apoptosis by a mechanism independent of oxidative stress, as evidenced by the fact that increases in caspase-3 activity occurred only when autoxidation of the amine was prevented.

Metabolism of cyclosporine after orthotopic liver transplantation.

The aim of this work was to determine whether the extensive metabolism of cyclosporine, acquired in a donor by treatment with an inducer of cytochrome P450 3A (P450 3A) (cyclosporine oxidase), was transmissible to the recipient by orthotopic liver transplantation. For this purpose, male Wistar rats were divided into five groups including: control animals (group C), animals treated with dexamethasone (an inducer of P450 3A, 50 or 300 mg/kg/day, for 4 days, group D), animals transplanted with the livers of control rats (group G) or with the livers of dexamethasone-induced rats (group GD), and animals treated with beta-naphthoflavone (an inducer of P450 1A, group B). All animals received a single i.v. dose of 10 mg/kg cyclosporine 24 hr after either the last dose of inducer or the transplantation. For each group of animals, the area under the curve (AUC) of cyclosporine was calculated from the curves of blood cyclosporine levels (by radioimmunoassay) against time; liver microsomes were assayed for cyclosporine oxidase activity by HPLC, erythromycin demethylase and P450 3A level by western blot with specific anti-P450 3A antibodies. The decrease in the AUC in groups D and GD with respect to C and G was correlated with increased level of P450 3A (4-5-fold with respect to control) as well as of microsomal cyclosporine oxidase. In addition, cyclosporine oxidase activity of liver microsomes was specifically inhibited by anti-P450 3A antibodies and troleandomycin. The animals in group B did not exhibit increased metabolism of cyclosporine either in vivo or in vitro. We conclude that: (1) cyclosporine is predominantly oxidized in the rat liver by a form of P450 from the 3A subfamily; (2) the extensive metabolism of cyclosporine acquired by donor rats after treatment with dexamethasone is transmissible to the recipients through orthotopic liver transplantation.

Saliva ELISA: a method for the diagnosis of chronic Chagas disease in endemic areas.

An indirect enzyme linked immunosorbent assay (ELISA) was applied to saliva to detect chronic infection by Trypanosoma cruzi in humans. Saliva samples from 114 Chagas' disease chronically infected individuals, characterized by three serological tests and clinical evaluation and from 100 healthy controls were tested for T. cruzi specific IgG antibodies. At dilution of 1 in 2, specific antibodies were detected in saliva samples from 103 of 114 samples from infected patients and 5 of 100 controls (sensitivity 90.4%, specificity 95%). There was no significant correlation between the antibody titre and cardiac or gastrointestinal tract disease. This assay possesses some advantages over other methods as saliva collection is non-invasive, requires no special equipment and whole saliva gave reproducible results. Although serology remains the gold standard for T. cruzi infection, these results suggest that T. cruzi specific salivary antibody detection may provide a screening diagnostic test and contribute to epidemiological studies of chronic trypanosomiasis infection in endemic areas.

Time-dependent oxidative stress caused by benznidazole.

Benznidazole (BZN) is a nitroimidazole derivative which has a notable trypanocide activity, and it is the only drug used in Brazil and Argentina for the treatment of Chagas' disease. The drug in current use is thought to act, at least in part, by inducing oxidative stress within the parasite. Imidazolic compounds are involved in the production of reactive oxygen species (ROS). In order to evaluate the effect of BZN on ROS production and on the antioxidant status of the host, male rats were treated for different periods of time (2, 4, 6, 10 and 30 days) with 40 mg BZN/kg body weight. After treatment, biomarkers of oxidative stress such as the activities of catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST) and glutathione reductase (GR), and also thiobarbituric acid reactive species (TBARS), reduced glutathione (GSH), total glutathione (TG) and oxidized glutathione (GSSG) concentrations, were measured in crude hepatic homogenates. Our results revealed that BZN is able to cause tissue damage as shown by increased TBARS content, inhibition of some antioxidants and induction of other antioxidants in a concentration- and time-dependent manner. The tissue damage measured as TBARS increased up to the 10th day of treatment. GST activity was inhibited during the BZN treatment. On the other hand, CAT and GR showed similar increased activities at the beginning, followed by decreased activities at the end of the treatment. After 30 days of treatment, GR activity remained low while CAT activity was high, compared to controls. The SOD activities remained unchanged throughout the experimental period. GSH showed lower values at the beginning of BZN treatment but the hepatic concentrations were enhanced at the end of the experimental period. Total glutathione showed a similar profile, and oxidized glutathione showed higher values in rats treated with BZN. In conclusion, these results indicate that, at therapeutic doses, BZN treatment elicits an oxidative stress in rat hepatocytes.

Influence of season and pollution on the antioxidant defenses of the cichlid fish acará (Geophagus brasiliensis).

The livers of Geophagus brasiliensis collected from both a non-polluted site and a polluted site were analyzed for different antioxidant defenses, O2 consumption, thiobarbituric acid-reactive substance (TBARS) levels, and histological damage. Compared to controls (116.6 +/- 26.1 nmol g-1), TBARS levels were enhanced at the polluted site (284.2 +/- 25.6 nmol g-1), as also was oxygen consumption (86.6 +/- 11.3 and 128.5 +/- 9.8 micromol O2 min-1 g-1, respectively). With respect to enzymatic antioxidants, increased catalase activities (8.7 +/- 1.3 and 29.2 +/- 2.4 mmol min-1 g-1, respectively), unchanged superoxide dismutase activities (767.2 +/- 113.3 and 563.3 +/- 70.2 U g-1, respectively), and diminished glutathione S-transferase activities (29.0 +/- 3.2 and 14.9 +/- 3.2 micromol min-1 g-1, respectively) were detected. Reduced glutathione (1.91 +/- 0.17 and 1.37 +/- 0.25 mM, respectively), oxidized glutathione (1.50 +/- 0.20 and 0.73 +/- 0.17 mM, respectively), and total glutathione (3.40 +/- 0.26 and 2.07 +/- 0.27 mM, respectively) concentrations were also below control values at the polluted site. Nevertheless, the observed ethoxyresorufin-O-deethylase activities (1.34 +/- 0.11 and 16.7 +/- 0.21 pmol min-1 mg-1, respectively) showed enhanced values at the polluted site. The main histological damage observed in the hepatocytes from fish collected at the polluted site was characterized by heavy lipid infiltration. Fish collected at the end of spring showed higher O2 consumption, higher superoxide dismutase and glutathione S-transferase activities, and higher total and oxidized glutathione concentrations compared to the beginning of autumn. No seasonal changes were observed in catalase activities, glutathione or TBARS levels. Fish chronically exposed to relatively high pollution levels seem to be unable to set up adequate antioxidant defenses, probably due to severe injury to their hepatocytes. The higher antioxidant defenses found at the end of spring are probably related to the enhanced activities during high temperature periods in thermoconforming organisms.

Sera from chronic chagasic patients depress cardiac electrogenesis and conduction.

We report results obtained with sera from 58 chronic chagasic patients that were evaluated for effects on heart rate and atrioventricular (AV) conduction in isolated rabbit hearts and screened for the presence of muscarinic and beta-adrenergic activity. We show that sera from 26 patients decreased heart rate, while 10 increased it and 22 had no effect. Additionally, sera from 20 of the 58 patients blocked AV conduction. Muscarinic activation seems to be involved in both effects, but is not the only mechanism, since atropine did not antagonize the decrease in heart rate in 23% of sera or AV block in 40%. Sera from patients with complex arrhythmias were significantly more effective in depressing both heart rate and AV conduction. Sera that induce increases in heart rate seem to operate exclusively through beta-adrenergic activation. Two of these sera, evaluated with respect to intercellular communication in primary cultures of embryonic cardiomyocytes were able to block gap junction conductance evaluated by a dye injection technique after 24-h exposure. The mechanisms underlying this uncoupling effect are currently being investigated.