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.

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)

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.

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.

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.

Oral cancer awareness at chemist's and herbalist's shops: new targets for educational interventions to prevent diagnostic delay.

OBJECTIVES: To assess whether chemist's and herbalist's shops were offering appropriate advice for patients seeking guidance on a potentially malignant oral lesion. MATERIAL AND METHODS: A cross-sectional study was undertaken using the standardised patient approach on a representative sample of chemist's and herbalists' shops in Galicia (Spain). The introductory statement was "I have a painful ulceration on the tongue for about a month now. What would you advise?" The study sample was selected by stratified random sampling for a 5% precision, and contacted by telephone. To disclose a hypothetical bias in telephone answers, another study was designed for two provinces where pharmacies were visited in one province and herbal shops in the other one. RESULTS: A total of 460 establishments out of 1534 were contacted: 306 pharmacies (66.5%) and 154 herbalist's shops (33.5%). Patients were adequately referred from pharmacies significantly more frequently than were from herbalist's shops, which mostly prescribe over-the-counter (OTC) remedies (86.4%). Community pharmacy assistants resulted more likely to recommend OTC remedies (55.6% vs. 13%) and significantly less likely to refer patients to a dentist or physician than pharmacists. The most frequent OTC offered at chemists' were mouthwashes, while herbalist's shops prescribed propoleum (50%) and tea tree (Melaleuca alternifolia) preparations (23.8%). CONCLUSION: New off-clinical counsellors (herbalists and pharmacy assistants) have been identified as potential creators of patient diagnostic delay in oral cancer, as well as the need for increasing oral cancer awareness amongst community pharmacists. Educational strategies to improve advice and referral should be designed for these collectives.

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.

Molecular chaperone Hsp90 as a target for oxidant-based anticancer therapies.

Hsp90 is a molecular chaperone involved in the stabilization of many oncoproteins that are required for the acquisition and maintenance of the so-called six major hallmarks of cancer cells. Various strategies have, therefore, been developed to inhibit the chaperone activity of Hsp90 and induce cancer cell death through the destabilization of its client proteins. Among these strategies, we have shown that generation of oxidative stress leads to the cleavage and deactivation of Hsp90. Because cancer cells are often deficient in antioxidant enzymes and exhibit higher basal levels of reactive oxygen species (ROS) than their normal counterparts, inducing a selective oxidative stress may be a promising approach for cancer treatment. Thus, many redox-modulating agents have, therefore, been developed or are undergoing clinical trials and Hsp90 represents a new target for oxidative stress-generating agents. The purpose of this article is to review the current state of knowledge about Hsp90 and the use of oxidative stress-generating agents in cancer treatment. We will illustrate the review with some of our results concerning the effects of oxidative stress on Hsp90 using various oxidative stress-generating systems based on different quinones in combination with a well-known reducing agent (i.e., ascorbate). Our results show that oxidative stress provokes the cleavage of Hsp90 in CML cells, as well as the degradation of its client protein Bcr-Abl and the deactivation of its downstream signaling pathways, namely MAPK and STAT5. Overall, these results highlight the potential interest of using oxidative stress to target Hsp90.

Redox-active quinones and ascorbate: an innovative cancer therapy that exploits the vulnerability of cancer cells to oxidative stress.

Cancer cells are particularly vulnerable to treatments impairing redox homeostasis. Reactive oxygen species (ROS) can indeed play an important role in the initiation and progression of cancer, and advanced stage tumors frequently exhibit high basal levels of ROS that stimulate cell proliferation and promote genetic instability. In addition, an inverse correlation between histological grade and antioxidant enzyme activities is frequently observed in human tumors, further supporting the existence of a redox dysregulation in cancer cells. This biochemical property can be exploited by using redox-modulating compounds, which represent an interesting approach to induce cancer cell death. Thus, we have developed a new strategy based on the use of pharmacologic concentrations of ascorbate and redox-active quinones. Ascorbate-driven quinone redox cycling leads to ROS formation and provoke an oxidative stress that preferentially kill cancer cells and spare healthy tissues. Cancer cell death occurs through necrosis and the underlying mechanism implies an energetic impairment (ATP depletion) that is likely due to glycolysis inhibition. Additional mechanisms that participate to cell death include calcium equilibrium impairment and oxidative cleavage of protein chaperone Hsp90. Given the low systemic toxicity of ascorbate and the impairment of crucial survival pathways when associated with redox-active quinones, these combinations could represent an original approach that could be combined to standard cancer therapy.

[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.

Quiste óseo aneurismático temporal en una niña de 8 años: descripción de un caso / Aneurysmal bone cyst of the temporal bone in a 8 yearsold rl: case report

El quiste óseo aneurismático (QOA) es una lesiónmuy infrecuente, de carácter benigno, no neoplásicaque aparece típicamente en edades tempranas de lavida, usualmente antes de la 3ª década de vida, siendoexcepcional en menores de 10 años.Exponemos el diagnóstico y tratamiento de una niñade 8 años con un QOA del hueso temporal izquierdo,una localización poco frecuente. Aunque las característicashistológicas están bien definidas, su etiopatogeniaaún no ha sido totalmente explicada. Actualmente laexéresis completa es el tratamiento de elección (AU)

Aneurysmal bone cyst (ABC) is a very rare, benign,non-neoplasic lession that tipically ocurs in the earlylife, usually before the 3rd decade, it´s exceptional inyoungers than 10 years.We report the diagnosis and treatment of an 8 yearsold girl with an ABC in the left temporal bone, a veryunusual location. Although the histologic caracteristicshave been well defined, its pathogenesis remains obscureand not totally explained. Total excision nowadaysis the treatment of choice (AU)

Correlação entre os testes da caminhada, marcha estacionária e TUG em hipertensas idosas / Correlation between the walk, 2-minute step and TUG tests among hypertensive older women

CONTEXTUALIZAÇÃO: O aumento de doenças crônicas em idosos, principalmente da Hipertensão Arterial Sistêmica, doença intimamente relacionada ao declínio da capacidade funcional, determina a necessidade do estudo de métodos de avaliação da realização das atividades, possibilitando detecção de níveis de capacidade funcional, prescrição de exercícios e acompanhamento das funções cardiovascular e motora. O teste da caminhada de 6 minutos (TC6'), o teste da Marcha Estacionária de 2 minutos (TME2') e o teste Timed Up and Go (TUG) são indicados para esta avaliação. Estudos em idosos saudáveis mostram a associação entre esses testes, facilitando a avaliação da capacidade funcional. Porém, em hipertensos, não existem estudos que avaliem a relação entre TC6', TME2'e TUG, justificando a realização desta pesquisa. OBJETIVOS: Verificar se existe associação entre endurance aeróbia e a mobilidade funcional em idosas hipertensas. MÉTODOS: Estudo observacional, analítico e transversal, com 32 hipertensas idosas, avaliadas por meio do TC6', TME2' e TUG. RESULTADOS:Houve correlação positiva moderada entre TC6' e TME2', r=0,36 (p=0,04) e correlação negativa moderada entre TC6'e TUG, r=-0,59 (p=0,000) e entre TME2' e TUG, r=-0,66 (p=0,000). CONCLUSÕES: Para hipertensas idosas, o TC6' pode ser substituído pelo TME2', assim como em idosos saudáveis. Quanto à correlação entre os TC6', TME2' e TUG, pode-se concluir que existe uma íntima relação entre resistência cardiovascular e mobilidade funcional; havendo menor resistência cardiovascular, há mobilidade funcional precária e vice-versa.

BACKGROUND: The increase in chronic diseases among older adults, especially systemic arterial hypertension, a disease that is closely related to declining functional capacity, has created the need to study methods for activity evaluation in order to detect functional capacity levels, prescribe exercises and monitor motor and cardiovascular function. The Six-Minute Walk Test (6MWT), Two-Minute Step Test (2MST) and Timed Up and Go Test (TUG) are indicated for such evaluations. Studies among healthy older adults have shown associations between these tests, thus aiding the evaluation of functional capacity. However, there are no studies on the relationships between the 6MWT, 2MST and TUG among hypertensive individuals, thus justifying the present research. OBJECTIVES: To investigate whether there is any association between aerobic endurance and functional mobility among hypertensive older women. METHODS:This was a cross-sectional observational and analytical study on 32 hypertensive older women who were evaluated using the 6MWT, 2MST and TUG. RESULTS:There was a moderate positive correlation between the 6MWT and 2MST (r=0.36; p=0.04), and there were moderate negative correlations between the 6MWT and TUG (r=-0.59; p=0.000) and between the 2MST and TUG (r=-0.66; p=0.000). CONCLUSIONS: For hypertensive older women, the 6MWT can be replaced by the 2MST; the same applied to healthy older adults. Regarding the correlation between the 6MWT, 2MST and TUG, it can be concluded that there is a close relationship between cardiovascular endurance and functional mobility. When there is lower cardiovascular endurance, there is precarious functional mobility and vice versa.

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.

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.

Characterization of rat heart alkaline phosphatase isoenzymes and modulation of activity.

Alkaline phosphatase (ALP) is important in calcification and its expression seems to be associated with the inflammatory process. We investigated the in vitro acute effects of compounds used for the prevention or treatment of cardiovascular diseases on total ALP activity from male Wistar rat heart homogenate. ALP activity was determined by quantifying, at 410 nm, the p-nitrophenol released from p-nitrophenylphosphate (substrate in Tris buffer, pH 10.4). Using specific inhibitors of ALP activity and the reverse transcription-polymerase chain reaction, we showed that the rat heart had high ALP activity (31.73 +/- 3.43 nmol p-nitrophenol.mg protein-1.min-1): mainly tissue-nonspecific ALP but also tissue-specific intestinal ALP type II. Both ALP isoenzymes presented myocardial localization (striated pattern) by immunofluorescence. ALP was inhibited a) strongly by 0.5 mM levamisole, 2 mM theophylline and 2 mM aspirin (91, 77 and 84%, respectively) and b) less strongly by 2 mM L-phenylalanine, 100 mL polyphenol-rich beverages and 0.5 mM progesterone (24, 21 to 29 and 11%, respectively). beta-estradiol and caffeine (0.5 and 2 mM) had no effect; 0.5 mM simvastatin and 2 mM atenolol activated ALP (32 and 36%, respectively). Propranolol (2 mM) tended to activate ALP activity and corticosterone activated (18%) and inhibited (13%) (0.5 and 2 mM, respectively). We report, for the first time, that the rat heart expresses intestinal ALP type II and has high total ALP activity. ALP activity was inhibited by compounds used in the prevention of cardiovascular pathology. ALP manipulation in vivo may constitute an additional target for intervention in cardiovascular diseases.