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Pancreatic carcinoma incidence showed a significant increase in men over the last few years and the prognosis remains poor. Patients are treated with different pharmacological plans with no evidence about gender-specific adverse effects. We aimed to investigate differences in the incidence of chemotherapy side effects in the treatment of pancreatic cancer, to provide insights toward a personalized assistance based in individual needs. The sample population is composed of 207 patients. Regression model highlighted the predictive role of female gender for alopecia, constipation, hand- foot syndrome, and epigastric pain. Also, considering single therapeutic schemes, gender differences have been reported. Moreover, evaluating the effect of age, a general reduced risk of toxicity has been reported in younger patients. To personalize chemotherapy and increase patient survival rate and life quality during the therapy, gender medicine and pharmacology studies are recommended. Key words: gender differences, adverse effects, drugs toxicity, chemotherapy, pancreatic carcinoma. La frequence du cancer du pancreas chez l'homme a decrit une courbe nettement ascendante au cours des dernieres annees et le pronostic demeure defavorable. Les patients sont traites a l'aide de differents schemas pharmacologiques sans donnees probantes quant aux effets indesirables specifiques a leur sexe. Nous avons vise a etudier les differences entre la frequence des effets indesirables de la chimiotherapie dans le traitement du cancer du pancreas en vue de fournir des elements de reflexion quant a l'aide personnalisee fondee sur des besoins individuels. La population echantillonnee est composee de 207 patients. Le modele de regression a mis en evidence le role predictif du sexe feminin quant a l'alopecie, a la constipation, au syndrome pied-main et aux douleurs epigastriques. Nous avons aussi rapporte des differences entre les sexes selon des schemas therapeutiques individuels. En outre, une evaluation selon l'age a permis de rapporter un decroissement general du risque de toxicite chez les patients jeunes. Nous recommandons de proceder a des etudes medicales et pharmacologiques selon le sexe en vue d'offrir aux patients une chimiotherapie personnalisee et de faire augmenter leur taux de survie de meme que leur qualite de vie pendant le traitement. [Traduit par la Redaction] Mots-cles : differences entre les sexes, effets indesirables, toxicite medicamenteuse, chimiotherapie, cancer du pancreas., 1. Introduction Recent studies demonstrate gender-specific incidence, progression, and severity of different tumors. Differences in parameters such as body weight, fat distribution, hormonal profile, metabolism, immune response, and genetics were [...]

The determination that Angeli's salt may have clinical application as a nitrogen oxide donor for treatment of cardiovascular diseases such as heart failure has led to renewed interest in the mechanism and products of thermal decomposition of the salt under physiological conditions. Several mechanisms are evaluated experimentally and by quantum mechanical calculations to determine whether HNO is in fact released from Angeli's salt in neutral, aerobic solution.

[F.sub.0][F.sub.1] ATP synthase activity is differently modulated by coronary reactive hyperemia before and after ischemic preconditioning in the goat. Am J Physiol Heart Circ Physiol 287: H2192-H2200, 2004. First published June 24, 2004; doi:10.1152/ajpheart.00327. 2004.--The amplitude of coronary reactive hyperemia (CRH), elicited by 15 s of ischemia, is reduced in hearts subjected to 5 min of ischemic preconditioning (IP). [F.sub.0][F.sub.1] ATP synthase activity and ATP concentration are also altered by IP. We hypothesized that [F.sub.0.][F.sub.1] ATP synthase is differently modulated by the inhibitor protein I[F.sub.1] during CRH elicited before (CR[H.sub.np]) and after (CR[H.sub.prec]) IP. Hemodynamic parameters were recorded in 10 anesthetized goats. Myocardial biopsies were obtained before IP ([C.sub.np]), during CR[H.sub.np], 4 and 6 min after the onset of CR[H.sub.np], after IP ([C.sub.prec]), during CR[H.sub.prec], and 4 min after CR[H.sub.prec] [F.sub.0][F.sub.1] ATP synthase activity, ATP concentration, and ATP-to-ADP ratio (ATP/ADP) were determined. Compared with CR[H.sub.np], IP blunted CR[H.sub.prec]. [F.sub.0][F.sub.1] ATP synthase activity transiently increased during CR[H.sub.np], decreased 4 min after CR[H.sub.np], and returned to control 2 min later; it was lower after IP ([C.sub.prec]) and did not change during and after CR[H.sub.prec]. All these changes in activity were modulated by I[F.sub.1]. During CR[H.sub.np], ATP concentration and ATP/ADP were reduced compared with [C.sub.np] and began to rise 6 min thereafter. During [C.sub.prec], both parameters were transiently reduced but increased during and after CR[H.sub.prec]. Hence, during CR[H.sub.np], [F.sub.0][F.sub.1] ATP synthase activity transiently increases and then decreases significantly. The short-lasting inhibition of the enzyme may explain why a few seconds of occlusion do not induce IP. After IP, [F.sub.0][F.sub.1] ATP synthase activity is blunted, and it is not affected by a subsequent 15 s of occlusion, which induces a blunted CR[H.sub.prec]. These results suggest that postischemic long-lasting inhibition of [F.sub.0][F.sub.1] ATP synthase activity may be a feature of the preconditioned heart. The increase in ATP concentration after preconditioning is in agreement with previous reports of reduced ATP hydrolysis by cytoplasmic ATPases. coronary circulation; energy metabolism; ischemia; mitochondria

NO produced in tumors can either positively or negatively regulate growth. To examine this dichotomy, effects of NO concentration and duration on the posttranslational regulation of several key proteins were examined in human breast MCF7 cells under aerobic conditions. We found that different concentration thresholds of NO appear to elicit a discrete set of signal transduction pathways. At low steady-state concentrations of NO ( 100 nM), whereas p53 serine 15 phosphorylation occurred at considerably higher levels (>300 nM). ERK phosphorylation was transient during NO exposure. HIF-1[alpha] stabilization paralleled the presence of NO, whereas p53 serine 15 phosphorylation was detected during, and persisted after, NO exposure. The dose-dependent effects of synthetic NO donors were mimicked by activated macrophages cocultured with MCF7 cells at varying ratios. ERK and HIF-1[alpha] activation was similar in breast cancer cell lines either mutant (MB231) or null (MB157) in p53. The stabilization of HIF-1[alpha] by NO was not observed with increased MCF7 cell density, demonstrating the interrelationship between NO and [O.sub.2] consumption. The findings show that concentration and duration of NO exposure are critical determinants in the regulation of tumor-related proteins. cancer | hypoxia | macrophage | inducible NO synthase

Endogenous formation of nitric oxide (NO) and related nitrogen oxides in the vascular system is critical to regulation of multiple physiological functions. An imbalance in the production or availability of these species can result in progression of disease. Nitrogen oxide research in the cardiovascular system has primarily focused on the effects of NO and higher oxidation products. However, nitroxyl (HNO), the one-electron-reduction product of NO, has recently been shown to have unique and potentially beneficial pharmacological properties. HNO and NO often induce discrete biological responses, providing an interesting redox system. This article discusses the emerging aspects of HNO chemistry and attempts to provide a framework for the distinct effects of NO and HNO in vivo. guanosine 3',5'-cyclic monophosphate; calcitonin gene-related peptide; Angeli's salt

In systemic lupus erythematosus (SLE) patients, most of the clinical manifestation share a vascular component triggered by endothelial dysfunction. Endothelial cells (ECs) activation occurs both on the arterial and venous side, and the high vascular density of kidneys accounts for the detrimental outcomes of SLE through lupus nephritis (LN). Kidney damage, in turn, exerts a negative feedback on the cardiovascular (CV) system aggravating risk factors for CV diseases such as hypertension, stroke and coronary syndrome among others. Despite the intensive investigation on SLE and LN, the role of endothelial dysfunction, as well as the underlying mechanisms, remains to be fully understood, with no specifically targeted pharmacological treatment. It is not known, in fact, if the activation pathway(s) in venous ECs are similar to the one in arterial ECs and doubts persist on the shared manifestation of microcirculation compared to macrocirculation. In this work, we aim to review the recent literature about the role of endothelial activation and dysfunction in the development of CV complications in SLE and LN patients. We, therefore, focus on arteriovenous similarities and differences and on specific pathways of great vessels compared to capillaries. Critically summarising the available data is of pivotal importance for both basic researchers and clinicians in order to develop and test new pharmacological approaches in the treatment of basic components of SLE and LN. [ABSTRACT FROM AUTHOR]