Dopamine-dependent changes of cortical excitability induced by transcranial static magnetic field stimulation in Parkinson's disease.

Transcranial static magnetic field stimulation (tSMS) is a recent low-cost non-invasive brain stimulation technique that decreases cortical excitability in healthy subjects. The objective of the present study was to test the ability of tSMS to modulate cortical excitability in patients with Parkinson's disease. We performed a randomized double-blind sham-controlled cross-over study to assess cortical excitability before and immediately after tSMS (or sham) applied for 10 min to the more affected motor cortex of patients with Parkinson's disease. Cortical excitability was quantified by the amplitude of motor evoked potentials (MEPs) elicited by single-pulse transcranial magnetic stimulation (TMS). tSMS significantly decreased MEP amplitudes in patients OFF medication (after overnight withdrawal of dopaminergic drugs), but not ON medication (after an acute dose of levodopa). The between-patients variability of tSMS-induced changes was significantly greater ON medication. The variability ON medication could be partly explained by disease progression, i.e. the more advanced the patient, the more likely it was to observe a switch from inhibitory tSMS plasticity OFF medication to paradoxical facilitatory plasticity ON medication. These results suggest that tSMS induces dopamine-dependent changes of cortical excitability in patients with Parkinson's disease.

Chitosan-coated mesoporous MIL-100(Fe) nanoparticles as improved bio-compatible oral nanocarriers.

Nanometric biocompatible Metal-Organic Frameworks (nanoMOFs) are promising candidates for drug delivery. Up to now, most studies have targeted the intravenous route, related to pain and severe complications; whereas nanoMOFs for oral administration, a commonly used non-invasive and simpler route, remains however unexplored. We propose here the biofriendly preparation of a suitable oral nanocarrier based on the benchmarked biocompatible mesoporous iron(III) trimesate nanoparticles coated with the bioadhesive polysaccharide chitosan (CS). This method does not hamper the textural/structural properties and the sorption/release abilities of the nanoMOFs upon surface engineering. The interaction between the CS and the nanoparticles has been characterized through a combination of high resolution soft X-ray absorption and computing simulation, while the positive impact of the coating on the colloidal and chemical stability under oral simulated conditions is here demonstrated. Finally, the intestinal barrier bypass capability and biocompatibility of CS-coated nanoMOF have been assessed in vitro, leading to an increased intestinal permeability with respect to the non-coated material, maintaining an optimal biocompatibility. In conclusion, the preservation of the interesting physicochemical features of the CS-coated nanoMOF and their adapted colloidal stability and progressive biodegradation, together with their improved intestinal barrier bypass, make these nanoparticles a promising oral nanocarrier.

Chronic mercury exposure at different concentrations produces opposed vascular responses in rat aorta.

Mercury chloride exposure for 30 days decreases NO bioavailability and increases oxidative stress. However, the mechanisms underlying the effects of mercury on the cardiovascular system are not completely understood, and it is not known if they are dose-dependent or if some concentrations have no harmful effects. Thus, we investigated the effects of chronic exposure to doses low (half) and high (2.5-fold higher) than that needed to obtain 29 nmol/L of HgCl2 on the vascular function. Three-month-old male Wistar rats received intramuscular (i.m.) HgCl2 for 30 days and were divided in three groups: lower (Low Hg); higher (High Hg); and saline was used as the control. High Hg exposure increased the contractile response to phenylephrine (PHE) in aortic rings, but Low Hg reduced it. The hyporesponsiveness in the Low Hg rats was blunted by endothelial denudation and NOS inhibition with l-NAME (100 µmol/L). The phosphorylated-eNOS/eNOS protein ratio increased in the aortas of Low Hg rats. In the High Hg group, endothelial denudation increased the PHE-induced contractions, while l-NAME had no effects and indomethacin (10 µmol/L), losartan (10 µmol/L) and apocynin (30 µmol/L) reduced this response. In the High Hg group, protein levels of the NADPH oxidase subunit gp91phox and cyclooxygenase-2 increased. Our results support previous suggestions that High Hg increases oxidative stress that might activate an inflammatory cascade and the renin-angiotensin system. However, very low Hg concentrations below the level considered safe still reduced vascular reactivity, suggesting the need for special attention to continuous exposure as a putative cause of increased cardiovascular risk.

Current status of selected oral peptide technologies in advanced preclinical development and in clinical trials.

The development of oral dosage forms that allows absorption of therapeutic peptides to the systemic circulation is one of the greatest challenges for the pharmaceutical industry. Currently, a number of technologies including either mixtures of penetration enhancers or protease inhibitors and/or nanotechnology-based products are under clinical development. Typically, these formulations are presented in the form of enteric-coated tablets or capsules. Systems undergoing preclinical investigation include further advances in nanotechnology, including intestinal microneedle patches, as well as their combination with regional delivery to the colon. This review critically examines four selected promising oral peptide technologies at preclinical stage and the twelve that have progressed to clinical trials, as indicated in www.clinicaltrials.gov. We examined these technologies under the criteria of peptide selection, formulation design, system components and excipients, intestinal mechanism of action, efficacy in man, and safety issues. The conclusion is that most of the technologies in clinical trials are incremental rather than paradigm-shifting and that even the more clinically advanced oral peptide drugs examples of oral bioavailability appear to yield oral bioavailability values of only 1-2% and are, therefore, only currently suitable for a limited range of peptides.

Role of COX-2-derived PGE2 on vascular stiffness and function in hypertension.

BACKGROUND AND PURPOSE: Prostanoids derived from COX-2 and EP receptors are involved in vascular remodelling in different cardiovascular pathologies. This study evaluates the contribution of COX-2 and EP1 receptors to vascular remodelling and function in hypertension. EXPERIMENTAL APPROACH: Spontaneously hypertensive rats (SHR) and angiotensin II (AngII)-infused (1.44 mg · kg(-1) · day(-1), 2 weeks) mice were treated with the COX-2 inhibitor celecoxib (25 mg · kg(-1) · day(-1) i.p) or with the EP1 receptor antagonist SC19220 (10 mg · kg(-1) · day(-1) i.p.). COX-2(-/-) mice with or without AngII infusion were also used. KEY RESULTS: Celecoxib and SC19220 treatment did not modify the altered lumen diameter and wall : lumen ratio in mesenteric resistance arteries from SHR-infused and/or AngII-infused animals. However, both treatments and COX-2 deficiency decreased the augmented vascular stiffness in vessels from hypertensive animals. This was accompanied by diminished vascular collagen deposition, normalization of altered elastin structure and decreased connective tissue growth factor and plasminogen activator inhibitor-1 gene expression. COX-2 deficiency and SC19220 treatment diminished the increased vasoconstrictor responses and endothelial dysfunction induced by AngII infusion. Hypertensive animals showed increased mPGES-1 expression and PGE2 production in vascular tissue, normalized by celecoxib. Celecoxib treatment also decreased AngII-induced macrophage infiltration and TNF-α expression. Macrophage conditioned media (MCM) increased COX-2 and collagen type I expression in vascular smooth muscle cells; the latter was reduced by celecoxib treatment. CONCLUSIONS AND IMPLICATIONS: COX-2 and EP1 receptors participate in the increased extracellular matrix deposition and vascular stiffness, the impaired vascular function and inflammation in hypertension. Targeting PGE2 receptors might have benefits in hypertension-associated vascular damage.

Association between maltreatment and polydrug use among adolescents.

Different studies have related sexual and physical abuse during childhood and adolescence to the development of substance abuse disorders. Nevertheless, we are not aware of the role that other more common maltreatment types, such as neglect, will play among the most risky pattern of consumption: the polydrug use. A clinical sample of 655 adolescents, divided into two groups: polydrug users and non-polydrug users, were assessed on their pattern of drug consumption, history of childhood maltreatment, current psychopathology and their family history of alcoholism. Polydrug users had a greater prevalence of all types of maltreatment, although the most associated to this group were sexual abuse and emotional neglect. Other relevant variables to adolescent consumption were: the diagnosis of depressive disorder, the presence of anxiety traits and the family history of alcohol dependence. Polydrug users have higher risks of having had problems during infancy and adolescence, such as maltreatment and other psychopathological conditions, with the addition of family history of alcoholism. Accordingly, practitioners should take into account that those variables may influence polydrug abuse because it is the most risky pattern for subsequent dependence of substances, and they should always be considered during treatment.

Nanotherapies for the treatment of ocular diseases.

The topical route is the most frequent and preferred way to deliver drugs to the eye. Unfortunately, the very low ocular drug bioavailability (less than 5%) associated with this modality of administration, makes the efficient treatment of several ocular diseases a significant challenge. In the last decades, it has been shown that specific nanocarriers can interact with the ocular mucosa, thereby increasing the retention time of the associated drug onto the eye, as well as its permeability across the corneal and conjunctival epithelium. In this review, we comparatively analyze the mechanism of action and specific potential of the most studied nano-drug delivery carriers. In addition, we present the success achieved until now using a number of nanotherapies for the treatment of the most prevalent ocular pathologies, such as infections, inflammation, dry eye, glaucoma, and retinopathies.

Sobrecarga y Burnout en cuidadores informales del adulto mayor / Overload and Burnout among aged informal caregivers / Sobrecarga e Burnout com cuidadores informais do idoso

Objetivo: Conocer las condiciones personales, de sobrecarga y su relación con el Síndrome de Burnout en el cuidador informal del adulto mayor. Método: Estudio correlacional y transversal. Muestreo no probabilístico, por conveniencia. Muestra: 52 cuidadores informales de ancianos de ambos sexos. Se utilizó cédula de datos personales, la escala de Zarit y el cuestionario Maslach Burnout Inventory. El procesamiento de datos se realizó con el Statistical Package for the Social Sciences versión 20. Resultados: La media de edad de los cuidadores fue de 44 años, 58% están casados, 50% tienen escolaridad media superior, 45% son hijos de los seniles (35% son las hijas), el 27% trabajan como profesionistas, 73% tienen de 1 a 6 años cuidando al anciano; 42% dedica de 6-15 horas a su cuidado; 58% padece sobrecarga, con significancia (r = 0.442, p = 001) con las horas diarias dedicadas al cuidado. El Síndrome de Burnout mostró bajo riesgo en todas las dimensiones: Agotamiento Emocional 67%, Deshumanización 80% y Realización Personal 73%, aunque más del 20% lo padece en alguna dimensión. Conclusiones: La sobrecarga y el síndrome de Burnout en los cuidadores familiares se encontraron bajos. El factor relacionado con la sobrecarga y él Burnout fue el tiempo diario dedicado al cuidado. Con base en los resultados, se propone establecer programas preventivos de entrenamiento acerca del cuidado dirigidos a familiares de ancianos; con el fin de contribuir al bienestar de los cuidadores.

Objective: To explore the personal conditions associated with work overload and the Syndrome of Burnout among aged informal caregivers. Method: Correlational and transversal study using by-convenience not-probabilistic sampling. Sample: 52 aged informal caregivers of both sexes. A personal data form, the Zarit scale, and the Maslach Burnout Inventory questionnaire were all used. Data were processed with the Statistical Package for the Social Sciences version 20. Results: The care providers average age was 44 years old, 58% reported being married, 50% said they had a mid-high level education, 45% were sons of the elderly (35% were daughters), 27% said they worked as professionals, 73% stated they had a 1- 6 year-experience taking care of elders, 42% said that they usually devote between 6 and 15 hours daily to their care activities, and 58% turned out to be suffering from a work overload (r = .442, p=.001). A low Burnout Syndrome risk was found in all the corresponding dimensions: Emotional Fatigue 67%, Dehumanization 80%, and Personal Accomplishment 73%, though more than 20% of the respondents were shown to be suffering from the syndrome in at least one dimension. Conclusions: Work overloads and the Burnout Syndrome among the aged family caregivers were found to be low. An important factor associated with the work overload and the Burnout Syndrome was the time per day devoted to the care. Based on the results, it is suggested to establish preventive training programs related to caring and aimed at the aged family caregivers with the objective of contributing to the wellbeing of these specific caregivers.

Objetivo: Conhecer as condições pessoais, de sobrecarga e sua relação com a síndrome de Burnout no cuidador informal do idoso. Método: Estudo correlacional e transversal. Amostragem não probabilística por conveniência. Amostra: 52 cuidadores informais de idosos de ambos os sexos. Utilizou-se a cédula de dados pessoais, a escala de Zarit e o questionário Maslach Burnout Inventory. O processamento de dados realizou-se com o Statistical Package for the Social Sciences versão 20. Resultados: A média de idade dos cuidadores foi de 44 anos, 58% são casados, 50% são de escolaridade de ensino médio, 45% são filhos dos idosos (35% são as filhas), 27% trabalham como profissionais, 73% cuidam o idoso de 1 a 6 anos, 42% dedica ao cuidado de 6 a 15 horas, 58% padece de sobrecarga com significância (r=.442, p=001) pelo cuidado dedicado diariamente. A síndrome de Burnout mostrou um risco baixo em todas as dimensões: esgotamento emocional 67%, desumanização 80% e realização pessoal 73%, ainda que mais do 20% padeça em alguma dimensão. Conclusões: A sobrecarga e a síndrome de Burnout nos cuidadores familiares encontram-se baixos. O fator relacionado com a sobrecarga e o Burnout foi pelo cuidado dedicado diariamente. Com base nos resultados, propõem-se estabelecer programas preventivos de treino em volta do cuidado dirigido a familiares de idosos, com o fim de contribuir para o bem-estar dos cuidadores.

HuR mediates the synergistic effects of angiotensin II and IL-1ß on vascular COX-2 expression and cell migration.

BACKGROUND AND PURPOSE: Angiotensin II (AngII) and IL-1ß are involved in cardiovascular diseases through the induction of inflammatory pathways. HuR is an adenylate- and uridylate-rich element (ARE)-binding protein involved in the mRNA stabilization of many genes. This study investigated the contribution of HuR to the increased expression of COX-2 induced by AngII and IL-1ß and its consequences on VSMC migration and remodelling. EXPERIMENTAL APPROACH: Rat and human VSMCs were stimulated with AngII (0.1 µM) and/or IL-1ß (10 ng · mL(-1)). Mice were infused with AngII or subjected to carotid artery ligation. mRNA and protein levels were assayed by quantitative PCR, Western blot, immunohistochemistry and immunofluorescence. Cell migration was measured by wound healing and transwell assays. KEY RESULTS: In VSMCs, AngII potentiated COX-2 and tenascin-C expressions and cell migration induced by IL-1ß. This effect of AngII on IL-1ß-induced COX-2 expression was accompanied by increased COX-2 3' untranslated region reporter activity and mRNA stability, mediated through cytoplasmic HuR translocation and COX-2 mRNA binding. These effects were blocked by ERK1/2 and HuR inhibitors. VSMC migration was reduced by blockade of ERK1/2, HuR, COX-2, TXAS, TP and EP receptors. HuR, COX-2, mPGES-1 and TXAS expressions were increased in AngII-infused mouse aortas and in carotid-ligated arteries. AngII-induced tenascin-C expression and vascular remodelling were abolished by celecoxib and by mPGES-1 deletion. CONCLUSIONS AND IMPLICATIONS: The synergistic induction of COX-2 by AngII and IL-1ß in VSMCs involves HuR through an ERK1/2-dependent mechanism. The HuR/COX-2 axis participates in cell migration and vascular damage. HuR might be a novel target to modulate vascular remodelling.

Toll-like receptor 4 contributes to vascular remodelling and endothelial dysfunction in angiotensin II-induced hypertension.

BACKGROUND AND PURPOSE: Toll-like receptor 4 (TLR4) signalling contributes to inflammatory cardiovascular diseases, but its role in hypertension and the associated vascular damage is not known. We investigated whether TLR4 activation contributed to angiotensin II (AngII)-induced hypertension and the associated vascular structural, mechanical and functional alterations. EXPERIMENTAL APPROACH: AngII was infused (1.44 mg · kg(-1) · day(-1), s.c.) for 2 weeks in C57BL6 mice, treated with a neutralizing anti-TLR4 antibody or IgG (1 µg · day(-1); systolic BP (SBP) and aortic cytokine levels were measured. Structural, mechanical and contractile properties of aortic and mesenteric arterial segments were measured with myography and histology. RT-PCR and Western blotting were used to analyse these tissues and cultured vascular smooth muscle cells (VSMC) from hypertensive rats (SHR). KEY RESULTS: Aortic TLR4 mRNA levels were raised by AngII infusion. Anti-TLR4 antibody treatment of AngII-treated mice normalised: (i) increased SBP and TNF-α, IL-6 and CCL2 levels; (ii) vascular structural and mechanical changes; (iii) altered aortic phenylephrine- and ACh-induced responses; (iv) increased NOX-1 mRNA levels, superoxide anion production and NAD(P)H oxidase activity and effects of catalase, apocynin, ML-171 and Mito-TEMPO on vascular responses; and (v) reduced NO release and effects of L-NAME on phenylephrine-induced contraction. In VSMC, the MyD88 inhibitor ST-2825 reduced AngII-induced NAD(P)H oxidase activity. The TLR4 inhibitor CLI-095 reduced AngII-induced increased phospho-JNK1/2 and p65 NF-κB subunit nuclear protein expression. CONCLUSIONS AND IMPLICATIONS: TLR4 up-regulation by AngII contributed to the inflammation, endothelial dysfunction, vascular remodelling and stiffness associated with hypertension by mechanisms involving oxidative stress. MyD88-dependent activation and JNK/NF-κB signalling pathways participated in these alterations.

Poly-L-asparagine nanocapsules as anticancer drug delivery vehicles.

This work presents for the first time the development of novel poly-L-asparagine (PASN) nanocapsules and the in vitro evaluation of their potential as anticancer drug delivery systems. The design of PASN nanocapsules was inspired by the well-known avidity of cancer cells for the amino acid L-asparagine together with the expected ability of this hydrophilic polymer to escape to the mononuclear phagocytic system. Besides, these nanocapsules have an oily reservoir, which enables the efficient encapsulation of lipophilic drugs. PASN nanocapsules were obtained by an emulsification-polymer layer deposition process, which involves using a cationic surfactant as a bridge for the interaction of PASN with the lipid core. PASN nanocapsules showed sizes of around 170-200 nm and negative zeta potential values (around -20 mV to -40 mV). The model anticancer drug docetaxel was efficiently encapsulated (around 75%) and retained within the nanocapsule's structure upon dilution in a simulated physiological medium. Moreover, these nanocapsules exhibited the ability to interact with the NCI-H460 human cancer cells and to enhance the cellular toxicity of the anticancer drug. All these features together with their adequate stability profile render these nanocapsules a new attractive platform for anticancer intracellular drug delivery.

Vaccine delivery carriers: insights and future perspectives.

Vaccination is undoubtedly the most effective health intervention for disease prevention and eradication. Nevertheless, currently there is still a need for improving immunization coverage worldwide. A promising strategy to achieve this goal nowadays relies on the use of delivery carriers capable of inducing an effective immune response and providing improved stability, safety and cost effectiveness. This article focuses on analyzing the critical aspects in the design of these carriers, and reviewing the state of the art of currently marketed formulations and those in advanced clinical development. These vaccine delivery carriers include emulsions, liposomes and polymeric particulate carriers. Finally, particular attention is given to the evolution in the design of polymeric nanocarriers, which have been receiving increasing attention and hold promise to generate novel platforms for needle-free administration and single-dose vaccination.

Intracellular delivery of docetaxel using freeze-dried polysaccharide nanocapsules.

This article describes the development of a freeze-dried formulation of chitosan (CS) nanocapsules containing docetaxel (DCX) and the evaluation of its efficacy in the NCI-H460 cancer cell line. More specifically, two prototypes of nanocapsules differing in their coating, CS alone or in combination with poloxamer 188 were developed using the solvent displacement technique. These prototypes (150 nm and +45 mV) exhibited high encapsulation efficiencies of DCX (78%) and very similar release profiles. The nanocapsules made of solely CS could be freeze-dried and reconstituted without altering their particle size distribution. CS nanocapsules were tested for their ability to deliver intracellularly the anticancer drug DCX. The results showed that CS nanocapsules maintained the antiproliferative effect of the drug and that it was not affected by the freeze-drying process. Moreover, it was found that this cytostatic effect of DCX was related to its intracellular delivery in the cancer cells.

Perfil sociodemográfico y de intereses profesionales de los estudiantes de licenciatura en enfermería / Socio-demographic profile and professional interests of students of Bachelor's degree in nursing

Introducción: Aunque en los servicios de salud a nivel mundial existe deficiencia de personal de enfermería, en América Latina el índice de deserción en las escuelas de enfermería es elevado; esta problemática recae en trabajadores en ejercicio quienes deben brindar cuidado enfermero en situaciones de cansancio y estrés. La problemática lleva a pensar que no existen características adecuadas en los estudiantes que ingresan para cursar favorablemente la carrera. Objetivo: Determinar las características sociodemográficas, económicas, familiares, de antecedentes escolares e intereses profesionales de estudiantes que ingresan a estudiar la carrera de Enfermería. Suponemos una relación entre deserción e intereses u objetivos que guiaron a alumnos en la selección de carrera, sus características socio-económicas-familiares y del plantel que provienen. Metodología: Estudio transversal y descriptivo, se consideró el 100% de las cédulas de tutoría aplicadas a estudiantes de Enfermería que ingresaron entre 2001 y 2006. Los datos sociodemográficos, económicos y familiares se obtuvieron por medio de preguntas abiertas o cerradas, para clasificar nivel socioeconómico se utilizó la propuesta de Sigmarket, los intereses profesionales se evaluaron a partir de una escala tipo likert. Resultados: El perfil obtenido mostró una población joven, predominantemente solteros, que no realizan trabajo remunerado, dependen económicamente de sus padres, de condiciones socioeconómicas precarias, sus intereses están orientados hacia la obtención de conocimientos y aspectos de carácter social Conclusiones: Fue importante identificar una tendencia, aunque no significativa estadísticamente, de permanencia en mayor medida de los alumnos con condiciones sociales más precarias, y aquellos cuyos intereses de orden social se ubican en el nivel más alto.

Introduction: Although it exists a deficiency in nursing staff at a global level in health services, in Latin America the rate of dropout in nursing schools is high; this problem lies over workers who must provide nurse care in situations of fatigue and stress. The problem leads us to think there are no appropriate characteristics for students to successful fulfill their career. Objective: to determine the socio demographic, economic and family characteristics, school background and professional interests of students entering nursing. We assume an existing relationship between dropout, the interests or goals that guided students in the selection of the career in nursing, the socio-economic-family characteristics and the institution of origin. Methodology: cross-sectional and descriptive study that considered the 10000% of admission interviews made to incoming nursing students from 200001 to 200006. The socio-demographic, economical and familiar data were obtained from closed and openended questions; the Sigmarket proposal was used for the classification of the socioeconomic level, the professional interests were evaluate from a likert scale. Results; the obtained profile showed a young population, mainly single, that doesn't have a paid job and depends from their parents economically, from a low socio-economic conditions, their interests are focus towards the acquisition of knowledge and aspects of social nature. Conclusions: it was important to identify a mayor tendency, although not statistically significant, of continuing the career from part of the students with lower social conditions and those whose social interests are located in the highest level.

Evolving architectural patterns in microbial colonies development.

Semithin sections of colonies of three ATCC strains (Staphylococcus aureus, Escherichia coli, and Candida albicans) showed that their internal structure had specific patterns that evolved over the time. These patterns generally were defined by the presence of different layers composed of microorganisms with variable population densities and dead cells. The observed structures in this study could be explained as a particular form of biofilm with an air-semisolid interface.

The role of cyclooxygenase (COX)-2 derived prostanoids on vasoconstrictor responses to phenylephrine is increased by exposure to low mercury concentration.

We have previously demonstrated that chronic exposure to low-dose of mercury induced endothelial dysfunction and increased vasoconstrictor responses. The aim of this work was to investigate if mercury exposure alters contractile prostanoids production from cyclooxygenase-2 (COX-2) and its contribution to phenylephrine responses. For this, aortic segments from 3-month old Wistar rats daily treated with HgCl(2) (1(st) dose 4.6 microg/kg, subsequent dose 0.07 microg/kg/day, i.m.) or vehicle for 30 days were used. Mercury treatment did not affect systolic blood pressure but increased phenylephrine-induced vasoconstriction. The non selective COX inhibitor, indomethacin (10 micromol/l) reduced the response to phenylephrine more in aortic segments from mercury-treated than control rats. The selective COX-2 inhibitor NS 398 (1 micromol/l), the thromboxane A(2)/prostaglandin H(2) receptor (TP) antagonist SQ 29,548 (1 micromol/l), the TXA(2) synthase inhibitor furegrelate (1 micromol/l), the EP(1) receptor antagonist SC 19220 (1 micromol/l) and the AT(1) receptor antagonist losartan (10 micromol/l) reduced phenylephrine response only in vessels from mercury-treated rats. TXA(2) and PGE(2) levels were greater in the incubation medium of vessels from treated than untreated rats; NS 398 decreased these levels only in the mercury group. COX-2 protein was localized in adventitial and endothelial cells. Aortic COX-2 mRNA expression and plasma angiotensin converting enzyme activity were greater in mercury-treated rats. These results suggest that treatment with low doses of mercury increases the release of COX-2-derived vasoconstrictor prostanoids and its participation in phenylephrine responses. The increased activation of the renin-angiotensin system after mercury treatment might be associated to this increased COX-2 activity.