Predictive validity of the Braden scale for assessing risk of developing pressure ulcers and dependence-related lesions.

OBJECTIVE: In 2014, a new theoretical model explained the mechanism of the development of pressure ulcers (PUs) and that of seven types of lesions known as dependence-related lesions (DRL). The aim of this study was to calculate the incidence of DRL that have been classified as PUs and to check the predictive validity of the Braden scale for assessing DRL in accordance with the new theoretical model in an intensive care unit (ICU). Method This longitudinal, prospective study was conducted in a Spanish ICU. The patients were monitored for 14 days in the ICU until they developed DRL, died, or were discharged. The patients' risk of developing DRL was assessed each day using the Braden scale. The following parameters were taken as reference for validating the scale: sensitivity (Se), specificity (Sp), positive and negative predictive values (PPV and NPV, respectively), relative risk (RR) and the area under the receiver operating characteristic (ROC) curve. RESULTS: Of the 295 patients included in the study, 27.5% developed DRL, which 50.6% were categorised as PUs, 17.3% caused by moisture, and 13.6% caused by friction. The rest were categorised as caused by a combination of factors. Risk according to the Braden scale was greater in the group of patients with DRL than in the group of patients without. The highest risk score provided the best predictive validity parameters for the DRL (Se 0.90, Sp 0.26, PPV 0.31, NPV 0.78 and RR 3.15 [confidence interval (CI) 95%: 1.42-6.96]). These vaules show the individuals at risk are well detected, although it is at the expense of generating a number of false positive cases. CONCLUSIONS: The Braden scale has demonstrated a moderate capacity for predicting PUs and DRL caused by moisture, but no capacity for predicting DRL caused by friction.

[The adapting of a care plan after Kennedy terminal ulcer diagnosis]. / Adecuación del plan de cuidados ante el diagnóstico de úlcera terminal de Kennedy.

A 69 year old man was admitted to the Intensive Care Unit (ICU) from the Emergency Department due to severe respiratory failure. Due to unsuccessful non-invasive mechanical ventilation, endotracheal intubation was performed. A category I ulcer in coccyx was detected 48h after admission. Eight hours later, a double erythema (the second one darker than the first one) with displacement between 30-45° over the bony prominence suggested there was a deep tissue injury. The lesion progressed rapidly during the next 24h. The shape and the rapid evolution of the injury lead us to diagnose a Kennedy terminal ulcer (KTU). At 72h after the admission, and once the causes of acute decompensation were ruled out, limitation of life-sustaining treatment was decided. An individualised plan of care was drawn up with the aim of identifying problems in a patient with KTU evolving from a critical to a terminal situation. Our overall objectives (NOC) were to adapt the care plan based on a realistic approach. Nursing interventions (NIC) included actions such as pain management, conservative treatment of the injury, agony care and support to help the family to make decisions. CONCLUSION: The diagnosis of KTU helped the health care team in the decision-making process when they considered limiting the life support, as well as in the adapting of the care plan to the actual situation.

Analysis of expression and function of the co-stimulatory receptor SLAMF1 in immune cells from patients with systemic lupus erythematosus (SLE).

The signaling lymphocytic activation molecule SLAMF1 (CD150) is a co-stimulatory molecule that is expressed by most immune cells, including T regulatory (Treg) lymphocytes. Since different abnormalities have been reported regarding the number and function of Foxp3+ Treg cells in patients with systemic lupus erythematosus (SLE), we decided to analyze the expression and function of CD150 in these regulatory lymphocytes in this condition. We isolated peripheral blood mononuclear cells from 20 patients with SLE, and 20 healthy controls. The expression of SLAMF1 was determined by multi-parametric flow cytometry and the suppressive function of CD4+CD25+ lymphocytes, upon engagement or not of CD150 with an agonistic monoclonal antibody, was analyzed by an assay of inhibition of cell proliferation. We observed a significantly increased expression of SLAMF1 by CD3+CD4+ helper T cells and CD19+ B cells in patients with SLE and active disease. However, similar levels of SLAMF1 expression were detected in Foxp3+ Treg cells from patients and controls. In contrast, a higher proportion of SLE patients increased their suppressive function of Treg cells upon CD150 engagement compared to healthy controls. Our data suggest that SLAMF1 is another significant piece in the intricate defective immune-regulatory function of patients with SLE.

[Validation of EMINA and EVARUCI scales for assessing the risk of developing pressure ulcers in critical patients]. / Validación de las escalas de valoración de riesgo de úlceras por presión EMINA y EVARUCI en pacientes críticos.

OBJECTIVE: To contribute to the validation of the EMINA and EVAUCI scales for assessing the risk of pressure ulcers in the critical patient and compare their predictive capacity in this same context. METHOD: Prospective study from December 2012 until June 2013. SETTING: Polyvalent intensive care unit of 14 beds in a reference hospital for two sanitary areas. PATIENTS: patients of 18 years of age or older and without pressure ulcers were included. They were followed until development of a pressure ulcer of grade I or greater, medical discharge, death or 30 days. MAIN VARIABLES: presence of ulcers, daily score of the risk of developing pressure ulcers through EMINA and EVARUCI evaluation. The validity of both scales was calculated using sensitivity, specificity, and positive and negative predictive value. The level of significance was P≤0.05. RESULTS: A total of 189 patients were evaluated. 67.2% were male with a mean age of 59.4 (DE: 16,8) years old, 53 (28%) developed pressure ulcers, being the incidence rate of 41 ulcers per 1000 admission days. The mean day of diagnosis was 7.7 days (DE: 4,4) and the most frequent area was the sacrum. The sensitivity and specificity for the mean of observations was 94.34 (IC95% 87.17-100) and 33.33 (IC95% 25.01-41.66) for the EMINA scale for a risk>10 and 92.45 (IC95% 84.40-100) and 42.96 (IC95% 34.24-51.68) for the EVARUCI scale for a risk of>11. CONCLUSIONS: No differences were found in predictive capacity of both scales. For sensitivities>90%the scales show to be insufficiently specific in the pressure ulcer risk detection in critical patients.

Distribution and accumulation of Cd, Cu, Hg, Pb and Zn in the surface sediments of El Tobari Lagoon, central-East Gulf of California: An ecosystem associated with agriculture and aquaculture activities.

The purpose of this research is to provide a comprehensive assessment of the concentration levels and spatial variability of cadmium (Cd), copper (Cu), mercury (Hg), lead (Pb) and zinc (Zn) in El Tobari Lagoon in surface sediments during two seasons for several geochemical variables that could explain the observed heavy metal variability. Seventy-two surface sediments samples were collected in 12 different sites of the El Tobari Lagoon. Sediment samples were dried and subjected to acid extraction using a microwave system and five metals (Cd, Cu, Hg, Pb and Zn) were measured using atomic adsorption spectrometry. A certificate sediment material and blanks were used as quality control purposes. The enrichment factor (EF) and the index of geoaccumulation (Igeo) were calculated as index of metals contamination for the sediments, using aluminum as the conservative element. The five metals examined in sediments from El Tobari Lagoon exhibited a linear correlation with Al as result of the large specific surface areas of these sediment components and the chemical affinities between them. The metals contents in sites of the El Tobari Lagoon were variable, and Cd, Cu and Hg presented a seasonal behavior. The enrichment factor and index of geoaccumulation analysis indicated that Cd and Hg exhibited a certain extent (EF for Cd ranged from 4.10 to 10.29; EF for Hg ranged from 2.77 to 12.89) of anthropogenic pollution, while Cu showed sporadic (EF ranged from 0.43 to 2.54) anthropogenic contamination. The highest concentrations of Cd, Cu and Hg were found in the sites that regularly received discharge effluents from agriculture and aquaculture.

Comparative bioaccumulation of trace metals using six filter feeder organisms in a coastal lagoon ecosystem (of the central-east Gulf of California).

The Tobari Lagoon, located in the central-east coast of the Gulf of California, receives effluents from the Yaqui Valley, one of the most extensive agricultural areas of México. The Tobari Lagoon also receives effluents from nearby shrimp farms and untreated municipal sewage. Surface sediment samples and six different species of filter feeders (Crassostrea corteziensis, Crassostrea gigas, Chione gnidia, Anadara tuberculosa, Chione fluctifraga, and Fistulobalanus dentivarians) were collected during the dry and the rainy seasons and analyzed to determine concentrations of cadmium (Cd), copper (Cu), mercury (Hg), lead (Pb), and zinc (Zn). Seasonal variations in metal concentrations in sediment were evident, especially for Cd, Cu, Hg, and Zn. The total and bioavailable concentrations of the five metals are not elevated in comparison to other areas around the world. The percentages of bioavailable respect to total concentrations of the metals varied from 0.6 % in Hg to 50.2 % for Cu. In the organisms, Hg showed the lowest concentrations (ranged from 0.22 to 0.65 µg/g) while Zn showed the highest (ranged from 36.6 to 1,702 µg/g). Linear correlations between the levels of Cu, Pb, and Zn in the soft tissues of C. fluctifraga and C. gnidia, and A. tuberculosa and C. gnidia were found. Seasonal and interspecies variations in the metal levels in filter feeders were found; F. dentivarians, C. corteziensis, and C. gigas exhibited the highest levels, could be used as biomonitors of metals contamination in this area.

Wide variation in spatial genetic structure between natural populations of the European beech (Fagus sylvatica) and its implications for SGS comparability.

Identification and quantification of spatial genetic structure (SGS) within populations remains a central element of understanding population structure at the local scale. Understanding such structure can inform on aspects of the species' biology, such as establishment patterns and gene dispersal distance, in addition to sampling design for genetic resource management and conservation. However, recent work has identified that variation in factors such as sampling methodology, population characteristics and marker system can all lead to significant variation in SGS estimates. Consequently, the extent to which estimates of SGS can be relied on to inform on the biology of a species or differentiate between experimental treatments is open to doubt. Following on from a recent report of unusually extensive SGS when assessed using amplified fragment length polymorphisms in the tree Fagus sylvatica, we explored whether this marker system led to similarly high estimates of SGS extent in other apparently similar populations of this species. In the three populations assessed, SGS extent was even stronger than this previously reported maximum, extending up to 360 m, an increase in up to 800% in comparison with the generally accepted maximum of 30-40 m based on the literature. Within this species, wide variation in SGS estimates exists, whether quantified as SGS intensity, extent or the Sp parameter. Consequently, we argue that greater standardization should be applied in sample design and SGS estimation and highlight five steps that can be taken to maximize the comparability between SGS estimates.

[Pressure ulcers in the critical patient: detection of risk factors]. / Úlceras por presión en el enfermo crítico: detección de factores de riesgo.

INTRODUCTION: Patients admitted to intensive care units (ICU) are more vulnerable to the appearance of pressure ulcers. This is the reason why the highest rates of pressure ulcers (PU) incidence and prevalence are found in the ICU. This study has aimed to identify risk factors related to the appearance of PU in critically ill patients. PATIENTS AND METHOD: This was a prospective and observational study that included all patients admitted for more than 24 h from October 2009 to June 2010. Dependent variable: Appearance of PU. INDEPENDENT VARIABLES: APACHE II score, risk assessment score (EMINA), body mass index (BMI), support surface, nutrition, norepineprhine, sedation and care support devices. Data analyses: Kaplan-Meyer survival and Cox regression analysis. Significance p < 0.05. RESULTS: A total of 236 patients were included. A significant association was found to BMI≥30 (RR: 2.51), EMINA >10 (RR: 2.96), hyperproteic nutrition (RR: 0.946), turning (RR: 0.88), sedation (RR: 0.95), polyurethane nasogastric feeding tube (RR: 0.94), dynamic support surface (RR:0.88). Significant association of p < 0.1 for Norepinephrine (RR: 2.34). CONCLUSIONS: BMI≥ 30, EMINA and norepinephrine are predictive factors of risk for PU development. Sedation days, dynamic support surfaces, hyperproteic nutrition, turning, and polyurethane nasogastric feeding tube were established as protective factors against PU.

A ten-year monitoring of essential and non-essential elements in the dolphinfish Coryphaena hippurus from the southern Gulf of California.

The concentrations of As, Cd, Cu, Pb and Zn were measured in muscle tissue of Coryphaena hippurus captured in the southern Gulf of California to determine inter-annual variations and their relation with environmental parameters for the period 2006-2015; additionally, health risk to consumers was assessed according to levels of studied elements and rate of fish consumption in northwest Mexico. During 2014 and 2015 the levels of As, Cd, Cu, and Zn were significantly lower than the rest of the years; in the case of As, it was also significantly lower in 2010. Oceanic Niño Index was negatively correlated with Zn concentrations in fish, while sea surface temperature was negatively correlated with Zn, Pb and Cd concentrations in dolphinfish. The simultaneous occurrence of the analyzed elements in muscle of dolphinfish indicated that health effects on consumers are not likely to occur; nevertheless, fishermen with elevated fish consumption might be at risk.

[Prevention of mechanical ventilator-associated pneumonia: a comparison of two different oral hygiene methods]. / Prevención de la neumonía asociada a la ventilación mecánica: estudio comparativo de dos métodos de higiene oral.

INTRODUCTION: Oral hygiene (OH) forms a part of the patient's safety in the prevention of mechanical ventilator-associated pneumonia (VAP). The dental plaque index (DP) is considered as a quality marker for OH. HYPOTHESIS: The association of electric toothbrush and conventional OH in intubated patients decreases the DP and incidence of VAP. OBJECTIVE: To verify the reduction of DP in patients receiving OH and electric toothbrush and its association with to the decrease of VAP incidence. MATERIALS AND METHODS: A 3-year long randomized, single blind and prospective study conducted in a 14-bed polyvalent intensive care unit. Patients were included when there was more than 48hours of mechanical ventilation and no expected respiratory infection. Patients were randomized into two groups: Standard (OH with chlorhexidine) (GS) and Raspall (Standard OH with electric dental brush) (GR). The VAP was identified following clinical, medical and microbiological criteria. The DP and halitosis were observed daily. Oral and pharyngeal swabs were collected during the first 5 days. RESULTS: 147 patients were included. Mean age was 53.9±17.5. No significant differences were found in the VAP incidence between the two groups (OR=0.78; 95% IC, 0.36-1.68; p=0.56). The relation between halitosis and DP was p=0.7. The dental plaque index on the 5th day was 1.98 (n=60) in GR and 2.04 (n=57) in GS (p=0.3). The dental plaque index on the 10th day was 1.68 (n=29) in GR and 1.91 (n=32) in GS (p=0.7). CONCLUSIONS: There is a tendency towards a decrease in the DP which is clearing in the GR group and no relation between VAP and greater DP or halitosis.

Human adipose-derived mesenchymal stem cells reduce inflammatory and T cell responses and induce regulatory T cells in vitro in rheumatoid arthritis.

OBJECTIVES: Adult mesenchymal stem cells were recently found to suppress effector T cell and inflammatory responses and have emerged as attractive therapeutic candidates for immune disorders. In rheumatoid arthritis (RA), a loss in the immunological self-tolerance causes the activation of autoreactive T cells against joint components and subsequent chronic inflammation. The aim of this study is to characterise the immunosuppressive activity of human adipose-derived mesenchymal stem cells (hASCs) on collagen-reactive T cells from patients with RA. METHODS: The effects of hASCs on collagen-reactive RA human T cell proliferation and cytokine production were investigated, as well as effects on the production of inflammatory mediators by monocytes and fibroblast-like synoviocytes from patients with RA. RESULTS: hASCs suppressed the antigen-specific response of T cells from patients with RA. hASCs inhibited the proliferative response and the production of inflammatory cytokines by collagen-activated CD4 and CD8 T cells. In contrast, the numbers of IL10-producing T cells and monocytes were significantly augmented upon hASC treatment. The suppressive activity of hASCs was cell-to-cell contact dependent and independent. hASCs also stimulated the generation of FoxP3 protein-expressing CD4(+)CD25(+) regulatory T cells, with the capacity to suppress collagen-specific T cell responses. Finally, hASCs downregulated the inflammatory response and the production of matrix-degrading enzymes by synovial cells isolated from patients with RA. CONCLUSIONS: The present work identifies hASCs as key regulators of immune tolerance, with the capacity to suppress T cell and inflammatory responses and to induce the generation/activation of antigen-specific regulatory T cells.

Seasonal variations in the concentrations of metals in Crassostrea corteziensis from Sonora, México.

This study examines seasonal variations in the concentrations of Cd, Cu, Pb, and Hg in experimentally cultured Crassostrea corteziensis, an oyster species known to have high resistance to physical and chemical stressors. The highest levels of Cd (4.92 mg/kg), Cu (3.45 mg/kg), and Pb (0.67 mg/kg) were detected in oyster samples collected during the summer, while Hg concentrations were similar (0.03 to 0.04 mg/kg) throughout all seasons. Results indicate that except for Cd, Crassostrea corteziensis accumulates metals to levels below those recommended by the US. FDA and the Mexican government. For Cd, its concentration correlates more strongly with the temperature of the oyster's environment rather than to the oyster growth cycle.

[Scarring after Mustarde otoplasty: importance of cures and post-operative follow-up of the patients]. / Escaras tras otoplastia de Mustardé: importancia de las curas y seguimiento postoperatorio de los pacientes.

INTRODUCTION: In the treatment protocol for patients with Mustardé otoplasties we use tennis head sweatbands for 2 months (to be worn all the time in the first month and only at night in the second month) to protect the correction obtained and to avoid traumatisms. MATERIAL AND METHODS: We describe the cases of 3 patients who underwent Mustardé otoplasty and presented sloughs in the anterior edge of the antehelix that are secondary to the pressure of the compression bandage. RESULTS: One patient operated for unilateral malformation suffered bilateral scars (in the operated ear and in the healthy one). This prove that the scars are secondary to the dressings not to surgery. In two patients the sloughs evolved into the formation of nodular hypertrophic scars, which were slowly corrected with silicone dressings and externally applied corticosteroids and moisturising creams in one patient and had to be resected in the other. CONCLUSIONS: It is important to give a detailed explanation to the parents about the mission and characteristics of the sweatbands, and also about the need to frequently check their correct placing. This is to avoid a complication that, without spoiling the final result of the otoplasty, reduces patient satisfaction and extends the recovery period.

Human adult stem cells derived from adipose tissue protect against experimental colitis and sepsis.

BACKGROUND AND AIMS: Inflammatory bowel diseases (IBDs) are associated with uncontrolled innate and adaptive immunity against normal constituents, including commensal bacteria and microbial products. Mesenchymal stem cells (MSCs) suppress effector T cell responses and have beneficial effects in various immune disorders. This work investigates the therapeutic effects of human adipose-derived MSCs (hASCs) in various models of IBD and sepsis. METHODS: Acute and chronic colitis was induced in mice with dextran sulfate sodium. Sepsis was induced by caecal ligation and puncture or by endotoxin injection. Colitic and septic mice were treated intraperitoneally with hASCs or murine ASCs, and diverse disease clinical signs and mortality were determined. The levels of various inflammatory cytokines and chemokines, T helper 1(Th1)-type response and generation of regulatory T cells (Treg) were determined in affected organs. RESULTS: Systemic infusion of ASCs significantly ameliorated the clinical and histopathological severity of colitis, abrogating weight loss, diarrhoea and inflammation, and increasing survival. The therapeutic effect was associated with downregulation of the Th1-driven inflammatory responses. ASCs decreased a wide panel of inflammatory cytokines and chemokines and increased interleukin 10 (IL10), acting on macrophages. hASCs also impaired Th1 cell activation in both colonic mucosa and draining lymph nodes. The induction of IL10-secreting Treg was partially involved in the therapeutic effect of hASCs. Moreover, ASCs protected from severe sepsis by reducing the infiltration of inflammatory cells in various target organs and by downregulating the production of various inflammatory mediators. CONCLUSIONS: hASCs emerge as key regulators of immune/inflammatory responses in vivo and as attractive candidates for cell-based treatments for IBD and sepsis.

Microspatial population genetic structure of the Mediterranean shrub Fumana thymifolia.

Fumana thymifolia (Cistaceae) is an insect-pollinated, gravity-dispersed evergreen shrub, which is a common component of fire-prone Mediterranean shrubland ecosystems. Despite the availability of basic knowledge on its ecology, little is known of its breeding system and no information is available on its population genetic structure. We explored the within-population genetic structure of this species using amplified fragment length polymorphism (AFLP) molecular markers and related this to predictions based on its breeding system, pollen and seed dispersal. Existing information on the reproductive ecology of F. thymifolia was supplemented by artificial pollination experiments. We determined that self-fertilisation can occur in F. thymifolia but results in reduced fruit set. Significant genetic structuring was detected within the population, a likely consequence of localised seed dispersal in combination with a mixed mating system. In a study site covering approximately 0.5 ha, amova revealed that approximately 9% of genetic variability was distributed among population subsamples. Significant spatial genetic structure was detected, with kinship coefficients being significantly elevated above the null expectation in the first six distance classes (maximum 5 m), and a value of Sp of up to 0.0342, comparable with species having similar ecological characteristics. Weak isolation by distance at the plot scale was detected, suggesting that insect-mediated pollen flow is non-random, despite being more extensive than seed dispersal. Fumana thymifolia provides a promising model for the investigation of both short- and long-term population dynamics in relation to fire frequency within this plant community.

[Postoperative pain in patients undergoing elective laparoscopic cholecystectomy with low versus standard-pressure pneumoperitoneum. A randomized clinical trial.]. / Dolor posquirúrgico en pacientes sometidos a colecistectomía laparoscópica electiva con neumoperitoneo de baja presión o de presión estándar: un ensayo clínico.

BACKGROUND: Laparoscopic cholecystectomy is the gold standard in the management of symptomatic gallstone disease. Postoperative abdominal and shoulder-tip pain are the main adverse side effects. AIM: To determine whether the low-pressure pneumoperitoneum (7 mmHg) decreases postoperative pain in patients undergoing laparoscopic cholecystectomy compared with standard pressure pneumoperitoneum (12-15 mmHg). MATERIAL AND METHODS: Double-blind clinical trial that included 68 patients divided into two groups: low-pressure and standard pressure pneumoperitoneum. Main variables assessed were abdominal pain at 6, 12 and 24 hours (by visual analogue scale), the incidence of shoulder- tip pain, time and quality of exposure of the surgical field. Variables were compared using Chi square and T-Student, considering significance at p<0.05. RESULTS: The demographic characteristics of patients were similar in both groups. Abdominal pain was significantly less at 12 and 24 hours in the group with low-pressure pneumoperitoneum (p=0.02). The presence of shoulder-tip pain occurred more frequently in the group with standard- pressure pneumoperitoneum (p=0.007). CONCLUSIONS: Low-pressure pneumoperitoneum significantly reduces abdominal and shoulder tip pain. Key words: pneumoperitoneum, laparoscopic cholecystectomy, postoperative pain, shoulder pain, complications, Mexico.

Regulation of endothelial nitric oxide synthase expression in the vascular wall and in mononuclear cells from hypercholesterolemic rabbits.

BACKGROUND: We recently obtained evidence demonstrating that cultured bovine endothelial cells contain cytosolic proteins that form complexes with the 3'-untranslated region of endothelial nitric oxide synthase (eNOS) mRNA and are associated with its destabilization. The aim of this study was to determine the presence of such proteins and eNOS expression in hypercholesterolemic rabbits as an in vivo model of endothelial dysfunction. METHODS AND RESULTS: Endothelium-dependent relaxation to acetylcholine and the calcium ionophore A23187 was reduced in aortic segments from hypercholesterolemic rabbits compared with controls. Treatment of hypercholesterolemic rabbits with cerivastatin (0.1 mg. kg body wt(-1). d(-1)) restored endothelium-dependent relaxation. Aortic eNOS expression was reduced in hypercholesterolemic rabbits and was accompanied by enhanced binding activity of a 60-kDa cytosolic protein and reduced stability of eNOS mRNA. Cerivastatin treatment upregulated eNOS expression and reduced the interaction of the cytosolic protein with the 3'-untranslated region of eNOS mRNA. Mononuclear cells from hypercholesterolemic rabbits also showed a marked reduction of eNOS expression and eNOS mRNA stability and an increase in binding activity of the cytosolic protein, which were also prevented by cerivastatin treatment. CONCLUSIONS: These results demonstrate the presence of a 60-kDa protein that binds to eNOS mRNA and reductions in eNOS expression in both vascular wall and mononuclear cells that are prevented by cerivastatin.

Expression of an endothelial-type nitric oxide synthase isoform in human neutrophils: modification by tumor necrosis factor-alpha and during acute myocardial infarction.

OBJECTIVES: The purpose of this study was to determine whether human neutrophils express an endothelial-type nitric oxide synthase (eNOS), and to study the effect of tumor necrosis factor-alpha (TNF-alpha) on its expression. BACKGROUND: Several studies have demonstrated the presence of a constitutively expressed nitric oxide svnthase (NOS) in neutrophils. Cardiovascular disease is characterized by increased levels of plasma TNF-alpha, a cytokine that has demonstrated eNOS messenger ribonucleic acid (mRNA) destabilization in cultured endothelial cells. METHODS: Neutrophils were obtained from healthy volunteers and from patients with acute myocardial infarction (AMI). RESULTS: Human neutrophils express eNOS mRNA and eNOS protein. Stimulation of neutrophils with TNF-alpha decreased eNOS protein expression by reducing eNOS mRNA stabilization. In the present study, we also show that the cytosol of human neutrophils contains proteins that bind to a specific region within the 3'-untranslated region (3'-UTR) of eNOS mRNA. Tumor necrosis factor-alpha increased the binding of the cytosolic proteins to the 3'-UTR of eNOS mRNA. Simvastatin reduced the TNF-alpha-related binding activity of neutrophil cytosolic proteins to eNOS mRNA, which was associated with its protective effect on eNOS protein expression. The in vivo reproduction of the in vitro findings was performed in neutrophils obtained from patients with AMI and showed a diminished expression of eNOS protein, which was associated with increased binding of the cytosolic proteins. CONCLUSIONS: These observations demonstrate that human neutrophils express eNOS, which is downregulated by TNF-alpha and during AMI. This effect is associated with increased binding of neutrophil cytosolic proteins to the 3'-UTR of eNOS mRNA.

Role of nitric oxide in the control of apoptosis in the microvasculature.

Cell death occurs by either apoptosis or necrosis. Apoptosis is a cellular event in which a sequence of biochemical and morphological changes conclude in the death of the cell. Apoptosis is an important mechanism to control the number of cells and maintain tissue architecture. Nitric oxide (NO) is a multifunctional molecule that is synthesized by a family of enzymes, namely nitric oxide synthases (NOS). NO is implicated in several physiological functions within the microvascular environment, i.e. regulation of vascular tone, antiplatelet and antileukocyte properties and modulation of cell growth. Several investigations have demonstrated effects of NO on gene transcription. In this regard, NO has been also implicated in the apoptotic processes. The goal of the present review is to summarize the current knowledge about the relationship between NO and different genes involved in the apoptotic phenomena with focus in the cells of the microvascular environment, i.e. monocytes/macrophages, endothelium and vascular smooth muscle cells. Different studies have revealed that stimulation and inhibition of different genes are required to stimulate apoptosis. NO modulates the expression of bcl-2 family members, p53, interleukin-1 beta-converting enzyme family proteases and the cytokine receptor Fas. Therefore, NO generated from NO donors or synthesized by NOS induces cell death via apoptosis in a variety of different cell types. On the other hand, in the endothelial cells NO seems to have a relevant role in the maintenance of the confluent endothelial monolayer inhibiting apoptotic-related mechanisms. Furthermore, the redox states of the cells play an important role in the effects of NO as promotor of apoptosis. There have been exciting advances in the understanding of the molecular relationship between apoptosis and NO. Therefore, NO could be an important mediator to consider in the context of future therapeutic applications particularly considering apoptosis as a mechanism to maintain vascular architecture.

Endogenous angiotensin II produced by endothelium regulates interleukin-1beta-stimulated nitric oxide generation in rat isolated vessels.

The endothelium is a source of several factors that regulate vascular functions. Angiotensin II is one of the main active factors released by the endothelium. The aim of the present work was to analyze the role of angiotensin II released by the endothelium in the regulation of the inducible nitric oxide synthase expression in rat isolated aortic vessels. Interleukin-1beta (0.03 U/L) stimulated nitrite release by the aortic vessels. The nitrite released was less in vessels with endothelium than in deendothelialized aortic segments. This effect was accompanied by a reduced expression of the inducible nitric oxide synthase in the aortic rings with endothelium. Exogenous angiotensin II inhibited IL-1beta-stimulated inducible nitric oxide synthase protein expression in both deendothelialized vessels and those with endothelium, although with reduced ability on the aortic segments with endothelium by a nitric oxide-independent mechanism. In the aortic rings with endothelium, either inhibition of the AT-1 receptor with losartan or blocking of angiotensin II generation with fosinopril enhanced interleukin-1beta-stimulated inducible nitric oxide synthase protein expression. In conclusion, the endothelium decreases inducible nitric oxide synthase expression in the vascular wall. Angiotensin II released from endothelial cells is a main mediator responsible for this inhibition through an AT-1-type receptor-dependent mechanism.