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1.
Contemp Clin Trials ; 78: 126-132, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30739002

RESUMO

OBJECTIVE: Few randomized trials have evaluated the use of non-invasive ventilation (NIV) for early acute respiratory failure (ARF) in non-intensive care unit (ICU) wards. The aim of this study is to test the hypothesis that early NIV for mild-moderate ARF in non-ICU wards can prevent development of severe ARF. DESIGN: Pragmatic, parallel group, randomized, controlled, multicenter trial. SETTING: Non-intensive care wards of tertiary centers. PATIENTS: Non-ICU ward patients with mild to moderate ARF without an established indication for NIV. INTERVENTIONS: Patients will be randomized to receive or not receive NIV in addition to best available care. MEASUREMENTS AND MAIN RESULTS: We will enroll 520 patients, 260 in each group. The primary endpoint of the study will be the development of severe ARF. Secondary endpoints will be 28-day mortality, length of hospital stay, safety of NIV in non-ICU environments, and a composite endpoint of all in-hospital respiratory complications. CONCLUSIONS: This trial will help determine whether the early use of NIV in non-ICU wards can prevent progression from mild-moderate ARF to severe ARF.

2.
Case Rep Crit Care ; 2018: 1205613, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30018829

RESUMO

Bacterial meningitis and septicemia are invasive bacterial diseases, representing a significant cause of morbidity and mortality worldwide. Both conditions are characterized by an impressive inflammatory response, resulting rapidly in cerebral edema, infarction, hydrocephalus, and septic shock with multiple organ failure. Despite advances in critical care, outcome and prognosis remain critical. Available adjunctive treatments to control the inflammatory response have shown encouraging results in the evolution of patients with sepsis and systemic inflammation, but meningococcal or pneumococcal infection has not been investigated. We herein report five patients with similar critical pathological conditions, characterized by pneumococcal or meningococcal sepsis and treated with hemoadsorption for cytokine removal. All patients showed a progressive stabilization in hemodynamics along with a rapid and marked reduction of catecholamine dosages, a stabilization in metabolic disorders, and less-than-expected loss of extremities. Therapy proved to be safe and well tolerated. From this first experience, extracorporeal cytokine removal seems to be a valid and safe therapy in the management of meningococcal and pneumococcal diseases and may contribute to the patient stabilization and prevention of severe sequelae. Further studies are required to confirm efficacy in a larger context.

3.
Crit Care Med ; 45(2): e236-e237, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28098645
4.
Crit Care Med ; 44(12): 2139-2144, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27513539

RESUMO

OBJECTIVE: Noninvasive ventilation is a life-saving technique increasingly used to treat acute respiratory failure. Noninvasive ventilation has been applied mostly in ICUs, but several reasons brought to an increasing application of noninvasive ventilation in ordinary wards. Few articles evaluated the outcomes of patients receiving noninvasive ventilation including long-term follow-up. The aim of the present study was to assess 1-year survival rate of patients treated with noninvasive ventilation outside the ICU for acute respiratory failure of heterogeneous causes and to identify the predictors of long-term mortality. DESIGN: Prospective, observational, pragmatic study. SETTING: Ordinary wards of a teaching hospital. PATIENTS: Consecutive patients treated with noninvasive ventilation for acute respiratory failure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two-hundred and twenty-patients were enrolled. Mortality rates at 30-day, 90-days, and 1-year follow-up were 20%, 26%, and 34%. When excluding patients with "do-not-resuscitate" status, mortality rates were 13%, 19%, and 28%. The multivariate analyses identified solid cancer, pneumonia in hematologic patients, and do-not-resuscitate status as independent predictors of mortality with postoperative acute respiratory failure associated with improved survival. The same predictors were confirmed when excluding do-not-resuscitate patients from the analyses. CONCLUSIONS: Noninvasive ventilation applied in ordinary wards was effective, with long-term outcomes not different from those reported for ICU settings. Solid cancer, pneumonia in hematologic malignancies, and do-not-resuscitate status predicted mortality, whereas patients with postoperative acute respiratory failure had the best survival rate. Additional studies are required to evaluate noninvasive ventilation efficacy in the wards compared with ICU.


Assuntos
Ventilação não Invasiva/mortalidade , Insuficiência Respiratória/terapia , Doença Aguda , Idoso , Feminino , Humanos , Masculino , Ventilação não Invasiva/métodos , Estudos Prospectivos , Insuficiência Respiratória/mortalidade , Análise de Sobrevida
5.
Crit Care Med ; 44(7): 1347-52, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26992064

RESUMO

OBJECTIVE: Mechanical ventilation contributes to diaphragmatic atrophy and dysfunction, and few techniques exist to assess diaphragmatic function: the purpose of this study was to quantify diaphragm atrophy in a population of critically ill mechanically ventilated patients with ultrasound and to identify risk factors that can worsen diaphragmatic activity. DESIGN: Prospective observational study. SETTING: ICU of a 1,200-bed university hospital. PATIENTS: Newly intubated adult critically ill patients. INTERVENTIONS: Diaphragm thickness in the zone of apposition was measured daily with ultrasound, from the first day of mechanical ventilation till discharge to the main ward. MEASUREMENTS AND MAIN RESULTS: Daily atrophy rate (ΔTdi/d) was calculated as the reduction in percentage from the previous measurement. To analyze the difference in atrophy rate (ΔTdi/d), ventilation was categorized into four classes: spontaneous breathing or continuous positive airway pressure; pressure support ventilation 5-12 cm H2O (low pressure support ventilation); pressure support ventilation greater than 12 cm H2O (high pressure support ventilation); and controlled mechanical ventilation. Multivariate analysis with ventilation support and other clinical variables was performed to identify risk factors for atrophy. Forty patients underwent a total of 153 ultrasonographic evaluations. Mean (SD) ΔTdi/d was -7.5% (12.3) during controlled mechanical ventilation, -5.3% (12.9) at high pressure support ventilation, -1.5% (10.9) at low pressure support ventilation, +2.3% (9.5) during spontaneous breathing or continuous positive airway pressure. At multivariate analysis, only the ventilation support was predictive of diaphragm atrophy rate. Pressure support predicted diaphragm thickness with coefficient -0.006 (95% CI, -0.010 to -0.002; p = 0.006). CONCLUSIONS: In critically ill mechanically ventilated patients, there is a linear relationship between ventilator support and diaphragmatic atrophy rate.


Assuntos
Estado Terminal , Diafragma/patologia , Respiração Artificial/efeitos adversos , Ultrassonografia , Adulto , Idoso , Atrofia , Diafragma/diagnóstico por imagem , Feminino , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ventiladores Mecânicos
6.
Crit Care Med ; 43(8): 1559-68, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25821918

RESUMO

OBJECTIVES: We aimed to identify all treatments that affect mortality in adult critically ill patients in multicenter randomized controlled trials. We also evaluated the methodological aspects of these studies, and we surveyed clinicians' opinion and usual practice for the selected interventions. DATA SOURCES: MEDLINE/PubMed, Scopus, and Embase were searched. Further articles were suggested for inclusion from experts and cross-check of references. STUDY SELECTION: We selected the articles that fulfilled the following criteria: publication in a peer-reviewed journal; multicenter randomized controlled trial design; dealing with nonsurgical interventions in adult critically ill patients; and statistically significant effect in unadjusted landmark mortality. A consensus conference assessed all interventions and excluded those with lack of reproducibility, lack of generalizability, high probability of type I error, major baseline imbalances between intervention and control groups, major design flaws, contradiction by subsequent larger higher quality trials, modified intention to treat analysis, effect found only after adjustments, and lack of biological plausibility. DATA EXTRACTION: For all selected studies, we recorded the intervention and its comparator, the setting, the sample size, whether enrollment was completed or interrupted, the presence of blinding, the effect size, and the duration of follow-up. DATA SYNTHESIS: We found 15 interventions that affected mortality in 24 multicenter randomized controlled trials. Median sample size was small (199 patients) as was median centers number (10). Blinded trials enrolled significantly more patients and involved more centers. Multicenter randomized controlled trials showing harm also involved significantly more centers and more patients (p = 0.016 and p = 0.04, respectively). Five hundred fifty-five clinicians from 61 countries showed variable agreement on perceived validity of such interventions. CONCLUSIONS: We identified 15 treatments that decreased/increased mortality in critically ill patients in 24 multicenter randomized controlled trials. However, design affected trial size and larger trials were more likely to show harm. Finally, clinicians view of such trials and their translation into practice varied.


Assuntos
Cuidados Críticos/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Feminino , Fibrose/terapia , Humanos , Hipnóticos e Sedativos/administração & dosagem , Hipotermia Induzida/mortalidade , Masculino , Estudos Multicêntricos como Assunto , Decúbito Ventral , Reprodutibilidade dos Testes , Projetos de Pesquisa , Respiração Artificial/métodos , Respiração Artificial/mortalidade , Ácido Tranexâmico/sangue
10.
Biochem J ; 446(1): 1-7, 2012 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-22835215

RESUMO

The activity of key metabolic enzymes is regulated by the ubiquitin ligases that control the function of the cyclins; therefore the activity of these ubiquitin ligases explains the coordination of cell-cycle progression with the supply of substrates necessary for cell duplication. APC/C (anaphase-promoting complex/cyclosome)-Cdh1, the ubiquitin ligase that controls G(1)- to S-phase transition by targeting specific degradation motifs in cell-cycle proteins, also regulates the glycolysis-promoting enzyme PFKFB3 (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3) and GLS1 (glutaminase 1), a critical enzyme in glutaminolysis. A decrease in the activity of APC/C-Cdh1 in mid-to-late G(1) releases both proteins, thus explaining the simultaneous increase in the utilization of glucose and glutamine during cell proliferation. This occurs at a time consistent with the point in G(1) that has been described as the nutrient-sensitive restriction point and is responsible for the transition from G(1) to S. PFKFB3 is also a substrate at the onset of S-phase for the ubiquitin ligase SCF (Skp1/cullin/F-box)-ß-TrCP (ß-transducin repeat-containing protein), so that the activity of PFKFB3 is short-lasting, coinciding with a peak in glycolysis in mid-to-late G(1), whereas the activity of GLS1 remains high throughout S-phase. The differential regulation of the activity of these proteins indicates that a finely-tuned set of mechanisms is activated to fulfil specific metabolic demands at different stages of the cell cycle. These findings have implications for the understanding of cell proliferation in general and, in particular, of cancer, its prevention and treatment.


Assuntos
Proliferação de Células , Enzimas/metabolismo , Glucose/metabolismo , Glutamina/metabolismo , Redes e Vias Metabólicas , Animais , Ciclo Celular , Humanos , Ubiquitina-Proteína Ligases/metabolismo
11.
Proc Natl Acad Sci U S A ; 108(52): 21069-74, 2011 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-22106309

RESUMO

During cell division, the activation of glycolysis is tightly regulated by the action of two ubiquitin ligases, anaphase-promoting complex/cyclosome-Cdh1 (APC/C-Cdh1) and SKP1/CUL-1/F-box protein-ß-transducin repeat-containing protein (SCF-ß-TrCP), which control the transient appearance and metabolic activity of the glycolysis-promoting enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, isoform 3 (PFKFB3). We now demonstrate that the breakdown of PFKFB3 during S phase occurs specifically via a distinct residue (S(273)) within the conserved recognition site for SCF-ß-TrCP. Glutaminase 1 (GLS1), the first enzyme in glutaminolysis, is also targeted for destruction by APC/C-Cdh1 and, like PFKFB3, accumulates after the activity of this ubiquitin ligase decreases in mid-to-late G1. However, our results show that GLS1 differs from PFKFB3 in that its recognition by APC/C-Cdh1 requires the presence of both a Lys-Glu-Asn box (KEN box) and a destruction box (D box) rather than a KEN box alone. Furthermore, GLS1 is not a substrate for SCF-ß-TrCP and is not degraded until cells progress from S to G2/M. The presence of PFKFB3 and GLS1 coincides with increases in generation of lactate and in utilization of glutamine, respectively. The contrasting posttranslational regulation of PFKFB3 and GLS1, which we have verified by studies of ubiquitination and protein stability, suggests the different roles of glucose and glutamine at distinct stages in the cell cycle. Indeed, experiments in which synchronized cells were deprived of either of these substrates show that both glucose and glutamine are required for progression through the restriction point in mid-to-late G1, whereas glutamine is the only substrate essential for the progression through S phase into cell division.


Assuntos
Divisão Celular/fisiologia , Glutaminase/metabolismo , Glicólise/fisiologia , Fosfofrutoquinase-2/metabolismo , Processamento de Proteína Pós-Traducional/fisiologia , Proteínas Ligases SKP Culina F-Box/metabolismo , Complexos Ubiquitina-Proteína Ligase/metabolismo , Ciclossomo-Complexo Promotor de Anáfase , Primers do DNA/genética , Citometria de Fluxo , Glucose/metabolismo , Glutamina/metabolismo , Células HeLa , Humanos , Immunoblotting , Plasmídeos/genética , Ubiquitinação
13.
Proc Natl Acad Sci U S A ; 108(13): 5278-83, 2011 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-21402913

RESUMO

During cell proliferation, the abundance of the glycolysis-promoting enzyme, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, isoform 3 (PFKFB3), is controlled by the ubiquitin ligase APC/C-Cdh1 via a KEN box. We now demonstrate in synchronized HeLa cells that PFKFB3, which appears in mid-to-late G1, is essential for cell division because its silencing prevents progression into S phase. In cells arrested by glucose deprivation, progression into S phase after replacement of glucose occurs only when PFKFB3 is present or is substituted by the downstream glycolytic enzyme 6-phosphofructo-1-kinase. PFKFB3 ceases to be detectable during late G1/S despite the absence of Cdh1; this disappearance is prevented by proteasomal inhibition. PFKFB3 contains a DSG box and is therefore a potential substrate for SCF-ß-TrCP, a ubiquitin ligase active during S phase. In synchronized HeLa cells transfected with PFKFB3 mutated in the KEN box, the DSG box, or both, we established the breakdown routes of the enzyme at different stages of the cell cycle and the point at which glycolysis is enhanced. Thus, the presence of PFKFB3 is tightly controlled to ensure the up-regulation of glycolysis at a specific point in G1. We suggest that this up-regulation of glycolysis and its associated events represent the nutrient-sensitive restriction point in mammalian cells.


Assuntos
Ciclo Celular/fisiologia , Glicólise/fisiologia , Fosfofrutoquinase-2/metabolismo , Proteínas Ligases SKP Culina F-Box/metabolismo , Complexos Ubiquitina-Proteína Ligase/metabolismo , Sequência de Aminoácidos , Ciclossomo-Complexo Promotor de Anáfase , Proliferação de Células , Estabilidade Enzimática , Glucose/metabolismo , Células HeLa , Humanos , Ácido Láctico/metabolismo , Dados de Sequência Molecular , Fosfofrutoquinase-2/genética , Interferência de RNA
14.
Proc Natl Acad Sci U S A ; 107(44): 18868-73, 2010 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-20921411

RESUMO

Cell proliferation is accompanied by an increase in the utilization of glucose and glutamine. The proliferative response is dependent on a decrease in the activity of the ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C)-Cdh1 which controls G1-to-S-phase transition by targeting degradation motifs, notably the KEN box. This occurs not only in cell cycle proteins but also in the glycolysis-promoting enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3 (PFKFB3), as we have recently demonstrated in cells in culture. We now show that APC/C-Cdh1 controls the proliferative response of human T lymphocytes. Moreover, we have found that glutaminase 1 is a substrate for this ubiquitin ligase and appears at the same time as PFKFB3 in proliferating T lymphocytes. Glutaminase 1 is the first enzyme in glutaminolysis, which converts glutamine to lactate, yielding intermediates for cell proliferation. Thus APC/C-Cdh1 is responsible for the provision not only of glucose but also of glutamine and, as such, accounts for the critical step that links the cell cycle with the metabolic substrates essential for its progression.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Glutaminase/metabolismo , Glutamina/metabolismo , Fase S/fisiologia , Linfócitos T/metabolismo , Complexos Ubiquitina-Proteína Ligase/metabolismo , Motivos de Aminoácidos , Ciclossomo-Complexo Promotor de Anáfase , Proteínas Cdh1 , Proteínas de Ciclo Celular/genética , Fase G1/fisiologia , Glutaminase/genética , Glutamina/genética , Humanos , Ácido Láctico/metabolismo , Fosfofrutoquinase-2/genética , Fosfofrutoquinase-2/metabolismo , Linfócitos T/citologia , Complexos Ubiquitina-Proteína Ligase/genética
16.
G Ital Cardiol (Rome) ; 11(1): 12-9, 2010 Jan.
Artigo em Italiano | MEDLINE | ID: mdl-20380337

RESUMO

Mechanical ventilation is the most common invasive treatment for acute respiratory failure in intensive care units. According to non-intensivist clinicians, ventilation could be considered as a therapy for blood gas exchange, even though positive pressure ventilation can be extremely dangerous for injured lung tissue. Despite constant advances in ventilation software and modalities, aimed at optimizing patient/ventilator adjustment, the scientific community has addressed major attention in new protective strategies to ventilate the lung, trying to prevent and reduce life-threatening iatrogenic injuries that may derive from inappropriate use of mechanical ventilation. In this review we describe the main ventilation techniques as well as new emerging methodologies. The physiological bases on which the acute respiratory distress syndrome network has significantly changed the strategy for ventilation in patients with acute respiratory distress syndrome are also discussed. Non-invasive ventilation, including both continuous positive airway pressure and pressure support ventilation, is considered the gold standard for chronic obstructive pulmonary disease exacerbations. There is an increasing interest in the clinical use of non-invasive ventilation outside intensive care units. Although many studies have analyzed risks and benefits of non-invasive ventilation in the intensive care setting, feasibility and organization processes to perform this technique in the non-intensive wards, by preserving efficacy and safety, need to be debated.


Assuntos
Respiração com Pressão Positiva , Insuficiência Respiratória/terapia , Respiradores de Pressão Negativa , Doença Aguda , Humanos , Unidades de Terapia Intensiva , Síndrome do Desconforto Respiratório do Adulto/terapia , Insuficiência Respiratória/etiologia , Resultado do Tratamento
17.
Biochem J ; 421(2): 163-9, 2009 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-19442239

RESUMO

AMPK (AMP-activated protein kinase) is a key regulator of cellular energy because of its capacity to detect changes in the concentration of AMP. Recent evidence, however, indicates the existence of alternative mechanisms of activation of this protein. Mitochondrial ROS (reactive oxygen species), generated as a result of the interaction between nitric oxide and mitochondrial cytochrome c oxidase, activate AMPKalpha1 in HUVECs (human umbilical-vein endothelial cells) at a low oxygen concentration (i.e. 3%). This activation is independent of changes in AMP. In the present study we show, using HUVECs in which AMPKalpha1 has been silenced, that this protein is responsible for the expression of genes involved in antioxidant defence, such as manganese superoxide dismutase, catalase, gamma-glutamylcysteine synthase and thioredoxin. Furthermore, peroxisome proliferator-activated-coactivator-1, cAMP-response-element-binding protein and Foxo3a (forkhead transcription factor 3a) are involved in this signalling pathway. In addition, we show that silencing AMPKalpha1 in cells results in a reduced mitochondrial and eNOS (endothelial NO synthase) content, reduced cell proliferation, increased accumulation of ROS and apoptosis. Thus AMPKalpha1 in HUVECs regulates both their mitochondrial content and their antioxidant defences. Pharmacological activation of AMPKalpha1 in the vascular endothelium may be beneficial in conditions such as metabolic syndrome, Type 2 diabetes and atherosclerosis, not only because of its bioenergetic effects but also because of its ability to counteract oxidative stress.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Antioxidantes/metabolismo , Células Endoteliais/enzimologia , Endotélio Vascular/enzimologia , Proteínas Quinases Ativadas por AMP/genética , Proliferação de Células , Células Cultivadas , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Inativação Gênica , Humanos , Mitocôndrias/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
18.
J Environ Manage ; 90(3): 1404-12, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18922619

RESUMO

In this paper, we investigate whether people's knowledge of the past influences their preferences and values towards future landscape change. "Knowledge of the past" is one aspect of the information set held by individuals, and a well-established finding in economics is that changes in information can change preferences and values. The particular aspects of knowledge of the past we work with here are: (i) awareness of past landuse, as represented by woodland cover and (ii) awareness of differing and sometimes contradictory literary impressions of this past landscape. The case studies used here relate to prospective changes in woodland cover in two UK national parks, the Lake District and the Trossachs. We find that people who are made aware that the landscape has changed over time, or that perceptions of the landscape have changed over time, are more likely to favour changes to the current landscape (are less likely to favour the status quo). Knowledge of the past therefore seems to have an impact on preferences for future landscapes. We also investigate the impacts on preferences of how "special", how "wild" and how "worked in" people perceive the landscapes of these two national parks to be.


Assuntos
Agricultura , Conservação dos Recursos Naturais/tendências , Participação da Comunidade , Ecossistema , Monitoramento Ambiental , Conhecimento , Plantas , Escócia , Inquéritos e Questionários
19.
Intensive Care Med ; 35(2): 339-43, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19018515

RESUMO

OBJECTIVE: To report data about "real-life" treatments with non-invasive ventilation for acute respiratory failure (ARF), managed outside intensive care units by anaesthesiologists acting as a medical emergency team. DESIGN: Observational study; prospectively collected data over a 6-month period in a single centre. SETTING: Non-intensive wards in a University Hospital with 1,100 beds. PATIENTS: Consecutive patients with ARF for whom a ventilatory support was indicated but tracheal intubation was not appropriated or immediately needed. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Patient's characteristics, safety data, short-term outcome and organizational aspects of 129 consecutive treatments were collected. The overall success rate was 77.5%, while 10.1% were intubated and 12.4% died (all of them were "do not attempt resuscitation" patients). The incidence of treatment failure varied greatly among different diseases. Complications were limited to nasal decubitus (5%), failure to accomplish the prescribed ventilatory program (12%), malfunction of the ventilator (2%) and excessive air leaks from face mask (2%) with no consequences for patients. Three patients became intolerant to NIV. The work-load for the MET was high but sustainable: on average NIV was applied to a new case every 34 h and more than three patients were simultaneously treated. CONCLUSIONS: Under the supervision of a MET, in our institution NIV could be applied in a wide variety of settings, outside the ICU, with a high success rate and with few complications.


Assuntos
Serviços Médicos de Emergência/estatística & dados numéricos , Unidades de Terapia Intensiva , Equipe de Assistência ao Paciente , Quartos de Pacientes/estatística & dados numéricos , Respiração com Pressão Positiva/estatística & dados numéricos , Insuficiência Respiratória/terapia , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Edema Cardíaco/epidemiologia , Edema Cardíaco/terapia , Feminino , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia/epidemiologia , Pneumonia/terapia , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/terapia , Edema Pulmonar/epidemiologia , Edema Pulmonar/terapia , Recursos Humanos
20.
Proc Natl Acad Sci U S A ; 103(14): 5379-84, 2006 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-16565215

RESUMO

Vascular endothelial cells are highly glycolytic and consume relatively low amounts of oxygen (O(2)) compared with other cells. We have confirmed that oxidative phosphorylation is not the main source of ATP generation in these cells. We also show that at a low O(2) concentration (<1%) endogenous NO plays a key role in preventing the accumulation of the alpha-subunit of hypoxia-inducible factor 1. At higher O(2) concentrations (1-3%) NO facilitates the production of mitochondrial reactive oxygen species. This production activates the AMP-activated protein kinase by a mechanism independent of nucleotide concentrations. Thus, the primary role of mitochondria in vascular endothelial cells may not be to generate ATP but, under the control of NO, to act as signaling organelles using either O(2) or O(2)-derived species as signaling molecules. Diversion of O(2) away from endothelial cell mitochondria by NO might also facilitate oxygenation of vascular smooth muscle cells.


Assuntos
Endotélio Vascular/metabolismo , Mitocôndrias/fisiologia , Transdução de Sinais/fisiologia , Adenilato Quinase/metabolismo , Sequência de Bases , Western Blotting , Células Cultivadas , Primers do DNA , Endotélio Vascular/enzimologia , Endotélio Vascular/ultraestrutura , Ativação Enzimática , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Mitocôndrias/enzimologia , Mitocôndrias/metabolismo , Óxido Nítrico/fisiologia , Fosforilação Oxidativa , Oxigênio/metabolismo
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