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2.
Am J Physiol Endocrinol Metab ; 303(6): E729-39, 2012 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-22739109

RESUMO

Several catabolic states (sepsis, cancer, etc.) associated with acute inflammation are characterized by a loss of skeletal muscle due to accelerated proteolysis. The main proteolytic systems involved are the autophagy and the ubiquitin-proteasome (UPS) pathways. Among the signaling pathways that could mediate proteolysis induced by acute inflammation, the transcription factor NF-κB, induced by TNFα, and the transcription factor forkhead box O (FOXO), induced by glucocorticoids (GC) and inhibited by IGF-I, are likely to play a key role. The aim of this study was to identify the nature of the molecular mediators responsible for the induction of these muscle proteolytic systems in response to acute inflammation caused by LPS injection. LPS injection robustly stimulated the expression of several components of the autophagy and the UPS pathways in the skeletal muscle. This induction was associated with a rapid increase of circulating levels of TNFα together with a muscular activation of NF-κB followed by a decrease in circulating and muscle levels of IGF-I. Neither restoration of circulating IGF-I nor restoration of muscle IGF-I levels prevented the activation of autophagy and UPS genes by LPS. The inhibition of TNFα production and muscle NF-κB activation, respectively by using pentoxifilline and a repressor of NF-κB, did not prevent the activation of autophagy and UPS genes by LPS. Finally, inhibition of GC action with RU-486 blunted completely the activation of these atrogenes by LPS. In conclusion, we show that increased GC production plays a more crucial role than decreased IGF-I and increased TNFα/NF-κB pathway for the induction of the proteolytic systems caused by acute inflammation.


Assuntos
Fator de Crescimento Insulin-Like I/metabolismo , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Atrofia Muscular/metabolismo , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima , Animais , Autofagia/efeitos dos fármacos , Glucocorticoides/efeitos adversos , Glucocorticoides/antagonistas & inibidores , Proteínas I-kappa B/genética , Proteínas I-kappa B/metabolismo , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like I/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas Musculares/antagonistas & inibidores , Proteínas Musculares/genética , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/imunologia , Atrofia Muscular/sangue , Atrofia Muscular/imunologia , Atrofia Muscular/prevenção & controle , NF-kappa B/antagonistas & inibidores , Complexo de Endopeptidases do Proteassoma/efeitos dos fármacos , Complexo de Endopeptidases do Proteassoma/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise/efeitos dos fármacos , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/genética , Regulação para Cima/efeitos dos fármacos
3.
J Intensive Care Med ; 18(2): 100-4, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-15189656

RESUMO

Previous research found that in noncritically ill patients, thoracocentesis has an unpredictable effect on oxygenation, possibly due to re-expansion pulmonary edema and systemic hypotension. The authors performed a retrospective analysis to study the effect of tube thoracostomy on oxygenation in ICU patients, and the complications associated with it. The authors reviewed the charts of 58 ICU patients in whom 74 procedures were performed. Demographic data, APACHE II score, and indication for thoracocentesis were retrieved from the patient's file. The P(a)O(2)/FiO(2) ratio was calculated before, 12, 24, and 48 hours after tube thoracostomy. P(a)O(2)/FiO(2) ratios at the mentioned time intervals were compared using 1-way analysis of variances (ANOVA) with repeated measures. Logistic regression analysis was used to identify factors associated with a good response to treatment. Age of the patients was 53 +/- 19.0 years (range, 17-88), APACHE II score was 21 +/- 8.3 (range, 6-38), and median length of stay was 13.5 days (interquartile range, 7-25). The volume drained during the first 24 hours was 1077 +/- 667 ml. P(a)O(2)/FiO(2) ratio was 185 +/- 79.3 before chest drainage, 197 +/- 79.1 at 12 hours, 217 +/- 88.9 at 24 hours, and 233 +/- 99.8 at 48 hours. In only 54% of the procedures, a response to therapy was present. Multivariate analysis identified a P(a)O(2)/FiO(2) below 180 to be independently associated with improvement in oxygenation. At 24 and 48 hours, the P(a)O(2)/FiO(2) ratio was significantly higher than before drainage (P <.001). There were 13 complications in 11 procedures (14.9%). The authors' results suggest that tube thoracostomy can be used as an adjunct in the treatment of selected patients with hypoxemic respiratory failure in the ICU. A low P(a)O(2)/FiO(2) seems to be a good predictor of response to therapy. However, the complication rate is considerable, especially in patients with a prolonged ICU stay.


Assuntos
Tubos Torácicos , Cuidados Críticos/métodos , Drenagem , Hipóxia/terapia , Insuficiência Respiratória/terapia , Toracostomia , APACHE , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Bélgica , Gasometria , Causalidade , Tubos Torácicos/efeitos adversos , Estado Terminal , Drenagem/efeitos adversos , Drenagem/métodos , Feminino , Hospitais Universitários , Humanos , Hipóxia/etiologia , Hipóxia/metabolismo , Hipóxia/fisiopatologia , Tempo de Internação/estatística & dados numéricos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/metabolismo , Insuficiência Respiratória/fisiopatologia , Estudos Retrospectivos , Toracostomia/efeitos adversos , Toracostomia/métodos , Fatores de Tempo , Resultado do Tratamento
4.
Eur J Emerg Med ; 6(3): 207-14, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10622384

RESUMO

There are few data on the use of two-level non-invasive positive pressure ventilation (two-level nIPPV) in the initial treatment of severe acute respiratory failure in emergency departments (ED). In a prospective, non-randomized, pilot study, we assessed (1) the feasability of this method in an ED, (2) its effect on clinical and laboratory data, and (3) its effect on the need of intubation and the final outcome of patients. During a 1-year period all eligible patients admitted for acute respiratory failure, with absence of improvement after periods of specific classic treatments, were included in the study. Each patient received a specific classic treatment and two-level nIPPV with a two-level positive pressure ventilator through a face mask. We recorded parameters on admission, after 15 and 45 minutes of nIPPV and at the end of nIPPV. Sixty-two patients were included: 29 with acute pulmonary oedema (APO), 16 with acute exacerbation of chronic obstructive pulmonary disease (COPD), four with asthma, and 13 with various diseases. In the APO-group, we observed a statistically significant improvement of respiratory and pulse rates, diastolic blood pressure, pH, PaCO2 and SaO2. In acute exacerbation of COPD, we observed only a statistical improvement of respiratory and pulse rates without any significant change of PaCO2 and pH. In the two other groups, there was a clinical, gasometric and haemodynamic improvement in all patients. Four patients were intubated and 10 died, but none in the ED or in the first 24 hours after hospital admission. We were able to institute two-level nIPPV for severe acute respiratory failure in an ED without complications. Its addition to the rest of classic specific treatment seems to bring about a rapid improvement of various clinical and laboratory parameters in most patients. We found no deleterious effect of nIPPV when implemented for short periods of time in the emergency department setting.


Assuntos
Respiração com Pressão Positiva/métodos , Insuficiência Respiratória/terapia , Doença Aguda , Idoso , Asma/complicações , Asma/fisiopatologia , Emergências , Estudos de Viabilidade , Feminino , Humanos , Pneumopatias Obstrutivas/complicações , Pneumopatias Obstrutivas/fisiopatologia , Masculino , Insuficiência Respiratória/complicações , Insuficiência Respiratória/fisiopatologia , Índice de Gravidade de Doença
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