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BACKGROUND: One of the most commonly used hypnotics is propofol. Several studies performed in cardiac surgery suggested an increased mortality in patients receiving a propofol-based total intravenous anaesthesia. Furthermore, the possibility of infections and the 'propofol syndrome' have suggested that propofol might be dangerous. Nonetheless, propofol is widely used in different settings because of its characteristics: fast induction, rapid elimination, short duration of action, smooth recovery from anaesthesia, few adverse effects, no teratogenic effects, characteristics that have undoubtedly contributed to its popularity. The effect of propofol on survival is unknown. We decided to carry out a meta-analysis of all randomized controlled studies ever performed on propofol vs. any comparator in any clinical setting. METHODS: Pertinent studies were independently searched in BioMedCentral, PubMed, Embase, Clinicaltrial.gov, and Cochrane Central Register of Clinical Trials by expert investigators. The following inclusion criteria were used: random allocation to treatment, comparison between propofol and any comparator in any clinical setting. RESULTS: One hundred thirty-three studies randomizing 14,516 patients were included. No differences in mortality between patients receiving propofol [349/6957 (5.0%)] vs. any comparator [340/7559 (4.5%)] were observed in the overall population [risk ratio = 1.05, 95% confidence interval (0.93 to 1.18), P = 0.5] and in several sub-analyses. CONCLUSION: Inspite of theoretical concerns, propofol has no detrimental effect on survival according to the largest meta-analysis of randomized trials ever performed on hypnotic drug.
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Anestesia Intravenosa , Propofol/farmacologia , Procedimentos Cirúrgicos Cardíacos/mortalidade , Humanos , Propofol/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Non-invasive ventilation (NIV) has been used to prevent or to treat perioperative acute respiratory failure (ARF). Intraoperative prophylactic and therapeutic use of NIV could be of interest to patients with anticipated difficulty in postoperative weaning from mechanical ventilation or to patients refusing tracheal intubation. Intraoperative NIV might also be useful when deep sedation is required, as this can cause respiratory depression. PubMed, Embase, Google Scholar, and Cochrane Library were searched for pertinent studies. Inclusion criteria were NIV use during surgery and adult patients; the exclusion criteria were NIV application only in the preoperative or postoperative periods, paediatric patients, NIV applied as negative pressure ventilation. Thirty papers including 618 patients were included for final analysis. Intraoperative therapeutic NIV to treat ARF was reported for 92 patients and in all those cases, including six Caesarean sections, surgery was completed uneventfully. Intraoperative prophylactic NIV to avoid ARF was described in 24 patients with severe respiratory limitation and in 502 healthy patients during deep sedation. Three patients could not be successfully ventilated due to upper airway obstruction, but no further complication was reported. Intraoperative NIV appears feasible, safe, and potentially useful, particularly when tracheal intubation is best avoided. However, high-quality, randomized studies are required.
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Complicações Intraoperatórias/terapia , Ventilação não Invasiva/métodos , Insuficiência Respiratória/terapia , Sedação Consciente/efeitos adversos , Contraindicações , Humanos , Cuidados Intraoperatórios/métodos , Intubação Intratraqueal , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/prevenção & controleRESUMO
BACKGROUND: Single dilator technique (SDT) and guide wire dilating forceps (GWDF) are the two most commonly used techniques of percutaneous dilatational tracheostomy (PDT) in critically ill adult patients. We performed a meta-analysis of randomised, controlled trials comparing intraoperative, mid-term and late complications of these two techniques. METHODS: Pertinent studies were searched in BioMedCentral, PubMed, Embase and the Cochrane Central Register of clinical trials. We selected all randomised studies comparing SDT and GWDF techniques in adult critically ill patients published in a peer-reviewed journal. RESULTS: Among 1040 retrieved studies, five eligible studies randomising 363 patients (181 to GWDF, 182 to SDT) were identified. The incidence of the composite outcome difficult cannula insertion/difficult dilation or failure was higher with the GWDF technique (15.5% vs. 4.9 %, P = 0.02). Moreover, intraprocedural bleeding was more common in the GWDF group (19.3% vs. 7.6% in SDT group, P = 0.018). A trend towards an increased incidence of fracture of tracheal rings was noted in the SDT group (6.5% vs. 0.5% in the GWDF group, P = 0.13). No difference in mid-term or long-term complications was observed. CONCLUSION: GWDF technique is associated with a higher incidence of intraprocedural bleeding and of technical difficulties in completing the procedure (difficult cannula insertions/difficult dilations or failures) compared with the SDT technique. No differences were identified in mid-term and long-term complications. Further studies comparing SDT and GWDF in the general population and in subgroups of high-risk patients (like obese or hypoxaemic patients) are warranted.
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Instrumentos Cirúrgicos , Traqueostomia/métodos , Adulto , Perda Sanguínea Cirúrgica , Estado Terminal , Interpretação Estatística de Dados , Humanos , Período Intraoperatório , Viés de Publicação , Ensaios Clínicos Controlados Aleatórios como Assunto , Reprodutibilidade dos Testes , Traqueostomia/efeitos adversos , Traqueostomia/instrumentaçãoRESUMO
BACKGROUND: Many studies have compared desflurane, isoflurane, sevoflurane, total i.v. anaesthesia (TIVA), or all in cardiac surgery to assess their effects on patient survival. METHODS: We performed standard pairwise and Bayesian network meta-analyses; the latter allows indirect assessments if any of the anaesthetic agents were not compared in head-to-head trials. Pertinent studies were identified using BioMedCentral, MEDLINE/PubMed, Embase, and the Cochrane Library (last updated in June 2012). RESULTS: We identified 38 randomized trials with survival data published between 1991 and 2012, with most studies (63%) done in coronary artery bypass grafting (CABG) patients with standard cardiopulmonary bypass. Standard meta-analysis showed that the use of a volatile agent was associated with a reduction in mortality when compared with TIVA at the longest follow-up available [25/1994 (1.3%) in the volatile group vs 43/1648 (2.6%) in the TIVA arm, odds ratio (OR)=0.51, 95% confidence interval (CI) 0.33-0.81, P-value for effect=0.004, number needed to treat 74, I(2)=0%] with results confirmed in trials with low risk of bias, in large trials, and when including only CABG studies. Bayesian network meta-analysis showed that sevoflurane (OR=0.31, 95% credible interval 0.14-0.64) and desflurane (OR=0.43, 95% credible interval 0.21-0.82) were individually associated with a reduction in mortality when compared with TIVA. CONCLUSIONS: Anaesthesia with volatile agents appears to reduce mortality after cardiac surgery when compared with TIVA, especially when sevoflurane or desflurane is used. A large, multicentre trial is warranted to confirm that long-term survival is significantly affected by the choice of anaesthetic.
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Anestésicos Inalatórios , Anestésicos Intravenosos , Procedimentos Cirúrgicos Cardíacos/métodos , Anestesia Geral/métodos , Anestesia Geral/mortalidade , Teorema de Bayes , Procedimentos Cirúrgicos Cardíacos/mortalidade , Desflurano , Humanos , Isoflurano/análogos & derivados , Éteres Metílicos , Ensaios Clínicos Controlados Aleatórios como Assunto , Sevoflurano , Análise de SobrevidaRESUMO
BACKGROUND: Percutaneous dilatational tracheostomy (PDT) is a common procedure in intensive care units and the identification of the best technique is very important. We performed a systematic review and meta-analysis of randomized studies comparing different PDT techniques in critically ill adult patients to investigate if one technique is superior to the others with regard to major and minor intraprocedural complications. METHODS: BioMedCentral and other database of clinical trials were searched for pertinent studies. Inclusion criterion was random allocation to at least two PDT techniques. Exclusion criteria were duplicate publications, nonadult studies, and absence of outcome data. STUDY DESIGN: Population, clinical setting, and complications were extracted. RESULTS: Data from 1130 patients in 13 randomized trials were analyzed. Multiple dilators, single-step dilatation, guide wire dilating forceps, rotational dilation, retrograde tracheostomy, and balloon dilation techniques were always performed in the intensive care unit. The different techniques and devices appeared largely equivalent, with the exception of retrograde tracheostomy, which was associated with more severe complications and more frequent need of conversion to other techniques when compared with guide wire dilating forceps and single-step dilatation techniques. Single-step dilatation technique was associated with fewer failures than rotational dilation, and fewer mild complications in comparison with balloon dilation and guide wire dilating forceps (all P < 0.05). CONCLUSIONS: Among the six analyzed techniques, single-step dilatation technique appeared the most reliable in terms of safety and success rate. However, the number of available randomized trials was insufficient to confidently assess the best PDT technique.
Assuntos
Traqueostomia/métodos , Adulto , Cateterismo , Estado Terminal , Interpretação Estatística de Dados , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Reprodutibilidade dos Testes , Resultado do TratamentoRESUMO
OBJECTIVE: Continuous positive airway pressure (CPAP) is an important therapeutic tool in COVID-19 acute respiratory distress syndrome (ARDS) since it improves oxygenation, reduces respiratory rate and can prevent intubation and intensive care unit (ICU) admission. CPAP during pronation has seldom been described and never during sedation. DESIGN: Case series. SETTING: High dependency unit of San Carlo University Hospital (Potenza, Italy). PATIENTS: Eleven consecutive patients with COVID-19 ARDS. INTERVENTION: Helmet CPAP in prone position after failing a CPAP trial in the supine position. MAIN VARIABLE OF INTEREST: Data collection at baseline and then after 24, 48 and 72h of pronation. We measured PaO2/FIO2, pH, lactate, PaCO2, SpO2, respiratory rate and the status of the patients at 28-day follow up. RESULTS: Patients were treated with helmet CPAP for a mean±SD of 7±2.7 days. Prone positioning was feasible in all patients, but in 7 of them dexmedetomidine improved comfort. PaO2/FIO2 improved from 107.5±20.8 before starting pronation to 244.4±106.2 after 72h (p<.001). We also observed a significantly increase in Sp02 from 90.6±2.3 to 96±3.1 (p<.001) and a decrease in respiratory rate from 27.6±4.3 to 20.1±4.7 (p=.004). No difference was observed in PaCO2 or pH. At 28 days two patients died after ICU admission, one was discharged in the main ward after ICU admission and eight were discharged home after being successfully managed outside the ICU. CONCLUSIONS: Helmet CPAP during pronation was feasible and safe in COVID-19 ARDS managed outside the ICU and sedation with dexmedetomidine safely improved comfort. We recorded an increase in PaO2/FIO2, SpO2 and a reduction in respiratory rate.
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COVID-19 , Síndrome do Desconforto Respiratório , Pressão Positiva Contínua nas Vias Aéreas , Humanos , Unidades de Terapia Intensiva , Pronação , Síndrome do Desconforto Respiratório/terapia , SARS-CoV-2 , VigíliaRESUMO
There is no consensus on which drugs/techniques/strategies can affect mortality in the perioperative period of cardiac surgery. With the aim of identifying these measures, and suggesting measures for prioritized future investigation we performed the first International Consensus Conference on this topic. The consensus was a continuous international internet-based process with a final meeting on 28 June 2010 in Milan at the Vita-Salute University. Participants included 340 cardiac anesthesiologists, cardiac surgeons, and cardiologists from 65 countries all over the world. A comprehensive literature review was performed to identify topics that subsequently generated position statements for discussion, voting, and ranking. Of the 17 major topics with a documented mortality effect, seven were subsequently excluded after further evaluation due to concerns about clinical applicability and/or study methodology. The following topics are documented as reducing mortality: administration of insulin, levosimendan, volatile anesthetics, statins, chronic ß-blockade, early aspirin therapy, the use of pre-operative intra-aortic balloon counterpulsation, and referral to high-volume centers. The following are documented as increasing mortality: administration of aprotinin and aged red blood cell transfusion. These interventions were classified according to the level of evidence and effect on mortality and a position statement was generated. This International Consensus Conference has identified the non-surgical interventions that merit urgent study to achieve further reductions in mortality after cardiac surgery: insulin, intra-aortic balloon counterpulsation, levosimendan, volatile anesthetics, statins, chronic ß-blockade, early aspirin therapy, and referral to high-volume centers. The use of aprotinin and aged red blood cells may result in increased mortality.
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Procedimentos Cirúrgicos Cardíacos/mortalidade , Cuidados Críticos , Anestesia , HumanosRESUMO
OBJECTIVE: Continuous positive airway pressure (CPAP) is an important therapeutic tool in COVID-19 acute respiratory distress syndrome (ARDS) since it improves oxygenation, reduces respiratory rate and can prevent intubation and intensive care unit (ICU) admission. CPAP during pronation has seldom been described and never during sedation. DESIGN: Case series. SETTING: High dependency unit of San Carlo University Hospital (Potenza, Italy). PATIENTS: Eleven consecutive patients with COVID-19 ARDS. INTERVENTION: Helmet CPAP in prone position after failing a CPAP trial in the supine position. MAIN VARIABLE OF INTEREST: Data collection at baseline and then after 24, 48 and 72h of pronation. We measured PaO2/FIO2, pH, lactate, PaCO2, SpO2, respiratory rate and the status of the patients at 28-day follow up. RESULTS: Patients were treated with helmet CPAP for a mean±SD of 7±2.7 days. Prone positioning was feasible in all patients, but in 7 of them dexmedetomidine improved comfort. PaO2/FIO2 improved from 107.5±20.8 before starting pronation to 244.4±106.2 after 72h (p<.001). We also observed a significantly increase in Sp02 from 90.6±2.3 to 96±3.1 (p<.001) and a decrease in respiratory rate from 27.6±4.3 to 20.1±4.7 (p=.004). No difference was observed in PaCO2 or pH. At 28 days two patients died after ICU admission, one was discharged in the main ward after ICU admission and eight were discharged home after being successfully managed outside the ICU. CONCLUSIONS: Helmet CPAP during pronation was feasible and safe in COVID-19 ARDS managed outside the ICU and sedation with dexmedetomidine safely improved comfort. We recorded an increase in PaO2/FIO2, SpO2 and a reduction in respiratory rate.
RESUMO
Objective: Continuous positive airway pressure (CPAP) is an important therapeutic tool in COVID-19 acute respiratory distress syndrome (ARDS) since it improves oxygenation, reduces respiratory rate and can prevent intubation and intensive care unit (ICU) admission. CPAP during pronation has seldom been described and never during sedation.DesignCase series.SettingHigh dependency unit of San Carlo University Hospital (Potenza, Italy).PatientsEleven consecutive patients with COVID-19 ARDS.InterventionHelmet CPAP in prone position after failing a CPAP trial in the supine position.Main variable of interestData collection at baseline and then after 24, 48 and 72h of pronation. We measured PaO2/FIO2, pH, lactate, PaCO2, SpO2, respiratory rate and the status of the patients at 28-day follow up.ResultsPatients were treated with helmet CPAP for a mean±SD of 7±2.7 days. Prone positioning was feasible in all patients, but in 7 of them dexmedetomidine improved comfort. PaO2/FIO2 improved from 107.5±20.8 before starting pronation to 244.4±106.2 after 72h (p<.001). We also observed a significantly increase in Sp02 from 90.6±2.3 to 96±3.1 (p<.001) and a decrease in respiratory rate from 27.6±4.3 to 20.1±4.7 (p=.004). No difference was observed in PaCO2 or pH. At 28 days two patients died after ICU admission, one was discharged in the main ward after ICU admission and eight were discharged home after being successfully managed outside the ICU.Conclusions: Helmet CPAP during pronation was feasible and safe in COVID-19 ARDS managed outside the ICU and sedation with dexmedetomidine safely improved comfort. We recorded an increase in PaO2/FIO2, SpO2 and a reduction in respiratory rate (AU)
Objetivo: La ventilación con presión positiva continua (CPAP) es una opción terapéutica útil en pacientes con síndrome de dificultad respiratoria aguda (SDRA) secundaria a infección por coronavirus 2019 (COVID-19) porque mejora la oxigenación, disminuye la frecuencia respiratoria y puede prevenir la intubación orotraqueal y así la admisión en la unidad de cuidados intensivos (UCI). El uso de la CPAP en pronación se ha descrito raramente, y nunca en pacientes con sedación superficial.DiseñoSerie de casos.ÁmbitoUnidad de cuidados intensivos del Hospital San Carlo (Potenza, Italia).PacientesOnce casos consecutivos de pacientes con SDRA secundario a infección por COVID-19.IntervencionesCasco y CPAP y en posición de prono, después de fracasar una sesión de una hora de CPAP en posición supina.Variables de interés principalesDatos clínicos registrados antes de iniciar la primera sesión de 12h de pronación y a las 24, 48 y 72h. Los datos registrados fueron PaO2/FiO2, pH, lactatos, PaCO2, SpO2, frecuencia respiratoria y visita de seguimiento a los 28días.ResultadosTodos los pacientes fueron tratados con CPAP y casco durante una media ±DE de 7±2,7. La posición de prono se realizó con éxito en los 11 pacientes, pero 7 pacientes recibieron dexmetodomidina para mejorar el confort.El valor de PaO2/FiO2 mejoró desde 107,5±20,8 antes de la pronación hasta 244,4±106,2 después de 72h (p<0,001). Se observó un aumento significativo de la SpO2 desde un basal de 90,6±2,3 hasta 96±3,1 a las 72h (p<0,001) y una reducción de la frecuencia respiratoria desde 27,6±4,3 hasta 20,1±4,7 (p=0,004). No se observaron diferencias en los valores de PaCO2 o de pH. A los 28días dos pacientes habían fallecido, uno permanecía todavía ingresado en la planta después de la dimisión de la UCI y ocho fueron remitidos al domicilio después de ser tratados en la planta sin necesidad de ingreso en la UCI.Conclusio: nesLa CPAP con casco durante la posición de prono fue segura y eficaz
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Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Pressão Positiva Contínua nas Vias Aéreas , Síndrome do Desconforto Respiratório/terapia , Síndrome do Desconforto Respiratório/virologia , Decúbito Ventral , Unidades de Terapia IntensivaRESUMO
The purpose of this study was to evaluate the direct effect of oxygen free radicals produced by ultrasonic irradiation on ubiquinone and to compare the efficiency with which the antioxidant can compete with these radicals when it is both in aqueous solution and within the lipid bilayer. The main product obtained after insonation of aqueous solutions of ubiquinone-0 was ubiquinol, moreover some degradation occurred. The direct electron donor responsible for most of the ubiquinol generated by ultrasonic irradiation appeared to be superoxide radical. Addition reactions of hydroxyl radicals with aromatic ring structure led probably to degradation products of ubiquinone, which were not identified. Experiments were also performed to evaluate the efficiency with which ubiquinone-3 could react with oxygen radicals when it was within the lipid bilayer. The effect of presence or absence of a net surface charge was studied selecting a suitable bilayer including dimyristylphosphatidic acid or stearylamine in uncharged dimyristylphosphatidylcholine vesicles. In these systems hydroxyl radicals did not represent a potential danger for the antioxidant, the reaction between superoxide and ubiquinone-3 instead was significant only in positively charged membranes and gave rise to ubiquinol. It is suggested that ubiquinone acts as an antioxidant by stopping the propagation reaction.
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Bicamadas Lipídicas , Fosfolipídeos , Superóxidos , Ubiquinona , Antioxidantes/farmacologia , Radicais Livres , Superóxido Dismutase/farmacologia , UltrassomRESUMO
We investigated the kinetics of mitochondrial ATPase in bovine heart mitochondria and submitochondrial particles upon treatment with phospholipase A2, or upon addition of n-butanol to perturb the lipid protein interactions. The changes observed are the following: (1) Lipid removal or perturbation with butanol is accompanied by loss of ATPase activity with decrease of both V and of the KM for ATP. (2) There are changes of activation energy of ATPase activity at temperatures above the discontinuity normally observed for membrane-bound enzymes in mitochondria. In particular, butanol abolishes the discontinuity, and induces a constant activation energy of about 32 kcal/mol in the range 8--37 degrees C. (3) Butanol modifies the pH dependence of ATPase shifting the pH optimum from around 10 to less alkaline values. The optimum for Mg2+ concentrations is increased by the solvent. (4) Treatment with phospholipase A2 results in a removal of oligomycin-sensitive ATPase, whereas butanol addition prevents oligomycin inhibition of ATPase. (5) In beef heart mitochondria, a spin-labelled analog of the inhibitor, dicyclohexyl carbodiimide, did not show any change in environment upon butanol addition, unlike that found in mitochondria from Saccharomyces cerevisiae.
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Adenosina Trifosfatases/metabolismo , Mitocôndrias Cardíacas/enzimologia , Mitocôndrias/enzimologia , Fosfolipídeos/fisiologia , Partículas Submitocôndricas/enzimologia , Animais , Butanóis/farmacologia , Bovinos , Cinética , Magnésio/farmacologia , Mitocôndrias Cardíacas/efeitos dos fármacos , Oligomicinas/farmacologia , Fosfolipases , Partículas Submitocôndricas/efeitos dos fármacos , TermodinâmicaRESUMO
The aim of this study was to investigate oxidative cell injury in rat thymocytes under conditions of radical generation exterior to the cell utilizing the thermolabile azocompound 2,2'-azobis(2-amidinopropane) dihydrochloride to generate peroxyl radicals at a constant and reproducible rate. This initiator, being water-soluble and endowed with a positive charge, is suitable for studies on oxidative damage of biomembranes induced in the external water environment. The relationship between cell viability, lipid and thiol oxidation and chain-breaking antioxidant depletion was studied. During the first hour of treatment cell viability decreased slightly, protein sulfhydryl groups were consumed slowly and no significant production of conjugated dienes occurred. After 90 min of incubation, when thymocyte permeability started to increase, the concentration of alpha-tocopherol decreased gradually, significant changes of polyunsaturated fatty acids occurred and a rapid phase of thio oxidation commenced. It can be concluded that, under conditions of an exogenous oxidant challenge, initially the cell membrane provides a physical barrier to the entrance of radicals to the thymocyte. When peroxyl radicals gain access to the membrane and the molecular barrier begins to disorganize, the oxidizable cellular components become susceptible to massive attack.
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Peróxidos/toxicidade , Linfócitos T/citologia , Timo/citologia , Amidinas/metabolismo , Animais , Antioxidantes/metabolismo , Sobrevivência Celular , Peroxidação de Lipídeos , Masculino , Oxirredução , Ratos , Ratos Wistar , Compostos de Sulfidrila/metabolismo , Linfócitos T/efeitos dos fármacos , Timo/efeitos dos fármacos , Vitamina E/metabolismoRESUMO
Modern Critical Care aims at improving patient-centered outcomes, not limited to survival. Recently, along with traditional research evaluating single drugs or procedures, more elusive elements have been evaluated, like organizational and teamwork aspects, delivery of critical care before Intensive Care Unit (ICU) admission and after discharge. The aim of this review is to offer an up-to-date, comprehensive, and maybe "visionary" big picture of Critical Care in the near future beyond its traditional boundaries. In particular, we wish to suggest key elements that will allow a leap forward in terms of quality of care. Patient-centeredness will be the main issue, taking the patient's wishes into account more than in the past. This means improving communication with patients and their relatives, and pursuing a holistic approach: we should pay more attention to natural light, noise reduction, music, prevention of sleep fragmentation, soft colors for walls, privacy, psychological support. An open visiting policy should be the standard. End-of-Life practices should become centered on patient wishes and dignity. Rapid response teams will bring timely critical care services to patients outside ICUs, preventing avoidable adverse events and unplanned ICU admission. In ICU, standardized protocols, checklists, daily goals sheets, advanced information technology and multidisciplinary rounds will improve quality of care and safety. Multicenter studies will be made easier and research should become part of daily practice in most ICU. Finally, the post ICU syndrome should be prevented and treated by a well-designed longitudinal care model taking care of patients from the ICU to the outpatient setting.
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Previous reports have shown that vitamin B(6)deficiency leads to peroxidative stress in rat organs. In this paper, we evaluated the effects on lipid peroxidation of short-term (six weeks) dietary administration of marginal contents of vitamin B(6). A further risk factor of susceptibility to peroxidation was the presence of fish oil with higher contents of n-3 polyunsaturated fatty acid (LCPUFA). The contemporaneous vitamin B(6)deficiency and presence of fish oil caused a C18:2 increase, a C20:4 decrease, and replacement of some n-6 LCPUFA with n-3 LCPUFA, without changes in the unsaturation index. In liver, TBARS production did not show any differences between dietary conditions, whereas the activities of glutathione-dependent enzymes were stimulated. In heart, fish oil increased lipid peroxidation, especially in the vitamin B(6)-deficient group.
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Antioxidantes/farmacologia , Dieta , Óleos de Peixe/farmacologia , Metabolismo dos Lipídeos , Piridoxina/farmacologia , Animais , Ácidos Graxos/metabolismo , Ácidos Graxos Insaturados/farmacologia , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Peroxidação de Lipídeos , Fígado/metabolismo , Masculino , Miocárdio/metabolismo , Óleos de Plantas/farmacologia , Ratos , Ratos Wistar , Substâncias Reativas com Ácido Tiobarbitúrico , Vitamina E/metabolismoRESUMO
Delta-6-desaturase (D6D) activity is influenced by many nutritional and non-nutritional factors, among which one of the most important is aging. D6D activity could be susceptible to the dual influence of aging itself and of nutritional deficiencies, due to the reduced intake and/or absorption of essential nutrients. Particularly, vitamin B6 deficiency might be a crucial factor for D6D activity in aged people. Using 20 month old Sprague-Dawley rats fed a diet with a subnormal level of vitamin B6, we evaluated D6D activity for linoleic acid (LA) and alpha-linolenic acid (ALA) in liver microsomes, and the fatty acid composition of microsomal total lipids. We observed a diminished D6D activity for LA and also for ALA in vitamin B6-deficient animals, being approximately 63% and 81% respectively of the corresponding activity in control rats. As a consequence, significant modifications in the relative molar content of microsomal fatty acids were observed. The content of arachidonic and docosahexaenoic acid, the main products of the conversion of LA and ALA respectively, decreased, LA content increased and a decrease in the unsaturation index was observed in liver microsomes of B6-deficient rats. The foregoing results suggest that the impairment of D6D activity by vitamin B6 deficiency might be an important factor in decreasing the synthesis of n-6 and n-3 PUFAs. This may be particularly important in aging, where D6D activity is already impaired.
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Envelhecimento/fisiologia , Ácidos Graxos Dessaturases/fisiologia , Ácidos Graxos/metabolismo , Microssomos Hepáticos/metabolismo , Deficiência de Vitamina B 6/metabolismo , Animais , Dieta , Linoleoil-CoA Desaturase , Fígado/metabolismo , Masculino , Proteolipídeos/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
To define the molecular mechanism(s) of resveratrol inhibition of lipid peroxidation we have utilized model systems that allow us to study the different reactions involved in this complex process. Resveratrol proved (a) to inhibit more efficiently than either Trolox or ascorbate the Fe2+ catalyzed lipid hydroperoxide-dependent peroxidation of sonicated phosphatidylcholine liposomes; (b) to be less effective than Trolox in inhibiting lipid peroxidation initiated by the water soluble AAPH peroxyl radicals; (c) when exogenously added to liposomes, to be more potent than alpha-tocopherol and Trolox, in the inhibition of peroxidation initiated by the lipid soluble AMVN peroxyl radicals; (d) when incorporated within liposomes, to be a less potent chain-breaking antioxidant than alpha-tocopherol; (e) to be a weaker antiradical than alpha-tocopherol in the reduction of the stable radical DPPH*. Resveratrol reduced Fe3+ but its reduction rate was much slower than that observed in the presence of either ascorbate or Trolox. However, at the concentration inhibiting iron catalyzed lipid peroxidation, resveratrol did not significantly reduce Fe3+, contrary to ascorbate. In their complex, our data indicate that resveratrol inhibits lipid peroxidation mainly by scavenging lipid peroxyl radicals within the membrane, like alpha-tocopherol. Although it is less effective, its capacity of spontaneously entering the lipid environment confers on it great antioxidant potential.
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Antioxidantes/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Picratos , Estilbenos/farmacologia , Ácido Ascórbico/farmacologia , Bepridil/análogos & derivados , Bepridil/metabolismo , Compostos de Bifenilo , Cromanos/farmacologia , Sequestradores de Radicais Livres/farmacologia , Radicais Livres/metabolismo , Técnicas In Vitro , Ferro/metabolismo , Lipossomos , Resveratrol , Vitamina E/farmacologiaRESUMO
In an experimental system where both Fe2+ autoxidation and generation of reactive oxygen species is negligible, the effect of FeCl2 and FeCl3 on the peroxidation of phosphatidylcholine (PC) liposomes containing different amounts of lipid hydroperoxides (LOOH) was studied; Fe2+ oxidation, oxygen consumption and oxidation index of the liposomes were measured. No peroxidation was observed at variable FeCl2/FeCl3 ratio when PC liposomes deprived of LOOH by triphenylphosphine treatment were utilized. By contrast, LOOH containing liposomes were peroxidized by FeCl2. The FeCl2 concentration at which Fe2+ oxidation was maximal, defined as critical Fe2+ concentration [Fe2+]*, depended on the LOOH concentration and not on the amount of PC liposomes in the assay. The LOOH-dependent lipid peroxidation was stimulated by FeCl3 addition; the oxidized form of the metal increased the average length of radical chains, shifted to higher values the [Fe2+]* and shortened the latent period. The iron chelator KSCN exerted effects opposite to those exerted by FeCl3 addition. The experimental data obtained indicate the kinetics of LOOH-dependent lipid peroxidation depends on the Fe2+/Fe3+ ratio at each moment during the time course of lipid peroxidation. The results confirm that exogenously added FeCl3 does not affect the LOOH-independent but the LOOH-dependent lipid peroxidation; and suggest that the Fe3+ endogenously generated exerts a major role in the control of the LOOH-dependent lipid peroxidation.
Assuntos
Compostos Férricos/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Peróxidos Lipídicos/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Catálise , Lipossomos , Consumo de Oxigênio/efeitos dos fármacos , Estimulação QuímicaRESUMO
With a view to determining the antioxidant effectiveness of ubiquinol, the autoxidation of egg phosphatidylcholine initiated by an azocompound was studied both in homogeneous solution and in liposomes, either in the presence or in the absence of ubiquinol-3. The results show that ubiquinol behaves as a chain-breaking antioxidant by trapping lipid peroxyl radicals, its inhibition rate constant being about one half of that of alpha-tocopherol in both systems under investigation. In organic solvents the stoichiometric factor was found approx. 2 and in liposomes approx. 0.5, i.e. one fourth of that of alpha-tocopherol. We suggest that the lower value found in model membranes is due to autoxidation of the quinol itself by a radical chain reaction taking place at the polar interface. Ubiquinol-3 exhibits a sparing effect toward alpha-tocopherol, both in liposomes and in tert-butanol. It is suggested, on a thermodynamic basis, that the regeneration of vitamin E from the corresponding radical is more likely to occur by reaction with the ubisemiquinone rather than with the ubiquinol. Although these results, obtained in in vitro systems, can not be directly extrapolated to an in vivo system, they may be useful to clarify the antioxidant role of ubiquinol in biomembranes.
Assuntos
Antioxidantes/farmacologia , Ubiquinona/análogos & derivados , Sequestradores de Radicais Livres , Técnicas In Vitro , Peroxidação de Lipídeos/efeitos dos fármacos , Lipossomos , Soluções , Ubiquinona/farmacologia , Vitamina ERESUMO
Primary pancreatic lymphoma (PPL) is a rare form of extranodal lymphoma (less than 0.5% of pancreatic tumors) originating from the pancreatic parenchyma. Histopathological examination is usually mandatory to obtain a definitive diagnosis since symptoms and radiological features are quite similar to those of other pancreatic masses. Percutaneous fine-needle aspiration (FNA) of the pancreas requires experienced cytopathologists as well as advanced immunohistochemical assays to obtain a final diagnosis on a small amount of tissue. A 46-year-old man complaining of watery diarrhea and severe weight loss (more than 20 kg) for more than 1 year was admitted to our hospital due to severe diabetic crisis. Enlarged lymph nodes (2.5 x 1 cm) were found at the right axillary stations. Abdominal ultrasound revealed the presence of a large hyperechogenic mass, mainly located at the pancreatic head. Abdominal computed tomography scan confirmed a diffuse enlargement of the head and body of the pancreas associated with lymphadenopathy along the lesser gastric curvature. Percutaneous ultrasound-guided FNA of the pancreas as well as gross biopsy of the axillary lymph nodes were unable to identify the nature of the mass. Diagnostic laparoscopy was performed: several enlarged lymph nodes along the lesser gastric curvature were revealed. Multiple biopsies of the pancreatic head were taken and lymphadenectomy along the lesser curvature and the hepatic hilus was also performed. The definitive histopathological examination of the pancreatic specimen revealed a primary low-grade non-Hodgkin B cell pancreatic lymphoma. The postoperative course was unremarkable; the patient underwent systemic chemotherapy regime for low-grade B cell Hodgkin lymphoma and he was symptom free at 9-month follow-up.