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1.
Langenbecks Arch Surg ; 400(4): 463-9, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25682056

RESUMO

BACKGROUND: The benefit of thromboembolism prophylaxis in cholecystectomy is controversial. This population-based study report on the incidence of and risk factors for symptomatic venous thromboembolism (VTE) after cholecystectomy. METHOD: All cholecystectomies registered in the Swedish Register of Gallstone Surgery and Endoscopic Retrograde Cholangiopancreatography (GallRiks) between 2006 and 2011 were reviewed. By linking patient data to the Swedish National Patient Register (NPR), the 30-day postoperative incidence of VTE (deep venous thrombosis [DVT] and/or pulmonary embolism [PE]) was identified. Age- and gender-standardized incidence ratio (SIR) for deep venous thrombosis (DVT) and pulmonary embolism (PE) were calculated. Multivariable analysis determined risk factors for VTE by calculating odds ratio (OR). RESULTS: Altogether 62,488 procedures were registered and postoperative VTE was seen in 154 (0.25%) patients. DVT was seen in 36 (0.06%) patients and PE in 25 (0.04%) patients within 30 days after surgery. The SIR for DVT was 22.2 (95% confidence interval (CI) 13.1-31.3) and for PE 5.6 (95% CI 2.3-8.9). Risk factors for VTE within 30 days after cholecystectomy were age >70 years (odds ratio [OR] = 2.69; 95% confidence interval [CI] 1.68-4.30), open cholecystectomy (OR = 1.95; CI 1.31-2.92), operation time >120 min (OR = 1.66; CI 1.18-2.35), acute cholecystitis (OR = 1.69; CI 1.18-2.42), and previous history of VTE (OR = 50.5; CI 27.3-92.8). Thromboembolism prophylaxis (TP) increased the risk for postoperative bleeding (OR = 1.72; 1.44-2.05). CONCLUSION: The incidence of VTE after cholecystectomy is low and thromboembolism prophylaxis (TP) increases the risk for postoperative bleeding. Patients with previous VTE events should be given TP when undergoing cholecystectomy.


Assuntos
Colecistectomia , Embolia Pulmonar/epidemiologia , Tromboembolia Venosa/epidemiologia , Trombose Venosa/epidemiologia , Humanos , Incidência , Análise Multivariada , Sistema de Registros , Medição de Risco , Fatores de Risco
2.
World J Surg ; 39(6): 1413-20, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25665674

RESUMO

INTRODUCTION: The postoperative installation of isotonic saline in the abdomen has been suggested as a method to reduce the effect of local toxins, thereby reducing postoperative pain in patients undergoing laparoscopic surgery. The aim of this randomized prospective double-blind trial was to assess whether installation of isotonic saline can reduce postoperative pain and nausea following laparoscopic cholecystectomy (LC). METHODS: Altogether 71 LC patients were randomized to either intra-abdominal instillation of isotonic saline group (S) (n = 36) or no saline (NS) group (n = 35) at the end of surgery. Data were collected by means of questionnaires. The postoperative recovery profile questionnaire was answered prior to surgery and 1 week postoperatively, SF-36 prior to surgery and at 1 month postoperatively, and a pain diary recording a Visual Analogue Scale score each day during the first week. RESULTS: The overall response rate was 94%. No significant differences were seen between the groups regarding abdominal and shoulder pain. However, the NS group reported more pain (NS = 53 %, S = 29 %) and fatigue (NS = 50%, S = 35%) than the S group postoperative day 7. Moreover, the most frequently reported problem in both groups 7 days after surgery was getting back to normal life (60%). Females reported a slower recovery profile than males and also more postoperative symptoms day 7. HRQoL results were similar between the groups. CONCLUSION: Instillation of isotonic saline does not improve recovery after laparoscopic cholecystectomy. Postoperative pain was more often reported in the NS group than in the S group, though the difference was not significant.


Assuntos
Colecistectomia Laparoscópica/efeitos adversos , Dor Pós-Operatória/prevenção & controle , Cloreto de Sódio/administração & dosagem , Abdome , Dor Abdominal/etiologia , Dor Abdominal/prevenção & controle , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Instilação de Medicamentos , Soluções Isotônicas/administração & dosagem , Masculino , Pessoa de Meia-Idade , Náusea/etiologia , Náusea/prevenção & controle , Dor Pós-Operatória/etiologia , Estudos Prospectivos , Qualidade de Vida , Fatores Sexuais , Dor de Ombro/etiologia , Dor de Ombro/prevenção & controle , Fatores de Tempo
3.
Pancreatology ; 11(5): 464-8, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21968430

RESUMO

BACKGROUND: The Harmless Acute Pancreatitis Score (HAPS) is a scoring algorithm to identify patients with nonsevere acute pancreatitis. The aim of this study was to evaluate the reproducibility of HAPS outside its original study setting. METHOD: Baseline information of all hospitalized patients with acute pancreatitis at Karolinska University Hospital, Stockholm, Sweden, between 2004 and 2009 was collected. The parameters constituting HAPS were signs of peritonitis, hematocrit and serum creatinine levels. Since hematocrit was not available in all patients, complete sample analysis was performed by replacing hematocrit with hemoglobin (strongly correlated with hematocrit; r = 0.86). RESULTS: In total, 531 patients with a first-time or a recurrent attack of acute pancreatitis were included. Among 353 patients with complete information on parameters constituting HAPS, 79 patients were predicted to have a nonsevere course, of whom 1 patient developed severe acute pancreatitis. The specificity of HAPS in predicting a nonsevere course of acute pancreatitis was 96.3% (95% CI: 81.0-99.9) with a corresponding positive predictive value of 98.7% (95% CI: 93.1-100). Complete sample analysis replacing hematocrit with hemoglobin level predicted a nonsevere course in 182 patients, of whom 2 patients had severe acute pancreatitis (94.3% specificity and 98.9% positive predictive value). CONCLUSION: HAPS is a highly specific scoring algorithm that predicts a nonsevere course of acute pancreatitis. Therefore, HAPS might be an additional tool in the clinical assessment of acute pancreatitis where early screening is important to treat the patients at an optimal level of care.


Assuntos
Pancreatite/diagnóstico , APACHE , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Creatinina/sangue , Feminino , Hematócrito , Hemoglobinas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Peritonite/diagnóstico , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Suécia
4.
J Intern Med ; 269(4): 410-9, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21054584

RESUMO

OBJECTIVES: Low-grade systemic inflammation, oxidative stress and peripheral insulin resistance are intimately associated and contribute to the increased risk of cardiovascular complications in advanced chronic kidney disease (CKD). Because altered adipose tissue activities have previously been linked to pathophysiological processes in various inflammatory and metabolic diseases we hypothesized that the uraemic milieu in patients with CKD may interact with the adipose tissue, provoking an unfavourable shift in its transcriptional output. DESIGN: Twenty-one adipokine mRNAs were quantified in abdominal subcutaneous adipose tissue (SAT) biopsies and serum/plasma concentrations of inflammatory markers and related protein products were measured. SETTING: The study was conducted at the Karolinska University Hospital, Huddinge, and Karolinska Institutet, Stockholm, Sweden. SUBJECTS: Thirty-seven patients with CKD [15 women, median 58 (interquartile range 49-65) years] and nine nonuraemic individuals [four women, age 62 (45-64) years] were recruited prior to initiation of peritoneal dialysis catheter insertion or elective hernia repair/laparoscopic cholecystectomy, respectively. RESULTS: Even after correction for body mass index, SAT from patients showed a significant upregulation of inflammatory pathway genes interleukin 6 (3.0-fold, P=0.0002) and suppressor of cytokine signalling 3 (2.5-fold, P=0.01), as well as downregulation of leptin (2.0-fold, P=0.03) and the oxidative stress genes uncoupling protein 2 (1.5-fold, P=0.03) and cytochrome b-245, alpha polypeptide (1.5-fold, P=0.005), in relation to controls. CONCLUSIONS: These gene expression differences suggest that inflammatory and oxidative stress activities may be important features of the intrinsic properties of uraemic adipose tissue, which may have significant effects on the uraemic phenotype.


Assuntos
Mediadores da Inflamação/metabolismo , Falência Renal Crônica/metabolismo , Gordura Subcutânea/metabolismo , Adipocinas/biossíntese , Adipocinas/genética , Adulto , Idoso , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Regulação da Expressão Gênica , Humanos , Inflamação/etiologia , Inflamação/metabolismo , Resistência à Insulina/genética , Falência Renal Crônica/complicações , Falência Renal Crônica/genética , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/genética , RNA Mensageiro/genética
5.
Acta Anaesthesiol Scand ; 50(6): 699-705, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17004330

RESUMO

BACKGROUND: After an ischemia time of 1 h during aortic aneurysm surgery, muscle glutathione redox-status is not altered, indicating that this ischemic insult is well within the scavenging capacity of muscle glutathione, the most important endogenous scavenger. In the present study, the impact of elective aorto-bifemoral bypass surgery, involving a longer ischemia time, on muscle glutathione and its redox-status was investigated. METHODS: Leg muscle biopsies were obtained pre-operatively, at maximal ischemia, after 10 min and 24 h of reperfusion from 12 patients undergoing aorto-bifemoral bypass surgery. Muscle glutathione, free amino acids and energy-rich compounds were determined. RESULTS: Clamping times were 113 (99-120 min); median (quartiles). At maximal ischemia, muscle lactate increased by 7.5 (4.0-10.7) mmol/kg dry weight (dw) (P < 0.001) and phosphocreatine (PCr) decreased by 14.6 (8.9-23.3) mmol/kg dw (P < 0.001). At maximal ischemia, reduced glutathione (GSH) was unaltered but muscle glutamate decreased by 0.51 (0.30-0.85) mmol/kg wet weight (ww) (P < 0.001). At 24 h post-operatively, the reduced glutathione decreased by 0.47 (0.34-0.65) mmol/kg (ww) (P < 0.001) without changes in oxidized glutathione (GSSG) or in glutathione redox-status. Cysteine and glycine, the two other constituent amino acids to glutathione, did not change during the study period. CONCLUSION: Ischemia of 2 h during aorto-bifemoral bypass was associated with changes in muscle energy-rich compounds but without any changes in glutathione redox-status. A decreased antioxidative capacity, as reflected by a decrease in muscle glutathione concentrations, was seen 24 h post-operatively, still without changes in glutathione redox-status. This is not different from the changes seen after abdominal surgery not involving ischemia-reperfusion.


Assuntos
Glutationa/metabolismo , Isquemia/patologia , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/metabolismo , Procedimentos Cirúrgicos Vasculares , Idoso , Aminoácidos/metabolismo , Anestesia Geral , Metabolismo Energético , Feminino , Humanos , Claudicação Intermitente/etiologia , Ácido Láctico/metabolismo , Perna (Membro)/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Oxirredução , Projetos Piloto , Estudos Prospectivos , Fluxo Sanguíneo Regional/fisiologia , Reperfusão , Compostos de Sulfidrila/metabolismo
6.
Clin Nutr ; 25(2): 260-74, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16698129

RESUMO

Undernutrition as well as specific nutrient deficiencies have been described in patients with Crohn's disease (CD), ulcerative colitis (UC) and short bowel syndrome (SBS). The present guideline gives evidence-based recommendations for the indication, application and type of formula of enteral nutrition (EN) (oral nutritional supplements (ONS) or tube feeding (TF)) in these patients. It was developed in an interdisciplinary consensus-based process in accordance with officially accepted standards and is based on all relevant publications since 1985. ONS and/or TF in addition to normal food is indicated in undernourished patients with CD or CU to improve nutritional status. In active CD EN is the first line therapy in children and should be used as sole therapy in adults mainly when treatment with corticosteroids is not feasible. No significant differences have been shown in the effects of free amino acid, peptide-based and whole protein formulae for TF. In remission ONS is recommended only in steroid dependent patients in CD. In patients with SBS TF should be introduced in the adaptation phase and should be changed with progressing adaptation to ONS in addition to normal food.


Assuntos
Nutrição Enteral/normas , Gastroenterologia/normas , Colite Ulcerativa/terapia , Doença de Crohn/terapia , Europa (Continente) , Humanos , Padrões de Prática Médica , Síndrome do Intestino Curto/terapia
7.
Intensive Care Med ; 31(8): 1072-8, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15999254

RESUMO

OBJECTIVE: This study investigated the temporal changes in whole-blood and plasma glutathione in ICU patients with multiple organ failure. DESIGN AND SETTING: Prospective and descriptive pilot study performed in an ICU with eight beds at a university hospital. PATIENTS: Critically ill patients (n=11) with multiple organ failure and ICU stay of at least 6 days were consecutively included. Patients with chronic obstructive pulmonary disease (n=21) and healthy volunteers (n=10) were used as reference groups. MEASUREMENTS AND RESULTS: Whole-blood and plasma glutathione were measured every 72 h. Total glutathione and the reduced fraction were determined in whole blood. The oxidized fraction and the redox status were calculated from these values. In plasma only the total concentration was determined. Patients were studied for 6-15 days. Nutrition was supplied according to routines supplying basal needs including glutamine. Both total and reduced glutathione was found to be depleted in whole blood compared to the reference groups. Redox status indicated continuing oxidative stress. Plasma glutathione showed higher values in total concentrations than the reference groups. CONCLUSIONS: This study demonstrates that glutathione remains depleted in whole blood. This contrasts to what has previously been shown in skeletal muscle where a restitution of glutathione concentration is seen.


Assuntos
Glutationa/sangue , Insuficiência de Múltiplos Órgãos/sangue , Adulto , Idoso , Cuidados Críticos , Estado Terminal , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Fatores de Tempo
8.
Intensive Care Med ; 29(12): 2193-2198, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14566458

RESUMO

OBJECTIVE: This study investigated the changes over time in glutathione and its constituent amino acids in skeletal muscle of ICU patients with multiple organ failure. DESIGN AND SETTING: Prospective and descriptive pilot study in two medium-sized ICUs with ten beds. PATIENTS: Critically ill patients ( n=10) with multiple organ failure and with an expected ICU stay longer than 6 days were included during their initial 3 days after admission to the ICU. MEASUREMENTS AND RESULTS: Muscle biopsy and blood samples were taken on days 0, 3, and 6 after inclusion and total, reduced, and oxidized glutathione and the related amino acids were determined. During the study period both total and reduced glutathione increased and was in the normal range on day 6. The constituent amino acids normalized during the study period as well. CONCLUSIONS: This pilot study demonstrates a recovery of muscle glutathione concentrations in critically ill patients with ongoing multiple organ failure within 1 week. Restoration of muscle glutathione seems to be a biological process of high priority in this group of patients.


Assuntos
Glutationa/metabolismo , Insuficiência de Múltiplos Órgãos/metabolismo , Músculo Esquelético/metabolismo , APACHE , Idoso , Aminoácidos/sangue , Aminoácidos/metabolismo , Cromatografia Líquida de Alta Pressão , Feminino , Glutationa/isolamento & purificação , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/sangue , Oxirredução , Projetos Piloto
9.
Clin Sci (Lond) ; 104(3): 275-82, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12605586

RESUMO

Glutathione is quantitatively the most important endogenous scavenger system. Glutathione depletion in skeletal muscle is pronounced following major trauma and sepsis in intensive care unit patients. Also, following elective surgery, glutathione depletion occurs in parallel with a progressive decline in muscle glutamine concentration. The present study was designed to test the hypothesis that glutamine supplementation may counteract glutathione depletion in a human trauma model. A homogeneous group of patients (n = 17) undergoing a standardized surgical procedure were prospectively randomly allocated to receive glutamine (0.56 g x day(-1) x kg(-1)) or placebo as part of isonitrogenous and isocaloric nutrition. Percutaneous muscle biopsies and blood samples were taken pre-operatively and at 24 and 72 h after surgery. The concentrations of muscle glutathione and related amino acids were determined in muscle tissue and plasma. In the control (unsupplemented) subjects, total muscle glutathione had decreased by 47+/-8% and 37+/-11% and reduced glutathione had decreased by 53+/-10% and 45+/-16% respectively at 24 and 72 h after surgery (P < 0.05). In contrast, in the glutamine-supplemented group, no significant post-operative decreases in total or reduced glutathione were seen following surgery. Muscle free glutamine had decreased at 72 h after surgery in both groups, by 41.4+/-14.8% (P < 0.05) in the glutamine-supplemented group and by 46.0+/-14.3% (P < 0.05) in the control group. In conclusion, the present study demonstrates that intravenous glutamine supplementation attenuates glutathione depletion in skeletal muscle in humans following standardized surgical trauma.


Assuntos
Glutamina/uso terapêutico , Glutationa/metabolismo , Músculo Esquelético/metabolismo , Nutrição Parenteral Total/métodos , Cuidados Pós-Operatórios/métodos , Idoso , Aminoácidos/sangue , Aminoácidos/metabolismo , Biópsia , Método Duplo-Cego , Feminino , Glutamina/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Estudos Prospectivos , Neoplasias Retais/cirurgia
10.
Anesth Analg ; 93(5): 1344-50, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11682427

RESUMO

UNLABELLED: We studied the effects of different preoperative oral fluid protocols on preoperative discomfort, residual gastric fluid volumes, and gastric acidity. Two-hundred-fifty-two elective abdominal surgery patients (ASA physical status I-II) were randomized to preparation with a 12.5% carbohydrate drink (CHO), placebo (flavored water), or overnight fasting. The CHO and Placebo groups were double-blinded and were given 800 mL to drink on the evening before and 400 mL on the morning of surgery. Visual analog scales were used to score 11 different discomfort variables. CHO did not increase gastric fluid volumes or affect acidity, and there were no adverse events. The visual analog scale scores in a control situation were not different between groups. During the waiting period before surgery, the CHO-treated group was less hungry and less anxious than both the other groups (P < or = 0.05). CHO reduced thirst as effectively as placebo (P < 0.0001 versus Fasted). Trend analysis showed consistently decreasing thirst, hunger, anxiety, malaise, and unfitness in the CHO group (P < 0.05). The Placebo group experienced decreasing unfitness and malaise, whereas nausea, tiredness, and inability to concentrate increased (P < 0.05). In the Fasted group, hunger, thirst, tiredness, weakness, and inability to concentrate increased (P < 0.05). In conclusion, CHO significantly reduces preoperative discomfort without adversely affecting gastric contents. IMPLICATIONS: Discomfort during the period of waiting before elective surgery can be reduced if patients are prepared with a carbohydrate-rich drink, compared with preoperative oral intake of water or overnight fasting. Visual analog scales can provide useful information about preoperative discomfort in elective surgery patients.


Assuntos
Carboidratos da Dieta/administração & dosagem , Cuidados Pré-Operatórios/métodos , Adulto , Idoso , Colecistectomia Laparoscópica , Método Duplo-Cego , Procedimentos Cirúrgicos Eletivos , Jejum , Feminino , Ácido Gástrico/metabolismo , Mucosa Gástrica/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Masculino , Pessoa de Meia-Idade , Medição da Dor/efeitos dos fármacos , Placebos
12.
Surgery ; 129(5): 576-86, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11331450

RESUMO

BACKGROUND: Muscle protein catabolism, reflected by a decrease in glutamine (GLN), a decrease in muscle protein synthesis, and a negative nitrogen balance can be reduced by either administration of GLN or growth hormone (GH). In this study, the effects of a combination of GH and GLH were studied. METHODS: Patients (n = 16) undergoing abdominal operation were given total parenteral nutrition (TPN) containing either GLN alone or GLN together with GH (GH/GLN) during 3 postoperative days. The amino acid concentration and protein synthesis in muscle tissue and the nitrogen balance were measured. RESULTS: GH/GLN reduced nitrogen losses compared with GLN alone (-5.8 +/- 1.4 g nitrogen versus -10.6 +/- 1.1 g nitrogen, P <.05). GH/GLN maintained muscle GLN at preoperative levels compared with a 47.5% +/- 6.3% decline in the GLN group. A similar decrease was seen in the fractional synthesis rate of muscle protein postoperatively in both groups. CONCLUSIONS: GH has an additive effect given together with GLN on muscle amino acid metabolism, preventing the decrease in the GLN concentration in skeletal muscle and diminishing the loss of whole body nitrogen. However, the improvements in muscle amino acid concentrations and nitrogen loss were not associated with differences between the groups in muscle protein synthesis postoperatively.


Assuntos
Abdome/cirurgia , Glutamina/farmacocinética , Hormônio do Crescimento Humano/administração & dosagem , Músculo Esquelético/metabolismo , Nitrogênio/metabolismo , Nutrição Parenteral Total , Idoso , Nitrogênio da Ureia Sanguínea , Feminino , Ácido Glutâmico/sangue , Glutamina/administração & dosagem , Glutamina/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Musculares/biossíntese , Proteínas Musculares/metabolismo , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos
13.
Clin Physiol ; 21(1): 44-50, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11168296

RESUMO

Eight healthy volunteers were given an infusion containing cortisol, glucagon and adrenaline during 6 h. Muscle biopsies were taken before and at 6, 12 and 24 h. During the infusion serum cortisol, glucagon, glucose and insulin were increased. The stress hormone infusion induced characteristic changes in the muscle and plasma amino acid patterns similar to those seen early in protein catabolism. Muscle glutamine decreased at 12 and 24 h by -18.2 +/- 3.8 and -28.8 +/- 4.8%, respectively. The branched chain amino acids decreased at 6 h by -54.6 +/- 4.2% while increased levels (by 54.7 +/- 13.1%) were seen at 24 h. Plasma amino acids decreased during the infusion period and returned to basal during the postinfusion period. Despite a short-term infusion during 6 h the muscle amino acid pattern was still affected at 12 and 24 h and some of the changes were more accentuated at those timepoints as compared with the changes seen at 6 h.


Assuntos
Aminoácidos/sangue , Anti-Inflamatórios/administração & dosagem , Epinefrina/administração & dosagem , Hidrocortisona/administração & dosagem , Músculo Esquelético/metabolismo , Estresse Fisiológico/metabolismo , Simpatomiméticos/administração & dosagem , Adulto , Anti-Inflamatórios/sangue , Glicemia , Epinefrina/sangue , Glucagon/administração & dosagem , Glucagon/sangue , Humanos , Hidrocortisona/sangue , Insulina/sangue , Masculino , Simpatomiméticos/sangue
14.
Proc Nutr Soc ; 58(3): 677-80, 1999 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10604202

RESUMO

Muscle tissue serves as a protein reservoir which is mobilized to meet the specific metabolic needs associated with various catabolic conditions in human subjects, such as trauma and critical illness. Glutathione is one of the most abundant short-chain peptides and a major source of non-protein thiol in the body, and tissue glutathione concentration is related to its oxidative capacity. Skeletal muscle is relatively unique with respect to a variety of metabolic properties, such as oxidative potential, patterns of amino acid utilization, and antioxidant enzyme activity. The glutathione concentration is not influenced by food intake, or by food deprivation. Moreover, there is no diurnal variation on muscle glutathione levels. Following elective surgery the muscle concentration of GSH (the reduced form) decreases by 40% 24 h post-operatively, while the concentration of GSSG (the oxidized form) remains unaltered. During critical illness a similar decrease in the GSH concentration is seen, but in addition a change in the redox status indicative of an elevated GSSG level occurs. Furthermore, correlations between the concentrations of glutamine as well as glutamate and GSH exist in these patients. From available evidence accumulated it is clear that glutathione plays a pivotal role in the maintenance of the intracellular redox status, the antioxidant vitamin levels, and the antioxidant enzyme functions under various metabolic conditions. The effectiveness of glutathione protection in the individual tissue depends on the tissue concentration of glutathione as well as the capacity of the tissue to import GSH and to export GSSG. The mechanisms by which catabolism regulates tissue glutathione levels and the enzyme activities associated with the gamma-glutamyl cycle are not completely understood and further studies need to be conducted.


Assuntos
Antioxidantes/farmacologia , Estado Terminal , Glutationa/metabolismo , Estado Nutricional , Glutamina/metabolismo , Humanos , Músculo Esquelético/metabolismo , Oxirredução
15.
Int J Colorectal Dis ; 14(3): 137-42, 1999 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10460903

RESUMO

Glutamine is a dispensable amino acid, a fact which is particularly important for intensive care patients, and it can be used as an oxidative substrate in processes which require prompt regulation of quantitatively large flows. The production and transport of glutamine from skeletal muscle may be inadequate in patients under intensive care, hence supplemented nutrition has been suggested. Improved long-term survival has been reported, which makes glutamine treatment one of the very few therapeutic strategies that improves outcome in intensive care. This overview deals with the metabolic and physiologic features and updates the clinical documentation of the field.


Assuntos
Glutamina , Necessidades Nutricionais , Avaliação de Resultados em Cuidados de Saúde , Glutamina/administração & dosagem , Glutamina/metabolismo , Glutamina/farmacologia , Humanos , Unidades de Terapia Intensiva , Mucosa Intestinal/fisiologia , Músculo Esquelético/fisiologia , Análise de Sobrevida
17.
Curr Opin Clin Nutr Metab Care ; 2(6): 487-92, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10678678

RESUMO

Glutathione is quantitatively the most important antioxidant and scavenger. In addition it has a number of important functions in amino acid transport across membranes, in protein synthesis and degradation, in gene regulation and in cellular redox regulation. It becomes more and more evident that depletion of glutathione is associated with states of severe diseases. From this perspective, the possibility of manipulating the availability of glutathione becomes a very attractive form of treatment. In this review, new insights into pathophysiology and the regulation of glutathione metabolism, in addition to effects of precursors to and stimulants of glutathione synthesis, are covered. It is very likely that glutathione precursors will soon be an important pharmacological tool for treatment in a number of diseased states.


Assuntos
Glutationa/metabolismo , Acetilcisteína/administração & dosagem , Acetilcisteína/metabolismo , Animais , Cisteína/administração & dosagem , Cisteína/metabolismo , Glutamina/administração & dosagem , Glutamina/metabolismo , Glutationa/biossíntese , Humanos , Precursores de Proteínas/administração & dosagem , Precursores de Proteínas/metabolismo , Ácido Pirrolidonocarboxílico , Tiazóis/administração & dosagem , Tiazóis/metabolismo , Tiazolidinas
18.
Am J Physiol ; 275(2): E359-65, 1998 08.
Artigo em Inglês | MEDLINE | ID: mdl-9688640

RESUMO

To gain insight into cellular metabolism underlying the glutathione (GSH) alterations induced by surgical trauma, we assessed postoperative skeletal muscle GSH metabolism and its redox status in 10 patients undergoing elective abdominal surgery. Muscle biopsy specimens were taken from the quadriceps femoris muscle before and at 24 and 72 h after surgery. GSH concentrations decreased by 40% at 24 h postoperatively compared with the paired preoperative values (P < 0.001) and remained low at 72 h (P < 0.01). The concentration of GSH disulfide (GSSG) did not significantly change throughout the study period, whereas the total GSH (as GSH equivalent) concentration decreased after surgery. Of the GSH constituent amino acids, the concentration of cysteine remained unchanged throughout the study period (from 28.2 +/- 10.1 preoperatively to 29.4 +/- 13.9 at 24 h postoperatively and to 28.3 +/- 15.6 micromol/kg wet wt at 72 h postoperatively). Despite a reduction in glutamate concentration by 40% 24 h after surgery, no correlation was established between GSH and glutamate concentrations postoperatively. Activity of gamma-glutamylcysteine synthetase did not change significantly after surgery, whereas GSH synthetase activity decreased postoperatively (from 66.4 +/- 19.1 preoperatively to 41.0 +/- 10.5 24 h postoperatively, P < 0.01, and to 46.0 +/- 11.7 microU/mg protein 72 h postoperatively, P < 0.05). The decrease of GSH was correlated to the reduced GSH synthetase activity seen at 24 h postoperatively. These results indicate that the skeletal muscle GSH pool is diminished in patients after surgical trauma. The depletion of the GSH pool is associated with a decreased activity of GSH synthetase, indicating a decreased GSH synthetic capacity in skeletal muscle tissue.


Assuntos
Procedimentos Cirúrgicos Eletivos , Glutationa/metabolismo , Músculo Esquelético/metabolismo , Ferimentos e Lesões/metabolismo , Idoso , Feminino , Glutamato-Cisteína Ligase/metabolismo , Ácido Glutâmico/metabolismo , Dissulfeto de Glutationa/metabolismo , Glutationa Sintase/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Fatores de Tempo
19.
J Clin Endocrinol Metab ; 83(5): 1566-72, 1998 May.
Artigo em Inglês | MEDLINE | ID: mdl-9589657

RESUMO

Acquired GH resistance together with reduced skeletal muscle mass are found in patients with increased protein catabolism due, for example, to sepsis, trauma, or major surgery. Both administration of glutamine-containing parenteral nutrition and GH treatment have been found to diminish this catabolism. The effects of GH are mediated in part by insulin-like growth factor I (IGF-I) that is produced in the liver and locally in GH target tissues. The aim of this study was to investigate the effect of GH treatment on expression of the IGF-I gene and GH receptor (GHR) gene in skeletal muscle after major surgery. A new quantitative RT-PCR-based assay was established to measure IGF-I gene expression. Metabolically healthy patients, without significant preoperative weight loss, who were undergoing elective abdominal surgery were included in the study. Five patients (one woman and four men) were treated with daily injections of GH (0.3 IU/kg.day) in addition to being given total parenteral nutrition including glutamine (0.28 g/kg.day). The control group consisted of eight patients (three women and five men), who were given glutamine-enriched total parenteral nutrition but no GH. A muscle biopsy was taken from the lateral portion of the quadriceps femoris muscle preoperatively (day 0) after induction of anesthesia. A second biopsy was taken under local anesthesia on postoperative day 3. Total ribonucleic acid (RNA) was extracted from the muscle biopsies, and IGF-I messenger RNA (mRNA) and GHR mRNA were measured by competitive quantitative RT-PCR assays. IGF-I mRNA and GHR mRNA levels were related to the expression of a housekeeping gene (cyclophilin). In the control group, IGF-I mRNA levels decreased from 1505 +/- 265 (mean +/- SEM) transcripts/cpm cyclophilin on day 0 to 828 +/- 172 on day 3 (P < 0.05). In contrast, IGF-I mRNA levels did not change in the GH-treated group (1188 +/- 400 transcripts/cpm cyclophilin on day 0 vs. 1089 +/- 342 transcripts/cpm cyclophilin on day 3). No statistically significant changes were seen in GHR expression. We conclude that administration of GH prevents the reduction in IGF-I gene expression in skeletal muscle after abdominal surgery.


Assuntos
Abdome/cirurgia , Expressão Gênica , Hormônio do Crescimento Humano/uso terapêutico , Fator de Crescimento Insulin-Like I/genética , Músculo Esquelético/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biópsia , Proteínas de Transporte/sangue , Feminino , Glutamina/administração & dosagem , Hormônio do Crescimento Humano/administração & dosagem , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/química , Nutrição Parenteral Total , Reação em Cadeia da Polimerase , RNA Mensageiro/análise , DNA Polimerase Dirigida por RNA , Receptores da Somatotropina/genética
20.
Clin Nutr ; 17(5): 205-10, 1998 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10205340

RESUMO

In this descriptive study total parenteral nutrition (TPN) without glutamine was administered over 2 days to patients undergoing laparoscopic cholecystectomy (n = 8) and to volunteers (n = 8). Effects on muscle amino acids and nitrogen economy were studied. Muscle protein synthesis, determined by ribosome and polyribosome concentrations were measured in the patients. In both patients and volunteers the muscle amino acid patterns indicated muscle protein catabolism. Decreases in glutamine were seen in both groups (21.8 +/- 4.6% in patients and 17.5 +/- 5.4% in the volunteers). In both groups a negative nitrogen balance was seen (-4.1 +/- 1.2 gram and -10.3 +/- 2.4 gram respectively). The patients also showed decreased ribosome (by 13.7 +/- 4.5%) and polyribosome concentration (by 17.4 +/- 4.6%), indicating a decrease in muscle protein synthesis. No comparisons are made between the two groups since they are not comparable. However, it is concluded in these two descriptive studies, that during these conditions, TPN does not prevent muscle protein catabolism either during basal conditions or after a minor surgical trauma such as laparoscopic cholecystectomy.


Assuntos
Aminoácidos/metabolismo , Colecistectomia , Laparoscopia , Músculo Esquelético/metabolismo , Nitrogênio/metabolismo , Nutrição Parenteral Total , Aminoácidos/sangue , Feminino , Glutamina/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Musculares/biossíntese , Proteínas Musculares/metabolismo , Ribossomos/metabolismo
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