Protein metabolism and gene expression in skeletal muscle of critically ill patients with sepsis

2011 ◽  
Vol 122 (3) ◽  
pp. 133-142 ◽  
Author(s):  
Maria Klaude ◽  
Maiko Mori ◽  
Inga Tjäder ◽  
Thomas Gustafsson ◽  
Jan Wernerman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Degradation ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Proteolytic Enzyme ◽  
Muscle Wasting ◽  
Muscle Protein ◽  
Synthesis Rate ◽  
Normal Muscle ◽  
Enzyme Systems

Muscle wasting negatively affects morbidity and mortality in critically ill patients. This progressive wasting is accompanied by, in general, a normal muscle PS (protein synthesis) rate. In the present study, we investigated whether muscle protein degradation is increased in critically ill patients with sepsis and which proteolytic enzyme systems are involved in this degradation. Eight patients and seven healthy volunteers were studied. In vivo muscle protein kinetics was measured using arteriovenous balance techniques with stable isotope tracers. The activities of the major proteolytic enzyme systems were analysed in combination with mRNA expression of genes related to these proteolytic systems. Results show that critically ill patients with sepsis have a variable but normal muscle PS rate, whereas protein degradation rates are dramatically increased (up to 160%). Of the major proteolytic enzyme systems both the proteasome and the lysosomal systems had higher activities in the patients, whereas calpain and caspase activities were not changed. Gene expression of several genes related to the proteasome system was increased in the patients. mRNA levels of the two main lysosomal enzymes (cathepsin B and L) were not changed but, conversely, genes related to calpain and caspase had a higher expression in the muscles of the patients. In conclusion, the dramatic muscle wasting seen in critically ill patients with sepsis is due to increased protein degradation. This is facilitated by increased activities of both the proteasome and lysosomal proteolytic systems.

scholarly journals Protein delivery in intermittent and continuous enteral nutrition with a protein-rich formula in critically ill patients - A protocol for the prospective randomised controlled proof-of-concept Protein Bolus Nutrition (Pro BoNo) study

2020 ◽  
Author(s):  
Simona Reinhold ◽  
Désirée Yeginsoy ◽  
Alexa Hollinger ◽  
Atanas Todorov ◽  
Lionel Tintignac ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Critically Ill ◽  
Enteral Feeding ◽  
Critically Ill Patients ◽  
Muscle Wasting ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Secondary Outcome ◽  
Pro Bono ◽  
Randomised Controlled

Abstract Background Critically ill patients rapidly develop muscle wasting resulting in sarcopenia, long-term disability and higher mortality. Bolus nutrition (30-60 min period), while having a similar incidence of aspiration as continuous feeding, seems to provide metabolic benefits through increased muscle protein synthesis due to higher leucine peaks. To date, clinical evidence on achievement of nutritional goals and influence of bolus nutrition on skeletal muscle metabolism in ICU patients is lacking. The aim of the Pro BoNo study (Protein Bolus Nutrition) is to compare intermittent and continuous enteral feeding with a specific high-protein formula. We hypothesise that target quantity of protein is reached earlier (within 36 hours) by an intermittent feeding protocol with a favourable influence on muscle protein synthesis.Methods Pro BoNo is a prospective randomised controlled study aiming to compare the impact of intermittent and continuous enteral feeding on preventing muscle wasting in 60 critically ill patients recruited during the first 48 hours after ICU admission. The primary outcome measure is the time until the daily protein target (≥1.5 g protein/kg bodyweight/24h) is achieved. Secondary outcome measures include tolerance of enteral feeding and evolution of glucose, urea and IGF-1. Ultrasound and muscle biopsy of the quadriceps will be performed.Discussion The Basel Pro BoNo study aims to collect innovative data on the effect of intermittent enteral feeding of critically ill patients on muscle wasting.Trial registration ClinicalTrials.gov Identifier: NCT03587870, registered July 16, 2018. Swiss National Clinical Trial Portal identifier: SNCTP000003234, last updated July 24, 2019.

scholarly journals Protein delivery in intermittent and continuous enteral nutrition with a protein-rich formula in critically ill patients - A protocol for the prospective randomised controlled proof-of-concept Protein Bolus Nutrition (Pro BoNo) study

2020 ◽  
Author(s):  
Simona Reinhold ◽  
Désirée Yeginsoy ◽  
Alexa Hollinger ◽  
Atanas Todorov ◽  
Lionel Tintignac ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Critically Ill ◽  
Enteral Feeding ◽  
Critically Ill Patients ◽  
Muscle Wasting ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Secondary Outcome ◽  
Pro Bono ◽  
Randomised Controlled

Abstract Background Critically ill patients rapidly develop muscle wasting resulting in sarcopenia, long-term disability and higher mortality. Bolus nutrition (30-60 min period), while having a similar incidence of aspiration as continuous feeding, seems to provide metabolic benefits through increased muscle protein synthesis due to higher leucine peaks. To date, clinical evidence on achievement of nutritional goals and influence of bolus nutrition on skeletal muscle metabolism in ICU patients is lacking. The aim of the Pro BoNo study ( Pro tein Bo lus N utriti o n) is to compare intermittent and continuous enteral feeding with a specific high-protein formula. We hypothesise that target quantity of protein is reached earlier (within 36 hours) by an intermittent feeding protocol with a favourable influence on muscle protein synthesis. Methods Pro BoNo is a prospective randomised controlled study aiming to compare the impact of intermittent and continuous enteral feeding on preventing muscle wasting in 60 critically ill patients recruited during the first 48 hours after ICU admission. The primary outcome measure is the time until the daily protein target (≥1.5 g protein/kg bodyweight/24h) is achieved. Secondary outcome measures include tolerance of enteral feeding and trajectory of glucose, urea and IGF-1. Ultrasound and muscle biopsy of the quadriceps will be performed. Discussion The Basel Pro BoNo study aims to collect innovative data on the effect of intermittent enteral feeding of critically ill patients on muscle wasting.

scholarly journals Protein delivery in intermittent and continuous enteral nutrition with a protein-rich formula in critically ill patients - A protocol for the prospective randomised controlled proof-of-concept Protein Bolus Nutrition (Pro BoNo) study

2020 ◽  
Author(s):  
Simona Reinhold ◽  
Désirée Yeginsoy ◽  
Alexa Hollinger ◽  
Atanas Todorov ◽  
Lionel Tintignac ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Critically Ill ◽  
Enteral Feeding ◽  
Critically Ill Patients ◽  
Muscle Wasting ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Secondary Outcome ◽  
Pro Bono ◽  
Randomised Controlled

Abstract Background Critically ill patients rapidly develop muscle wasting resulting in sarcopenia, long-term disability and higher mortality. Bolus nutrition (30-60 min period), while having a similar incidence of aspiration as continuous feeding, seems to provide metabolic benefits through increased muscle protein synthesis due to higher leucine peaks. To date, clinical evidence on achievement of nutritional goals and influence of bolus nutrition on skeletal muscle metabolism in ICU patients is lacking. The aim of the Pro BoNo study (Protein Bolus Nutrition) is to compare intermittent and continuous enteral feeding with a specific high-protein formula. We hypothesise that target quantity of protein is reached earlier (within 36 hours) by an intermittent feeding protocol with a favourable influence on muscle protein synthesis. Methods Pro BoNo is a prospective randomised controlled study aiming to compare the impact of intermittent and continuous enteral feeding on preventing muscle wasting in 60 critically ill patients recruited during the first 48 hours after ICU admission. The primary outcome measure is the time until the daily protein target (≥1.5 g protein/kg bodyweight/24h) is achieved. Secondary outcome measures include tolerance of enteral feeding and evolution of glucose, urea and IGF-1. Ultrasound and muscle biopsy of the quadriceps will be performed. Discussion The Basel Pro BoNo study aims to collect innovative data on the effect of intermittent enteral feeding of critically ill patients on muscle wasting. Trial registration ClinicalTrials.gov Identifier: NCT03587870, registered July 16, 2018. Swiss National Clinical Trial Portal identifier: SNCTP000003234, last updated July 24, 2019.

scholarly journals Effects of synbiotic supplementation on energy and macronutrients homeostasis and muscle wasting of critical care patients: study protocol and a review of previous studies

2020 ◽  
Author(s):  
Najmeh Seifi ◽  
Mohammad Safarian ◽  
Mohsen Nematy ◽  
Reza Rezvani ◽  
Majid Khadem-Rezaian ◽  
...  
Keyword(s):  
Critical Care ◽  
Gut Microbiota ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Muscle Wasting ◽  
Muscle Protein ◽  
Controlled Trial ◽  
Clinical Prognosis ◽  
Synbiotic Supplementation ◽  
Critical Care Patients

Abstract Background: Among critically ill patients, regardless of the heterogeneity of disease state, an extreme and persistent dysbiosis occurs. Dysbiosis in critically ill patients may make them prone to hospital-acquired infections, sepsis, multi-organ failure (MOF), energy homeostasis disturbance, muscle wasting, and cachexia. Modulation of gut microbiota through synbiotics can be considered as a potential treatment for muscle wasting and macronutrients homeostasis disturbances. Methods: This is a prospective, single center, double-blind; a parallel randomized controlled trial that aimed to evaluate the effects of synbiotic supplementation on energy and macronutrient ‎homeostasis and muscle wasting in critical care patients.‎ A total of 40 hemodynamically- stable adult critically ill patients who receive enteral nutrition via nasogasteric tube (NGT) in the 24-48h after admission will be included in this study. Eligible patients will be randomly assigned to receive Lactocare (ZistTakhmir) capsules 500 mg every 12h or a placebo capsule which contains only the sterile maize starch and is similar to synbiotic capsules for 14 days. The synbiotic and placebo capsules will be given through nasogastric tube, separately from gavage, after feeding. Discussion: Gut microbiota modulation through synbiotics is proposed to improve clinical prognosis and reduce infectious complications, ventilator dependency and ICU stay by improving energy and macronutrient homeostasis and reducing muscle protein catabolism.

Quercetin enhances the antitumor effect of trichostatin A and suppresses muscle wasting in tumor-bearing mice

2018 ◽  
Vol 9 (2) ◽  
pp. 871-879 ◽  
Author(s):  
Shu-Ting Chan ◽  
Cheng-Hung Chuang ◽  
Yi-Chin Lin ◽  
Jiunn-Wang Liao ◽  
Chong-Kuei Lii ◽  
...  
Keyword(s):  
Protein Degradation ◽  
Antitumor Effect ◽  
Muscle Wasting ◽  
Muscle Protein ◽  
Trichostatin A ◽  
Tumor Bearing ◽  
Muscle Protein Degradation

Quercetin prevents TSA-induced muscle wasting by down-regulating FOXO1 mediated muscle protein degradation.

scholarly journals Ultrasonography to measure quadriceps muscle in critically ill patients: A literature review of reported methodologies

2019 ◽  
Vol 47 (5) ◽  
pp. 423-434 ◽  
Author(s):  
Luke M Weinel ◽  
Matthew J Summers ◽  
Lee-Anne Chapple
Keyword(s):  
Layer Thickness ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Muscle Wasting ◽  
Muscle Layer ◽  
Quadriceps Muscle ◽  
Cross Sectional Area ◽  
Muscle Size ◽  
Sectional Area ◽  
Cross Sectional

Muscle wasting in the intensive care unit (ICU) is common and may impair functional recovery. Ultrasonography (US) presents a modern solution to quantify skeletal muscle size and monitor muscle wasting. However, no standardised methodology for the conduct of ultrasound-derived quadriceps muscle layer thickness or cross-sectional area in this population exists. The aim of this study was to compare methodologies reported for the measurement of quadriceps muscle layer thickness (MLT) and cross-sectional area (CSA) using US in critically ill patients. Databases PubMed, Ovid, Embase, and CINAHL were searched for original research publications that reported US-derived quadriceps MLT and/or CSA conducted in critically ill adult patients. Data were extracted from eligible studies on parameters relating to US measurement including anatomical location, patient positioning, operator technique and image analysis. It was identified that there was a clear lack of reported detail and substantial differences in the reported methodology used for all parameters. A standardised protocol and minimum reporting standards for US-derived measurement of quadriceps muscle size in ICU is required to allow for consistent measurement techniques and hence interpretation of results.

scholarly journals Muscle wasting in the critically ill patient: how to minimise subsequent disability

2020 ◽  
Vol 81 (4) ◽  
pp. 1-9
Author(s):  
Luke Flower ◽  
Zudin Puthucheary
Keyword(s):  
Critically Ill ◽  
Psychological Health ◽  
Critically Ill Patients ◽  
Muscle Wasting ◽  
Critically Ill Patient ◽  
Muscle Loss ◽  
Post Discharge ◽  
Mortality And Morbidity ◽  
Muscle Breakdown ◽  
Physical And Psychological Health

Muscle wasting in critically ill patients is the most common complication associated with critical care. It has significant effects on physical and psychological health, mortality and quality of life. It is most severe in the first few days of illness and in the most critically unwell patients, with muscle loss estimated to occur at 2–3% per day. This muscle loss is likely a result of a reduction in protein synthesis relative to muscle breakdown, resulting in altered protein homeostasis. The associated weakness is associated with in an increase in both short- and long-term mortality and morbidity, with these detrimental effects demonstrated up to 5 years post discharge. This article highlights the significant impact that muscle wasting has on critically ill patients' outcomes, how this can be reduced, and how this might change in the future.

Total and net muscle protein breakdown in infection determined by amino acid effluxes

1990 ◽  
Vol 258 (5) ◽  
pp. E856-E863 ◽  
Author(s):  
J. Sjolin ◽  
H. Stjernstrom ◽  
G. Friman ◽  
J. Larsson ◽  
J. Wahren
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Urinary Excretion ◽  
Protein Degradation ◽  
Muscle Protein ◽  
Human Infection ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Skeletal Muscle Protein ◽  
Mild Disease

The present investigation was undertaken to study whether, in human infection of varying severity, peripheral 3-methylhistidine efflux and urinary excretion are associated with net protein degradation and to estimate the protein synthesis rate from the combined effluxes of 3-methylhistidine, tyrosine, and phenylalanine. Quadruplicate femoral arteriovenous differences of 3-methylhistidine, tyrosine, and phenylalanine were multiplied by leg plasma flow in 15 infected patients. Leg effluxes for 3-methylhistidine, tyrosine, and phenylalanine were -0.074 +/- 0.011, -2.57 +/- 0.43, and -3.17 +/- 0.44 mumol/min, respectively. There was a significant linear relationship (P less than 0.01) between the effluxes of tyrosine and phenylalanine and the efflux and urinary excretion of 3-methylhistidine. A significant release of tyrosine and phenylalanine was observed in patients studied at the 3-methylhistidine level seen in normal healthy subjects. It is concluded that in infection 1) there is an increased breakdown of skeletal muscle protein and a reduced rate of protein synthesis, with the latter being relatively more important in patients with mild disease; and 2) urinary 3-methylhistidine excretion is associated with net skeletal muscle protein degradation for the patient group studied.

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