Track topics on Twitter Track topics that are important to you
Background: Skeletal muscle wasting or decrease in muscle mass occurs as a result of alteration in the body's mechanisms to make or break muscle protein. In animal models, the pathway termed as 'ubiquitin-proteasome pathway' (UPP) is primarily responsible for the regulation of skeletal muscle protein loss in wasting conditions and during infection(sepsis). Skeletal muscle wasting is noticed in patients having major surgery due to the inflammatory reaction triggered by special group of proteins called cytokines (inflammatory proteins), resulting in reduced muscle strength, impaired capacity to fight infections, change in bowel function, increased clinical complications and prolonged recovery. Major surgery also leads to decreased sensitivity to hormone known as insulin, resulting in 'diabeteslike'state.
We hypothesize that susceptibility of patients undergoing major abdominal surgery, to skeletal muscle wasting and insulin resistance, is determined by stress response to surgery over time, leading to changes in the pathways that make or break muscle protein, namely the Akt/Foxo signalling and UPP. Therefore, the aim of this study is to establish the underlying mechanisms of skeletal muscle wasting and insulin resistance in patients undergoing major abdominal surgery.
Experimental plan Fifteen adult patients undergoing major open elective abdominal surgery will be included in this nonrandomized study.
1. To study the expression proteins and metabolites involved in UPP mediated protein degradation, in blood and muscle biopsy samples.
2. To correlate the effects of surgery on the release of bacteria in blood from the bowel.
The analysis of the samples will include the following techniques, namely, RTPCR, ELISA, western blotting and metabolomics.
Establishing the association between these signaling mechanisms and expression of the individual proteins secondary to inflammation following surgery and infection would enable application of suitable therapeutic strategies that could reduce the inflammatory response to benefit all patients undergoing surgery.
Observational Model: Cohort, Time Perspective: Prospective
Skeletal Muscle Wasting
Major abdominal surgery
University Hospitals Nottingham Queen's Medical Centre
Enrolling by invitation
University of Nottingham
Published on BioPortfolio: 2014-08-27T03:13:16-0400
Skeletal muscle atrophy is associated with catabolic conditions such as major surgical interventions and leads to reduced muscle strength, increased clinical complications and prolonged co...
Single-centre observational study over one year investigating the mechanisms of muscle homeostasis in patients with acute skeletal muscle atrophy following major aortic surgery
This study aims to investigate the effect of beta-hydroxy-beta-methylbutyrate (HMB) on skeletal muscle wasting, physical function, strength and quality of life in survivors of critical ill...
The current project was designed to examine dynamic changes in muscle wasting during sepsis. Researchers will focus the mitochondrial dysfunction of muscle cells and investigate the role o...
The purpose of this study is to assess if bimagrumab is safe and effective in patients with muscle wasting (atrophy) after hip fracture surgery.
With aging and other muscle wasting diseases, men and women undergo similar pathological changes in skeletal muscle: increased inflammation, enhanced oxidative stress, mitochondrial dysfunction, satel...
Muscle ring finger 1 (MuRF1) is a muscle-specific ubiquitin E3 ligase activated during clinical conditions associated with skeletal muscle wasting. Yet, there remains a paucity of therapeutic interven...
Elevated levels of inflammatory molecules are the key players in muscle wasting/atrophy leading to human morbidity. TNFα is a well-known pro-inflammatory cytokine implicated in the pathogenesis of mu...
Severe burns are typically followed by hypermetabolism characterized by significant muscle wasting, which causes considerable morbidity and mortality. The aim of the present study was to explore the u...
Acute kidney injury (AKI) is a common complication in patients undergoing major abdominal surgery. Various recent studies using modern standardized classifications for AKI reported a variable incidenc...
A heterogeneous group of inherited MYOPATHIES, characterized by wasting and weakness of the SKELETAL MUSCLE. They are categorized by the sites of MUSCLE WEAKNESS; AGE OF ONSET; and INHERITANCE PATTERNS.
Large, multinucleate single cells, either cylindrical or prismatic in shape, that form the basic unit of SKELETAL MUSCLE. They consist of MYOFIBRILS enclosed within and attached to the SARCOLEMMA. They are derived from the fusion of skeletal myoblasts (MYOBLASTS, SKELETAL) into a syncytium, followed by differentiation.
Involuntary weight loss of greater than 10 percent associated with intermittent or constant fever and chronic diarrhea or fatigue for more than 30 days in the absence of a defined cause other than HIV infection. A constant feature is major muscle wasting with scattered myofiber degeneration. A variety of etiologies, which vary among patients, contributes to this syndrome. (From Harrison's Principles of Internal Medicine, 13th ed, p1611).
A subtype of mitochondrial ADP, ATP translocase found primarily in heart muscle (MYOCARDIUM) and skeletal muscle (MUSCLE, SKELETAL).
Abnormal increase in skeletal or smooth muscle tone. Skeletal muscle hypertonicity may be associated with PYRAMIDAL TRACT lesions or BASAL GANGLIA DISEASES.
Arthritis Fibromyalgia Gout Lupus Rheumatic Rheumatology is the medical specialty concerned with the diagnosis and management of disease involving joints, tendons, muscles, ligaments and associated structures (Oxford Medical Diction...
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...