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Sepsis is a frequent complication in patients in intensive care units (ICU). Diaphragm weakness,one of the most common symptoms observed, can lead to weaning problemsduring mechanical ventilation. Over the last couple of years, members of thetransforming growth factor (TGF) β family,such as myostatin, activin A and TGF-β1,have beenreported to strongly trigger the activation of protein breakdown involved in muscle wasting. The aim of this study was to investigate the effect of TGF-βinhibitorLY364947on the diaphragm during chronic sepsis.Rats were separated into four groups exposed to different experimental conditions: (i) Control group, (ii) Septic group, (iii) Septic group with inhibitor from day 0 (LY D0), and (iv) Septic group with inhibitor from day 1 (LY D1). Sepsis was induced in ratsby cecal ligation and puncture, and carried out for seven days.Chronic sepsis was responsible for a decrease inbody weight, food intake anddiaphragm's mass. The inhibitor was able to abolish diaphragm wasting only in the LY D1 group. Similarly, LY364947 had a beneficial effect on the diaphragm contraction only for the LY D1 group. SMAD3 was over-expressed and phosphorylated within rats in the Septic group;however this effect was reversed by LY364947. Calpain-1 and -2 as well as MAFbx were over-expressedwithin individuals in theSeptic group. Yet, calpain-1 and MAFbx expressions were decreased by LY364947With this work, we demonstrate for the first time that the inhibition of TGF-β pathway during chronic sepsisprotects the diaphragm from wasting and weaknessas early asone day post infection. This could lead to more efficient treatment and care for septic patients in ICU.
This article was published in the following journal.
Name: Shock (Augusta, Ga.)
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Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by HYPOTENSION despite adequate fluid infusion, it is called SEPTIC SHOCK.
Acute neurological dysfunction during severe SEPSIS in the absence of direct brain infection characterized by systemic inflammation and BLOOD BRAIN BARRIER perturbation.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activa
Blood infection that occurs in an infant younger than 90 days old. Early-onset sepsis is seen in the first week of life and most often appears within 24 hours of birth. Late-onset occurs after 1 week and before 3 months of age.
A condition of involuntary weight loss of greater then 10% of baseline body weight. It is characterized by atrophy of muscles and depletion of lean body mass. Wasting is a sign of MALNUTRITION as a result of inadequate dietary intake, malabsorption, or hypermetabolism.
Antiretroviral Therapy Clostridium Difficile Ebola HIV & AIDS Infectious Diseases Influenza Malaria Measles Sepsis Swine Flu Tropical Medicine Tuberculosis Infectious diseases are caused by pathogenic...
Sepsis, septicaemia and blood poisoning
Septicaemia (another name for blood poisoning) refers to a bacterial infection of the blood, whereas sepsis can also be caused by viral or fungal infections. Sepsis is not just limited to the blood and can affect the whole body, including the organ...
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