Degree of Agreement Between Infant Serum and Salivary Concentration of Leptin and Adiponectin and Its Association With Infants' Feeding.

Background: Leptin and adiponectin, two adipokines involved in glucose and lipid metabolism, have been linked to regulation of growth in early infancy, energy balance, and metabolic disorders in childhood. The aim of this study was to determine if concentrations of leptin and adiponectin could be measured reliably in infants' saliva, to evaluate the degree of agreement with infant serum levels, and to explore their association with infant feeding status.

Methods: A total of 34 infants were recruited after birth and followed for 20 weeks.

Diaphragm Abnormalities in Patients with End-Stage Heart Failure: NADPH Oxidase Upregulation and Protein Oxidation.

Patients with heart failure (HF) have diaphragm abnormalities that contribute to disease morbidity and mortality. Studies in animals suggest that reactive oxygen species (ROS) cause diaphragm abnormalities in HF. However, the effects of HF on ROS sources, antioxidant enzymes, and protein oxidation in the diaphragm of humans is unknown.

Proteomic analysis of media from lung cancer cells reveals role of 14-3-3 proteins in cachexia.

Aims: At the time of diagnosis, 60% of lung cancer patients present with cachexia, a severe wasting syndrome that increases morbidity and mortality. Tumors secrete multiple factors that contribute to cachectic muscle wasting, and not all of these factors have been identified. We used Orbitrap electrospray ionization mass spectrometry to identify novel cachexia-inducing candidates in media conditioned with Lewis lung carcinoma cells (LCM).

Mitochondria dysfunction in lung cancer-induced muscle wasting in C2C12 myotubes.

Aims: Cancer cachexia is a syndrome which results in severe loss of muscle mass and marked fatigue. Conditioned media from cachexia-inducing cancer cells triggers metabolic dysfunction in skeletal muscle, including decreased mitochondrial respiration, which may contribute to fatigue. We hypothesized that Lewis lung carcinoma conditioned medium (LCM) would impair the mitochondrial electron transport chain (ETC) and increase production of reactive oxygen species, ultimately leading to decreased mitochondrial respiration.

Neutral sphingomyelinase-3 mediates TNF-stimulated oxidant activity in skeletal muscle.

Aims: Sphingolipid and oxidant signaling affect glucose uptake, atrophy, and force production of skeletal muscle similarly and both are stimulated by tumor necrosis factor (TNF), suggesting a connection between systems. Sphingolipid signaling is initiated by neutral sphingomyelinase (nSMase), a family of agonist-activated effector enzymes. Northern blot analyses suggest that nSMase3 may be a striated muscle-specific nSMase.

Muscle-specific calpastatin overexpression prevents diaphragm weakness in cecal ligation puncture-induced sepsis.

Recent work indicates that infections are a major contributor to diaphragm weakness in patients who are critically ill and mechanically ventilated, and that diaphragm weakness is a risk factor for death and prolonged mechanical ventilation. Infections activate muscle calpain, but many believe this is an epiphenomenon and that other proteolytic processes are responsible for infection-induced muscle weakness. We tested the hypothesis that muscle-specific overexpression of calpastatin (CalpOX; an endogenous calpain inhibitor) would attenuate diaphragm dysfunction in cecal ligation puncture (CLP)-induced sepsis.

TNF signals via neuronal-type nitric oxide synthase and reactive oxygen species to depress specific force of skeletal muscle.

TNF promotes skeletal muscle weakness, in part, by depressing specific force of muscle fibers. This is a rapid, receptor-mediated response, in which TNF stimulates cellular oxidant production, causing myofilament dysfunction. The oxidants appear to include nitric oxide (NO); otherwise, the redox mechanisms that underlie this response remain undefined.

Sphingomyelinase depresses force and calcium sensitivity of the contractile apparatus in mouse diaphragm muscle fibers.

Diseases that result in muscle weakness, e.g., heart failure, are characterized by elevated sphingomyelinase (SMase) activity.

Doxorubicin acts via mitochondrial ROS to stimulate catabolism in C2C12 myotubes.

Doxorubicin, a commonly prescribed chemotherapeutic agent, causes skeletal muscle wasting in cancer patients undergoing treatment and increases mitochondrial reactive oxygen species (ROS) production. ROS stimulate protein degradation in muscle by activating proteolytic systems that include caspase-3 and the ubiquitin-proteasome pathway. We hypothesized that doxorubicin causes skeletal muscle catabolism through ROS, causing upregulation of E3 ubiquitin ligases and caspase-3.

Prion protein expression and functional importance in skeletal muscle.

Unlabelled: Skeletal muscle expresses prion protein (PrP) that buffers oxidant activity in neurons.

Aims: We hypothesize that PrP deficiency would increase oxidant activity in skeletal muscle and alter redox-sensitive functions, including contraction and glucose uptake. We used real-time polymerase chain reaction and Western blot analysis to measure PrP mRNA and protein in human diaphragm, five murine muscles, and muscle-derived C2C12 cells.

Beyond atrophy: redox mechanisms of muscle dysfunction in chronic inflammatory disease.

Chronic inflammatory diseases such as heart failure, cancer and arthritis have secondary effects on skeletal muscle that cause weakness and exercise intolerance. These symptoms exacerbate illness and make death more likely. Weakness is not simply a matter of muscle atrophy.

Doxorubicin causes diaphragm weakness in murine models of cancer chemotherapy.

Doxorubicin is a chemotherapeutic agent prescribed for a variety of tumors. While undergoing treatment, patients exhibit frequent symptoms that suggest respiratory muscle weakness. Cancer patients can receive doxorubicin chemotherapy through either intravenous (IV) or intraperitoneal (IP) injections.

TNF/TNFR1 signaling mediates doxorubicin-induced diaphragm weakness.

Doxorubicin, a common chemotherapeutic agent, causes respiratory muscle weakness in both patients and rodents. Tumor necrosis factor-α (TNF), a proinflammatory cytokine that depresses diaphragm force, is elevated following doxorubicin chemotherapy. TNF-induced diaphragm weakness is mediated through TNF type 1 receptor (TNFR1).

Sphingomyelinase stimulates oxidant signaling to weaken skeletal muscle and promote fatigue.

Sphingomyelinase (SMase) hydrolyzes membrane sphingomyelin into ceramide, which increases oxidants in nonmuscle cells. Serum SMase activity is elevated in sepsis and heart failure, conditions where muscle oxidants are increased, maximal muscle force is diminished, and fatigue is accelerated. We tested the hypotheses that exogenous SMase and accumulation of ceramide in muscle increases oxidants in muscle cells, depresses specific force of unfatigued muscle, and accelerates the fatigue process.

Physical inactivity and muscle weakness in the critically ill.

Patients in the intensive care unit commonly develop muscle weakness. In part, this reflects loss of mechanical loading due to physical inactivity, bed rest, or immobilization. Mechanical unloading stimulates a complex adaptive response that results in muscle atrophy and loss of specific force.

Doxorubicin acts through tumor necrosis factor receptor subtype 1 to cause dysfunction of murine skeletal muscle.

Cancer patients receiving doxorubicin chemotherapy experience both muscle weakness and fatigue. One postulated mediator of the muscle dysfunction is an increase in tumor necrosis factor-alpha (TNF), a proinflammatory cytokine that mediates limb muscle contractile dysfunction through the TNF receptor subtype 1 (TNFR1). Our main hypothesis was that systemic doxorubicin administration would cause muscle weakness and fatigue.

Interleukin-1 stimulates catabolism in C2C12 myotubes.

Interleukin-1 (IL-1) is an inflammatory cytokine that has been linked to muscle catabolism, a process regulated by muscle-specific E3 proteins of the ubiquitin-proteasome pathway. To address cellular mechanism, we tested the hypothesis that IL-1 induces myofibrillar protein loss by acting directly on muscle to increase expression of two critical E3 proteins, atrogin1/muscle atrophy F-box (MAFbx) and muscle RING-finger 1 (MuRF1). Experiments were conducted using mature C2C12 myotubes to eliminate systemic cytokine effects and avoid paracrine signaling by nonmuscle cell types.

Stretch-stimulated glucose uptake in skeletal muscle is mediated by reactive oxygen species and p38 MAP-kinase.

Alternatives to the canonical insulin-stimulated pathway for glucose uptake are exercise- and exogenous reactive oxygen species (ROS)-stimulated glucose uptake. We proposed a model wherein mechanical loading, i.e.

TNF induction of atrogin-1/MAFbx mRNA depends on Foxo4 expression but not AKT-Foxo1/3 signaling.

Murine models of starvation-induced muscle atrophy demonstrate that reduced protein kinase B (AKT) function upregulates the atrophy-related gene atrogin-1/MAFbx (atrogin). The mechanism involves release of inhibition of Forkhead transcription factors, namely Foxo1 and Foxo3. Elevated atrogin mRNA also corresponds with elevated TNF in inflammatory catabolic states, including cancer and chronic heart failure.

TNF-alpha acts via TNFR1 and muscle-derived oxidants to depress myofibrillar force in murine skeletal muscle.

Tumor necrosis factor-alpha (TNF) diminishes specific force of skeletal muscle. To address the mechanism of this response, we tested the hypothesis that TNF acts via the type 1 (TNFR1) receptor subtype to increase oxidant activity and thereby depress myofibrillar function. Experiments showed that a single intraperitoneal dose of TNF (100 microg/kg) increased cytosolic oxidant activity (P < 0.

IFN-gamma does not mimic the catabolic effects of TNF-alpha.

Cachexia is common in chronic inflammatory diseases and is attributed, in part, to an elevation of circulating proinflammatory cytokines. TNF-alpha is the prototype in this category. IFN-gamma is also thought to play a role, but the evidence supporting this model is primarily indirect.

Oxidative stress, chronic disease, and muscle wasting.

Underlying the pathogenesis of chronic disease is the state of oxidative stress. Oxidative stress is an imbalance in oxidant and antioxidant levels. If an overproduction of oxidants overwhelms the antioxidant defenses, oxidative damage of cells, tissues, and organs ensues.

Bowman-Birk inhibitor concentrate prevents atrophy, weakness, and oxidative stress in soleus muscle of hindlimb-unloaded mice.

Antigravity muscles atrophy and weaken during prolonged mechanical unloading caused by bed rest or spaceflight. Unloading also induces oxidative stress in muscle, a putative cause of weakness. We tested the hypothesis that dietary supplementation with Bowman-Birk inhibitor concentrate (BBIC), a soy protein extract, would oppose these changes.