Background and Purpose: Skeletal muscle dysfunction is a major comorbidity of chronic obstructive pulmonary disease (COPD). This type of muscle dysfunction may be a direct consequence of oxidative insults evoked by cigarette smoke (CS) exposure. The present study examined the effects of a potent Nox inhibitor and reactive oxygen species (ROS) scavenger, apocynin, on CS-induced muscle dysfunction.Experimental Approach: Male BALB/c mice were exposed to either room air (sham) or CS generated from nine cigarettes per day, 5 days a week for 8 weeks, with or without the coadministration of apocynin (5 mgÁkg À1 , i.p.). C2C12 myotubes exposed to either hydrogen peroxide (H 2 O 2 ) or water-soluble cigarette smoke extract (CSE) with or without apocynin (500 nM) were used as an experimental model in vitro.Key Results: Eight weeks of CS exposure caused muscle dysfunction in mice, reflected by 10% loss of muscle mass and 54% loss of strength of tibialis anterior which were prevented by apocynin administration. In C2C12 myotubes, direct exposure to H 2 O 2 or CSE caused myofibre wasting, accompanied by $50% loss of muscle-derived insulin-like growth factor (IGF)-1 and two-fold induction of Cybb, independent of cellular inflammation. Expression of myostatin and MAFbx, negative regulators of muscle mass, were up-regulated under H 2 O 2 but not CSE conditions.Apocynin treatment abolished CSE-induced Cybb expression, preserving muscle-derived IGF-1 expression and signalling pathway downstream of mammalian target of rapamycin (mTOR), thereby preventing myofibre wasting.
Conclusion and Implications:Targeted pharmacological inhibition of Nox-derived ROS may alleviate the lung and systemic manifestations in smokers with COPD.
Background and Purpose: Cigarette smoking (CS) is the major risk factor for developing COPD and related skeletal muscle dysfunction. It has been postulated that CS exposure may directly causes muscle dysfunction via the induction of oxidative stress. The present study examined the effect of a potent Nox inhibitor and ROS scavenger, apocynin on CS-induced muscle dysfunction. Experimental Approach: Male BALB/c mice were exposed to either room air (sham) or CS generated from 9 cigarettes per day, 5 days a week for 8 weeks with or without apocynin treatment (5 mg•kg-1 w/v, intraperitoneal injection). C2C12 myotubes exposed to either hydrogen peroxide (H2O2) or water-soluble cigarette smoke extract (CSE) with or without apocynin (500 nM), was set up as an experimental model in vitro. Key Results: Eight weeks of CS exposure caused significant lung inflammation and muscle dysfunction in mice; evidenced by a 10% loss in muscle mass and 54% loss in contractile function of tibialis anterior, attributable to altered myogenic homeostasis and protein oxidation. These effects were prevented by apocynin administration. In C2C12 myotubes, direct exposure to H2O2 or CSE caused myofiber wasting, which was associated with altered myogenic homeostasis marked by˜50% loss in muscle-derived insulin-like growth factor (IGF)-1 and 1.5-fold increase in myostatin expression. Apocynin treatment completely attenuated CSE-induced Nox2 expression, preserving muscle-derived IGF-1 expression and downstream mammalian target of rapamycin (mTOR) signaling pathway, thereby preventing myofiber wasting. Conclusion and Implications: Targeted pharmacological inhibition of Nox-derived ROS may alleviate the lung and systemic manifestations in smokers with COPD.
Introduction: Osteopathy in Australia faces an uncertain future as an unprecedented number of graduates enter the profession. While most are destined to work in private practice, workforce data suggests that limited career diversity and practitioner maldistribution are associated with growing rates of job dissatisfaction and professional attrition. Cultivating employability skills that promote diverse careers is the responsibility of education providers, yet it is unclear whether existing osteopathy programs are achieving this. Our aim was to determine if osteopathic curricula provide the employability skills required to prepare graduates for diverse careers.Methods: This study was conducted as part of a larger project by RMIT University and Osteopathy Australia entitled “Strategic plan for the osteopathy profession 2030”. A two-part approach was utilised. Part A involved a comparison of core learning outcomes (contained within current Australian osteopathy curricula) against key employability skills required for success in a diverse range of careers. A consensus development panel was consulted in Part B to capture the perspectives of experts in the field. Results: Content analysis and expert panel discussions identified the curricula has a strong focus on critical thinking, communication and problem solving and less focus on teamwork, leadership, initiative and enterprise and technological skills. Furthermore, osteopathy programs offer limited elective and micro-credentialing opportunities. Conclusions: Career diversity and increased job satisfaction for osteopathy graduates may be achieved by empowering them with the skills to succeed in careers beyond private practice. This calls for curriculum reforms and expanded elective and micro-credentialing options to enable students to broaden their skills and widen their options.
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