Frontiers in physiology
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Frontiers in physiology · Jan 2018
Dexamethasone Protects Against Tourniquet-Induced Acute Ischemia-Reperfusion Injury in Mouse Hindlimb.
Extremity injuries with hemorrhage have been a significant cause of death in civilian medicine and on the battlefield. The use of a tourniquet as an intervention is necessary for treatment to an injured limb; however, the tourniquet and subsequent release results in serious acute ischemia-reperfusion (IR) injury in the skeletal muscle and neuromuscular junction (NMJ). Much evidence demonstrates that inflammation is an important factor to cause acute IR injury. ⋯ Treatment with dexamethasone at the beginning of reperfusion (1 mg/kg, i.p.) significantly inhibited expression of TNFα and IL-1β, reduced rupture of the muscle sarcolemma and infarct size (24.8 ± 2.0%), and improved direct muscle stimulation-induced gastrocnemius muscle contraction in 24-h IR mice. However, this anti-inflammatory drug did not improve NMJ morphology and function, and sciatic nerve-stimulated skeletal muscle contraction in 24-h IR mice. The data suggest that one-time treatment with dexamethasone at the beginning of reperfusion only reduced structural and functional impairments of the skeletal muscle but not the NMJ through inhibiting inflammatory cytokines.
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Frontiers in physiology · Jan 2018
ReviewBiomarkers for Pulmonary Vascular Remodeling in Systemic Sclerosis: A Pathophysiological Approach.
Pulmonary arterial hypertension (PAH) is a severe complication of systemic sclerosis (SSc) associated with high morbidity and mortality. There are several biomarkers of SSc-PAH, reflecting endothelial physiology, inflammation, immune activation, extracellular matrix, metabolic changes, or cardiac involvement. Biomarkers associated with diagnosis, disease severity and progression have been identified, however, very few have been tested in a prospective setting. ⋯ Established heart related markers, such as N-terminal fragment of A-type natriuretic peptide/brain natriuretic peptide (NT-proANP, NT-proBNP) or troponin I/T are elevated in SSc-PAH but are not specific for the right ventricle and may be increased to the same extent in left heart disease. Taken together, there is no universal specific biomarker for SSc-PAH, however, there is a pattern of markers that is strongly associated with a risk of vascular complications in SSc patients. Further comprehensive, multicenter and prospective studies are warranted to develop reliable algorithms for detection and prognosis of SSc-PAH.
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Frontiers in physiology · Jan 2018
ReviewExosomes: Basic Biology and Technological Advancements Suggesting Their Potential as Ischemic Heart Disease Therapeutics.
Exosomes are small nano-sized vesicles that deliver biologically active RNA molecules and proteins to recipient cells through binding, fusion or endocytosis. There is emerging evidence that endogenous exosomes released by cardiovascular cells and progenitor cells impact cell survival and proliferation, thus regulating angiogenesis, cardiac protection and repair. These cardioprotective and regenerative traits have the potential to translate in to novel therapeutic options for post-ischaemic cardiac regeneration, thus potentially delaying the progression to ischaemic heart failure. ⋯ Similarly, manipulation of exosomes surface proteins' expression to target exosomes to specific cells and tissues is doable. In addition, nature-inspired synthetic exosomes can be assembled to deliver specific clues to the recipient cells, including proliferative and differentiation stimuli, or shed paracrine signals enabling to reconstructing the heart homeostatic micro-environment. This review will describe exosome biogenesis and emerging evidence of exosome-mediated regenerative cell-to-cell communications and will conclude discussing possibilities of using exosomes to treat ischemic heart disease.
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Frontiers in physiology · Jan 2018
TNF-α Increases Production of Reactive Oxygen Species through Cdk5 Activation in Nociceptive Neurons.
The participation of reactive oxygen species (ROS) generated by NOX1 and NOX2/NADPH oxidase has been documented during inflammatory pain. However, the molecular mechanism involved in their activation is not fully understood. We reported earlier a key role of Cyclin-dependent kinase 5 (Cdk5) during inflammatory pain. ⋯ Interestingly, TNF-α increased immunodetection of p35 protein and NOX1 and NOX2/NADPH oxidase complexes in primary culture of trigeminal ganglia neurons. Finally, the cytosolic regulator NOXO1 was significantly translocated to plasma membrane after TNF-α treatment and roscovitine blocked this effect. Altogether these results suggest that Cdk5 activation is implicated in the ROS production by NOX1 and NOX2/NADPH oxidase complexes during inflammatory pain.
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Frontiers in physiology · Jan 2018
Periodic Fluctuation of Tidal Volumes Further Improves Variable Ventilation in Experimental Acute Respiratory Distress Syndrome.
In experimental acute respiratory distress syndrome (ARDS), random variation of tidal volumes (VT ) during volume controlled ventilation improves gas exchange and respiratory system mechanics (so-called stochastic resonance hypothesis). It is unknown whether those positive effects may be further enhanced by periodic VT fluctuation at distinct frequencies, also known as deterministic frequency resonance. We hypothesized that the positive effects of variable ventilation on lung function may be further amplified by periodic VT fluctuation at specific frequencies. ⋯ Cycle-by-cycle analysis of lung mechanics suggested intertidal recruitment/de-recruitment in P10. Lung histologic damage and inflammation did not differ among groups. In this experimental model of severe ARDS, periodic VT fluctuation at a frequency of 0.05 Hz improved oxygenation during variable ventilation, suggesting that deterministic resonance adds further benefit to variable ventilation.