Mito-kaede photoactivation and chase experiment for mitophagy: optimizing flux measurement via fluid exchange system.

Modulating autophagy and mitophagy, vital cellular quality control systems, offer therapeutic potential for critical illnesses. However, limited drug screening options hinder progress. We present a novel assay using the photoswitchable fluorescent reporter, mito-Kaede, to quantify mitophagy flux.

Morphine induces inflammatory responses via both TLR4 and cGAS-STING signaling pathways.

Background: Opioid activation of the microglia or macrophage Toll-like receptor 4 (TLR4) and associated inflammatory cytokine release are implicated in opioid-induced hyperalgesia and tolerance. The cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS-STING) signaling pathway, activated by double-stranded DNA including mitochondrial DNA (mtDNA), has emerged as another key mediator of inflammatory responses. This study tested the hypothesis that morphine induces immune inflammatory responses in microglia and macrophages involving TLR4 and cGAS-STING pathway.

Alterations in Cytoskeleton and Mitochondria in the Development and Reversal of Steatosis in Human Hepatocytes.

Background & Aims: Alterations in mitochondrial morphology and function and increased oxidative stresses in hepatocytes are well established in nonalcoholic fatty liver disease (NAFLD). Patients can undergo lifestyle changes, especially in earlier NAFLD stages, to reverse disease-induced phenotypes on a gross level. Yet, little is known about whether mitochondrial function and injuries recover upon reversal.

Mechanism of pulmonary immunosuppression: extrapulmonary burn injury suppresses bacterial endotoxin-induced pulmonary neutrophil recruitment and neutrophil extracellular trap (NET) formation.

Pulmonary immunosuppression often occurs after burn injury (BI). However, the reasons for BI-induced pulmonary immunosuppression are not clearly understood. Neutrophil recruitment and neutrophil extracellular trap (NET) formation (NETosis) are important components of a robust pulmonary immune response, and we hypothesized that pulmonary inflammation and NETosis are defective after BI.

GTS-21 attenuates loss of body mass, muscle mass, and function in rats having systemic inflammation with and without disuse atrophy.

Muscle changes of critical illness are attributed to systemic inflammatory responses and disuse atrophy. GTS-21 (3-(2,4-dimethoxy-benzylidene)anabaseine), also known as DMBX-A) is a synthetic derivative of the natural product anabaseine that acts as an agonist at α7-acetylcholine receptors (α7nAChRs). Hypothesis tested was that modulation of inflammation by agonist GTS-21 (10 mg/kg b.

Role of Elevated Fibrinogen in Burn-Induced Mitochondrial Dysfunction: Protective Effects of Glycyrrhizin.

Introduction: Skeletal muscle wasting and weakness with mitochondrial dysfunction (MD) are major pathological problems in burn injury (BI) patients. Fibrinogen levels elevated in plasma is an accepted risk factor for poor prognosis in many human diseases, and is also designated one of damage-associated molecular pattern (DAMPs) proteins. The roles of upregulated fibrinogen on muscle changes of critical illness including BI are unknown.

Ultrasound-Guided Regional Anesthesia for Pediatric Burn Reconstructive Surgery: A Prospective Study.

Pediatric patients face multiple reconstructive surgeries to reestablish function and aesthetics postburn injury. Often, the site of the harvested graft for these reconstructions is reported to be the most painful part of the procedure and a common reason for deferring these reconstructive procedures. This study in pediatric burn patients undergoing reconstructive procedures examined the analgesia response to local anesthetic infiltration versus either a single ultrasound-guided regional nerve block of the lateral femoral cutaneous nerve (LFCN) or a fascia iliaca compartment block with catheter placement and continuous infusion.

Midazolam exacerbates morphine tolerance and morphine-induced hyperactive behaviors in young rats with burn injury.

Midazolam and morphine are often used in pediatric intensive care unit (ICU) for analgesia and sedation. However, how these two drugs interact behaviorally remains unclear. Here, we examined whether (1) co-administration of midazolam with morphine would exacerbate morphine tolerance and morphine-induced hyperactive behaviors, and (2) protein kinase C (PKC) would contribute to these behavioral changes.

A single injection of botulinum toxin decreases the margin of safety of neurotransmission at local and distant sites.

Background: We tested the hypothesis that a single injection of botulinum toxin not only has local, but also distant effects on muscle function, biochemistry, and pharmacodynamics of atracurium.

Methods: Botulinum toxin (2.5 U) was injected into the tibialis muscle of anesthetized rats (n = 26).

Nociceptive behavior following hindpaw burn injury in young rats: response to systemic morphine.

Objective: Develop a burn injury model in young age rats.

Background: Management of pain after burn injury in pediatric patients is an unresolved clinical issue.

Methods: A burn injury model in young rats of 3-4 weeks old was developed by briefly immersing the dorsal part of the right hindpaw in a hot water bath (85°C) for 12 seconds under pentobarbital anesthesia.

Measurement of muscle strength in the intensive care unit.

Traditional (indirect) techniques, such as electromyography and nerve conduction velocity measurement, do not reliably predict intensive care unit-acquired muscle weakness and its clinical consequences. Therefore, quantitative assessment of skeletal muscle force is important for diagnosis of intensive care unit-acquired motor dysfunction. There are a number of ways for assessing objectively muscle strength, which can be categorized as techniques that quantify maximum voluntary contraction force and those that assess evoked (stimulated) muscle force.

Increased sensitivity to a nondepolarizing muscle relaxant in a patient with acquired neuromyotonia.

Neuromyotonia is a disorder of hyperexcitability of the peripheral nerve. It has electromyographic features of spontaneous, continuous, irregularly occurring doublets, or multiplets of motor unit potential discharges. Neuromyotonia is characterized by both myokymic and neuromyotonic discharges.

In vivo micro-circulation measurement in skeletal muscle by intra-vital microscopy.

Background: Regulatory factors and detailed physiology of in vivo microcirculation have remained not fully clarified after many different modalities of imaging had invented. While many macroscopic parameters of blood flow reflect flow velocity, changes in blood flow velocity and red blood cell (RBC) flux does not hold linear relationship in the microscopic observations. There are reports of discrepancy between RBC velocity and RBC flux, RBC flux and plasma flow volume, and of spatial and temporal heterogeneity of flow regulation in the peripheral tissues in microscopic observations, a scientific basis for the requirement of more detailed studies in microcirculatory regulation using intravital microscopy.

A rat model of unilateral hindpaw burn injury: slowly developing rightwards shift of the morphine dose-response curve.

Management of pain after burn injury is an unresolved clinical issue. In a rat model of hindpaw burn injury, we examined the effects of systemic morphine on nociceptive behaviors following injury. Injury was induced by immersing the dorsal part of one hindpaw into a hot water bath (85 degrees C) for 4, 7, or 12 s under pentobarbital anesthesia.