Ultrasound Shear Wave Elastography for Noninvasive Diagnosis of Acute Compartment Syndrome Using a Novel In Vivo Turkey Model.

INTRODUCTION: Acute Compartment Syndrome (ACS) is a severe trauma caused by elevated intra-muscle-compartment pressure (ICP). The current standard method for diagnosis is to insert a needle into the muscle sterilely under anesthesia. However, to secure the environment is sometimes not easy and leads to delays in diagnosis. Recently, we have focused on shear wave ultrasound elastography (SWE) as an alternative, which can be done concisely in unclean environment and without anesthesia. We would like to report the usefulness of SWE for ACS diagnosis using 2-pedal walking turkey model recently developed in our lab. MATERIALS AND METHODS: A total of 32 1-year-old Bourbon turkeys were used. 5% solution of chicken albumin was infused continuously into the tibialis cranialis (TC) muscle using IV pump. The ICP was increased stepwise from 0 to 50 mmHg. During the rising of ICP, the correlation between values of SWE (kPa) and ICP (mmHg) was measured. After the ICP reached 50 mmHg, half of the turkeys were maintained at this pressure for 2 hours and the rest for 6 hours. After infusion, a fasciotomy was performed on the half turkey. Half of the turkeys were euthanized after 2 weeks and the rest after 6 weeks. SWE of TC muscle and walking gait data on turkeys using a portable walkway system were measured weekly until euthanasia. At euthanasia, isometric tetanic muscle force (ITF) tests to TC muscle and histological evaluations were performed. RESULTS: SWE value (kPa) was highly significantly correlated to the actual ICP (mmHg) (R2 = 0.91). Stance of ACS side leg were significantly extended, and swing of the control side shortened from the second to the third week after ACS in the 6 hours infusion-no-fasciotomy group (P < 0.05*). ITF was significantly reduced mainly in the 6 hours infusion group (P < 0.05*). Histological evaluation revealed that in the 6 hours infusion and 6 weeks survival group, both the muscle fiber and intercellular distances were significantly expanded (P < 0.05). CONCLUSION: SWE seems to be a substitute measure of ICP in diagnosing ACS. With regard to our in vivo ACS model using turkey, survival at 50 mmHg ICP for 6 hours and 6 weeks post ACS would be an appropriate situation.

Sulfasalazine promotes ferroptosis through AKT-ERK1/2 and P53-SLC7A11 in rheumatoid arthritis.

OBJECTIVE: Ferroptosis has been reported to play a role in rheumatoid arthritis (RA). Sulfasalazine, a common clinical treatment for ankylosing spondylitis, also exerts pathological influence on the progression of rheumatoid arthritis including the induced ferroptosis of fibroblast-like synoviocytes (FLSs), which result in the perturbated downstream signaling and the development of RA. The aim of this study was to investigate the underlying mechanism so as to provide novel insight for the treatment of RA. METHODS: CCK-8 and Western blotting were used to assess the effect of sulfasalazine on FLSs. A collagen-induced arthritis mouse model was constructed by the injection of collagen and Freund's adjuvant, and then, mice were treated with sulfasalazine from day 21 after modeling. The synovium was extracted and ferroptosis was assessed by Western blotting and immunofluorescence staining. RESULTS: The results revealed that sulfasalazine promotes ferroptosis. Compared with the control group, the expression levels of ferroptosis-related proteins such as glutathione peroxidase 4, ferritin heavy chain 1, and solute carrier family 7, member 11 (SLC7A11) were lower in the experimental group. Furthermore, deferoxamine inhibited ferroptosis induced by sulfasalazine. Sulfasalazine-promoted ferroptosis was related to a decrease in ERK1/2 and the increase of P53. CONCLUSIONS: Sulfasalazine promoted ferroptosis of FLSs in rheumatoid arthritis, and the PI3K-AKT-ERK1/2 pathway and P53-SLC7A11 pathway play an important role in this process.