Repurposing Auranofin, an Anti-Rheumatic Gold Compound, to Treat Acne Vulgaris by Targeting the NLRP3 Inflammasome

Activation of the NLRP3 inflammasome is critical for host defense as well as the progression of inflammatory diseases through the production of the proinflammatory cytokine IL-1β, which is cleaved by active caspase-1. It has been reported that overactivation of the NLRP3 inflammasome contributes to the development and pathology of acne vulgaris. Therefore, inhibiting activation of the NLRP3 inflammasome may provide a new therapeutic strategy for acne vulgaris. In this study, we investigated whether auranofin, an anti-rheumatoid arthritis agent, inhibited NLRP3 inflammasome activation, thereby effectively treating acne vulgaris.Auranofin suppressed NLRP3 inflammasome activation induced by Propionibacterium acnes, reducing the production of IL-1β in primary mouse macrophages and human sebocytes. In a P. acnes-induced acne mouse model, injection of P. acnes into the ears of mice induced acne symptoms such as redness, swelling, and neutrophil infiltration. Topical application of auranofin (0.5 or 1%) to mouse ears significantly reduced the inflammatory symptoms of acne vulgaris induced by P. acnes injection. Topical application of auranofin led to the downregulation of the NLRP3 inflammasome activated by P. acnes in mouse ear skin. These results show that auranofin inhibits the NLRP3 inflammasome, the activation of which is associated with acne symptoms. The results further suggest that topical application of auranofin could be a new therapeutic strategy for treating acne vulgaris by targeting the NLRP3 inflammasome.

Ankle Arthrodesis: A Comparison of Anterior Approach and Transfibular Approach

BACKGROUND: The purpose of this study was to compare clinical and radiological results of arthrodesis performed by the anterior approach and by the transfibular approach in ankle osteoarthritis. METHODS: Sixty patients underwent open arthrodesis (38 by the anterior approach and 22 by the transfibular approach). The visual analogue scale score and the American Orthopedic Foot and Ankle Society (AOFAS) score were examined clinically, and radiological examination was performed on the alignment of the lower extremity and bone union. RESULTS: Both groups showed significant improvement in AOFAS score (from 39.8 to 58.3 in the anterior approach group and from 44.5 to 60.7 in the transfibular approach group). There was no significant difference in AOFAS score at the last follow-up in both groups. The time to fusion was 13.5 weeks in the anterior approach group and 11.8 weeks in the transfibular approach group. Nonunion occurred in four cases in the anterior approach group and in one case in the transfibular approach group. CONCLUSIONS: Ankle arthrodesis by the anterior approach and the transfibular approach showed comparably good clinical results.

Biphasic Increase of Pro-inflammatory Cytokines in Mice Lung after Irradiation / 결핵및호흡기질환

BACKGROUND: The pathophysiologic mechanisms of radiation-induced lung injury should be elucidated to enhance the therapeutic efficacy of radiotherapy and to manage patients exposed to serious radiation by accident. It has been suggested that pro-inflammatory cytokines play an important role in radiation-induced effect on the lung. This study was aimed to investigate changes in pro-inflammatory cytokines such as TNF-alpha, MIP-2, IL-1beta and HMGB1, a newly recognized inflammatory mediator. METHODS: The chests of BALB/c mice were selectively irradiated with single fraction of 20 Gy and then sacrificed at indicated times. Pathologic changes in the lung were examined after H&E staining. The expression level of pro-inflammatory cytokines was evaluated by ELISA kits in lung homogenate and in serum. RESULTS: Radiation induced inflammatory changes and mild fibrosis in lung. Biphasic increase of TNF-alpha and IL-1beta was found in lung homogenate at 4 hours and at 3 weeks after radiation. The elevation in the second phase tended to be more intense. However, there was no similar change in serum. MIP-2 level was slightly increased in lung homogenate at 4 hours, but not at 3 weeks. HMGB1 was increased at 3 weeks in serum while there was no significant change in lung homogenate. CONCLUSION: Radiation induced a biphasic increase in TNF-alpha and IL-1beta. The effective control of second phase cytokine elevation should contribute to preventing severe lung fibrosis caused by radiation.

Malignant Nodular Hidradenoma: A Case Report

Malignant nodular hidradenoma is a rare skin appendageal tumor, and its imaging findings have not been previously described. We experienced the case of a large malignant nodular hidradenoma of the left upper arm in a 71-year-old woman. MRI revealed a large, lobular, poorly circumscribed, soft tissue mass at the left upper arm, and the mass showed homogeneous enhancement. 18F-FDG PET/CT showed hypermetabolic activity in the left upper arm mass with a maximal standard uptake value of 19.

A Case of Dialysis-related Amyloidosis of the Hip and Cervical Spine: Imaging Findings

Dialysis-related amyloidosis is a complication of long-term hemodialysis and it is characterized by the accumulation of beta2-microglobulin in the osteoarticular structures. We describe here the imaging findings of a case of dialysis-related amyloidosis involving the hip and cervical spine in a 62-year-old woman who received long-term dialysis. We focus here on the CT and MR imaging findings of the cervical spine and we include a review of the relevant literatures.

Metastatic Spinal Epidural Leiomyoma: A Case Report

We report here on a case of a spinal extradural leiomyoma in a 67-year-old woman, and this tumor was in a very unusual location for a leiomyoma. Because the patient underwent hysterectomy for a uterine leiomyoma 20 years ago, we can speculate that the spinal lesion was a metastatic leiomyoma.

Ceftriaxone-Associated Biliary Pseuodolithiasis: Sonographic and CT Findings

Ceftriaxone is known to induce a precipitation in the gallbladder that mimics gallstones on sonography in the children and adults. "Biliary pseudolithiasis" is now used to describe this reversible, benign complication accompanying ceftriaxone therapy. It is important to be aware of this adverse effect because it does not need any specific treatment. To our knowledge, there have not been any reports of CT findings of ceftriaxone-associated biliary pseudolithiasis in literature. We herein report two cases of ceftriaxone-associated biliary pseudolithiasis with sonographic and CT findings, which were completely resolved after the cessation of ceftriaxone therapy.

Transarterial Embolization of Acute Intercostal Artery Bleeding

PURPOSE: To report our experiences of transarterial embolization for acute intercostal artery bleeding. MATERIALS AND METHODS: A retrospectively analysis of the causes, clinical manifestations, angiographic findings and transarterial embolization technique in 8 patients with acute intercostal artery bleeding, with a review of the anatomical basis. RESULTS:The causes of intercostal artery bleeding were iatrogenic and traumatic in 88 and 12% of cases, respectively. Active bleeding from the collateral intercostal or posterior intercostal arteries was angiographically demonstrated in 75 and 25% of cases, respectively. Transarterial embolization successfully achieved hemostasis in all cases. However, two patient with hypovolemic shock expired due to a massive hemothorax, despite successful transarterial embolization. CONCLUSION: Intercostal access should be performed through the middle of the intercostal space to avoid injury to the collateral intercostal artery. Transarterial embolization is an effective method for the control of intercostal artery bleeding.

Gd(DTPA)2--enhanced, and Quantitative MR Imaging in Articular Cartilage

PURPOSE: Early degeneration of articular cartilage is accompanied by a loss of glycosaminoglycan (GAG) and the consequent change of the integrity. The purpose of this study was to biochemically quantify the loss of GAG, and to evaluate the Gd(DTPA)2--enhanced, and T1, T2, rho relaxation map for detection of the early degeneration of cartilage. MATERIALS AND METHODS: A cartilage-bone block in size of 8mmx10 mm was acquired from the patella in each of three pigs. Quantitative analysis of GAG of cartilage was performed at spectrophotometry by use of dimethylmethylene blue. Each of cartilage blocks was cultured in one of three different media: two different culture media (0.2 mg/ml trypsin solution, 1mM Gd (DTPA)2- mixed trypsin solution) and the control media (phosphate buffered saline (PBS)). The cartilage blocks were cultured for 5 hrs, during which MR images of the blocks were obtained at one hour interval (0 hr, 1 hr, 2 hr, 3 hr, 4 hr, 5 hr). And then, additional culture was done for 24 hrs and 48 hrs. Both T1-weighted image (TR/TE, 450/22 ms), and mixed-echo sequence (TR/TE, 760/21-168ms; 8 echoes) were obtained at all times using field of view 50 mm, slice thickness 2 mm, and matrix 256x512. The MRI data were analyzed with pixel-by-pixel comparisons. The cultured cartilage-bone blocks were microscopically observed using hematoxylin & eosin, toluidine blue, alcian blue, and trichrome stains. RESULTS: At quantitation analysis, GAG concentration in the culture solutions was proportional to the culture durations. The T1-signal of the cartilage-bone block cultured in the Gd(DTPA)2- mixed solution was significantly higher (42% in average, p0.05). However the focal increase in T1 relaxation time at superficial and transitional layers of cartilage was seen in Gd(DTPA)2- mixed culture. Toluidine blue and alcian blue stains revealed multiple defects in whole thickness of the cartilage cultured in trypsin media. CONCLUSION: The quantitative analysis showed gradual loss of GAG proportional to the culture duration. Microimagings of cartilage with Gd(DTPA)2--enhancement, relaxation maps were available by pixel size of 97.9x195 micrometer. Loss of GAG over time better demonstrated with Gd(DTPA)2--enhanced images than with T1, T2, rho relaxation maps. Therefore Gd(DTPA)2--enhanced T1-weighted image is superior for detection of early degeneration of cartilage.