Thomas H. Leung,1,2 Lillian F. Zhang,1 Jing Wang,1 Shoucheng Ning,3 Susan J. Knox,3 and Seung K. Kim1,4,5
1Department of Developmental Biology, 2Department of Dermatology, 3Department of Radiation Oncology, 4Howard Hughes Medical Institute, and 5Department of Medicine, Oncology Division, Stanford University School of Medicine, Stanford, California, USA.
Nuclear factor-κB (NF-κB) regulates cellular responses to inflammation and aging, and alterations in NF-κB signaling underlie the pathogenesis of multiple human diseases. Effective clinical therapeutics targeting this pathway remain unavailable. In primary human keratinocytes, we found that hypochlorite (HOCl) reversibly inhibited the expression of CCL2 and SOD2, two NF-κB–dependent genes. In cultured cells, HOCl inhibited the activity of inhibitor of NF-κB kinase (IKK), a key regulator of NF-κB activation, by oxidizing cysteine residues Cys114 and Cys115. In NF-κB reporter mice, topical HOCl reduced LPS-induced NF-κB signaling in skin. We further evaluated topical HOCl use in two mouse models of NF-κB–driven epidermal disease. For mice with acute radiation dermatitis, topical HOCl inhibited the expression of NF-κB–dependent genes, decreased disease severity, and prevented skin ulceration. In aged mice, topical HOCl attenuated age-dependent production of p16INK4a and expression of the DNA repair gene Rad50. Additionally, skin of aged HOCl-treated mice acquired enhanced epidermal thickness and proliferation, comparable to skin in juvenile animals. These data suggest that topical HOCl reduces NF-κB–mediated epidermal pathology in radiation dermatitis and skin aging through IKK modulation and motivate the exploration of HOCl use for clinical aims.
Eric Clayman, MD; Zackery Beauchamp, BS; Jared Troy, MD
Abstract
Background. Orthopedic hardware infections often require hardware removal or replacement. In some situations, hardware removal is not possible or would require amputation. Thus, a method of in-situ hardware salvage could significantly improve patient outcomes. Hypochlorous acid is a broad-spectrum antimicrobial solution with rapid effectiveness in biofilm impairment.
Methods. This article presents 2 patients with orthopedic hardware infection. Patient A had recurrent draining sinuses from an intramedullary nail in the femur. The orthopedic surgery team recommended above-knee amputation if hardware salvage was not possible. Patient B had a degloving injury of the right upper extremity with radius and ulna fractures that required revascularization and free flap coverage; when hardware infection developed, hardware removal would have required external fixator placement. In both patients, hypochlorous acid was used intraoperatively during debridement to soak the hardware for 5 minutes. Closed suction drains were placed along the hardware, and postoperative instillations of hypochlorous acid were placed through the drains for 5 minutes 1 to 2 times a day for 4 days for Patient A and 7 days for Patient
Results. On follow-up at 10 months for Patient A and at 9 months for Patient B, there was no evidence of recurrent hardware infection. Hardware was successfully salvaged in both patients.
Conclusions. Hypochlorous acid is an effective and safe topical antimicrobial agent for recurrent infections due to hardware-associated biofilm. Postoperative instillations of 0.025% hypochlorous acid through closed suctions drains may improve hardware salvage rates and optimize
Keywords PhaseOne Hypochlorous Acid Hardware Salvage Infected Hardware Biofilm
This article is excerpted from the《Frontiers in Pharmacology》by Wound World
伤口世界平台生态圈,以“关爱人间所有伤口患者”为愿景,连接、整合和拓展线上和线下的管理慢性伤口的资源,倡导远程、就近和居家管理慢性伤口,解决伤口专家的碎片化时间的价值创造、诊疗经验的裂变复制、和患者的就近、居家和低成本管理慢性伤口的问题。
2019广东省医疗行业协会伤口管理分会年会
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