Basavraj Nagoba, Ajay Gavkare, Abhijit Rayate, Sachin Mumbre, Arunkumar Rao, Basavraj Warad, Neeta Nanaware, Nawab Jamadar

Basavraj Nagoba, Department of Microbiology, MIMSR Medical College, Latur 413512, Maharashtra, India

Ajay Gavkare, Department of Physiology, MIMSR Medical College, Latur 413512, Maharashtra, India

Abhijit Rayate, Basavraj Warad, Department of Surgery, MIMSR Medical College, Latur 413512, Maharashtra, India

Sachin Mumbre, Department of Community Medicine, Ashwini Rural Medical College, Solapur 413001, Maharashtra, India

Arunkumar Rao, Department of Orthopedics, MIMSR Medical College, Latur 413512, India

Neeta Nanaware, Department of Physiology, Government Medical College, Latur 413512, Maharashtra, India

Nawab Jamadar, Department of Anesthesiology, MIMSR Medical College, Latur 413512, Maharashtra, India

Corresponding author: Basavraj Nagoba, PhD, Assistant Dean, Research, Professor, Department of Microbiology, MIMSR Medical College, Vishwanathpuram, Ambejogai Road, Latur 413512, Maharashtra, India. 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。

Abstract

Management of diabetic foot ulcers is the biggest challenge to the clinician, as conventional antibiotic therapies and local wound care have their own limitations. They are not effective for control of infections and promotion of healing because of cytotoxic effects. In view of cytotoxicity of routinely used topical antiseptic agents, this article focuses on the search of an ideal topical antiseptic agent that is safe and effective in controlling infectious agents and also in promoting the healing process. This review focuses on the use of various acids such as citric, acetic, hyaluronic, and hypochlorous acids as topical agents in diabetic foot infections. This article also focuses on the different roles of acids in the treatment of diabetic foot infections.

Key Words: Diabetic foot ulcer; Infection; Management; Topical agents; Acids; Role of acids

Core Tip: Diabetic foot ulcer is the most serious complication of diabetes mellitus. The biggest challenge is to find an ideal topical antiseptic agent that is safe and effective in controlling infectious agents and promoting the healing process. This article focuses on

the use of acids as topical agents to control diabetic foot infections, with special emphasis on the different roles of citric, acetic, hyaluronic, and hypochlorous acids in the effective management of diabetic foot ulcers.

Citation: Nagoba B, Gavkare A, Rayate A, Mumbre S, Rao A, Warad B, Nanaware N, Jamadar N. Role of an acidic environment in the treatment of diabetic foot infections: A review. World J Diabetes 2021; 12(9): 1539-1549

Maximillian A. Weigelt,^1,* Stephanie A. McNamara,¹ Daniela Sanchez,² Penelope A. Hirt,¹ and Robert S. Kirsner¹

¹Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery, Miller School of Medicine, University of Miami, Miami, Florida, USA.

²Boston University School of Medicine, Boston, Massachusetts, USA.

Significance: Biofilms in vivo are small densely packed aggregations of microbes that are highly resistant to host immune responses and treatment. They attach to each other and to nearby surfaces. Biofilms are difficult to study and identify in a clinical setting as their quantification necessitates the use of advanced microscopy techniques such as confocal laser scanning microscopy. Nonetheless, it is likely that biofilms contribute to the pathophysiology of chronic skin wounds. Reducing, removing, or preventing biofilms is thus a logical approach to help clinicians heal chronic wounds.

Recent Advances: Wound care products have demonstrated varying degrees of efficacy in destroying biofilms in in vitro and preclinical models, as well as in some clinical studies.

Critical Issues: Controlled studies exploring the beneficial role of biofilm eradication and its relationship to healing in patients with chronic wounds are limited. This review aims to discuss the mode of action and clinical significance of currently available antibiofilm products, including surfactants, dressings, and others, with a focus on levels of evidence for efficacy in disrupting biofilms and ability to improve wound healing outcomes.

Future Directions: Few available products have good evidence to support antibiofilm activity and wound healing benefits. Novel therapeutic strategies are on the horizon. More high-quality clinical studies are needed. The development of noninvasive techniques to quantify biofilms will facilitate increased ease of research about biofilms in wounds and how to combat them.

Keywords: biofilm, wound, healing, treatment, therapy

Rahmi Dianty^1,2 , Junki Hirano^1,2 , Itsuki Anzai^1,3 , Yuta Kanai^1,4 , Tsuyoshi Hayashi⁵ , Masae Morimoto⁶ , Chikako Kataoka-Nakamura⁶ , Sakura Kobayashi⁵ , Kentaro Uemura^1,2 , Chikako Ono^1,2 , Tokiko Watanabe^1,3,7 , Takeshi Kobayashi^1,4,7 , Kosuke Murakami⁵ , Kenji Kikuchi⁸ , Kunimoto Hotta⁸ , Toshikazu Yoshikawa⁸ , Shuhei Taguwa^{1,2,7 *} and Yoshiharu Matsuura^{1,2,7 *}

¹ Laboratory of Virus Control, Center for Infectious Disease Education and Research, Osaka University, Osaka, Japan, 2Laboratory of Virus Control, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan, 3Laboratory of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan, 4Laboratory of Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan, 5Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan, 6Innovative Vaccine Research and Development Center, The Research Foundation for Microbial Diseases of Osaka University, Osaka, Japan, 7 Center for Advanced Modalities and DDS, Osaka University, Osaka, Japan, 8Louis Pasteur Center for Medical Research, Kyoto, Japan

It is essential to employ efficient measures to prevent the transmission of pathogenic agents during a pandemic. One such method involves using hypochlorous acid (HClO) solution. The oxidative properties of HClO water (HAW) can contribute to its ability to eliminate viral particles. Here, we examined a highly purified slightly acidic hypochlorous acid water (Hp-SA-HAW) obtained from the reverse osmosis membrane treatment of an electrolytically-generated SA-HAW for its anti-viral activity and mode of action on viral proteins. Hp-SA-HAW exhibited broad-spectrum antiviral effects against various viruses, including adenovirus, hepatitis B virus, Japanese encephalitis virus (JEV), and rotavirus. Additionally, Hp-SA-HAW treatment dose-dependently resulted in irreversibly aggregated multimers of the JEV envelope and capsid proteins. However, Hp-SA-HAW treatment had no discernible effect on viral RNA, indicating that Hp-SA HAW acts against amino acids rather than nucleic acids. Furthermore, Hp-SA-HAW substantially reduced the infectivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including the ancestral variant and other multiple variants. Hp-SA-HAW treatment induced the aggregation of the SARS-CoV-2 spike and nuclear proteins and disrupted the binding of the purified spike protein of SARS-CoV-2 to human ACE2. This study demonstrates that the broad-spectrum virucidal activity of highly purified HClO is attributed to viral protein aggregation of virion via protein oxidation.

KEYWORDS

hypochlorous acid, virucide, SARS-CoV-2, oxidation, protein aggregation

T. Fukuyama¹ | B. C. Martel¹ | K. E. Linder² | S. Ehling¹ | J. R. Ganchingco¹ | W. B€aumer^1,3

Summary

Background: It has been reported that topical hypochlorous acid (HOCl) formulations lead to relief of itch in human patients with atopic dermatitis; however, the specific antipruritic mechanism of action remains unclear.

Objective: To confirm itch relief and reduction of lesions in a mouse model of atopic dermatitis and to elucidate possible HOCl’s mode of action.

Methods: In this study, the effects of topical administration of HOCl hydrogel (0.05%) on atopic dermatitis-like lesions in NC/Nga mice model as well as in vitro effects of HOCl on dorsal root ganglia neurons and mouse bone marrow-derived dendritic cells (mBMDCs) were investigated. NC/Nga mice were sensitized with house dust mite allergen and treated topically with HOCl hydrogel both preventively and therapeutically against established lesions. Allergen challenge was continued during HOCl hydrogel application.

Results: Treatment with HOCl hydrogel prevented the development of lesions and scratching bouts during the whole observation period. When administered after full development of lesions, HOCl reduced lesions and scratching behaviour to a similar extent as a positive control 0.1% betamethasone dipropionate ointment. The reduced inflammatory response by HOCl treatment was demonstrated by reduced secretion of inflammatory cytokines in affected skin tissue from NC/Nga mice. In addition, HOCl significantly reduced IL-12 production in mBMDC. The diminished scratching behaviour was confirmed by impaired response to several pruritogens in dorsal root ganglia neurons excised from NC/Nga mice after termination of the studies. The response to the stimuli was also reduced by pre-incubation of sensory neurons from untreated BALB/c mice with 0.0001% HOCl. Conclusions and Clinical Relevance: These data indicate a direct reduction in sensory response by HOCl, leading to significantly reduced itch and inflammation in vivo.

KEYWORDS

atopic dermatitis, dorsal root ganglia, hypochlorous acid, IgE, IL-13, IL-4, NC/Nga mice, sensory neurons