Browsing by Subject "Wound"

Now showing 1 - 3 of 3
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    Ketoconazole Resistant Candida albicans is Sensitive to a Wireless Electroceutical Wound Care Dressing
    (Elsevier, 2021) Khona, Dolly K.; Roy, Sashwati; Ghatak, Subhadip; Huang, Kaixiang; Jagdale, Gargi; Baker, Lane A.; Sen, Chandan K.; Surgery, School of Medicine
    Wireless electroceutical dressing (WED) fabric kills bacteria and disrupts bacterial biofilm. This work tested, comparing with standard of care topical antibiotic ketoconazole, whether the weak electric field generated by WED is effective to manage infection caused by ketoconazole-resistant yeast Candida albicans. WED inhibited Candida albicans biofilm formation and planktonic growth. Unlike ketoconazole, WED inhibited yeast to hyphal transition and downregulated EAP1 curbing cell attachment. In response to WED-dependent down-regulation of biofilm-forming BRG1 and ROB1, BCR1 expression was markedly induced in what seems to be a futile compensatory response. WED induced NRG1 and TUP1, negative regulators of filamentation; it down-regulated EFG1, a positive regulator of hyphal pathway. Consistent with the anti-hyphal properties of WED, the expression of ALS3 and HWP1 were diminished. Ketoconazole failed to reproduce the effects of WED on NRG1, TUP1 and EFG1. WED blunted efflux pump activity; this effect was in direct contrast to that of ketoconazole. WED exposure compromised cellular metabolism. In the presence of ketoconazole, the effect was synergistic. Unlike ketoconazole, WED caused membrane depolarization, changes in cell wall composition and loss of membrane integrity. This work presents first evidence that weak electric field is useful in managing pathogens which are otherwise known to be antibiotic resistant.
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    The role of retinoids in the regeneration of the axolotl spinal cord
    (2015-07-17) Kirk, Maia P.; Chernoff, Ellen A. G.; Belecky-Adams, Teri; Baucum II, A. J.
    Retinoids play an important role in tissue patterning during development as well as in epithelial formation and health. In the mammalian central nervous system, the meninges are a source of retinoids for brain tissue. Retinoid production has been described in juvenile Axolotl ependymal cells. Retinoid effects may possess a significant role in the regeneration-permissive interaction of the meninges and ependyma of the Axolotl spinal cord after penetrating injury. During spinal cord regeneration in urodele amphibians, the pattern of retinoid production changes as the meninges interact with the injury-reactive ependymal cells reconstructing the injured spinal cord. In order to determine which components of the retinoid metabolism and intracellular signaling pathway act in Urodele spinal cord regeneration, we employed antibody/horseradish peroxidase staining of both intact and regenerating Axolotl spinal cord tissues obtained from adult animals as well as cell culture techniques to determine expression of three retinoid pathway components: Cellular Retinoic Acid Binding Protein II (CRABP 2), Cellular Retinol Binding Protein I (CRBP 1), and Retinaldehyde Dehydrogenase II (RALDH 2). Current results demonstrate the following in the intact cord: 1) CRBP 1 is expressed in the pia and dura mater meningeal layers, in gray matter neurons (including their axonal processes), and the ependymal cell radial processes that produce the glia limitans, 2) CRABP 2 is expressed in the arachnoid and/or dura mater meningeal layers surrounding the spinal cord, and 3) RALDH 2 is expressed in the meninges as well as cytoplasm of grey matter neurons and some ependymal/sub-ependymal cells. In the regenerating cord, CRBP 1 is expressed in ependymal cells that are undergoing epithelial-to-mesenchymal transition (EMT), as is CRABP 2. RALDH 2 staining is very strong in the reactive meninges; in addition, expression is also upregulated in the cytoplasmic and perinuclear regions of reactive grey matter neurons, including motor neurons and in the apical region of ependymal. Preliminary studies culturing reactive meninges and ependymal cells together suggested that the meninges could drive re-epithelialization of the reactive ependymal cells. Experiments to characterize this interaction show an unusual proliferation pattern: Proliferating Cell Nuclear Antigen (PCNA) labeling is present in intact and regenerating cord ependymal cells. However, in culture, the presence of meninges results in no proliferation proximal to the explant, but extensive proliferation in leading cell outgrowth; also, the cultured meninges is positive for RALDH2. In summary, the intact adult cord shows meningeal production of RA, which is upregulated following injury; in addition, during this time, RA production is upregulated in the adult ependymal cells as well. In culture, the reactive meninges appears to modulate the behavior of reactive ependymal cells.
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    Staphylococcus aureus Biofilm Infection Compromises Wound Healing by Causing Deficiencies in Granulation Tissue Collagen
    (Wolters Kluwer, 2020-06) Roy, Sashwati; Santra, Suman; Das, Amitava; Dixith, Sriteja; Sinha, Mithun; Ghatak, Subhadip; Ghosh, Nandini; Banerjee, Pradipta; Khanna, Savita; Mathew-Steiner, Shomita; Das Ghatak, Piya; Blackstone, Britani N.; Powell, Heather M.; Bergdall, Valerie K.; Wozniak, Daniel J; Sen, Chandan K.; Surgery, School of Medicine
    Objective: The objective of this work was to causatively link biofilm properties of bacterial infection to specific pathogenic mechanisms in wound healing. Background: Staphylococcus aureus is one of the four most prevalent bacterial species identified in chronic wounds. Causatively linking wound pathology to biofilm properties of bacterial infection is challenging. Thus, isogenic mutant stains of S. aureus with varying degree of biofilm formation ability was studied in an established preclinical porcine model of wound biofilm infection. Methods: Isogenic mutant strains of S. aureus with varying degree (ΔrexB > USA300 > ΔsarA) of biofilm-forming ability were used to infect full-thickness porcine cutaneous wounds. Results: Compared with that of ΔsarA infection, wound biofilm burden was significantly higher in response to ΔrexB or USA300 infection. Biofilm infection caused degradation of cutaneous collagen, specifically collagen 1 (Col1), with ΔrexB being most pathogenic in that regard. Biofilm infection of the wound repressed wound-edge miR-143 causing upregulation of its downstream target gene matrix metalloproteinase-2. Pathogenic rise of collagenolytic matrix metalloproteinase-2 in biofilm-infected wound-edge tissue sharply decreased collagen 1/collagen 3 ratio compromising the biomechanical properties of the repaired skin. Tensile strength of the biofilm infected skin was compromised supporting the notion that healed wounds with a history of biofilm infection are likely to recur. Conclusion: This study provides maiden evidence that chronic S. aureus biofilm infection in wounds results in impaired granulation tissue collagen leading to compromised wound tissue biomechanics. Clinically, such compromise in tissue repair is likely to increase wound recidivism.