scholarly journals Investigating auranofin for the treatment of infected diabetic pressure ulcers in mice and dermal toxicity in pigs

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Haroon Mohammad ◽  
Nader S. Abutaleb ◽  
Alexandra M. Dieterly ◽  
L. Tiffany Lyle ◽  
Mohamed N. Seleem
Keyword(s):  
Staphylococcus Aureus ◽  
Growth Factors ◽  
Pressure Ulcers ◽  
Systemic Toxicity ◽  
Topical Agent ◽  
Bacterial Burden ◽  
Dermal Toxicity ◽  
Porcine Skin ◽  
Histopathologic Analysis ◽  
Pro Inflammatory Cytokines

AbstractBacterial infection of pressure ulcers (PUs) are a notable source of hospitalization for individuals with diabetes. This study evaluated the safety profile and efficacy of auranofin to treat diabetic PUs infected with methicillin-resistant Staphylococcus aureus (MRSA). PUs were infected with MRSA in diabetic TALLYHO/JngJ mice and then treated with topical auranofin (2%), topical mupirocin (2%), or oral clindamycin (30 mg/kg) for four days. PUs were harvested post-treatment to enumerate bacterial burden and determine expression of cytokines/growth factors. Landrace cross pigs were exposed topically to auranofin (1%, 2%, and 3%) for 4–14 days and evaluated for signs of localized or systemic toxicity. Auranofin eradicated MRSA in PUs within four days (7.92-log10 reduction) in contrast to mupirocin (2.15-log10 reduction) and clindamycin (0.73-log10 reduction). Additionally, auranofin treatment resulted in decreased expression of pro-inflammatory cytokines and increased expression of biomarkers associated with re-epithelization of wounded tissue, confirmed with histopathologic analysis. No significant histopathologic lesions were present on porcine skin sites exposed to topical auranofin. Additionally, minimal accumulation of plasma gold and no systemic toxicity was observed in pigs exposed to topical auranofin. Auranofin appears to be a potent and safe topical agent to further investigate for treatment of mild-to-moderate MRSA-infected diabetic PUs.

scholarly journals The Antimicrobial and Anti-Inflammatory Effects of Silver Nanoparticles Synthesised from Cotyledon orbiculata Aqueous Extract

Nanomaterials ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1343
Author(s):  
Caroline Tyavambiza ◽  
Abdulrahman Mohammed Elbagory ◽  
Abram Madimabe Madiehe ◽  
Mervin Meyer ◽  
Samantha Meyer
Keyword(s):  
Staphylococcus Aureus ◽  
Silver Nanoparticles ◽  
Metallic Nanoparticles ◽  
Methicillin Resistance ◽  
Antimicrobial Activities ◽  
Transmission Electron ◽  
Anti Inflammatory ◽  
Anti Inflammation ◽  
Important Medicinal Plant ◽  
Pro Inflammatory Cytokines

Cotyledon orbiculata, commonly known as pig’s ear, is an important medicinal plant of South Africa. It is used in traditional medicine to treat many ailments, including skin eruptions, abscesses, inflammation, boils and acne. Many plants have been used to synthesize metallic nanoparticles, particularly silver nanoparticles (AgNPs). However, the synthesis of AgNPs from C. orbiculata has never been reported before. The aim of this study was to synthesize AgNPs using C. orbiculata and evaluate their antimicrobial and immunomodulatory properties. AgNPs were synthesized and characterized using Ultraviolet-Visible Spectroscopy (UV-Vis), Dynamic Light Scattering (DLS) and High-Resolution Transmission Electron Microscopy (HR-TEM). The antimicrobial activities of the nanoparticles against skin pathogens (Staphylococcus aureus, Staphylococcus epidermidis, Methicillin Resistance Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans) as well as their effects on cytokine production in macrophages (differentiated from THP-1 cells) were evaluated. The AgNPs from C. orbiculata exhibited antimicrobial activity, with the highest activity observed against P. aeruginosa (5 µg/mL). The AgNPs also showed anti-inflammatory activity by inhibiting the secretion of pro-inflammatory cytokines (TNF-alpha, IL-6 and IL-1 beta) in lipopolysaccharide-treated macrophages. This concludes that the AgNPs produced from C. orbiculata possess antimicrobial and anti-inflammation properties.

scholarly journals EFFECT OF EXOPOLISACCHARIDES OF LACTIC ACID BACTERIA ON THE SYNTHESIS OF PROINFLAMMATORY CYTOKINES BY MACROPHAGIC MICE IN PHAGOCYTOSIS OF STAPHYLOCOCCUS AUREUS

2018 ◽  
pp. 67-71
Author(s):  
G. T. Uryadova ◽  
E. A. Gorelnikova ◽  
N. A. Fokina ◽  
A. S. Dolmashkina ◽  
L. V. Karpunina
Keyword(s):  
Staphylococcus Aureus ◽  
Lactic Acid ◽  
Lactic Acid Bacteria ◽  
Lactococcus Lactis ◽  
Inflammatory Cytokines ◽  
Proinflammatory Cytokines ◽  
Streptococcus Thermophilus ◽  
Ambiguous Effect ◽  
Pro Inflammatory Cytokines

Aim. Study of the effect of exopolysaccharides (EPS) of lactic acid cocci on cytokine activity of macrophages of mice with phagocytosis in vitro Staphylococcus aureus 209-P. Materials and methods. The EPS of Streptococcus thermophilus and Lactococcus lactis B-1662 was used in the work. At 13, 5 and 7, AMP and PMP were isolated and the phagocytosis process was modeled in vitro. After 30 minutes, 1, 6 and 24 hours, the content of pro-inflammatory cytokines IL-1a and TNF-a was determined. Results. EPSs had an ambiguous effect on the production of cytokines. The greatest effect on the synthesis was provided by EPS of S. thermophilus. Conclusion. The results of the study allow us to talk about the possibility of using EPS of S. thermophilus as a preventive immunomodulator for correction of the cytokine status of animals.

scholarly journals Neutrophil survival and c-kit+-progenitor proliferation in Staphylococcus aureus–infected skin wounds promote resolution

Blood ◽  
2011 ◽  
Vol 117 (12) ◽  
pp. 3343-3352 ◽  
Author(s):  
Min-Ho Kim ◽  
Jennifer L. Granick ◽  
Cindy Kwok ◽  
Naomi J. Walker ◽  
Dori L. Borjesson ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bone Marrow ◽  
Progenitor Cells ◽  
Polymorphonuclear Neutrophils ◽  
Immune Protection ◽  
Infected Wound ◽  
Bacterial Burden ◽  
Cutaneous Wound ◽  
Neutrophil Survival ◽  
Infected Skin

AbstractPolymorphonuclear neutrophils (PMNs) are critical for the formation, maintenance, and resolution of bacterial abscesses. However, the mechanisms that regulate PMN survival and proliferation during the evolution of an abscess are not well defined. Using a mouse model of Staphylococcus aureus abscess formation within a cutaneous wound, combined with real-time imaging of genetically tagged PMNs, we observed that a high bacterial burden elicited a sustained mobilization of PMNs from the bone marrow to the infected wound, where their lifespan was markedly extended. A continuous rise in wound PMN number, which was not accounted for by trafficking from the bone marrow or by prolonged survival, was correlated with the homing of c-kit+-progenitor cells from the blood to the wound, where they proliferated and formed mature PMNs. Furthermore, by blocking their recruitment with an antibody to c-kit, which severely limited the proliferation of mature PMNs in the wound and shortened mouse survival, we confirmed that progenitor cells are not only important contributors to PMN expansion in the wound, but are also functionally important for immune protection. We conclude that the abscess environment provides a niche capable of regulating PMN survival and local proliferation of bone marrow–derived c-kit+-progenitor cells.

Growth Factors in the Repair of Partial Thickness Porcine Skin Wounds

1997 ◽  
Vol 100 (3) ◽  
pp. 657-664 ◽  
Author(s):  
Karl Breuing ◽  
Christoph Andree ◽  
Giselle Helo ◽  
Jaromir Slama ◽  
Paul Y. Liu ◽  
...  
Keyword(s):  
Growth Factors ◽  
Skin Wounds ◽  
Porcine Skin ◽  
Partial Thickness

scholarly journals Evaluation of Analogs of Reutericyclin as Prospective Candidates for Treatment of Staphylococcal Skin Infections

2009 ◽  
Vol 53 (9) ◽  
pp. 4028-4031 ◽  
Author(s):  
Julian G. Hurdle ◽  
Raghunandan Yendapally ◽  
Dianqing Sun ◽  
Richard E. Lee
Keyword(s):  
Staphylococcus Aureus ◽  
Clinical Isolates ◽  
Topical Agent ◽  
Skin Infections ◽  
Drug Resistant ◽  
Topical Antibiotics ◽  
Superficial Skin ◽  
Staphylococcal Skin Infections

ABSTRACT The potential for reutericyclin derivatives to be used as topical antibiotics to treat staphylococcal skin infections was investigated. All reutericyclins inhibited the growth of clinical isolates of drug-resistant Staphylococcus aureus. Unlike the standard topical agent mupirocin, most reutericyclin derivatives eradicated staphylococcal biofilms. Moreover, two compounds formulated in hydrophilic petrolatum (10%, wt/wt) were efficacious in treating S. aureus superficial skin infections in mice. These data exemplify the prospect of developing reutericyclins as new topical antibiotics.

scholarly journals Effect of Coadministration of Vancomycin and BMP-2 on Cocultured Staphylococcus aureus and W-20-17 Mouse Bone Marrow Stromal CellsIn Vitro

2012 ◽  
Vol 56 (7) ◽  
pp. 3776-3784 ◽  
Author(s):  
A. H. Nguyen ◽  
S. Kim ◽  
W. J. Maloney ◽  
J. C. Wenke ◽  
Y. Yang
Keyword(s):  
Staphylococcus Aureus ◽  
Bone Marrow ◽  
Growth Factors ◽  
Bone Cell ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mouse Bone Marrow ◽  
Content Type ◽  
Proliferation And Differentiation ◽  
Dual Administration

ABSTRACTIn this study, we aimed to establish anin vitrobacterium/bone cell coculture model system and to use this model for dose dependence studies of dual administration of antibiotics and growth factorsin vitro. We examined the effect of single or dual administration of the antibiotic vancomycin (VAN) at 0 to 16 μg/ml and bone morphogenetic protein-2 (BMP-2) at 0 or 100 ng/ml on both methicillin-sensitiveStaphylococcus aureusand mouse bone marrow stromal cells (W-20-17) under both mono- and coculture conditions. Cell metabolic activity, Live/Dead staining, double-stranded DNA (dsDNA) amounts, and alkaline phosphatase activity were measured to assess cell viability, proliferation, and differentiation. An interleukin-6 (IL-6) enzyme-linked immunosorbent assay (ELISA) kit was used to test the bone cell inflammation response in the presence of bacteria. Our results suggest that, when delivered together in coculture, VAN and BMP-2 maintain their primary functions as an antibiotic and a growth factor, respectively. Most interestingly, this dual-delivery type of approach has shown itself to be effective at lower concentrations of VAN than those required for an approach relying strictly on the antibiotic. It may be that BMP-2 enhances cell proliferation and differentiation before the cells become infected. In coculture, a dosage of VAN higher than that used for treatment in monoculture may be necessary to effectively inhibit growth ofStaphylococcus aureus. This could mean that the coculture environment may be limiting the efficacy of VAN, possibly by way of bacterial invasion of the bone cells. This report of a coculture study demonstrates a potential beneficial effect of the coadministration of antibiotics and growth factors compared to treatment with antibiotic alone.

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