Dual Antimicrobial and Anti-inflammatory Activity of a Nitric Oxide-releasing Topical Medication in Atopic Dermatitis
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE141571 | GEO | 2020/11/23
REPOSITORIES: GEO
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Project description:Dual Antimicrobial and Anti-inflammatory Activity of a Nitric Oxide-releasing Topical Medication in Atopic Dermatitis
| PRJNA593988 | ENA
Project description:The beginning of the end (BOTE) sign has been proposed to describe well-recognized clinical signs of inflammation (including erythema, induration, and scale) that predict imminent resolution of molluscum contagiosum (MC). This phenomenon has never been prospectively studied. An integrated analysis of two prospective, 12-week, randomized, double-blind clinical trials of topical nitric oxide-releasing SB206 gel evaluated an association between BOTE sign and MC lesion reduction. Of 707 randomized patients, ~80% exhibited BOTE signs regardless of treatment assignment. At week 12, MC lesion counts decreased from baseline by 50.7% for baseline BOTE+ versus 29.1% for BOTE- (P = 0.0015) vehicle-treated patients compared with a 63.3% decrease for baseline BOTE+ versus 51.7% for BOTE- (P = 0.0194) SB206-treated patients. Among vehicle-treated patients, 48 (22.3%) who were never BOTE+ had an 18.5% reduction from baseline in MC lesion counts versus a 34.0% reduction in 165 patients (76.7%) who experienced BOTE at any time, suggesting that the projected duration of lesion clearance for patients with 18-20 MC lesions is 15 months for BOTE- versus 6 months for BOTE+ patients. Patients who were both BOTE+ and treated with SB206 had the greatest reduction in MC lesion count. SB206 may trigger BOTE signs and shorten the duration of MC infection. The two studies whose data are analyzed in this study are registered at ClinicalTrials.gov with the identifiers NCT03927703 and NCT03927716.
| S-EPMC8659381 | biostudies-literature
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| S-EPMC6461158 | biostudies-literature
Project description:Nonhealing and chronic
| S-EPMC9888637 | biostudies-literature
Project description:A series of secondary amine-modified cyclodextrin (CD) derivatives was synthesized with diverse exterior terminal groups (i.e., hydroxyl, methyl, methoxyl, and primary amine). Subsequent reaction with nitric oxide (NO) gas under alkaline conditions yielded N-diazeniumdiolate-modified CD derivatives. Adjustable NO payloads (0.6-2.4 ?mol/mg) and release half-lives (0.7-4.2 h) were achieved by regulating both the amount of secondary amine precursors and the functional groups around the NO donors. The bactericidal action of these NO-releasing cyclodextrin derivatives was evaluated against Pseudomonas aeruginosa, a Gram-negative pathogen, with antibacterial activity proving dependent on both the NO payload and exterior modification. Materials containing a high density of NO donors or primary amines exhibited the greatest ability to eradicate P. aeruginosa. Of the materials prepared, only the primary amine-terminated heptasubstituted CD derivatives exhibited toxicity against mammalian L929 mouse fibroblast cells. The NO donor-modified CD was also capable of delivering promethazine, a hydrophobic drug, thus demonstrating potential as a dual-drug-releasing therapeutic.
| S-EPMC6790977 | biostudies-literature
Project description:Low and high molecular weight alginate biopolymers were chemically modified to store and release potentially therapeutic levels of nitric oxide (NO). Carbodiimide chemistry was first used to modify carboxylic acid functional groups with a series of small molecule alkyl amines. The resulting secondary amines were subsequently converted to N-diazeniumdiolate NO donors via reaction with NO gas under basic conditions. NO donor-modified alginates stored between 0.4-0.6 ?mol NO·mg-1. In aqueous solution, the NO-release kinetics were diverse (0.3-13 h half-lives), dependent on the precursor amine structure. The liberated NO showed bactericidal activity against Pseudomonas aeruginosa and Staphylococcus aureus with pathogen eradication efficiency dependent on both molecular weight and NO-release kinetics. The combination of lower molecular weight (?5 kDa) alginates with moderate NO-release durations (half-life of ?4 h) resulted in enhanced killing of both planktonic and biofilm-based bacteria. Toxicity against human respiratory epithelial (A549) cells proved negligible at NO-releasing alginate concentrations required to achieve a 5-log reduction in viability in the biofilm eradication assay.
| S-EPMC6759059 | biostudies-literature
Project description:PurposeManagement of atopic dermatitis (AD) typically requires application of topical treatments, often multiple times a day. The cosmetic properties and burdensome application of these treatments can be detrimental to quality of life (QoL). Patients who achieve good disease control through use of systemic therapies may reduce the frequency and amount of topical applications, improving QoL. This study aimed to quantify the utility and disutility for topical AD treatment processes.MethodsSeven vignettes describing different skincare regimens for people with moderate-to-severe AD were developed with input from healthcare professionals. 484 respondents from the general population completed time trade-off items for each vignette. Utility values for each regimen, and disutilities associated with the impact of changes to skincare regimens, were calculated. Analysis of variance assessed differences between skincare regimens.ResultsAs skincare regimens increased in intensity (0.7968 for the most intense; 0.9999 for the least), utility values decreased. There were no statistically significant differences between skincare regimens followed by patients with good disease control (0.9862 to 0.9999); however, when compared to those involving topical corticosteroids and emollient combinations (0.7968 to 0.8835), significant differences were observed (p?<?0.001). The largest disutilities (0.1521 to 0.1705) were between skincare regimens describing the use of topical corticosteroids plus emollient and those followed by patients with good disease control.ConclusionsThe application of topical treatments has a detrimental effect on QoL, which increases with the duration and frequency of applications. Further research is needed to investigate how health and process utilities interact and both can be integrated into medical decision-making.
| S-EPMC6698259 | biostudies-literature
Project description:Objective: To review the efficacy and safety of crisaborole and its place in therapy for the management of mild to moderate atopic dermatitis (AD). Data Sources: A literature search of PubMed (data inception to February 2019) was performed using the search terms crisaborole and atopic dermatitis. Supplementary sources included the Journal of the American Academy of Dermatology Guidelines of Care for the Management of Atopic Dermatitis, clinicaltrials.gov data, manufacturer prescribing information, and article bibliographies. Study Selection and Data Extraction: Relevant English-language studies and those conducted in humans were considered and reviewed. Abstracts from clinical trials and drug reviews were reviewed. Phases I, II, III, and long-term safety studies were included. Data Synthesis: Data from multiple clinical trials have demonstrated the effectiveness and safety of crisaborole topical ointment. Patients treated with crisaborole experienced improvement in AD symptoms based on improvement in the Investigator’s Static Global Assessment and the AD Severity Index scores. Crisaborole has a limited adverse event profile and low systemic absorption. Relevance to Patient Care and Clinical Practice: Crisaborole is the first topical phosphodiesterase 4 inhibitor indicated for the treatment of mild to moderate AD. Its place in therapy is along with topical calcineurin inhibitors as a second-line option for patients who are recalcitrant to or unable to use topical corticosteroids. Conclusions: Crisaborole is a safe and efficacious second-line option for the treatment of mild to moderate AD in patients 2 years of age and older.
| S-EPMC6600556 | biostudies-literature
Project description:In this study, the ability of porous silicon nanoparticles (PSi NPs) to entrap and deliver nitric oxide (NO) as an effective antibacterial agent is tested against different Gram-positive and Gram-negative bacteria. NO was entrapped inside PSi NPs functionalized by means of the thermal hydrocarbonization (THC) process. Subsequent reduction of nitrite in the presence of d-glucose led to the production of large NO payloads without reducing the biocompatibility of the PSi NPs with mammalian cells. The resulting PSi NPs demonstrated sustained release of NO and showed remarkable antibacterial efficiency and anti-biofilm-forming properties. These results will set the stage to develop antimicrobial nanoparticle formulations for applications in chronic wound treatment.
| S-EPMC4109794 | biostudies-literature
Project description:The preparation of electrospun polymer microfibers with nitric oxide (NO)-release capabilities is described. Polymer solutions containing disodium 1-[2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (PROLI/NO), a low-molecular-weight NO donor, were electrospun to generate fibers ranging from 100-3000 nm in diameter capable of releasing NO upon immersion in aqueous solutions under physiological conditions (pH 7.4, 37 °C), with kinetics depending on polymer composition and fiber diameter. The NO release half-life for PROLI/NO-doped electrospun fibers was 2-200 times longer than that of PROLI/NO alone. The influence of polymer concentration, applied voltage, capillary diameter, solution conductivity, flow rate, and additives on fiber properties are reported and discussed with respect to potential applications.
| S-EPMC3045468 | biostudies-literature