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In Vivo (Athens, Greece) 2023This study aimed to research the effects of Harkány healing water on oxidative stress. The study was performed in a randomized, placebo-controlled, double-blind setup. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND/AIM
This study aimed to research the effects of Harkány healing water on oxidative stress. The study was performed in a randomized, placebo-controlled, double-blind setup.
PATIENTS AND METHODS
Twenty patients with psoriasis who underwent a 3-week-long inward balneotherapy-based rehabilitation were enrolled. Psoriasis Area and Severity Index (PASI) score and Malondialdehyde (MDA) - a marker of oxidative stress - were determined, on admission and before discharge. Patients were treated with dithranol.
RESULTS
The mean PASI score - determined on admission and before discharge - decreased significantly after the 3-week-long rehabilitation 8.17 vs. 3.51 (p<0.001). The baseline MDA value of patients with psoriasis was significantly higher compared to controls (3.0±3.5 vs. 8.4±7.4) (p=0.018). MDA levels of patients receiving placebo water increased significantly compared to MDA levels of patients receiving healing water (p=0.049).
CONCLUSION
The effectiveness of dithranol resides in the formation of reactive oxygen species. No increased oxidative stress was found in the patients treated with healing water, thus healing water seems to be protective against oxidative stress. However, further research is needed to confirm these preliminary results.
Topics: Humans; Pilot Projects; Anthralin; Oxidative Stress; Balneology; Psoriasis; Water
PubMed: 36881082
DOI: 10.21873/invivo.13153 -
Nature Chemistry Oct 2022Aqueous organic redox flow batteries offer a safe and potentially inexpensive solution to the problem of storing massive amounts of electricity produced from...
Aqueous organic redox flow batteries offer a safe and potentially inexpensive solution to the problem of storing massive amounts of electricity produced from intermittent renewables. However, molecular decomposition represents a major barrier to commercialization-and although structural modifications can improve stability, it comes at the expense of synthetic cost and molecular weight. Now, utilizing 2,6-dihydroxy-anthraquinone (DHAQ) without further structural modification, we demonstrate that the regeneration of the original molecule after decomposition represents a viable route to achieve low-cost, long-lifetime aqueous organic redox flow batteries. We used in situ (online) NMR and electron paramagnetic resonance, and complementary electrochemical analyses to show that the decomposition compound 2,6-dihydroxy-anthrone (DHA) and its tautomer, 2,6-dihydroxy-anthranol (DHAL) can be recomposed to DHAQ electrochemically through two steps: oxidation of DHA(L) to the dimer (DHA) by one-electron transfer followed by oxidation of (DHA) to DHAQ by three-electron transfer per DHAQ molecule. This electrochemical regeneration process also rejuvenates the positive electrolyte-rebalancing the states of charge of both electrolytes without introducing extra ions.
Topics: Anthralin; Electrolytes; Ions; Mitoxantrone; Oxidation-Reduction
PubMed: 35710986
DOI: 10.1038/s41557-022-00967-4 -
Dermatologic Therapy Sep 2019Alopecia areata (AA) is a chronic inflammatory, recurrent, tissue-specific autoimmune disease, mediated by autoreactive CD8+ T cells, occurring in genetically...
Alopecia areata (AA) is a chronic inflammatory, recurrent, tissue-specific autoimmune disease, mediated by autoreactive CD8+ T cells, occurring in genetically predisposed individuals. Targeting intrabulbar and peribulbar lymphocytic infiltrate by using squaric acid dibutyl ester and diphenylcyclopropenone (DPCP) in contact immunotherapy is by far the best chemotherapy for AA. The aim of this work was to evaluate the efficacy and safety of combination therapy with DPCP and anthralin in chronic extensive AA. A total of 24 patients (12 were treated only with DPCP and 12 with DPCP and anthralin for at least 24 weeks) were evaluated. Complete hair regrowth was observed in 62.5 and 18.2% of the patients who received DPCP and combination therapy, respectively (p = .04). Hair regrowth duration was different in both groups. The DPCP therapy is superior to the combination therapy with DPCP and anthralin in terms of efficacy, the time of onset of hair regrowth, and the time of completion of hair regrowth, Moreover, combination therapy has more side effects in combination therapy group have been discussed in this work.
Topics: Administration, Topical; Adolescent; Adult; Alopecia Areata; Anthralin; Child; Child, Preschool; Chronic Disease; Cyclopropanes; Dermatologic Agents; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Hair; Humans; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Young Adult
PubMed: 31237076
DOI: 10.1111/dth.13010 -
Frontiers in Medicine 2021SARS-Cov2 has raised concerns among dermatologists regarding psoriasis and its respective treatments. Comorbidities, which induce the expression of the proprotease...
SARS-Cov2 has raised concerns among dermatologists regarding psoriasis and its respective treatments. Comorbidities, which induce the expression of the proprotease furin have been associated with severe course of COVID-19. Furin and angiotensin converting enzyme 2 (ACE2) play a major role in viral host cell entry of SARS-Cov2. To evaluate mRNA expression of Furin and ACE2 from blood cells in psoriasis patients, and whether systemic or topical treatment reduces expression levels. This observational translational study analyzed blood samples from patients from a clinical trial and samples retrieved from the biobank of the Psoriasis Registry Austria (PsoRA). Furin and ACE2 expression levels were analyzed prior to as well as 3 and 12-24 months after start of biologic treatment with either ustekinumab or secukinumab. Additionally, the study analyzed expression levels prior to, 6 days after start of dithranol treatment and 4-6 weeks after end of dithranol treatment. Furin mRNA expression was significantly increased at baseline in the biologic (4.9 ± 2.6 fold, < 0.0001) and in the dithranol group (2.7 ± 1.4 fold, < 0.001) compared to controls. There was a trend for arthritis patients to express more furin than patients with psoriatic skin involvement only (5.26 ± 2.30 vs. 3.48 ± 2.27, = 0.078). Analyzing furin mRNA expression after treatment initiation with secukinumab or ustekinumab revealed a normalization of levels after 3 and 12 to 24 months. Similar findings were obtained for patients treated with dithranol, with significantly decreased expression levels 6 days after start of dithranol treatment and also at follow-up, (4-6 weeks after dithranol treatment had been terminated). ACE2 expression levels did not differ from controls at any timepoint, regardless of biologic or topical treatment. Significantly overexpressed levels of furin were observed in untreated patients, and, thus, these patients may be at risk for infection and a severe course of COVID-19. However, the data indicate that successful therapeutic intervention in psoriasis, by systemic biologic or topical treatment, can efficiently reduce furin levels in blood cells, possibly limiting the risk of psoriasis patients for a severe COVID-19 course. ClinicalTrials.gov, identifier NCT02752672.
PubMed: 33644099
DOI: 10.3389/fmed.2021.624462 -
International Journal of Nanomedicine 2024Improving the treatment of psoriasis is a serious challenge today. Psoriasis is an immune-mediated skin condition affecting 125 million people worldwide. It is commonly...
Revolutionizing Psoriasis Topical Treatment: Enhanced Efficacy Through Ceramide/Phospholipid Composite Cerosomes Co-Delivery of Cyclosporine and Dithranol: In-Vitro, Ex-Vivo, and in-Vivo Studies.
PURPOSE
Improving the treatment of psoriasis is a serious challenge today. Psoriasis is an immune-mediated skin condition affecting 125 million people worldwide. It is commonly treated with cyclosporine-A (CsA) and dithranol (DTH). CsA suppresses the activation of T-cells, immune cells involved in forming psoriatic lesions. Meanwhile, DTH is a potent anti-inflammatory and anti-proliferative drug that effectively reduces the severity of psoriasis symptoms such as redness, scaling, and skin thickness. CsA and DTH belong to BCS class II with limited oral bioavailability. We aim to develop a drug delivery system for topical co-delivery of CsA and DTH, exploring its therapeutic potential.
METHODS
Firstly, we developed a niosomal drug delivery system based on ceramide IIIB to form Cerosomes. Cerosomes were prepared from a mixture of Ceramide, hyaluronic acid, and edge activator using a thin-film hydration technique. To co-deliver CsA and DTH topically for the treatment of psoriasis. These two hydrophobic drugs encapsulated into our synthesized positively charged particle cerosomes.
RESULTS
Cerosomes had an average particle size of (222.36 nm± 0.36), polydispersity index of (0.415±0.04), Entrapment Efficiency of (96.91%± 0.56), and zeta potential of (29.36±0.38mV) for selected formula. In vitro, In silico, in vivo, permeation, and histopathology experiments have shown that cerosomes enhanced the skin penetration of both hydrophobic drugs by 66.7% compared to the CsA/DTH solution. Imiquimod (IMQ) induced psoriatic mice model was topically treated with our CsA/DTH cerosomes. We found that our formulation enhances the skin penetration of both drugs and reduces psoriasis area and severity index (PASI score) by 2.73 times and 42.85%, respectively, compared to the CsA/DTH solution. Moreover, it reduces the levels of proinflammatory cytokines, TNF-α, IL-10, and IL-6 compared to CsA/DTH solution administration.
CONCLUSION
The Cerosomes nano-vesicle-containing CsA/DTH represents a more promising topical treatment for psoriasis, giving new hope to individuals with psoriasis, compared to commercial and other conventional alternatives.
Topics: Humans; Animals; Mice; Anthralin; Cyclosporine; Phospholipids; Ceramides; Administration, Cutaneous; Psoriasis; Skin; Disease Models, Animal
PubMed: 38344440
DOI: 10.2147/IJN.S443812 -
Experimental Dermatology Jun 2021Topical dithranol is effective in autoimmune conditions like alopecia areata, inducing hair regrowth in a high percentage of cases. Exact mechanisms of dithranol in...
Topical dithranol is effective in autoimmune conditions like alopecia areata, inducing hair regrowth in a high percentage of cases. Exact mechanisms of dithranol in alopecia areata, with seemingly healthy epidermis besides altered hair follicles, are not well understood. To better understand dithranol's mechanisms on healthy skin, we analysed its effect on normal murine as well as xenografted human skin. We found a strong increase in mRNA expression of anti-microbial peptides (AMPs) (eg Lcn2, Defb1, Defb3, S100a8, S100a9), keratinocyte differentiation markers (eg Serpinb3a, Flg, Krt16, Lce3e) and inflammatory cytokines (eg Il1b and Il17) in healthy murine skin. This effect was paralleled by inflammation and disturbed skin barrier, as well as an injury response resulting in epidermal hyperproliferation, as observed in murine and xenografted adult human skin. This contact response and disturbed barrier induced by dithranol might lead via a vicious loop between AMPs such as S100a8/a9 (that led to skin swelling itself after topical application) and cytokines such as IL-1β to an immune suppressive environment in the skin. A better understanding of the skin's physiologic response to dithranol may open up new avenues for the establishment of novel therapeutics (including AMP-related/interfering molecules) for certain skin conditions, such as alopecia areata.
Topics: Alopecia Areata; Animals; Anthralin; Antimicrobial Peptides; Cytokines; Dermatologic Agents; Humans; Interleukin-1beta; Keratinocytes; Mice; Mice, Inbred BALB C
PubMed: 33629779
DOI: 10.1111/exd.14310 -
International Journal of Nanomedicine 2020Reactive oxygen species (ROS)-induced oxidative stress plays a key role in the pathogenesis and progression of psoriasis by causing inflammation. Antioxidative...
PURPOSE
Reactive oxygen species (ROS)-induced oxidative stress plays a key role in the pathogenesis and progression of psoriasis by causing inflammation. Antioxidative strategies eradicating ROS may serve as effective and easy treatment options for psoriasis, while nanozymes with intrinsic antioxidant enzyme-like activity have not been explored for psoriasis treatment. The aim of this study is to fabricate β-cyclodextrins (β-CDs)-modified ceria nanoparticles (β-CDs/CeO NPs) with drug-loaded and multimimic-enzyme activities for combinational psoriasis therapy.
METHODS
The β-CDs/CeO NPs were synthesized by a hydrothermal method using unmodified β-CDs as a protecting agent. The structure, size and morphology were analyzed by dynamic light scattering, transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FTIR) spectroscopy. Considering the superoxide dismutase (SOD)- and catalase-mimetic activities, the in vitro antioxidant activity of the β-CDs/CeO2 NPs was investigated. After dithranol (DIT) was loaded, the drug-loading capacity and release profile were determined by UV-visible light spectrophotometer and high-performance liquid chromatography. The anti-psoriatic efficacy was studied in the imiquimod (IMQ)-induced mouse model on the basis of morphological evaluation, psoriasis area and severity index calculation (PASI), and inflammatory cytokine expression.
RESULTS
The average particle size of the blank β-CDs/CeO NPs was 60.89±0.32 nm with a polydispersity index (PDI) of 0.12, whereas that of the DIT-loaded NPs was 79.38±1.06 nm with a PDI of 0.27. TEM results showed the as-prepared NPs formed a uniform quasi-spherical shape with low polydispersity. XPS indicates synthesized NPs have a mixed Ce/Ce valence state. FTIR spectroscopy confirmed the presence of β-CDs and DIT in the NPs. Inhibition of superoxide anion rate by NPs could be reached to 79.4% in the presence of 200 µg/mL, and elimination of HO efficiency reached about 50% in the presence of 40 µg/mL, demonstrating excellent superoxide dismutase- and catalase-mimicking activities, thereby providing remarkable cryoprotection against ROS-mediated damage. Furthermore, β-CDs on the surface endowed the NPs with drug-loading function via host-guest interactions. The entrapment efficiency and drug loading of DIT are 94.7% and 3.48%, respectively. The in vitro drug release curves revealed a suitable release capability of DIT@β-CDs/CeO NPs under physiological conditions. In IMQ-induced psoriatic model, the DIT@β-CDs/CeO NPs exhibited excellent therapeutic effect.
CONCLUSION
This study may pave the way for the application of nanozyme β-CDs/CeO NPs as a powerful tool for psoriasis therapy.
Topics: Animals; Catalase; Cell Line; Cell Survival; Cerium; Combined Modality Therapy; Free Radical Scavengers; Hydrodynamics; Imiquimod; Male; Mice, Inbred BALB C; Nanoparticles; Particle Size; Photoelectron Spectroscopy; Psoriasis; Reactive Oxygen Species; Skin; Spectroscopy, Fourier Transform Infrared; Superoxide Dismutase; Tumor Necrosis Factor-alpha; beta-Cyclodextrins
PubMed: 32368038
DOI: 10.2147/IJN.S246783 -
JAAD Case Reports Jul 2020
PubMed: 32743037
DOI: 10.1016/j.jdcr.2020.05.022 -
Contribution of LDI and MALDI for the Characterization of a Lignocellulosic-Based Pyrolysis Bio-Oil.Journal of the American Society For... Aug 2023In recent years, various alternatives to fossil fuels have been developed. One of them involves the production of bio-oils from lignocellulosic-based biomass through...
In recent years, various alternatives to fossil fuels have been developed. One of them involves the production of bio-oils from lignocellulosic-based biomass through pyrolysis. However, bio-oils present numerous heteroatoms and, in particular, oxygen atoms that need to be removed by an upgrading process. To optimize these processes, it is necessary to have good knowledge of the composition of the bio-oils at the molecular level. This work aims to establish the usefulness of laser desorption ionization (LDI) and matrix-assisted laser desorption/ionization (MALDI) techniques on lignocellulosic biomass-based bio-oils. Using a Fourier transform ion cyclotron mass spectrometer (FTICR MS), we showed that MALDI gives more information than LDI. The selectivity of a series of MALDI matrices was investigated, showing that some matrices are selective toward compound families and others ionize a wider range of compounds. In this study, nine proton-transfer matrices and three electron-transfer matrices were used and compared to results obtained in LDI. Dithranol, acetosyringone, and graphene oxide were the three promising matrices selected from all matrices, giving an overall characterization of oxygenated classes in a bio-oil. They allowed the ionization of many more species covering a wide range of polarity, aromaticity, and mass with a homogeneous relative intensity for all molecular classes such as lignin-derivative species, sugars, and lipid-derivative species.
Topics: Humans; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Pyrolysis; Plant Oils; Lasers
PubMed: 37477530
DOI: 10.1021/jasms.3c00197 -
Der Hautarzt; Zeitschrift Fur... Jun 2021We present a case of a 46-year-old woman suffering from active inflammatory alopecia areata universalis. After frustrating use of topical and systemic glucocorticoids,...
We present a case of a 46-year-old woman suffering from active inflammatory alopecia areata universalis. After frustrating use of topical and systemic glucocorticoids, cream PUVA (psoralen and ultraviolet A) therapy and dithranol in increasing dosage, the patient was treated with 2 × 5 mg per day tofacitinib per os. After about 4-6 months, hair growth commenced, which led to full regrowth of scalp hair over the 18 months of therapy, which was well tolerated. The case shows impressively that the off-label application of tofacitinib is a therapeutic option for alopecia areata.
Topics: Alopecia; Alopecia Areata; Female; Humans; Middle Aged; Piperidines; Pyrimidines; Pyrroles
PubMed: 33044559
DOI: 10.1007/s00105-020-04704-1