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Dermatologic Therapy May 2020We present the results on retrospective analysis about the efficacy of Certolizumab pegol (CZP), an antitumor necrosis factor-alpha agent, as monotherapy on skin...
We present the results on retrospective analysis about the efficacy of Certolizumab pegol (CZP), an antitumor necrosis factor-alpha agent, as monotherapy on skin psoriasis (PsO) in patients affect both by psoriatic arthritis (PsA) and mild-severe PsO. To date, the CZP is authorized for the treatment of PsA, PsO beyond that rheumatoid arthritis, axial spondyloarthritis/ankylosing spondylitis, and Crohn's. Assessments included an evaluation of the Psoriasis Area and Severity Index (PASI). Twelve patients (9M and 3F mean age 57.8 ± 8 years) were enrolled in our study. Nine patients had been previously treated with others biologic agents, three patients were naïve. Clinical and laboratory evaluations including PASI, erythrosedimentation rate, and C-reactive protein were performed at baseline (BL), at Week 12 (W12), Week 24 (W24), and Week 52 (W52) of treatment. Although the combination between methotrexate and CZP is allowed, we included, in our study, patients treated only with CZP. In such a way as to be as specific as possible, topical corticosteroids, vitamin D derivatives, retinoid creams, anthralin derivatives as well as p-UVA or UV-B have been forbidden to enrolled patients. With the same purpose, all the patients used the identical moisturizing cream two times a day. Mean PASI score decreased from 18 (BL) to 0 (W52) as follows: 18 at BL, 4 at W12, 0 at W24, and 0 at W52. Severe adverse events were not reported. Safety evaluations were performed every 3 months: liver and renal functions were monitored in all patients during the treatment, and no patient presented abnormal values. To the best of our knowledge, this is the first report that highlights the efficacy of CZP as monotherapy in psoriasis with mild to severe cutaneous involvement. Although to date the drug is authorized only for PsA, our results demonstrate that CZP is safe and effective on both cutaneous and joint components representing, therefore, an effective option in the treatment of cutaneous symptoms of PsO. Limitations of our study are presented by the relatively short observation time (W52) and by numeric small study group. Long-term data with a larger number of enrolled patients are necessary in order to confirm our preliminary observations.
Topics: Aged; Antirheumatic Agents; Arthritis, Psoriatic; Certolizumab Pegol; Double-Blind Method; Humans; Immunosuppressive Agents; Middle Aged; Psoriasis; Retrospective Studies; Treatment Outcome
PubMed: 32291887
DOI: 10.1111/dth.13409 -
International Journal of Pharmaceutics Apr 2020The paper demonstrates the potential of photoacoustics for the identification of the mechanisms underlying drug transport through tissue-mimicking systems. Photoacoustic...
The paper demonstrates the potential of photoacoustics for the identification of the mechanisms underlying drug transport through tissue-mimicking systems. Photoacoustic experiments were performed for a model transdermal delivery system, consisting of drug dithranol (in pharmaceutical form) and dodecanol-collodion (DDC) membrane. The spectroscopic data revealed a single-path photodegradation of dithranol in Vaseline (dithranol → danthrone, characterized by the 1st order decay rate of (7.85 ± 0.31)·10 s), and a multipath degradation in the DDC system, involving danthrone and the unknown compound (characterized by the absorption band at ~400 nm) as the final products. The desorption experiments performed enabled the identification of the unknown compound as the photodegradation product of dithranol molecules bound to the membrane matrix. The result led to the incorporation of the adsorption effects and heterogeneous structure of the membrane into the hydrodynamical model of mass transport. The model was tested against the photoacoustic depth-profiling data for dithranol permeation through DDC. The analysis allowed the dispersion and advection coefficients to be determined (D' = (2.05 ± 0.03)⋅10 cm s and v' = (-5.55 ± 0.05)⋅10 cm s, respectively). Moreover, it was found, that the dithranol photodegradation rate in the non-steady state system is slower compared to the steady-state case; the effect was attributed to different permeation rates of dithranol and mobile Vaseline particles through the membrane.
Topics: Administration, Cutaneous; Anthralin; Biological Transport; Drug Stability; Membranes, Artificial; Petrolatum; Pharmaceutical Preparations; Photoacoustic Techniques; Skin Absorption
PubMed: 32194208
DOI: 10.1016/j.ijpharm.2020.119233 -
Frontiers in Microbiology 2020Influenza virus RNA-dependent RNA polymerase (vRdRp) does not have capping activity and relies on the capped RNAs produced by the host RNA polymerase II (RNAPII). The...
Influenza virus RNA-dependent RNA polymerase (vRdRp) does not have capping activity and relies on the capped RNAs produced by the host RNA polymerase II (RNAPII). The viral polymerases process the capped RNAs to produce short capped RNA fragments that are used as primers to initiate the transcription of viral mRNAs. This process, known as cap-snatching, can be targeted by antiviral therapeutics. Here, anthralin was identified as an inhibitor against influenza a virus (IAV) infection by targeting the cap-snatching activity of the viral polymerase. Anthralin, an FDA-approved drug used in the treatment of psoriasis, shows antiviral activity against IAV infection and . Importantly, anthralin significantly reduces weight loss, lung injury, and mortality caused by IAV infection in mice. The mechanism of action study revealed that anthralin inhibits the cap-binding function of PB2 subunit and endonuclease activity of PA. As a result, viral mRNA transcription is blocked, leading to the decreases in viral RNA replication and viral protein expression. In conclusion, anthralin has been demonstrated to have the potential of an alternative antiviral against influenza virus infection. Also, targeting the captive pocket structure that includes the N-terminus of PA endonuclease domain and the C-terminal of PB2 cap-binding domain of IAV RdRp may be an excellent strategy for developing anti-influenza drugs.
PubMed: 32132985
DOI: 10.3389/fmicb.2020.00178 -
Journal of Cutaneous Medicine and... 2020Psoriasis is a chronic, inflammatory disease with a varying degree of clinical presentations. Managing psoriasis has always been arduous due to its chronicity and its...
Psoriasis is a chronic, inflammatory disease with a varying degree of clinical presentations. Managing psoriasis has always been arduous due to its chronicity and its propensity to relapse. Prior to the development of targeted biologic therapies, there were few effective treatments for psoriasis. Ancient psoriasis therapies included pinetar, plant extracts, psychotherapy, arsenic, and ammoniated mercury. In the 19th century, chrysarobin was developed. Then, in the early half of the 20th century, anthralin and coal tar were in widespread use. In the latter half of the 20th century, treatments were limited to topical first-line therapies, systemic drugs, and phototherapy. However, as the treatment of psoriasis has undergone a revolutionary change with the development of novel biologic therapies, patients with moderate to severe psoriasis have been able to avail therapies with high efficacy and durability along with an acceptable safety profile. This article is a brief historical review of the management of psoriasis prior to the inception of biologics and with the development of novel biologic therapies.
Topics: Ammonia; Anthracenes; Arsenic; Biological Therapy; Canada; Coal Tar; Dermatologic Agents; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Mercuric Chloride; Phototherapy; Plant Extracts; Psoriasis
PubMed: 32003582
DOI: 10.1177/1203475420903682 -
Acta Dermatovenerologica Croatica : ADC Dec 2019The prevalence of psoriasis is 2% of the world's population (1). Inverse psoriasis is characterized by the development of erythematous shiny plaques at intertriginous...
The prevalence of psoriasis is 2% of the world's population (1). Inverse psoriasis is characterized by the development of erythematous shiny plaques at intertriginous areas of the body. The prevalence of only anogenital involvement appears to be low, but involvement of the anogenital area together with other areas is found in up to 45% of patients with psoriasis (2). A 21-year-old female student with a 3-month history of mild psoriasis (erythematosquamous plaque on the elbows and nail pitting on the nails of the hand) was referred to our Department. One month earlier, suddenly appearance of erythematous, smooth, clearly demarcated plaques was observed on the labia majora, the mons pubis, the perineal and perianal region together with a brownish hyperkeratotic papule on the pubic region (Figure 1, a-b). The patient underwent excisional biopsy at the Department of Surgery, and the pathohistological finding was unavailable to us. The elbows were treated with corticosteroid-keratolytic preparation, whereas the anogenital lesions were treated with moderately potent topical corticosteroids. In addition to anogenital erythema, on clinical examination we noticed an erythematosquamous plaque on the site of excision with a hyperkeratotic verrucous papule on the edge of the lesion (the Koebner phenomenon on the site of skin injury). In the pubic region, we noticed two hyperkeratotic papules and a few verrucous papules on labia majora. Localized dermatophyte or candida infection were excluded with a KOH test and scrapings culture. Serology for syphilis, HIV, and hepatitis were negative. Cervical Pap smear was normal. Biopsy of erythematosus lesion from the mons pubis was conclusive for psoriasis, and of the keratotic papule with the genital wart with positive HPV 6 and 11. The patient's older sister had chronic plaque psoriasis. We employed physically ablative methods like liquid nitrogen cryosurgery, electrocauterization, and curettage, applied topical agents like 0.5% podophyllotoxin solution, 20% podophyllin, and 80% trichloroacetic acid, and treated the psoriatic lesions with a short course of moderate-potency corticosteroids and tacrolimus ointment. All therapeutic attempts were ineffective for curing both diseases. Our patient either had psoriasis with sparse genital warts or exacerbation of multiple anogenital warts (Figure 2, a-b). Anogenital psoriasis is a skin disease that causes great discomfort. The disease-related quality of life is significantly reduced, especially regarding sexual behavior. Therapy for either anogenital psoriasis or genital warts is not entirely satisfactory. Many topical agents suitable for use on the psoriatic lesions on the body, such as coal tar, anthralin, vitamin D derivatives or retinoids, may be too irritating in the anogenital region. The most useful therapy for treatment of anogenital psoriasis are moderately potent topical corticosteroids and topical tacrolimus or pimecrolimus (1). However, corticosteroid-induced atrophy is possible in intertriginous sites. The Koebner phenomenon isomorphic response is the appearance of new skin lesions on areas of cutaneous injury in otherwise healthy skin (3). About 25% of patients with psoriasis have elicitation of psoriatic lesions by injury to the skin (4). Other than in patients with psoriasis, the Koebner phenomenon can be found in other skin diseases like vitiligo, lichen planus, lichen nitidus, pityriasis rubra pilaris, flat warts, and keratosis follicularis (Darier disease) (5). According to Eyre at al., about 67% patients with psoriasis (4) present with clearing of psoriatic lesions following skin injury (positive "reverse" Koebner reaction) (4). There is no single treatment for genital warts that is 100% effective, and different types of treatment are very often combined. Accepted methods of treatment involve chemical and physical destruction or removal (6). Since psoriasis koebnerizes, any destructive technique may exacerbate the psoriasis. Coexistence of anogenital psoriasis and HPV presents a huge therapeutic problem because a therapy for psoriasis such as corticosteroids can provoke appearance and/or reappearance of HPV infection, while some therapies for anogenital warts, like cryotherapy, curettage, laser ablation, electrosurgery, or surgery can provoke the appearance and/or reappearance of psoriatic infection due to the Koebner phenomenon.
Topics: Condylomata Acuminata; Female; Humans; Psoriasis; Young Adult
PubMed: 31969241
DOI: No ID Found -
The Journal of Organic Chemistry Jan 2020The role of the chemical environment in promoting anthralin/O reactions was discovered using neat solvents to model the amino acids of a cofactor-independent oxygenase....
The role of the chemical environment in promoting anthralin/O reactions was discovered using neat solvents to model the amino acids of a cofactor-independent oxygenase. Experimental and computational results highlight the importance of the substrate-enolate, which is accessed via energetically small, escalating steps in which the ground-state keto-isomer is tautomerized to an enol and then ionized by solvent. The resulting ion-pair is poised for spontaneous electron transfer to O. Similar activation may be exploited in biological/nonbiological oxidations involving O.
PubMed: 31830417
DOI: 10.1021/acs.joc.9b03133 -
JAMA Dermatology Jan 2020Treatment of psoriasis is associated with improved quality of life (QOL) in those with the disease. However, in daily clinical practice, the association between the...
IMPORTANCE
Treatment of psoriasis is associated with improved quality of life (QOL) in those with the disease. However, in daily clinical practice, the association between the degree of psoriasis clearance and QOL has not been studied to date, especially in the pediatric population.
OBJECTIVES
To identify the association between the degree of psoriasis improvement (as measured by the Psoriasis Area Severity Index [PASI] and body surface area [BSA] response) and QOL (as measured by the Children's Dermatology Life Quality Index [CDLQI]) in pediatric psoriasis, and to assess the association of treatment type with QOL, independent of psoriasis improvement.
DESIGN, SETTING, AND PARTICIPANTS
Data used in this single-center cohort study were extracted from the Child-CAPTURE (Continuous Assessment of Psoriasis Treatment Use Registry), a prospective, observational, daily clinical practice cohort of all children (aged <18 years) with a psoriasis diagnosis who attended the outpatient clinic of the Department of Dermatology at the Radboud University Medical Center in Nijmegen, the Netherlands, between September 3, 2008, and May 4, 2018. All records of treatment episodes with CDLQI, PASI, and BSA scores were included in the analysis.
EXPOSURES
Patients were treated according to daily clinical care. Treatments were clustered into topical, dithranol, conventional systemic, and biological treatments. Because of low numbers of UV-B phototherapy, this treatment was not assessed.
MAIN OUTCOMES AND MEASURES
Primary outcomes were mean change of CDLQI scores per PASI and BSA response categories (0 to <50, 50 to <75, 75 to <90, and ≥90) and mean CDLQI change per treatment categories.
RESULTS
In total, 319 patients (median [interquartile range] age, 10.0 [7.0] years; 183 female [57.4%]) were analyzed for PASI score improvement (399 treatment episodes) and improvement in BSA involvement (366 treatment episodes). The greatest improvements in CDLQI scores were seen in the PASI ≥90 response category, with an estimated marginal mean change in CDLQI score of -6.6 (95% CI, -7.5 to -5.7). The greatest improvements in CDLQI scores were also observed in the BSA ≥90 response category, with an estimated marginal mean change in CDLQI score of -6.8 (95% CI, -7.5 to -6.1). Systemic treatment demonstrated a greater degree of improvement of CDLQI compared with topical treatment, independent of PASI response categories.
CONCLUSIONS AND RELEVANCE
This cohort study in a real-world setting found that the greatest improvements in QOL were associated with PASI 90 or greater, a decrease in BSA involvement of 90% or greater, and systemic treatments. These findings suggest that reaching PASI 90 or greater and decreasing BSA involvement by at least 90% may be clinically meaningful treatment goals that will help pediatric patients with psoriasis reach optimal QOL.
Topics: Administration, Oral; Administration, Topical; Adolescent; Biological Products; Child; Child, Preschool; Dermatologic Agents; Female; Follow-Up Studies; Humans; Injections; Male; Netherlands; Prospective Studies; Psoriasis; Quality of Life; Severity of Illness Index; Treatment Outcome; Ultraviolet Therapy
PubMed: 31774449
DOI: 10.1001/jamadermatol.2019.3717 -
Journal of the American Academy of... Jan 2020Psoriasis is a chronic, multisystem, inflammatory disease that affects approximately 1% of children, with onset most common during adolescence. This guideline addresses...
Psoriasis is a chronic, multisystem, inflammatory disease that affects approximately 1% of children, with onset most common during adolescence. This guideline addresses important clinical questions that arise in psoriasis management and provides evidence-based recommendations. Attention will be given to pediatric patients with psoriasis, recognizing the unique physiology, pharmacokinetics, and patient-parent-provider interactions of patients younger than 18 years old. The topics reviewed here mirror those discussed in the adult guideline sections, excluding those topics that are irrelevant to, or lack sufficient information for, pediatric patients.
Topics: Adolescent; Adrenal Cortex Hormones; Anthralin; Biological Products; Calcineurin Inhibitors; Cardiovascular Diseases; Child; Child, Preschool; Coal Tar; Comorbidity; Cyclosporine; Dermatologic Agents; Dyslipidemias; Evidence-Based Medicine; Humans; Infant; Infant, Newborn; Inflammatory Bowel Diseases; Insulin Resistance; Mental Health; Metabolic Syndrome; Methotrexate; Nicotinic Acids; Obesity; Photochemotherapy; Psoriasis; Retinoids
PubMed: 31703821
DOI: 10.1016/j.jaad.2019.08.049 -
Antonie Van Leeuwenhoek Feb 2020Halophytic plants growing in harsh desert environments are rich reservoirs of unique endophytic microorganisms. Here, healthy fresh plants of the families Tamaricaceae...
Halophytic plants growing in harsh desert environments are rich reservoirs of unique endophytic microorganisms. Here, healthy fresh plants of the families Tamaricaceae and Amarantaceae at three saline locations in Iran were investigated for their bioactive endophytic fungi. Among a vast number of isolates, eight isolates were identified as Humicola fuscoatra (Sordariomycetes, Pezizomycotina, Ascomycota) by microscopy and representative DNA sequences of the 5.8S rDNA (ITS) and partial β-tubulin (TUB2). Those isolates were halotolerant, and highly bioactive, so that their intra- and extra-cellular metabolites possessed in vitro antifungal, antibacterial and antiproliferative activities, against a number of fungal and bacterial plant pathogens including the fungi Arthrobotrys conoides, Pyrenophora graminea, Pyricularia grisea and the bacteria Agrobacterium tumefaciens, Pseudomonas syringae and Xanthomonas oryzae. Chemical analyses of metabolites from the endophytes using HNMR, CNMR, NOESY, COSY, HMBC, HSQC, DEPT, TOCSY and EI MASS techniques identified 3,8-dihydroxy-1-methyl-9,10-anthracenedione (aloesaponarin II; an anthraquinone derivative), 1,8,9-anthracenetriol structure (chrysarobin; an anthranol derivative) and 2,4-di-tert-butylthiophenol in fungal extracts. To the best of our knowledge, this is the first report of endophytic association of halotolerant H. fuscoatra isolates with Tamaricaceae and Amarantaceae, and their bioactivity against plant pathogens. Also, the capability of chrysarobin and aloesaponarin II production is new to the fungal kingdom. These findings may find application in agriculture, pharmacology, and biotechnology.
Topics: Amaranthaceae; Anthracenes; Anthralin; Anthraquinones; Ascomycota; DNA, Bacterial; DNA, Ribosomal; Salt-Tolerant Plants; Tamaricaceae
PubMed: 31584108
DOI: 10.1007/s10482-019-01336-x -
Journal of Colloid and Interface Science Nov 2019The aim of the work was to exploit a methodology based on contact angle measurements for the purpose of membrane transport studies. Special attention has been paid to a...
The aim of the work was to exploit a methodology based on contact angle measurements for the purpose of membrane transport studies. Special attention has been paid to a model system of pharmacological relevance, consisting of the drug dithranol (from semisolid Vaseline suspension) in contact with an artificial skin barrier. The drug permeation has been monitored by the surface wettability evolution during the drug transport process. The surface wettability parameters, such as: surface free energy, 2D film pressure, contact angle hysteresis (CAH) and surface excess for long and short adsorption time intervals, have been derived from dynamic contact angle measurements of the probe liquid drops deposited on the outermost membrane layer. The analysis has allowed the apparent Arrhenius-type energy barrier for the drug surface adsorption (E/RT = -8.04 ± 0.84 at 295 K), the characteristic lag-time of the transport process (t = 20 ± 1.9 min) and the diffusion coefficient of the drug through the membrane (D = 1.25 ± 0.24·10 cm s) to be determined. The latter one remains in a good agreement with literature data for the same system investigated by means of spectroscopic methods.
PubMed: 31398563
DOI: 10.1016/j.jcis.2019.07.111