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International Journal of Molecular... Mar 2023Skin is a major administration route for drugs, and all transdermal formulations must be tested for their capability to overcome the cutaneous barrier. Therefore,...
Skin is a major administration route for drugs, and all transdermal formulations must be tested for their capability to overcome the cutaneous barrier. Therefore, developing highly reliable skin models is crucial for preclinical studies. The current in vitro models are unable to replicate the living skin in all its complexity; thus, to date, excised human skin is considered the gold standard for in vitro permeation studies. However, skin explants have a limited life span. In an attempt to overcome this problem, we used an innovative bioreactor that allowed us to achieve good structural and functional preservation in vitro of explanted human skin for up to 72 h. This device was then used to set up an in vitro inflammatory model by applying two distinct agents mimicking either exogenous or endogenous stimuli: i.e., dithranol, inducing the contact dermatitis phenotype, and the substance P, mimicking neurogenic inflammation. Our in vitro system proved to reproduce inflammatory events observed in vivo, such as vasodilation, increased number of macrophages and mast cells, and increased cytokine secretion. This bioreactor-based system may therefore be suitably and reliably used to simulate in vitro human skin inflammation and may be foreseen as a promising tool to test the efficacy of drugs and cosmetics.
Topics: Humans; Hydrodynamics; Skin; Administration, Cutaneous; Skin Absorption; Inflammation; Pharmaceutical Preparations
PubMed: 37047256
DOI: 10.3390/ijms24076284 -
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 -
ELife Jun 2020Despite the introduction of biologics, topical dithranol (anthralin) has remained one of the most effective anti-psoriatic agents. Serial biopsies from human psoriatic...
Despite the introduction of biologics, topical dithranol (anthralin) has remained one of the most effective anti-psoriatic agents. Serial biopsies from human psoriatic lesions and both the c-Jun/JunB and imiquimod psoriasis mouse model allowed us to study the therapeutic mechanism of this drug. Top differentially expressed genes in the early response to dithranol belonged to keratinocyte and epidermal differentiation pathways and IL-1 family members (i.e. but not elements of the IL-17/IL-23 axis. In human psoriatic response to dithranol, rapid decrease in expression of keratinocyte differentiation regulators (e.g. involucrin, and ), antimicrobial peptides (e.g. ß-defensins like S100 proteins like ), chemotactic factors for neutrophils (e.g. ) and neutrophilic infiltration was followed with much delay by reduction in T cell infiltration. Targeting keratinocytes rather than immune cells may be an alternative approach in particular for topical anti-psoriatic treatment, an area with high need for new drugs.
Topics: Animals; Anthralin; Chemokines, CXC; Dermatologic Agents; Interleukin-1; Keratinocytes; Mice; Neutrophils; Pore Forming Cytotoxic Proteins; Psoriasis; Serpins; Signal Transduction; Skin
PubMed: 32484435
DOI: 10.7554/eLife.56991 -
Anais Brasileiros de Dermatologia 2021
Randomized Controlled Trial
Topics: Administration, Topical; Alopecia Areata; Anthralin; Cyclopropanes; Humans
PubMed: 33849753
DOI: 10.1016/j.abd.2020.06.018 -
World Journal of Plastic Surgery Mar 2022A 16-year-old female with psoriasis presented to our Plastic Surgery Department with a significant chemical burn to the neck, upper torso and left cheek (TBSA 6%). She...
A 16-year-old female with psoriasis presented to our Plastic Surgery Department with a significant chemical burn to the neck, upper torso and left cheek (TBSA 6%). She applied a concoction of cream prescribed by her dermatologist in her native country, Poland when she returned to the United Kingdom. A few hours after application she developed a burn with pH of 5. A review of the cream revealed a mixture of 19% dithranol and 5% salicylic acid. This combination is recognized for managing psoriasis, however the strength of dithranol in the combination given is of a high concentration (normally <3%). This alone can cause a burn to the skin if left for a prolonged period of time. Salicylic acid is an enhancer which augments the stability of dithranol and increases its penetration and efficacy. The concentration of 5% is also on the higher end. Our patient was admitted for pain relief and further irrigation till normalization of the pH which was achieved after 3 days. A worrying aspect in our patients' case is that she was given the cream to commence at home. High concentration preparation is normally commenced in a controlled setting under medical supervision.
PubMed: 35592224
DOI: 10.52547/wjps.11.1.138 -
NPJ Vaccines Jun 2023
PubMed: 37349361
DOI: 10.1038/s41541-023-00689-9 -
Molecules (Basel, Switzerland) Jan 20231,8-dihydroxy-9-anthrone are tricyclic compounds with a ketone group in the middle ring and two hydroxyl groups substituted in the side-aromatic rings what results in...
1,8-dihydroxy-9-anthrone are tricyclic compounds with a ketone group in the middle ring and two hydroxyl groups substituted in the side-aromatic rings what results in formation of two intramolecular hydrogen bonds in which the oxygen atom from the ketone group is the proton acceptor. 1,8-dihydroxy-9-anthrones in which intramolecular proton transfer between C10 and CO in the middle ring occurs, can exist in a tautomeric keto-enol equilibrium. For anthralin, the most important representative of this group, this equilibrium has been studied previously, but it has not been studied for its derivatives. Substituents in the middle ring change the geometry of 1,8-dihydroxy-9-anthrones so they are also expected to affect the keto-enol equilibrium. It is also important to study the effect of intramolecular hydrogen bonds on the structure of both tautomeric forms. It was found that the nature of the substituent in the middle ring could affect the antioxidant properties of the investigated compound.
Topics: Anthralin; Protons; Electrons; Anthracenes; Alcohols; Ketones
PubMed: 36615539
DOI: 10.3390/molecules28010344 -
Cureus May 2024Background Psoriasis is a papulosquamous disease with variable morphology, distribution, severity, and course. Chronic plaque psoriasis, or psoriasis vulgaris, is the...
Background Psoriasis is a papulosquamous disease with variable morphology, distribution, severity, and course. Chronic plaque psoriasis, or psoriasis vulgaris, is the most common form of psoriasis. Present available preparations for mild to moderate chronic plaque psoriasis for topical use are local corticosteroids, coal tar, dithranol, tazarotene, calcipotriol, tapinarof, and calcineurin inhibitors. However, every preparation has its disadvantages. Calcipotriol, an active form of vitamin D, is available in topical form for dermatological use. Chronic plaque psoriasis is the chief medical use of calcipotriol for mild to moderate form. Methotrexate has dramatic results in psoriasis when used systemically. Now, topical formulation is being advocated in localized psoriasis, which is not associated with the side effects of the systemic form. Therefore, this study aimed to compare the effectiveness of topical calcipotriol and topical methotrexate on the basis of the psoriasis area severity index (PASI) in patients of chronic plaque psoriasis and compare their safety in terms of adverse effects. Methodology The total number of patients included in the study was 60. They were divided into two groups, with 30 patients each. One group was prescribed ointment calcipotriol 0.005% twice daily local application (Group C). The other group was prescribed methotrexate gel 1% twice daily local application (Group M). The patients were followed up on the fourth and eighth weeks, and at each time, thorough clinical examinations were conducted for all patients. The PASI score was calculated in each patient every time. Safety was assessed by biochemical parameters, and tolerability was assessed by the incidence of adverse effects. All the patients included in the study were investigated at baseline, fourth week, and eighth week. The data collected were transferred to a master chart and analyzed. Results For the patients in group C, the mean PASI score at 0 week was 5.93 ± 2.62, while at four weeks, the mean PASI score declined to 1.67 ± 1.13, and at eight weeks, the mean PASI score further declined to 0.67 ± 0.68. For the patients in group M, the mean PASI score at 0 week was 5.91 ± 2.22, while at four weeks, the mean PASI score declined to 1.91 ± 1.11, and at eight weeks, the mean PASI score further declined to 0.89 ± 0.72. Furthermore, there was no significant difference in the mean PASI score at various time points when compared between the two groups (p-value = 0.761, 0.296, 0.079, respectively). Thus, both drugs seem to be effective in treating mild- to moderate-grade chronic plaque psoriasis. Most of the patients in both groups showed marked clearance of the lesions. However, there were six patients in the calcipotriol group showing complete clearance of the lesions having mild-degree plaque psoriasis, as compared to three patients in the methotrexate group. In the present study, based on the comparison of safety and tolerability, four out of 30 patients (13.3%) in the calcipotriol group suffered skin irritation, whereas six out of 30 patients (20%) in the methotrexate group complained of a burning sensation. The adverse effects seen in the patients were transient and mild. Conclusion Topical calcipotriol and methotrexate were effective in reducing lesions in patients with chronic mild to moderate plaque psoriasis. Both drugs were well tolerated with mild and transient adverse effects and did not alter hematological and biochemical parameters.
PubMed: 38854231
DOI: 10.7759/cureus.59878 -
Cell and Tissue Research Dec 2020Inflammation of the cutaneous orofacial tissue can lead to a prolonged alteration of neuronal and nonneuronal cellular functions in trigeminal nociceptive pathways. In...
Inflammation of the cutaneous orofacial tissue can lead to a prolonged alteration of neuronal and nonneuronal cellular functions in trigeminal nociceptive pathways. In this study, we investigated the effects of experimentally induced skin inflammation by dithranol (anthralin) on macrophage activation in the rat trigeminal ganglion. Tissue localization and protein expression levels of ionized calcium-binding adaptor molecule 1 (Iba1), a macrophage/microglia-specific marker, and proliferation/mitotic marker antigen identified by the monoclonal antibody Ki67 (Ki67), were quantitatively analyzed using immunohistochemistry and western blots in control, dithranol-treated, dithranol- and corticosteroid-treated, and corticosteroid-treated trigeminal ganglia. Chronic orofacial dithranol treatment elicited a strong pro-inflammatory effect in the ipsilateral trigeminal ganglion. Indeed, daily dithranol treatment of the orofacial skin for 3-5 days increased the number of macrophages and Iba1 protein expression in the maxillary subregion of the ipsilateral ganglion. In the affected ganglia, none of the Iba1-positive cells expressed Ki67. This absence of mitotically active cells suggested that the accumulation of macrophages in the ganglion was not the result of resident microglia proliferation but rather the extravasation of hematogenous monocytes from the periphery. Subsequently, when a 5-day-long anti-inflammatory corticosteroid therapy was employed on the previously dithranol-treated orofacial skin, Iba1 immunoreactivity was substantially reduced in the ipsilateral ganglion. Collectively, our findings indicate that both peripheral inflammation and subsequent anti-inflammatory therapy affect macrophage activity and thus interfere with the functioning of the affected sensory ganglion neurons.
Topics: Adrenal Cortex Hormones; Animals; Inflammation; Macrophages; Male; Rats; Skin; Trigeminal Ganglion
PubMed: 32696216
DOI: 10.1007/s00441-020-03244-3 -
Cureus Mar 2024Background and objective Alopecia areata (AA) is a reiterative and nonscarring type of hair loss that can affect any hairy area of the body, particularly the scalp. It...
Background and objective Alopecia areata (AA) is a reiterative and nonscarring type of hair loss that can affect any hairy area of the body, particularly the scalp. It manifests as patchy or confluent hair loss with variations in demographics and ethnicity. There are numerous treatment options available, including topical and systemic steroids, topical minoxidil, dithranol, tacrolimus, psoralen and ultraviolet therapy (PUVA), contact immunotherapy, and oral immunosuppressive drugs. However, no previous contrast for efficacy is present between the topical betamethasone versus topical minoxidil alone in our population. This study aims to compare the efficacy of topical betamethasone dipropionate versus topical minoxidil in patients with AA. Methodology A nonrandomized controlled study was conducted at the Department of Dermatology, Jinnah Hospital Lahore, incorporating the data of patients between July 26, 2016, and January 26, 2017, after obtaining institutional ethical approval. One hundred patients with alopecia, either on the scalp or any other hairy part, from both genders, aged between 18 and 50 years, were included in the study. Two groups were created, and patients were assigned to these groups based on the clinician's choice. Group A patients were administered betamethasone dipropionate (0.05%) lotion twice daily on affected areas for 12 weeks. Group B patients were administered minoxidil (5%) solution twice daily on affected areas for 12 weeks. A four-week follow-up plan was followed. A five-point scale score system was used for alopecia grading. After 12 weeks, the hair regrowth score (RGS) was used to compare the efficacy of treatment between the two groups. Results A total of 100 patients with grades S1 to S3 AA of less than three months duration were enrolled. Two groups were created, with 50 patients in each group. The mean age in Group A was 29.08 ± 6.51 years, while in Group B, it was 29.38 ± 6.62 years. In Group A, there were 76% males and 24% females, while in Group B, there were 74% males and 26% females. Comparison of efficacy of topical betamethasone dipropionate versus topical minoxidil in patients with AA demonstrated a greater efficacy of 74% (Grade 3 and Grade 4 responses) in Group A, while in Group B, only 42% of patients showed efficacy. A statistically significant difference was found, with a -value of 0.001. No serious side effects were noted. Conclusions Our study concluded that topical betamethasone dipropionate (0.05%) lotion has statistically significantly higher efficacy compared to topical minoxidil (5%) solution in patients with AA.
PubMed: 38623137
DOI: 10.7759/cureus.56282