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International Journal of Women's Health 2024Vulvar intraepithelial neoplasia (VIN), the precursor lesion of vulvar squamous cell carcinoma (VSCC), may present as pruritic or asymptomatic lichenified plaques...
The Importance of p16 and p53 Immunohistochemical Staining in Diagnosing Vulvar Lichen Simplex Chronicus Mimicking Vulvar Intraepithelial Neoplasia with False-Positive Human Papillomavirus Type 66.
Vulvar intraepithelial neoplasia (VIN), the precursor lesion of vulvar squamous cell carcinoma (VSCC), may present as pruritic or asymptomatic lichenified plaques surrounded by single or multiple discrete or confluent macules or papules. VIN is divided into high-grade squamous intraepithelial lesion (HSIL), which is human papillomavirus (HPV)-driven, and differentiated VIN (DVIN), which develops independently of HPV. Histopathological examination and HPV genotyping polymerase chain reaction (PCR) tests should be performed to distinguish between HSIL and DVIN. Lichenified plaques surrounded by multiple papules are found not only in VIN but also in vulvar lichen simplex chronicus (LSC). This chronic inflammatory skin disease mostly appears in labia majora and is triggered by sweating, rubbing, and mental stress. IHC staining of p16 and p53 are recommended as the most commonly used biomarkers for VIN in diagnostically challenging cases. IHC staining is also beneficial to confirm the accuracy of the HPV detection technique, as p16-negative staining may also represent a false-positive result. We report a case of the importance of p16 and p53 IHC staining in diagnosing vulvar LSC mimicking VIN with false-positive HPV-66. The patient was previously diagnosed with VIN based on clinical examination. HPV-66 was detected by PCR from a vulvar biopsy sample. Histopathological examination revealed stromal lymphocytic infiltration with non-specific chronic dermatitis; neither atypia nor koilocyte was observed. Both p16 and p53 IHC staining were negative. The patient was diagnosed and treated as vulvar LSC with 10 mg cetirizine tablet, emollient, and 0.1% mometasone furoate cream. Clinical improvement was observed as the lesions became asymptomatic hyperpigmented macules in the 4 weeks of follow-up, without recurrence after 3 years of follow-up. Both p16 and p53 IHC staining might help distinguish HSIL and DVIN mutually and from other vulvar mimics in diagnostically challenging cases.
PubMed: 38196407
DOI: 10.2147/IJWH.S439825 -
Archives of Dermatological Research Jan 2024A myriad of therapeutic modalities for alopecia areata are available; however, none is of high level of evidence, creating an immense need for the evaluation of other... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
A myriad of therapeutic modalities for alopecia areata are available; however, none is of high level of evidence, creating an immense need for the evaluation of other treatment modalities, of which topical sodium valproate is of potential role via proposed decrease in beta-catenin breakdown, despite its well-known side effect of hair fall as an oral therapy.
OBJECTIVE
Evaluating the efficacy and the safety of sodium valproate (SV)-loaded nanospanlastics, in comparison to topical corticosteroids, this is the currently available gold standard topical treatment for patchy AA.
METHODOLOGY
A total of 66 patients with patchy AA were randomly assigned to receive either topical mometasone furoate lotion or topical SV applied twice daily to all patches except a control patch, which was left untreated. Clinical, trichoscopic and biochemical assessments of beta-catenin tissue levels and Axin-2 gene expression were carried out at baseline and after 3 months.
RESULTS
Both therapeutic modalities were comparable. Potential efficacy was highlighted by significant improvement in the representative patch, the largest treated patch, to the control patch, the smallest untreated patch in both steroid and valproate groups (p = 0.027, 0.003 respectively). Both beta-catenin levels and Axin-2 gene expression were reduced after treatment, pointing to the inhibitory effect of dominating uncontrolled inflammatory milieu. Baseline beta-catenin was found to significantly negatively correlate with improvement in the representative patch in patients with baseline level above 0.42 ng/ml (p = - 0.042).
CONCLUSION
Both topical SV and steroids are of comparable modest efficacy. Thus, further evaluation of SV is due in combination with intralesional steroids and other anti-inflammatory treatment modalities, together with developing individualized approaches based on baseline beta-catenin level.
GOV IDENTIFIER
NCT05017454, https://clinicaltrials.gov/ct2/show/NCT05017454 .
Topics: Humans; Alopecia Areata; Valproic Acid; beta Catenin; Axin Protein; Treatment Outcome
PubMed: 38170256
DOI: 10.1007/s00403-023-02785-1 -
Molecules (Basel, Switzerland) Nov 2023Mometasone furoate is a synthetic corticosteroid used in the treatment of skin inflammatory conditions, hay fever and asthma. The industrial manufacturing routes to...
Mometasone furoate is a synthetic corticosteroid used in the treatment of skin inflammatory conditions, hay fever and asthma. The industrial manufacturing routes to mometasone furoate are generally accompanied by the formation of numerous process impurities that need to be detected and quantified, as requested by regulatory authorities. The ready availability of such impurities in the required quantity and purity is therefore essential for toxicological studies, analytical method development and process validation. Herein, we report the multi-gram scale preparation of 21'-chloro-(16'α-methyl-3',11',20'-trioxo-pregna-1',4'-dien-17'-yl)-furan-2-carboxylate (mometasone furoate EP impurity C), one of the known impurities of mometasone furoate. This study also includes the systematic investigation of the final acylation step, as well as the characterization of the difuroate enol ether intermediate and its conversion to the target impurity C.
Topics: Humans; Mometasone Furoate; Pregnadienediols; Asthma; Acylation
PubMed: 38067588
DOI: 10.3390/molecules28237859 -
Skin Health and Disease Dec 2023Atopic dermatitis (AD) is one of the most common inflammatory skin diseases. It is associated with significant itch and impaired quality of life. Systemic treatments are...
BACKGROUND
Atopic dermatitis (AD) is one of the most common inflammatory skin diseases. It is associated with significant itch and impaired quality of life. Systemic treatments are efficient but associated with side effects. Novel topical treatments with a favourable safety profile are needed. SNG100 is a novel composition of hydrocortisone 1% in a cream base comprising sulphated polysaccharide (SPS; extracted from in-house cultivated Porphyridium Cruentum unicellular algae), a well-known hydrating, moisturising and a skin barrier repairing agent.
OBJECTIVES
To assess the safety, usability and efficacy of SNG100 cream in patients aged ≥6 years with moderate AD.
METHODS
In this proof of concept phase I, double-blind, randomised trial, participants received one of three treatments for 14 days: SNG100 twice daily (BID), hydrocortisone 1% BID or mometasone furoate once daily (QD). The primary endpoint was the safety and tolerability of SNG100 cream compared to hydrocortisone 1% and mometasone furoate. The secondary endpoint was the subject's usability of SNG100. Exploratory efficacy endpoints included percent change from baseline in SCOring AD (SCORAD), Eczema Area and Severity Index, Patient-Oriented Eczema Measure, Dermatology Life Quality Index, pruritus Numerical Rating Score (NRS), peak pruritus-NRS and Investigator's Global Assessment. Subjects were also followed up without any treatment for additional 14 days.
RESULTS
Overall, 66 participants were screened, and 60 patients were randomised. SNG100 demonstrated a high safety profile, similar to marketed products hydrocortisone 1% and mometasone furoate 0.1%, with no unanticipated drug safety related events. SNG100 and mometasone furoate 0.1% cream achieved almost similar and statistically significant greater percentage reductions from baseline in SCORAD as compared to hydrocortisone 1% cream. SNG100 demonstrated significant improvement in NRS as compared to hydrocortisone 1% cream. Remarkably, SNG100 led to a lasting effect with only 29.4% of subjects returning to IGA3 during the follow-up period compared to 50% and 38.9% in the hydrocortisone 1% and in mometasone furoate treatment arms, respectively.
CONCLUSIONS
Topical SNG100 is an effective, safe, and well-tolerated innovative treatment for moderate AD. Trial registration number: NCT04615962 (Topical Cream SNG100 for Treatment in Moderate AD Subjects).
PubMed: 38047249
DOI: 10.1002/ski2.293 -
Biomedicines Sep 2023Mometasone furoate (MF) is a kind of glucocorticoid with extensive pharmacological actions, including inhibiting tumor progression; however, the role of MF in head and...
Mometasone furoate (MF) is a kind of glucocorticoid with extensive pharmacological actions, including inhibiting tumor progression; however, the role of MF in head and neck squamous cell carcinoma (HNSCC) is still unclear. This study aimed to evaluate the inhibitory effect of MF against HNSCC and investigate its underlying mechanisms. Cell viability, colony formation, cell cycle and cell apoptosis were analyzed to explore the effect of MF on HNSCC cells. A xenograft study model was used to investigate the effect of MF on HNSCC in vivo. The core targets of MF for HNSCC were identified using network pharmacology analysis, TCGA database analysis and real-time PCR. Molecular docking was performed to determine the binding energy. Protein tyrosine phosphatase non-receptor type 11 (PTPN11)-overexpressing cells were constructed, and then, the cell viability and the expression levels of proliferation- and apoptosis-related proteins were detected after treatment with MF to explore the role of PTPN11 in the inhibitory effect of MF against HNSCC. After cells were treated with MF, cell viability and the number of colonies were decreased, the cell cycle was arrested and cell apoptosis was increased. The xenograft study results showed that MF could inhibit cell proliferation via promoting cell apoptosis in vivo. PTPN11 was shown to be the core target of MF against HNSCC via network pharmacology analysis, TCGA database analysis and real-time PCR. The molecular docking results revealed that PTPN11 exhibited the strongest ability to bind to MF. Finally, MF could attenuate the effects of increased cell viability and decreased cell apoptosis caused by PTPN11 overexpression, suggesting that MF can inhibit the progression of HNSCC by regulating PTPN11. MF targeted PTPN11, promoting cell cycle arrest and cell apoptosis, and consequently exerting effective anti-tumor activity.
PubMed: 37892971
DOI: 10.3390/biomedicines11102597 -
BMC Chemistry Oct 2023Two simple, accurate and precise chromatographic methods have been developed and validated for estimating Mupirocin (MUP) in two binary mixtures. Mixture (1); with...
Two simple, accurate and precise chromatographic methods have been developed and validated for estimating Mupirocin (MUP) in two binary mixtures. Mixture (1); with Fluticasone propionate (FLU) together with two of their impurities, namely; Pseudomonic acid-D (Pseud-D) and Fluticasone impurity C (FIC). Mixture (2); with Mometasone furoate (MF) along with Pseud-D impurity. High performance thin layer chromatography (HPTLC-densitometry) and high performance liquid chromatography (RP-HPLC) were the two proposed methods. In the HPTLC method, good separation of both mixtures was achieved by using HPTLC plates pre-coated with silica gel 60 F as stationary phase and the mobile phase consisted of toluene: chloroform: ethanol at a ratio of (5: 4: 2, by volume). The detection was carried out at 220 nm for MUP and 254 nm for FLU, MF, Pseud-D and FIC. In the HPLC method, chromatographic separation was carried out using Agilent Eclipse XDB (250 mm×4.6 mm, 5 μm) C18 column. For mixture (1), a mobile phase of methanol: sodium di-hydrogen phosphate (pH 3.0) was applied in stepwise gradient elution starting at ratios of (50: 50, v/v) and then switching to (80: 20, v/v) after 7 min at a flow rate of 1 mL.min. Detection was performed using diode array detector at 220 nm for MUP and Pseud-D and 240 nm for FLU and FIC. For mixture (2), the same mobile phase was used, but in isocratic elution in the ratio (80: 20, v/v) at flow rate of 1 mL.min and detection at 220 nm for MUP and Pseud-D and 248 nm for MF. The two methods successfully separated the cited drugs and were used to determine the drugs in pure form as well as pharmaceutical dosage forms. Validation was done as per International Council on Harmonization guidelines. Furthermore, the greenness of the proposed methods compared to the reported method, was evaluated as per the National Environmental Method Index, analytical Eco scale, Green Analytical Procedure Index and Analytical Greenness metric approaches.
PubMed: 37891646
DOI: 10.1186/s13065-023-01055-5 -
Asian Pacific Journal of Allergy and... Dec 2023Intranasal corticosteroid (INCS) has a beneficial effect on ocular symptoms in allergic rhinitis (AR). To our knowledge, the cost-effectiveness of available INCS for AR... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Intranasal corticosteroid (INCS) has a beneficial effect on ocular symptoms in allergic rhinitis (AR). To our knowledge, the cost-effectiveness of available INCS for AR with ocular symptoms is yet to be demonstrated.
OBJECTIVE
To evaluate the cost-effectiveness of INCSs including Budesonide (BANS), Mometasone furoate (MFNS), Triamcinolone (TANS), and Fluticasone furoate (FFNS) on ocular symptoms associated with AR in the Thai context.
METHODS
The percentage of effectiveness in improving total ocular symptoms score (TOSS) was derived from the result of a meta-analysis that estimated the SMD of each INCS treatment compared to placebo as clinical input parameters. A cost-effectiveness analysis based on a decision-tree model to assess one-year costs and outcomes from a Thai societal perspective. The outcomes were to compare incremental cost-effectiveness ratio (ICER). Probabilistic sensitivity analyses (PSA) were also conducted to capture parameter uncertainties.
RESULTS
13 eligible RCTs with a total of 3,722 patients with SAR were included in the analysis. The percentage of effectiveness of FFNS, MFNS, TANS, and BANS was 59.89%, 45.60%, 24.89%, and 16.00%, respectively. The ICER of FFNS, MFNS, and TANS is THB-6,539.92, 4,593.83, and 1,401.24 compared to BANS. CECA result showed the probability of using FFNS is considered cost-effective in 87.50% of cases from zero value followed by MFNS (0.80%), TANS (5.40%), and BANS (6.30%). With a threshold greater than THB20,000, FFNS is considered a cost-effective strategy.
CONCLUSIONS
FFNS is a cost-effective option compared to alternative INCSs in Thailand for treating AR with ocular symptoms.
Topics: Humans; Rhinitis, Allergic, Seasonal; Cost-Effectiveness Analysis; Rhinitis, Allergic; Administration, Intranasal; Adrenal Cortex Hormones; Mometasone Furoate; Anti-Allergic Agents; Treatment Outcome
PubMed: 37874315
DOI: 10.12932/AP-070823-1669 -
Journal of Experimental Pharmacology 2023Interleukin 17 (IL-17) and interferon gamma (IFN-γ) play a role in the pathogenesis of psoriasis vulgaris (PV). Topical corticosteroids are still utilised as first-line...
BACKGROUND
Interleukin 17 (IL-17) and interferon gamma (IFN-γ) play a role in the pathogenesis of psoriasis vulgaris (PV). Topical corticosteroids are still utilised as first-line therapy for mild to moderate PV. However, long-term use of corticosteroid is associated with various side effects. Linn. (Ciplukan) possesses anti-inflammatory properties that could serve as a potential alternative topical therapy for PV.
OBJECTIVE
To assess the efficacy of topical ciplukan as an anti-inflammatory agent targeting the expression of IL-17 and IFN-γ.
METHODS
Psoriasis was induced using imiquimod cream, therefore divided into five groups. Group I, the psoriasis control group, received only imiquimod cream. Groups C1 and C2 received imiquimod cream followed by a mixture of Ciplukan and vaseline in a 1:2 and 1:4 ratio, respectively. Group M, the standard therapy group, received imiquimod cream, followed by mometasone furoate cream. Lastly, group V, the vehicle group, received imiquimod cream followed by vaseline album. Expression of IL-17 and IFN-γ in mice's skin tissue was analysed using reverse transcription polymerase chain reaction (RT-PCR) after seven days of treatment.
RESULTS
The mean expression of IL-17 in Group C1 (22.60) was significantly lower (p = 0.012) than in the psoriasis control group (23.60), and there was no significant difference (p = 0.613) in Group M (22.41). The mean expression of IFN-γ in Group C1 (26.97) and Group C2 (27.03) was also significantly lower (p = 0.026 and p = 0.026, respectively) than Group I (28.80), and there was no significant difference (p = 0.180 and p = 0.093, respectively) than Group M (26.03).
CONCLUSION
Expression of IL-17 and IFN-γ in the ciplukan group is lower than in the psoriasis control group, and there is no significant difference compared to the standard therapy group.
PubMed: 37842316
DOI: 10.2147/JEP.S427615 -
International Journal of Nanomedicine 2023We designed a 0.05% mometasone furoate (MF) nanocrystal dispersion and investigated whether the application of MF nanocrystals in nasal formulations enhanced local...
PURPOSE
We designed a 0.05% mometasone furoate (MF) nanocrystal dispersion and investigated whether the application of MF nanocrystals in nasal formulations enhanced local absorption compared to traditional nasal MF formulations (CA-MF).
METHODS
MF nanocrystal dispersions (MF-NPs) were prepared by bead milling MF microcrystal dispersions (MF-MPs) consisting of MF, 2-hydroxypropyl-β-cyclodextrin, methylcellulose, and purified water. Pluronic F-127 combined with methylcellulose, Pluronic F-68, or carbopol was used as a base for in situ gelation (thickener). MF concentrations were measured using high-performance liquid chromatography, and nasal absorption of MF was evaluated in 6 week-old male Institute of Cancer Research (ICR) mice.
RESULTS
The particle size range of MF prepared with the bead mill treatment was 80-200 nm, and the nanoparticles increased the local absorption of MF, which was higher than that of CA-MF and MF-MPs. In addition, unlike the results obtained in the small intestine and corneal tissue, the high absorption of nanocrystalline MF in the nasal mucosa was related to a pathway that was not derived from energy-dependent endocytosis. Moreover, the application of the in situ gelling system attenuated the local absorption of MF-NPs, owing to a decrease in drug diffusion in the dispersions.
CONCLUSION
We found that nanoparticulation of MF enhances local intranasal absorption, and nasal bioavailability is higher than that of CA-MF. In addition, we demonstrate that viscosity regulation is an important factor in the design of nasal formulations based on MF nanocrystals. These findings provide insights for the design of novel nanomedicines with enhanced nasal bioavailability.
Topics: Male; Animals; Mice; Mometasone Furoate; Nasal Absorption; Nasal Mucosa; Methylcellulose
PubMed: 37841023
DOI: 10.2147/IJN.S430952 -
Saudi Pharmaceutical Journal : SPJ :... Nov 2023: Limited data exists on the use of rivaroxaban for the treatment of pediatric patients. This report presents a case of probable rivaroxaban-induced Erythema Multiforme...
: Limited data exists on the use of rivaroxaban for the treatment of pediatric patients. This report presents a case of probable rivaroxaban-induced Erythema Multiforme in Children. A female patient aged 5.5 years with antiphospholipid syndrome (APS) was administered oral rivaroxaban tablets 2.5 mg twice a day for 16 days. Subsequently, the patient developed a slight itching sensation on both feet and buttocks without an apparent cause. The following day, erythema multiforme appeared across the body in a scattered pattern. The erythema presented higher than the skin surface and partially merged into areas of the skin. Following an increase in the extent and degree of the erythema, all oral medications were ceased. Treatment with dexamethasone sodium phosphate injection, mometasone furoate cream, and mucopolysaccharide polysulfate cream resulted in an improvement of erythema multiforme. The erythema diminished and did not deteriorate subsequent to changing from rivaroxaban tablets to warfarin sodium tablets, and receiving nadroparin calcium injection.
PubMed: 37829191
DOI: 10.1016/j.jsps.2023.101801