Risk of Paradoxical Eczema in Patients Receiving Biologics for Psoriasis.

Importance: Biologics used for plaque psoriasis have been reported to be associated with an atopic dermatitis (AD) phenotype, or paradoxical eczema, in some patients. The risk factors for this are unknown. Objective: To explore risk of paradoxical eczema by biologic class and identify factors associated with paradoxical eczema. Design, Setting, and Participants: This prospective cohort study used data from the British Association of Dermatologists Biologics and Immunomodulators Register for adults treated with biologics for plaque psoriasis who were seen at multicenter dermatology clinics in the UK and Ireland. Included participants were registered and had 1 or more follow-up visits between September 2007 and December 2022. Exposures: Duration of exposure to tumor necrosis factor (TNF) inhibitors, interleukin (IL) 17 inhibitors, IL-12/23 inhibitors, or IL-23 inhibitors until paradoxical eczema onset, treatment discontinuation, last follow-up, or death. Main Outcomes and Measures: Incidence rates of paradoxical eczema, paradoxical eczema risk by biologic class, and the association of demographic and clinical variables with risk of paradoxical eczema were assessed using propensity score-weighted Cox proportional hazards regression models. Results: Of 56 553 drug exposures considered, 24 997 from 13 699 participants were included. The 24 997 included exposures (median age, 46 years [IQR, 36-55 years]; 57% male) accrued a total exposure time of 81 441 patient-years. A total of 273 exposures (1%) were associated with paradoxical eczema. The adjusted incidence rates were 1.22 per 100 000 person-years for IL-17 inhibitors, 0.94 per 100 000 person-years for TNF inhibitors, 0.80 per 100 000 person-years for IL-12/23 inhibitors, and 0.56 per 100 000 person-years for IL-23 inhibitors. Compared with TNF inhibitors, IL-23 inhibitors were associated with a lower risk of paradoxical eczema (hazard ratio [HR], 0.39; 95% CI, 0.19-0.81), and there was no association of IL-17 inhibitors (HR, 1.03; 95% CI, 0.74-1.42) or IL-12/23 inhibitors (HR, 0.87; 95% CI, 0.66-1.16) with risk of paradoxical eczema. Increasing age (HR, 1.02 per year; 95% CI, 1.01-1.03) and history of AD (HR, 12.40; 95% CI, 6.97-22.06) or hay fever (HR, 3.78; 95% CI, 1.49-9.53) were associated with higher risk of paradoxical eczema. There was a lower risk in males (HR, 0.60; 95% CI, 0.45-0.78). Conclusions and Relevance: In this study, in biologic-treated patients with psoriasis, paradoxical eczema risk was lowest in patients receiving IL-23 inhibitors. Increasing age, female sex, and history of AD or hay fever were associated with higher risk of paradoxical eczema. The overall incidence of paradoxical eczema was low. Further study is needed to replicate these findings.

Ameliorative effect of nebivolol in doxorubicin-induced cardiotoxicity.

This study aimed to investigate the potential of nebivolol in preventing doxorubicin-induced cardiotoxicity by targeting the inflammatory, oxidative, and apoptotic pathways. Twenty-eight male rats were randomly divided into four groups, each consisting of seven rats. The control group received standard diets and unrestricted access to water. The rats in the normal saline (N/S) group were administered a 0.9% normal saline solution for two weeks. The doxorubicin group (the "induced group") received doxorubicin at a dosage of 2.5 mg/kg three times per week for two weeks. The nebivolol group received an oral dose of 4 mg/kg of nebivolol for the same duration. The cardiac tissues of rats treated with doxorubicin exhibited increased levels of tumor necrosis factor, interleukin-1, malondialdehyde, and caspase-3 compared to the normal saline control group (p<0.05), along with decreased levels of total antioxidant capacity and Bcl-2. These results show that doxorubicin is harmful to the heart. The administration of nebivolol significantly reduced the cardiotoxic effects induced by doxorubicin, as indicated by a statistically significant decrease in the levels of inflammatory markers, specifically tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß) (p<0.05). The nebivolol group exhibited a significant decrease in malondialdehyde levels, which serves as a signal of oxidation, in cardiac tissue compared to the doxorubicin-only group (p<0.05). Additionally, the nebivolol group showed a significant increase in overall antioxidant capacity. Nebivolol dramatically attenuated doxorubicin-induced cardiotoxicity in rats, likely by interfering with oxidative stress, the inflammatory response, and the apoptotic pathway.

Integrated proteomics and genomics analysis of paradoxical eczema in psoriasis patients treated with biologics.

BACKGROUND: Few studies have explored the immunology and genetic risk of paradoxical eczema occurring as an adverse event of biologic therapy in patients with psoriasis. OBJECTIVES: We sought to describe the systemic inflammatory signature of paradoxical eczema using proteomics and explore whether this is genetically mediated. METHODS: This study used the Olink Target 96 Inflammation panel on 256 serum samples from 71 patients with psoriasis and paradoxical eczema, and 75 controls with psoriasis to identify differentially expressed proteins and enriched gene sets. Case samples from 1 or more time points (T1 prebiologic, T2 postbiologic, and T3 postparadoxical eczema) were matched 1:1 with control samples. Genes contributing to enriched gene sets were selected, and functional single nucleotide polymorphisms used to create polygenic risk scores in a genotyped cohort of 88 paradoxical eczema cases and 3124 psoriasis controls. RESULTS: STAMBP expression was lower in cases at T1 than in controls (log-fold change: -0.44; adjusted P = .022); no other proteins reached statistical significance at equivalent time points. Eleven gene sets including cytokine and chemokine pathways were enriched in cases at T2 and 10 at T3. Of the 39 proteins contributing to enriched gene sets, the majority are associated with the atopic dermatitis serum proteome. A polygenic risk score including 38 functional single nucleotide polymorphisms linked to enriched gene sets was associated with paradoxical eczema (adjusted P = .046). CONCLUSIONS: The paradoxical eczema systemic inflammatory proteome trends toward atopic dermatitis at a gene-set level and is detectable before onset of the phenotype. This signature could be genetically determined.

Correlation of Celiac Diseases with Candida Spp. Based on Anti-gliadin Antibodies.

A variety of Candida spp. can be found as a natural commensal fungus in various parts of the human body. This fungus may be associated with various diseases such as celiac disease (CD). Gliadin, a component of the gluten protein complex that is mostly found in wheat, is the main inducer of CD. A number of studies have demonstrated that patients infected with Candida can develop CD, and vice versa. C. albicansis presumed to induce CD because it has a protein homologous to gliadin in its cell wall called Hwp1. Despite the non-specificity of the anti-gliadin test, the detection of antibodies against anti-gliadin (AGA) and anti-tissue transglutaminase (anti-tTG) are important in the diagnosis of CD. Some evidence is now available to support the hypothetical correlation between Candida spp. and CD, as high levels of AGA have been found in patients infected with candidiasis without CD. Further study is needed to confirm this relationship.

Parity in Correlation with Stage and Estrogen Receptor Type in Breast Cancer.

BACKGROUND: Parity is related to breast cancer in various ways. Its effects on the development of breast cancer are not independent and should be investigated at the same time as other reproductive factors. The association between parity and stage and type of breast cancer receptor was studied. METHODS: Parity was established for 75 patients with estrogen receptor (ER) positive breast cancer and 45 patients with ER-negative breast cancer. The stages of breast cancer were also determined. RESULTS: Breast cancer was found to have an association with high parity (≥ 3 parities). Significantly, most patients were diagnosed with stage II breast cancer, and this was especially frequent in patients with high parity. Stage IIB was most common, particularly among those 40-49 years old. ER-positive and ER-negative stage II breast cancer were both common among patients with high parity. CONCLUSION: Breast cancer, particularly at stage II, is associated with high parity. Parity is also associated with type of breast cancer, based on estrogen receptor category. This finding supports the recommendation that breast cancer should be screened in women with a high parity. Increased births should be considered a risk factor particularly for stage II breast cancer independent of cancer type.

A Positive or Negative Connection of Diabetes Mellitus to the Oral Microbiota.

Common noncommunicable diabetes mellitus disease has many complications in several parts of the human body. The oral cavity is one of the areas affected by diabetes mellitus conditions. The most common complications of diabetes mellitus in oral areas include increased drying of the mouth and increased oral diseases resulting from either microbial activity, such as dental caries, periodontal diseases, and oral candidiasis, or physiological problems, such as oral cancer, burning mouth syndrome, and temporomandibular disorders. Diabetes mellitus also has an impact on the diversity and quantity of oral microbiota. Oral infections promoted by diabetes mellitus mainly result from disturbance of the balance between different species of oral microbiota. Some oral species may be positively or negatively correlated with diabetes mellitus, while others may not be affected at all. The most numerous species in the presence of diabetes mellitus are those of phylum Firmicutes of bacteria such as hemolytic Streptococci, Staphylococcus spp., Prevotella spp., Leptotrichia spp., and Veillonella and species of the fungus Candida. Proteobacteria spp. and Bifidobacteria spp. are common microbiota that are negatively impacted by diabetes mellitus. In general, the effect of diabetes mellitus could include all types of oral microbiota, whether it is bacteria or fungi. The 3 types of association between diabetes mellitus and oral microbiota that will be illustrated in this review are increase, decrease, or lack of impact. As final inclusion, a great number of oral microbiota have increased in the presence of diabetes mellitus.

Antimicrobial Activity of the Nanoparticle Form of Greens (Lemon, Black Seeds or Flax) with Silver on Drug-resistant Human Pathogens.

BACKGROUND: Synthesizing a green source that has antimicrobial activity in nanoparticles is a novel and exciting approach to pharmaceutical science with promising results. OBJECTIVE: Green-silver nanoparticles (G-AgNPs) were evaluated for their antimicrobial action on drugresistant pathogens. METHODS: Lemon, black seeds, and flax were selected as green sources to synthesize nanoparticles formed with silver. Physical and chemical characteristics of these preparations were identified. The antimicrobial activities of the prepared compounds against drug-resistant clinical isolates of seven bacteria and five fungi were identified by disk diffusion and dilution methods. RESULTS: The nanoparticle characteristics were confirmed by physical and chemical measurements. Lemon extract with silver nanoparticles (L-AgNP) showed more antimicrobial action, particularly on Gram-positive bacteria and Candida albicans. Silver nanoparticles with black seeds (B-AgNP) and flax (F-AgNP) had only antibacterial effects on a single bacterium (Enterobacter cloacae). Escherichia coli, Staphylococcus aureus, and two fungi, Candida glabrata and Candida utilis, showed resistance to all nanoparticles from plants. CONCLUSION: Lemon with silver nanoparticle is an effective plant product for use against various drugresistant species of human pathogens. Further pharmaceutical studies are required to verify the suitability of this form of the drug for human use. Another plant is recommended for testing against the most resistant strains of pathogens.

Atopic Polygenic Risk Score Is Associated with Paradoxical Eczema Developing in Patients with Psoriasis Treated with Biologics.

Biologic therapies for psoriasis can cause paradoxical eczema. The role of genetic factors in its pathogenesis is unknown. To identify risk variants, we conducted a GWAS of 3,212 patients with psoriasis, of whom 88 developed paradoxical eczema. Two lead SNPs reached genome-wide significance (P ≤ 5 × 10-8) for association with paradoxical eczema: rs192705221 (near UNC5B, P = 9.52 × 10-10) and rs72925168 (within SLC1A2, P = 1.66 × 10-9). Genome-wide significant SNPs from published GWAS were used to generate polygenic risk scores (PRSs) for atopic eczema, general atopic disease, or a combination, which were tested for association with paradoxical eczema. Improvement over a clinical risk model was assessed by the area under the curve. All three atopy polygenic risk scores were associated with paradoxical eczema (P < 0.05); polygenic risk score for a combination of atopic eczema and general atopic disease had the strongest association (OR = 1.83, 95% CI = 1.17-2.84, P = 0.0078). Including atopic polygenic risk scores in the multivariable model, which included age, sex, atopic background, and psoriatic arthritis history, increased the area under the curve from 0.671 to 0.681-0.686. Atopic genetic burden is associated with paradoxical eczema occurring in biologic-treated patients with psoriasis, indicating shared underlying mechanisms. Incorporating genetic risk may improve treatment outcome prediction models for psoriasis.

The effect of immunomodulators on seroconversion after BNT162b2 and AZD1222 vaccines in patients with immune-mediated inflammatory diseases: a prospective cohort study.

BACKGROUND: Biologic and nonbiologic immunomodulators, used to treat immune-mediated inflammatory diseases (IMIDs), could impair the immune response to COVID-19 vaccines and thus vaccine effectiveness. OBJECTIVES: Our objective was to investigate the association between biologic and nonbiologic immunomodulators and seroconversion following the first and second dose of COVID-19 vaccines in patients with IMIDs. METHODS: Serum samples were collected following the first or second dose of the BNT162b2 or AZD1222 vaccines from patients receiving biologic and/or nonbiologic immunomodulators for one or more of psoriasis, psoriatic arthritis, rheumatoid arthritis, inflammatory bowel disease or systemic lupus erythematosus. Seroconversion was defined as a positive Roche Elecsys® Anti-SARS-CoV-2 S (spike protein subunit S1/receptor binding domain) immunoassay (≥ 0.8 U mL-1). Association between immunomodulator exposure and seroconversion was assessed using logistic regression, adjusting for age and sex. RESULTS: After excluding those with prior COVID-19, post-first vaccine dose samples from 193 participants and post-second dose samples from 312 participants were included in the analysis. Following the first vaccine dose, 17.6% (n = 34) of participants did not seroconvert. Seroconversion was reduced for those on nonbiologic [adjusted odds ratio (OR) 0.29, 95% confidence interval (CI) 0.12-0.69] or combined nonbiologic and biologic treatment (adjusted OR 0.14, 95% CI 0.045-0.45) compared with those on biologic monotherapy. Subgroup analysis demonstrated reduced odds of seroconversion in those on methotrexate (adjusted OR 0.097, 95% CI 0.19-0.49) or prednisolone treatment (adjusted OR 0.044, 95% CI 0.002-1.00) relative to tumour necrosis factor-α inhibitor monotherapy. No participants receiving rituximab (n < 5) seroconverted after the first vaccine dose. Following the second vaccine dose, 1.6% of all participants did not seroconvert. Non-seroconversion was associated with receiving rituximab (n = 3 of 4) compared with those receiving other therapies (n = 2 of 308, P < 0.001). Post hoc analyses demonstrated that non-seroconversion was associated with age [adjusted OR 0.18, 95% CI 0.037-0.93 for those aged 60 years and over (reference category age 18-39 years)], but not sex, ethnicity or vaccine type. CONCLUSIONS: Treatment with nonbiologics, particularly methotrexate, is associated with impaired seroconversion following two BNT162b2 or AZD1222 vaccine doses, in patients with IMIDs. These findings are consistent with those of other published studies. While this could indicate reduced protection against COVID-19, the immunological parameters that correlate most closely with vaccine effectiveness need to be defined to reach this conclusion.

Global Guidelines in Dermatology Mapping Project (GUIDEMAP): a systematic review of alopecia areata clinical practice guidelines.

INTRODUCTION: Alopecia areata (AA) is a nonscarring alopecia with an estimated global prevalence of 2% and limited data on the efficacy of current treatment. Clinical practice guidelines (CPGs) provide recommendations based on best available evidence. It is unclear how many AA CPGs are available globally. AIM: To systematically search for and identify CPGs on AA and to critically appraise their quality using validated tools. METHODS: We performed a literature search to identify CPGs published between October 2014 and April 2021, using the following databases: MEDLINE, Embase, National Institute for Health and Care Excellence (NICE), Guidelines International Network, Emergency Care Research Institute guidelines trust, Australian CPGs, Turning Research Into Practice database and DynaMed. The systematic review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework. Three critical appraisal tools were used: Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument, Lenzer's red flags and United States Institute of Medicine's (IOM) criteria of trustworthiness. RESULTS: In total, six AA CPGs from seven manuscripts (one CPG was in two parts published in separate papers) were included. The majority (four of six) of the CPGs focused on treatment. Four CPGs (total of five papers) were in English and two CPGs were only available in the original language (one Russian and one Japanese). All AA CPGs demonstrated low quality in several domains in the AGREE II appraisal, including stakeholder involvement and applicability, with the latter being deemed the worst domain for all CPGs, with an average of 29%. The mean (SD) number of Lenzer's red flags for the included CPGs was 3.4 (1.5) out of a total of 8 possible red flags, while the IOM criteria showed 1.6 (0.8) 'fully met' criteria and 3.1 (1.2) 'not met' out of a total of 9 criteria. CONCLUSION: We found a limited number of AA CPGs, all of which had significant methodological deficiencies. We encourage guideline development groups to use validated checklists/tools to develop reliable and trustworthy CPGs.

Azilsartan improves doxorubicin-induced cardiotoxicity via inhibiting oxidative stress, proinflammatory pathway, and apoptosis.

Azilsartan, a known angiotensin receptor blocker, has shown potential in reducing 24-hour blood pressure and may have protective effects against cardiac complications. Increased oxidative stress in cardiac tissue is directly related to the cardiac complications of doxorubicin. This study investigated whether azilsartan could mitigate doxorubicin-induced cardiotoxicity. We divided 28 male rats into four groups: the control group receiving a standard diet and water, the vehicle group given DMSO orally for two weeks, doxorubicin group receiving 2.5 mg/kg of doxorubicin three times a week for two weeks, and azilsartan group treated with 5 mg/kg/day of azilsartan orally and doxorubicin. Doxorubicin-induced cardiotoxicity was evidenced by a significant increase in TNF-α, IL-1ß, MDA, and caspase-3 levels and significantly decreased TAC and Bcl-2 levels in the cardiac tissues of treated rats compared to the DMSO and control groups. Azilsartan significantly decreased doxorubicin-induced cardiotoxicity, as evidenced by a decline in serum levels of both TNF-α and IL-1ß. Additionally, MDA significantly decreased in the cardiac tissue, although TAC was significantly increased when comparing the azilsartan group to the group receiving doxorubicin-only. These results suggest that azilsartan effectively reduced doxorubicin-induced cardiotoxicity, likely by mitigating apoptosis, inflammation, and oxidative stress in cardiac tissues.

Dipyridamole ameliorates doxorubicin-induced cardiotoxicity.

Dipyridamole is a platelet inhibitor with antithrombotic properties that can help prevent stroke recurrence. Twenty-eight male rats were divided randomly into four groups (7 rats in each group). Control group: rats received a natural diet and water. Normal saline group: rats received 0.9% normal saline for two weeks. Doxorubicin group (induced group): rats received 2.5 mg/kg three times a week for two weeks. Dipyridamole group (dipyridamole treated group): received dipyridamole (6 mg/kg/daily) orally for two weeks. Doxorubicin caused cardiotoxicity as indicated by a significant increase in tumor necrosis factor-α, interleukin-6, malondialdehyde, and caspase-3 level (P<0.05), while total antioxidant capacity and Bcl-2 levels were significantly reduced in cardiac tissues of rats in the doxorubicin group compared to the normal saline control group (P<0.05). Dipyridamole significantly ameliorates doxorubicin-induced cardiotoxicity, as suggested by a significant decrease in inflammatory markers (tumor necrosis factor-α and interleukin-6) (P<0.05). Moreover, the cardiac tissue level of oxidative marker malondialdehyde was significantly decreased (P<0.05), and total antioxidant capacity significantly increased in the dipyridamole group in comparison to the doxorubicin-only group (P<0.05). Dipyridamole exerted a significant heart-protective effect against doxorubicin-induced cardiotoxicity in rats, probably via interfering with oxidative stress, inflammatory response, and apoptotic pathway. The goal of this study was to investigate the potential protective effect of dipyridamole against doxorubicin-induced cardiotoxicity via interfering with pro-inflammatory, oxidative, and apoptotic pathways.

The influence of age, menstrual state and body mass index on the relation between osteopenia and osteoporosis associated with breast cancer.

Osteoporosis and body mass index (BMI) have been reported to be associated with breast cancer. The correlation between other types of bone loss and breast cancer requires further illustrative evidence. Effect of age and menstrual state on the relationship of osteoporosis, osteopenia and BMI with breast cancer was evaluated in this study. Two hundred breast cancer patients and 200 breast cancer-free patients were included in a case-control study. Bone mineral density (BMD) and BMI were determined in all subjects. Postmenopause was the most frequent menstrual state. osteopenia was found to be significant in breast cancer patients and osteoporosis was significant in another group of women. There was no significant difference between breast cancer patients and control women in terms of age and menstrual status. Obesity was common in all subjects. In conclusion, bone loss rates are significantly low in breast cancer patients relative to healthy women. There was no significant impact of age, menstrual status or BMI on the development of osteopenia or osteoporosis in breast cancer patients. In addition, BMD analytical results may identify the appropriate treatment for bone loss. A routine check-up of osteopenia or osteoporosis is highly recommended for breast cancer patients.Impact StatementWhat is already known on this subject? Breast cancer may be associated with a wide variety of human body parameters. These parameters can include age, body mass index (BMI), obesity and menstrual status. There is also a correlation between osteoporosis and breast cancer.What do the results of this study add? Osteopenia is the most frequent form of bone loss among women with breast cancer. In contrast, osteoporosis as the worst stage of bone loss is unusual in these patients. Factors such as age, menstruation and BMI have no effect on the development of breast cancer.What are the implications of these findings for clinical practice and/or further research? Identification of the type of bone loss in women with breast cancer is essential to determine the appropriate type of therapy.

Paradoxical eczema in patients with psoriasis receiving biologics: a case series.

Atopic eczema and psoriasis are chronic, inflammatory dermatoses that can significantly affect the quality of life of those affected. Although both diseases are common, they rarely occur together. Severe psoriasis can be treated with biologic therapies targeting specific cytokine pathways involved in disease pathogenesis. There are reports of paradoxical eczema developing in biologic-treated patients with psoriasis, sometimes necessitating treatment discontinuation and thus leading to poor disease control. This retrospective case series identified 36 such events occurring in 23 patients. All currently available biologic classes were implicated. Eosinophilia (n = 19) and elevated serum IgE (n = 3) were identified in some cases. Treatment strategies included no treatment, topical corticosteroids, broad-acting systemic agents, and discontinuation or switch of biologic therapy. Two patients had persistent eczema and psoriasis despite discontinuation of all biologic therapies.

Early diagnosis of aspergillosis in asthmatic and rheumatoid arthritis patients by Aspergillus galactomannan antigen assay: a case-control study in Karbala providence.

OBJECTIVE: Aspergillosis is an opportunistic systemic infection caused by members of Aspergillus spp. in various parts of the human body. Chronic diseases such as rheumatoid arthritis (RA) and asthma may encourage the development of aspergillosis under specific conditions. Thus, aspergillosis was investigated in patients with RA and asthma based on detection of galactomannan antigen. METHODS: A case-control study was performed to involve 184 subjects, distributing in four groups: 55 patients with RA, 54 with asthma, 27 with both RA and asthma, and 48 healthy individuals. Serum was collected from involved subjects for detection of human Aspergillus galactomannan by ELISA. The optical density index (ODI) at cutoff <0.5 was used to determine the infection. RESULTS: Aspergillosis was more frequently diagnosed in females with RA and both RA and asthma in opposite to the males. It also was found in most common in middle-aged subjects. There was no significant difference in measurement of GM between all patient groups and healthy individuals. CONCLUSION: Aspergillosis can develop in either immunocompetent or immunocompromised individuals. Patients with either RA or RA and asthma are more susceptible to acquired aspergillosis than those with only one disease. Application of GM for diagnosis of aspergillosis may show a nonsignificant results when it uses alone and needs other investigation tests.

Synthesis and antifungal activity of novel griseofulvin nanoparticles with zinc oxide against dermatophytic fungi: Trichophyton mentagrophytes and Trichophyton verrucosum: A primary study.

Background and Purpose: Dermatophytoses is an important type of skin disease caused by dermatophytes. The long-term treatment of this disease with standard antifungal agents may be improved through the application of nanotechnology. This study aimed to prepare nanoparticles of griseofulvin with zinc oxide and assess its antifungal action. Materials and Methods: Nanoparticles of griseofulvin with zinc oxide (GF-ZnO NPs) were prepared. Physical characteristics of new preparation and antidermatophytic action against two species of dermatophytes (Trichophyton mentagrophytes and Trichophyton verrucosum) were investigated. Testing of two species was considered a primary test for antifungals of griseofulvin nanoparticles. Results: Physical examination indicated that GF-ZnO NPs had typical nanoparticle characteristics. A new formulation showed effective inhibitory action against two fungal species with higher efficiency than that of griseofulvin. T. mentagrophytes required a higher MIC value (0.0625 µg/mL) of GF-ZnO NPs than that required by T. verrucosum (0.031 µg/mL). Conclusion: GF-ZnO NPs revealed an effective action against dermatophytes compared to griseofulvin alone. Nanoparticles containing griseofulvin may be used in the development of a novel drug for the treatment of dermatophytosis.

Antifungal activity of essential oils against itraconazole-resistant pathogenic Candida isolated from vulvovaginal candidiasis.

Background and Purpose: Fungal infection by species of pathogenic Candida with antifungal resistance is currently a serious problem. Treatment with new medications is becoming more challenging to manage this type of infection. The present study aimed to investigate the antifungal effect of essential oils (EOs) against itraconazole-resistant species of pathogenic Candida. Materials and Methods: Seven essential oils were tested on 15 clinical isolates of itraconazole-resistant Candida from patients with vulvovaginal candidiasis. The antifungal action of selected EOs was evaluated using the disc diffusion method with the determination of the minimum inhibitory concentration (MIC) of effective Eos. Results: Radish EO was the most effective type against all Candida isolates with MICs between 3.125% and 6.25% (v/v) .It also had a stronger effect than itraconazole. Six other EOs showed antifungal effects at varying concentrations and were dependent upon the type of isolate. Low concentrations of these six EOs were more effective against many isolates than their high concentrations. Moreover, camphor and linseed EOs were less effective on isolates. Conclusion: Radish EO has a strong antifungal activity against itraconazole-resistance species of Candida, even more than itraconazole. The antifungal action of some EOs can be increased through the use of low concentrations.

Bimekizumab: a dual IL-17A and IL-17F inhibitor for the treatment of psoriasis and psoriatic arthritis.

INTRODUCTION: Interleukin (IL)-17 is critical in the pathogenesis of psoriasis and psoriatic arthritis (PsA) with most data suggesting that IL-17A alone was the key cytokine. However, in vitro and in vivo studies have suggested dual blockade of IL-17A and IL-17 F may be more effective than IL-17 A blockade alone. Bimekizumab is the first human monoclonal antibody to exert simultaneous specific inhibition of IL-17A and IL-17 F, and has been studied in several phase II/III trials for psoriasis and PsA. AREAS COVERED: Bimekizumab is not currently licensed for use. A literature search identified clinical trials examining the efficacy and safety of bimekizumab for psoriasis and PsA, and these were critically appraised. EXPERT OPINION: Clinical trials of bimekizumab have been promising, demonstrating a rapid onset of response and superior efficacy compared to three currently licensed biologics: secukinumab, ustekinumab, and adalimumab. Bimekizumab maintains a high level of efficacy with maintenance dosing intervals of 8 weeks, compared with 4 weeks for currently licensed IL-17A antagonists. No unexpected adverse events have been identified, although mild-to-moderate fungal infections occur in approximately 10%. Studies over longer time periods involving additional active comparators would be valuable in further defining the role of bimekizumab amongst currently available treatments.

Prophylaxis and Therapeutic Ability of Inactivated Dermatophytic Vaccine Against Dermatophytosis in the Rabbits as an Animal Model

Objectives: Dermatophytosis is a group of cutaneous diseases widely distributed in human and animals. It causes serious infection in some human cases and economic losses in farm animals. The primary aim of this study is to conduct an investigation of prophylaxis and a potential therapeutic vaccine against dermatophytosis. Materials and Methods: The rabbit was chosen as an animal model of dermatophytosis for a case control study conducted in two parts. Inactivated cells of Trichophyton mentagrophytes were prepared for use as a vaccine. The prophylaxis part included vaccination of rabbits with the prepared vaccine either alone or with Freund's adjuvant, followed by infection with the same fungus. The second part included treatment of infected rabbits with an inactivated vaccine. Results: The prepared vaccine showed prophylactic ability against infection with T. mentagrophytes for more than 6 months without requiringan adjuvant and also revealed at herapeutic ability in infected animals after a short time (16 days), compared with the control group. Conclusion: Inactivated vaccine gives animals durable protection and shortens the treatmenttime for infection with dermatophytosis.

Molecular Docking Analysis of Anti-Severe Acute Respiratory Syndrome-Coronavirus 2 Ligands against Spike Glycoprotein and the 3-Chymotrypsin-Like Protease.

BACKGROUND: The severe acute respiratory syndrome-like disease coronavirus disease 2019 (COVID-19) is a disastrous global pandemic with 16,288,490 infected cases and 649,884 deaths. Until now, no effective treatments are found. METHODS: The virus uses the 3-chymotrypsin-like protease for inducing the activity of the viral polyproteins and the spike (S) glycoprotein for human cell entry through the human angiotensin-converting enzyme 2 receptor. Blocking the active binding sites of these molecules might be beneficial for decreasing the activity of the virus and suppressing the viral entry to the human cells. Here, docking methods were used to identify a group of ligands may perform the blocking operations. RESULTS: The results revealed the strongest binding affinities, sorted high to low, for tadalafil (Cialis) (phosphodiesterase type 5 inhibitor, tirofiban (antiplatelet), paraxanthine (central nervous system stimulant), dexamethasone, gentian violet cation (triphenylmethane), salbutamol, and amlodipine (calcium channel blocker). CONCLUSION: These substances may provide vital help for further clinical investigation in fighting against the current global pandemic of the COVID-19.