Biomedical applications of tyrosinases and tyrosinase inhibitors.

Tyrosinase is involved in several human diseases, among which hypopigmentation and depigmentation conditions (vitiligo, idiopathic guttate hypomelanosis, pityriasis versicolor, pityriasis alba) and hyperpigmentations (melasma, lentigines, post-inflammatory and periorbital hyperpigmentation, cervical idiopathic poikiloderma and acanthosis nigricans). There are increasing evidences that tyrosinase plays a relevant role in the formation and progression of melanoma, a difficult to treat skin tumor. Hydroquinone, azelaic acid and tretinoin (all-trans-retinoic acid) are clinically used in the management of some hyperpigmentations, whereas many novel chemotypes acting as tyrosinase inhibitors with potential antimelanoma action are being investigated. Kojic acid, hydroquinone, its glycosylated derivative arbutin, or the resorcinol derivative rucinol are used in cosmesis in creams as skin whitening agents, whereas no antimelanoma tyrosinase inhibitor reached clinical trials so far, although thiamidol is a recently approved new tyrosinase inhibitor for the treatment of melasma. Kojic acid and vitamin C are used for avoiding vegetable/food oxidative browning due to the tyrosinase-catalyzed reactions, whereas bacterial enzymes show potential in biotechnological applications, for the production of mixed melanins, for protein cross-linking reactions, for producing phenol(s) biosensors, of for the production of L-DOPA, an anti-Parkinson's disease drug.

Exploring the Co-occurrence of dermatophyte infection and ichthyosis: A report of 3 cases.

Dermatophyte infections frequently pose diagnostic challenges, especially when occurring alongside ichthyosis, a genetic skin disorder characterized by dry, thickened, scaly skin. This case series outlines three cases where dermatophyte infections overlapped with ichthyosis, emphasizing the complexities in clinical identification and differential diagnosis. Atypical clinical presentations in these cases led to initial misdiagnoses. Ichthyosis, a genetic skin disorder characterized by thickened and scaly skin, creates an environment conducive to dermatophyte settlement, complicating the diagnostic process. The cases highlight the importance of considering fungal infections, even when clinical features deviate from the expected course. A vigilant diagnostic approach, including mycological examinations, is crucial for accurate identification and timely management.

Management of Neisseria gonorrhoeae infection: from drug resistance to drug repurposing.

INTRODUCTION: Neisseria gonorrhoeae is a common sexually transmitted disease connected with extensive drug resistance to many antibiotics. Presently, only expanded spectrum cephalosporins (ceftriaxone and cefixime) and azithromycin remain useful for its management. AREAS COVERED: New chemotypes for the classical antibiotic drug target gyrase/topoisomerase IV afforded inhibitors with potent binding to these enzymes, with an inhibition mechanism distinct from that of fluoroquinolones, and thus less prone to mutations. The α-carbonic anhydrase from the genome of this bacterium (NgCAα) was also validated as an antibacterial target. EXPERT OPINION: By exploiting different subunits from the gyrase/topoisomerase IV as well as new chemotypes, two new antibiotics reached Phase II/III clinical trials, zoliflodacin and gepotidacin. They possess a novel inhibition mechanism, binding in distinct parts of the enzyme compared to the fluoroquinolones. Other chemotypes with inhibitory activity in these enzymes were also reported. NgCAα inhibitors belonging to a variety of classes were obtained, with several sulfonamides showing MIC values in the range of 0.25-4 µg/mL and significant activity in animal models of this infection. Acetazolamide and similar CA inhibitors might thus be repurposed as antiinfectives. The scientific/patent literature has been searched for on PubMed, ScienceDirect, Espacenet, and PatentGuru, from 2016 to 2024.

Inhibition of pathogenic bacterial carbonic anhydrases by monothiocarbamates.

Carbonic anhydrases (CAs) from the pathogenic bacteria Nesseria gonorrhoeae and vancomycin-resistant enterococci (VRE) have recently been validated as antibacterial drug targets. Here we explored the inhibition of the α-CA from N. gonorrhoeae (α-NgCA), of α- and γ-class enzymes from Enterococcus faecium (α-EfCA and γ-EfCA) with a panel of aliphatic, heterocyclic and aryl-alkyl primary/secondary monothiocarbamates (MTCs). α-NgCA was inhibited in vitro with KIs ranging from 0.367 to 0.919 µM. The compounds inhibited the α-EfCA and γ-EfCA with KI ranges of 0.195-0.959 µM and of 0.149-1.90 µM, respectively. Some MTCs were also investigated for their inhibitory effects on the growth of clinically-relevant N. gonorrhoeae and VRE strains. No inhibitory effects on the growth of VRE were noted for all MTCs, whereas one compound (13) inhibited the growth N. gonorrhoeae strains at concentrations ranging from 16 to 64 µg/mL. This suggests that compound 13 may be a potential antibacterial agent against N. gonorrhoeae.

Autoimmune bullous dermatoses in cancer patients treated by immunotherapy: a literature review and Italian multicentric experience.

Cutaneous immune-related adverse events are frequently associated with immune checkpoint inhibitors (ICIs) administration in cancer patients. In fact, these monoclonal antibodies bind the cytotoxic T-lymphocyte antigen-4 and programmed cell death-1/ligand 1 leading to a non-specific activation of the immune system against both tumoral cells and self-antigens. The skin is the most frequently affected organ system appearing involved especially by inflammatory manifestations such as maculopapular, lichenoid, psoriatic, and eczematous eruptions. Although less common, ICI-induced autoimmune blistering diseases have also been reported, with an estimated overall incidence of less than 5%. Bullous pemphigoid-like eruption is the predominant phenotype, while lichen planus pemphigoides, pemphigus vulgaris, and mucous membrane pemphigoid have been described anecdotally. Overall, they have a wide range of clinical presentations and often overlap with each other leading to a delayed diagnosis. Achieving adequate control of skin toxicity in these cases often requires immunosuppressive systemic therapies and/or interruption of ICI treatment, presenting a therapeutic challenge in the context of cancer management. In this study, we present a case series from Italy based on a multicenter, retrospective, observational study, which included 45 patients treated with ICIs who developed ICI-induced bullous pemphigoid. In addition, we performed a comprehensive review to identify the cases reported in the literature on ICI-induced autoimmune bullous diseases. Several theories seeking their underlying pathogenesis have been reported and this work aims to better understand what is known so far on this issue.

A monkeypox virus infection mimicking primary syphilis.

Given the current monkeypox virus (MPXV) outbreak in at-risk men who have sex with men (MSM), clinicians should consider MPXV a differential diagnosis of syphilis, in any patient with a solitary painless genital nodule.

New Screening Strategy Combining Anal Papanicolaou and Human Papillomavirus Tests for Human Papillomavirus-Related Anal Cancer: A Prospective, Single-Center Study.

BACKGROUND: The objective of this study was to evaluate the performance of a combined approach of liquid-based anal cytology and human papillomavirus (HPV) testing in predicting patients who should undergo high-resolution anoscopy for the early detection of anal cancer and anal intraepithelial neoplasia (AIN)-2+. METHODS: We conducted a prospective single-center quality improvement study. We consecutively enrolled men who had sex with men (MSM) attending our sexually transmitted disease clinic to undergo anal Papanicolaou (Pap) and HPV tests. All patients with an abnormal anal Pap test result and/or positive HPV test result underwent high-resolution anoscopy. RESULTS: We enrolled 217 MSM, 80 HIV-positive patients, and 137 HIV-negative patients. Cytology showed a sensitivity of 100%, a specificity of 64.1%, an accuracy of 66.7%, a positive predictive value (PPV) of 15.7%, and a negative predictive value (NPV) of 100% for the detection of AIN-2+. The high-risk (HR)-HPV test showed sensitivity, specificity, accuracy, PPV, and NPV of 100%, 36.4%, 40%, 9.4%, and 100%, respectively. The combination of abnormal cytology with identification of infection by at least 1 HR-HPV strain on the HPV test had a sensitivity of 100%, a specificity of 73%, an accuracy of 74.6%, a PPV of 19.1%, and an NPV of 100%. CONCLUSION: Anal HR-HPV testing, complementary to cytology, improves the diagnostic accuracy of screening for anal cancer.

Liquid-based anal cytology as a screening tool for prevention of anal cancer in at-risk populations: a single-center retrospective analysis on 111 patients

Objective: Squamous cell carcinoma of the anus (SCCA) is associated with human papillomavirus (HPV) infection in almost 90% of the cases. Its incidence is alarmingly high among men who have sex with men (MSM) and continues to increase at an average rate of 2% per year. The objective of the present study is to evaluate the usefulness and performance of liquid-based anal cytology as a screening tool for prevention and early detection of SCCA in a cohort of at-risk men. Method: We conducted a retrospective study including 111 MSM, aged between 22 and 62 years old, who underwent anal cytological screening with a liquid-based Pap test at our sexually transmitted diseases (STDs) clinic from January 2015 to March 2017. Results: Out of 111 anal smears, 57 (51,4%) resulted negative, 42 (37,8%) abnormal, and 12 (10,8%) unsatisfactory for the cytological evaluation. Only patients with an abnormal cytology underwent anoscopy and subsequent biopsy. The histological results were as follows: negative for squamous intraepithelial lesion (SIL) in 5 cases, low-grade SIL (L-SIL) in 21, high-grade SIL (H-SIL) in 5, SCCA in 1. Five patients had a normal anoscopy and biopsy was not taken. Conclusion: Liquid-based cytology, reducing the "darkening factors" typical for the conventional smears, has a higher positive predictive value than the traditional technique. Moreover, a cytological diagnosis of atypical squamous cells of undetermined significance (ASC-US) or L-SILmay hide a severe dysplasia or even a carcinoma. Thus, all patients with an abnormal anal cytology at any grade should be considered for anoscopy. (AU)

Non-scarring patchy alopecia: What else, apart from alopecia areata?

A 67-year-old woman presented with a 3-month history of patchy alopecia areata (AA)-like hair loss and multiple painful enlarged lymph nodes at cervical, nuchal, and left axillary site. The patient was on follow-up for IgM monoclonal gammopathy of undetermined significance, stable for many years. A punch biopsy from a patch of the temporal scalp revealed the presence of B-cell lymphoid infiltrates consistent with marginal zone B-cell lymphoma (MZL). Other staging examinations were conducted to make a definitive diagnosis of nodal MZL with secondary cutaneous involvement. The patient showed a complete remission of the alopecia, without evidence of scarring, after immunochemotherapy for lymphoma.

Photodynamic therapy with topical photosensitizers in mucosal and semimucosal areas: Review from a dermatologic perspective.

Photodynamic Therapy is a procedure based on the interaction between a Photosensitizer, a light source with a specific wavelength and oxygen. The aim of this review is to provide a brief and updated analysis of scientific reports on the use of PDT with topical PS in the management of oncological, infectious, and inflammatory disorders involving mucosal and semimucosal areas, with a specific focus on diseases of dermatologic interest.