Follicular induction and CK20+ Merkel cells overlying cutaneous focal mucinosis.

BACKGROUND: Cutaneous focal mucinosis (CFM) or focal dermal mucinosis is a benign reactive process categorized as a primary mucinosis. Skin biopsy is essential for diagnosis, as the clinical appearance is often non-specific. Follicular induction is a phenomenon whereby the epidermis is induced by an underlying process to form primitive or mature hair follicles, and is commonly seen overlying dermatofibromas. Follicular induction has been rarely described in CFM. METHODS: We performed a retrospective histological review of lesions of CFM confirmed by skin biopsy from 2010 to 2015 in our department. RESULTS: We found that 11% (11/98) of CFM lesions showed follicular induction. Cytokeratin 20 (CK20) immunostaining was performed on all 11 of these biopsies that showed follicular induction and highlighted an increased density of CK20+ Merkel cells within the basaloid epidermal proliferations. CONCLUSION: As superficial basal cell carcinomas (BCC) often show a mucinous stroma around the basaloid islands, CFM with follicular induction may closely mimic a BCC histologically, particularly in superficial shave biopsies. Therefore, it is important that dermatopathologists be aware of this phenomenon. Furthermore, CK20+ staining within the basaloid epithelial proliferations may be helpful in differentiating CFM with follicular induction from a BCC.

Follicular induction overlying a dermatofibrosarcoma protuberans.

The term "induction" has been used to describe epidermal changes overlying a dermatofibroma (DF). Follicular induction is most often associated with DF, but can be observed in other lesions, including focal mucinosis, nevus sebaceous, seborrheic keratosis, wart, neurofibroma, and scars. Dermatofibrosarcoma protuberans (DFSP) is a malignant fibrohistiocytic tumor that may be difficult to distinguish from DF. In contrast to DF, the epidermis overlying DFSP is usually attenuated or ulcerated. Here, we report a case of DFSP exhibiting follicular induction of the overlying epidermis. This epidermal change has been rarely reported in DFSP and may present a diagnostic pitfall in superficially sampled lesions.

The biology, structure, and function of eyebrow hair.

Eyebrow hair serves many important biologic and aesthetic functions. This article reviews the structure and function of the hair follicle, as well as hair follicle morphogenesis and cycling. Eyebrow hair follicles share the same basic structure as hair follicles elsewhere on the body, but are distinguished by their shorter anagen (growing) phase. Knowledge of the hair follicle structure and cycle is important for understanding the pathophysiology of alopecia, as diseases affecting the stem cell portion of the hair follicle in the bulge region may cause permanent hair loss. Furthermore, therapeutic agents that target distinct phases and hormones involved in the hair cycle may be useful for promoting hair growth.

High-Throughput Screen of Microbial Metabolites Identifies F1FO ATP Synthase Inhibitors as New Leads for Naegleria fowleri Infection.

Primary amebic meningoencephalitis (PAM), a brain infection caused by a free-living ameba Naegleria fowleri, leads to an extensive inflammation of the brain and death within 1-18 (median 5) days after symptoms begin. Although natural products have played a significant role in the development of drugs for over a century, research focusing on identifying new natural product-based anti-N. fowleri agents is limited. We undertook a large-scale ATP bioluminescence-based screen of about 10,000 unique marine microbial metabolite mixtures against the trophozoites of N. fowleri. Our screen identified about 100 test materials with >90% inhibition at 50 µg/mL and a dose-response study found 20 of these active test materials exhibiting an EC50 ranging from 0.2 to 2 µg/mL. Examination of four of these potent metabolite mixtures, derived from our actinomycete strains CNT671, CNT756, and CNH301, resulted in the isolation of a pure metabolite identified as oligomycin D. Oligomycin D exhibited nanomolar potency on multiple genotypes of N. fowleri, and it was five- or 850-times more potent than the recommended drugs amphotericin B or miltefosine. Oligomycin D is fast-acting and reached its EC50 in 10 h, and it was also able to inhibit the invasiveness of N. fowleri significantly when tested on a matrigel invasion assay. Since oligomycin is known to manifest inhibitory activity against F1FO ATP synthase, we tested different F1FO ATP synthase inhibitors and identified a natural peptide leucinostatin as a fast-acting amebicidal compound with nanomolar potency on multiple strains.

Miconazole-like Scaffold is a Promising Lead for Naegleria fowleri-Specific CYP51 Inhibitors.

Developing drugs for brain infection by Naegleria fowleri is an unmet medical need. We used a combination of cheminformatics, target-, and phenotypic-based drug discovery methods to identify inhibitors that target an essential N. fowleri enzyme, sterol 14-demethylase (NfCYP51). A total of 124 compounds preselected in silico were tested against N. fowleri. Nine primary hits with EC50 ≤ 10 µM were phenotypically identified. Cocrystallization with NfCYP51 focused attention on one primary hit, miconazole-like compound 2a. The S-enantiomer of 2a produced a 1.74 Å cocrystal structure. A set of analogues was then synthesized and evaluated to confirm the superiority of the S-configuration over the R-configuration and the advantage of an ether linkage over an ester linkage. The two compounds, S-8b and S-9b, had an improved EC50 and KD compared to 2a. Importantly, both were readily taken up into the brain. The brain-to-plasma distribution coefficient of S-9b was 1.02 ± 0.12, suggesting further evaluation as a lead for primary amoebic meningoencephalitis.

Pregnancy-associated acquired arteriovenous malformation of the nail unit: a novel cause of localized erythronychia.

Localized longitudinal erythronychia describes a solitary red streak limited to a single nail unit. Localized longitudinal erythronychia can be caused by both benign and malignant entities. Most commonly, the cause is a benign process, such as an onychopapilloma. We report a case of an acquired subungual arteriovenous malformation that presented as localized longitudinal erythronychia during pregnancy. To our knowledge, this is the first report of localized longitudinal erythronychia arising from a pregnancy-associated arteriovenous malformation of the nail unit.

A Broad Spectrum Antiparasitic Activity of Organotin (IV) Derivatives and Its Untargeted Proteomic Profiling Using Leishmania donovani.

Metals have been used in medicine since ancient times for the treatment of different ailments with various elements such as iron, gold and arsenic. Metal complexes have also been reported to show antibiotic and antiparasitic activity. In this context, we tested the antiparasitic potential of 10 organotin (IV) derivatives from 4-(4-methoxyphenylamino)-4 oxobutanoic acid (MS26) against seven eukaryotic pathogens of medical importance: Leishmania donovani, Trypanosoma cruzi, Trypanosoma brucei, Entamoeba histolytica, Giardia lamblia, Naegleria fowleri and Schistosoma mansoni. Among the compounds with and without antiparasitic activity, compound MS26Et3 stood out with a 50% effective concentration (EC50) of 0.21 and 0.19 µM against promastigotes and intracellular amastigotes of L. donovani, respectively, 0.24 µM against intracellular amastigotes of T. cruzi, 0.09 µM against T. brucei, 1.4 µM against N. fowleri and impaired adult S. mansoni viability at 1.25 µM. In terms of host/pathogen selectivity, MS26Et3 demonstrated relatively mild cytotoxicity toward host cells with a 50% viability concentration of 4.87 µM against B10R cells (mouse monocyte cell line), 2.79 µM against C2C12 cells (mouse myoblast cell line) and 1.24 µM against HEK923 cells (human embryonic kidney cell line). The selectivity index supports this molecule as a therapeutic starting point for a broad spectrum antiparasitic alternative. Proteomic analysis of host cells infected with L. donovani after exposure to MS26Et3 showed a reduced expression of Rab7, which may affect the fusion of the endosome with the lysosome, and, consequently, impairing the differentiation of L. donovani to the amastigote form. Future studies to investigate the molecular target(s) and mechanism of action of MS26Et3 will support its chemical optimization.

The HoVert technique: a novel method for the sectioning of alopecia biopsies.

BACKGROUND: Cicatricial forms of alopecia, including lichen planopilaris (LPP) and discoid lupus erythematosus (DLE), may present with overlapping clinical features. In such cases, histopathological examination may provide key information for resolving the differential diagnosis. Optimally, microscopical analysis for alopecia requires both vertical and horizontal sections, and this may necessitate multiple samples. Here, we present what we term the "HoVert" technique, which produces horizontal and vertical sections from a single biopsy. We hypothesize that the HoVert technique should be useful for differentiating DLE from LPP. METHODS: A formalin-fixed 4 mm punch scalp biopsy is transected approximately 1 mm below the skin surface to create an epidermal disc and a lower portion. The epidermal disc is bisected and embedded in conventional fashion to obtain vertical sections. The lower portion is serially sectioned and embedded to obtain horizontal sections. RESULTS: The HoVert technique yields vertical sections permitting visualization of the epidermis, the dermal-epidermal junction and perijunctional inflammation. The technique also provides horizontal sections that permit analysis of follicle number, follicle type, perifollicular inflammation and scarring. Evaluation of both vertical and horizontal sections from a single scalp biopsy maximizes the histopathological information obtained and enhances the diagnosis of LPP or DLE in specific cases. CONCLUSIONS: We believe that the HoVert technique represents a simple and diagnostically effective tool in differentiating LPP from DLE. It may also be applicable to the assessment of other forms of alopecia.