The uses of naltrexone in dermatologic conditions.

BACKGROUND: Naltrexone in standard and reduced doses is efficacious in many inflammatory and acantholytic disorders. OBJECTIVE: We summarized the current data of naltrexone that are relevant to dermatologic practice. METHODS: An English language PubMed literature search was performed using the terms naltrexone, low-dose naltrexone, Hailey-Hailey, psoriasis, lichen planopilaris, alopecia, opioid, opioid receptor, treatment, dermatology, monitoring, side effect, skin, pruritus, cutaneous, acantholytic, and Darier. RESULTS: Opioid receptors are found throughout the skin and affect cell proliferation, migration, and adhesion. µ Opioid receptors have been found in all layers of the epidermis, while δ receptors are concentrated at cell junctions and can reduce desmoglein expression. Typical doses of naltrexone result in continuous binding to receptors. Low doses result in intermittent blockade with increased ligand and receptor expression, potentiating their effect. LIMITATIONS: Our review was restricted to the English language literature. CONCLUSION: Naltrexone affects inflammation, cell adhesion, and keratinocyte proliferation and migration. While low-dose naltrexone has demonstrated efficacy in treating patients with Hailey-Hailey disease, further dose-ranging studies are needed. Data suggest that naltrexone could be helpful in the treatment of pruritus and a variety of inflammatory and acantholytic skin diseases that are refractory to other treatments. At higher doses, liver function tests should be monitored on a periodic basis.

Complications associated with intimate body piercings.

Intimate body piercings involving the nipple and genitalia have increased in prevalence in both men and women. Despite this increase, there is a deficiency in the literature regarding the short and long-term complications of body piercings, including an increased risk of infection, malignancy, and structural damage to the associated tissue. Breast abscesses associated with nipple piercing can be mistaken as inflammatory carcinoma. Male genital piercings have been associated with urethral rupture, paraphimosis, urethral obstruction, scar formation, and squamous cell carcinoma, whereas female genital piercings may lead to a higher risk of pregnancy and sexually transmitted infections. There are additional problems related to piercings during pregnancy and thereafter. Nipple piercings can hinder breast feeding by inhibiting the milk letdown reflex, increasing nipple sensitivity, and causing discomfort to the infant. Removal of genital piercings during pregnancy could introduce bacteria into the piercing tract, but retaining the piercings could theoretically hinder childbirth. Prevention of complications is critical. Patients must understand the risks of piercings and disclose relevant medical conditions to the practitioner before the procedure. The piercings should be carried out in a hygienic and sterile manner. Finally, physicians should maintain a non-judgmental attitude to encourage patients to seek medical care for complications.

Corrigendum: Complications associated with intimate body piercings.

The original article was published on July15, 2017 and corrected on August 15, 2018.The revised version of the article includes a correction to the spelling of an author. The change appears in the revised online PDF copy of this article.

α- and ß-Santalols Directly Interact with Tubulin and Cause Mitotic Arrest and Cytotoxicity in Oral Cancer Cells.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, with no major advancements in treatment over the past 40 years. The current study explores the biological effects of East Indian sandalwood oil (EISO) and its two major constituents, α- and ß-santalol, against a variety of HNSCC lines. All three agents exhibited cytotoxic effects and caused accumulation of cells in the G2/M phases of the cell cycle. Additionally, treatment with these agents caused formation of multipolar mitotic spindles similar to those observed upon treatment of cells with compounds that affect microtubule polymerization. Indeed, the santalols, as well as EISO, inhibited the polymerization of purified tubulin, indicating for the first time that these compounds have the ability to directly bind to tubulin and affect microtubule formation. Modeling studies suggest that the santalols can weakly bind to the colchicine site on tubulin, and topical administration of EISO to a HNSCC xenograft inhibited tumor growth with no observed toxicities. Therefore, santalols can directly interact with tubulin to inhibit the polymerization of microtubules, similarly to established classes of chemotherapeutic agents, albeit with greatly reduced potency that is not associated with the classic toxicity associated with most other compounds that interact directly with tubulin.

Melampodium leucanthum, a source of cytotoxic sesquiterpenes with antimitotic activities.

A new tricyclic sesquiterpene, named meleucanthin (1), was isolated from an extract of the leaves and branches of Melampodium leucanthum, along with four known germacranolide sesquiterpene lactones, leucanthin-A (2), leucanthin-B (3), melampodin-A acetate (4), and 3α-hydroxyenhydrin (5). The chemical structure of 1 was elucidated by analysis of 1D and 2D NMR and mass spectrometric data. All compounds exhibited antiproliferative and cytotoxic efficacy against PC-3 and DU 145 prostate cancer cells, as well as HeLa cervical cancer cells, with IC50 values ranging from 0.18 to 9 µM. These compounds were effective in clonogenic assays and displayed high cellular persistence. They were also found to be capable of circumventing P-glycoprotein-mediated drug resistance. Mechanism of action studies showed that 4 caused an accumulation of cells in the G2/M phase of the cell cycle, and 2-5 caused the formation of abnormal mitotic spindles. These results suggest the cytotoxic effects of these germacranolides involve inhibition of mitotic spindle function, and it is likely that other mechanisms additionally contribute to cell death. These studies also demonstrate the possibility of isolating new, biologically active compounds from indigenous Texas plants.