Concomitant Antihyperalgesic and Antitumor Effects of Gabapentin in a Murine Cancer Pain Model.

Cancer pain may be the consequence of physical nerve compression by a growing tumor. We employed a murine model to study whether gabapentin was able to regulate tumor growth, in addition to controlling hyperalgesic symptoms. A fluorescent melanoma cell line (B16-BL6/Zs green) was inoculated into the proximity of the sciatic nerve in male C57BL/6 mice. The tumor gradually compressed the nerve, causing hypersensitivity. Tumor growth was characterized via in vivo imaging techniques. Every other day, gabapentin (100 mg/Kg) or saline was IP administered to each animal. In the therapeutic protocol, gabapentin was administered once the tumor had induced increased nociception. In the preventive protocol, gabapentin was administered before the appearance of the positive signs. Additionally, in vitro experiments were performed to determine gabapentin's effects on cell-line proliferation, the secretion of the chemokine CCL2, and calcium influx. In the therapeutically treated animals, baseline responses to noxious stimuli were recovered, and tumors were significantly reduced. Similarly, gabapentin reduced tumor growth during the preventive treatment, but a relapse was noticed when the administration stopped. Gabapentin also inhibited cell proliferation, the secretion of CCL2, and calcium influx. These results suggest that gabapentin might represent a multivalent strategy to control cancer-associated events in painful tumors.

Cuttlefish Ink Melanin Encapsulated in Nanolipid Bubbles and Applied Through a Micro-Needling Procedure Easily Stains White Hair Facilitating Photoepilation.

BACKGROUND: Photothermolysis of unwanted hair depends on the presence of melanin in the hair follicle as the chromophore, but is not effective in patients with non-pigmented, melanin-sparse hair shafts and follicles. This split-scalp, double-blind study was to monitor the efficacy of melanin bound in nanosomes to inject exogenous melanin into the hair follicles thus potentiating successful photothermolysis.
MATERIAL AND METHODS: Twelve patients, phototypes II-III, with white or very fair hair, were treated with a compound containing melanin encapsulated in nanosomes (Melaser®) together with a fluorescent marker. Two equal 6 cm² areas were marked on each side of the occiput of the subjects. The compound was applied to a randomly selected experimental side on each patient (area A), and a saline solution applied in the same manner to the contralateral control side (area B). Penetration of the melanin into the hair follicle was assessed using optical and fluorescence microscopy. Also, condition of hair structure was checked in vivo after standard laser settings used for epilation.
RESULTS: A slight transient erythema was observed in those areas where the compound was applied with some perifollicular edema. No such effects were noticed in those areas where saline solution was applied. No persistent complications such as scarring, hypo- or hyperpigmentation were observed in any of the experimental or control areas. Under fluorescence microscopy, the hair structures in the areas to which the compound had been applied showed a clear melanin deposit confirmed by the immunofluorescence intensity, which was highest at 2 hours after application. By optical microscopy, external melanin was deposited in hair follicles. Tests with standard settings for epilation were efficacious in damaging melanin-marked white hair.
CONCLUSION: This study strongly suggests the safety and efficacy of the application of nanosomes encapsulating melanin for the introduction of melanin into hair follicles. Changes noticed in the hair structure compromising its viability indicated potential application of this external melanin marker for white hair photoepilation.

J Drugs Dermatol. 2016;15(5):615-625.

Photodynamic therapy with low-strength ALA, repeated applications and short contact periods (40-60 minutes) in acne, photoaging and vitiligo.

Topical aminolevulinic acid (ALA) photodynamic therapy (PDT) is currently being used for the treatment of actinic keratosis of the face and scalp. This study reports the results obtained after three to four treatments with ALA-PDT in patients with acne (n=12), photoaging (n=8) and vitiligo (n=6). ALA was applied on large areas (e.g., full face) and at very low strengths (1-2%). Side effects were minimal and self-limited.

Actualización y reflexiones en Sexología / News and thoughts on sexology

Se presenta en esta sección una revisión de los artículos científicos de mayor impacto publicados entre septiembre y noviembre del 2023 en las revistas internacionales sobre Sexología con mayor reconocimiento a nivel nacional e internacional.(AU)

A nutritional supplement containing lactoferrin stimulates the immune system, extends lifespan, and reduces amyloid ß peptide toxicity in Caenorhabditis elegans.

Lactoferrin is a highly multifunctional glycoprotein involved in many physiological functions, including regulation of iron absorption and immune responses. Moreover, there is increasing evidence for neuroprotective effects of lactoferrin. We used Caenorhabditis elegans as a model to test the protective effects, both on phenotype and transcriptome, of a nutraceutical product based on lactoferrin liposomes. In a dose-dependent manner, the lactoferrin-based product protected against acute oxidative stress and extended lifespan of C. elegans N2. Furthermore, Paralysis of the transgenic C. elegans strain CL4176, caused by Aß1-42 aggregates, was clearly ameliorated by treatment. Transcriptome analysis in treated nematodes indicated immune system stimulation, together with enhancement of processes involved in the oxidative stress response. The lactoferrin-based product also improved the protein homeostasis processes, cellular adhesion processes, and neurogenesis in the nematode. In summary, the tested product exerts protection against aging and neurodegeneration, modulating processes involved in oxidative stress response, protein homeostasis, synaptic function, and xenobiotic metabolism. This lactoferrin-based product is also able to stimulate the immune system, as well as improving reproductive status and energy metabolism. These findings suggest that oral supplementation with this lactoferrin-based product could improve the immune system and antioxidant capacity. Further studies to understand the molecular mechanisms related with neuronal function would be of interest.

Phosphatidylcholine liposomes as carriers to improve topical ascorbic acid treatment of skin disorders.

Liposomes have been intensively investigated as carriers for different applications in dermatology and cosmetics. Ascorbic acid has potent antioxidant and anti-inflammatory properties preventing photodamage of keratinocytes; however, due to its instability and low skin penetration, an appropriate carrier is mandatory to obtain desirable efficacy. The present work investigates the ability of a specific ascorbate phosphatidylcholine (PC) liposome to overcome the barrier of the stratum corneum and deliver the active agent into the dermis to prevent photodamage. Abdominal skin from ten patients was used. Penetration of PC liposomes was tested ex vivo in whole skin, epidermis, and dermis by means of fluorescein and sodium ascorbate. Histology and Franz diffusion cells were used to monitor the percutaneous absorption. Ultraviolet (UV)-high performance liquid chromatography was used to analyze diffusion of sodium ascorbate through the different skin layers, while spectrofluorimetry and fluorescent microscopy were used for fluorescein monitoring. UVA/UVB irradiation of whole skin was applied to analyze the antioxidant capacity by Trolox assay and anti-inflammatory effects by tumor necrosis factor alpha and interleukin 1 beta enzyme-linked immunoassay. PC liposomal formulation improved skin penetration of fluorescein and ascorbate. Fluorescein PC liposomes showed better diffusion through epidermis than dermis while ascorbate liposomes showed better diffusion through the dermis than the epidermis. Ascorbate PC liposomes showed preventive antioxidant and anti-inflammatory properties on whole human skin irradiated with UVA/UVB. In summary, ascorbate PC liposomes penetrate through the epidermis and allow nonstable hydrophilic active ingredients reach epidermis and dermis preventing skin photodamage.

Microneedling dilates the follicular infundibulum and increases transfollicular absorption of liposomal sepia melanin.

Encapsulation of chemicals in liposomes and microneedling are currently used techniques to enhance the penetration of several substances through skin and hair. In this study, we apply a liposomal melanin-fluorescein compound to an ex vivo model of human skin, using a new electrical microneedling device (Nanopore turbo roller). The product was applied by hand massage (A) or with the assistance of the electrical roller for 2 minutes (B). An additional test was performed free of product and with only the E-roller (C). Histological changes and product absorption were evaluated by optical and fluorescent microscopy 60 and 90 minutes after the treatment. Site B showed larger deposits of melanin-fluorescein at superficial and deep levels of hair structures in comparison to site A. Light, epidermal deposits of the melanin-fluorescein complex were also observed. Sites B and C showed a significant widening (47%) of the follicular infundibulum which could explain the increased penetration of the formulation. Microneedling also removed the scales and sebum residues in the neighborhood of the infundibulum. Targeting hair follicles with melanin may be useful to dye poorly pigmented hairs, improving laser hair removal. The procedure accelerates the delivery of melanin into hair structures allowing an even absorption, larger pigment deposits, and deeper penetration of the formulation into the hair.