Chemical-Induced Oral Squamous Cell Neoplasms in Rodents: An Overview of NTP 2-Year Cancer Studies.

Oral cancer is the seventh most common malignancy worldwide, and lifestyle factors participate in its development. Rodent studies can help identify substances that contribute to its development and provide information on the early stages of carcinogenicity. The National Toxicology Program (NTP) has conducted more than 500 short-term and 2-year toxicology and carcinogenicity studies in rodents, and some of the tested compounds resulted in oral cancer. Our goal was to review the NTP carcinogenic studies to describe those chemicals that have oral carcinogenic outcome in rodents. For this project, we reviewed the results from all NTP carcinogenicity studies and a board-certified veterinary pathologist reviewed the slides from all neoplasms in the oral cavity that were considered treatment related. We have identified 26 chemicals with an adverse effect in the oral cavity. Fourteen chemicals demonstrated clear evidence of carcinogenicity in the oral cavity. We provide information on the carcinogenic findings in rodents together with a detailed description of the morphologic aspects of the oral cancers and speculate that the carcinogenic effects can be induced by different pathological modes of action. The findings reviewed here provide indicators for potential oral carcinogenesis processes in rodent models, which can be further investigated in future mechanistic studies.

Acral peeling skin syndrome resulting from a novel homozygous mutation in the CSTA gene-A report of two cases.

Acral peeling skin syndrome is a rare genodermatosis characterized by asymptomatic peeling of the acral skin. It is usually caused by biallelic mutations in the gene TGM5. However, biallelic mutations in the CSTA gene have also been described to cause APSS with exfoliative ichthyosis, so far in only five pedigrees. Here, we report two new pedigrees, each with one patient having APSS, due to a novel CSTA mutation.

The toxicologic pathology aspects of selected natural herbal products and related compounds.

Herbal products have been in use for many years, but they are becoming more and more popular in recent years, and they are currently in widespread use throughout the world. In this review article we describe the histopathologic findings found after exposure to 12 dietary herbals in studies conducted in rodent model systems. Clear or some evidence for carcinogenic activity was seen with 6 herbals, with the liver being the most common organ affected. The intestine was affected by two herbals (aloe vera nondecolorized extract and senna), three had no clear evidence for carcinogenic activity and one was cardiotoxic (Ephedrine and Ephedra in combination with caffeine). Information from these studies can help to better understand potential target organs for further evaluation from exposure to various herbal products.

Design and Evaluation of Dissolvable Microneedles for Treating Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease caused predominantly by immune dysregulation. The global impact of AD continues to increase, making it not only a significant public health issue but also a risk factor for progression into other allergic phenotype disorders. Treatment of moderate-to-severe symptomatic AD involves general skin care, restoration of the skin barrier function, and local anti-inflammatory drug combinations, and may also require systemic therapy, which is often associated with severe adverse effects and is occasionally unsuitable for long-term use. The main objective of this study was to develop a new delivery system for AD treatment based on dissolvable microneedles containing dexamethasone incorporated in a dissolvable polyvinyl alcohol/polyvinylpyrrolidone matrix. SEM imaging of the microneedles showed well-structured arrays comprising pyramidal needles, fast drug release in vitro in Franz diffusion cells, an appropriate mechanical strength recorded with a texture analyzer, and low cytotoxicity. Significant clinical improvements, including in the dermatitis score, spleen weights, and clinical scores, were observed in an AD in vivo model using BALB/c nude mice. Taken together, our results support the hypothesis that microneedle devices loaded with dexamethasone have great potential as a treatment for AD and possibly for other skin conditions as well.