Stephen B. Tucker

Variation in cutaneous sensation between synthetic pyrethroid insecticides

Synthetic pyrethroids are potent insecticides, utilized for food protection and general pest control. Numerous investigations have indicated that ultra‐low volume applications are effective and may eliminate the developing problem of resistance to the currently utilized insecticides. The most, prominent health symptom that accompanies topical contact with these agents appears to be a cutaneous sensation, paresthesia. In this investigation, a substantial difference in the degree of paresthesia was noted between the formulated prude of 4 synthetic pyrethroids. Also, dl‐alpha tocopheryl acetate was statistically validated as an efficacious therapeutic agent for cutaneous exposure to these insecticides

Inhibition of Cutaneous Paresthesia Resulting from Synthetic Pyrethroid Exposure

ABSTRACT: Synthetic pyrethroids are potent lipophilic insecticides recognized as nerve toxins. Their increased usage in recent years has established them as a serious competitor against the currently available pesticides. Reported cases of occupational exposure have noted the presence of paresthesia without the clinical symptoms of erythema, edema, or vesiculation. Pilot studies were performed with six prophylactic agents to assess their capability of preventing or ameliorating the paresthesia that accompanies exposure. Vitamin E oil (dl‐alpha tocopheryl acetate) proved the most efficacious.

Primary irritant contact dermatitis from synthetic pyrethroid insecticide exposure

Synthetic pyrethroids are widely used insecticides with numerous applications, varying from food protection to general pest control. Humans are capable of tolerating greater acute and chronic exposures to the pyrethroids than to many other insecticides. An abnormal cutaneous sensation (paresthesia) is known to occur after dermal contact with the pyrethroids. Recent field studies have indicated that a primary irritant contact dermatitis may also develop. This investigation evaluated dermal irritancy from cutaneous synthetic pyrethroid application to albino rabbits. Through repeated daily applications of either fenvalerate or permethrin, a slight erythema was noted visually which correlated with increased cutaneous blood flow measured by laser Doppler velocimetry. Histopathological changes were also documented, but no significant differences were detected in edema or thermal variation.

Ciclopirox gel in the treatment of patients with interdigital tinea pedis

Background  Tinea pedis (athlete’s foot) is the most common fungal infection in the general population. Ciclopirox, a broad‐spectrum hydroxypyridone antifungal, has proven efficacy against the organisms commonly implicated in tinea pedis: Trichophyton rubrum, T. mentagrophytes and Epidermophyton floccosum.

Irritant dermatitis from tetrachloroisophthalonitrile

Tetrachloroisophthalonitrile (TCPN) is an agricultural and horticultural fungicide used throughout the world. Recent studies have suggested that it may be a potential health hazard on dermal exposure due to innate toxic and allergenic properties (1, 2). However, no prior investigation has been able to determine the noneffective level for irritant contact dermatitis from occupational exposure to this potent fungicide. Numerous assays presently exist for irritancy evaluation (3). With proper forethought and attention to details, these models may be used reliably to predict when an agent will elicit irritant contact dermatitis. In this particular investigation, the Marzulli-Maibach open cumulative irritation assay was chosen because the multiple application sequence closely duplicated working conditions with the fungicide. It also provided an opportunity for making daily observations on the treated animals (4). This model was first evaluated with unoccluded test sites and later repeated with partly occluded sites.

CHRONIC ULTRAVIOLET EXPOSURE-INDUCED p53 GENE ALTERATIONS IN SENCAR MOUSE SKIN CARCINOGENESIS MODEL

Alterations of the tumor suppresser gene p53 have been found in ultraviolet radiation (UVR) related human skin cancers and in UVR-induced murine skin tumors. However, links between p53 gene alterations and the stages of carcinogenesis induced by UVR have not been clearly defined. We established a chronic UVR exposure-induced Sencar mouse skin carcinogenesis model to determine the frequency of p53 gene alterations in different stages of carcinogenesis, including UV-exposed skin, papillomas, squamous-cell carcinomas (SCCs), and malignant spindle-cell tumors (SCTs). A high incidence of SCCs and SCTs were found in this model. Positive p53 nuclear staining was found in 10/37 (27%) of SCCs and 12/24 (50%) of SCTs, but was not detected in normal skin or papillomas. DNA was isolated from 40 paraffin-embedded normal skin, UV-exposed skin, and tumor sections. The p53 gene (exons 5 and 6) was amplified from the sections by using nested polymerase chain reaction (PCR). Subsequent single-strand conformation polymorphism (SSCP) assay and sequencing analysis revealed one point mutation in exon 6 (coden 193, C-->A transition) from a UV-exposed skin sample, and seven point mutations in exon 5 (codens 146, 158, 150, 165, and 161, three C-->T, two C-->A, one C-->G, and one A-->T transition, respectively) from four SCTs, two SCCs and one UV-exposed skin sample. These experimental results demonstrate that alterations in the p53 gene are frequent events in chronic UV exposure-induced SCCs and later stage SCTs in Sencar mouse skin.

Comparison of therapeutic agents for synthetic pyrethroid exposure

Synthetic pyrethroids are highly active insecticides that possess a low mammalian toxicity, are rapidly metabolized, and leave practically no residue in the biosphere (1 ). All pyrethroids are lipophilic compounds that are practically insoluble in water and are recognized as nerve poisons. Increased usage in the past 7 years has established pyrethroids as a major class of pesticide chemicals (2). With increased usage, the number of reports of cutaneous dysesthesia among individuals occupationally exposed to synthetic pyrethroids has also increased (3). The cutaneous sensation that results from exposure typically occurs without erythema, edema, vesiculation or any other sign of dermal irritation. A new assay method, developed in this laboratory, has proven to be extremely sensitive in the detection of this dermal sensation ( 4).

EXPRESSION OF Hras-p21 AND KERATIN K13 IN UVR-INDUCED SKIN TUMORS IN SENCAR MICE

An ultraviolet radiation (UVR)-induced Sencar mouse skin carcinogenesis model was established to investigate the expression of Hras-p21 and keratin K13 in different stages of carcinogenesis, including UV-exposed nontumor skin, papillomas, squamous-cell carcinomas (SCCs), and malignant spindle-cell tumors (SCTs). Expression of Hras-p21 and K13 was examined in paraffin-embedded tumor sections by using immunohistochemical, immunofluorescent, and double staining techniques with specific antibodies. Positive Hras-p21 staining was detected in 1/3 (33%) papillomas, 24/36 (67%) of SCCs, but not in UVR-exposed nontumor skin or SCTs. Positive staining of the malignant progression marker K13 was found in 22/36 (61%) of SCCs only. Coexpression of Hras-p21 and K13 was found in 17/36(47%) SCCs. H-ras exons 1 and 2 were amplified from skin/tumor sections by using nested polymerase chain reaction (PCR). PCR-based single-strand conformation polymorphism (SSCP) analysis and gene sequencing revealed three point mutations, one in UVR-exposed nontumor skin (codon 56), and two in SCCs (codons 13 and 21). There were no clear relationships between point mutations of H-ras and the positive staining of Hras-p21 and K13. These results indicate that overexpression of ras-p21 in conjunction with aberrant expression of K13 is a frequent event in UVR-induced SCCs in Sencar mouse skin. Point mutation of the H-ras gene appeared to be a rare event in UVR skin carcinogenesis and not to be responsible for overexpression of Hras-p21.

Intralesional and perilesional treatment of skin cancers

In the following chapter, various intralesional and perilesional agents that have been used in the treatment of skin cancers will be presented by practitioners familiar with their use. The four medications reviewed have been in widespread use for many years in the treatment of cutaneous neoplasms and extracutaneous neoplastic and inflammatory conditions. Therefore, the efficacy, toxicity, delivery, indications, and costs for these agents are well established, and they are widely available. However, the most common routes of administration for such medications are oral, intravenous, and topical. An intralesional and perilesional approach to therapy is less often utilized, leading to less familiarity in clinical practice. It is our hope that a detailed review of these agents delivered in such a manner, along with a variety of clinical examples, will facilitate their use in practice and increase the variety of treatment options available to patients with cutaneous tumors.