Permeation and reservoir formation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[a]pyrene (B[a]P) across porcine esophageal tissue in the presence of ethanol and menthol.

Environmental influences may affect carcinogen absorption and residency in the tissues of the aero-digestive tract. We quantified the effect of ethanol and menthol on the rates of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[a]pyrene (B[a]P) absorption using a fully validated in vitro diffusion system, capable of accurately and precisely quantifying tobacco carcinogen permeation and reservoir formation in porcine esophageal mucosa. Confocal microscopy was employed to visualize the location of B[a]P in the exposed membranes. Markedly different extents of permeation and reservoir formation for the tobacco carcinogens were recorded in the presence of ethanol and menthol. The water-soluble NNK permeated the membrane rapidly, while the lipophilic B[a]P did not appreciably diffuse through the tissue. Significantly different extents of reservoir formation were observed for the different carcinogens and in the presence of the different penetration-enhancer solvents. Alcohol (at 5% concentration) did not influence the permeation or reservoir formation of NNK. A mentholated donor solution (0.08%) both decreased the flux of NNK and significantly increased the tissue reservoir formation. The magnitude of the reservoir formed by B[a]P was relatively extensive (even though membrane permeation rates were negligible), being greatest in the presence of both ethanol and menthol. This suggests synergy between the two penetration-enhancer species acting on this carcinogen. Confocal microscopy studies confirmed that there was an appreciable intra-cellular, and specifically nuclear, association of the B[a]P species during the reservoir formation process. The aqueous solubility of the diffusing species and the presence of penetration enhancers appeared to be key factors in the absorption and cellular binding processes. The results presented support the hypothesis that the use of mentholated cigarettes, or the concomitant consumption of alcohol while smoking, may have marked effects on the fate of tobacco chemicals. This finding may help to explain elevated rates of esophageal squamous cell carcinoma in African Americans.

Esophageal cancer disparities in South Carolina: early detection, special programs, and descriptive epidemiology.

Because of its high fatality rate and our inability to detect esophageal disease early in its development, esophageal cancer represents a significant medical and public health challenge. The mortality statistics underline the importance of focusing on prevention of these conditions as a matter of state and national public health priority. Unfortunately, the measures needed for primary prevention of these conditions do not seem as clear-cut for populations at highest risk of this disease (i.e., AAs) as for the populations represented in most epidemiologic studies. Our incomplete knowledge about the etiology of esophageal cancer, especially squamous cell carcinomas in AAs and adenocarcinomas in EAs, preclude developing and disseminating effective preventive measures. Clearly, the prevention and control of esophageal cancers represent a different paradigm compared to other tobacco-related cancers of the upper aerodigestive tract. Data from a number of studies indicate that disparities exist in esophageal cancer incidence between racial groups and between geographical locations within South Carolina, and that these disparities are continuing to increase. The reasons for these disparities are only beginning to receive attention. They probably will be found to be complex and multifaceted. A combination of genetic factors, environmental influences (e.g., those related to diet), and the deleterious changes associated with smoking and alcohol consumption are the obvious parameters that should be the focus of initial epidemiologic data collection and assessment. Issues around dietary assessment, a major area of expertise among researchers in South Carolina, must be addressed in these studies. Much remains to be done for us to understand how research, health care, and educational efforts in the state of South Carolina might influence the detection, care, treatment, and, ultimately, reduction in esophageal cancer incidence and mortality rates. An important step in the process will be to coordinate data-collection efforts between clinicians, researchers, and concerned community members in South Carolina. This would allow comprehensive background profiles of patients to be collected for studies ranging from those focusing on the basic biology of the disease and its etiology to those aimed at understanding the role of health services and the effect of policy. In order to design and implement the full range of research needed to understand what we can do to prevent and control esophageal cancer in our state, it is our intention to engage all of the stakeholders within South Carolina; including community members, cancer survivors, cancer care providers, researchers, and individuals at high risk of esophageal cancer. With its large proportion of rural, socioeconomically deprived African Americans, what is learned about esophageal cancer in South Carolina will have national, and perhaps international, relevance.

Penetration enhancement of transdermal delivery--current permutations and limitations.

In order to achieve enhanced topical drug delivery, it is necessary to make physical or biomolecular structural alterations to the stratum corneum by suitable techniques or by the use of specific chemical agents or drug carriers. The role of the chemical penetration enhancer is to reversibly alter the barrier properties of the stratum corneum by disruption of the membrane structures or by maximizing drug solubility within the skin. Alternatively, permeant delivery to the dermal vasculature using one of several physical methods to reduce diffusional resistance within the skin may be used to promote drug penetration. In the present article, we summarize the major facets of the diverse spectrum of penetration enhancement techniques that include modification of the stratum corneum, lipid-based delivery systems, drug/vehicle interactions, bypassing the stratum corneum, and electrical techniques of enhancement.