The Effect of Saline Iontophoresis on Skin Integrity in Human Volunteers: I. Methodology and Reproducibility

This study, conducted in 36 human volunteers, was an evaluationof the effects of saline iontophoresis on skin temperature,irritation, and barrier function. The major objectives wereto assess the effects of low-level ionic currents, to validatethe proposed methodology of assessment, and to establish reproducibilityin repeated saline iontophoresis applications. This was thefirst of a multistage study designed to assess the safety of24-hr saline iontophoresis episodes at selected currents andcurrent densities. Since an iontophoresis patch challenges theskin harrier both by occluding the skin surface and by passingionic current through the skin, the experimental protocol wasdesigned to permit measurement of the contribution of each ofthese processes to the overall response. In this first stagewe investigated the effect of 10 min of current delivery, at0.1 mA/cm² on a 1-cm² area patch and 0.2 mA/cm² on a 6.5-cm²area patch compared to unpowered control patches. Twelve subjectswere tested under each condition on two separate occasions toexamine reproducibility of the response variable measurements.A further 12 subjects were tested once under the 0.2 mA/cm 6.5-cm2condition. Skin irritation was evaluated via repeated measurementsof transepidermal water loss, capacitance, skin temperature,skin color, and a visual scoring system, before the iontophoresisepisode and after patch removal. No damage to skin harrier functionin terms of skin-water loss or skin-water content was detected.Slight, subclinical, short-lasting erythema was observed forboth conditions. Assessment of correlation coefficients showedhighly statistically significant indications of reproducibilityfor all five response variables measured. The experimental design,in combination with a repeated measures analysis, provided clearseparation of the occlusion and ionic current components ofthe iontophoretic patch challenge. Further, the repeated measuresanalysis gave a highly sensitive assessment of skin irritationand resolution after patch removal. We conclude that the experimentalmethodology is appropriate for assessing possible changes inskin integrity resulting from saline iontophoresis under similaroperating conditions for longer durations and for other skinchallenges from which a subclinical response is expected.     

Pulmonary Bioavailability and Fine Particle Enrichment of 2,3,7,8-Tetrachlorodibenzo-p-dioxin in Respirable Soil Particles

The pulmonary bioavailability of 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD) and the enrichment of polychlorinated dioxins (PCDDs)and furans (PCDFs) in fine particles were evaluated to assessthe implications that these factors have on risk and exposureassessments. Respirable subfractions of PCDD-contaminated soilfrom a former 2,4,5-trichlorophenoxyacetic acid manufacturingsite were isolated by chemical dispersion and gravity sedimentation.Analysis of the subfractions revealed that there was a size-dependentenrichment of PCDDs and PCDFs, with smaller particles more highlycontaminated. TCDD was enriched up to 33-fold as compared tounfractionated soil. Soil and laboratory-recontaminated galliumoxide, which served as the positive control, were administeredby intratracheal instillation to female Sprague-Dawley rats.Animals were terminated up to 28 days following treatment andpulmonary bioavailability of TCDD was assessed by hepatic enzymeinduction and TCDD concentration. Enzyme induction was dependenton the duration of exposure with up to 56 and 918% increasesin cytochrome P450 and aryl hydrocarbon hydroxylase (AHH) activity,respectively, following exposure to PCDD-contaminated soil.There was no significant difference in AHH induction betweenanimals which received contaminated soil and those treated withthe positive control. Hepatic concentration of TCDD in soil-exposedrats was 115, 101, and 179% of positive controls at 1, 7, and28 days post-treatment, suggesting that the soil or co-contaminantsinfluenced retention of TCDD in the liver. These data indicatethat the relative pulmonary bioavailability of TCDD on respirablesoil particles is 100% as compared to laboratory-recontaminatedgallium oxide and that PCDDs and PCDFs are highly enriched onrespirable particles. Utilization of these results will reducethe uncertainty and improve the accuracy of envi ronmental riskassessments of PCDDs and PCDFs.     

Human monoclonal antibodies against Plasmodium falciparum: production, stabilization and characterization

Nine human monoclonal antibodies (MoAbs) recognizing 7 different antigenic structures of blood-stages of the human malarial parasite P. falciparum (Pf) were produced by Epstein-Barr virus transformed B-cell lines (EBV-TCL) with or without fusion to the lymphoblastoid cell line KR4. The peripheral blood B-lymphocytes were obtained from 8 Gambian donors immune to Pf malaria. Two of the EBV-TCL could be expanded and maintained for more than 6 months but neither one could be cloned. Six additional EBV-TCL were stabilized after fusion with the KR4 lymphoblastoid cell line. All resulting hybridomas permitted easy cloning. Some of the MoAbs produced distinct fluorescent staining patterns of asexual Pf blood-stage parasites when using high-resolution digitized video-intensified fluorescence microscopy. Antigens on 195 kD and 155 kD proteins were recognized by 3 and 1 MoAb, respectively, using Western blotting and immunoprecipitation techniques.     

Demographic Characteristics and the Frequency of Heavy Drinking as Predictors of Self-reported Drinking Problems

The distribution of both heavy drinking and drinking problems are well known from several previous studies. Not surprisingly, drinking problems are more prevalent among the demographic groups where heavy drinking is also more prevalent. This well-known conjunction, however, does little to determine whether some groups are more likely than others to experience drinking problems when we control for the amount of alcohol consumed. Here, this question is punned through a multiple regression analysis in which the dependent variable is a score on a drinking problem scale and the independent variables are: the frequency of heavy drinking occasions, sex, age, marital status, region, urbanicity, income, and education. The results indicate that none of these demographic variables had a strong association with the reported problem level.