Human thermoregulatory responses during heat exposure after artificially induced sunburn.

Thermoregulatory responses in the heat (ambient temperature 49 degrees C, 20% relative humidity, 1 m/s wind) were investigated in 10 unacclimated men during 50 min of cycle ergometer exercise (approximately 53% of maximal aerobic power) after a 10-min rest before as well as 24 h and 1 wk after twice the minimal erythemal dose of UV-B radiation that covered approximately 85% of the body surface area. In 7 subjects esophageal temperature (Tes) was recorded while in all 10 subjects five-site skin and rectal temperatures, heart rate, and back, left forearm, and shielded (12 cm2 area) right forearm sweating rates (msw) were recorded at 15-s intervals. Venous blood was collected before and after exercise-heat stress. Mean skin temperature, Tes, rectal temperature, heart rate, and total body sweating rate were not significantly (P greater than 0.05) affected by sunburn. Pre- and postexercise values of hematocrit, hemoglobin, plasma protein, plasma volume, and plasma osmolality were also not affected (P greater than 0.05) by sunburn. Analysis of presunburn and post-sunburn data showed that the Tes intercept for sweating (degrees C) was unaffected (P greater than 0.05), but msw/Tes and final msw from the left forearm (msw/Tes 0.24 +/- 0.02 vs. 0.17 +/- 0.01 mg.cm-2.min-1. degrees C-1, P less than 0.05; msw 0.60 +/- 0.05 vs. 0.37 +/- 0.02, mg.cm-2.min-1, P less than 0.05) and back (msw/Tes 0.43 +/- 0.03 vs. 0.36 +/- 0.01 mg.cm-2.min-1. degrees C-1, P = 0.052; msw 1.08 +/- 0.09 vs. 0.74 +/- 0.05 mg.cm-2.min-1, P less than 0.05) were significantly reduced 24 h postsunburn.(ABSTRACT TRUNCATED AT 250 WORDS)

Human thermoregulatory responses during cold water immersion after artificially induced sunburn.

Thermoregulatory responses during cold-water immersion (water temperature 22 degrees C) were compared in 10 young men before as well as 24 h and 1 wk after twice the minimal erythemal dose of ultraviolet-B radiation that covered approximately 85% of the body surface area. After 10 min of seated rest in cold water, the mean exercised for 50 min on a cycle ergometer (approximately 51% of maximal aerobic power). Rectal temperature, regional and mean heat flow (hc), mean skin temperature from five sites, and hearrt rate were measured continuously for all volunteers while esophageal temperature was measured for six subjects. Venous blood samples were collected before and after cold water immersion. The mean skin temperature was higher (P less than 0.05) throughout the 60-min cold water exposure both 24 h and 1 wk after sunburn compared with before sunburn. Mean hc was higher (P less than 0.05) after 10 min resting immersion and during the first 10 min of exercise when 24 h postsunburn was compared with presunburn, with the difference attributed primarily to higher hc from the back and chest. While rectal temperature and heart rate did not differ between conditions, esophageal temperature before immersion and throughout the 60 min of cold water immersion was higher (P less than 0.05) when 24 h postsunburn was compared with presunburn. Plasma volume increased (P less than 0.05) after 1 wk postsunburn compared with presunburn, whereas plasma protein concentration was reduced (P less than 0.05). After exercise cortisol was greater (P less than 0.05) 24 h postsunburn compared with either presunburn or 1 wk postsunburn.(ABSTRACT TRUNCATED AT 250 WORDS)

Industry-funded dermatologic research within academia in the United States: fiscal and ethical considerations.

Private-sector funding of biomedical research within academia may come from industry, foundations, the dermatologists themselves, and the public at large. Industry-funding is of benefit to both academia and industry. Industry may fund clinical and basic research and product testing. Industry is more willing to fund product testing and clinical research than basic research. Funds for dermatologic research may be obtained from manufacturers of drugs, medical devices, cosmetics, soaps, and detergents. Questions of academic freedom arise when research is funded by industry. The results of academic research are in the public domain; the results of intramural industry research are often proprietary, i.e., "trade secrets." When there is industry funding within academia, any restraints on publication should be held to a minimum and be temporary. Publication should occur in a timely fashion, although recognizing the need for delayed publication if the results concern patentable material. When there is a consultantship, pre-arranged terms of agreement may restrict communication. Patents usually are held by the investigator's institution. The funding company may be granted world-wide, royalty-bearing licenses. Conflicts of interest may arise during any research endeavor; this warrants close attention when the research is industry funded. Stock ownership, speaker fees, blind contracts, etc., should be avoided. In any communication, funding agreements should be stated. Indirect costs are a "necessary evil." There are non-research expenditures associated with all research projects for which the institution is justified in requesting compensation. Indirect costs must have definite connections to a project. As industrial funding of research within academia increases, various facets of the academia-industry relationship are receiving increasing attention. Several aspects of conflicts of interest and indirect costs must yet be resolved. When faced openly and directly, all of these issues are manageable and need not reduce the benefits to both industry and academia that are inherent in this relationship. Federal funding of academic research uses tax dollars; industry funding comes from private capital. Academia will benefit from the funding of academic biomedical research by industry. The ultimate beneficiary of the funding of academic research by industry, however, will be society at large as the medical advances derived from sound biomedical research and carefully controlled clinical trials aid patients. A solidly established academia-industry relationship is essential to the effective funding by industry of biomedical research within academia.

Effects of UVA (320-400 nm) on the barrier characteristics of the skin.

The stratum corneum serves as the major barrier to the entrance of most molecules into the skin. In the studies presented here, the effects of UVA radiation (320-400 nm) on the barrier capacity of human stratum corneum were examined. Penetration of a homologous series of primary alcohols through unirradiated (control) and UVA-irradiated (test) human epidermis was determined in vitro. Permeability constants, kp, were calculated. Mean ratios of permeability constants for UVA-irradiated and unirradiated epidermis (mean kp test)/(mean kp control) ranged from 2.3 to 3.0 for methanol and from 2.2 to 2.5 for ethanol. These mean ratios were determined using different pieces of epidermis from the same piece of skin for test and control samples. When kp control and kp test were determined on the same piece of epidermis on successive days, the ratios (kp test/kp control) were similar to the mean ratios determined on different pieces of epidermis. For other primary alcohols, propanol, butanol, hexanol, and heptanol, UVA radiation did not alter their permeability constants significantly. Partition coefficients, Km, were determined for ethanol and heptanol using UVA-irradiated and unirradiated stratum corneum. For ethanol, irradiation resulted in a 1.5 to 2.6 times increase in Km. For heptanol, irradiation caused no change in Km. These results demonstrate that the barrier capacity of stratum corneum for small, polar, primary alcohols is diminished (permeability increases) and for higher molecular weight less polar alcohols, is unaffected by small doses of UVA radiation. This increased permeability of small polar alcohols through human skin may be due to enhanced partitioning into UVA-irradiated stratum corneum, which was not apparent for a higher molecular weight less polar alcohol.

Efficiency of opaque photoprotective agents in the visible light range.

"Opaque" physical sunscreens are important for photoprotection of individuals with visible light and UV-A photosensitivity such as those with porphyria, drug photoallergy, and polymorphous light eruption. Diffuse spectral transmittance of various thicknesses of opaque sunscreen formulations were measured from 350- to 800-nm range using a spectrophotometer equipped with an integrating sphere. Transmission through 20% zinc oxide paste was high and decreased minimally despite large increases in the sunscreen layer thickness. Adding a visible light absorber such as iron oxide to scattering sunscreens, however, substantially lowered transmittance below that predicted by the product of the transmittances for each component alone. Opaque sunscreens protected against hematoporphyrin derivative photosensitization of albino guinea pig skin; these results were quantitatively consistent with the in vitro findings. Poor photoprotection against visible light is obtained with white paste sunscreens, even if thick layers are applied. The addition of pigments to such sunscreens, however, greatly enhances photoprotection and cosmetic acceptability.

Controlled removal of human stratum corneum by pulsed laser.

A new method is presented for controlled removal of the stratum corneum of human skin. An excimer laser (193 nm wavelength, 14 ns pulsewidth) was used to remove stratum corneum from in vitro human skin samples by an ablative process. The tritiated water (3H2O) permeability constant and electrical resistance of skin samples were measured in a diffusion chamber apparatus to quantify the enhancement of skin permeability. Each laser pulse ablates about a micrometer of stratum corneum, which allows controlled removal of tissue. The maximum specific enhancement of the 3H2O permeability constant obtained after complete stratum corneum removal depends on the laser pulse energy used. The most gentle laser ablation, achieved with a radiant exposure of 70 mJ/cm2 per pulse, produced a 124-fold enhancement, which is comparable to that achieved after stratum corneum removal by tape-stripping or removal of epidermis by mild heat treatment. Rapid tissue ablation occurred at higher radiant exposures of 170-480 mJ/cm2 per pulse, but only a 45-fold enhancement of permeability was achieved. The precision with which stratum corneum can be ablated using excimer laser pulses may allow further basic research on the internal structure of stratum corneum and on the re-epithelization in controlled wounds. The technique may prove useful clinically to enhance percutaneous transport in applications such as topical delivery of drugs, patch testing, and percutaneous blood gas monitoring.

Penetration of benzene through human skin.

Although it is known that benzene may be absorbed from inhaled air, the amount that may enter the system by percutaneous absorption is less well established. We have measured the penetration of benzene through human abdominal skin in vitro from solutions in water, gasoline, hexadecane, and isooctane and found permeability constants which averaged 111.0, 1.4, 0.9, and 3.7 X 10(-3) cm X h-1, respectively. The stratum corneum/water partition coefficient for benzene has been measured and averages 30.0. The partition coefficients for the other vehicles are very low and cannot be measured by the method used for water. A new method is presented for calculating these coefficients, however, and they are 0.11, 0.14, 0.17, and 0.19 for gasoline, hexane, isooctane, and hexadecane. The flux of benzene through epidermis in vitro from air saturated with benzene at 31 degrees C averages 1.0 microliter cm-2 X h-1. Solvents may alter the barrier characteristics of the stratum corneum. Polar and nonpolar molecules probably traverse the stratum corneum via different pathways. By measuring the change in the permeability constants for tritiated water (a polar molecule) and for benzene (a relatively nonpolar molecule) before and after exposure to different solvents, alterations of the polar and nonpolar pathways have been shown to differ. Since benzene penetrates normal intact human skin more rapidly than many small organic molecules, and is potentially toxic, the skin should be considered a portal of entry for benzene. Good hygiene should be maintained and care taken to avoid lengthy exposure to solvents containing benzene.

The diffusion of water across the stratum corneum as a function of its water content.

The flux of tritiated water (HTO) through pieces of stratum corneum at four different levels of hydration has been measured. The concentration of water in the stratum corneum, the concentration of HTO in the presenting solution, and the thickness, density, and weight per unit area of the dry stratum corneum are known. The thickness of the hydrated stratum corneum and the permeability and diffusion constants of HTO were calculated. From these in vitro data it is possible to calculate the in vivo thickness of the stratum corneum, its water concentration profile, and the flux of water (transepidermal water loss) at environments of different relative humidities. Both the transepidermal water loss and the water concentration profile change very little as the environmental relative humidity increases from 0 to 80%. The small decrease in the water concentration of the surface layers of cells as the relative humidity becomes very low, however, may cause an observable alteration in the physical characteristics of the surface layers.

Observations on the mechanism of the protective action of sunscreens.

A method is described for measuring the entrance into excised skin of ultraviolet radiation absorbing chemicals (UVRACs) following their application to the cutaneous surface in volatile, partially volatile or nonvolatile vehicles. Also a method is presented for observing changes in optical density (OD) of a sheet of stratum corneum subsequent to the application of an UVRAC and then washing it from the surface. Using these methods, p-aminobenzoic acid (PABA) and 2-ethylhexyl p-dimethyl aminobenzoate (O-PABA) have been studied. In the presence or absence of the nonvolatile vehicle, isopropyl myristate (IM), significant amounts of PABA enter the skin but almost all of the O-PABA remains on the surface. Nevertheless subsequently PABA is more easily removed by water than is O-PABA. When either UVRAC is applied to excised stratum corneum, the OD of the tissue increases immediately; only with PABA is there a further increase as it enters the skin. In vivo, delayed erythemal responses to 280-400 nm radiation of persons to whom the UVRACs are applied correlate well with the observations made on excised skin.

Photosynthesis of previtamin D3 in human skin and the physiologic consequences.

Photosynthesis of previtamin D3 can occur throughout the epidermis in the dermis when hypopigmented Caucasian skin is exposed to solar ultraviolet radiation. Once previtamin D3 is formed in the skin, it undergoes a temperature-dependent thermal isomerization that takes at least 3 days to complete. The vitamin D-binding protein preferentially translocates the thermal product, vitamin D3, into the circulation. These processes suggest a unique mechanism for the synthesis, storage, and slow, steady release of vitamin D3 from the skin into the circulation.