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Biomedical subjects

D L Bissett

Publications and source records attributed to D L Bissett.

16 recordsLinked to original sources

Time-dependent decrease in sunscreen protection against chronic photodamage in UVB-irradiated hairless mouse skin.

To determine the time dependence of sunscreen protection against chronic photodamage in hairless mice, the time was varied (0-8 h) between topical sunscreen treatment and UVB radiation exposure. Sunscreen products with labeled sun protection factor (SPF) values of 2, 4 and 8 were evaluated; these values were verified in a guinea pig model for SPF determinations. When applied immediately prior to UVB radiation exposure, these sunscreen products were very effective in prevention of skin wrinkling and tumor formation. Onset of photodamage was delayed, the delay being greater with higher SPF values. However, the sunscreen actives were rapidly lost from the skin surface, and their protective effect diminished strikingly as the time between treatment and irradiation increased. For daily protection against chronic photodamage, this suggests a need for photoprotectants with greater substantivity to achieve a high level of protection throughout the day.

Animals

Chronic ultraviolet radiation-induced increase in skin iron and the photoprotective effect of topically applied iron chelators.

In the skin of albino hairless mice (Skh:HR-1) there is a basal level of non-heme iron. Chronic exposure of mice to sub-erythemal doses of ultraviolet (UV) B radiation results in an increased skin level of non-heme iron. The iron increase may be the result of a UVB radiation-induced increase in vascular permeability, which we measured in vivo with the dye marker Evans Blue. We also observed greater non-heme iron in sun-exposed vs non-exposed body sites of human skin, suggesting that similar events occur in man. Iron may have a role in skin photodamage by participating in formation of reactive oxygen species. These species have been implicated in skin photodamage. It is known that iron can contribute to oxygen radical production by acting catalytically in the formation of species such as hydroxyl radical. While the basal level of skin iron may be available for catalysis, the elevated iron content of UV-exposed skin increases the potential for iron-catalyzed radical production. Topical application of certain iron chelators to Skh albino hairless mice dramatically delayed the onset of UVB radiation-induced skin photodamage. Non-chelating analogs provided no significant protection.

2,2'-Dipyridyl

Acute and chronic ultraviolet radiation induction of epidermal ornithine decarboxylase activity in hairless mice.

The effects of acute, multiple, and chronic exposure of hairless mice to ultraviolet radiation (UVR) on induction of epidermal ornithine decarboxylase (ODC) (EC 4.1.1.17) activity were investigated. Acute UVR exposure results in a biphasic time course of induction of epidermal ODC activity. Enzyme activity maxima occur at 3 and 24 h postirradiation. The biphasic time course is observed in two different strains of hairless mice (Skh:HR-1 and Jackson HRS/J) when the UVR source is either UBV fluorescent tubes or a solar simulator. The ratio of 24-h/3-h postirradiation ODC activity increases with increasing UVR dose. UVR induction of ODC activity was not significant below the mouse minimum erythemal dose (MED). The 3- and 24-h ODC activities have similar apparent Kms for ornithine (34 and 50 microM, respectively), and thermal stabilities at 52 degrees C (t1/2 = 23 and 18 min, respectively), and exhibit similar half-lives in vivo (t1/2 = 15 and 18 min, respectively). Multiple UVR exposure experiments showed 24-h ODC activity is sensitive to the preexposure history of the mouse, while 3-h ODC is not. Preexposure of hairless mice to several sub-MED levels of simulated solar radiation (SSR) specifically suppresses induction of 24-h ODC by a follow-up 2 x MED of SSR. Preexposure to a single 2 x MED of SSR specifically enhances induction of 24-h ODC induced by a second 2 x MED of SSR administered 48 h after the first. The 3-h ODC was not significantly affected by either preexposure regimen. Preexposure to a single high or low dose of UVA radiation did not affect epidermal ODC activity nor had an effect on ODC induction by UVB radiation. Several weeks of chronic exposure to UVB radiation elevated basal levels of epidermal ODC substantially (up to 350-fold). In these chronically irradiated mice, exposure to 2 x MED SSR resulted in a further 3.5-fold increase in ODC activity over the elevated basal level. These data reveal novel properties of epidermal cell expression of ODC activity in response to acute and chronic UVR insult. The results provide additional insight into the use of ODC as a marker for skin photodamage.

Animals

Chronic ultraviolet B radiation-induced biochemical changes in the skin of hairless mice.

Skh:HR-1 hairless mice were irradiated chronically with sub-erythemal doses of UVB radiation, and a number of biochemical parameters in the skin were determined after 6, 12, 18, and 24 wk of exposure. The parameters measured were water, collagen, elastin, and glycosaminoglycan content; collagenase and elastase levels; and Bz-Tyr-OEt (N-benzoyl-L-tyrosine ethyl ester) and BAPNA (alpha-N-benzoyl-DL-arginine-p-nitroanilide) hydrolyzing activities. Data for UVB radiation-exposed and chronological age-matched control mice were compared with respect to unit area and to unit mass of skin. On a unit area of skin basis, UVB radiation exposure increased the level of most parameters. The particular exceptions were collagen and collagenase which remained constant. On a mass of skin basis, though, there is an apparent decrease in collagen content because of the increase in the other skin components. This suggests that there is insufficient collagen in UVB radiation-exposed skin to support the increasing mass of the tissue.

Animals

Photoprotective effect of topical anti-inflammatory agents against ultraviolet radiation-induced chronic skin damage in the hairless mouse.

Albino hairless mice (Skh:HR-1) exposed chronically to suberythemal doses of ultraviolet (UV) radiation display visible and histological alterations in the skin. One alteration is an increase in dermal cellularity, including inflammatory cells. This suggested a role for inflammation in chronic photodamage. We evaluated the photoprotective effect of topical hydrocortisone, ibuprofen, and naproxen against photodamage. All 3 agents protected against UVB radiation-induced visible wrinkling, tumor formation, and histological alterations. Hydrocortisone and naproxen were also evaluated for protection against UVA radiation-induced visible skin sagging and histological alterations. Both were very effective. These data indicate that chronic topical application of anti-inflammatory agents provides broad solar UV spectrum photoprotection.

Administration, Cutaneous

Photoprotective effect of superoxide-scavenging antioxidants against ultraviolet radiation-induced chronic skin damage in the hairless mouse.

Albino hairless mice (Skh:HR-1) exposed chronically to suberythemal doses of ultraviolet radiation develop visible skin changes, histological alterations, and tumors. Topical treatment of mice with solutions of superoxide-scavenging antioxidants (such as alpha-tocopherol, ascorbic acid, propyl gallate and Trolox) prior to each UVB radiation exposure reduced significantly the severity of these events. Tocopherol esters and ascorbyl palmitate were not as effective as the parent compounds in providing protection. The data suggest a role for superoxide in UVB radiation-induced skin photoaging and the protective potential of superoxide scavengers. In contrast, the severity of UVA radiation-induced mouse skin damage was not reduced by topical application of the antioxidants tested here.

Animals

Protective effect of topically applied conjugated hexadienes against ultraviolet radiation-induced chronic skin damage in the hairless mouse.

Albino hairless mice (SkH:HR-1) exposed chronically to suberythemal doses of ultraviolet B (UVB) radiation display visible skin wrinkling and tumors. Topical treatment of mice with solutions of conjugated dienes (2,4-hexadien-1-ol and derivatives of it) prior to each UVB radiation exposure reduces significantly the severity of these visible alterations. Chronic suberythemal doses of ultraviolet A radiation induce skin sagging, a distinctly different visible skin alteration. The severity of skin sagging is not reduced by topical application of the conjugated dienes tested here.

Animals

Wavelength dependence of histological, physical, and visible changes in chronically UV-irradiated hairless mouse skin.

Albino hairless mice (Skh: HR-1) exposed chronically to sub-erythemal doses of UV radiation display physical, visible and histological alterations. Using narrow bandwidth radiation covering the UV radiation spectrum from 280-380 nm, the wavelength dependence of these alterations was determined. The wavelength dependence spectra indicate that for all but one parameter measured (skin sagging), UV-B radiation is considerably more efficient than UV-A radiation in producing changes in the skin. However, in natural sunlight there is considerably more UV-A than UV-B radiation, providing the potential for UV-A to have a larger contribution to skin damage than UV-B. This argues in favor of using broad spectrum photoprotective agents to shield the skin adequately from UV-induced aging. The spectra were also used to develop potential associations among events by determining which events occur at similar wavelengths. There seems to be a correspondence between mouse visible skin wrinking (UV-B event) and two histological events: increase in glycosaminoglycans and alteration in collagen. There was no obvious correspondence among UV-A-induced events.

Animals

Preparation and characterization of a reconstituted stratum corneum film as a model membrane for skin transport.

A zwitterionic surfactant, 6-eicosyldimethyl ammoniohexanoate (C20AH), completely disaggregates stratum corneum into individual cells. The cells can be cast into a film of reconstituted stratum corneum (RSC). Such films prepared from pig and human skin mimic intact human stratum corneum in microscopic, mechanical, and barrier evaluations. The films are useful as model membranes for skin transport experiments.

Animals

Role of protein and calcium in stratum corneum cell cohesion.

The work reported here indicates that protein and calcium have roles in stratum corneum cell cohesion. A zwitterionic surfactant, 6-octadecyldimethyl ammoniohexanoate (C18AH), was found to completely disaggregate pig and human stratum corneum into intact, individual cells. This method of disaggregation provided a tool to determine the role of tissue components in cell cohesion. The C18AH disaggregation of pig and human stratum corneum was accelerated by proteolytic enzyme and ethylenediaminetetraacetate (EDTA). The C18AH disaggregation could be blocked by pretreatment of the stratum corneum with the serine-type proteolytic enzyme inhibitor phenylmethylsulfonyl fluoride (PMSF). The blockage could be overcome by addition of proteolytic enzyme or divalent metal ion chelator. These and other data indicate the importance of protein and calcium in stratum corneum cell cohesion.

Animals

Genetic evidence for the physiological significance of the D-tagatose 6-phosphate pathway of lactose and D-galactose degradation in staphylococcus aureus.

Mutants of Staphylococcus aureus were isolated which were unable to utilize d-galactose or lactose, but which were able to utilize all other carbohydrates tested. Growth of the mutants on a peptone-containing medium was inhibited by d-galactose. Of those mutants selected for further study, one (tagI2) was missing d-galactose 6-phosphate isomerase, one (tagK3) was missing d-tagatose 6-phosphate kinase, and one (tagA4) was missing d-tagatose 1, 6-diphosphate aldolase. Each of these mutants accumulated the substrate of the missing enzyme intracellularly. Spontaneous revertants of each of the mutants simultaneously regained their ability to utilize d-galactose and lactose, lost their sensitivity to d-galactose, regained the missing enzymatic activities, and no longer accumulated intermediates of the d-tagatose 6-phosphate pathway. These data support our previous contention that the physiologically significant route for the metabolism of d-galactose and the d-galactosyl moiety of lactose in S. aureus is the d-tagatose 6-phosphate pathway. Furthermore, a mutant constitutive for all three enzymes of this pathway was isolated, indicating that the products of the tagI, tagK, and tagA genes are under common genetic control. This conclusion was supported by the demonstration that d-galactose 6-phosphate isomerase, d-tagatose 6-phosphate kinase, and d-tagatose 1, 6-diphosphate aldolase are coordinately induced in the parental strain.

Aldehyde-Lyases