Protection against photodynamic therapy (PDT)-induced photosensitivity by fabric materials.

"Special" highly protective fabrics are now available that offer broad-spectrum protection in preventing sunburn, and possibly other types of photodamage. It is important to know to what extent these fabrics are capable of protecting the wearer against skin cancer, photosensitivity disorders, and inadvertent phototoxic reactions from photodynamic therapy (PDT). We assess the ability of one such special (Solumbra) fabric and one "typical" summer fabric to provide protection against PDT phototoxicity produced in tape-stripped Sk-1 hairless mice by topical 5-aminolevulinic acid (ALA) and (primarily) visible light (360-800 nm). Since ALA-derived photosensitizers absorb most of the visible spectrum, results from these studies give a good indication of the photoprotective capability of these fabrics throughout this region. Mice were irradiated dorsally with a Kodak slide projector equipped with a 300 W tungsten-halogen lamp (I0 = 48.3 mW/cm2). After determining the minimal phototoxic dose (MPD) to be 1.40 +/- 0.4 J/cm2, we irradiated the tape-stripped ALA-sensitized mice through the stretched test fabrics with appropriate multiples of the MPD. The special fabric provided protection against 25-30 MPD visible light between 360-800 nm in 14/14 mice. The typical fabric failed to provide protection against 2.5 MPD of the same spectrum. No phototoxic or other adverse responses were seen with either the ALA or light control. In conclusion, the Solumbra fabric is much more protective against ALA photosensitization than the typical fabric. Both appear better at blocking UV than visible light.

Chronic exposure of Sk-1 hairless mice to narrow-band ultraviolet A (320-355 nm)

Several recent investigations collectively suggest that the role of ultraviolet A (UVA) in chronic actinic skin damage may be greater than originally thought. In the present work, the output of a xenon-arc solar-simulator passed through a Bausch & Lomb monochromator in conjunction with a 2-mm Schott WG-320 filter produced narrow-band UVA centered at 338 nm, half-band width 24 nm, I0 = 3.4 +/- 0.3 mW/cm2. We chronically irradiated 10 Sk-1 albino hairless mice 5 times per week for 18 weeks, starting with 1.25 J/cm2, for 33 irradiation days, sequentially followed by 1.50 J/cm2 (34 days), 1.8 J/cm2 (10 days), 2.0 J/cm2 (22 days) to afford a total UVA dose of 154.3 J/cm2 over 99 irradiation days. Erythema was noted clinically by day 6, which persisted throughout the irradiation. During the irradiation period, some scaling, consistent with mild epidermal hyperplasia was noted during irradiation days 37-56. This response later regressed despite continued chronic irradiation. Hematoxylin and eosin examination immediately after the final irradiation revealed a mild inflammatory response, with some dermal restructuring. At the end of the experiment, no significant signs of epidermal hyperplasia or (pre)malignant lesions were seen, although some stratum corneum thickening was noted. Marked dermal collagen damage and moderate elastosis was also evident. We believe that the observed differences in results reported in previous studies are in large part due to differences in light sources and irradiation protocols.

Zidovudine as an immunomodulatory agent.

In view of the increase of HIV infection in women, and of transplacental infectivity, 3'-azido-3'-deoxythymidine (zidovudine) is being explored to control infection in offspring. Zidovudine toxicity in humans and experimental animals is well documented. However, information on immunotoxicity in pregnant females and their offspring is lacking. We exposed pregnant female mice to zidovudine to provide data, and perhaps baseline evaluation, on zidovudine immunotoxicity in primiparous females and their progeny. In pregnant mice exposed to zidovudine (0.2 mg/ml) in drinking water, enhancement of the mixed lymphocyte response (MLR) occurs; suppression is not seen until the 7th month. Profound, persistent suppression is seen in their progeny first detected at one week of age. Suppression in virgin females occurs 1 month after treatment, which persists through the seventh month. The antibody forming cell response is enhanced in primiparous females and their offspring, but is not affected in virgin females. After weekly alternation of oral treatment with two 0.5 ml intravenous injections at 0.2 mg/ml, MLR suppression occurs after 1 month in primiparous females, while in their progeny and in virgins enhancement is seen first; in progeny suppression is observed at 3 months. Thus, zidovudine is immunosuppressive for T-cell mediated immunity and the kind of modulation is a function of treatment regimen.

Protection against UV photocarcinogenesis by fabric materials.

BACKGROUND: Clothing fabrics have long been considered effective protection against short-term and long-term sun damage. Recently, special "highly UV-protective" fabrics have been developed specifically for photosensitive patients. OBJECTIVE: To determine if one such fabric will protect hairless mice against (pre)malignant lesions under conditions that will produce skin cancers through a typical summer fabric of moderate sun protection factor (SPF). METHODS: After prior determination of minimal erythemal dose, four sets of 10 animals were divided into the following groups: (A) dark control (no irradiation); (B) positive control (no fabric); (C) "typical summer" fabric (SPF = 6.5 +/- 1.0); and (D) "special" fabric (SPF > 30 across a broad spectrum). Mice were irradiated on the dorsal surface 5 days per week, with biweekly incremental increases (roughly 20% of the starting dose), for 12 weeks. Group B started at 6.3 J/cm2, with biweekly increases of 1.45 J/cm2 (total dose, 596 J/cm2); groups After irradiation, mice were observed for clinical and histologic signs of pre(malignant lesions for an additional 12 weeks. RESULTS: At the end of the 12-week irradiation period, nine mice in group B and six mice in group C had actinic keratosis-like lesions, whereas one mouse in group B and two mice in group C had squamous cell carcinoma. By week 24, all mice in groups B and C had squamous cell carcinoma. Mice in groups A and D showed no discernable reaction at any time. Biopsy specimens confirmed the clinical results. CONCLUSION: Typical summer clothing fabrics may offer inadequate protection against skin cancer and pose high risk to chronically photosensitive patients. The use of appropriate sun protective apparel should offer effective protection to photosensitive patients against short-term and long-term photodamage.

In vivo depigmentation by hydroxybenzene derivatives.

Certain mono- and dihydroxybenzene derivatives are selectively cytotoxic for melanocytes in vivo, and can cause depigmentation of skin and hair. We produced selective melanocytotoxicity/hair depigmentation in C57Bl mice by injection of 0.032-1.0% p-t-butylcatechol (tBC) or p-hydroxyanisole (MMEH) in physiological saline. No depigmentation occurred on injection of 3,4-dihydroxyphenylalanine (DOPA) or 3,4-dihydroxyphenylacetic acid (DOPAC). Light- and electron-microscopic examination of biopsy specimens taken from depigmented areas indicates selective melanocyte damage as early as 2 h post-injection. Melanocytes from anagen hair are most susceptible to depigmentation. All four compounds are substrates for tyrosinase, but only tBC and MMEH generate their respective isolable 1,2-benzoquinones, tBCQ and MMEHQ. These caused depigmentation in C57Bl mice to a comparable degree to the parent compounds. DOPA- and DOPAC-quinones (DOPAQ and DOPACQ) are not spectroscopically detectable in solution, suggesting extremely low steady-state levels of these compounds. The net observed rate of reaction of the respective 1,2-quinone with 300 microM bovine serum albumin (BSA) in vitro varies widely, with tBCQ >> MMEHQ = DOPACQ >> DOPAQ. The results are consistent with a mechanism involving attack of -SH on melanosomal proteins and/or enzymes by tyrosinase-generated 1,2-quinones. This mechanism evidently differs from that involved in in vitro hydroxybenzene melanocytotoxicity of melanoma cells, in which active oxygen intermediates generated by hydroxybenzene autoxidation play a significant role. The most reliable prognosticator of in vivo depigmentation appears to be the ability of the depigmenter to form a spectroscopically stable 1,2-quinone which is capable of reacting with protein -SH.

Carotid body of Camelus dromedarius.

The carotid body of the camel is located between a mass of loose connective tissue at the point of separation of the internal carotid artery from the carotid trunk. A capsule-like connective tissue sheath sends strands in between the parenchyme of this organ and separates lobes and lobules, making it disseminated in type, as in man and in the horse. Two distinct types of cells were found in the parenchyma. Type I cells with specific electton-dense, cored vesicles, and type II cells with protoplasmic extensions. Unlike the previously reported arrangement in the carotid body of some species, the type I cells have direct contact with the basement membrane of glomi and capillaries. Synaptic contacts were seen on both cell types.