Value of the cutaneous basophil hypersensitivity (CBH) response for distinguishing weak contact sensitization from irritation reactions in the guinea pig.

Numerous studies of the histology of allergic contact dermatitis reactions to potent allergens in guinea pigs and humans have indicated that there is significant tissue infiltration with basophilic leukocytes. In this study we determined whether this histologic finding could be of value in distinguishing weak sensitization reactions from primary irritation, thereby aiding in the predictive identification of weak or moderate contact allergens. Guinea pigs were sensitized by the Buehler test method. Skin reactions were graded 24, 48, and 72 h post-challenge with duplicate patch sites biopsied at the 24- or 72-h grading timepoints. The biopsies were fixed, embedded in glycol methacrylate, thin sectioned, and Giemsa stained. The number of basophils per 400 leukocytes were counted along the upper dermis just below the dermal/epidermal junction. Challenge patch sites from animals sensitized to a relatively low dose of the strong contact allergen, oxazolone, were compared with patch sites from animals challenged only with a strong irritant, sodium lauryl sulfate (SLS). Compared to normal skin (7.5 +/- 1.0 basophils/400 leukocytes +/- SEM) only the oxazolone patch sites showed significant basophil infiltration (36.8 +/- 6.5), despite the fact that the skin reactions to the low oxazolone challenge dose were relatively weak. SLS patch sites showed no basophil infiltration above normal skin levels (4.8 +/- 0.9). Subsequent blinded studies compared weak/moderate presumptive sensitization reactions (as defined by accepted visual skin grading criteria) to various chemicals (citronellal, vanillin, cinnamic aldehyde, and ethylenediamine) to primary irritation reactions to the same chemicals. In each case, low-challenge-dose sensitization sites on previously treated (induced) animals showed mean basophil infiltration (range, 11.9-69.2 basophils/400 leukocytes) significantly greater than higher-dose irritant reactions (range, 1.6-13.3). The range for normal skin was 0.2-10.2 and the range for strong patch reactions to higher concentrations of oxazolone was 59.8-209.3. These data strongly indicate that light-microscopic quantitation of the CBH response can be used to distinguish relatively weak to moderate contact sensitization reactions from primary irritation reactions to the same chemicals.

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.

Effects of variation of necropsy time and fasting on liver weights and liver components in rats.

In rats, percent liver weight loss is greater than percent body weight loss within the 8 A.M.-4 P.M. period of the working day. The liver weight loss is principally the result of decreased water content, either carbohydrate (glycogen) bound water in rats with access to feed, or protein bound water in rats fasted overnight. During this period, percent kidney weight loss is approximately equal to percent body weight loss. To optimize the sensitivity of kidney and liver weight evaluation, it is recommended that rats be fasted overnight and that relative liver and kidney weights be expressed based on body weights taken immediately prior to necropsy. Since these procedures will not entirely eliminate necropsy time-related organ weight differences, the animal necropsy sequence must be randomized to distribute the remaining differences across all treatment groups.

Spermatid giant cells, tubular hypospermatogenesis, spermatogonial swelling, cytoplasmic vacuoles, and tubular dilatation in the testes of normal rabbits.

Testes of 36 normal New Zealand white rabbits (8, 15, 18, 26, and greater than 52 weeks of age) were examined by light and electron microscopy. The incidence and number of affected tubules were determined for spermatid giant cells, focal tubular hypospermatogenesis, cytoplasmic swelling of spermatogonia, intracytoplasmic vacuoles in seminiferous epithelium, and tubular dilatation. Spermatogenesis commenced at 15-18 weeks of age and was present in all rabbits by 18 weeks. Spermatid giant cells occurred in 96% of rabbits 15 weeks of age and older. Focal hypospermatogenesis was present in 14-57% of testes once active spermatogenesis began. Ninety-seven percent of testes in all age groups combined had spermatogonial swelling. Infrequent dilated seminiferous tubules were present in five rabbits. Ultrastructurally, spermatid giant cells were round cells with multiple nuclei that appeared to arise by widening of narrow intercellular bridges that normally connect spermatogenic epithelial cells. Pale-staining spermatogonia consisted of cytoplasmic and nuclear swelling with disruption of plasma and nuclear membranes. Tubules with spermatogonial swelling were more numerous in 15- and 18-week-old rabbits. There were no significant differences in incidence or extent of spermatid giant cells, focal hypospermatogenesis, cytoplasmic vacuoles, or tubular dilatation between age groups after spermatogenesis commenced. Although the cause of these changes is not known, they were frequent findings in normal rabbits 15 weeks of age and older.