INDUCTION OF PSORIASIFORM CHANGES IN GUINEA PIG SKIN BY PROPRANOLOL

Background. The ability of β-adrenergic blocking agents to induce psoriasis as an adverse effect prompted us to use such an agent to induce psoriasis in guinea pigs. Methods. Thirty female albino guinea pigs were divided into four groups. Group 1 received propranolol, 0.1 mg/day, dissolved in 2 mL of normal saline, orally by gavage for 30 days. Group 2 was given the same treatment, but in addition intradermal injections of propranolol with Freund's complete adjuvant, injected at weekly intervals. Group 3 (five animals) received 2 mL saline, and group 4 additional injections of adjuvant without propranolol. Groups 3 and 4 served as normal controls. Results. All animals of group 2 (which received propranolol orally and in addition intradermal injections of adjuvant) developed psoriasiform epidermal hyperplasia with acanthosis. Parakeratosis, papillomatosis, and formation of microabscesses, all characteristic signs of psoriasis, have not been seen in any of the skin samples of this group. Skin samples from group 1 animals receiving propranolol orally showed normal epidermis and dermis. They showed exactly the same histologic picture as the control groups 3 and 4. Conclusions. Beta-blockers given orally for 30 days do not cause any significant skin changes in guinea pigs. When given with a weekly intradermal injection of Freund's complete adjuvant, they cause psoriasiform epidermal hyperplasia. Although the overall histologic appearance of the skin of group 2 resembled psoriasis, it lacked important histologic features characteristic of this disease. It seems, therefore, that the model, per se, does not fulfill the initial expectations as an experimental model for psoriasis; however, this model has potential in the study of adverse drug reactions. Perhaps by introducing modifications to the experimental protocol, we may succeed also in developing a better model for experimental psoriasis.     

PENICILLIN AND CEPHALOSPORIN—INDUCED RASH IN GUINEA PIGS

Guinea pigs primed for delayed type hypersensitivity (DH) to antibiotics such as penicillin G (PCG), carbenicillin (CBPC), sulbenicillin (SBPC), ampicillin (ABPC), cephalexin (CEX), cephalothin (CET) and cephazolin (CEZ) by immunization in mycobacterial adjuvant developed a generalized rash (GR) and flare-up of previous test sites when challenged peritoneally with high doses of specific antigen. The GR was delayed in time, and histologically characterized by dilated and compacted small vessels and leucocytic infiltrations into the upper dermis. Animals immunized with CEX or CET developed a strong GR despite the absence of detectable antibodies. Hapten-carrier specificity and cross-reactivity in the GR system were essentially the same as those observed in skin testing of DH, but differed from those in the hemagglutination system. Accordingly, the GR shares many of the properties of DH skin test reactions: time course, histology, development despite an absence of detectable antibodies, carrier specificity, cross-reactivity. This experimentally induced rash may be a useful model for delayed type, generalized, exanthematic drug eruptions in man.     

INTRAEPIDERMAL FREE NERVE ENDINGS RELATING TO EPIDERMAL MELANOCYTES IN SPOTTED GUINEA PIGS

Intraepidermal free nerve endings were studied in spotted (black and white) guinea pigs. Specimens were obtained from black, gray, and white areas. Twenty blocks were made from each area and sections were examined by electron microscopy. Intraepidermal free nerve endings were found in the interfollicular epidermis of all three areas. The distribution density for the black areas was about twice that for the white areas. The frequency in the gray areas was intermediate between that for the black areas and that for the white areas. Intraepidermal free nerve endings contacted the melanocytes directly in the interspaces between the basal lamina of the epidermis and the cytomembrane of the melanocyte or the dendrite of the melanocyte in the intercellular spaces between basal keratinocytes. In most cases, their axons were ensheathed by Schwann cells. In some cases, a part of the axon expanded like a balloon about 200–300 nm in diameter. The ballooning structure contained several vacuoles about 40–60 nm in diameter. These vacuoles seemed to have been secreted into the extracellular spaces. In such cases, an accumulation of dense materials was observed along the opposed membrane of the vacuole and the cytomembrane of the melanocyte. In other cases, the cytomembranes of axons and those of melanocytes seemed to form synapse-like structures.     

MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF) IN GUINEA PIGS AND HUMANS WITH DELAYED HYPERSENSITIVITY

When lymph node cells from PPD-sensitive guinea pigs were incubated with PPD for 20–24 hours, they produced a soluble mediator which inhibited the migration of normal guinea pig peritoneal exudate cells (GP-PEC) out of capillary tubes. Also, human lymphocytes stimulated by antigen produced a soluble mediator which inhibited migration of normal GP-PEC and peripheral leukocytes. Guinea pig migration inhibitory factor (MIF) was eluted in the 34,000–67,000 molecular weight (MW) region of cultured supernatants. Human MIF was harvested from the 25,000 MW region of cultured supernatants from human lymphocytes fractionated on Sephadex G-100. Intradermal injection of the MIF into normal guinea pigs provoked reactions characterized by erythema and induration. The histologic response was found to be similar to that induced by antigen injection into sensitized animals. MIF from antigen stimulated lymphocytes may not have species specificity between guinea pig and human, although their molecular weights are different. No correlation was found between delayed skin reactivity induced by antigen in vivo and MIF production in vitro, and it is suggested that a substance inhibitory to MIF activity may be released in the lymphocyte culture.     

GUINEA PIG ENDOTHELIAL CELLS IN CULTURE

In pursuit of a model for the studies of endothelial cells in a readily available experimental animal, culture methods and the in vitro characteristics of endothelial cells isolated from guinea pig aorta are described. Endothelial cells were harvested by trypsinization with perfusion techniques and cultured in Eagle's minimal essential medium supplemented with 10% fetal calf serum. Their passage cultivation was possible for more than six months and they have maintained the in vitro morphological characteristics of endothelial cells. The cell doubling time of the passaged endothelial cells was 115–131 hours. The growth of guinea pig aorta endothelial cells was satisfactory in Eagle's minimal essential medium containing guinea pig serum and fetal calf serum, but not horse and calf serum. Of the various concentrations of fetal calf serum in Eagle's minimal essential medium, 3% fetal calf serum did not activate cell growth and 10% fetal calf serum induced the best growth; in 20% concentration of fetal calf serum the cell growth rate decreased as compared with the rate in 10% fetal calf serum. DNA synthesis (³H-thymidine uptake) of the cells in 20% fetal calf serum was less than that in 10% fetal calf serum. These results have no relation to cell generation nor to the cell density. With respect to the type of media supplemented with 10% fetal calf serum, Dulbecco's modified Eagle's medium, RPMI ?1640 and Eagle's minimal essential medium were satisfactory for the cultivation of guinea pig aorta endothelial cells, but Medium-199 was unsuitable. By adding endothelial cell growth supplement (75, 150 mcg) or fibroblast growth factor (100, 200 ng) to Eagle's minimal essential medium containing 3% fetal calf serum, the cell growth was stimulated approximately three times. Fibronectin-coated wells did not activate cell growth.     

ELECTRONMICROSCOPIC STUDY OF HYPOPIGMENTED LESIONS IN LEPROSY

Summary.— The electronmicroscopic appearance of the epidermis in 2 cases of indeterminate leprosy was studied. There was a significant decrease in the number of melanocytes and several of those present showed signs of depressed activity and atrophy. Langerhans cells were increased in number and seemed to replace the melanocytes. Further study is indicated to elucidate the pathogenesis of melanocyte inactivity and reduction in number.     

SKIN LESIONS IN HIV-POSITIVE AND HIV-NEGATIVE PATIENTS IN SOUTH INDIA

Background. Various dermatologic conditions have been reported to occur with increased frequency in human immunodeficiency virus (HIV)-positive individuals, but there are only a few studies comparing the prevalences of skin diseases in HIV-positive patients with those in matched HIV-negative controls. Methods. Skin lesions in 129 HIV-positive patients and 258 HIV-negative controls were studied prospectively over an 18-month period from October 1991 to March 1993. Results. Oral Candida, tinea cruris, and ichthyosis were significantly more common in HIV-positive patients compared to controls. Several other dermatologic conditions were found only in the HIV-positive group. Conclusions. The pattern of skin lesions in Indian patients with HIV infection may be different from that in the West.     

SURVEY OF SKIN LESIONS IN THE FILIPINO ELDERLY

One hundred elderly Filipino patients, aged 60 and over were surveyed to identify past and present skin complaints, and the dermatologic findings on a total cutaneous examination. All patients were consulting at the dermatology clinical of a teaching hospital in the Philippines. The elderly were keen to recall past hypersensitivity reactions because of their dramatic symptoms. The most common dermatologic problem prompting consultation was lichen simplex chronicus. Although the population size was limited, dermatoses in the Filipino elderly were not uncommon, and they were also subject to the stigmata of aging. Similarities and differences to two American surveys are noted.     

INCIDENCE OF MELANOMA IN SURGICALLY REMOVED PIGMENTED LESIONS

1277 surgically removed pigmented lesions sent to South Western Area Pathology Services (SWAPS) serving a demographicaly well defined area of about 240,000 inhabitants during a 4½ year period were reviewed. Of these 72 were malignant melanoma and 14 were interpreted as dysplastic naevi. The sex, age and site distribution are presented.     

SKIN MICROVASCULAR LESIONS IN CHRONIC DIFFUSE HEPATIC DISEASES

Skin biopsies obtained from the hand have been evaluated by histological and histochemical techniques, in twenty patients with a confirmed diagnosis of chronic diffuse hepatopathies and in ten healthy controls. In patients with chronic hepatic disease, skin biopsies show microvascular lesions, characterized by thickening of the PAS-positive basement membrane and endothelial alterations, similar to those found in diabetic patients. These lesions did not exist in the healthy control group.     

SQUAMOUS CARCINOMAS DEVELOPING IN BILATERAL LESIONS OF NECROBIOSIS LIPOIDICA

Squamous cell carcinomas developed in bilateral pretibial lesions of necrobiosis lipoidica in a 39 year old non-diabetic male. The tumours and areas of necrobiosis were successfully excised and repaired with full thickness skin grafts. Despite the chronic scarring and at times ulcerative nature of necrobiosis lipoidica, complicating squamous cell carcinomas have infrequently been reported.     

FIBRINOLYTIC ACTIVITY IN LESIONS PRODUCED BY MONOCHROMATOR ULTRAVIOLET IRRADIATION IN VARIOUS PHOTODERMATOSES

SUMMARY.– Histological and fibrinolytic activity (FA) changes were studied in skin exposed to visible light and u.v. radiation from a monochromator. There was a marked difference in the early and late lesions produced by irradiation. Late lesions showed loss of fibrinolysis and early lesions showed little or no such change.
Absence of fibrinolysis was found in upper dermal vessels in the more delayed sunburn papule reaction and in the delayed reaction in polymorphic light eruption (PLE) and actinic reticuloid, with heavy mononuclear infiltrates appearing as early as I hr. after irradiation. The lesions of PLE and "actinic reticuloid" showed absence of FA. There was no loss of fibrinolysis in the urticarial lesions of solar urticaria (as long as 5 hr. after irradiation) and in the porphyric skin reaction, or in light exposed porphyric skin.
These results suggest that impairment of fibrinolysis may play an important part in the delayed reaction to sunburn in the normal, in PLE, actinic reticuloid and photosensitivity with tetrachlorsalicylanilide. By contrast, impairment of fibrinolysis is not a feature of idiopathic solar urticaria or of the more or less acute porphyric photosensitive skin reaction.