Endothelin-1 in Human SkinBull, H.A.; Dowd, P.M.
doi: 10.1159/000247187pmid: 8324270
Endothelin-1 (ET-1) was originally identified as an endothelium-derived peptide with potent local constrictor and systemic pressor effects. Consequently it was implicated as a mediator in the control of systemic as well as peripheral vascular tone. The intense activity that followed the discovery of ET-1 has shown that endothelium is not the only site of synthesis nor is smooth muscle the sole target. ET-1 is capable of initiating and regulating an array of cellular responses including contraction, proliferation, synthesis of extracellular matrix proteins and induction of proto-oncogene expression. This diversity of function is paralleled by an increasing number of mediators capable of inducing synthesis of ET-1 in an ever increasing array of cell types. ET-1 is also a neuropeptide; mRNA for ET-1 has been identified by in situ hybridization in human spinal cord and dorsal root ganglia, and ET-1 was shown to modulate adrenergic neurotransmission at the neuro-effector junction. This review will highlight some of the recent advances in our understanding of the mechanisms regulating the synthesis of and cellular responses to ET-1 with particular reference to its potential role in the maintenance of cutaneous homeostasis and in the pathophysiology of cutaneous diseases.
Aedes albopictus in Europe: A New Challenge for DermatologistsRebora, A.; Rongioletti, F.; Raineri, V.
doi: 10.1159/000247188pmid: 8324281
A patient is reported who was bitten by Aedes albopictus, commonly known as tiger mosquito. The biology of the insect, originally living in the forests of southeastern Asia, and its role in transmitting exotic infectious agents is discussed. Up to this day, only Albania and northern Italy have been colonized, but the biologic characteristics of the insect make its spreading all over Europe highly probable, unless serious attempts to eradicate it are quickly undertaken. Dermatologists should think of the tiger mosquito in the presence of painful, purpuric, large wheals and when patients report a history of multiple attack during daylight.
Fabry’s Disease: Heterozygous Form of Different Expression in Two Monozygous Twin SistersMarguery, M.C.; Giordano, F.; Parant, M.; Samalens, G.; Levade, T.; Salvayre, R.; Maret, A.; Calvas, P.; Bourrouillou, G.; Cantala, P.; Bazex, J.
doi: 10.1159/000247189pmid: 8324287
A 26-year-old woman presented widespread angiokeratomas predominantly in a swimsuit distribution pattern associated with acroparesthesia in all four limbs. The tentative diagnosis of Fabry’s disease (FD) was confirmed by optical and electron-microscopic findings and by appropriate biochemical testing. The work-up showed ocular and renal manifestations of the disease. The monozygous twin sister of the patient was asymptomatic although she was shown to be heterozygous for the enzymatic defect. These 2 cases illustrate the concept of extreme lyonization which can explain observed phenotypic differences in heterozygous females with X-linked hereditary diseases. The father and mother of the patient were shown to be noncarriers of the trait, suggesting de novo mutation in the twin pregnancy. However, biochemical testing for the detection of FD heterozygous females cannot rule out the possibility of the mother being heterozygous with normal enzyme activity.
Effects of Sodium Lauryl Sulfate on Human Skin in Organ Culture: Comparison with All-Trans-Retinoic Acid and Epidermal Growth FactorVarani, J.; Fligiel, S.E.G.; Perone, P.; Inman, D.R.; Voorhees, J.J.
doi: 10.1159/000247191pmid: 8324272
Human skin organ cultures were established from 2-mm punch biopsies and incubated under serum-free conditions in basal medium containing either 0.15 or 1.4 mM extracellular Ca<sup>2+</sup>. Organ cultures were treated with concentrations of sodium lauryl sulfate (SLS) that had previously been shown to support growth of human epidermal keratinocytes and human dermal fibroblasts in monolayer culture. Epidermal growth factor (EGF), alone and in combination with insulin and bovine pituitary extract, fetal bovine serum and all-trans retinoic acid (RA) were also examined for comparative purposes. The addition of SLS to culture medium containing low extracellular Ca<sup>2+</sup> had no effect on the viability or histological appearance of the organ-cultured skin. Complete degeneration of the tissue occurred in the presence of SLS just as it did under control conditions. When SLS was added to culture medium containing high extracellular Ca<sup>2+</sup>, the basal layer of keratinocytes was much thinner than under control conditions. When EGF or EGF in combination with insulin and pituitary extract were utilized in place of SLS, identical results were obtained. That is, there was no preservation of the basal epithelial layer in the presence of low-Ca<sup>2+</sup> culture medium and in the presence of high-Ca<sup>2+</sup> culture medium, the basal layer was thinner than in control tissue. Virtually identical results were also obtained in medium containing 10% fetal bovine serum. In contrast, when RA was included in low-Ca<sup>2+</sup> culture medium, the basal epithelium was maintained in a viable, histologically healthy condition. However, normal epithelial differentiation did not occur and the upper layers of the epidermis separated from the basal cells. When RA was added to the high-Ca<sup>2+</sup>-containing culture medium, the epidermis was increased in thickness over that seen in the absence of RA. These data suggest that in spite of the ability of all of these agents to induce proliferation of skin cells in monolayer culture, there may be significant differences among them in their ability to influence the biology of skin.
Methimazole (2-Mercapto 1-Methyl Imidazole) in Psoriasis – Results of an Open TrialElias, A.N.; Goodman, M.M.; Rohan, M.K.; Alpern, K.; Barr, R.J.
doi: 10.1159/000247192pmid: 8324273
Methimazole, an antithyroid drug, was orally administered, in an open trial, in a dose of 20 mg every 12 h for 8 weeks to 8 volunteers with long-standing psoriasis. 3-mm punch biopsies were taken from the lesions at the start and at the end of the study. Clinical response was assessed using the Psoriasis Areas Severity Index score. Methimazole produced marked to moderate improvement in the clinical scores in the majority of patients. Histological scores were also significantly improved in all patients. Unexpectedly, thyroid function tests were not affected by methimazole therapy in all but one patient, and none of the patients developed drug-induced cytopenia. Methimazole may be an effective therapeutic agent in the management of psoriasis; it most probably exerts its therapeutic effect by acting on the immune system.
Topical Treatment of Penile Condylomata acuminata with Podophyllotoxin 0.3% Solution, 0.3% Cream and 0.15% CreamSyed, T.A.; Lundin, S.
doi: 10.1159/000247193pmid: 8324274
The purpose of this comparative open study was to determine the clinical efficacy of 0.3% podophyllotoxin both in 70% ethanolic solution and cream preparations on genital warts. Three parallel trial preparations, 0.3% solution, 0.3% and 0.15% cream, were randomly allocated to 60 circumcised Asian males (mean age 19.5 years), with the diagnosis of genital condyloma. Patients applied the trial preparation twice a day for 3 consecutive days. If total elimination was not achieved with one trial, it was extended to 3 similar cycles, in total of 4 weeks duration. Response was calculated with a response rate formula. After 3 weeks of treatment all the patients in the 0.3% solution group were evaluated as cured, with mild localized erythema and burning sensation. In the 0.3% cream preparation group, 75% of the patients were cured, and the remaining 25% were found to be cured after 4 treatments. In the 0.15% cream preparation group, 70% of the patients were evaluated as completely cured after 4 weeks. Non-objective, moderate to mild localized adverse symptoms were reported by both the active cream groups. Three of 54 patients (90%) with complete cure showed relapses after 16 weeks. It was concluded that 0.3% podophyllotoxin is more efficacious in ethanolic solution than in cream preparations.
Solid Persistent Facial Edema of Acne: Successful Treatment with Isotretinoin and KetotifenJungfer, B.; Jansen, T.; Przybilla, B.; Plewig, G.
doi: 10.1159/000247194pmid: 8324275
A 20-year-old man suffering from acne vulgaris since the age of 12 developed a solid persistent inflammatory edema of the face through the last 2 years. The edema was resistent to conventional treatment of acne including various systemic and topical antibiotics, isotretinoin and interferon-gamma. Histopathologic examination revealed an extensive fibrosis of the middle and deeper corium with a dense lymphohistiocytic perivascular infiltrate, notably with many mast cells. The therapeutic combination of oral isotretinoin (0.5 mg/kg body weight daily) and ketotifen (2 mg daily) led to complete resolution of all facial lesions. The pathogenesis of persistent edema remains mysterious but may be related to chronic inflammation resulting in obstruction of lymph vessels or fibrosis induced by mast cells.
Erythema multiforme-like Eruption in Association with Severe Headache following PyritinolNachbar, F.; Korting, H.C.; Vogl, T.
doi: 10.1159/000247196pmid: 8324277
A 46-year-old woman presented with an unusual erythema multiforme-like eruption and severe headache 10 days after treatment with pyritinol for cerebral concussion. Histopathologic findings were consistent with erythema multiforme. Skin lesions and headache cleared after withdrawal of the drug. According to neurological examination and magnetic resonance imaging of the brain, the headache may have resulted from a slight, pyritinol-induced vasculitis. Previous reports on severe pyritinol-induced side effects and possible pathogenetic mechanisms are reviewed. Since pyritinol cannot be considered as an essential drug for cerebral concussion, adverse effects as described here raise doubts as to its general use in the given indication.