Endotoxin-induced L-arginine pathway produces nitric oxide and modulates the Ca2+-activated K+ channel in cultured human dermal papilla cells.

Endotoxin includes an enzyme that synthesizes nitric oxide (NO) from l-arginine (NO synthase) in vascular smooth muscles cells, macrophages, and fibroblasts, leading to the release of NO. We evaluated the release of NO and its intracellular action on the Ca2+-activated K+ channel (KCa channel) in cultured human dermal papilla cells by use of the electron paramagnetic response (EPR) spin trapping method and the patch clamp technique. In dermal papilla cells pretreated for 24 h with endotoxin (1 microgram/microliter), application of 1 microM L-arginine generated NO, although no measurable release of NO was observed in cells without endotoxin pretreatment, as determined by the EPR spin trapping method. With the patch clamp technique, we found that the KCa channel of dermal papilla cells had high conductance and was voltage dependent. In addition, after endotoxin pretreatment, the extracellular application of 100 microM l-arginine modulated the KCa channel in the cell-attached patch configurations. In inside-out patch configuration, however, NO produced by L-arginine itself did not modulate the Kca channel. The modulation of the KCa channel was suppressed by pretreatment with 100 microM N omega-nitro-L arginine methyl ester, and inhibitor of inducible and constitutive NO synthases. Methylene blue, a blocker of guanylate cyclase, inhibited the L-arginine-induced activation of the Kca channel. Theses results indicate that the endotoxin-induced L-arginine pathway cell generates No, which consequently modulated the KCa channel in cultured human dermal papilla cells by increasing of cyclic GMP-dependent phosphorylation.

Severe dermographism after topical therapy with diphenylcyclopropenone for alopecia universalis.

We describe here a 19-year-old Japanese man with an 11-year history of alopecia universalis, who, after the 1st application of a 0.003% diphenylcyclopropenone (DPCP) solution to the whole scalp, developed acute contact dermatitis at the test site, together with widespread severe dermographism. Every 3 weeks, persistence of the severe urticarial reaction and efficacy of treatment were monitored by constant pressure stimuli in a series of pressure tests, and subsequently evaluated by laser Doppler flowmetry (LDF). Although, on pressure tests, the urticarial response was found to significantly improve after starting treatment, erythematous responses continued to appear for nearly 3 months. The persistent course of these side-effects in our patient strongly suggests that precautions must currently be taken in the therapeutic use of potent sensitizers such as DPCP.

A case of dermatomyositis complicated by thrombotic thrombocytopenic purpura.

A 60-year-old man with dermatomyositis was admitted to our hospital because of dyspnea and hypertension. He had high fever and convulsive seizures after admission. Laboratory examinations showed hemolytic anemia, thrombocytopenia, and renal failure. A clinical diagnosis of thrombotic thrombocytopenic purpura (TTP) was made. He failed to respond to plasma exchange therapy, pulse therapy with methylprednisolone, high-dose gamma-globulin therapy, and antiplatelet therapies with ticlopidine, dipyridamole and a prostacyclin analog of beraprost sodium. He died on his 17th day in hospital. Autopsy examination revealed widespread microthrombi in his kidneys, lungs, spleen, and intestine. Only seven cases of dermatomyositis or polymyositis complicated by TTP have been cited in the literature. TTP was fatal in 6 of these 7 cases. Early diagnosis and prompt treatment may improve the outcome of TTP patients with dermatomyositis. Dermatologists should keep in mind that TTP occasionally arises as a serious complication of dermatomyositis.