The effects of Hochu-ekki-to in patients with atopic dermatitis resistant to conventional treatment.

Hochu-ekki-to is one of Kampo formulas containing Astragalus root, liquorice, jujube, ginseng, white Atractylodes rhizome, fresh ginger and Chinese angelica root. This formula has been identified as an effective drug to improve the function of digestive systems and to strengthen defensive systems against many kinds of infections. We examined serum IgE levels and eosinophils before and after the administration of Hochu-ekki-to in patients with recalcitrant atopic dermatitis. The increased numbers of eosinophils was statistically decreased after 3 months' use of this formula. Serum IgE levels showed a tendency to decrease after the administration of this substance.

Diet and Japanese herbal medicine for recalcitrant atopic dermatitis: efficacy and safety.

We have been utilizing Kampo, a Japanese herbal medicine, together with lifestyle advice, for recalcitrant atopic dermatitis. To estimate the safety and efficacy of the treatment, we administered Kampo formulas to patients in whom conventional treatment failed to improve symptoms, along with dietary advice recommending traditional Japanese food. The therapeutic effects of Kampo formulas were assessed in 95 patients with recalcitrant atopic dermatitis who consulted our clinic from January to June, 2000. The overall result was 'markedly effective" in 19 patients (20%), "moderately effective" in 33 (35%), "slightly effective" in 36 (38%) and "ineffective" in four (4%). Three patients dropped out of the study. No adverse reactions in laboratory data were noted in examined patients. The most commonly used formula was Hochu-ekki-to containing Astragalus root, liquorice, jujube, ginseng, white Atractylodes rhizome, fresh ginger and Chinese Angelica root. Diet and Japanese herbal medicine are thought to be useful as an alternative therapy of intractable atopic dermatitis.

Hochu-ekki-to suppresses development of dermatitis and elevation of serum IgE level in NC/Nga mice.

The Japanese herbal medicine Hochu-ekki-to (Chinese name: Bu-Zhong-Yi-Qi-tang) is composed of ten species of medical plants and is used for many therapeutic purposes such as recovery from weakness, dysfunction of the digestive system and fatigue. In certain groups of patients with intractable atopic dermatitis this prescription has shown clinical effectiveness. We examined the ability of Hochu-ekki-to to inhibit dermatitis and IgE production in atopic NC/Nga mice. Oral administration of Hochu-ekki-to suppressed spontaneous dermatitis and serum IgE levels in NC/Nga mice. This finding provides evidence that Hochu-ekki-to may have immunological effects in atopic dermatitis.

Induction of cutaneous delayed hypersensitivity reactions in mice sensitized with intragastrically administered hapten: activation of Langerhans cells in the sensitization and elicitation phases.

BACKGROUND: As seen in atopic dermatitis, allergic diseases often produce lesions both in the gastrointestinal tract and the skin, suggesting the involvement of an immunological relationship between the two organs in the pathogenesis. OBJECTIVES: To study the role of gastric and epidermal Langerhans cells (LCs) in the sensitization and elicitation phases, respectively, of cutaneous delayed-type hypersensitivity (DTH) reactions to intragastrically administered hapten. METHODS: BALB/c mice, which were subjected to intragastric administration of trinitrochlorobenzene 5 days previously, received an elicitative challenge of the same hapten to the ear skin. Sections of the ear were immunostained for CD4 and CD8. Epidermal sheets of the ear and epithelial sheets of the forestomach were immunostained for I-A and observed under a confocal laser scanning microscope. RESULTS: Cutaneous DTH reactions were induced in mice, as demonstrated by an increase in ear thickness and a prominent infiltration of CD4+ and CD8+ lymphocytes at 24-36 h after the elicitative challenge. In the elicitation phase, epidermal LCs showed a significant increase in size, indicating in vivo activation, at 24 h. In the sensitization phase, gastric LCs increased in size at 2 h, became round at 6 h, and decreased in number at 24 h, possibly representing the sequential events of LC activation and migration from the epithelium. CONCLUSIONS: The present study demonstrated that gastric LCs and epidermal LCs were activated in vivo in the sensitization and elicitation phases, respectively, of cutaneous DTH reactions in orally sensitized mice.

Selective activation of p38 mitogen-activated protein kinase cascade in human neutrophils stimulated by IL-1beta.

We investigated activation of mitogen-activated protein kinase (MAPK) subtype cascades in human neutrophils stimulated by IL-1beta. IL-1beta induced phosphorylation and activation of p38 MAPK and phosphorylation of MAPK kinase-3/6 (MKK3/6). Maximal activation of p38 MAPK was obtained by stimulation of cells with 300 U/ml IL-1beta for 10 min. Extracellular signal-regulated kinase (ERK) was faintly phosphorylated and c-Jun N-terminal kinase (JNK) was not phosphorylated by IL-1beta. IL-1beta primed neutrophils for enhanced release of superoxide (O(2)(-)) stimulated by FMLP in parallel with increased phosphorylation of p38 MAPK. IL-1beta also induced O(2)(-) release and up-regulation of CD11b and CD15, and both responses were inhibited by SB203580 (p38 MAPK inhibitor), suggesting that p38 MAPK activation mediates IL-1beta-induced O(2)(-) release and up-regulation of CD11b and CD15. Combined stimulation of neutrophils with IL-1beta and G-CSF, a selective activator of the ERK cascade, resulted in the additive effects when the priming effect and phosphorylation of p38 MAPK and ERK were assessed. IL-1beta induced phosphorylation of ERK and JNK as well as p38 MAPK in human endothelial cells. These findings suggest that 1) in human neutrophils the MKK3/6-p38 MAPK cascade is selectively activated by IL-1beta and activation of this cascade mediates IL-1beta-induced O(2)(-) release and up-regulation of CD11b and CD15, and 2) the IL-1R-p38 MAPK pathway and the G-CSF receptor-ERK pathway work independently for activation of neutrophils.

Granulomatous slack skin: an ultrastructural study.

BACKGROUND: Granulomatous slack skin is a rare lymphoproliferative disorder characterized clinically by gradual development of pendulous folds of lax erythematous skin in flexural areas, and histologically by non-necrotizing granuloma, with numerous multinucleated giant cells, mononuclear histiocytes, and atypical lymphocytes associated with loss of elastic fibers. Although there are many reports describing the histological and immunophenotypic features of this disease, only a few have described the ultrastructural features. METHODS: Here we report a case of granulomatous slack skin and describe the ultrastructural findings. RESULTS AND CONCLUSION: We could detect some previously not noted abnormal findings in multinucleated giant cells, histiocytes, and atypical lymphocytes.

Lymphocytic aleukemic leukemia cutis.

A 21-year-old male patient had localized papules on the chest and arms. Biopsy of a lesion showed it to be a malignant lymphoid neoplasm, and immunohistochemical studies confirmed a lymphoblastoma origin. Aberrant lymphoid cells were noted in the cutaneous blood vessels, but simultaneous examination of the peripheral blood showed no evidence of leukemia. One month elapsed before observable leukemic cells were found in the blood and sternal marrow, confirming the diagnosis of acute lymphocytic leukemia. Examination of a cutaneous biopsy specimen led to early diagnosis of the disease.

Squamous cell carcinoma of the scrotum.

A patient with psoriasis was found to have a large skin tumor on his scrotum. He had received psoralen and ultraviolet A radiation therapy to control psoriasis. Histopathologic study revealed that the tumor was a well-differentiated squamous cell carcinoma. We present this rare case and suggest that the genitalia be shielded during ultraviolet therapy.

Twenty-nail dystrophy (trachyonychia) caused by lichen planus in a patient with alopecia universalis and ichthyosis vulgaris.

A 7-year-old girl with alopecia universalis had dystrophy of all 20 nails. A nail biopsy specimen disclosed features of lichen planus. The patient also had ichthyosis vulgaris and hypogammaglobulinemia. We are not aware of any previous reports of these associations, which we believe to be noncoincidental.

Subcorneal pustular dermatosis in a patient with hyperthyroidism.

A case of subcorneal pustular dermatosis (SPD) is reported in a 48-year-old man with a 2-year history of hyperthyroidism (Graves' disease). SPD has been reported in association with IgA monoclonal gammopathy, but to our knowledge it has not been associated with hyperthyroidism. The coexistence of hyperthyroidism and SPD suggests that immunologic factors may play a role in the pathogenesis of SPD.

Synthesis of polymer-coated mixed-functional packing materials for direct analysis of drug-containing serum and plasma by high-performance liquid chromatography.

Silicone polymer-coated mixed-functional (PCMF) silica packing materials were developed for the direct determination of drugs contained in serum or plasma. The new stationary phases were prepared by the following three-step procedure: (1) coating porous silica with a silicone polymer; (2) partial introduction of hydrophobic groups; and (3) introduction of hydrophilic groups. Two PCMFs were synthesized, one having polyoxyethylene groups as hydrophilic groups (PCMF-POE) and the other having oligoglyceryl groups (PCMF-OG). PCMF-POE showed higher recoveries for injected proteins and a greater overall retention for drug molecules than PCMF-OG. PCMF-POE did not show any column deterioration in 500 serum sample injections (10 ml in total).

Human maximization testing of D&C Yellow no. 10 and Yellow no. 11.

By the maximization test, using 0.5% D&C Yellow no. 11 in pet., 15 of 20 human volunteers became contact sensitized. All reacted to a challenge concentration of 1000 ppm and one down to 1 ppm. The high allergenic potential of this dyestuff was confirmed. There were no cross reactions to purified samples of D&C Yellow no. 10. In contrast, 5% solutions of pure D&C Yellow no. 10 failed to sensitize human subjects. Cross reactions to this substance in persons sensitized to D&C Yellow no. 11 are due to impurities.

D&C nos. 10 and 11: chemical composition analysis and delayed contact hypersensitivity testing in the guinea pig.

D&C Yellow no. 11 was found to consist predominantly of quinophthalone together with other minor components, though not 6'-methylquinophthalone. Quinophthalone was found to be a strong sensitizer in guinea pigs by means of a modified testing technique, and its threshold concentration for induction and challenge was 10 ppm. Purified D&C Yellow no. 10, which was found to consist of 6 derivatives of sodium sulfonated quinophthalone, did not sensitize or elicit a cross-reaction in quinophthalone-sensitized guinea pigs even at a challenge concentration of 5%. Commercial D&C Yellow no. 10 contained 0.95-170 ppm of quinophthalone, and it is suggested that skin sensitization by D&C Yellow no. 10 is caused by contaminating quinophthalone.