A 13-week oral dose subchronic toxicity study of gardenia yellow containing geniposide in rats.

Gardenia yellow powders A, B and C, containing geniposide at 0.284%, 0.938% and 2.783%, respectively, were administered orally to male and female SD rats as 3% feed admixtures for 13-weeks to evaluate any potential toxicity. Mean geniposide intake values were 5.72, 18.9 and 56.3mg/kg/day in groups receiving these feed admixtures, respectively. All animals survived the duration of the study. The following findings were evident in the gardenia yellow C group: chromatouria, slightly increased plasma total bilirubin, blackish brown discoloration of the kidneys and liver, brown pigments in the proximal tubular epithelium of the kidneys. Slightly increased plasma total bilirubin was considered to be due to interference of metabolite of geniposide with the system of measurement and not to be a toxic effect since there were no related changes in histopathology of the liver or in any blood chemistry parameters. Other findings were limited to pigmentations or discolorations attributable to metabolites of geniposide. No treatment-related effects were evident on body weight, food consumption, ophthalmology, hematology or organ weights in any group. Therefore, it was concluded that 3-month ingestion of the gardenia yellow powder containing geniposide at 2.783% (approximately 60 mg/kg/day as geniposide intake) does not cause any severe toxic effects.

Hyperthermic treatment of Bowen's disease with disposable chemical pocket warmers: a report of 8 cases.

Bowen's disease is a form of squamous cell carcinoma in situ, in which local hyperthermia may be efficacious. We studied 8 patients with Bowen's disease to ascertain whether hyperthermia can be effective against it. As a heat source, disposable chemical pocket warmers were applied daily with pressure directly to the lesion site while the patient was awake, and the clinical course was observed for 4 to 5 months. The lesion was then excised and examined to determine the histopathologic effects. The results showed efficacy in 6 cases, in which the nodular and invasive lesions and the erythematous patches abated; then the lesions disappeared, leaving deposits of pigment (complete remission). In one case, the signs improved by at least 50% (partial remission); in the other case, there was only slight palliation (no response). As for the posttreatment histopathologic effects, tumor cells were eliminated in 3 cases, isolated tumor cells were seen in 3 cases, and there was no change in 2. Although the treatment did not yield perfect results, it represents a major improvement of hyperthermic therapy and is one effective method of treating Bowen's disease.

Processing of cathepsins L, B and D in psoriatic epidermis.

Proteinase activity is increased in psoriatic epidermis. To elucidate the involvement of enzymes in psoriatic epidermis, the expression of cathepsins, L, B and D was investigated by Western blotting and immunohistological studies. Normal epidermis contained abundant inactive precursors (39 kDa) of cathepsins L and B and an inactive intermediate form (45 kDa) of cathepsin D. Cathepsin L in psoriasis was processed to a variable extent from the precursor to a single-chain form (30 kDa) and a mixture of single- and heavy-chain (25 kDa) forms of the active mature enzyme, corresponding to the immunohistological staining patterns 'diffuse dense', 'small granular', and unevenly distributed 'condensed granular'. Cathepsin B showed a mixture of precursor form (39 kDa) and single-chain (30 kDa) forms and was expressed as a 'diffuse dense' staining pattern in the mid-spinous layer and as a 'condensed' pattern in the upper spinous and granular layers. Cathepsin D was processed to the heavy-chain (31 kDa) form of activated mature enzyme with small granular staining and a mixture of heavy-chain and degraded protein (28 kDa) with larger and more condensed granular staining. The distribution patterns of 'small granular' cathepsin L, and of cathepsins B and D expression in suprabasal keratinocytes were very similar to that of involucrin. After complete clinical resolution of psoriasis by 8-methoxypsoralen plus UVA treatment, the expression of the three cathepsins was normalized. These results suggest that cathepsins L, B and D in forms activated to a variable extent may be involved in the pathology of psoriasis.

Hyperthermic treatment of chromomycosis with disposable chemical pocket warmers. Report of a successfully treated case, with a review of the literature.

A case of chromomycosis in which hyperthermia proved effective is reported. The patient was a 56-year-old male bean curd maker who, without any previous history of minor trauma, developed on the extensor side of the left upper arm an eczematous lesion that underwent gradual radial expansion. The lesion showed a well-defined, 7 x 10 cm infiltrated erythematous plaque with the central area healed and, at the upper and lower borders, adherent scales and crusts on the surface. Histological examination revealed granulomatous changes in the dermis, as well as sclerotic cells within giant cells and microabscesses. On culturing, Fonsecaea pedrosoi was isolated. The patient was treated with disposable chemical pocket warmers, which were secured over the lesion with a rather tight elastic bandage, so that they kept the affected area warm for 24 hours a day. After a month of such hyperthermic treatment, the erythema and infiltration had decreased considerably, and microscopic examination and culture of the crusts both yielded negative results. Examination of biopsy specimens of the lesion after the third month showed that it had cicatrized. The treatment was stopped after 4 months, and no relapse occurred. We also summarize the published results of local hyperthermic treatment of chromomycosis in Japan.

Hyperthermic treatment of sporotrichosis: experimental use of infrared and far infrared rays.

We used pocket warmers and infrared and far infrared rays to treat 14 cases of sporotrichosis, 7 in children and 7 in adults. There were 9 cases of the fixed cutaneous type and 5 of the lymphocutaneous type; 6 were located on the face and 8 on the limbs. Four cases were treated with pocket warmers, 5 with infrared rays, and 5 with far infrared rays. All lesions treated with pocket warmers were facial lesions in children; infrared and far infrared ray treatments were used in 3 children and 7 adults, 2 on facial lesions and 8 on lesions on the extremities. In treatments with infrared and far infrared rays, the amount of heat was greater than with the pocket warmers, and one 15-min treatment daily was sufficient to yield satisfactory results, but this method is difficult to use on children and on the face, and 40-min treatments two or three times a week proved unsatisfactory. Infrared and far infrared ray treatments allow the length of a single treatment to be reduced by three-quarters, in comparison with one pocket warmer treatment.

An evaluation of broad-spectrum sunscreens against topical PUVA-induced erythema.

Protection against topical PUVA with broad-spectrum sunscreens was investigated. A protection factor against topical PUVA was established for broad-spectrum sunscreens against topical PUVA-induced erythema.

Effects of hyperthermia on phagocytosis and intracellular killing of Sporothrix schenckii by polymorphonuclear leukocytes.

The effects of hyperthermia on phagocytosis and killing of Sporothrix schenckii by polymorphonuclear leukocytes (PMNs) were investigated in order to clarify the mechanism of local thermotherapy for sporotrichosis. Yeast cells of S. schenckii, PMNs and serum were incubated at 37 degrees C or 40 degrees C for 2 or 4 hours. Rate of phagocytosis and killing rate (rate of germination) were estimated, and their processes were observed by transmission electron microscopy. There was no effect of hyperthermia on the phagocytosis rate, but the killing rate increased significantly at 40 degrees C. Electron microscopic examination showed an increase of granularity in the yeast cytoplasm, elongation and fragmentation of the cell membrane. The ultrastructural changes were basically identical under both temperatures, but the degree of these changes was higher at 40 degrees C than at 37 degrees C. Although both intact and degenerated yeasts were found in the same conditions, their transient forms were few, suggesting that the PMN-killing process was completed promptly.

The effects of heat on Sporothrix schenckii in vitro and in vivo.

In order to clarify the mechanism of action of topical thermotherapy on sporotrichosis, the effects of heat on Sporothrix schenckii in vitro and in vivo were investigated by observing the percentage germination and the ultrastructure. When the spores were heated to 42 degrees C, it took 10 hr with the conidia, 2 hr with the yeast-like cells and 1 hr with the spores in vivo to reduce the germination rates to 10%. The percentage germination curves were reduced slowly at first but later exponentially. Changes in the ultrastructure became evident in 2 hr with the yeast-like cells and in 8 hr with the conidia. The ribosome count declined and amorphous dense materials appeared in the cytoplasm and mitochondria. In vivo, the outstanding feature of the heated spores was the diversity of internal ultrastructural changes encountered and morphological changes. These were observed at 1 hr post treatment.