New formulation of chemical peeling agent: histological evaluation in sun-damaged skin model in hairless mice.

BACKGROUND: chemical peelings injure the superficial skin, which is then restored by healing of the wound. OBJECTIVES: to document the acute and chronic histological changes produced by applying chemical peeling agents used clinically to the UVB-irradiated skin of hairless mice, which served as a model of sun-damaged skin. DESIGN: three chemical peeling agents, 30% salicylic acid, dissolved in macrogol (a new formulation), 35% trichloroacetic acid (TCA) dissolved in distilled water and 20% glycolic acid dissolved in glycerin were applied to the backs of UVB-irradiated hairless mice. Untreated, irradiated areas of skin served as controls. Specimens were evaluated histologically at 3, 14, 28, and 70 days. RESULTS: chronic UVB irradiation produced an irregular hypertrophy of the epidermis. The treated areas of irradiated skin recovered by day 70. At 28 days, all skin specimens treated with chemical peeling agents exhibited a unique connective tissue layer composed of fine collagen fibers beneath the epidermis. While 35% TCA produced severe tissue damage marked by inflammation up to day 14, no inflammatory infiltrates were seen with 30% salicylic acid in macrogol at 70 days. CONCLUSIONS: chemical peeling with 30% salicylic acid dissolved in macrogol led to reorganization of the epidermis and a rebuilding of the superficial dermal connective tissue important in reducing wrinkles, and without evidence of inflammatory infiltrates in an animal model of sun-damaged skin. Findings suggest a possible clinical benefit.

Local antibody production and immune complex formation in rats experimentally infected with Angiostrongylus cantonensis.

The systemic humoral immune responses and tissue localization of worm-antigen, antibodies (IgG), and complement (C3) were examined in rats experimentally infected with Angiostrongylus cantonensis. While the worms remained in the subarachnoid space, it was infiltrated with plasma cells and lymphoid cells containing IgM and IgG. When the infiltration of these cells became more pronounced, the serum antibody titer began to increase. At the same time, deposits of IgM, IgG, and C3 were found in the glomeruli of the kidney. A number of eggs were observed in the lungs, enclosed in granulomatous tissues. Infiltrates of plasma cells including IgM and IgG, and deposits of IgM, IgG, and C3 were detected around the eggs and in the granulomatous tissues. A marked increase in serum antibody was observed. A. cantonensis larvae induce local antibody (IgM and IgG) production in the central nervous system prior to an increase of serum antibody titer. Measurement of cerebrospinal fluid antibody titer at an early stage of infection may confirm infection. The larvae showed no evidence of damage in spite of marked local antibody production in the central nervous system. The eggs in the lungs stimulated both local and systemic antibody production, and immune complexes were formed in the lung and the circulatory system. Immune complexes may participate in the formation of granuloma.

Histologic changes in the skin of hairless mice following peeling with salicylic acid.

OBJECTIVE: To clarify the histologic alterations produced by the application of salicylic acid solution, which has been used effectively in chemical peeling without producing a wound or inflammation. DESIGN: We applied 7.5%, 15.0%, and 30.0% salicylic acid in solutions of ethanol or macrogol to the backs of hairless mice for 20 minutes. The skin was histologically evaluated immediately and at 1, 3, 12, 24, and 48 hours following treatment. SETTING: The Department of Dermatology, Faculty of Medicine, Kyushu University, Fukuoka, Japan. MAIN OUTCOME MEASURES: A loss of cornified cells was the only morphologic alteration associated with the treatment, and was followed by the activation of the epidermal basal cells and the underlying fibroblasts. RESULTS: The 7.5% and 15. 0% salicylic acid solutions produced few histologic changes, whereas the 30.0% salicylic acid in both vehicles macerated and then exfoliated the cornified cells. As the epidermis became thinner, the residual epidermal cells became flattened and were rearranged parallel to the tensile surface load. The cornified material within the hair follicles also became macerated, dilated the follicles, and then dropped off. An apparent increase occurred in the number of cells in the S phase in the epidermal basal cells in 24 hours, leaving the follicular cells unchanged. As the cornified layer thickened in 48 hours, the epidermal cells below it and the underlying fibroblasts resumed their random pretherapy arrangement. Except for the occasional infiltrate of lymphocytes, no degenerative or inflammatory changes occurred. While similar changes occurred with each vehicle, they were relatively faster with the ethanol preparations. CONCLUSION: The present results suggest that the architecture of the epidermis and the papillary dermis can be regenerated by simply injuring the cornified layer by using topical agents such as salicylic acid that do not cause degeneration or inflammation.

The influence of celomic membranes and a tunnel between celomic cavities on cancer metastasis in poultry.

The roles of celomic membranes and celomic structures in preventing cancer metastasis were examined. The relationship between a tunnel in the peritoneal cavity of hens and the cancer metastasis was also investigated. A tunnel between the right and left dorsal hepatic cavities was found in almost half of healthy hens. The tunnel was also found in 17% of hens with cancer. Neoplastic cells were detected in the ascitic fluid of 79% of hens with effusions. Metastasis was most severe in the intestinal peritoneal and left dorsal hepatic cavities, whereas the right dorsal hepatic cavity showed the least involvement. Severe inflammatory responses were found within the metastatic membranes, resulting in an increase in their thickness. In tumor-bearing hens, crevasse-like splits were present within the membranes at the layers of loose connective tissues. It appears that the splits prevent further invasion by the cancer cells. There were no successful lesions on the inner surfaces of air sacs. It is suggested that the tunnel in the peritoneal cavity enhances cancer metastasis. We also conclude that the celomic membranes and their structure in hens retard the spread of cancer by functioning as a barrier against direct spread of the cancer cells.

Estradiol receptors and ovalbumin in adenocarcinoma of hens.

The origin of adenocarcinomas in 10 hens was studied using an assay for estradiol receptors (ERs) and ovalbumin. ERs were found in nine tumors, and ovalbumin was present in eight tumors. Hormonal regulation of this cancer is indicated, and it is suggested that the origin of the tumor is probably the glands of the oviduct.

A study on the origin of adenocarcinoma in fowls using immunohistological technique.

When tumor tissues collected from 12 hens suffering from so-called adenocarcinoma were stained with antisera by the indirect immunofluorescent method, all of the tissues appeared to contain ovalbumin. We suggest that most adenocarcinomas in the thoracoabdomen of mature hens are oviductal in origin.

Studies of hydroxypropylmethylcellulose acetate succinate on fertility in rats.

A fertility study was carried out in Slc: SD rats orally administered Hydroxypropylmethylcellulose acetate succinate (HPMCAS), a useful pharmaceutical excipient, at dose levels of 625, 1,250 and 2,500 mg/kg/day. Male rats were treated with HPMCAS from 60 days before pairing until the completion of mating. Female rats received HPMCAS for 22 days, from 14 days prior to mating up to Day 7 of gestation. All pregnant females were sacrificed on Day 21 of gestation and all fetuses were examined for abnormalities. No abnormal signs were seen in mating or fertility in the rat treated with HPMCAS. No external, internal and skeletal anomalies attributable to HPMCAS were observed in the fetuses. It was concluded that HPMCAS had no harmful effect on mating, fertilization, implantation, or embryonic development.

Teratological studies of hydroxypropylmethylcellulose acetate succinate in rats.

A teratogenicity study was carried out in S1c: SD rats orally administered Hydroxypropylmethylcellulose acetate succinate (HPMCAS), a useful pharmaceutical excipient, at dose levels of 625, 1,250 and 2,500 mg/kg/day for a period of 11 days from day 7 to day 17 of gestation. Two-thirds of the pregnant females in each group were sacrificed on Day 21 of gestation and their fetuses were examined. The remaining dams were allowed to litter naturally, and the postnatal development of the offsprings was observed. The incidences of external, internal, and skeletal anomalies were not significantly increased in the fetuses of any treated groups. HPMCAS caused no effects on parturition, lactation, postnatal growth and reproductive ability of the male and female offspring.

Teratological study of hydroxypropylmethylcellulose acetate succinate in rabbits.

A teratological study was carried out in New Zealand White rabbits in order to examine the teratogenic potentiality of HPMCAS, a useful pharmaceutical excipient. HPMCAS was orally administered at dose levels of 625, 1,250 and 2,500 mg/kg/day for a period of 13 days from day 6 to day 18 of gestation. All pregnant females were sacrificed on day 29 of gestation and their fetuses were examined. The administration of HPMCAS during a period of organogenesis produced no embryotoxic and teratogenic effects as well as no influence on behavior, appearance and growth of animals.

Effects on offspring induced by oral administration of hydroxypropylmethylcellulose acetate succinate to the female rats in peri- and post-natal periods.

A perinatal and postnatal study was carried out in Slc: SD rats orally administered Hydroxypropylmethylcellulose acetate succinate (HPMCAS), a useful pharmaceutical excipient, at dose levels of 625, 1,250 and 2,500 mg/kg/day for a period from day 17 of gestation to day 21 after delivery. All pregnant rats were allowed to litter naturally, and the postnatal development of the offsprings was observed. In the administered group of 2500 mg/kg, the liver weight was significantly increased in males and showed a tendency to increase in females as compared with control. No significant differences between the control group and the administered groups were found in postnatal growth and differentiation, behavior and reproductive ability of male and female offsprings.

Pityriasis lichenoides-like eruption occurring during therapy for myelogenous leukemia.

A 61-year-old Japanese man with chronic myelogenous leukemia developed pityriasis lichenoides-like eruptions during chemotherapy. Histopathological features were also consistent with the disease. The eruption in this case may have been an allergic reaction arising in a depressed immunity induced by chemotherapy.

Cutaneous sarcoid reactions during long-term remission in a patient with acute myelogenous leukemia.

A 68-year-old Japanese man with acute myelogenous leukemia, in long-term remission, developed cutaneous sarcoid reactions on his trunk and extremities. This may suggest that sarcoid-like granulomas be considered as a nonspecific cutaneous sign of underlying leukemia.

A case of connective tissue nevus associated with seborrheic keratosis-like eruption, atrophic scar, alopecia, and microtia.

We report a 44-year-old Japanese man who had connective tissue nevus, seborrheic keratosis-like eruptions, atrophic scars on his hands and feet, alopecia, and microtia. These concurrent abnormalities are distinct from previously described multiple malformation syndromes.

Neurothekeoma.

Neurothekeoma is a rare, benign cutaneous tumor with a fairly distinctive histologic appearance and characteristic clinical features. A second typical case of neurothekeoma in Japan, occurring on the dorsal aspect of the right hand, is presented.

[Monitoring of the cryptococcus count in the cerebrospinal fluid with negative cultures in two cases of serious cryptococcal meningitis].

We monitored the cryptococcus count in the cerebrospinal fluid(CSF) using the filter technique in two cases of serious cryptococcal meningitis during the course of treatment with antifungal agents. Lumbar puncture was performed once a week, and 1 ml of CSF was filtered through a Millipore filter(5.0-micron pore for cells), followed by staining of the filters with Alcian blue. All of the cryptococci on the filter were counted under a light microscope at a magnification of x 100. More than 500/ml and 2,000/ml of cryptococci were still observed in the CFS in Cases 1 and 2, respectively, in whom CFS cultures for Cryptococcus neoformans became negative after 4 weeks of treatment. Even though the treatment with antifungal agents were continued in these cases, cryptococci could still be observed for 5 weeks and 60 weeks on the filter preparations of Cases 1 and 2, respectively, after the CSF cultures became negative. The cryptococcal antigen could also be detected in the CSF during the positive filter preparations in these cases. At autopsy in Case 2, patchy lepromeningeal inflammatory lesions with the characteristic capsules of cryptococci were observed in the subarachnoid space. These observations suggest that cryptococci, which persisted in the CSF despite the negative cultures, were responsible for the lesions in the subarachnoid space and protracted clinical course in the two cases of cryptococcal meningitis.