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Homogenates of human skin metabolize progesterone-4-14C to the sane products as whole skin. Studies with subcellular fractions obtained by differential centrifugation indicate the presence in skin of a membrane-bound 5α-reductase and a soluble 20α-hydroxysteroid dehydrogenase (20α-HSD), both of which utilize TPNH as cofactor. The 20α-HSD has a pH optimum of 6.2 and a Km of approximately 7 μM. Unlike placental preparations, the 105,000 × g supernatant fraction prepared from human skin has more 20α-HSD than 17β-hydroxy-steroid dehydrogenase activity. This soluble skin enzyme acting on steroid hormones is distinct from previously reported particulate enzymes. [ABSTRACT FROM AUTHOR]

Multiple polypoid projections of granulation tissue developed in two patients receiving isotretinoin for acne. Histological study of the lesions revealed increased amounts of non-sulphated acid mucopolysaccharides in the ground substance of the granulation tissue stroma. Complete resolution occurred following curettage with or without chemical cautery. The role of isotretinoin in the development of these lesions is discussed. [ABSTRACT FROM AUTHOR]

Three new triterpenes, 2alpha-acetoxy-3beta,19alpha-dihydroxy-11alpha,12alpha-epoxy-ursan-28,13beta-olide, 3beta-acetoxy-2alpha,19alpha-dihydroxy-11alpha,12alpha-epoxy-ursan-28,13beta-olide and 2-O-acetyl-euscaphic acid together eight known triterpenes were isolated from the roots and stems of Cecropia catharinensis. Their structures were determined by detailed analysis of NMR spectra and the relative configurations established by difference nOe experiments. In addition, four flavonoid glucosides (vitexin, isovitexin, orientin and isoorientin) were found in the leaves.

Objective: To evaluate the benefits, risks, and costs of antimicrobial regimens used for selective decontamination of the digestive tract (SDD) in intensive care unit (ICU) patients., Data Sources: Information was obtained from clinical trials, review articles, abstracts, and textbooks. Key indexing terms included antibiotics, selective decontamination, and infections., Study Selection: Research articles describing controlled clinical trials of SDD in medical or surgical ICU patients were reviewed. Trials that investigated transplant, cirrhotic, leukemic, or oncology patient populations were excluded., Data Extraction: The details of studies that evaluated nosocomial infection or nosocomial pneumonia rates were extracted. These included study design, demographics, SDD regimens, severity of illness scores, and colonization, infection, and mortality rates., Data Synthesis: The use of SDD in mechanically ventilated surgical or trauma ICU patients reduces the incidence of colonization, nosocomial pneumonia, and overall infection rates, but does not change the overall mortality rate. Administration of antibiotic and antifungal agents in a nasogastric suspension is required for SDD. The addition of systemic prophylactic antibiotics or oropharyngeal paste was not required to decrease nosocomial infections. The most frequently studied SDD regimen (colistin/amphotericin B/tobramycin) is not feasible for use in the US because of exorbitant drug costs. Less expensive alternatives include norfloxacin/nystatin, or colistin/nystatin/gentamicin., Conclusions: Additional research is required before SDD regimens can be routinely recommended in surgical and trauma ICU patients. A multicenter study is warranted to determine the long-range benefits, potential for resistance, and cost-effectiveness of SDD.

Neurotropic melanoma is a rare tumor with a biphasic growth pattern associated with a change in morphology from melanocytic features toward Schwann cell features. The tumor thereby develops a capacity for infiltrating nerves which may result in clinically evident cranial neuropathies, most commonly of the fifth and seventh cranial nerves. The histology of this lesion is difficult to interpret; it often erroneously appears fibrous in origin and may be considered to be benign. Despite this benign appearance histologically, the tumor behaves aggressively with multiple local recurrences and possible CNS invasion by either direct perineural growth or distant metastases. We review the literature of neurotropic melanomas and report a 46th case which describes a typical course with neural invasion. Although a rare cause of cranial neuropathies, the neurologist should consider this entity in the differential diagnosis and the history of a recurrent skin lesion of the face should be sought whenever examining such a patient.

We have adapted the neutral red uptake assay for quantitative assessment of injury to fibroblast cultures by potential phototoxins. Tetracycline derivatives, quinolone derivatives, and chlorpromazine were used as model compounds for development of the assay. Human fibroblasts were incubated with potential phototoxins, the cell cultures irradiated with UV, and the capacity for neutral red uptake determined. Demeclocycline and doxycycline, two known photosensitizers, showed a 94% and 95% decrease of neutral red uptake, respectively, indicating photo-induced cytotoxicity. Minocycline, a non-photosensitizing tetracycline derivative, showed no decrease in uptake. Tetracycline, a weak phototoxin, showed minor (10%) decrease at equivalent concentrations (20 micrograms/ml). Microscopic observation of neutral red uptake and cell damage paralleled the spectrophotometric findings. Chlorpromazine, a non-tetracycline phototoxin, showed 91% decrease. An additional group of phototoxic drugs, quinolone antibacterials, were studied. Nalidixic acid, ofloxacin, ciprofloxacin, and norfloxacin all demonstrated phototoxicity, with nalidixic acid showing the greatest decrease in neutral red uptake. This methodology may provide a useful rapid method to quantify phototoxic potential of new drugs or suspected phototoxins.

Isotretinoin administered subcutaneously to male hamsters results in marked involution of the sebaceous glands of the flank organ without discernible effort on the other androgen-dependent structures, pigmented hair follicles, and dermal melanocytes. Treatment of androgen-stimulated female hamsters with isotretinoin prevented the androgen-induced growth of the sebaceous glands but not the formation of large pigmented hairs and dermal pigment cells. Etretinate, in comparable dosage, did not show the inhibitor effect on sebaceous gland growth. The hamster flank organ seems a promising system for assessment of the sebaceous gland inhibitory activity of retinoids and may be predictive for therapeutic activity in acne.

Forty patients with tinea pedis were treated for six weeks in a double-blind study with a tolciclate or placebo solution. The tolciclate solution demonstrated moderate efficacy compared with placebo. The finding of positive KOH preparations in a significant number of tolciclate-treated patients with persistently negative cultures suggests that the vehicle used (polyethylene glycol-400) may not provide adequate penetration of this effective antifungal agent. No adverse effects were noted.

Mycophenolic acid, a new chemotherapeutic agent for the treatment of psoriasis, is known to be rapidly conjugated on absorption and to circulate largely in the form of its glucuronide conjugate. Since this metabolite does not readily penetrate intact cells and is cleaved by the enzyme beta-glucuronidase to yield free mycophenolic acid, the ability of preparations of mouse skin to cleave mycophenolic glucuronide was studied. The time course of mycophenolic acid liberation by such preparations and the dependence upon the amount of enzyme preparation were demonstrated. Preparations of mouse skin and mouse liver, kidney, spleen, lung, heart and small intestine were assayed for beta-glucuronidase activity using p-nitrophenyl-beta-D-glucuronide as substrate. Skin yielded preparations with higher beta-glucuronidase activity per/mg protein than any of the other organs tested. When expressed on the basis of beta-glucuronidase activity recovered per milligram of tissue DNA, skin, liver and kidney showed higher levels than the other organs tested.

The relative topical efficacy of indomethacin and diflumidone, a novel non-steroidal antiinflammatory drug, for the suppression of ultraviolet-light (290-320 nm region; UVB)-induced erythema has been compared in a randomized, double-blind, placebo-controlled study in man. During the early phases of erythema development (3-6 h) following the administration of 3 minimal erythema doses (MED) of UVB, a single topical application of diflumidone and of indomethacin were found to be equal in their ability to inhibit the development of erythema compared to untreated or placebo-treated sites. At 24 h after application, the indomethacin-treated sites had significantly less erythema than did the diflumidone-treated sites. Pigmentation of test sites at 5 and 14 days following irradiation was indistinguishable at the diflumidone, placebo, or untreated sites, but relatively less pigment developed at the indomethacin-treated sites.

The anatomic, biochemical, and physical changes occurring in the skin with aging are reviewed and discussed. An attempt is made to distinguish between changes resulting from accumulated injury from environmental factors and the changes of aging per se.

The effect of subcutaneously administered 13-cis-retinoic acid and an aromatic retinoid (Ro 10-9359) on the sebaceous glands of the hamster flank organ were compared. As previously reported, 13-cis-retinoic acid caused a marked diminution of sebaceous gland size without affecting other androgen dependent structures. The aromatic retinoid derivative showed no effect upon any of the flank organ components. Studies utilizing androgen stimulated female confirmed our previous finding that 13-cis-retinoic acid prevented the growth of sebaceous glands without affecting the development of dermal pigmentation or large pigmented hair follicles. The aromatic retinoid derivative showed slight, if any, effect upon sebaceous gland size and no effect upon pigmentation or pigmented follicle development. The findings with this model system suggest that any efficacy of Ro 10-9359 in the treatment of acne would be by some mode other than the inhibition of sebum production.

A noninvasive technique of pulsed ultrasound was used to determine the long-term changes in skin thickness resulting from intradermal injections of triamcinolone acetonide (TA). Injections of 0.1 ml of either saline or a suspension containing 5 mg/ml or 10 mg/ml of TA were made at selected sites on the forearms of two human volunteers. The corticosteroid-treated sites showed a maximal decrease of 30% to 40% of the original skin thickness at 4 to 8 weeks after a single injection. A transient thinning was observed at control sites injected with saline. A greater degree of thinning was seen at the site injected with 10 mg/ml of TA as compared to the site injected with 5 mg/ml of TA. The thinning at the corticosteroid injection sites persisted at least 18 weeks after the single corticosteroid injection but had approached normal thickness values by 44 weeks following treatment. Pulsed ultrasound may be useful as a noninvasive technique for monitoring the effects of intradermally injected corticosteroids on human skin thickness and may also be useful in assessing intrinsic atrophogenic potentials of different corticosteroid molecules in human skin and the duration of action of various injectable formulations of a corticosteroid.

The efficacy of orally administered mycophenolic acid (MPA), an inhibitor of guanosine monophosphate (GMP) synthesis, for the treatment of psoriasis, was studied in a double-blind fashion. Of twenty-one patients completing the study period, ten of eleven patients treated with MPA had a greater than 25% decrease in severity score compared with only two of ten patients treated with placebo. The placebo group had a slight increase in severity score compared to almost 50% reduction in the average severity score of the MPA-treated group. After termination of the double-blind portion of the study, the placebo group was treated with MPA and showed a 60% decrease in severity score. Adverse effects encountered included anorexia, nausea, vomiting, and diarrhea. One patient had an uncomplicated episode of herpes zoster. Other than a mild decrease hemoglobin, no hematologic toxicity was noted.

Generalized staphylococcal scalded skin syndrome (SSSS) is a toxin-related epidermolytic disease that predominantly affects previously healthy infants and children younger than 5 years. In contrast, the majority of the reported adult cases have been associated with underlying diseases, suggesting that immunosuppression and renal insufficiency are important predisposing conditions for this age group. We report herein a case of adult-type SSSS in an anephric 10-year-old boy. Patients undergoing hemodialysis who have chronic renal failure may be uniquely predisposed to the SSSS by virtue of their decreased glomerular filtration rate, associated uremic immunodeficiency, and a high incidence of Staphylococcus aureus bacteremia.

Administration of 13-cis-retinoic acid subcutaneously to mature male hamsters produced a marked decrease in the size of the sebaceous glands of the flank organ, without diminution of other hormonally dependent structures of the flank organs. Subcutaneous administration of 13-cis-retinoic acid to female hamsters treated simultaneously with injections of testosterone enanthate prevented the androgen-induced growth of the flank organ sebaceous glands but did not prevent the growth of other hormonally dependent structures such as the dermal pigment cells and large pigmented hair follicles. The sebaceous gland progressively decreased during 3 weeks of treatment and the effect persisted at least 3 weeks after cessation of treatment but was completely reversed by 6 mos after treatment. In vitro studies of testosterone metabolism by hamster flank organ indicated the lack of inhibition of 5 alpha-reduction by 13-cis-retinoic acid. It seems likely that systemically administered 13-cis-retinoic acid, unlike antiandrogens, exerts a specific extrahormonal effect on the sebaceous glands of the hamster flank organ without affecting other androgen dependent cells.