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Biomedical subjects

S Don

Publications and source records attributed to S Don.

33 records · Page 2Linked to original sources

In vitro transdermal delivery of a melanotropic peptide through human skin.

A superpotent analogue of alpha-MSH, (Nle4,D-Phe7)-alpha-MSH, when applied topically to mice induces darkening of follicular melanocytes throughout the skin. In vitro studies have demonstrated delivery of the peptide across mouse but not rat skin. This variation in permeability of skin of animal models prompted us to use human skin in vitro. The melanotropin was applied to the surface of human skin samples through a permeation apparatus and allowed to penetrate for 24 h at 36 degrees C. Passage of the analogue was shown by both bioassay and radioimmunoassay. These assays correlated well and demonstrated both the presence and the biologic integrity of the peptide after transdermal passage. Regional differences were noted in the degree of transdermal penetration. In addition, split thickness skin allowed greater penetration suggesting dermal binding of the hormone. This study is the first to show that a melanotropic peptide can be delivered transdermally through human skin in vitro. This has potential importance in the development of therapies for hypopigmentary disorders and for the stimulation of skin tanning without ultraviolet light.

Administration, Cutaneous↗

Detection of rejection in renal allografts. Evaluation with duplex sonography and DTPA renal scintigraphy with kidney/aorta perfusion ratios.

Duplex sonography and technetium-99m DTPA renal scintigraphy have been used to distinguish acute rejection from other forms of renal allograft dysfunction. In this study, duplex sonography and renal scintigraphy were compared as methods to detect rejection. Eighty-four episodes of renal allograft dysfunction that had concurrent duplex sonography and renal scintigraphy over a 17-month period were reviewed. During the duplex sonography examinations the resistive index (RI) was measured from the renal cortex. Scintigrams were evaluated for allograft perfusion and function. The kidney to aorta (K/A) ratio was calculated from the upstroke of the perfusion curve. All diagnoses were established by clinical criteria. Histologic proof was available in 49 cases. There were two episodes of hyperacute rejection, 30 episodes of acute rejection, 14 episodes of chronic rejection, and 38 episodes of dysfunction without rejection. Using an RI greater than or equal to 0.70, the sensitivity and specificity for detecting acute rejection were 90% and 76%, respectively, compared with 37% and 76% for renal scintigraphy. The K/A ratio was not helpful in the diagnosis of rejection.

Aorta↗

Duplex Doppler US of renal allografts: causes of elevated resistive index.

The authors retrospectively investigated the utility of the resistive index (RI) in evaluating the major causes of renal allograft dysfunction. Three hundred fourteen duplex US studies in 162 patients with 150 episodes of renal allograft dysfunction within a 17-month period were reviewed. Histologic findings were available in 69 cases. Three patients had hyperacute rejection with a mean RI of 0.85 +/- 0.049. There were 37 episodes of acute rejection (mean RI, 0.76 +/- 0.054) and 22 instances of chronic rejection (mean RI, 0.71 +/- 0.065). Ureteral obstruction (nine cases; mean RI, 0.72 +/- 0.026) was the only cause of allograft dysfunction other than rejection with a mean RI greater than 0.70. Mean RI values associated with rejection were significantly elevated above those in the 88 cases of dysfunction without rejection (mean, 0.64 +/- 0.064) and in baseline examinations (mean, 0.63 +/- 0.066). The results identified two causes of increased RI values in addition to acute rejection: chronic rejection and ureteral obstruction.

Cyclosporins↗

The effects of bergapten and sunlight on cutaneous pigmentation.

The effects of bergapten-containing preparations in sunlight-induced skin pigmentation were evaluated. Oil and lotion vehicles with bergapten/UV-B sunscreen or sunscreen alone were applied to the backs of subjects twice weekly for 4 weeks and the subjects were exposed to gradually increasing doses of midday sunlight. The degree of skin darkening was assessed by clinical examination, reflectometry, and light microscopy of skin biopsy specimens. At 5 weeks, 1 week after the last sunlight exposure, the sites treated with either the bergapten/UV-B sunscreen lotion or the lotion vehicle were significantly darker than the sites treated with the sunscreen lotions without bergapten. Oil preparations produced less clearcut results, possibly because of a less potent sunscreen or because the bergapten did not leave the vehicle and absorb into the epidermis. In type I skin, the bergapten/sunscreen and the oil vehicle alone produced the same amount of tanning; both yielded more tanning than the sunscreen in oil by clinical examination. The findings were not confirmed by reflectometry or by light microscopy. Thus, we conclude that bergapten added to a UV-B sunscreen lotion preparation can increase skin pigmentation over the sunscreen alone when one is exposed to sunlight. The bergapten/UV-B sunscreen combination is a potentially useful product since one can develop a psoralen and UV-A-induced tan while being protected from UV-B-induced sunburn by the UV-B sunscreen incorporated into the formulation.

5-Methoxypsoralen↗

Transdermal delivery of a melanotropic peptide hormone analogue.

We previously reported that topical application of [Nle4,D-Phe7]alpha-MSH, a superpotent analogue of alpha-melanocyte stimulating hormone, to mice induces a darkening of follicular melanocytes throughout the skin. We now report that the melanotropin analogue can be delivered across mouse but not rat skin in an in vitro model system. Passage of the analogue from the topically applied vehicle (polyethylene glycol) across the skin into a subcutaneous receiving vessel was demonstrated by both bioassay as well as by radioimmunoassay. The bioassay data demonstrate that percutaneous absorption of the melanotropin did not result in loss of biological activity of the peptide. The differential penetration of the peptide across rodent skin reveals that one cannot predict percutaneous absorption of a substance across the stratum corneum from studies on a single species. The present results are the first to demonstrate, by direct quantitative measurements, that a bioactive peptide can be delivered across the vertebrate integument in vitro. These studies point out the potential of a topically applied melanotropin for tanning of the skin and possibly for treatment of certain hypopigmentary disorders.

Administration, Cutaneous↗

Specific increase in polyamine levels in chick embryo cells transformed by Rous sarcoma virus.

Chick embryo fibroblasts and chorioallantoic membranes of chick embryos infected with oncogenic or nononcogenic viruses were analyzed for polyamines. Nononcogenic viruses (influenze, Newcastle disease, or vaccinia virus) had no effect on the polyamine content of chorioallantoic membranes. Transformation of chorioallantoic membranes by a wild-type or temperature-sensitive mutant strain of Rous sarcoma virus under permissive conditions (37 degrees) caused a 2- to 4-fold increase in cellular spermidine and putrescine content. Only putrescine accumulated in chick embryo fibroblasts transformed by Rous sarcoma virus at 37 degrees. At the nonpermissive temperature (42 degrees), the temperature-sensitive mutant, unlike the wild-type strain, did not alter cellular morphology or polyamine content.

Allantois↗

Polyamine metabolism in normal and in virus-transformed chick embryo fibroblasts.

The effect of transformation by Rous sarcoma virus on the ornithine decarboxylase levels of chick embryo fibroblasts was studied. Infection with Rous sarcoma virus resulted in increased ornithine decarboxylase activity which preceded morphological alterations by at least 24 hr. The ornithine decarboxylase levels of normal controls, unlike those in Rous sarcoma virus-infected cells, declined with age, so that the enzyme activity of transformed cells was increased twentyfold 5 days postinfection. Infection with a temperature-sensitive mutant of Rous sarcoma virus, T5, stimulated ornithine decarboxylase activity of chick embryo fibroblasts at the permissive (37 degrees) but not at the nonpermissive (42 degrees) temperature. The ornithine decarboxylase activity of T5-infected cells shifted from 42 degrees to 37 degrees increased within 2 hr and reached the levels of wild-type, Schmidt-Ruppin-17A-transformed cells in 11 hr. When T5-transformed fibroblasts were shifted to the nonpermissive temperature, ornithine decarboxylase activity decreased fivefold within 4 hr and paralleled the levels of normal controls in 11 hr. Shifting of temperatures of incubation caused comparable alterations in cellular putrescine but not in spermine or spermidine content.

Avian Sarcoma Viruses↗