Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hairless mouse has been used as a model to distinguish between local and systemic atrophogenic effects of topical steroids. Hydrocortisone-17-butyrate, betamethasone-17-valerate, budesonide and clobetasol-17-propionate were applied topically daily for 21 days. Skinfold thickness and dermal DNA synthesis of treated and untreated skin were evaluated as parameters of local and systemic atrophogenicity. Further, body weight gain and thymus weight were assessed as markers of systemic activity. With respect to local effects, skin thickness and dermal DNA synthesis both proved to be good parameters. Of the systemic parameters, thymic involution and body weight gain paralleled quite well the skin thinning on the untreated side. The results confirmed the potency differences of the steroids. Furthermore, they emphasize the usefulness of the hairless mouse to assess the relative safety with respect to local and systemic side effects of chronically applied topical corticosteroids.
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PMID:The hairless mouse as a model for study of local and systemic atrophogenic effects following topical application of corticosteroids. 167 10

In this investigation skin fold thinning was determined after topical application of several potent corticosteroids in hairless mice using a simple mechanical measuring device. The skin thinning effect of prednicarbate was compared with other corticosteroids (amcinonide, beta-methasone-17-valerate, clobetasol-17-propionate, diflorasone-17,21-diacetate, hydrocortisone-21-acetate). Prednicarbate produced a clear thinning of skin. Like other tested dermatocorticoids prednicarbate caused a significant atrophy of the mouse tail epidermis. By prednicarbate the 3H-thymidine triphosphate incorporation into epidermal DNA was inhibited.
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PMID:Investigation of the skin thinning effect of prednicarbate and other corticoids in mouse skin. 327 51

Retinoids profoundly influence epidermal differentiation, but neither the nature of their antikeratinizing activity nor their mechanism of action is known. In this study, we have correlated morphologic and histochemical findings with an assessment of stratum cohesion and water barrier integrity in adult hairless mice treated with either 13-cis-retinoic acid or the aromatic retinoid, RO 10-9359. Both the synthetic retinoids produced dose-dependent alterations in transepidermal water loss, which were about 5 to 10 times greater in RO 10-9359-treated animals. In contrast to essential fatty acid deficiency, where diminished intercellular lamellar lipids may account for defective barrier function, these lipid-rich structures were intact in retinoid-treated tissues. Instead, retinoids produced both epidermal and stratum corneum loosening, manifested both by the ready production of intraepidermal friction blisters and by ease of removal of cornified cells by tape stripping. Dyshesion correlated with loss of desmosomes and intra- and intercellular accumulation of amorphous material in the upper epidermis. Since these deposits lacked the tinctorial properties of mucin, dyshesion could not be ascribed to the development of mucous metaplasia. Finally, dyshesion could not be attributed to either gain or loss of membrane sugars demonstrated with rhodamine-conjugated lectins, since these changed only late in the course of retinoid treatment. We conclude that the antikeratinizing basis for retinoid activity comprises: (1) dose-dependent alterations in transepidermal water loss and (2) epidermal and stratum corneum loosening, which may, in turn, lead to loss of epidermal cohesion and abnormal barrier function. Neither mucous metaplasia nor stratum corneum thinning appear to play a major role.
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PMID:Retinoid effects on epidermal structure, differentiation, and permeability. 693 40

Small springs were implanted in the backskin of hairless mice to determine the effects of mechanical stretching on epidermal proliferation. The controls consisted of sham operated animals, in which the implanted springs did not exert any tension so as to identify any effect due to surgical trauma, and unoperated animals. There was a significant rise in the mitotic index after one day in both experimental and sham operated animals and a slight thinning of the stretched epidermis. After 2 days the mitotic index and thickness of the epidermis of the stretched skin were greater than that of the sham operated or unoperated control group, and these differences were maintained after 4 days and were significant. At this time the stretched epidermis showed a hyperplastic response with a thickening of all cell layers. It appears that tension due to stretching increases the mitotic activity of the epidermis leading to an increased progenitor cell population and subsequent tissue hyperplasia.
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PMID:The stretching of mouse skin in vivo: effect on epidermal proliferation and thickness. 735

The effects of a sympathetic neurotoxin, 6-hydroxydopamine (6-OHDA), on hair growth in neonatal mice were examined. Newborn mice were injected once subcutaneously in the mid-dorsal region with 6-OHDA (0.3 mg/g body weight) and bovine serum albumin (BSA) or with BSA only (controls) on day 0. By day 10, distinct areas of hairless skin were observed surrounding the sites treated with 6-OHDA. The areas of hairless skin were smaller at 15 days of age and were covered with hair by 20 days of age. Control sites injected with BSA only were indistinguishable from the surrounding skin at all ages examined. Microscopic and morphometrical analyses of skin obtained from the neonatal mice at various ages showed that the hairless skin in 6-OHDA-treated mice was thinner than the skin of control animals. The thinning of the skin and delay in hair growth induced by 6-OHDA treatment showed a significant difference from the skin of control animals injected with BSA only. Immunohistochemical experiments demonstrated that the administration of 6-OHDA had caused the complete depletion of tyrosine hydroxylase-immunoreactive fibers (sympathetic fibers) around blood vessels and piloerector muscles and in nerve bundles throughout the dermis and subcutaneous tissue. These findings indicate that the sympathetic neurons are associated with skin thickness and hair growth in neonatal mice.
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PMID:Inhibition of hair growth by subcutaneous injection of a sympathetic neurotoxin, 6-hydroxydopamine in neonatal mice. 762 11

1. The possibility of preventing and treating glucocorticoid-induced skin atrophy with KH 1060 (the potent 20-epi-22-oxa-24a-homo-26,27-dimethyl analogue of 1,25-dihydroxyvitamin D3) was examined in a hairless mouse model. 2. KH 1060 (0.625-6.25 pmol cm-2 of skin) applied topically for 7 days together with 2.5 nmol cm-2 betamethasone-17-valerate prevented, in a concentration-dependent manner, the development of epidermal, dermal and total skin thinning caused by the glucocorticoid. The effect of KH 1060 on the epidermis occurred at a lower dose than on the dermis, and at doses above 1.25 pmol cm-2 KH 1060 caused epidermal hyperplasia. 3. KH 1060 (2.5 pmol cm-2) prevented the development of betamethasone-associated skin atrophy in mice during a long-term (4 weeks) treatment, and reversed established cutaneous glucocorticoid atrophy. 4. Radiolabelling experiments with [35S]-sulphate and [3H]-proline in vivo revealed that KH 1060 stimulated the synthesis of sulphated glycosaminoglycans and hydroxyproline in skin treated with betamethasone. 5. These findings strongly suggest that KH 1060 prevents and reverses glucocorticoid-induced skin atrophy by stimulating epidermal proliferation and enhancing synthesis of extracellular matrix in the dermis.
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PMID:Inhibition of glucocorticoid-induced epidermal and dermal atrophy with KH 1060--a potent 20-epi analogue of 1,25-dihydroxyvitamin D3. 783 93

The influence of the vehicle on the release and permeation of fluconazole, a topical antifungal drug dissolved in Jojoba oil was evaluated. Series of Cutina lipogels (Cutina CPA [cetyl palmitate], CBS [mixture of glyceryl stearate, cetearyl alcohol, cetyl palmitate, and cocoglycerides], MD [glyceryl stearate], and GMS [glyceryl monostearate]) in different concentrations as well as gel microemulsion were prepared. In-vitro drug release in Sorensen's citrate buffer (pH 5.5) and permeation through the excised skin of hairless mice, using a modified Franz diffusion cell, were performed. The rheological behavior and the apparent viscosity values for different gel bases were measured before and after storage under freezing conditions at -4 degrees C and were taken as measures for stability of network structure. Candida albicans was used as a model fungus to evaluate the antifungal activity of the best formula achieved. The results of in vitro drug release and its percutaneous absorption showed that the highest values from gel microemulsion were assured. The rheological behavior of the prepared systems showed pseudoplastic (shear-thinning) flow indicating structural breakdown of the existing intermolecular interactions between polymeric chains. Moreover, the stability study revealed no significant difference between viscosity before and after storage for different formulae except for CPA Cutina lipogel (using analysis of variance [ANOVA] test at level of significance.05). The antifungal activity of fluconazole showed the widest zone of inhibition with gel microemulsion. The gel microemulsion is an excellent vehicle for fluconazole topical drug delivery.
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PMID:The development of Cutina lipogels and gel microemulsion for topical administration of fluconazole. 1291 29

The autosomal recessive gene hairless (hr) is responsible for the complete hairlessness in mice homozygous for this gene. Hair shedding that begins at the age of 10 days is caused by an abnormal cycle of hair follicle development disturbed at the catagen stage. This results in enhanced programmed cell death (apoptosis) and ultimately leads to the complete hair follicle destruction and shedding of all hairs by the age of three weeks. To study the phenotypic expression of the hr gene in a chimeric organism, we have obtained 12 chimeric mice hr/hr <--> +/+ by means of aggregation of early embryos hr/hr and +/+. In chimeric mice, the hair shedding has begun two days later than in the hr/hr mice. By day 23 of postnatal development, hairless areas were present on the coat of chimeric mice or the latter were completely hairless depending on the percentage of the hr/hr mutant component. In four chimeras with high content of the mutant component (68-76%), the hair shedding process was similar to that in the hr/hr mice, though it was accomplished two days later. In three chimeras with 48-51% of the mutant component, alternating hairless and hair-covered bands were observed. These data suggest that the hr gene acts in epidermal cells of a hair follicle, because epidermal cell clones in embryonic skin migrate in the lateral-ventral direction coherently and without mixing. However, some chimeras displayed a pattern which was not so clear-cut: the band borders were illegible and hairs partly covered the hairless areas. In some chimeras, the uniform thinning of the coat was observed. Analysis of the effects of the hr mutant gene in chimeric mice differing in the ratio between mutant (hr/hr) and normal (+/+) components in tissues suggests that the hr gene acts in the epidermal cells of the hair follicle. The interactions between cells have an essential effect on the mode and degree of the hr gene expression, which leads to distortion of the "ectodermal" coat pattern in chimeras.
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PMID:[Analysis of the effects of mutant hairless genes in chimeric mice]. 1458 95

Physicians should be careful not to underestimate the emotional impact of hair loss for some patients. Patients may present with focal patches of hair loss or more diffuse hair loss, which may include predominant hair thinning or increased hair shedding. Focal hair loss can be further broken down into scarring and nonscarring. Scarring alopecia is best evaluated by a dermatologist. The cause of focal hair loss may be diagnosed by the appearance of the patch and examination for fungal agents. A scalp biopsy may be necessary if the cause of hair loss is unclear. Alopecia areata presents with smooth hairless patches, which have a high spontaneous rate of resolution. Tinea capitis causes patches of alopecia that may be erythematous and scaly. Male and female pattern hair losses have recognizable patterns and can be treated with topical minoxidil, and also with finasteride in men. Sudden loss of hair is usually telogen effluvium, but can also be diffuse alopecia areata. In telogen effluvium, once the precipitating cause is removed, the hair will regrow.
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PMID:Diagnosing and treating hair loss. 1967 3

Sulfur mustard (SM, bis(2-chloroethyl)sulfide) is a bifunctional alkylating agent that causes dermal inflammation, edema and blistering. To investigate the pathogenesis of SM-induced injury, we used a vapor cup model which provides an occlusive environment in which SM is in constant contact with the skin. The dorsal skin of SKH-1 hairless mice was exposed to saturated SM vapor or air control. Histopathological changes, inflammatory markers and DNA damage were analyzed 1-14 days later. After 1 day, SM caused epidermal thinning, stratum corneum shedding, basal cell karyolysis, hemorrhage and macrophage and neutrophil accumulation in the dermis. Cleaved caspase-3 and phosphorylated histone 2A.X (phospho-H2A.X), markers of apoptosis and DNA damage, respectively, were increased whereas proliferating cell nuclear antigen (PCNA) was down-regulated after SM exposure. By 3 days, epithelial cell hypertrophy, edema, parakeratosis and loss of epidermal structures were noted. Enzymes generating pro-inflammatory mediators including myeloperoxidase and cyclooxygenase-2 were upregulated. After 7 days, keratin-10, a differentiation marker, was evident in the stratum corneum. This was associated with an underlying eschar, as neoepidermis began to migrate at the wound edges. Trichrome staining revealed increased collagen deposition in the dermis. PCNA expression in the epidermis was correlated with hyperplasia, hyperkeratosis, and parakeratosis. By 14 days, there was epidermal regeneration with extensive hyperplasia, and reduced expression of cleaved caspase-3, cyclooxygenase-2 and phospho-H2A.X. These findings are consistent with the pathophysiology of SM-induced skin injury in humans suggesting that the hairless mouse can be used to investigate the dermatoxicity of vesicants and the potential efficacy of countermeasures.
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PMID:Structural changes in the skin of hairless mice following exposure to sulfur mustard correlate with inflammation and DNA damage. 2167 37


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