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

Twenty eight patients with various dermatological conditions were treated orally with the new aromatic derivate of retinoic acid, Ro 10-9359. The initial average dose was 48,3 mg/day and the maintenance dose was 26,6 mg/day. Duration of treatment ranged between 3 to 6 months. Evolution of erythema, infiltration and hyperkeratosis showed changes statistically significant (p < 0,05) and excellent to good results were obtained in 23 out of the 28 treated patients. On the basis of this study it is concluded that Ro 10-9359 is a promising drug for the treatment of several skin diseases, specially ichthyosis, Darier's disease, oral lichen planus, erythrokeratoderma variabilis and psoriasis. No serious side effects were reported; dryness of the lips, scaling of palms and soles, pruritus and thinning of the skin were the most common. In no case treatment was discontinued due to side effects. Laboratory controls did not show deviations from the normal values.
 ...
PMID:[Oral treatment of various dermatosis with the aromatic derivative of retinoic acid Ro 10-9359]. 39 25

The aromatic retinoic acid derivative Ro 10-9359 was administered orally to 25 severe psoriatic patients (14 with generalized plaques, 7 erythrodermic, 4 pustular). The initial dose was 25 mg/20 kg body weight daily for 4 weeks; afterwards the same posology was given every other day during several months (Max : 18 months). Excellent results were obtained in 16 patients (64 p. 100) particularly in severe erythrodermic and pustular psoriasis. However, under follow-up therapy relapses sometimes occurred leading to temporary resumption of initial posology. The most important side effects are cheilitis, palmoplantar scaling with thinning of the skin, hyperhidrosis and diffuse hair loss. A slight increase of transaminases and of alkaline phosphatases was found in a few patients. The Ro 10-9359 compound is a very useful new therapy of severe psoriasis.
 ...
PMID:[Oral treatment of severe psoriasis with a new aromatic retinoid (Ro 10-9359) (author's transl)]. 74 93

3-(4-methoxyphenyl)-3-methylbutylester, propenoic acid (MPMBE; CAS no. 71617-10-2), a UVB-light filter used for sun protection of the skin, was administered once daily by intragastric gavage to pregnant Wistar rats on days 6-15 of gestation. Doses of 0.25 ml/kg/day (study group: D0.25), 0.75 ml/kg/day (D0.75) and 2.25 ml MPMBE/kg/day (D2.25) were applied. A positive control group (Pos) received 15 mg (all trans) retinoic acid/kg/day. MPMBE revealed some toxic effects in the dams of the group receiving the highest dose (D2.25): marked loss of body weight, polydipsia, reduced food consumption and intensified loss and thinning of hair. Only thinning or partial loss of hair without any other harmful effects was seen in the dams of group D0.75. An increase in embryonic deaths was striking in group D2.25; the living foetuses revealed signs of retarded development, but no major external or internal anomalies as signs of teratogenicity. This study was not able to present any teratogenic effects induced by MPMBE in the offspring, even at very high oral doses (> 2 g/kg/day) that caused substantial toxicity in the dams. In conclusion, concerning embryotoxicity an oral dose of 250 mg/kg/day MPMBE is regarded as a safe no-observed-effect level, whereas even 750 mg/kg/day MPMBE--following acknowledged rules--can be judged as a borderline no-observed-adverse-effect level.
 ...
PMID:Embryotoxicity study of propenoic acid, 3-(4-methoxyphenyl)-3-methylbutylester in the Wistar rat. 142 19

We have analyzed the effect of extracellular stimuli on the differentiation state of the CA77 thyroid C-cell line as a model to understand the control of neural crest cell differentiation. In contrast to the endocrine C-cell phenotype, we found that CA77 cells have a neuronal phenotype characterized by laminin-induced neurites, neuronal antigens, and calcitonin gene-related peptide (CGRP) mRNA expression. Treatment with dexamethasone and retinoic acid reversibly repressed some of these neuronal characteristics to induce features more characteristic of the parental C-cells. In the case of dexamethasone treatment, there was a partial retraction and thinning of neurites, an increased number of secretory vesicles in the cell bodies, and about a 10-fold decrease in DNA synthesis. Treatment with retinoic acid alone or in combination with dexamethasone caused decreased cell adhesion and an even more extensive retraction of the neurites. Dexamethasone also biased the steady state levels of the alternatively spliced transcripts from the calcitonin/CGRP gene to favor calcitonin relative to CGRP mRNA. While retinoic acid treatment decreased both calcitonin and CGRP mRNA levels, the combination of dexamethasone and retinoic acid still yielded the increase in calcitonin relative to CGRP mRNA. These results suggest that glucocorticoids and retinoic acid may contribute to a late and reversible differentiation of thyroid C-cells by partly repressing neuronal properties.
 ...
PMID:Neuronal properties of a thyroid C-cell line: partial repression by dexamethasone and retinoic acid. 156 64

Arotinoids, which are analogs of retinoic acid (RA) and retinol (RO) with the carbon skeleton in a rigid conformation, have more favorable therapeutic indices relative to all-trans-RA and all-trans-RO. The purpose of this investigation was to obtain preliminary in vivo toxicity data on SMR-2(analog of RO) and SMR-6 (analog of RA), arotinoids with promising activity (ED50's of 20 X 10(-11) and 5 X 10(-11) M, respectively; ED50 of RA = 1 X 10(-11) M) for reversal of keratinization in tracheal organ culture. A preliminary toxicity study was conducted in male B6D2F1 mice with gavage of retinoids in corn oil (0.01, 0.05, and 0.1 mg/kg/day of SMR-2 or SMR-6; 1, 5, and 10 mg/kg/day of RA as reference control). Due to lack of toxicity, each dose level for SMR-2 and SMR-6 was increased by 4-fold on Day 29 of dosing. The study was terminated on Day 57. Hypervitaminosis A (weight loss, alopecia, skin scaling, and bone thinning) was induced in the mid- and high-dose SMR groups; weight-gain depression was predominant in the high-dose RA group. The SMR compounds were approximately 100-fold more toxic, based on weight loss, than RA. In the SMR dose groups with hypervitaminosis A, white blood cell counts were elevated 2- to 4-fold; and there were microscopic lesions in skin, testes, epididymis, bone, thymus, bone marrow, peripheral lymph nodes, spleen, stomach, adrenal, and pituitary. The leukocytosis was attributed to leukopoiesis in spleen and bone marrow, which may be due to either a direct effect and/or a secondary response to a subacute inflammatory reaction in skin. Only peripheral lymph node hyperplasia was observed in SMR-2 and RA low-dose groups. Enlarged thymus, lymph node hyperplasia, leukopoiesis in spleen and bone marrow, elevated alkaline phosphatase with bone hypertrophy, and testicular degeneration were observed in the mid-dose RA group. The results indicate that immune stimulation may be a primary early response to retinoids and that skin, leukopoietic tissues, reproductive organs, stomach, and bone are primary targets for retinoid toxicity.
 ...
PMID:Preliminary toxicity profile of arotinoids SMR-2 and SMR-6 in male B6D2F1 mice. 360 38

When retinoic acid is locally applied to the anterior margin of developing chick wing buds on ion-exchange beads, dose-dependent changes in the skeletal pattern result. At low doses, additional digits develop. At high doses, there is thinning of the symmetrical wing. Local application of retinoic acid to the apex of the bud also leads to pattern changes, but in contrast normal wing patterns are almost always obtained following application posteriorly. These effects are manifest at 6-7 days after the operation although only a brief exposure (14-20 h) to retinoic acid is required. Therefore the morphology of wing buds was studied at shorter times after the start of treatment. The local application of retinoic acid to the wing bud margin leads to changes in extent of the apical ridge that can be detected at 24 h after application. The behaviour of the apical ridge with varying doses and positions of retinoic acid application has been analysed quantitatively and dose response curves obtained. At low doses of retinoic acid, the length of the apical ridge increases or remains constant, but then progressively decreases with higher doses. The progressive obliteration of the ridge starts first near the bead and then involves more distant parts of the bud. Thus the region of the ridge affected depends on the position at which the retinoic acid is applied. We propose that these effects on the apical ridge reflect dose-dependent responses to the local concentration of retinoic acid that varies with distance from the source. At high doses, the apical ridge disappears but at low doses it is maintained. Since grafts of polarizing region tissue also have a graded effect on ridge morphology, a possible interpretation of the retinoic acid effects is that tissue adjacent to the source is converted into polarizing region tissue. Alternatively, retinoic acid may act directly on the ridge cells. The changes in the extent of the apical ridge produced by retinoic acid lead to different forms of bud outgrowth. The form of the outgrowth depends on the dose of retinoic acid, the position of application and the interaction between the effects of the local source of retinoic acid and those of the polarizing region of the host bud. These considerations give some insights into why anterior application of retinoic acid leads to the development of additional digits whereas posterior application generally gives normal wings.
 ...
PMID:Retinoic acid and pattern formation in the developing chick wing: SEM and quantitative studies of early effects on the apical ectodermal ridge and bud outgrowth. 383 26

The response of mouse ear epidermal transglutaminase to single applications of anthralin, retinoic acid (both 59 micrograms/ear) or fluocinolone acetonide (2 micrograms/ear) was determined. Anthralin and retinoic acid caused inflammation and accumulation of epidermal protein and DNA, whereas fluocinolone acetonide resulted in ear thinning and decreased epidermal protein and DNA. Treatment with either anthralin or retinoic acid caused increases in absolute amounts of epidermal transglutaminase activity/ear. Anthralin increased this parameter 70-100% above acetone-treated controls from 48 hr through 7 days. Retinoic acid-treated ears showed a slower initial increase but peaked at 4 times control level by 96 hr before returning to normal at 7 days. Fluocinolone acetonide treatment had no effect on this parameter. The specific activity of epidermal transglutaminase (total epidermal transglutaminase/total soluble epidermal protein) was decreased by retinoic acid treatment; was maintained at normal levels by anthralin (except for the 7-day point where it decreased 50%); and was dramatically stimulated by fluocinolone acetonide. In the latter case, specific activity was more than 5 x control by 96 hr and still near this level at 7 days. Epidermal transglutaminase activity is a marker of differentiation, and protein and DNA accumulation an indication of growth. Thus, at the doses studied, retinoic acid favors growth over differentiation, anthralin maintains a normal to near normal ratio of growth to differentiation, and fluocinolone acetonide strongly favors differentiation over growth.
 ...
PMID:The effect of topical drugs on mouse ear epidermal transglutaminase activity. 612 46

This two phase study was designed to observe the toxicity and effectiveness of retinoids on oral leukoplakia. The study design included patients who had visible and measurable oral leukoplakia without history of synchronous oral cancer or oral cancer within the previous 2 years. Documentation of the lesion by direct measurement and photography, as well as a biopsy at the beginning and at the end of the study (for verification of the histologic appearance of the lesion), were performed in each patient. Sixteen patients with oral leukoplakia were treated with 13-cis-retinoic acid formulated in a troche in the strength of 1 mg. Three patients received 3 mg/day, 8 patients received 5 mg/day, and 5 patients received 10 mg/day. The initial visible responding event appeared to be a thinning of the leukoplakia with reduction in the whitish surface leaving a reddish, velvety epithelium. If resolution occurred, the velvety area became pink, assuming the color and texture of the normal adjacent mucosa. Toxicity of the drug appeared to be acceptable among the evaluable patients. Of the 11 patients, 3 demonstrated complete response and 6 demonstrated partial response after 6 months of treatment with the drug under study. Recurrences developed in two of the three patients with complete response, and neither of the two showed complete histologic and cytologic regression. One of the patients with partial response went on to complete response after cessation of treatment. Under the condition of our study, a treatment effect was observed with small amounts of topical 13-cis-retinoic acid and that the level of toxicity was acceptable.
 ...
PMID:Effect of retinoids on oral leukoplakia. 657 87

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.
 ...
PMID:Retinoid effects on epidermal structure, differentiation, and permeability. 693 40

Hypervitaminosis A and D is a potential cause of "hyena disease" in cattle, which results from premature growth-plate closure in long bones of calves. This study showed that vitamin A induced growth-plate closure if calves were given an intramuscular injection of vitamins A and D (2,000,000 IU and 300,000 IU, respectively) on the first day after birth and, in addition, vitamin A (30,000 IU/kg body weight) in a water dispersible form was added to the milk substitute daily. Gross lesions were observed in the proximal tibial growth plates of each of seven calves after 3 weeks of vitamin-A treatment. Microscopical examination showed commencing premature growth-plate closure in the proximal tibia at 2 weeks. After one week, the growth plate showed focal thinning, and there was premature endochondral ossification of columnar cartilage. Longitudinal bone growth was dramatically reduced before growth plate closure at one week (25 microns/day in a treated animal versus 136 microns/day in a control). Liver concentrations of retinol and retinyl palmitate became strikingly elevated at on week, and thereafter increased slowly until the third week. Elevation of plasma retinol and retinyl palmitate was rapid, reaching a maximum on day 10. Plasma all-trans-retinoic acid was undetectable in many samples from treated animals, but plasma concentrations of derivatives of retinoic acid (9-cis-retinoic acid, 13-cis-retinoic acid, 13-cis-4-oxoretinoic acid, and 9, 13 dicis-retinoic acid) were elevated. The vitamin-A intake required to induce growth-plate closure in calves was found to be exceedingly high. Vitamin-A toxicity must be considered as a potential cause of hyena disease, but it would seem likely that other factors also play a role.
 ...
PMID:Vitamin (A and D)-induced premature physeal closure (hyena disease) in calves. 917 48


1 2 Next >>