Paraqueratosis granular / Granular parakeratosis

La paraqueratosis granular es una entidad poco frecuente que se caracteriza por ser una alteración adquirida de la queratinización. Clínicamente se presenta como placas eritematoparduscas, ocasionalmente pruriginosas, que clásicamente aparecen en la axila y áreas intertriginosas. La histología es característica, donde se observa un engrosamiento de la capa córnea con una paraqueratosis compacta y persistencia de gránulos de queratohialina, mientras que el estrato granuloso se encuentra preservado. La etiología es desconocida, se postula la acción de factores irritantes físicos o químicos. La respuesta al tratamiento es variable. Presentamos un nuevo caso en una mujer de 50 años, con placas marronáceas abollonadas e hiperqueratósicas en ambas axilas, de dos años de evolución y con histología compatible, que presentó una buena respuesta al tratamiento con tacalcitol

Granular parakeratosis is a rare entity that results from an acquired disorder of keratinization.Clinically presents as dark erythematous plaques, occasionally pruritic, that usually involve the axilla and other intertriginous areas. The pathology is characteristic and consists of thickening of the stratum corneum with compact parakeratosis and retention of keratohyaline granules, whereas the stratum granulosum is preserved. The etiology is unknown although some factors such as irritating physical or chemical agents have been implicated. Treatment response is variable. We report a new case in a 50-year-old woman with brownish and hyperkeratotic plaques on both axillae, of two years duration, with a compatible pathology that showed a favorable response to tacalcitol

Differentiation-related pathways of 1 alpha,25-dihydroxycholecalciferol metabolism in human colon adenocarcinoma-derived Caco-2 cells: production of 1 alpha,25-dihydroxy-3epi-cholecalciferol.

We used the human colon adenocarcinoma-derived cell line Caco-2, which spontaneously differentiates in vitro, as a model system to investigate the metabolism of 1 alpha,25-dihydroxycholecalciferol in colon cancer cells. Subconfluent proliferating and confluent differentiating cells were incubated with 1 microM 1 alpha,25-dihydroxycholecalciferol for a period of 24 to 48 h. HPLC analysis of the lipid extract of both cells and media was performed to isolate and identify the various metabolites of 1 alpha,25-dihydroxycholecalciferol. Undifferentiated, highly proliferating Caco-2 cells metabolized 1 alpha, 25-dihydroxycholecalciferol into several side chain modified metabolites formed through the C-24 oxidation pathway. In contrast, no metabolites of the C-24 oxidation pathway were identified in differentiated Caco-2 cells. However, differentiated cells produced significant amounts of a metabolite which was less polar than 1 alpha, 25-dihydroxycholecalciferol on a straight phase HPLC system. This metabolite was identified as 1 alpha,25-dihydroxy-3alpha-cholecalciferol by comigration with a synthetic standard on two different HPLC systems and gas chromatography--mass spectrometry. Thus, we were able to demonstrate that the state of differentiation has a profound influence on 1 alpha,25-dihydroxycholecalciferol metabolism in colon cancer cells.

Tacalcitol.

Tacalcitol is a vitamin D3 analogue which is available in Japan as a 2 micrograms/g ointment for twice daily application and in Western markets as a 4 micrograms/g ointment for once daily application. Tacalcitol inhibits proliferation, and induces the differentiation, of keratinocytes. In addition, it appears to modulate inflammatory and immunological mediators in the skin which may be involved in the aetiology of psoriasis. No significant systemic drug absorption occurs after application of tacalcitol to the skin. Results of clinical trials indicate that topical tacalcitol is effective in the management of stable plaque psoriasis (and possibly pustular forms of the disease), and has a similar efficacy to topical betamethasone valerate in this setting. Application of tacalcitol ointment 4 micrograms/g once daily for up to 8 weeks did not cause hypercalcaemia or hypercalciuria. Mild local skin irritation has been reported in a variable proportion of patients (< or = 12%).

In vivo microautoradiography of [3H]1,24(OH)2D3 (tacalcitol) following topical application to normal rats and in vitro metabolism in human keratinocytes.

This study was conducted to investigate the mechanism of topical absorption of [3H]1,24(OH)2D3 (1,24-dihydroxyvitamin D3; tacalcitol) by applying an ointment containing 4 micrograms2/g [3H]1,24(OH)2D3 to the skin of rats using an occlusion method. Microautoradiography of the skin at the application site 1 h after topical treatment showed a high concentration of radiolabel in the stratum corneum, the epidermis and around the hair follicles. Radiolabel was also seen in the epidermis and hair follicle areas 8 h and 24 h after application. The radiolabel was distributed to a minor extent to the subcutaneous fat layer. Microautoradiography showed two routes of purcutaneous absorption of 1,24(OH)2D3: through the stratum corneum and epidermis into the microvessels, and through hair follicle areas into the bloodstream. After topical application of an ointment containing 4 micrograms/g or 40 micrograms/g [3H]1,24(OH)2D3 to the shaved neck skin of rats, the absorption rate, estimated by excretion in the urine and faeces, was about 30% of the total applied radioactivity. The main excretion route after topical application was in the faeces. Furthermore, 1,24(OH)2D3 added to human adult keratinocytes was not metabolized into other compounds, and only the unchanged compound was detected. These findings strongly suggest that 1,24(OH)2D3 distributed into the epidermis acts on epidermal keratinocytes. Topical application of 1,24(OH)2D3 appears to be a possible approach to the treatment of psoriasis and other skin diseases through its action on the 1,25(OH)2D3 receptor, which reportedly plays a very important role in the regulation of proliferation and differentiation of keratinocytes.

Tacalcitol ointment for psoriasis.

Transdermal absorption of tacalcitol from the ointment containing 2 micrograms/g was studied using hairless rat and human skin. In the animal experiments, a non-negligible amount of tacalcitol was absorbed transdermally, whereas in the case of human skin, this compound was hardly absorbed at all. A placebo-controlled double-blind right/left comparison confirmed that this ointment is effective and safe for the treatment of psoriasis.

Production and metabolic clearance of 1,25-dihydroxyvitamin D in men: effect of advancing age.

To determine whether aging alters the metabolism of 1,25-dihydroxyvitamin D [1,25-(OH)2D] in men, we measured the serum concentrations, MCRs, and production rates of 1,25-(OH)2D in healthy old (age, 72 +/- 5 yr; n = 9) and young men (age, 34 +/- 5 yr; n = 9) consuming a constant metabolic diet and in whom the glomerular filtration rate was greater than 1.2 mL/s.1.73 m-2. The results indicate that when dietary calcium and phosphorus are normal and glomerular filtration rate is not reduced, the serum concentrations, MCRs, and production rates of 1,25-(OH)2D in old men [83 +/- 22 pmol/L; 0.62 +/- 0.10 mL/s.70 kg ideal BW (IBW); 51 +/- 12 fmol/s.70 kg IBW, respectively] and young men (90 +/- 20 pmol/L; 0.56 +/- 0.09 mL/s.70 kg IBW; 52 +/- 13 fmol/s.70 kg IBW, respectively) are equivalent. Indices of serum PTH, however, were elevated in the elderly men. These results suggest that aging per se has little or no effect on the serum concentration, MCR, or production rate of 1,25-(OH)2D in men. Maintenance of a normal production rate of 1,25-(OH)2D in elderly men, however, may require increased circulating PTH. Most observed declines in serum 1,25-(OH)2D in elderly men are probably a consequence of decreased functional renal mass.

Vitamin D kinetics in vivo: effect of 1,25-dihydroxyvitamin D administration.

Administration of 1,25-dihydroxyvitamin D [1,25(OH)2D] can increase the metabolic clearance rate (MCR) of 25-hydroxyvitamin D [25(OH)D]. To determine whether administration of 1,25(OH)2D can also influence the metabolic clearance rates (MCR) of 1,25(OH)2D and 24,25-dihydroxyvitamin D 24,25(OH)2D, we measured metabolic clearance of 1,25(OH)2D, 24,25(OH)2D, and 25(OH)D in rats in which the serum concentration of 1,25(OH)2D was increased by continuous infusion. Infusion of 1,25(OH)2D (12 days at 75 pmol/day) increased serum 1,25(OH)2D from 128 +/- 11 to 244 +/- 14 pg/ml (P less than 0.005) and increased MCR from 169 +/- 13 to 210 +/- 9 microliters.min-1.kg-1 or 24% (P less than 0.025). Increasing serum 1,25(OH)2D to 330-360 pg/ml increased MCR 72%. Infusion of 1,25(OH)2D decreased serum 24,25(OH)2D from 3.5 +/- 0.5 to 2.4 +/- 0.3 ng/ml (P less than 0.05), increased MCR from 25 +/- 2 to 48 +/- 6 microliters.min-1.kg-1 (P less than 0.0025), and increased the production rate (PR) from 70 +/- 11 to 124 +/- 26 pg.min-1.kg-1 (P less than 0.05). Infusion of 1,25(OH)2D decreased serum 25(OH)D from 13.0 +/- 0.5 to 8.0 +/- 0.5 ng/ml (P less than 0.005) and increased MCR from 45 +/- 1 to 75 +/- 7 microliters.min-1.kg-1 (P less than 0.001) but had no effect on PR. The data indicate that increasing serum 1,25(OH)2D by chronic administration can increase the MCR of 1,25(OH)2D and suggest that 1,25(OH)2D can feedback regulate its serum concentration by regulating its MCR. The data also suggest that 1,25(OH)2D administration can increase the MCRs of 24,25(OH)2D and 25(OH)D.