Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The total membrane-bound ATP hydrolytic activity in human epidermis is due to the activities of at least three differently located enzymes, namely Mg++-activated ATPase, phosphomonoesterase and adenyl cyclase. Cytochemical studies on psoriatic epidermis with various inhibitory and stimulatory substances showed reduced activities of ATPase and phosphomonoesterase, and a lack of sensitivity of adenyl cyclase to specific stimulators such as isoproterenol and glucagon. Since no differences of basal adenyl cyclase activity were observed between normal and psoriatic human skin without stimulation, it seems likely that in psoriasis a latent defect of adenyl cyclase may exist, resulting in a deficient response of this enzyme to regulatory agents. In conclusion, the present study reveals that not a single enzyme but the entire membrane-bound nucleotide metabolism is altered in psoriatic keratinocytes, causing a disturbance of the membrane-bound energy utilization, similar to findings in proliferating tumour cells.
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PMID:Ultrastructural localization and differentiation of membrane-bound ATP utilizing enzymes including adenyl cyclase in normal and psoriatic epidermis. 17 85

In a multicentre, cooperative study into the treatment of extensive psoriasis with a new aromatic retinoid (Ro 10--9359) trichogram, liver function tests and the light erythema threshold were investigated. In some of the patients hair loss occurred, usually in the fifth to eighth week after a total dose of 1.9 g retinoid. In all cases this improved an average of six weeks after dose reduction or cessation of treatment. The trichogram in 27 patients showed a diffuse toxic hair loss. In 70% the effluvium was telogenic, in 22% telogen-dystrophic. GPT, GOT, alkaline phosphatase and prothrombin index showed no significant alterations during retinoid treatment. However, in individual cases there was a rise in GOT and GPT up to 80 U/l. Furthermore there was a statistical tendency in rising bilirubin levels. Finally there was no evidence for an increase in light sensitivity after three weeks of retinoid treatment. Measurement of the erythema threshold showed rather more a reduction in light sensitivity under treatment.
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PMID:[Hair growth, liver function and light sensitivity during oral retinoid therapy for psoriasis (author's transl)]. 43 1

Numerous laboratory parameters were examined 235 patients with generalized psoriasis treated orally with retinoid and in 35 patients treated topically with anthralin as control. Computer evaluation of the obtained data revealed statistical trends to elevation of the total serum bilirubin level and increasing number of blood monocytes after long-term oral treatment. No other statistically significant changes of the laboratory data were found. Particularly, the liver function tests (transaminases, prothrombin and alkaline phosphatase) showed no significant alterations. Only in a few cases did the retinoid compound have an influence on the GPT and GOT levels. The reasons for this individual sensitivity to the drug remain unknown. No significant alterations were found in the control group treated topically with anthralin.
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PMID:Laboratory investigations in patients with generalized psoriasis under oral retinoid treatment. A multicenter study of computerized data. 47 44

The retinoic acid derivative Ro 10-9359, given orally in maximum daily doses of 100 mg to 15 patients with psoriasis vulgaris, led to clearing of the lesions in 8 patients. The average period of treatment was 9 weeks. In 14 patients side-effects were observed, the most important being palmo-plantar desquamation, shivering, thirst and diffuse hair loss. In 2 patients scaling led to withdrawal. In 6 patients abnormal alkaline phosphatase and glutamic-aspartatic transaminase values, partly transient, developed (glutamicaspartatic transaminase, p less than 0.01).
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PMID:Treatment of psoriasis vulgaris with a new retinoic acid derivative Ro 10-9359; An uncontrolled clinical trial. 86 67

Thirty five patients with psoriasis (plaque type 26, guttate 3, pustular 4, and erythrodermic 2) were treated with oral mycophenolic acid for a period ranging from 52 to 104 weeks. The average follow-up was 89 weeks, and the dose schedule ranged from 2,400 to 7,200 mg daily. Excellent response was noted in 20 patients, good in 13 patients, and poor in 2. The most common clinical side effects were in the gastrointestinal tract, namely, diarrhea, nausea, abdominal cramps, and soft stools. A high incidence of herpes simplex, herpes zoster, and a flu-like syndrome was noted. Laboratory abnormalities consisted of mild blood hemoglobin reduction, one case of leukopenia (3,9000 WBCs per cubic millimeter), two cases with thrombocytopenia and mild elevation of alkaline phosphatase. Mycophenolic acid appears as a promising drug for the treatment of severe psoriasis.
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PMID:Mycophenolic acid in the treatment of psoriasis: long-term administration. 87 14

The analogue of calcitriol, calcipotriol (MC 903, Daivonex) has been proven effective in the treatment of psoriasis, when given topically. However, the possible influence of cutaneously absorbed MC 903 on calcium metabolism is still unclear. We evaluated various parameters of calcium metabolism in 17 psoriatic patients treated for 5.4 +/- 2.3 (mean +/- SD) weeks with MC 903, on 16 +/- 6% of the body surface. The dose administered (100 g of Daivonex corresponding to 5 mg of MC 903) decreased the PASI score by 40.9 +/- 20.0% (p less than 0.001). Among these patients, 12 were studied before and after MC 903 therapy. In none could be detected any change in protein-adjusted calcium, ionized Ca, plasma levels of creatinine, alkaline phosphatase, osteocalcin, intact parathyroid hormone (PTH), calcidiol and calcitriol, or in daily or fasting urinary excretion of Ca or cAMP. After an MC-903-free period, 9 patients received 1.5 micrograms/day of calcitriol orally for 7 days. Whereas this treatment did not control the skin relapse in most of the patients, it induced a significant increase in plasma levels of protein-adjusted Ca and calcitriol, and in 24-hour urinary Ca excretion, as well as a significant fall in PTH as compared with pretreatment values. These results indicate that 150 micrograms/day of MC 903, despite a possible 1% absorption, i.e. a systemic dose of 1.5 micrograms, did not produce any detectable alteration of Ca metabolism, whereas an equivalent dose of oral calcitriol was associated with significant changes. The threshold dose of topical calcipotriol that might induce alterations similar to 1.5 micrograms/day of oral calcitriol remains to be evaluated.
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PMID:Effects of topical calcipotriol on calcium metabolism in psoriatic patients: comparison with oral calcitriol. 180 90

Radiographic skeletal examinations were performed in sixteen adult patients who had received etretinate therapy for various keratinizing disorders (psoriasis vulgaris 13, pustular psoriasis 2, pustulosis palmoplantaris 1) over periods ranging from 0.7 to 4.5 years. The total dose of etretinate ranged from 5.1 to 36.5 g. In these patients, the frequency and the degree of skeletal alterations including hyperostosis, calcification of ligaments and periosteal thickening was found to be higher than that in age- and -sex matched, nontreated controls. Furthermore, almost all of these patients were asymptomatic and revealed no abnormalities in laboratory data, including levels of serum calcium, inorganic phosphate and alkaline phosphatase. It is necessary for patients who are undergoing long-term etretinate therapy to be examined regularly for such skeletal abnormalities.
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PMID:[Skeletal alterations associated with long-term etretinate therapy]. 189 Jul 51

An inflammatory response of the skin to dithranol-induced free radicals seems to be essential for its clinical efficacy. In normal volunteers this response was evaluated at the level of the microvasculature following 30 min, 2 h and 24 h applications, using a functional parameter (erythema) and a biochemical parameter (alkaline phosphatase). The results of 'short contact' and 24 h applications were similar. In all schedules a maximum erythema was seen 2-3 days after the application which had resolved totally after 6-8 days. A marked discrepancy was established between the duration of functional and biochemical abnormalities; the alkaline phosphatase activity reached a maximum 1 day after the culmination of the erythema and persisted up to at least 7 days after disappearance of the erythema. These findings are discussed in the light of the day-to-day management of psoriasis with dithranol.
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PMID:Studies on the time course of dithranol-induced inflammation by quantification of alkaline phosphatase. 196 79

A new 1,25-dihydroxyvitamin D3 analog, 22-oxa-1,25(OH)2D3, which may have pharmaceutical use, e.g., in the treatment of psoriasis, was studied using cultured MG-63 human osteosarcoma cells. We found that the new compound binds to 1,25-dihydroxyvitamin D receptors and regulates receptor mRNA levels like the natural ligand. Our results also indicate that 22-oxa-1,25(OH)2D3 induces the synthesis of osteocalcin and the activity of alkaline phosphatase in MG-63 cells through a receptor-mediated process identically with 1,25(OH)2D3.
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PMID:Affinity of 22-oxa-1,25(OH)2D3 for 1,25-dihydroxyvitamin D receptor and its effects on the synthesis of osteocalcin in human osteosarcoma cells. 216 70

It is now well established that epidermis, like many other tissues, contains a phospholipase A2 that is responsible for the initiation of the arachidonic acid cascade. Here we report that human epidermis also contains a second, quite distinct enzyme of the phospholipase A2 group, which is unique in its extreme activity against phospholipids in true solution. It also differs from the classic cutaneous enzyme in that (a) its activity is not reduced by pretreatment of the skin with corticosteroids in vivo nor by treatment of the epidermal homogenate with alkaline phosphatase in vitro, and (b) its activity is reduced, rather than increased, in the lesions of inflammatory diseases such as psoriasis. The enzyme seems to occur mainly in fully differentiated keratinocytes, its level being low in the basal cell layer of epidermis and in keratinocytes cultured in vitro. On the basis of these observations, we suggest that this new phospholipase A2 is responsible for the degradation of phospholipids that accompanies the terminal keratinization process.
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PMID:A unique phospholipase A2 in human epidermis: its physiologic function and its level in certain dermatoses. 244 92


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