Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neutrophil chemotaxis was assessed in 69 psoriatic patients and 37 healthy human subjects. It was found to be significantly enhanced in 52 untreated patients. In 20 patients treated with an orally-administered phosphodiesterase inhibitor, Diphylline, neutrophil chemotaxis was normal. The enhanced chemotactic response of neutrophils from untreated patients with minimal skin lesions was at least equal to the response of those from patients with extensive skin lesions. Preincubation of normal human leukocytes with plasma derived from patients with widespread lesions markedly reduced their chemotactic activity. Plasma derived from patients with extensive skin lesions exhibited marked chemoattracting properties in comparison with plasma from healthy subjects. It is postulated that the basic intrinsic abnormality of neutrophil function in psoriasis could be caused by a decreased cyclic AMP/cyclic GMP ratio, similar to the decreased cyclic AMP/cyclic GMP ratio found in the lesional epidermis of this disease. Plasma factors which influence chemotaxis in psoriasis are related to the extent of the eruption and their effect is contrary to the effect of the basic intrinsic abnormality of psoriatic neutrophils.
 ...
PMID:Neutrophil chemotaxis in psoriasis. 9 68

This study has been undertaken to elucidate the localization and the activity of cyclic nucleotide phosphodiesterase (PDE) in psoriatic epidermis compared to normal. The results showed that the evaluation of cytochemical methods may be difficult because of the various factors which interfere with the reaction and the considerable amount of background staining. Additionally, only the tissue bound particulate enzyme fraction may be demonstrated by cytochemical means. Nevertheless, the method did reveal that the activity of PDE, if any, is localized on the cytoplasmic membranes of the cells, independent of their origin, and not on the cell surface. Moreover, no differences were found between normal and psoriatic skin. It seems, therefore, that the intracellular degradation of cAMP remains unaltered in psoriasis.
 ...
PMID:Localization and activity of tissue bound cyclic nucleotide phosphodiesterase in normal and lack of changes in psoriatic human skin. 18 39

Although psoriasis is a genetically transferred disease, little is known of the factors causing spontaneous eruption of a proliferative lesion in apparently normal epidermis. Cell kinetic studies indicate an increased epidermal turnover in clinically normal and involved skin, but the pharmacological events regulating epidermopoiesis remain elusive. Possible candidates for the defect in psoriasis are the cyclic nucleotides with their associated enzyme systems. The cyclic AMP: cyclic GMP ratio appears to be reduced in lesional skin. Further phosphodiesterase inhibitors are reported to improve psoriasis. Since prostaglandins stimulate epidermal cyclic AMP in vitro they have been investigated, but with conflicting results. However, the prostaglandins' precursor, arachidonic acid, appears to be elevated in the psoriatic lesion. Epidermal levels of cyclic AMP are also elevated by histamine via H2 receptors and the possibility that histamine exerts a regulatory role needs to be investigated. In conclusion, the pharmacology of psoriasis is complex. Not only do we need to know which pharmacological agents are present in abnormal amounts but more importantly we need to know more about their interactions with one another and with their specific epidermal 'receptors'.
 ...
PMID:Pharmacology of psoriasis. 23 69

Delivery of dyphylline to the skin using liposomes was investigated. Xanthines are inhibitors of cAMP phosphodiesterase and have been considered for treatment of psoriasis. Dyphylline was chosen because of its solubility in water, which should allow for incorporation of higher concentrations within the liposomes. Liposomes containing dyphylline were prepared by a method using sonication. Transmission electron micrography (TEM) visualization showed small particles ranging from 40 to 100 nm, and particle size distribution determined by light scattering showed the vesicles to have an average diameter of 360 nm. The transdermal delivery of free dyphylline and dyphylline incorporated in unilamellar liposomes was measured from polyethylene glycol (PEG), Carbopol gel, a PEG enhancer base, and water. For comparison, similar experiments were carried out with theophylline as well. When the drugs were incorporated in Carbopol gel, a large difference was seen between their fluxes, with free dyphylline having the highest permeation, followed by liposomal dyphylline, and then theophylline. With the PEG enhancer base, a very high permeation of theophylline was observed relative to dyphylline and liposomal dyphylline. From the PEG base, liposomal dyphylline exhibited the lowest skin permeation flux relative to other bases. Using the PEG base for dyphylline incorporated in liposomes, a high skin partitioning of the drug, along with low transdermal permeation, was measured. These results may indicate that the drug is localized in the skin.
 ...
PMID:Dyphylline liposomes for delivery to the skin. 154 51

Epidermal cells from psoriatic lesions demonstrate a very low cAMP response to beta-adrenergic stimuli. We have shown that a similar abnormality occurs in dermal fibroblasts from affected areas of skin. The cells, after 5-12 passages in tissue culture, had a much reduced response to 10(-8) M and 10(-6) M isoproterenol when compared with fibroblasts from control subjects. The abnormality was not abolished by the addition of the phosphodiesterase inhibitor, 3-isobutyl-I-methylxanthine. Other putative agonists tested were vasoactive intestinal peptide and peptide histidine methionine. Neither of these had an effect on dermal fibroblasts from either normal controls or from lesions of psoriasis.
 ...
PMID:Beta-adrenergic stimulation of cyclic AMP is defective in cultured dermal fibroblasts of psoriatic subjects. 169 75

Epidermal calmodulin (CaM) has been reported to be elevated in psoriasis and to decrease following clearance of psoriasis with treatment. We set out to investigate whether any of the principle drugs used in the treatment of psoriasis had inherent CaM antagonist activity. Utilizing a CaM-activated phosphodiesterase we have demonstrated that even at very high concentrations, the systemic drugs etretinate, methotrexate, and 8-methoxypsoralen, and the topical agents hydrocortisone and crude coal tar showed minimal CaM inhibitory activity. Dithranol (anthralin), however, whether freshly prepared or oxidized, produced substantial inhibition of CaM activity and was demonstrated to be a potent competitive antagonist of CaM, suggesting another possible therapeutic mode of action of dithranol in psoriasis.
 ...
PMID:An investigation of the ability of antipsoriatic drugs to inhibit calmodulin activity: a possible mode of action of dithranol (anthralin). 301 2

The changes in cAMP, cGMP, adenylate cyclase, cyclic phosphodiesterase, and prostaglandins in psoriatic epidermal cells were compiled and critically discussed. The results of the pertinent studies permit the assumption that therapeutic approaches in psoriasis via the system of cyclic nucleotides and prostaglandins might be promising.
 ...
PMID:Cyclic nucleotides and prostaglandins in psoriasis. 624 71

Soluble cyclic GMP-phosphodiesterase was measured in normal and psoriatic epidermis. The specific activity of the enzyme was increased almost four-fold in involved compared with normal epidermis, and two- to three-fold in involved compared with uninvolved epidermis. The enzyme activity from all three sources was inhibited by 40-50% by ethylene glycol tetraacetic acid (EGTA). These results indicate that in addition to the reported enhanced capacity of psoriatic epidermis to generate cGMP, it has an increased ability to hydrolyse this nucleotide, although to a lesser degree than the augmentation found in soluble guanylate activity from psoriatic epidermis. These observations are compatible with the elevated steady-state levels of this nucleotide observed in the involved epidermis of psoriasis.
 ...
PMID:Cyclic GMP metabolism in psoriasis: increased activity of soluble epidermal cyclic GMP phosphodiesterase and its modulation by calcium. 626 Jan 27

The aim of this study was to determine whether levels of biologically active calmodulin are elevated in both lesional and uninvolved epidermis in psoriasis. Epidermal shave biopsies were obtained from normal controls and from both psoriatic plaques and nonlesional psoriatic skin. Following determination of the protein content, the calmodulin activity of the homogenized samples was then measured using a calmodulin-sensitive phosphodiesterase enzyme bioassay. In normal skin, calmodulin activity was 1.29 +/- 0.35 micrograms calmodulin mg-1 epidermal protein (mean +/- SEM, n = 12 volunteers) compared to 7.88 +/- 1.59 micrograms calmodulin mg-1 epidermal protein for plaque (n = 16 patients) and 10.19 +/- 2.35 micrograms calmodulin mg-1 epidermal protein for the uninvolved skin of 12 of these patients. The levels of biologically active calmodulin were therefore elevated in both plaque and uninvolved epidermis of patients with psoriasis compared to epidermis from normal volunteers. These results suggest that an abnormality in the regulation of calmodulin activity may be involved in the pathogenesis of psoriasis.
 ...
PMID:Biologically active calmodulin levels are elevated in both involved and uninvolved epidermis in psoriasis. 632 4

It has been proposed that immune dysfunction in psoriasis is a consequence of aberrant cyclic nucleotide metabolism. We have examined cyclic AMP responses to isoprenaline, histamine, and prostaglandin E2 in peripheral blood mononuclear leukocytes from patients with psoriasis, in the presence and absence of a potent cyclic AMP phosphodiesterase inhibitor. Stimulated and basal cyclic AMP levels in mononuclear leukocytes from psoriatics did not differ from those observed in mononuclear leukocytes from normal subjects, irrespective of the stimulant employed, either in the presence or in the absence of the phosphodiesterase inhibitor. These findings do not support the hypothesis that psoriasis is associated with either impaired beta-adrenergic reactivity or a more generalized abnormality of mononuclear leukocyte cyclic nucleotide metabolism.
 ...
PMID:Mononuclear leukocyte cyclic adenosine monophosphate responses in psoriasis are normal. 632 85


1 2 3 4 5 6 7 8 9 10 Next >>