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Query: UMLS:C0033860 (psoriasis)
 20,684 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The inflammatory reaction induced by the intradermal injection of arachidonic acid into the rabbit dermis has been investigated. Plasma extravasation was measured by the leakage of 125I-albumin into the tissues and polymorphonuclear leukocyte (PMNL) accumulation was assessed histologically. Arachidonic, 5,8,11,14,17-eicosapentaenoic and 8,11,14-eicosatrienoic acids, but not oleic, linoleic or linolenic acids, caused a concentration-related plasma extravasation following their intra-dermal injection. The plasma extravasation induced by arachidonic acid was dependent on PMNLs. PMNL infiltration and plasma extravasation into arachidonic acid-injected skin sites was inhibited by the mixed cyclo-oxygenase-lipoxygenase inhibitor, BW755C. Arachidonic acid-induced plasma extravasation was inhibited by cyclo-oxygenase and 5-lipoxygenase inhibitors but not by the Paf antagonist, kadsurenone. The inflammation induced by arachidonic acid in the rabbit dermis may be a useful model for evaluating 5-lipoxygenase inhibitors which could be potentially useful anti-inflammatory agents for the treatment of psoriasis and other inflammatory diseases.
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PMID:The inflammatory response of rabbit skin to topical arachidonic acid and its pharmacological modulation. 309 9

Eicosanoids may play a role in the pathophysiology of common inflammatory skin diseases such as psoriasis and atopic eczema. Their involvement offers the hope for development of new antiinflammatory drugs for use in dermatopharmacology. On the other hand, new findings also suggest a tissue protective role of prostanoids in skin. In addition, physiological functions of lipoxygenase-derived eicosanoids are emerging, which may serve to maintain cutaneous integrity and restore normal skin structure after injury.
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PMID:The physiology and pathophysiology of eicosanoids in the skin. 315 88

Topical 1% indomethacin had no effect on chronic stable plaque psoriasis in an open controlled study using subjective clinical scores nor in a randomised double-blind inert base controlled study using both subjective and objective measurements of lesional response; nor did it initiate or affect the development of psoriasis after cold injury. Previous studies are reviewed and it is concluded that the evidence does not support the hypothesis which relates psoriasis to eicosanoids produced by lipoxygenase activity.
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PMID:Lack of effect of topical indomethacin on psoriasis. 331 Nov 5

Psoriatic skin lesions are characterized by elevated levels of 5- and 12-lipoxygenase products (leukotrienes B4, C4, and D4, and 12-hydroxyeicosatetraenoic acid [12-HETE]), which can stimulate epidermal proliferation and induce skin inflammation. 15-Hydroxyeicosatetraenoic acid (15-HETE) has the potential to inhibit the activity of 5- and 12-lipoxygenases. The purpose of the present study was to determine the therapeutic effect of intralesional injections of 15-HETE. 15-HETE was formed by oxidation of arachidonic acid by soybean lipoxygenase, purified by reversed-phase high-performance liquid chromatography, and identified by mass spectrometric analysis. Thirteen patients took part in the investigation. Plaques with a diameter of approximately 1 cm were injected with 0.1 ml of 10 mumol/L 15-HETE, 0.1 ml of 1 mumol/L 15-HETE, or 0.1 ml of saline weekly. After 3 weeks the effect was evaluated clinically and histologically by an observer uniformed of the treatment given. We found that plaques injected with 10 mumol/L 15-HETE had cleared completely in four patients and improved considerably in seven. In one patient minimal improvement only was seen and in one patient no change was observed. Injection of 1 mumol/L 15-HETE was without effect in 11 patients and improvement was observed in two patients. Of the plaques injected with saline, minimal improvement was observed in one patient; otherwise the plaques had not changed. Injection of 0.1 ml of 10 mumol/L 15-HEPE (identical to 15-HETE except for five double bonds instead of four) induced only minimal improvement in one of four patients. The results imply that 15-HETE by a dose-dependent and stereospecific mechanism can improve psoriasis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Improvement of psoriasis vulgaris after intralesional injections of 15-hydroxyeicosatetraenoic acid (15-HETE). 334 12

Skin biopsies and scale extracts from 22 patients with psoriasis were examined for the presence of chemotactic lipoxygenase products of arachidonate metabolism. Heat-stable leukocyte chemotactic activity in aqueous extracts of 2-mm punch biopsies from involved and uninvolved patient skin was significantly elevated, compared to healed psoriatic skin and to skin of normal controls. Ether extracts (pH 3.0) from 13 mg of psoriatic scales contained a mean chemotactic activity corresponding to that of leukotriene B4, 5 X 10(-8) M. On reverse phase high-pressure liquid chromatography, the main chemotactic lipids in scale extracts were leukotriene B4 and 5-HETE. Since lipoxygenase products are potent mediators of inflammation, they may play an important role in the evolution and maintenance of psoriatic lesions.
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PMID:Identification of chemotactic lipoxygenase products of arachidonate metabolism in psoriatic skin. 609 49

The pathophysiologic significance of increased levels of lipoxygenase compounds in psoriatic lesions was assessed in a double-blind randomized clinical study with the 5-lipoxygenase inhibitor, benoxaprofen. Forty patients with psoriasis vulgaris were treated with 600 mg of oral benoxaprofen daily or a placebo for a period of eight weeks. Benoxaprofen therapy provided excellent treatment results in about 75% of the cases. In the placebo group, only minimal improvement occurred. Most patients receiving benoxaprofen therapy reported side effects including photosensitivity, onycholysis, milia, diarrhea, and edema. In two cases, benoxaprofen was withdrawn before completion of the treatment course because of photosensitivity. Benoxaprofen may affect psoriatic epidermis either directly by the inhibition of epidermal 5-lipoxygenase or indirectly by the inhibition of the accumulation of phagocytes in psoriatic lesions. Despite serious side effects from benoxaprofen therapy, lipoxygenase-inhibiting agents deserve further study in the treatment of psoriasis.
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PMID:Benoxaprofen improves psoriasis. A double-blind study. 640 2

Arachidonic acid can be converted via the cyclo-oxygenase and lipoxygenase pathways to biologically extremely potent products. The arachidonic acid metabolites - prostaglandins, prostacyclin, thromboxane, leukotrienes and hydroxy-fatty acids - are assumed to play a major role in the pathophysiology of inflammation. The skin shows an active arachidonic acid metabolism which is believed to be involved in the pathogenesis of psoriasis and different forms of dermatitis. Research into the biochemical basis of inflammation should lead to the introduction of new, pathogenetically oriented pharmacological principles in the treatment of these dermatoses.
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PMID:[Metabolism of arachidonic acid of the skin and its significance in the pathophysiology of inflammatory dermatosis]. 643 39

Products of lipoxygenase metabolism play a role in the pathogenesis of psoriasis. Four protoberberine alkaloids, berberine, oxyberberine, jatrorrhizine, columbamine, and two aporphine alkaloids, magnoflorine, and corytuberine, isolated from Mahonia aquifolium, were tested for lipoxygenase inhibition. Oxyberberine, corytuberine, and columbamine were the most potent lipoxygenase inhibitors tested, whereas berberine and magnoflorine exhibited only low potencies. A strong linear correlation (r = 0.866) between lipoxygenase inhibition and lipid antioxidant properties of these compounds was found. These data suggest that the mechanism of lipoxygenase inhibition by these alkaloids may be linked to the inhibition of lipid hydroperoxide substrate accumulation. Inhibition of lipoxygenase by these compounds may contribute to the therapeutic effect of M. aquifolium extracts in the treatment of psoriasis.
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PMID:Lipoxygenase inhibition and antioxidant properties of protoberberine and aporphine alkaloids isolated from Mahonia aquifolium. 748 Jan 90

Previous studies from other laboratories suggest that linoleic acid and its metabolites, hydroperoxyoctadecadienoic acids, play an important role in modulating the growth of some cells. A correlation has been demonstrated between hydroperoxyoctadecadienoic acids and conditions characterized by abnormal cell growth such as atherosclerosis and psoriasis. To determine if linoleic acid and its metabolites modulate cell growth in atherosclerosis, we measured DNA synthesis, protooncogene mRNA expression, and mitogen-activated protein kinase (MAPK) activation in vascular smooth muscle cells (VSMC). Linoleic acid induces DNA synthesis, c-fos, c-jun, and c-myc mRNA expression and MAPK activation in VSMC. Furthermore, nordihydroguaiaretic acid, a potent inhibitor of the lipoxygenase system, significantly reduced the growth-response effects of linoleic acid in VSMC, suggesting that conversion of linoleic acid to hydroperoxyoctadecadienoic acids (HPODEs) is required for these effects. HPODEs also caused significant induction of DNA synthesis, protooncogene mRNA expression, and MAPK activation in growth-arrested VSMC, suggesting that linoleic acid and its metabolic products, HPODEs, are potential mitogens in VSMC, and that conditions such as oxidative stress and lipid peroxidation which provoke the production of these substances may alter VSMC growth.
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PMID:Linoleic acid and its metabolites, hydroperoxyoctadecadienoic acids, stimulate c-Fos, c-Jun, and c-Myc mRNA expression, mitogen-activated protein kinase activation, and growth in rat aortic smooth muscle cells. 763 78

The purpose of the present study was to develop an ex vivo skin model to determine the capacity of lesional skin of psoriasis to form leukotriene B4 and other eicosanoids. Keratomed skin samples were incubated in the presence of the calcium ionophore A23187 and arachidonic acid for 45 min at 37 degrees C. After extraction of lipids, eicosanoids were determined by quantitative reversed-phase high-performance liquid chromatography in combination with specific radioimmunoassays. We found that stimulation of skin samples with A23187 and arachidonic acid increased the amount of leukotriene B4 4.0-fold. The 12-lipoxygenase product, 12-hydroxy-eicosatetraenoic acid, and the 15-lipoxygenase product, 15-hydroxy-eicosatetraenoic acid, were both increased 2.7-fold. The cyclooxygenase product, prostaglandin E2, was increased 8.0-fold. Similar incubations using psoriatic scales did not result in formation of eicosanoids. Incubations with the 5-lipoxygenase inhibitor RS43179 inhibited the formation of leukotriene B4 and prostaglandin E2 without significantly affecting the formation of 12-hydroxy-eicosatetraenoic acid and 15-hydroxy-eicosatetraenoic acid. These results reveal that lesional psoriatic skin ex vivo has the enzymatic capacity to increase the levels of eicosanoids. This provides an ex vivo skin model to determine whether putative lipoxygenase inhibitors are able to modulate the formation of eicosanoids in psoriatic skin.
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PMID:Modulation of eicosanoid formation by lesional skin of psoriasis: an ex vivo skin model. 810 16


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