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Biomedical subjects

K Kragballe

Publications and source records attributed to K Kragballe.

At least 109 records · Page 6Linked to original sources
PubMed1991

A hydrocolloid occlusive dressing plus triamcinolone acetonide cream is superior to clobetasol cream in palmo-plantar pustulosis.

The purpose of this study was to compare the therapeutic efficacy of a hydrocolloid dressing (Actiderm) over a medium strength corticosteroid (triamcinolone acetonide (TAA) 0.1% cream) with that of a highly potent corticosteroid (clobetasol propionate 0.05% cream) in palmo-plantar pustulosis and localized pustular psoriasis. It was a randomized, open, prospective, right-left comparative trial in 19 patients. The Actiderm dressing and the TAA cream were applied every third day, whereas the clobetasol cream was applied twice daily for 4 weeks. Both treatments resulted in a significant improvement. On completion of treatment, complete clearance was found in 13 patients (63%) with Actiderm plus TAA, but in only 3 patients (21%) with clobetasol (p = 0.001). Four weeks after stopping therapy, the clinical parameters had returned to their pre-treatment level, except for erythema on the Actiderm plus TAA treated lesions (p less than 0.05). No clinically important adverse effects were reported or observed; in particular there was no sign of skin atrophy at the end of study. The results of this study demonstrate that Actiderm applied over a medium strength corticosteroid every third day is highly effective against palmoplantar pustulosis and localized pustular psoriasis. However, it is necessary to develop treatment regimens to maintain the improvement achieved.

Adolescent↗
PubMed1990

[Polyunsaturated fatty acid preparations available on the Danish market. Composition and oxidative stability].

The emerging interest in essential polyunsaturated fatty acids has resulted in a number of products available in the Danish market. These products contain essential fatty acid oils rich in n-6 and n-3 fatty acids. The quality of these products plays a major role in planning prophylactic and clinical studies. This investigation therefore illustrates the quality and the contents of undesirable oxygenated compounds--peroxides and polymeric/oxidative components. Intake of these undesirable substances can theoretically contribute to the development of cancer. It is therefore of utmost importance to be aware of the quality of the product especially when relatively large doses are employed for a considerable period. Our results show that the oxidation values of the fish oil products are much higher than vegetable oils. Furthermore we observed higher amounts of polymerised/oxidised components in Pikasol although the peroxide value was relatively low. Okholm's fish oil and cod liver oil contain higher amounts of undesirable gadoleic and cetoleic acids. A quality control from the authorities is desirable as the consumer has only the producer's/importer's "assurances" to rely on and these are not always in accordance with the real facts.

Denmark↗
PubMed1990

Interaction of etretinate with methotrexate pharmacokinetics in psoriatic patients.

Combined treatment of psoriasis with methotrexate and etretinate may be associated with hepatoxicity. This study investigated the potential effects of steady state etretinate administration on methotrexate pharmacokinetics in six psoriatic patients. When compared with a matched group a significantly higher mean value for the maximum plasma concentration Cmax (992 nmol/L +/- 94 SE vs 721 nmol/L +/- 35 SE) for methotrexate was found (P less than .05) after intramuscular administration of 0.2 mg/kg body weight of the drug. In accordance with this finding mean values of the time (tmax) to reach Cmax, half-life of the absorption (t1/2ka) and the apparent volume of distribution at steady state Vss were also lower than in the control groups but did not deviate significantly. Total clearance differed very little and insignificantly between the two groups. Absorption and disposition rates of etretinate during combined treatment with methotrexate were not significantly altered compared with previous results in psoriatic patients only receiving etretinate. Overall, these results indicate that the apparently increased risk for developing hepatotoxic reactions during coadministration of methotrexate and etretinate cannot be explained by drug accumulation due to pharmacokinetic interaction. A possible influence on potential hepatotoxicity of an increase of Cmax for methotrexate cannot be excluded.

Drug Interactions↗
PubMed1990

Calcipotriol (MC 903), a novel vitamin D3 analogue stimulates terminal differentiation and inhibits proliferation of cultured human keratinocytes.

The hormonally active form of vitamin D3, 1,25-dihydroxy vitamin D3 [1,25-(OH)2-D3; calcitriol], regulates the differentiation and proliferation of epidermal keratinocytes in vitro. MC 903 (calcipotriol) is a novel vitamin D3 analogue which is at least 100 times less potent than 1,25-(OH)-2-D3 in its effects on calcium homeostasis. The present study compared the effects of MC 903 and 1,25-(OH)2-D3 on terminal differentiation and proliferation of cultured normal human keratinocytes. Keratinocytes were grown in McCoy's 5A medium supplemented with penicillin (50 IU/ml), streptomycin (50 micrograms/ml), L-serine (4 X 10(-4) M), and 10% human type AB serum. MC 903, 1,25-(OH)2-D3 or 1 alpha-OH-D3 (10(-12) M--10(-8) M) was added with each feeding when cultures became preconfluent. After incubation for 24 h with D3 vitamins, cultures were extracted for transglutaminase, and the enzyme activity was indexed against DNA content. The activity of transglutaminase, the enzyme responsible for cross-linking the proteins of the cornified envelope, was maximally stimulated by 388% with MC 903 (10(-8) M), by 328% with 1,25-(OH)2-D3 (10(-8) M), and by 27% with 1 alpha-OH-D3 (10(-8) M) compared with vehicle. After incubation for 2 weeks the number of keratinocytes with cornified envelopes had increased by 288% with MC 903 (10(-8) M), by 360% with 1,25-(OH)2-D3 (10(-8) M), and by 149% with 1 alpha-OH-D3 (10(-8) M) compared with vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcitriol↗
PubMed1990

Proliferation of adherent synovial fluid cell cultures is modified by eicosanoids.

Synovial fluid cells obtained from a carrageenan-induced chronic arthritis in the juvenile dog knee were allowed to adhere and proliferate in culture flasks. After twelve days secondary cultures were made and either 10(-8)M leukotriene B4 (LTB4), 25 microM 15-hydroxy-eicosatetraenoic acid (15-HETE), or both, were added and the cells were cultured for another 6 days. LTB4 is generated via the 5-lipoxygenase pathway of arachidonic acid metabolism and stimulates a number of phagocyte functions. Compared to control cells LTB4 increased proliferation in 9 out of 10 cell cultures (p less than 0.05). The 15-lipoxygenase product, 15-HETE, is not proinflammatory and is an endogenous inhibitor of 5-lipoxygenase. Addition of 15-HETE decreased proliferation of cell cultures by 23% (p less than 0.01). It is speculated that LTB4 in addition to its effect on phagocytes may play a role in synovial hyperproliferation observed in arthritis.

Animals↗
PubMed1990

Combination of topical calcipotriol (MC 903) and UVB radiation for psoriasis vulgaris.

The synthetic compound MC 903 (calcipotriol) is a structural analogue of the naturally occurring, biologically active 1,25-dihydroxyvitamin D3 [1,25-(OH)2-D3]. MC 903 and 1,25-(OH)2-D3 show similar receptor binding and comparable effects on cell differentiation. However, MC 903 appears to be at least 100 times less potent in its effects on calcium metabolism. In previous double-blind placebo-controlled studies, topical MC 903 has been shown to have a therapeutic effect in psoriasis. The present open study involving 20 patients with psoriasis vulgaris was a right/left comparison of the efficacy and tolerability of MC 903 ointment (50 micrograms/g) alone or with UVB radiation. After treatment for 8 weeks, topical MC 903 alone resulted in marked improvement in 66% of the patients and in clearance in 17%. Combination of topical MC 903 with UVB resulted in marked improvement in 50% of the patients and in clearance in 39%. These differences were not statistically significant. No significant change in serum calcium levels was detected. Two patients developed a facial dermatitis which disappeared spontaneously during continued treatment. These results show that the combination of topical MC 903 and UVB radiation is well tolerated. Larger-scale studies are warranted to answer the question whether UVB radiation induces a significant improvement of the antipsoriatic effect of topical MC 903.

Adult↗
PubMed1990

Synovitis reduced by inhibition of leukotriene B4. Carrageenan-induced gonarthritis studied in dogs.

The pathophysiologic significance of leukotriene B4 (LTB4) in arthritis was studied in dogs by unilateral intraarticular deposition of 15-hydroxy-eicosatetraenoic acid (15-HETE), an endogenous inhibitor of the formation and the effects of LTB4, in bilateral carrageenan-induced gonarthritis. LTB4 in synovial fluid was selectively inhibited in 15-HETE treated joints, the formation of prostaglandin E2 (PGE2) being largely unaffected. The clinical symptoms, intraarticular pressure, and extractable synovial fluid volume were reduced in treated joints. No effect could be discerned regarding blood flow in the synovial membrane, capsule, or juxta-articular bone as measured by tracer microspheres; and no effect on bone metabolism was found as judged by 99mTc-diphosphonate uptake. Thus, inhibition of LTB4 reduces joint exudation, but does not seem to interfere with changes in juxta-articular hemodynamics or bone metabolism following synovial inflammation.

Animals↗
PubMed1990

Twenty-nail dystrophy treated with topical PUVA.

A case of twenty-nail dystrophy treated with topical PUVA is described. The patient, a 19-year-old woman, had a 4-year history of a nail dystrophy involving all finger- and toe-nails. The finger-nail changes were treated with topical PUVA, dose 0.7-1.4 J/cm2 x 3/week. After 7 months excellent improvement was seen, while the untreated toe-nails were unaffected. A maintenance dose of 0.7 J/cm2 x 3/week was necessary to prevent recurrence. We suggest that topical PUVA is worth trying for the treatment of twenty-nail dystrophy.

Adult↗
PubMed1989

15-hydroxyeicosatetraenoic acid (15-HETE) specifically inhibits the LTB4-induced skin response.

15-Hydroxyeicosatetraenoic acid (15-HETE), a 15-lipoxygenase product of arachidonic acid, inhibits leukotriene B4 (LTB4)-induced chemotaxis of polymorphonuclear leukocytes (PMNs) in vitro. In this study the effects of intradermal injections of LTB4 were determined in the absence or presence of 15-HETE. For comparison intradermal injections of purified human complement split product C5a were performed in the absence or presence of 15-HETE. The skin response was evaluated by measuring the diameter of the wheal, the area of the flare and by intensity of the erythema (erythema index). LTB4 and C5a were injected at the concentration of 200 ng/ml. At this concentration the maximal skin response of LTB4 and C5a were equivalent. In contrast to C5a reaction, which resolved within 1 h, LTB4-induced skin response lasted up to 18 h. In all subjects the skin response was significantly decreased when LTB4 was injected together with 300 ng of 15-HETE. The decrease of wheal, flare, and erythema index averaged 81.9%, 56.6%, 53.6%, respectively, when all parameters were obtained at the maximal skin response. In contrast, the C5a-induced skin response was not affected by addition of 15-HETE, even when the final dose of 15-HETE was increased 10 times to 3 micrograms. The LTB4-induced reaction could last up to 18 h after injection. After the addition of 300 ng of 15-HETE the skin response resolved after 1 h. The present results demonstrate that 15-HETE is a specific inhibitor of the LTB4-induced skin response and brings additional evidence in support of the ability of 15-HETE to regulate the proinflammatory effects of LTB4 in vivo.

Adult↗
PubMed1989

Effect of auranofin on eicosanoids and protein kinase C in human neutrophils.

Auranofin (AF), a lipophilic chrysotherapeutic agent, was investigated for its effect on the formation of lipoxygenase products and the activity of protein kinase C in human neutrophils. We have previously shown that inhibition of LTB4 formation by 5-lipoxygenase (5-LO) inhibitors is intimately associated with a marked increased in 15-HETE in excess of arachidonic acid. The calcium- and phospholipid-dependent protein kinase, protein kinase C, is activated in FMLP- and A23187-stimulated neutrophils, is hypothesized to stimulate superoxide generation, and plays an essential role in eicosanoid production. AF dose-dependently inhibited the generation of leukotriene B4(LTB4) in FMLP-stimulated neutrophils, the ID50 was approximately 4.5 micrograms/ml. Unlike known 5-LO inhibitors, AF did not enhance the production of 15-HETE. In neutrophils stimulated with the calcium ionophore, A23187, AF did not inhibit the generation of LTB4 nor did AF change the 15-HETE levels. AF inhibited superoxide generation in FMLP-stimulated neutrophils dose-dependently, but did not change the activation of protein kinase C in the cells. We therefore conclude, that AF inhibition of LTB4 production in neutrophils is different from 5-lipoxygenase inhibitors and is elicited at a step distal to protein kinase C activation.

Auranofin↗
PubMed1989

15-Hydroxy-eicosatetraenoic acid (15-HETE) inhibits carrageenan-induced experimental arthritis and reduces synovial fluid leukotriene B4 (LTB4).

15-Hydroxy-eicosatetraenoic acid (15-HETE), a product of arachidonic acid, has no proinflammatory capacity, but can inhibit the formation and the chemotactic response of neutrophils to leukotriene B4 (LTB4), a potent mediator of inflammation. The purpose of the present study was to determine whether intraarticular administration of 15-HETE in carrageenan-induced acute arthritis might decrease the levels of LTB4 in synovial fluid and modify the arthritis. A bilateral acute knee joint arthritis was established in 7 dogs by intraarticular injections of carrageenan every third day. To the right joints, 15-HETE was administered both concomitantly with the carrageenan injections and continuously via an osmotic pump. In samples of synovial fluid obtained on day 0, 3 and 10 PGE2 and LTB4 were determined using reversed phase high performance liquid chromatography combined with radioimmunoassays and neutrophil chemokinesis. In the presence of 15-HETE the clinical severity of arthritis was significantly reduced and the volume of synovial effusate was decreased on an average by 42%. Furthermore, the relative number of neutrophils in histological sections of synovial tissue was decreased by 58%. Intraarticular caragheenan injections induced LTB4 formation, and maximum levels were obtained on day 3 (279.2 +/- 148.2 pg/joint). PGE2 was also present on day 3, but maximum levels were detected on day 10 (9.5 +/- 4.8 ng/joint). In joints injected with both carragheenan and 15-HETE the levels of LTB4 on days 3 and 10 were inhibited by 90% and 83%, respectively. For PGE2 a small but insignificant decrease was found on both day 3 and on day 10. These results show that LTB4 may be an important mediator of acute arthritis induced by carragheenan in dogs, and that intraarticular administration of 15-HETE can modify this arthritis by inhibiting LTB4 formation.

Animals↗
PubMed1989

Eicosanoids in skin of patients with atopic dermatitis: prostaglandin E2 and leukotriene B4 are present in biologically active concentrations.

The biochemical events leading to atopic dermatitis (AD) are unknown. Certain eicosanoids derived from arachidonic acid are potent mediators of skin inflammation and modulators of certain T-lymphocyte activities. The purpose of the present study was to determine whether eicosanoids are present in biologically active concentrations in the skin of adult patients with AD. The levels of the cyclooxygenase product, prostaglandin E2 (PGE2) and the lipoxygenase products, leukotriene B4 (LTB4), 12- and 15-hydroxyeicosatetraenoic acid were determined in biopsy specimens obtained by keratome from lesional, perilesional, and clinically unaffected skin of patients with AD. Methods for identification of eicosanoids included reversed-phase high-performance liquid chromatography combined with radioimmunoassays. Eicosanoid levels were at the same level in normal skin and in uninvolved skin of AD. Compared with uninvolved skin, both lesional and perilesional skin contained markedly elevated concentrations of PGE2 and LTB4: PGE2, 97.2 +/- 15.6 ng/gm of lesional skin and 128.3 +/- 27.2 ng/gm of perilesional skin; LTB4, 5.2 +/- 1.6 ng/gm of lesional skin and 3.2 +/- 0.6 ng/gm of perilesional skin. Compared with uninvolved skin, the levels of 12- and 15-hydroxyeicosatetraenoic acid were elevated sevenfold and elevenfold, respectively, in lesional skin, but did not reach biologically active concentrations. The results demonstrate that the inflammatory mediators PGE2 and LTB4 are present in lesional skin of atopic subjects in biologically active concentrations. Because these mediators are able to induce cutaneous inflammation and to modulate cellular immunity, they may be involved in the biochemical processes leading to AD.

Adolescent↗
PubMed1989

Eicosanoids in acute and chronic psoriatic lesions: leukotriene B4, but not 12-hydroxy-eicosatetraenoic acid, is present in biologically active amounts in acute guttate lesions.

The biochemical changes underlying the clinical manifestations of psoriasis are unknown. Certain chemotactic eicosanoids derived from arachidonic acid metabolism have been suggested to play important roles in psoriasis, because of their presence in lesional psoriatic skin and their ability to elicit skin inflammation and to stimulate epidermal proliferation. The purpose of the present study was to elucidate which eicosanoids might be involved in the early phases of the inflammatory processes of psoriasis. Eicosanoids were analyzed in scale and in lesional skin without scale both in acute guttate and chronic plaque psoriatic lesions. Methods for identification of eicosanoids included reversed-phase high-performance liquid chromatography combined with radioimmunoassay. Leukotriene B4 was present in both acute guttate and chronic plaque skin lesions in biologically active amounts (acute guttate lesions: 18.7 +/- 7.1 ng/g wet tissue in scale and 3.2 +/- 1.5 ng/g wet tissue in lesional skin without scale; chronic plaque lesions: 33.1 +/- 9.7 ng/g wet tissue in scale and 5.3 +/- 2.0 ng/g wet tissue in lesional skin without scale). 12- and 15-hydroxy-eicosatetraenoic acid (HETE) reached biologically active concentrations only in scale of chronic plaque lesions (1,512 +/- 282 and 1,441 +/- 411 ng/g wet tissue, respectively). The level of prostaglandin E2 in chronic plaque lesions was similar to the level in normal skin, while the level in acute guttate lesions was increased twofold (71.0 +/- 14.8 ng/g wet tissue). These results demonstrate that leukotriene B4, but not 12-HETE, is present in acute guttate psoriatic skin lesions in concentrations able to exert biologic effects. Leukotriene B4 may therefore participate in inflammatory changes of acute psoriasis.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗