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Biomedical subjects

T Ruzicka

Publications and source records attributed to T Ruzicka.

At least 325 records · Page 18Linked to original sources
PubMed1989

Cytochrome P-450-dependent omega-oxidation of leukotriene B4 in rodent and human epidermis.

Leukotriene B4 (LTB4,5-12-dihydroxy 6,8,10,14-eicosatetraenoic acid), an enzyme-catalyzed oxidation product of arachidonic acid, is a major inflammatory mediator. Human polymorphonuclear leukocytes and rodent hepatic microsomes catabolize LTB4 to 20-OH-LTB4 and 20-COOH-LTB4, which is mediated by a cytochrome P-450 catalyzed reaction termed the LTB4 omega-hydroxylase. In this study we investigated the catabolism of LTB4 in rat, guinea pig, and human epidermis. The incubation of 3H-LTB4 (9 microM) for 60 min in the presence of oxygen, NADPH, and epidermal microsomes prepared from neonatal fat (3.0 mg) or adult guinea pig (2.6 mg) resulted in the formation of 20-OH-LTB4 and 20-COOH-LTB4. Metabolite identification was based on co-chromatography on high pressure liquid chromatography with highly purified reference standards. The formation of 20-OH-LTB4 and 20-COOH-LTB4 was accompanied by the disappearance of LTB4. The rate of formation of 20-OH-LTB4 was 9-12-fold higher than that of 20-COOH-LTB4. Product formation was negligible with boiled microsomes, required NADPH and oxygen, was linear with respect to incubation time and protein, and was maximal at pH 7.4. LTB4-omega-hydroxylase activity was inhibited (greater than 90%) by carbon monoxide or 2-diethylaminoethyl-2,2-diphenylvalerate hydrochloride (SKF-525A) (1 mM), whereas alpha-naphthoflavone produced only moderate (13%) or no effects. Topical application of 3-methylcholanthrene and other conventional inducers of epidermal monooxygenase activities to neonatal rats (100 mg/kg, single treatment) did not result in an increase in epidermal LTB4-omega-hydroxylase activity. The addition of 3H-LTB4 (30 nmoles) to primary human keratinocytes followed by incubation at 37 degrees C resulted in time-dependent disappearance of LTB4 and appearance of 20-OH-LTB4 and 20-COOH-LTB4 in the medium. These results suggest that LTB4 is catabolized by the cytochrome P-450-dependent enzyme system in rodent and human skin and that this may participate in modulating the effects of this proinflammatory lipid in this tissue.

Animals↗
PubMed1989

Preventive effect of an E. coli-filtrate (Colibiogen) in polymorphous light eruption.

During the administration of Colibiogen, a commercially available E. coli-filtrate, there was a significant (P less than 0.01) increase of the test dose of UVA necessary to elicit skin lesions in nine patients with polymorphous light eruptions. Control tests performed in the same manner without the drug indicate that this was due to treatment. Colibiogen appears to be of value in the treatment of polymorphous light eruption (PLE).

Adult↗
PubMed1989

Leukotriene B4 receptors on neutrophils in patients with psoriasis and atopic eczema.

Polymorphonuclear leukocyte (PMNL) infiltration is an important characteristic in psoriatic lesions. Elevated concentrations of the chemoattractant eicosanoid leukotriene B4 (LTB4) are present in psoriatic skin. Its chemotactic activity is mediated via high affinity receptors on PMNL. The goal of our work was to ascertain whether PMNL infiltration in psoriasis can be accounted for by functional abnormalities of the circulating PMNL due to alterations in the LTB4 receptor density or affinity (or both). No significant difference was found between patients with psoriasis, healthy controls and patients with another inflammatory dermatosis (atopic eczema) with regard to the binding parameters of LTB4 receptors on PMNL. Our findings suggest that PMNL accumulation in psoriatic skin may be the result of an excess of cutaneous chemoattractant rather than the increased readiness of psoriatic PMNL to migrate towards LTB4 due to altered LTB4 receptor density or affinity.

Adolescent↗
PubMed1989

Leukotrienes in atopic eczema.

Involved skin in atopic eczema contains elevated levels of the 5-lipoxygenase metabolite of arachidonic acid, leukotriene B4. In addition, leukocytes of atopic eczema patients produce increased amounts of eicosanoids upon immunological challenge. These facts and the biological effects of eicosanoids suggest their involvement in the pathogenesis of cutaneous inflammation in atopic eczema, and may provide a new target for pharmacological treatment of this disease.

Dermatitis, Atopic↗
PubMed1988

Hemorrhagic bullous amyloidosis. A histologic, immunocytochemical, and ultrastructural study of two patients.

In patients with bullous hemorrhagic amyloidosis of the skin, the skin lesions were the first manifestations of a plasma cell dyscrasia. Both cases were characterized by similar clinical, histologic, and ultrastructural findings showing an intradermal blister within deposits of amyloid substances. Immunohistologic investigations with a panel of antibodies directed against amyloid fibril proteins showed reactivity of the amyloid deposits with an anti-A lambda serum in both patients.

Aged↗
PubMed1988

Evidence for LTB4/12-HETE binding sites in a human epidermal cell line.

We identified leukotriene B4 (LTB4)/12-hydroxyeicosatetraenoic acid (12-HETE) binding sites in a squamous cell cancer-derived human epidermal cell line. Analysis of the binding data revealed a single class of binding sites with a dissociation constant of 0.16 microM and a Bmax of 3.8 x 10(6) sites per cell. Competitive binding assays with various eicosanoids at 37 degrees C showed nearly equal binding of 12(S)-HETE, 12(R)-HETE and LTB4. 5(S)-HETE and LTB4-analogs bound with lesser affinity. Specific LTB4 binding at 37 degrees C could also be demonstrated in freshly isolated normal human keratinocytes. Since lipoxygenase-derived eicosanoids are thought to play an important role in hyperproliferative and inflammatory skin diseases, the identification of LTB4/12-HETE binding sites in keratinocytes could have implications for the development of new drugs controlling these disease processes.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1988

Eicosanoid release in polymorphous light eruption: selective UV-A-induced LTB4 generation by peripheral blood leukocytes.

The biochemical basis of ultraviolet-induced cutaneous inflammation in polymorphous light eruption (PLE) is not known. We investigated the potential role of eicosanoids--derivatives of arachidonic acid--as mediators of inflammation in this common disorder. 13 patients were investigated, in whom skin lesions could be experimentally reproduced by repeated UV-A but not UV-B irradiation. Peripheral blood leukocytes of these patients were irradiated with UV-A or UV-B, and the release of leukotriene B4 (LTB4), LTC4 and prostaglandin E2 (PGE2) was measured. Cells from PLE patients, but not healthy controls, released selectively high amounts of LTB4 in response to UV-A. The UV-A-induced LTB4 release was light-dose-dependent. This phenomenon was not observed with UV-B. The selective UV-A-induced release of LTB4 could play a major role in the pathophysiology of cutaneous inflammation in PLE.

Adult↗
PubMed1988

Polymorphous light eruption: eliciting and inhibiting wavelengths.

In 38 patients with polymorphous light eruption (PLE) photoprovocation tests were performed by applying 100 J/cm2 of UV-A to the extensor side of the upper arm on three consecutive days. Test sites were divided into four areas by covering the patients' skin with Schott glass filters WG 320, WG 335, WG 360, and GG 385 (or GG 395). In 17 patients typical skin lesions could be provoked in at least one test field. 10 patients reacted either at all test sites or at shorter wavelengths (simultaneously higher doses) only. In the remaining 7 patients test reactions did not occur underneath filters with lower cut-off points, whereas skin lesions were induced by radiation deprived of the shorter wavelengths passing through these filters. This observation suggests an inhibitory effect of shorter wavelengths in these cases.

Humans↗
PubMed1988

Antiallergic effects of the new histamine H1-receptor antagonist tazifylline in healthy atopic and non-atopic subjects.

Single oral doses (5, 10 and 15 mg) of the new H1-receptor antagonist 3,7-dihydro-7-[2-hydroxy-3-[4-[3-phenylthio) propyl]-1-piperazinyl]propyl-1,3-dimethyl-1H-purine-2,6-dione dihydrochloride (tazifylline, RS-49014) were administered at 7-day intervals to 12 atopic and 12 non-atopic volunteers in a double-blind randomised cross-over study. Antiallergic activity was evaluated from pre to 60 min post dose inhibitions of wheal and flare areas provoked by various cutaneous challenges. Atopic subjects showed greater skin reactivity than non-atopics to some challenges. Tazifylline was associated (in atopics and non-atopics) with statistically significant dose related inhibitions, of flare over 5-15 mg and of wheal (10-15 mg) induced by the more potent and reproducible challenges of codeine, 1% histamine and anti-IgE. Antiallergic activity of tazifylline in the 10-15 mg dose range was superior to 5 mg without the intervention of clinically significant sedative effects at any of the 3 dose levels tested.

Adult↗
PubMed1988

Efficiency of acitretin in the treatment of cutaneous lupus erythematosus.

Acitretin (etretin [Ro-10-1670]) is the major metabolite of etretinate with a much shorter elimination half-life. The drug was used in the treatment of 20 patients who had cutaneous lupus erythematosus. All patients responded to treatment, but in five, the result was unsatisfactory. In 15 patients, an excellent (total clearing) or good response (marked reduction of all lesions) was seen. In seven of them, acitretin was superior to previous therapy with antimalarials and/or systemic corticosteroids. In particular, five of six patients with subacute cutaneous lupus erythematosus showed complete clearing of their lesions, usually within two to four weeks. Side effects were the same as with etretinate. It is concluded that acitretin is a highly effective and well-tolerated drug in the treatment of cutaneous lupus erythematosus.

Acitretin↗
PubMed1988

The physiology and pathophysiology of eicosanoids in the skin.

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.

Animals↗
PubMed1988

[Steatocystoma multiplex conglobatum].

Two patients are described in whom steatocystoma multiplex conglobatum presented as recurrent axillary abscesses. This disease entity is rare and can easily be confused with hidradenitis suppurativa or acne conglobata.

Abscess↗
PubMed1987

[Subacute cutaneous lupus erythematosus: clinical aspects, immunology and therapy].

Subacute cutaneous lupus erythematosus (SCLE) is a distinct subset of cutaneous lupus erythematosus which is defined by clinical and immunological characteristics. With regard to clinical expression and prognosis, SCLE assumes an intermediate position within the spectrum of LE between purely cutaneous discoid and systemic lupus erythematosus. The main clinical characteristics of SCLE are extensive papulosquamous or anular lesions and photosensitivity. The disease is frequently associated with Sjögren's syndrome and systemic symptoms, mainly arthralgia. Renal involvement is, however, rare. Circulating Ro-antibodies represent the main autoimmune phenomenon. An immunogenetic disposition to develop SCLE is evidenced by the detection of the HLA-B8, DR3-phenotype in a large proportion of patients. Drug therapy comprises primarily glucocorticosteroids and antimalarials, but retinoids have recently also proved highly effective.

Adolescent↗
PubMed1987

[Allergy to local anesthetics].

Patch testing with the local anaesthetics benzocaine and caine mix frequently yields positive reactions. Their relevance with regard to local anaesthesia is not clear. We therefore performed prick and intracutaneous tests with a battery of local anaesthetics in a group on 104 patients with known contact allergic reactions to these substances. Prick testing always yielded negative results. Intracutaneous testing showed also only rare positive immediate and delayed hypersensitivity reactions. In addition, a clear correlation was seen between the sensitizing potential and chemical structure of the local anaesthetics. Substances with amide structure never showed, with the exception of butanilicaine, any positive reaction in contrast to procaine exhibiting an ester structure. From our results, it can be concluded that contact allergic patients can be subjected to injection local anaesthesia without a significant risk of allergic reaction. In addition, the results show the importance of the route of administration for the manifestation of an allergic reaction.

Anesthetics, Local↗
PubMed1987

Arachidonic acid metabolism in guinea pig Langerhans cells: studies on cyclooxygenase and lipoxygenase pathways.

Epidermal Langerhans cells are macrophage-like la+ leukocytes that are critically involved in cutaneous immune reactions. Because macrophages exert their immunoregulatory activity in part by generation of oxygenated arachidonic acid metabolites, we systematically studied arachidonic acid transformations by purified guinea pig Langerhans cells and compared them with mixed epidermal cells and Langerhans cell-depleted keratinocytes. Products formed from arachidonic acid by cell homogenates were measured after thin-layer or reverse-phase high-pressure liquid chromatographic separation. In addition, leukotriene B4 and C4 formation was assessed in supernatants of Ca ionophore A23187-challenged intact cells by radioimmunoassay. Mixed epidermal cells converted arachidonic acid predominantly via cyclooxygenase and 12-lipoxygenase pathways. The main products were prostaglandin D2 (PGD2) and 12-hydroxyeicosatetraenoic acid (12-Hete), although significant amounts of PGE2, PGF2 alpha, and 6-keto-PGF1 alpha were formed as well. PGD2 synthesis was dependent on the presence of reduced glutathione. The product spectrum formed by Langerhans cell-depleted keratinocytes was virtually indistinguishable from mixed epidermal cells. In contrast, Langerhans cells showed a markedly different metabolism of arachidonic acid. They exhibited an exceedingly high PGD2-generating capacity, whereas only minor amounts of 12-HETE and very low amounts of other prostaglandins were synthesized. The PGD2/12-HETE ratio was 1.22 for mixed epidermal cells and 4.37 for Langerhans cells. Leukotriene production from exogenous or endogenous arachidonic acid could not be demonstrated by either radioenzymatic or radioimmunologic detection methods. We conclude that guinea pig Langerhans cells transform arachidonic acid predominantly to PGD2, which might mediate significant immunoregulatory, inflammatory, and antitumoral activity in the skin.

Animals↗
PubMed1987

Allergy to local anesthetics: comparison of patch test with prick and intradermal test results.

The interrelation between immediate and delayed hypersensitivity reactions to local anesthetics is poorly understood. Especially, the relevance of positive patch test reactions to local anesthetics with regard to the compatibility of injected local anesthetics is unclear. We therefore subjected 104 patch test-positive probands to prick and intradermal tests with seven local anesthetic agents. All prick tests were negative. Only 14 patients showed positive reactions in intradermal tests: 11 with the ester local anesthetic procaine, one with the amide local anesthetic butanilicaine, and two with both. Procaine yielded both immediate and delayed reactions; butanilicaine, only immediate reactions. All other local anesthetics showed negative reactions. It is concluded that in patients with positive patch test reactions to local anesthetics and negative history of anaphylactoid reactions, positive skin test reactions to intradermal application are rare and that, therefore, the risk of anaphylactic reactions to injection anesthesia with amide local anesthetics, except butanilicaine, appears low in these patients.

Adult↗