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Biomedical subjects

T Herlin

Publications and source records attributed to T Herlin.

At least 55 records · Page 3Linked to original sources
PubMed1988

In vitro inhibition of leukotriene B4 formation by exogeneous 5-lipoxygenase inhibitors is associated with enhanced generation of 15-hydroxy-eicosatetraenoic acid (15-HETE) by human neutrophils.

Leukotrienes, products of the 5-lipoxygenase pathway of arachidonic acid metabolism, have been suggested to play a pathogenic role in psoriasis, because of their ability to induce skin inflammation and to stimulate epidermal proliferation. The 15-lipoxygenase product 15-hydroxy-eicosatetraenoic acid (15-HETE) has no proinflammatory capacity. In contrast, it can inhibit the activity of the 5-lipoxygenase. The purpose of the present study was to study the effect of 5-lipoxygenase inhibitors on the formation of 15-HETE by human neutrophils in vitro. Purified neutrophils were incubated with A 23187 (5 microM) and arachidonic acid (25 microM) with and without different inhibitors of 5-lipoxygenase activity (RS 43179, benoxaprofen, NDGA, and CP 66248). Methods for identifying eicosanoids included RP-HPLC and radioimmunoassay. Formation of leukotriene B4 was inhibited in a dose-dependent way, which was strongly correlated with a concomitant increase in the formation of 15-HETE (r = 0.97, p less than 0.01). The cyclooxygenase inhibitor indomethacin did not change 15-HETE formation. The stimulation of 15-HETE formation was not associated with cell damage as assessed by LDH release. Furthermore, identical incubations of T lymphocytes, characterized by a low 5-lipoxygenase activity, did not result in increased 15-HETE formation. These results show that inhibition of 5-lipoxygenase activity can lead to increased formation of 15-HETE. Because 15-HETE inhibits formation of 5-LO products, it may amplify the effect of 5-lipoxygenase inhibitors.

Arachidonate Lipoxygenases↗
PubMed1988

Improvement of psoriasis vulgaris after intralesional injections of 15-hydroxyeicosatetraenoic acid (15-HETE).

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)

Dose-Response Relationship, Drug↗
PubMed1988

Lipoxygenase products in experimental septic arthritis in dogs.

Induction of an experimental septic arthritis was performed in the juvenile dog knee by an intra-articular injection with Staphylococcus aureus. From plasma, lipoxygenase (LO) products of arachidonic acid were separated by reversed-phase high-performance liquid chromatography (RP-HPLC) after extraction of lipids. The plasma samples did not contain UV-detectable amounts of LO products other than the LTB4 metabolite 20-COOH-LTB4, and 12-HETE. Small amounts of chemokinetically active material were found coeluting with the eluate fraction of 20-COOH-LTB4, LTB4 and 12-HETE after RP-HPLC. After 48 hours of septic arthritis, resulting in a massive acute joint inflammation, no significant changes in LO products were observed.

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

Changes in lipoxygenase products from synovial fluid in carrageenan induced arthritis in dogs.

A non-suppurative chronic arthritis was induced in the juvenile dog knee by intra-articular instillations with Carrageenan. Lipoxygenase products of arachidonic acid were separated from synovial fluid by reversed-phase high-performance liquid chromatography (RP-HPLC). After ten weeks we observed an accumulation of leukotriene B4 (LTB4) in synovial fluid in five out of six experimental knees (0.94 to 5.5 ng/ml), as judged by integrated optical density. Biological activity of LTB4 was confirmed by chemokinesis. LTB4 was not detected in control knees. The 15-lipoxygenase products, 15-hydroxyeicosatetraenoic acid (15-HETE) and 13-hydroxy-9,11-octadecadienoic acid (13-HODD), being inhibitors of 5-lipoxygenase, were found in relatively high levels in the control knees compared to the arthritic knees. The results denote LTB4 as a pro-inflammatory local mediator during carrageenan-induced arthritis; possibly, the decreased levels of 15-HETE and 13-HODD in the arthritic knees may have a regulatory function, thus facilitating LTB4 generation.

Animals↗
PubMed1987

Heterogeneous distribution of lipoxygenase products in psoriatic skin lesions.

Several biologically active lipoxygenase products or arachidonic acid (AA) have been demonstrated in psoriatic skin lesions. The purpose of the present study was to determine the amounts of the different lipoxygenase products simultaneously in psoriatic skin. Slices of psoriatic skin were obtained at different levels with a keratome. Extracted lipids were identified by high performance liquid chromatography, UV-absorption spectrum, radioimmunoassay, and chemokinesis. Leukotriene B4 (LTB4), and 12- and 15-hydroxy-eicosatetraenoic acid (HETE) were detected in most psoriatic lesions. However, there was a remarkable variation from lesion to lesion. The biopsy specimens contained: 276.2 +/- 126.0 pg/g wet tissue of LTB4, 3,130.0 +/- 2,898.0 ng/g wet tissue of 12-HETE, and 3,633.0 +/- 1,692.0 ng/g wet tissue of 15-HETE. No correlation was found between the levels of the different lipoxygenase products. The content of each of the identified lipoxygenase products was higher in the superficial part of the biopsy specimen consisting of approximately two-thirds of the epidermis plus papillary dermis than in the lower part consisting of approximately one-third of the epidermis plus some reticular dermis. Also, there was a great variation from one anatomical region to another within the same patient. Because these lipoxygenase products possess different biological activities, the variation in their occurrence may be important for understanding their potential role in psoriasis. To determine which lipoxygenase products may be of pathogenic importance, analysis of early psoriatic lesions is warranted.

Humans↗
PubMed1987

Human monocyte and polymorphonuclear leukocyte chemotactic and chemokinetic responses to leukotriene B4 and FMLP.

Comparable investigations of the chemotactic and chemokinetic responses of purified monocytes (MO) and polymorphonuclear leukocytes (PMN) to leukotriene B4 (LTB4) and N-formyl-methionyl-leucyl-phenylalanine (FMLP) were made in this study. Using a sensitive and objective 51Cr-chemotactic assay, it was shown that both MO and PMN showed a bell-shaped response to LTB4 and FMLP, with a maximum response at 10(-8)M for both drugs. For PMN, the maximal response elicited by LTB4 was similar in magnitude to that produced by FMLP, whereas the MO chemotaxis induced by 10(-8)M FMLP was significantly higher than the response evoked by 10(-8)M LTB4. For both cell types, LTB4 at low concentrations (less than 10(-9)M) gave rise to higher chemotactic responses than FMLP. Chemokinesis was differentiated from chemotaxis, using a checkerboard system. At concentrations less than 10(-9)M the LTB4-evoked contribution of chemokinesis to the total migrational response was significantly higher than the chemokinetic contribution of FMLP. Preincubation with LTB4 produced only homologous chemotactic deactivation to subsequent LTB4 stimulation, whereas preincubation with FMLP resulted in diminished secondary response to both FMLP and LTB4. The degree of deactivation was dependent upon the dose of attractant used, with a LTB4 concentration of 10(-7)M leading to about 40% and 25% deactivation of PMN and MO, respectively. Preincubation with 10(-7)M FMLP led to about 50% and 32% suppression of the subsequent chemotactic response of PMN and MO, respectively.

Adult↗
PubMed1987

Chemotactic leukotriene B4 activity in plasma from children with arthritis.

Plasma from seventeen children with arthritis was investigated for the content of lipoxygenase products. Two of the patients had untreated juvenile chronic arthritis, three had a pyogenic joint infection, four had Henoch-Schonlein purpura and eight had reactive arthropathy. After lipid extraction, the lipoxygenase products were identified by high-performance liquid chromatography (HPLC). Chemotactic material coeluting with leukotriene B4 (LTB4) was found in plasma from the arthritis patients. Enhanced chemotactic activity of this compound was found in juvenile chronic arthritis and pyogenic arthritis patients, compared to the chemotactic activity in plasma from patients with Henoch-Schonlein purpura and reactive arthropathy. The findings may indicate that activation of lipoxygenases may play a role during the initiation of the inflammatory reaction in arthritis.

Adolescent↗
PubMed1987

Unusual immunophenotype displayed by histiocytes in haemophagocytic lymphohistiocystosis.

Extensive immunophenotypic studies in a 2 1/2 month old girl with haemophagocytic lymphohistiocytosis were performed to characterise the proliferating histiocytes of the disease. The cells strongly expressed conventional macrophage antigens, but unexpectedly, there was a dissociated expression of the CD1a antigen (reacting with the monoclonal antibody NA1/34 but not with OKT6) and intracellular S-100 protein by the haemophagocytic lymphohistiocytosis histiocytes. These findings indicate that there is a "hybrid" phenotype between the two main arms of the mononuclear phagocyte system--namely, Langerhans' cells and phagocytic macrophages.

Antibodies, Monoclonal↗
PubMed1986

Chemotactic lipoxygenase products in sera from patients with psoriasis.

Sera obtained from 12 patients with moderate to severe psoriasis were investigated for the presence of arachidonate lipoxygenase metabolites using reverse-phase high-performance liquid chromatography after extraction on silicic acid columns. Peaks which co-chromatographed with standards of synthetic leukotriene B4 (LTB4) were collected, and the material was tested for chemotactic activity. In the sera of 5 of the patients, chemotactic activity was demonstrable in these 'LTB4' peaks. Although minor peaks co-chromatographing with LTB4 were found in control sera, none of them contained chemotactic material. Isolated monocytes from the psoriasis patients showed enhanced chemotactic activity as compared to monocytes obtained from healthy controls. The results of our study support the view that abnormal 5-lipoxygenase activity is present in psoriasis. Further investigation is required to determine whether LTB4 is released from circulatory leukocytes or the skin.

Adult↗
PubMed1986

Defective monocyte and polymorphonuclear leukocyte chemotaxis and clinical characteristics in atopic dermatitis.

Using highly purified cell suspensions, monocyte (MO) and polymorphonuclear leukocyte (PMN) chemotaxis was measured by the 51Cr-labeled cells technique in 30 adult patients with atopic dermatitis (AD). MO chemotaxis was depressed in 60% of the patients; in one-third both MO and PMN chemotaxis was impaired. All patients with normal MO chemotaxis had normal PMN chemotaxis. The defective chemotaxis was related to the presence of cutaneous infection and to the activity of the disease. Cutaneous infection was observed in 70% of the patients with low MO and PMN chemotaxis. We found no relation between the chemotaxis defects and serum IgE levels. Presence of asthma in addition to AD did not influence the results. Preincubation of normal leukocytes with AD plasma did not alter the chemotactic responses. Plasma from atopics had a lower capacity for inducing migration than normal plasma using leukocytes from healthy subjects as test cells.

Adult↗
PubMed1986

Benoxaprofen in treatment of systemic sclerosis.

Ten patients with systemic sclerosis were treated with benoxaprofen, a potent lipoxygenase inhibitor, for a period of 6 months. In an attempt to evaluate the efficacy a number of physical disease parameters were followed during the trial. None of these parameters revealed any significant differences. There was, however, a trend for a change towards normalisation of a defect monocyte chemotaxis. In view of the slow and progressive nature of systemic sclerosis the present study leaves undetermined whether benoxaprofen exerts a beneficial effect on systemic sclerosis.

Adult↗
PubMed1985

Comparison of oxatomide and clemastine in the treatment of chronic urticaria. A double blind study.

A double-blind trial comparing a new antihistaminic agent (oxatomide) with clemastine was carried out in 30 patients with chronic urticaria. The study included over-all clinical assessment by patient and clinician as well as determination of excretion of 1,4-methylimidazoleacetic acid determined by a reversed-phase ion-pair high-performance liquid chromatographic method. It was found that the effect of oxatomide was equal to that of clemastine.

Adolescent↗