Biomedical subjects

H Bisgaard

Publications and source records attributed to H Bisgaard.

At least 109 records · Page 6Linked to original sources

PubMed1986

Chemotactic activity of LTB4 in man.

An improved skin window chamber technique has been developed and used for a quantitative study of the chemotactic effect of leukotriene B4 (LTB4). LTB4 (0.5 microM) was exposed to a skin window on the forearm of eight healthy volunteers, while phosphate buffered saline served as control in a skin window on the other forearm. Skin window exudates and samples of blood draining the skin window areas were collected after 1, 2, 4, 8, and 24 h. The samples were quantitated for the different types of leukocytes as well as the intra- and extracellular concentration of the eosinophilic cationic protein and lactoferrin as markers of eosinophil and neutrophil granulocytes. A significantly increased migration of neutrophil granulocytes into the skin window chamber containing LTB4 was found from the 2nd to the 8th hour after the initial LTB4 exposure. The eosinophils reached a significant peak at the 4th hour. The rise in the actual number of eosinophil cells did not reach significance, whereas measurements of the eosinophilic cationic protein in the cellular fraction of the exudate exhibited a significant increase as a reflection of the number of eosinophils. This highlights the potential clinical value of eosinophilic cationic protein measurements to reveal eosinophilia instead of the traditional eosinophil counts. Extracellular eosinophilic cationic protein and lactoferrin did not change significantly in the LTB4-exposed skin window, implying that LTB4 does not activate the eosinophils and neutrophils to exocytosis of their enzymes. The present in vivo results support the concept of LTB4 being a potent chemoattractant to neutrophil and less so to eosinophil granulocytes in humans, a chemoattractant that recruits the leukocytes but does not seem to activate them.

Adult↗

PubMed1986

New parameters for evaluation of blood flow in patients with leg ulcers.

Three new parameters have been introduced to provide data for quantitative evaluation of peripheral cutaneous blood flow in patients with leg ulcers. Reactive hyperemia was induced by occlusion of the blood flow for four minutes at the thigh-level. Blood flow was subsequently measured by laser-Doppler velocimetry in an unselected group of 14 patients with leg ulcers and a matched control group. The parameters used for evaluation was: 1) "peak flow" f(p), 2) divided by time to "peak flow" t(p), rendering a rate constant k (k = f(p)/t(p)) expressing the ability to increase blood flow abruptly in case of need. These parameters were all significantly reduced in the patients with leg ulcers, indicating that this simple and atraumatic technique was useful for discriminating blood flow values that may be relevant for healing time and with a sensitivity comparable to the measurements of distal systolic blood pressure. Distal systolic blood pressure measurements can still be considered to be of value when screening for arterial insufficiency in patients with leg ulcers. The values obtained were significantly lower in 36 patients with leg ulcers compared with 9 age-matched control persons.

Adult↗

PubMed1985

Bronchial hyperreactivity to leucotriene D4 and histamine in exogenous asthma.

Reactivity of the small and large airways to inhaled leucotriene D4, one of the leucotrienes that constitute slow reacting substance of anaphylaxis, was studied in eight patients with exogenous asthma and nine healthy subjects with no history of atopy. Non-cumulative dose response relations were constructed for leucotriene D4 in a randomised, double blind set up. Reactivity to the leucotriene was compared with reactivity to histamine in the two groups. Both groups reacted to leucotriene D4 with significant airway obstruction evident in forced expiratory volume in one second (FEV1), peak expiratory flow rate, maximal expiratory flow rate at 30% of forced vital capacity estimated from a partial flow volume curve initiated at 50% of vital capacity (V30), and an increase in volume of trapped gas. The airways of the patients were significantly (p less than 0.01) more reactive to leucotriene D4 than those of the controls. The differences were in order of magnitude, 10(2)-10(3) for FEV1 but only about 15 for V30 (p less than 0.05). The hyperreactivity of the airways of the asthmatic subjects to leucotriene D4 was comparable to that to histamine. Inhalation of leucotriene D4 caused pronounced dyspnoea only among the patients. The findings suggest a role for leucotriene D4 in human bronchial asthma.

Adolescent↗

PubMed1985

Leukotriene B4 produces hyperalgesia in humans.

During inflammation, pain receptors are sensitized by inflammatory mediators causing hyperalgesia. Leukotriene B4 (LTB4) is a potent chemoattractant for polymorphonuclear leukocytes in humans in vivo. In the present study we have demonstrated a reduction of the pain threshold in humans after intracutaneous deposition of LTB4. The pain threshold was quantitated by the "Marstock" method in which the testsubject reversed the direction of the temperature change of a thermostimulator whenever a painful temperature was reached. This enabled a quantitative description of the persons pain sensibility. After intracutaneous infiltration of LTB4 (10 microM) a highly significant decrease in the pain threshold could be detected as compared to control with a maximum effect between 6 and 24 h. The decrease in the pain threshold amounted to less than 15% when compared to control and corresponds with the published kinetics of the influx of polymorphonuclear leukocytes. These results support the hypothesis that LTB4 produces hyperalgesia indirectly through recruitment of polymorphonuclear leukocytes and not via a direct effect on the pain receptors. Inhibition of the lipoxygenase might be an advantageous adjunct to the effect of the Non Steroidal Anti-Inflammatory Drugs.

Humans↗

PubMed1985

Effects of synthetic leukotriene D-4 on the local regulation of blood flow in human subcutaneous tissue.

Prostaglandin E-1 and E-2 acts as vasodilators partly through inhibition of sympathetic nerves and partly through a direct action on smooth muscle. To elucidate the mechanisms of LTD-4 induced vasodilation, the vascular smooth muscle dependent auto-regulation of blood flow and the sympathetic reflex mechanism of the "vasoconstrictor reflex" was investigated in humans. Blood flow was measured in subcutaneous tissue after injection of 133-Xenon 1) alone, 2) mixed with lidocaine 20 mg/ml for sympathetic blockade, 3) mixed with PGE-2 0.1 ug/ml and 4) mixed with LTD-4 in concentrations of 5 and 20 microM. Blood flow was kept constant during elevation by 20 cm above heart level (preserved autoregulation) except after injection of PGE-2 and LTD-4 20 microM where a significant decrease was observed (defective smooth muscle function). During lowering by 45 cm, a decrease in blood flow by 50% was observed in experiment 1. This response was blocked by lidocaine and PGE-2, partially blocked by LTD-4 20 microM but unaffected by LTD 5 microM. LTD-4 affects vascular smooth muscle function but does not affect sympathetic reflexes in concentrations which does not have a direct smooth muscle action.

Adult↗

PubMed1985

Leukotriene- and histamine-induced increases in vascular permeability and interstitial transport in the skin.

The aim of the present study was to investigate the edema induced by leukotriene D4 (LTD4). Edema is the gross effect of increased blood flow and capillary permeability. Our objective was to elucidate the effect of LTD4 on edema generation without the influence of the concomitantly increased blood flow induced by this potent vasodilator. A new method was outlined measuring the exudation through skin windows of a macromolecular tracer [( 131I]albumin) and a micromolecular tracer [( 99Tc]pertechnetat). Exudation of [131I]albumin is a function of enhanced vascular permeability and interstitial transport and blood flow, whereas that of [99Tc] pertechnetat is mainly a function of blood flow. Thus a ratio of the 2 exudate measurements gives a specific estimate of the changes in vascular permeability and interstitial transport. Histamine was employed to establish the method. A dose-response relation was found for histamine in the dose range of 10(-4) to 10(-7) M. The effect of 10(-5) M LTD4 on vascular permeability and interstitial transport of macromolecules was indistinguishable from that of histamine in the same concentration. This property together with their well-known vasodilatory capabilities indicate that the leukotrienes of the slow-reacting substance of anaphylaxis may play a role in the vascular changes in the allergic-inflammatory reaction.

Adult↗

PubMed1985

Production of leukotrienes in human skin and conjunctival mucosa after specific allergen challenge.

The production of leukotrienes has been monitored in tear fluids from subjects following a conjunctival provocation test, and skin blister fluids following initiation of a Prausnitz-Kustner reaction. In tear fluids elevated levels of leukotriene C4 (LTC4)-immunoreactive material were measured following allergen challenge as compared to control tear fluid obtained by mechanical or reflex stimulation. Analysis by high performance liquid chromatography indicated the presence of LTC4, LTD4 and LTE4. In the skin, significantly elevated levels of LTC4-immunoreactive material were measured following allergen challenge in the Prausnitz-Kustner reaction. HPLC analysis indicated the presence of both LTC4 and LTD4. LTB4 immunoreactive material was detected both in the tear fluid and the skin tissue fluid. However, no significant increase occurred in either tissue after the allergic reactions. These results indicate that the SRS-A leukotrienes are released in vivo in man following allergen challenge, and indicate these mediators may be important in human allergic diseases.

Adolescent↗

PubMed1985

Eicosanoids in skin UV inflammation.

Several studies have implicated the eicosanoids as mediator substances in different types of UV inflammation. In human UV erythema, various arachidonic acid metabolites--mainly cyclooxygenase products--have been detected, particularly in skin exudates. The concentration and the sequence of release of the various eicosanoids vary in relation to the time course and the various types of UV-induced erythema. UVB, UVC but not UVA erythema at its maximum was only to some extent inhibited by indomethacin despite almost complete inhibition of the synthesis of prostaglandins E2 and F2 alpha. A major issue cannot, as yet, be answered satisfactorily: are one or a number of eicosanoids per se causing the erythema or are they only passive bystanders released by damage to cellular structures? Until further evidence has been provided, the causative role of E and F prostaglandins in relation to development of UV erythema is doubtful. By contrast, PGI2 is a more likely candidate in this respect, being synthesized and released close to the events occurring in the vessel walls. The lipoxygenase pathway is still too unexplored for proper evaluation with regard to a role in the pathogenesis, but the pharmacological properties of leukotrienes and hydroxy-fatty acids may qualify them as potential candidates alone or in a concert of mediator events occurring during the developments of UV inflammation.

Animals↗

PubMed1984

Leukotriene D4 increases nasal blood flow in humans.

The effect of leukotriene D4 on the nasal mucosal blood flow in humans was measured using a laser doppler flow meter. The leukotriene solution was applied topically to the nasal mucosa in 9 healthy subjects, and changes in blood flow were measured non-traumatically by the laser doppler instrument. The response showed a consistent increase in blood flow. A dose-response was found in the range of 0.063 - 4.0 nanomole. These results confirm an earlier study on the human skin, implicating leukotriene D4 as an important vasodilator in humans. No increase in nasal secretion was noted by the subjects tested.

Administration, Topical↗

PubMed1984

Detection of leukotriene C4-liked immunoreactivity in tear fluid from subjects challenged with specific allergen.

Tear fluid was obtained from allergic subjects from control eyes and eyes challenged with specific allergen and levels of leukotriene C4 (LTC4)-immunoreactivity determined by radioimmunoassay. Formal identification of the leukotrienes released was not possible but the levels of LTC4-immunoreactive material in allergen-challenged tear fluid (4.9 +/- 2.3 ng/ml, n = 9) were significantly higher (p less than 0.01) than those in control tear fluid (0.07 +/- 0.06 ng/ml, n = 9). These results provide evidence that leukotrienes, which account for the biological activity of slow reacting substance of anaphylaxis, may be released in allergic reactions in vivo in man.

Adult↗

PubMed1984

Quantitation of microcirculatory blood flow changes in human cutaneous tissue induced by inflammatory mediators.

The cutaneous microcirculation is a desirable model for pharmacologic and physiologic studies of inflammatory mediators. For exact measurements of the induced blood flow changes, two objective methods are introduced. The laser-Doppler flowmeter and the 133Xe washout technique have formerly been used for measurement of the undisturbed cutaneous blood flow. We have modified these methods to measure changes in the blood flow following intracutaneous deposition of a vasodilator, leukotriene D4. When compared with a metric estimate of the erythemal response, the two new methods were found to be more sensitive than the traditional estimate of cutaneous blood flow changes. Both methods exhibited a good sensitivity and reproducibility when applied simultaneously, although the 133Xe washout technique appeared to be able to separate interindividual differences that could not be recognized by the laser-Doppler technique. Even though the laser-Doppler technique is superior in simplicity of use, the 133Xe washout technique is recommended for exact measurements.

Adult↗

PubMed1984

A clinical comparison of aerosol and powder administration of beclomethasone dipropionate in childhood asthma.

Forty children with childhood asthma were conducted through a double-blind cross-over study to compare the effect of 400 micrograms beclomethasone dipropionate administered as aerosol and powder (Rotacaps). Children with severe asthma derived more benefit from the steroid administered as aerosol judged from their peak flow performance in the morning, although neither evening peak flow nor symptom scores revealed any difference. It is concluded that the Rotacaps are an advantageous supplement to available medication for the treatment of asthmatic children, although it should be observed that, using equal amounts of BDP, powder administration seems less effective than aerosol.

Adolescent↗

PubMed1984

Leukotrienes and prostaglandins in asthma.

Leukotrienes and prostaglandins possess properties which are central in the asthmatic reaction. They are bronchoconstrictors, they inhibit the mucociliary clearance, increase blood flow and permeability and thereby induce edema formation, and they attract and activate leukocytes. They are formed partly by allergic reactions and partly by a large number of other more non-specific reactions. Finally, the concentration of prostanoids has been found increased in the asthmatic reaction in vivo. The leukotrienes have not been traced in vivo in asthmatic attacks so far, but have been found in vivo in man in a specific type I allergic conjunctival reaction. Much evidence suggests that these mediators are relevant in asthmatic diseases, even though prostaglandin inhibitors have no effect in asthma. There still remains the need to investigate the influence on asthmatic diseases by as yet unavailable leukotriene blocking agents. Even though leukotrienes are judged today to be important mediators in asthma, it does not seem reasonable to expect that a single mediator is responsible for asthmatic diseases. Rather, it seems quite likely that asthma is caused by a complex interplay of a large number of mediators, circulating hormones, nervous mechanisms, receptor abnormalities, intracellular metabolic defects, etc. Despite this complexity, investigations in recent years have increased the knowledge of the biochemistry and human physiological effects of leukotrienes and prostaglandins which has created an improved understanding of the asthmatic reaction's pathophysiology, contributed a pharmacological rationale for previously used therapy, and stimulated new perspectives for specific pharmacological research.

Anti-Inflammatory Agents↗

PubMed1984

Effects of leukotrienes on neutrophil migration, and on production and action of lymphokines.

The effect of the leukotrienes LTB4, LTC4 and LTD4 on the production of the lymphokine leukocyte migration inhibitory factor (LIF) from human peripheral blood mononuclear cells was tested. LTC4 and LTD4 failed to influence LIF production by cells stimulated by antigen or the polyclonal T cell activator, phytohemagglutinin (PHA). LTB4, at concentrations 10(-7) to 10(-6) M, showed significant inhibition of antigen-induced LIF production but was without effect when cells were stimulated by PHA. The cell levels of cyclic adenosine monophosphate (cAMP) were unaffected by 2.5 X 10(-7) M LTB4 in the absence or presence of theophylline. These results indicate that LTB4 acts on the early effector stage of the immune response without affecting the cellular cAMP content.

Antibody Formation↗

PubMed1984

Human leukocyte cyclic AMP and cyclic GMP levels during chemotaxis in delayed type hypersensitivity.

Ten nickel-allergic patients and six healthy control subjects participated in a study of the morphology, kinetics and evolution of the cAMP and cGMP concentrations of migrated leukocytes, using an improved skin chamber technique. Also studied was the effect of nickel exposure in the chamber medium during development of an eczematous reaction in the nickel-allergic patients. Nickel exposure had a specific effect on the morphology, from the 24th hour to the end of the 48 h observation period, with a significant increase in the percentages of basophils, eosinophils and lymphocytes and a decrease of neutrophils. A significantly increased leukocyte migration rate (LMR) was observed from the 27th to 39th hour in six of the allergic patients exposed to nickel. There were no specific permanent changes in cAMP and cGMP concentrations during nickel exposure. The control chambers of the allergic patients and healthy controls had identical leukocyte morphology, LMR and leukocyte concentrations of cAMP and cGMP. However, no correlations were found between LMR, cAMP and cGMP in the eczema patients throughout the observation period.

Adult↗

PubMed1984

The possible role of LTD4 in asthma in humans investigated in vivo.

The bronchoconstrictor effect of LTD4 was tested in a double blind design in 9 healthy volunteers who inhaled 10 and 40 nmol synthetic LTD4, 10 and 100 mumol histamine, and placebo on 5 different days. As the nebulized testsolutions were administered via a settling bag, an even deposition on the airways could be expected, and consequently a relative predominans of the changes measuring the airflow in the small airways. Accordingly the PEF values were reduced by less than 5% for both active substances. The function of the small airways was measured by (1) the volume of trapped gas in percentage of the total lung capacity, and (2) maximal expiratory flow rate at 30% of vital capacity above residual volume, determined from partial flow-volume curves. A dose-dependent bronchial obstruction was revealed. LTD4 was 3 to 4 decades more potent than histamine on a log molar scale. Pronounced dyspnoea and systemic side effects were experienced after inhalation of histamine whereas LTD4 did not cause any symptoms. Adrenergic beta 2-agonist (Fenoterol) was in all cases capable of reversing the LTD4 induced bronchospasm. 6 patients with verified exogenous asthma were tested in a similar double blind set-up for their reactivity to LTD4. The asthmatics were hyperreactive to LTD4.

Adolescent↗

PubMed1983

The effect of leukotrienes C4 and D4 on microcirculatory flow in humans.

By quantifying the flare response, leukotrienes LTC4 and LTD4 were shown to increase the microcirculatory flow in a sigmoidal dose-response relation over the dose-range of 6.25-800 pmol. LTD4 was found to be more potent than LTC4 after 5 min, but not after 15 min, as estimated by this method. Laser-Doppler flowmeter studies confirmed that LTD4 is a more potent vasodilator than LTC4.

Blood Flow Velocity↗

PubMed1983

Leukotriene D4 induces bronchoconstriction in man.

The effect of leukotriene D4 (LTD4) on lung function was investigated in a controlled study on four normal subjects. A pronounced decrease in airflow was found after inhalation of less than 0.5 nmol, and was most pronounced in the variables generally accepted as indicators of the function of the small airways. No subjective symptoms were experienced.

Asthma↗