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Biomedical subjects

H Bisgaard

Publications and source records attributed to H Bisgaard.

34 records · Page 2Linked to original sources
PubMed1987

Nebulization and selective deposition of LTD4 in human lungs.

The process of nebulization and deposition of LTD4 was studied in detail. The concentration of LTD4 in a saline solution decreased by approximately 90% after 2 min of nebulization in a DeVilbiss 35B ultrasonic nebulizer. This decrease was prevented by diluting LTD4 in a phosphate buffer, pH 7.4. Nebulization of tritiated LTD4 in this phosphate buffer did not cause any appreciable deterioration of the leukotriene, as demonstrated by an unchanged ratio between radioactivity and LTD4 concentration in the test solution before and after nebulization as well as in the condensed aerosol. The aerosol generated by the DeVilbiss 35B ultrasonic nebulizer was shown to generate particles with a mass median diameter of 1.3 microns (dry particle size). Interposition of a settling bag reduced the amount of large particles, reducing the mass median diameter to 0.84 microns (dry particle size). Nine healthy volunteers were challenged on separate days with 40 nmol LTD4 or 100 mumol histamine, and the changes in FEV1 and partial flow volume curves initiated at 50% of vital capacity (Vmax30) were measured. A relative diffuse deposition pattern was ensured by inhalation via a settling bag. These results were compared to challenges with a relatively central deposition pattern as ensured by inhalation directly from the nebulizer with brisk inhalation maneuvers. The diffuse deposition pattern caused minimal changes in FEV1 but pronounced effect in Vmax30. The effects of LTD4 and histamine on FEV1 and Vmax30 changed in parallel when the deposition of the mediators was changed to a more central pattern. This indicates that the two mediators do not differ with respect to any selective effects on different parts of the airways.

Adult↗
PubMed1987

Risk factors for wheezing during infancy. A study of 5,953 infants.

Risk factors for the development of wheezing during infancy were studied in 5,953 children. The data for the study were collected from a large prospective investigation of children born in 1959-61, who had attended a one-year follow-up examination. Wheezing was diagnosed when the symptom had been observed at least once during the first year of life, not in conjunction with pneumonia, epiglottitis or acute laryngitis. Logit analysis was used for the purpose of assessing the causal effect of environmental and other factors on the risk of wheezing among infants. The assessment of a risk factor by means of regression technique, requires certain other variables to be included in the regression model. A general rule concerning inclusion of other variables has been formulated and applied to the above data. The study demonstrated that the risk of wheezing was affected by a number of factors--particularly environmental. Poor social environment increases the risk of wheezing, as does the mother's smoking, and placement of the baby in day-care. Boys experienced wheezing more often than girls. Premature infants are more liable to develop wheezing than mature children. Remarkably, children born in the period April through September develop wheezing, but not bronchitis, more often than children born in October through March.

Birth Weight↗
PubMed1987

Effect of N-acetylcysteine on the human nasal ciliary activity in vitro.

N-acetylcysteine (NAC) is widely used as a mucolytic agent, but the clinical and pharmacological effects of NAC are still unclear. It has recently been claimed in animal studies that NAC will stimulate ciliary beating frequency at low concentrations, while inhibiting beating at higher concentrations. Using a microphoto-oscillographic method combined with microperfusion technique, we studied the direct effect of NAC on human nasal cilia. NAC caused a direct dose- and time-related decrease in ciliary beating frequency, which was detectable at 2 mg/ml and reached statistically significant levels at 20 mg/ml. NAC at 200 mg/ml caused total cessation of movements within 15 s but this effect was completely reversible within 15 min of perfusion with medium alone. At no concentrations of NAC was beating frequency increased over base-line. NAC, however, had no effect on beating pattern. NAC seems to have a selective and fully reversible inhibitory effect on the beating frequency of human cilia in vitro.

Acetylcysteine↗
PubMed1986

A new technique for ranking vascular corticosteroid effects in humans using laser-Doppler velocimetry.

By combining laser-Doppler velocimetry with reactive hyperemia, induced by arterial occlusion of 4-min duration we have established a simple and atraumatic new ranking technique for assessing steroid potency. The experiments were performed in 19 healthy volunteers. Budesonide (Preferid) and placebo (vehicle) were applied under occlusion on the flexor aspect of the forearm for 2, 24, and 48 h. Blood flow was measured with a laser-Doppler flowmeter before and after arterial occlusion with a blood pressure cuff on the upper arm. The induced reactive hyperemia reaction was measured planimetrically on the registered curves. The steroid preparation caused a significant reduction of the hyperemia closely related to the application time. The reduction of the hyperemia was confirmed using the atraumatic 133Xe washout technique. In another group, hydrocortisone, hydrocortisone-butyrate (Locoid), budesonide (Preferid), and klobetasol (Dermovat) applied under occlusion for 1 h were compared. A significant dose-response relation corresponding to the expected rank-order efficacy was revealed. In 10 experiments, pretreatment with 50 mg indomethacin i.v. resulted in a significant reduction of the hyperemia reaction. As a hypothesis we therefore suggest that the reactive hyperemia reaction amplifies the vascular events and unmasks steroid-induced inhibition of the synthesis of arachidonic acid metabolites.

Adrenal Cortex Hormones↗
PubMed1986

Effect of leukotriene D4 on nasal mucosal blood flow, nasal airway resistance and nasal secretion in humans.

The possible role of leukotriene D4 (LTD4) in nasal allergy was investigated in healthy volunteers. Nasal blood flow, nasal airway resistance, nasal discharge and nasal itching and sneezing were examined. LTD4 was found to induce a dose-response related increase in nasal mucosal blood flow as measured by laser-Doppler flowmetry. Histamine exhibited similar effects on blood flow in the same concentration range. Nasal airway resistance as recorded by rhinomanometry, increased in a dose-related manner after topical LTD4. Nasal secretion was obtained by nasal lavage and estimated from a dilution principle. Topical LTD4 did not increase the amount of nasal secretion, whereas a dose-related increase was found after topical histamine. LTD4 did not cause itching, sneezing or other irritative symptoms. In conclusion, LTD4 may play a role in nasal allergy by increasing blood flow and nasal airway resistance. Itching, sneezing and discharge, however, are apparently not caused by LTD4 but can be accounted for by the release of histamine or other mediators.

Administration, Topical↗
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

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↗