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Biomedical subjects

R Brattsand

Publications and source records attributed to R Brattsand.

At least 37 records · Page 2Linked to original sources
PubMed1994

Seasonal variation in the function of blood monocytes obtained from healthy nonsmokers, asymptomatic smokers, and smokers with chronic bronchitis.

The present study focused on two questions: What effects do cigarette smoking and chronic bronchitis have on the function of the precursors of alveolar macrophages, the blood monocytes? Can seasonal variations affect the function of these cells? Phagocytic activity (the proportion of yeast-ingesting cells and the mean number of yeast particles per ingesting cell) and metabolism of arachidonic acid [secretion of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) in zymosan-stimulated cultures] were studied as markers of monocyte function during three seasons: spring (May-June), autumn (November-December), and winter (February). Smokers with chronic bronchitis (SCBs) and asymptomatic smokers (ASs) had a lower proportion (p < 0.05) of ingesting monocytes than healthy nonsmokers (HNSs) during spring, but not during the other two seasons. The secretion of PGE2 was highest during autumn and lowest during spring in the monocytes of all three groups. In autumn, LTB4 secretion was increased in the monocytes of HNSs (p < 0.05) but not in those of ASs and SCBs. LTB4 secretion was similar in all groups during the other two seasons. Cigarette smoking and chronic bronchitis seem to impair the function of monocytes and may thereby affect the systemic host defense activity. Cells collected during autumn were generally more active than those sampled in spring, indicating marked seasonal variation in the function of monocytes from all three groups.

Arachidonic Acid↗
PubMed1994

Diaryl tellurides as inhibitors of lipid peroxidation in biological and chemical systems.

Diaryl tellurides carrying electron-donating substituents in the para positions were found to efficiently inhibit peroxidation of rat hepatocytes, rat liver microsomes and a chlorobenzene solution of phosphatidylcholine. The most active compound in the microsomal assay, bis(4-dimethylaminophenyl) telluride, showed an IC50-value of 30 nM. This compound also caused a dose-dependent delay of the onset of the linear phase of microsomal peroxidation stimulated by iron/ADP/ascorbate. The peak oxidation potentials of the diaryl tellurides (0.50-1.14 V in MeCN) correlated linearly with the IC50-values in this assay, with a point of inflection around 0.85 V. In the hepatocyte system, all compounds showed similar protective activity. It is proposed that diaryl tellurides exert an antioxidative effect by deactivating both peroxides and peroxyl radicals under the formation of telluroxides. These oxides may regenerate the active divalent organotellurides upon exposure to a suitable reducing agent.

Animals↗
PubMed1994

Experimental granulomatous alveolitis in rat. Effect of antigen manipulation, smoke exposure and route of administration.

When Sephadex beads (0.45mg/kg b.w) are instilled intratracheally into rats, a granulomatous alveolitis with giant cell formation and fibrosis occurs. Moreover, the events in the alveolar region are paralleled by an eosinophil-dominated peribronchitis/bronchiolitis and perivasculitis. Bronchoalveolar lavage (BAL) shows a very distinct feature with an early pronounced neutrophil increase, followed by an increase of eosinophils and lymphocytes. BAL findings returned to normal after 1-2 weeks, but tissue morphology showed persistent inflammation with large numbers of eosinophils and to a lesser degree mononuclear cells, peribronchially and perivascularly several weeks after the instillation. Fragmentation of the Sephadex beads by ultrasonication dramatically diminished the response, giving a transient neutrophil alveolitis, without eosinophils and with no granuloma formation. On the other hand, when the Sephadex dose was divided into three, given 10 days apart, a more pronounced fibrosing activity occurred, with mast cells appearing in the collagen rich granulomas. Finally, smoke exposure had a significant suppressive effect upon the response. The numbers of cells in the interstitium as well as in the peribronchial and perivascular tissue were markedly decreased in the smoke exposed group compared to the controls. This decrease was mainly due to decreased numbers of mononuclear cells, while the numbers of eosinophils remained unchanged.

Animals↗
PubMed1993

Airway inflammation in smokers with nonobstructive and obstructive chronic bronchitis.

To assess the manifestation and location of airway inflammation in smokers with chronic bronchitis (CB) or chronic obstructive pulmonary disease (COPD), we lavaged the airways of 12 smokers with CB and 11 smokers with COPD and coexisting CB (OCB). For comparison, the airways of 5 asymptomatic smokers (AS) and 10 healthy nonsmokers (HNS) were lavaged. In all cases, the first lavage aliquot, labeled "bronchial lavage" (BL), was processed separately from the four subsequent aliquots, which were combined and labeled "bronchoalveolar lavage" (BAL). The composition of BL and BAL fluids indicate an ongoing inflammatory process in the airways of all three groups of smokers. CB patients with obstruction had significantly lower concentrations of inflammatory cells in the BL and BAL fluids compared with subjects with nonobstructed CB. Furthermore, airway obstruction, indicated by a reduced FEV1, was significantly correlated with the concentrations of glutathione (p < 0.001), myeloperoxidase (MPO; p < 0.01), and eosinophil cationic protein (ECP; p < 0.01) in BAL fluids. Taken together, these findings suggest that the manifestations of inflammation present in the airways of smokers with CB are different in those who have developed obstruction compared with those who have not.

Adult↗
PubMed1992

Alpha-(phenylselenenyl)acetophenone derivatives with glutathione peroxidase-like activity. A comparison with ebselen.

Here we describe a new class of organoselenium compounds possessing glutathione peroxidase-like activity. The parent compound, alpha-(phenylselenenyl)acetophenone (PSAP), increased the rate of reaction of glutathione with H2O2, tert-butylhydroperoxide, cumene hydroperoxide, linoleic acid hydroperoxide and dilinoleyl lecithin hydroperoxide by 7.0, 25.1, 34.1, 19.1 and 8.4-fold, respectively, as assessed by the oxidized glutathione (GSSG) reductase enzyme assay. Direct assay of the removal of hydrogen peroxide and glutathione from reaction mixtures confirmed the peroxidase-like activities of these selenoorganic compounds, but indicate that the conventional coupled GSSG reductase assay may be unsuitable for the assessment of the catalytic capacity of PSAP and Ebselen. One possible mechanism of catalysis by PSAP involves an initial oxidation at selenium. Thiol may then react with the selenoxide to yield a selenium (II) compound, H2O and a disulfide. Compounds derived from PSAP may provide potential selenium-based anti-inflammatory agents.

Acetophenones↗
PubMed1991

Cytotoxicity of human phagocytes studied in vitro in a novel model based on neutral red absorbtion.

The aim of these investigations was to establish a model for the study of neutrophil (NEU) and monocyte (MO) mediated cytotoxicity (TOX), and to study the protective actions of model protease inhibitor, peroxide scavengers and glucocorticoids in this model. Confluent human fibroblasts were used as target cells (T) and NEU and MO were used as effector cells (E), ratio E/T was 5-10:1. After triggering E with PMA (16-48 nM) for about 24 hours, remaining viable T were detected by incorporation of Neutral Red (NR). Oxidant-induced TOX was performed with H2O2 and t-BuOOH. In contrast to MO TOX, NEU TOX was inhibited by antiprotease and scavengers. On the other hand, MO TOX was inhibited by glucocorticosteroids. This indicates different TOX mechanisms by NEU and MO.

Absorption↗
PubMed1991

Attenuation of bradykinin-induced mucosal inflammation by topical budesonide in rat trachea.

The extravasation of plasma proteins and formation of interendothelial gaps in submucosal microvessels by mucosally-applied bradykinin (BK), were studied in the rat trachea. The effects of topical and systemic (s.c.) glucocorticoid budesonide (BUD) were investigated in the presence or absence of inhibitors of BK-degradtive enzymes (captopril and thiorphan 10 microM to inhibit angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP), respectively). Inhibition of these enzymes markedly increased the inflammatory responses to BK. Topical BUD (3 microM, 10 min contact, 90 min before BK) significantly decreased the volume of plasma in the tracheal lumen, both in the absence and presence of the enzyme inhibitors. Thus, the main anti-transudation mechanism of topical BUD is not related to modulation of BK-breakdown. However, this may be the mechanism for systemic BUD. Neither topical nor systemic BUD prevented interendothelial gap formation.

Administration, Topical↗
PubMed1991

Native fluorescence of extravasated proteins. A new method for quantitation of macromolecular vascular leakage.

Macromolecular vascular leakage into rat tracheal lumen is quantified by a new method that does not require the administration of an exogenous macromolecular tracer or dye to the animals. The magnitude of vascular leakage is determined by the concentration of extravasated plasma proteins measured by their native fluorescence and assayed against diluted plasma. Native fluorescence of proteins (PNF), when excited at 295 nm and measured at 340 nm, is almost exclusively due to tryptophan fluorescence. The PNF assay can be used in the range of protein concentration of 0.1-120 micrograms/mL. The results obtained in the PNF assay were found to be equivalent to the results from two other conventional assays where fluorescent or radioactive albumin was used as the external macromolecular tracer.

Animals↗
PubMed1991

An in situ preparation of rat trachea for studying the effects of mucosally applied anti-asthma drugs on mediator-induced plasma exudation.

An animal model is described for testing the effects of anti-asthma drugs on mediator-induced airway inflammation. An in situ segment of trachea is slowly perfused with normal saline in spontaneously breathing, anaesthetised rats. Both the anti-asthma drug and the inflammatory mediator can be applied directly to the airway mucosal surface at the same and/or different times. The amount of plasma in samples of perfusate is monitored. Application of a mediator, such as bradykinin, results in an increase in the amount of plasma in the tracheal lumen (and hence in the perfusate). Plasma in the perfusate can be estimated without injecting a labelled tracer for plasma exudation by using a protein native fluorescence (PNF) method as described by Miller-Larsson & Brattsand (3).

Administration, Topical↗
PubMed1990

Inflammatory indices for chronic bronchitis and chronic obstructive airway disease. Cell populations in bronchial and bronchoalveolar lavage.

The development of chronic bronchitis (CB) and chronic obstructive airway disease (COAD) seems to be related to inflammatory changes of airway structure. However, the cause and the exact location and type of these changes resulting in altered airway function are not known. Mucosal inflammation is characterized by the recruitment of granulocytes, macrophages and lymphocytes as well as by the shedding of epithelial cells. The present chapter discusses the usefulness of bronchial lavage (BL; 50 ml of lavage volume) directly followed by bronchoalveolar lavage (BAL; 200 ml), for the characterization and quantification of inflammation in proximal and peripheral airways, respectively. On the basis of results from the literature and a pilot study on CB patients with or without coexisting COAD, the following conclusions may be drawn: There is a profound difference in lavage cell composition and numbers between non-smokers and smokers. However, within the group of smokers there are few additional changes in cell numbers and composition when concomitant airway disease is present. The obstruction of the COAD patients is correlated to a reduced recovery of BL and BAL fluid. Furthermore, these patients seem to have a reduced number of most cell types in their BL. This diminitution is not just related to the reduced fluid recovery. The BL cells have a lower viability and BL macrophages have a reduced phagocytic capacity when compared with matching BAL cells. The viability of cells was lowest in BL from the COAD group. These findings may suggest that COAD entails a reduced transport of macrophages to the small airways and/or an enhanced turnover of these cells in the bronchi. Functional studies of lavage cells may supply additional, and perhaps more specific, information on the mechanisms involved in the inflammatory process.

Bronchi↗
PubMed1990

Seasonal variation in the phagocytic activity and arachidonic-acid metabolism of human blood monocytes in healthy non-smokers, smokers and chronic bronchitics.

Peripheral blood monocytes are precursor cells to alveolar macrophages (AMs). Many studies have been performed with a view to assessing the differences, in respect of morphology and function, between the AMs of smokers and those of non-smokers. Disturbed host-defence activity of smokers' AMs is reflected by, for instance, decreased phagocytic activity and impaired arachidonic acid metabolism. However, very little attention has been paid to the question what effects cigarette smoking and chronic bronchitis may have on the function of the precursors of these cells--the blood monocytes. The collection of blood monocytes is much less laborious than the sampling of AMs. Therefore, it would be a great advance if the deteriorated host defence in chronic bronchitis could be detected and followed by studies of blood monocytes. However, a seasonal variation in monocyte function, discussed in this paper, may counteract the advantage inherent in repeated sampling. This seasonal variation in cellular host-defence mechanisms should be taken into account when designing longitudinal intervention trials in chronic bronchitis.

Arachidonic Acid↗
PubMed1990

Effects of an inhaled corticosteroid, budesonide, on alveolar macrophage function in smokers.

Selected functions of alveolar macrophages obtained by bronchoalveolar lavage of 12 healthy smokers were examined before and after eight weeks' treatment with an inhaled glucocorticosteroid, budesonide (400 micrograms twice daily). After budesonide treatment spontaneous as well as opsonised zymosan triggered prostaglandin E2 (PGE2) secretion from harvested cells was reduced; no such reduction in opsonised zymosan triggered leukotriene B4 (LTB4) production was observed. Neither the capacity to phagocytose opsonised yeast particles nor the superoxide radical generation triggered by the calcium ionophore A23187, 4 beta-phorbol 12-myristate 13-acetate (PMA), or opsonised zymosan ex vivo were more than marginally affected by the glucocorticosteroid treatment in vivo. Lavage fluid concentrations of angiotensin converting enzyme (ACE), however, after treatment were twice those before treatment and concentrations of fibronectin were reduced to half. Albumin concentrations in lavage fluid were not affected by the glucocorticosteroid treatment. In separate experiments treatment of alveolar macrophages with 10(-7) or 10(-6) M budesonide overnight in vitro did not affect their superoxide radical or PGE2 generation but significantly blocked LTB4 release. These data indicate that inhaled gluco-corticosteroid treatment may affect synthesis or release (or both) of ACE and fibronectin by alveolar macrophages from healthy smokers whereas other functions of these cells, such as the generation of reactive oxygen derived products ex vivo, are only marginally affected.

Administration, Inhalation↗
PubMed1990

Effect of oral N-acetylcysteine (NAC) on volume and albumin content of respiratory tract fluid but not on epithelial secretory cell number in "smoking" rats.

This study was designed to look at the effect of N-acetylcysteine (NAC) on epithelial secretory cells and the respiratory tract fluid volume and albumin content from the lower airways of "bronchitic" rats. Rats were exposed either to tobacco smoke (TS), TS and NAC, or NAC alone. TS caused a significant increase in epithelial secretory cell number which was not reduced by concomitant NAC administration; NAC alone had no effect on cell numbers. TS increased respiratory tract fluid volume and albumin content by a small but non-significant amount, whereas TS and NAC increased the volume and albumin content by a greater and significant amount; NAC alone was also shown to significantly increase both fluid volume and albumin content.

Administration, Oral↗
PubMed1989

Development of glucocorticosteroids with enhanced ratio between topical and systemic effects.

A high potency at the application site and a low incidence of glucocorticoid side-effects form the desired profile of glucocorticosteroids for anti-inflammatory therapy. A new type of glucocorticosteroid 16,17-acetals with an improved topical/systemic activity ratio has been developed. Non-symmetric 16,17-acetal substitution increased the topical anti-inflammatory activity more than the systemic activity in rodents, whereas fluorine substitution in 9 alpha- or 6 alpha,9 alpha-positions increased the systemic more than the topical potency. The non-fluorinated, non-symmetric 16 alpha,17 alpha-acetal budesonide reached the highest ratio, which was five to ten times better than that of the earlier known 16,17-acetonides such as triamcinolone acetonide, or that of the 17 alpha-esters such as beclomethasone 17 alpha,21-dipropionate. Although budesonide and betamethasone 17 alpha,21-diproprionate have the same topical anti-inflammatory potency, the latter decreased plasma and urinary cortisol levels significantly more when ointment preparations were compared in volunteers. Budesonide is efficiently biotransformed in the liver to metabolites such as 6 beta-hydroxybudesonide and 16 alpha-hydroxyprednisolone, which are 50-100 times less potent than the parent steroid. In homogenates of rat or human adult livers budesonide is biotransformed two to five times more rapidly than desonide and triamcinolone acetonide.

Administration, Topical↗
PubMed1989

Prospects for future topical glucocorticoid development.

Current glucocorticoids are inactivated mainly in the liver. Results from studies of their catabolism; their concentration gradients in epidermis and upper and lower dermis after topical application to intact and injured skin; and the concentration needed to inhibit synthesis of human connective tissue by skin fibroblasts; suggest that their systemic and local adverse reactions would logically be reduced further by adding a rapid extrahepatic biotransformation. An ideal glucocorticoid should be locally inactivated during, or immediately after, absorption. The data available for three glucocorticoids with some extrahepatic metabolism suggest that such relatively labile steroids may have a more autoregulating absorption than that of the conventional, more stable, steroids. This means that in skin areas with a damaged stratum corneum, the balance between steroid influx and inactivation may favour anti-inflammatory activity, while that balance is insufficient in intact skin for a triggering of glucocorticosteroid activity. When the skin lesions heal, and the high influx rate tapers off, corticosteroid activity in the epidermis and dermis may be better cut off than with the conventional, metabolically stable, corticosteroids. The compounds subject to local metabolism available today appear to have only moderate topical corticosteroid activity. There are still no valid data to support a claim that their catabolic effects on the connective tissue of diseased skin are less than those of conventional topical steroids. However, novel glucocorticosteroids with a still better relation between high intrinsic glucocorticosteroid activity and rapid metabolic turnover in skin should be designed and tested.

Administration, Topical↗