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Biomedical subjects

T Sandström

Publications and source records attributed to T Sandström.

89 records · Page 5Linked to original sources
PubMed1991

The nitric oxide/heme protein complex as a biologic marker of exposure to nitrogen dioxide in humans, rats, and in vitro models.

In an effort to develop a biologic marker of exposure to nitrogen dioxide (NO2), we investigated the in vivo formation of a complex between heme proteins and nitric oxide (NO). In aqueous solution, NO2 disproportionates to NO and nitrate. The NO binds to the iron of heme proteins to form an electron spin resonance (ESR)-detectable complex. We have shown that when rat liver, lung, or nasal microsomes are exposed to 20 ppm NO2 in vitro, an ESR signal attributable to an NO/heme protein complex is detected. After inhalation exposure of rats to 20 ppm NO2 for 6 h, this same ESR signal was detected in microsomes prepared from the exposed rats' lungs or liver; microsomes prepared from the nasal tissue failed to yield any detectable signal. When we lavaged the lungs of rats exposed for 6 h to 0, 5, 10, 20, or 30 ppm NO2 and isolated the bronchoalveolar cell pellets, the NO/heme protein complex was detected in the cell pellets. We were able to demonstrate a dose-dependent relationship between the ESR signal intensity of the NO/heme protein complex and the NO2 exposure concentration. Finally, we used ESR to examine bronchoalveolar lavage cell pellets obtained from human volunteers exposed to either 1.5 or 4 ppm NO2, for 20 min every other day, for six exposures. No signal was found in any of the samples taken 3 wk prior to NO2 exposure, but an ESR signal attributable to the NO/heme protein complex was detected in every sample obtained after the 4 ppm NO2 exposure and in five of eight samples obtained after the 1.5 ppm NO2 exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Inflammatory cell response in bronchoalveolar lavage fluid after nitrogen dioxide exposure of healthy subjects: a dose-response study.

The combination of environmental chamber exposure and bronchoalveolar lavage (BAL) was used to study the effects of the common air pollutant nitrogen dioxide (NO2). Eighteen healthy nonsmokers were exposed to NO2 during 20 min in an exposure chamber during light bicycle ergometer work. All subjects were examined with BAL at least 3 wks before exposure, as a reference. The subjects were re-examined with BAL, in groups of eight, 24 h after exposure to 4, 7 and 10 mg NO2.m.3 (2.25, 4.0 and 5.5 ppm), respectively. An inflammatory cell response was found after exposure to all concentrations. An increase in the number of lymphocytes in BAL fluid was observed after 7 and 10 mg.m.3 (p less than 0.05 and 0.02, respectively). An increase in the number of mast cells, that appears to be dose-dependent, was found after exposure to all concentrations. The proportion of lysozyme positive alveolar macrophages was elevated after exposure to 7 mg.m.3. The inflammatory mediators fibronectin, hyaluronan, angiotensin converting enzyme (ACE) and beta 2-microglobulin were unchanged by exposure. Due to the findings of inflammatory cell changes far below the peak exposure limits for work places in industrialized countries, 9-18 mg.m.3, the safety of these limits is questioned. Studies are in progress in our laboratory using BAL to evaluate the effects of repeated NO2 exposure.

Adult↗
PubMed1990

Formoterol, a new long acting beta 2 agonist for inhalation twice daily, compared with salbutamol in the treatment of asthma.

Sixteen patients with stable chronic asthma participated in a double blind crossover study comparing the new inhaled long acting beta 2 agonist formoterol with salbutamol. Inhaled (n = 15) and oral steroid (n = 1) treatment were maintained at the same daily dose throughout the study. For four weeks the patients received either formoterol 24 micrograms twice daily or salbutamol 400 micrograms twice daily, plus additional puffs (with the same drug) when needed. Asthma symptoms, additional puffs of beta 2 agonist, peak expiratory flow (PEF), and side effects were recorded daily. During treatment with formoterol the patients used fewer additional puffs of beta 2 agonist, had better symptom scores, less disturbed sleep, more days without additional aerosol, and higher PEF both morning and evening than during salbutamol treatment. Thus formoterol 24 micrograms twice daily gave long lasting bronchodilatation and asthma symptoms were well controlled with regular twice daily administration.

Administration, Inhalation↗
PubMed1990

Bronchoalveolar mastocytosis and lymphocytosis after nitrogen dioxide exposure in man: a time-kinetic study.

The combination of environmental chamber exposure and bronchoalveolar lavage (BAL) was used to study the time-course of the cell response in the human lung to nitrogen dioxide (NO2). Healthy subjects were exposed for 20 min to 7 mg NO2.m-3 (4 ppm), a concentration which occurs indoors in industries and is below the peak exposure limit for work places in most countries, 10 mg.m-3 (5.5 ppm). BAL was performed in all subjects several weeks before exposure and 4, 8, 24 and 72 h after exposure, in eight subjects at each time. Mastocytosis and lymphocytosis were found in BAL fluid 4-24 h after exposure, with normalization after 72 h. A mild increase in lysozyme positive macrophages was found 24-72 h after exposure. The time-course of the human pulmonary cell response to NO2, demonstrated in BAL fluid, represents a new and previously not reported finding after exposure to this common air pollutant. Our findings are diverging from results obtained in animal studies, using approximately the same NO2 concentrations, indicating that the results from the animal studies may not be transferable to man.

Adult↗
PubMed1990

Structural characterization of bronchial mucosal biopsies from healthy volunteers: a light and electron microscopical study.

Bronchial mucosal biopsies were collected by flexible fibreoptic bronchoscopy (FFB) from normal healthy volunteers. The volunteers were not receiving any medication and had been free from respiratory infection for at least five weeks prior to the bronchoscopy. Biopsies with a minimum of 115 microns of undamaged perpendicularly sectioned epithelium were investigated by light and transmission electron microscopy. The height of the epithelium varied between 22-62.5 microns, with a median value of 41.5 microns. The volume density of the various epithelial cells in relation to the total epithelium was 61% for the ciliated and non-ciliated, non-secretory luminal cells, 6% for the goblet cells and 32% for the basal cells. The width of the lamina reticularis of the basement membrane ranged between 3-17.5 microns, with a median value of 8.5 microns. Blood vessels occupied 2.8% of the subepithelial tissue. Only a few inflammatory cells were seen in the connective tissue, volume density occupied by lymphocytes and polymorphonuclear granulocytes, 0.6% and 0.2% respectively. This study shows that structural damage is a common finding in biopsies collected by FFB. Mechanical damage of bronchial biopsies caused by the forceps should be considered before alterations in the epithelium are attributed to pulmonary disease.

Adult↗
PubMed1989

Is the short term limit value for sulphur dioxide exposure safe? Effects of controlled chamber exposure investigated with bronchoalveolar lavage.

Bronchoalveolar lavage (BAL) which has not previously been used in investigating the effect of sulphur dioxide (SO2) on the human lung was performed on 12 subjects before and after controlled chamber exposure with SO2 for 20 minutes. BAL fluid 24 hours after exposure with 10 mg SO2/m3 (4 ppm, 10 subjects) showed increased alveolar macrophage activity as judged by an increase in lysozyme positive macrophages. Twenty four hours after 20 mg/m3 (4 subjects) a further increase was seen, which was accompanied by an increase in total numbers of macrophages and lymphocytes. Seventy two hours after exposure (4 subjects) cell numbers had virtually returned to pre-exposure levels. These previously uninvestigated reactions indicate potentially noxious effects of SO2 in the lungs at exposure levels that are regarded as relatively safe.

Adult↗
PubMed1989

Cell response in bronchoalveolar lavage fluid after exposure to sulfur dioxide: a time-response study.

Bronchoalveolar lavage (BAL) has been performed in 22 healthy nonsmoking male volunteers after exposure to 8 ppm SO2 (20 mg/m3). The exposure level exceeds the US Short-Term Exposure Limit (STEL) of 5 ppm, but occurs as peak exposures in industrial indoor environments. Exposures were made during light work on a bicycle ergometer in an environmental exposure chamber for 20 min. BAL was performed 2 wk or more before exposure and 4, 8, 24, and 72 h after exposure in eight subjects at each time interval. Four hours after exposure significant increases were found in the numbers of lysozyme-positive macrophages, lymphocytes, and mast cells (p less than 0.02 to 0.05). Lymphocytes, lysozyme-positive macrophages, total count of alveolar macrophages, and total cell number increased to peak values 24 h after exposure (p less than 0.02 to 0.05). Seventy-two hours after exposure the cell numbers and distribution had returned to normal. The time course of the cell reactions found in BAL fluid after controlled SO2 exposure represents a new and previously not reported response to a noxious gas.

Adult↗
PubMed1989

Cell response in bronchoalveolar lavage fluid after sulfur dioxide exposure.

Environmental chamber exposure and bronchoalveolar lavage (BAL) were used to study the dose-response relationship between short-term exposure to sulfur dioxide (SO2) and inflammatory reactions in the human lung as reflected in BAL fluid. Healthy subjects were exposed to 10, 13, 20, or 30 mg/m3 for 20 min. BAL was performed several weeks preexposure and 24 h postexposure. Mast cells, lymphocytes, lysozyme positive macrophages, and the total number of macrophages were significantly increased after SO2 exposure. A dose-dependent increase in the cell response in BAL fluid was observed after exposure to 10-20 mg/m3, but no further increase was detected after 30 mg/m3. Inflammatory cell response was found in BAL fluid at SO2 levels that occur in industrial indoor environments worldwide, and cell response to SO2 was also seen below the short-term exposure limit of Sweden and many other countries (13 mg/m3).

Adult↗
PubMed1988

Decreased peripheral beta-adrenergic reactivity in asthmatics treated with oral beta 2-agonists.

Peripheral beta-adrenoceptor reactivity, measured as the dermal erythematous reaction to iontophoretically administered isoprenaline was studied in 41 asthmatics, 13 patients with allergic rhinoconjunctivitis and 21 healthy control subjects. The response of intact superficial dermal blood vessels to isoprenaline, which has previously been demonstrated to be beta 2-adrenoceptor mediated, was reduced in asthmatics treated with high dose, oral, slow-release beta 2-agonists compared to healthy controls. The response in asthmatics not treated with oral beta 2-agonists and in patients with allergic rhinoconjunctivitis did not differ from controls. Thus, the peripheral beta 2-adrenergic reactivity of intact human superficial blood vessels is affected by oral, slow-release beta 2-agonists.

Administration, Inhalation↗
PubMed1988

Increased peripheral alpha-adrenoceptor response in allergic asthmatics.

The peripheral alpha-adrenoceptor reactivity, measured as dermal blanching response to iontophoretically administered phenylephrine, was studied in 28 allergic asthmatics, 13 patients with allergic rhinoconjunctivitis and 21 healthy controls. The blanching response, which has previously been demonstrated to be mediated via alpha 1-adrenoceptors, was found to be significantly increased in allergic asthmatics compared with controls. It is suggested that there is an increased peripheral alpha-adrenoceptor reactivity in allergic asthma.

Adolescent↗
PubMed1988

Bambuterol: clinical effects of different doses of a long-acting bronchodilator prodrug.

Sixty-eight asthmatics participated in a dose-finding study on bambuterol, a terbutaline prodrug, administered once every evening. Bambuterol administrations of 0.185, 0.270 and 0.400 mg/kg gave effective and long-lasting bronchodilation, for at least 24 h, with the two higher doses probably close to the maximal effect of the drug. Bambuterol 0.400 mg/kg was associated with more adverse effects than bambuterol 0.185 mg/kg. The side effects were those expected in oral beta 2-agonist treatment and mainly experienced by patients who had not been on oral beta 2-agonists before. The most favourable of the investigated doses was found to be 0.270 mg/kg. It can not be excluded, however, that a somewhat lower dose may still be as beneficial. This will be investigated in forthcoming studies.

Adult↗
PubMed1985

Enhanced breakdown of bovine articular cartilage proteoglycans by conditioned synovial medium in vitro. The effect of glycosaminoglycan polysulfate.

The effect of glycosaminoglycan polysulfate (GAGPS, Arteparon) upon the breakdown of calf articular cartilage proteoglycans has been studied in vitro. GAGPS had no significant effect upon this breakdown when cartilage was cultured alone but significantly reduced the breakdown enhanced by conditioned medium from organ cultures of calf synovial membrane. Culturing the synovial membrane in the presence of GAGPS did not alter the capacity of conditioned medium to degrade cartilage proteoglycans.

Animals↗
PubMed1983

Direct visual detection of protein antigen: importance of surface concentration.

A new type of commercially available substrate was used for visualization of antigen binding to antibodies immobilized on the substrate surface. Addition of antigen induced sufficient increase of the protein layer to allow direct visualization, provided that the antibodies immobilized at the surface were immunosorbent isolated. This finding shows the importance of the surface concentration for direct optical visualization of antigen. The results are discussed in relation to previous reports that it is not possible to visualize directly the binding of protein antigen to surface-immobilized antibodies.

Animals↗
PubMed1982

The effect of continuous mechanical pressure upon the turnover of articular cartilage proteoglycans in vitro.

Fragments of calf articular cartilage maintained in organ culture were subjected to continuous mechanical pressure applied by means of lead weights of differing sizes. Increasing the pressure from approximately 7.5-30 kgfcm-2 proportionately decreased the breakdown of proteoglycans as measured by the release of [35S]sulphate from prelabeled cartilage. The difference was observed as early as 24 hours after culture. During the first 24 hours after removal of a 30 kgfcm-2 pressure the release of [35S]sulphate was slightly greater than that of the nonweight-bearing controls and then subsequently returned to the level of the controls. Application of a mechanical pressure of 30 kgfcm-2 to calf articular cartilage reduced the incorporation of [35S]sulphate to about half the level of the nonweight-bearing controls. A pressure of 15 kgfcm-2 had no significant effect upon [35S]sulphate incorporation. The production of lactate by the cartilage under the influence of 30 kgfcm-2 for 4 days was not significantly different from that of nonweight-bearing controls indicating the retained viability of the tissue. The present study indicates that proteoglycan metabolism of calf articular cartilage in vitro is capable of responding rapidly to variations in applied load. The potential importance of this finding in terms of the functional demands of articular cartilage is apparent, and it can be speculated that a failure of this adaptability of the chondrocytes is an important factor in the etiology of degenerative joint disease.

Animals↗
PubMedDate not supplied

Biological markers of exposure to SO2: S-sulfonates in nasal lavage.

S-sulfonate levels were measured in the nasal lavage (NAL) fluid of humans exposed to sulfur dioxide as a potential biological marker of exposure. These levels were determined by treating NAL fluid protein with cyanide to cleave the S-S linkage and release the sulfite. The cyanolytically released sulfite was measured by ion chromatography. In two experiments, humans were exposed to air or 1 ppm SO2 for 10 minute, and to air or 7 ppm SO2 for 20 minutes and lavaged immediately after exposure. Releasable sulfite levels in NAL fluid were 1.06 +/- 0.24 and 2.61 +/- 0.55 micrograms SO=3/mg protein, respectively (mean +/- SE, n = 5), for the first experiment, and 1.16 +/- 0.37 and 4.91 +/- 0.76 micrograms SO=3/mg protein, respectively (mean +/- SE, n = 8), for the second. The subjects in the former study were persons with asthma. In both experiments, S-sulfonate levels were statistically elevated in the exposed group compared with the control groups (p < 0.05, paired t-test). The same individuals in the second experiment received five additional 20-minute exposures to 7 ppm SO2 every other day, for a total of six exposures. NAL fluid taken at the conclusion of the final exposure had releasable sulfite levels of 4.99 +/- 1.36 micrograms SO=3/mg protein; these levels were statistically elevated relative to controls but were not elevated relative to the 1-day exposure (mean +/- SE, n = 8). The lack of accumulation of S-sulfonates after 6 days of short-term exposure suggests clearance of these compounds from the nasal passages within 24 hours. The levels of S-sulfonates observed in NAL fluid in this study are almost three orders of magnitude higher than those measured in plasma following similar SO2 exposures. Measurement of S-sulfonates in the nasal passage may be an effective short-term biomarker of exposure to SO2.

Adolescent↗