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Biomedical subjects

B Akesson

Publications and source records attributed to B Akesson.

At least 91 records · Page 5Linked to original sources

Pharmacokinetics of triethylamine and triethylamine-N-oxide in man.

The pharmacokinetics of the industrially important compound triethylamine (TEA) and its metabolite triethylamine-N-oxide (TEAO) were studied in four volunteers after oral and intravenous administration. TEA was efficiently absorbed from the gastrointestinal (GI) tract, rapidly distributed, and in part metabolized into TEAO. There was no significant first pass metabolism. TEAO was also well absorbed from the GI tract. Within the GI tract, TEAO was reduced into TEA (19%) and dealkylated into diethylamine (DEA; 10%). The apparent volumes of distribution during the elimination phase were 192 liters for TEA and 103 liters for TEAO. Gastric intubation showed that there was a close association between levels of TEA in plasma and gastric juice, the latter levels being 30 times higher. The TEA and TEAO in plasma had half-lives of about 3 and 4 hr, respectively. Exhalation of TEA was minimal. More than 90% of the dose was recovered in the urine as TEA and TEAO. The urinary clearances of TEA and TEAO indicated that in addition to glomerular filtration, tubular secretion takes place. For TEAO at high levels, the secretion appears to be saturable. The present data, in combination with those of earlier studies, indicate that the sum of TEA and TEAO in urine may be used for biological monitoring of exposure to TEA.

Administration, Oral↗

Deaths and tumors among workers grinding stainless steel.

This study examined a cohort of 1,164 males who, during the period 1927-1981, had been employed for 3 months or more in an industry that produced objects from stainless steel. These workers were exposed to the dust of grinding materials, grinding agents, and stainless steel. From 1975 to 1980, measurements of the total dust in the workroom air have shown levels of about one mg/m3 (consisting of chromium at about 0.1 mg/m3 and nickel at about 0.05 mg/m3) during grinding and several mg/m3 (chromium at about 0.01 mg/m3 and nickel at about 0.005 mg/m3) during polishing. Before 1950, the concentrations were probably considerably higher. Compared to a local reference population, a decrease in mortality (63 observed deaths, standardized mortality (SMR) = 0.79, 95% confidence limits CL = 0.61, 1.01) took place during the 1951-1983 observation period among 318 subjects who had been employed for at least five years, allowing a latency period of at least 20 years. Mortality from cancer of the colon/rectum increased (observed deaths = 6, SMR = 2.47, CL = 0.97, 5.58). The mortality from nonmalignant pulmonary disease did not increase (SMR = 0.29, CL = 0.01, 1.81). During the observation period (1958-1983), there was no significant overall excess of tumors (observed cases = 33, standardized morbidity [SMR] = 1.09, CL = 0.76, 1.54). However, tumor morbidity of the colon/rectum (observed 11, SMR = 2.83, CL = 1.47, 5.19) significantly increased. There were no cases of respiratory cancer (expected 4.7, CL = 0, 0.21). Thus, the results indicate an increased risk of intestinal cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromium↗

Metabolism of triethylamine in polyurethane foam manufacturing workers.

In 20 workers studied before, during, and after exposure to triethylamine (TEA) in a polyurethane-foam producing plant the amount of TEA and its metabolite triethylamine-N-oxide (TEAO) excreted in urine corresponded to an average of 80% of the inhaled amount. An average of 27% was TEAO, but with a pronounced interindividual variation. Older subjects excreted more than younger ones; less than 0.3% was excreted as diethylamine. The data indicate half-lives for TEA and TEAO excretion in urine of about 3 hr. The postshift level of TEA in urine and plasma are good indicators of the time-weighted average air level during the preceding work day, and might thus be used for biological monitoring. An air level of 10 mg/m3 (proposed occupational standard) corresponds to a urinary excretion of 65 mmol TEA/mol creatinine and a plasma level of 1.9 mumol/liter (biological exposure indices).

Adolescent↗

Small airways function in workers processing polyvinylchloride.

In a polyvinyl chloride (PVC) processing plant, 20 workers employed as machine attendants and calender operators, and thus exposed to PVC thermal degradation products (PTDP) and phthalic acid esters (PAE; up to 2 mg/m3), were studied. The control group was 19 unexposed workers. The exposed subjects had more symptoms from eyes and upper airways than the controls, probably mainly associated with PTDP. Two (10%) exposed workers had mild work-related asthma vs no control; five (25%) vs one (5%) symptoms of unspecific bronchial hyperreactivity. One exposed subject had a significantly raised level of IgG against phthalic anhydride, indicating that sensitization can occur in PVC processing. No significant differences were found between exposed and control subjects with regard to spirometry (VC, FEV1, FEF50, FEF75) or volume of trapped gas (VTG, an indicator of small airways disease) before or after metacholine inhalation. Thus, we could not find effects of PTDP or PAE on the small airways.

Adult↗

Effect of selenium supplementation on the distribution of selenium among plasma proteins of a patient with maple syrup urine disease.

Selenium (Se) status was studied in a patient with classical maple syrup urine disease (MSUD) receiving Se supplement. The basal plasma Se concentration was 0.06 mumol/l increasing to 2.1 mumol/l after 40 days of supplementation. When the plasma Se distribution was analysed by gel filtration, a major peak was seen close to the high molecular weight proteins with a second peak in the albumin region. When the Se dose was decreased in a stepwise manner from 50 micrograms/day to 25 micrograms/day and then to 17 micrograms/day plasma Se decreased, but the proportion of plasma Se in the two protein peaks did not change. In a healthy girl not supplemented with Se, the proportion of plasma Se in the albumin region was somewhat lower. In the MSUD patient glutathione peroxidase activity was initially low, and increased ten-fold during Se supplementation. The study indicates that the Se requirement for plasma glutathione peroxidase activity was fulfilled at the lowest dose of Se used and that Se is incorporated into several plasma proteins after supplementation.

Blood Proteins↗

Lipolysis of polyenoic fatty acid esters of human chylomicrons by lipoprotein lipase.

Human chylomicrons, obtained from chylous pleural fluid of a patient with mesothelioma, were incubated with bovine milk lipoprotein lipase. No difference in the release of different C16-C18 fatty acids as unesterified fatty acids, or in their appearance in diacylglycerols, was observed. The rate of lipolysis of arachidonic (20:4), and eicosapentaenoic (20:5) acid ester bonds of chylomicron triacylglycerols was slower, and a larger proportion of these fatty acids accumulated in mono- and diacylglycerols. The hydrolysis pattern for docosahexaenoic acid (22:6) was intermediary between that of the C16-C18 fatty acids and that of 20:4 and 20:5. The data suggest that the presence of a double bond at position 5 in the eicosanoid precursors may be important for the rate of lipolysis. The relative resistance of the 20:4- and 20:5- esters of chylomicrons to lipoprotein lipase may be important for the tissue distribution of these fatty acids.

Arachidonic Acid↗

Fat malabsorption in patients before and after total gastrectomy, studied by the triolein breath test.

The feasibility of using the triolein breath test to demonstrate fat malabsorption was evaluated in a prospective study of patients before and after total gastrectomy and Roux-en-Y reconstruction. Two of 11 patients had subnormal fat absorption before the operation, but 1 and 6 months after the operation 9 of 11 patients had subnormal fat absorption. Peak expiratory 14CO2 (median (range] at the three investigations was 3.9%/h (2.1-5.9%/h), 2.1%/h (1.4-4.5%/h), and 2.0%/h (1.2-6.0%/h), respectively. Patients who underwent a Nissen fundoplication were used as controls. They had normal fat absorption both before and after operation. Serum amylase was not appreciably affected by total gastrectomy and was similar to control values. In contrast, serum albumin decreased 1 month after gastrectomy and recovered after 6 months. In control patients pre- and post-operative albumin concentrations did not differ and were comparable to preoperative albumin values in the total gastrectomy group. The lowered fat absorption may be explained by duodenal bypass with decreased pancreatic stimulation, and it may in part explain the weight loss in patients operated on with total gastrectomy.

Aged↗

Comparison among five mutagenicity assays in workers producing polyurethane foams.

Thirty-two male individuals exposed to isocyanates and amines during the production of plastic foams and 20 male referents were studied by cytogenetic methods (chromosomal aberrations, sister chromatid exchanges and micronuclei in lymphocytes) and by urinary mutagenic assays (thioether concentrations and mutagenic activity with Salmonella TA98 and E. Coli WP2 uvrA). The occupational exposure was monitored by measurements of toluene diisocyanate and N-methylmorpholine in work-room air. The levels were below the current Swedish hygienic standards. Although all parameters, except the sister chromatid exchanges, showed increased mean values for the exposed group compared to the referents, only the urinary thioether concentrations differed significantly. The study was, however, non-conclusive with regard to a genetic effect of the occupational exposure as measured by the cytogenetic parameters. This may be due to the low exposure level. In the micronuclei frequencies there was a significant effect of age. Smoking significantly affected the SCE frequencies, the thioether concentrations and the mutagenic activities in the Salmonella assay. There were statistically significant correlations between the urine specimens collected during one working day and the following morning with regard to the mutagenic activities in the Salmonella and E. coli assays, and in the thioether concentrations as well. The association between the different cytogenetic and urinary mutagenic assays were weak but there were several statistically significant correlation coefficients, indicating that the variables may have a common metabolic background.

Adult↗

Heparin interacts with a selenoprotein in human plasma.

The major selenium-containing peak at gel filtration of human serum on Sephadex G-150 had a Kav of 0.19, but at chromatography of heparinized plasma this peak had a Kav of 0.01, indicating an interaction between heparin and a major selenium-containing protein. The addition of protamine abolished the effect of heparin. The heparin-interacting protein was not identical to glutathione peroxidase. The data explain some previous discrepancies on selenium distribution in plasma due to the use of different anticoagulants.

Blood Proteins↗

Correlation between plasma levels of selenium and antithrombin-III.

Patients with previous myocardial infarction were tested for antithrombin-III (AT-III) activity and selenium levels in their plasma and compared with sex- and age-matched healthy control individuals. Patients and controls showed a positive correlation between AT-III and selenium levels (r = 0.27, p = 0.015). After calculatory adjustment for this correlation, selenium was found to be significantly negatively correlated with disease. Multivariate analysis of differences between patients and controls indicated that triglyceride levels in serum had the greatest discriminatory ability (r2 = 0.169), followed by AT-III (r2 = 0.072) and selenium (r2 = 0.056). The increased AT-III levels were correlated with the use of warfarin and beta blockers in the patients, but these drugs could not explain the comparatively low selenium levels in the patients. Serum total cholesterol and plasma fatty acid composition had no discriminatory power in multivariate testing. The various fatty acid did not show co-variation with the selenium levels. The clinical significance of these observations is not clear, but they are consistent with the hypothesis that selenium is an important determinant in cardiovascular disease. The relation between AT-III and selenium should be further evaluated.

Antithrombin III↗

Experimental study on the metabolism of triethylamine in man.

Five healthy volunteers were exposed by inhalation to triethylamine (TEA; four or eight hours at about 10, 20, 35, and 50 mg/m3), a compound widely used as a curing agent in polyurethane systems. Analysis of plasma and urine showed that an average of 24% of the TEA was biotransformed into triethylamine-N-oxide (TEAO) but with a wide interindividual variation (15-36%). The TEA and TEAO were quantitatively eliminated in the urine. The plasma and urinary concentrations of TEA and TEAO decreased rapidly after the end of exposure (average half time of TEA was 3.2 h). There was an excellent association between air levels of TEA and the urinary concentrations in samples obtained within two hours of the end of exposure. Thus the urinary level of TEA taken in this period is useful as a biological monitoring of exposure. An air concentration of 10 mg/m3 corresponds to an average urinary concentration of about 40 mmol/mol creatinine (at sedentary work).

Administration, Inhalation↗

Distribution of selenium and glutathione peroxidase in plasma compared in healthy subjects and rheumatoid arthritis patients.

The distribution of selenium and glutathione peroxidase activity in plasma was compared in samples from healthy adult controls and patients with rheumatoid arthritis. Plasma was separated by gel filtration, and selenium was measured in the eluted fractions by means of graphite furnace atomic absorption spectrometry with Zeeman background correction. Most of the selenium in plasma of healthy controls was seen in proteins that migrated close to immunoglobulin G, and that had an apparent molecular weight at the peak of 174 kDa. One major peak of glutathione peroxidase activity with an apparent molecular weight of 99 kDa was unmatched by any significant peak in selenium content. Thus, there was only limited correspondence between the elution patterns of selenium and glutathione peroxidase activity. Also, in patients with active rheumatoid arthritis, selenium was distributed amongst plasma proteins with a wide range of molecular weights. The major selenium peak was less pronounced in patients, but the amount of selenium in other parts of the chromatogram was not different from that in controls. Further work is necessary to define the occurrence of different selenoproteins in plasma in patients and in healthy subjects.

Aged↗

Trace element alterations in infectious diseases.

Trace elements like copper, zinc, iron and selenium have a significant influence on the function of the immune system. We studied plasma levels of trace elements in 53 patients with acute bacterial and viral infections. In bacterial infections (septicaemia, pneumonia, erysipelas and meningitis) the plasma concentrations of selenium, iron and zinc were decreased. Plasma copper was unchanged in patients with erysipelas, but increased in other types of bacterial infections. Although the patients with viral infections showed similar shifts of the trace elements as were observed in patients with bacterial infections, the changes were not as pronounced. A plasma selenium value below 0.8 mumol/l was found in only 6% of the patients with viral infections in contrast to 63% of the patients with septicaemia or 57% of the patients with pneumonia. Furthermore, in viral infections 60% of the zinc values were below the mean level of 12.8 mumol/l observed in healthy controls as compared with 90% of the values in patients with sepsis or 92% of the values in patients with pneumonia. The onset of change in trace elements occurred within a few days and persisted for several weeks. These changes seem to be non-specific and are independent of the agent causing infection. The different types of infections were followed by changes in most of the plasma proteins which are known to be associated with an inflammatory reaction. The changes in plasma proteins were most pronounced in patients with sepsis and pneumonia. Patients with sepsis having a high degree of inflammation did not show a positive correlation between the severity of the disease--as judged by plasma proteins--and the alterations of trace elements.

Bacterial Infections↗

Intestinal absorption of phosphatidylcholine and triglyceride after ileal resection.

The intestinal absorption of (14C)oleoyl moieties in triglyceride and phospholipid was investigated by means of (14C)phosphatidylcholine and (14C)triolein breath tests. In patients who had undergone ileal resection the absorption of both phosphatidylcholine and triglyceride was subnormal, as reflected by a lower production of 14CO2. In healthy subjects the production of expiratory 14CO2 after oral administration of (14C)phosphatidylcholine was slightly higher than after administration of (14C)triolein. This was also observed in the patient group, indicating that the absorption of both triglyceride and phospholipid was decreased to similar extents, although triglyceride absorption tended to be more affected after major ileal resection. In patients with lipid malabsorption the proportion of linoleic acid in serum phosphatidylcholine was subnormal, and the decrease was correlated to the decrease in lipid absorption. The concentration in serum of selenium, alpha-tocopherol, and carotene but not of ascorbic acid and retinol was subnormal after ileal resection.

Adolescent↗

Visceral improvement following combined plasmapheresis and immunosuppressive drug therapy in progressive systemic sclerosis.

In a two-year prospective therapeutic trial, 15 patients with progressive systemic sclerosis (PSS) were treated with immunosuppressive drug therapy with or without long-term plasmapheresis. Before the trial all patients had severe involvement of either the esophagus, lungs or kidneys. One patient died of renal failure and another 2 patients withdrew unimproved. In the remaining 12 patients, objective improvement occurred in all but one. The degree and extent of skin involvement decreased significantly (p less than 0.01). Cineradiography revealed increased esophageal motility in 4 patients. Pulmonary function measured as total lung capacity and static lung compliance improved (p less than 0.01). In 4 patients the number of premature atrial or ventricular contractions at 24 h ECG monitoring decreased, as did the concentrations of immunoglobulins and ANA titres in serum. Although it could not be ascertained whether the clinical improvement was associated with combined therapy or immunosuppressive drug treatment alone, our results suggest that immunosuppressive therapy is beneficial in advanced PSS.

Adult↗

Effect of selenium supplementation on the distribution of selenium in plasma proteins of healthy subjects.

The influence of an increased intake of selenium on the distribution of this element among plasma proteins was studied. 200 micrograms of yeast selenium was given to healthy subjects daily for 8 weeks, and then the subjects refrained from selenium supplementation for 16 weeks. Plasma selenium increased almost two-fold during supplementation, and most of the increase occurred during the first 4-week-period. Plasma glutathione peroxidase activity increased only marginally. At all times studied, most of the selenium in plasma was located in proteins, migrating close to immunoglobulin G on gel filtration. The selenium content of this fraction was only moderately increased after supplementation for 8 weeks, and instead more marked increases occurred in the regions for high-molecular-weight proteins and albumin. This change implied that the distribution of selenium approached that of total protein, and we therefore conclude that most of the increase in plasma selenium occurred via unspecific incorporation of selenium into a wide variety of proteins. Sixteen weeks after the end of supplementation the selenium distribution had essentially returned to that before supplementation.

Adult↗