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Biomedical subjects

H Johnsen

Publications and source records attributed to H Johnsen.

48 records · Page 3Linked to original sources

Metabolism of T-2 toxin by blood cell carboxylesterases.

Human and rat blood hydrolysed T-2 toxin along two different pathways giving HT-2 toxin and neosolaniol as primary metabolites, respectively. Neosolaniol represents a metabolic pathway different from that obtained by liver. Rat erythrocytes formed neosolaniol as a primary metabolite whereas white blood cells hydrolysed T-2 toxin to HT-2 toxin. Human erythrocytes formed both HT-2 toxin and neosolaniol whereas all human white cells produced only HT-2 as the primary metabolite. The enzymes responsible for hydrolysis of T-2 toxin to HT-2 toxin in white blood cells and T-2 toxin to neosolaniol in red blood cells were all identified as carboxylesterases by use of specific inhibitors. The ratio between trichothecene hydrolysis and 4-nitrophenyl butyrate hydrolysis varied among the different cell fractions indicating that specific isoenzymes are involved.

Animals↗

Cytotoxicity and effects of T2-toxin on plasma proteins involved in coagulation, fibrinolysis and kallikrein-kinin system.

The activity of both the coagulation and fibrinolytic systems was markedly depressed 24 h after a sublethal dose of T-2 toxin. T-2 toxin was active as an anticoagulant at low doses, which did not affect the basal state of the animals. The kallikrein-kinin system was also affected by depletion of the prekallikrein, which indicates increased bradykinin levels in plasma. At the same time there was an increased activity of some clinically relevant enzymes in serum, indicating tissue injuries caused by T-2 toxin. All effects observed in this study reached their maximum within 24 h after administration, which corresponds to the time animals usually die when receiving a lethal dose. T-2 toxin does not, however, seem to affect the protease enzymes by reduced protein synthesis, because of early onset of the effects, nor does it act as a trigger itself. The effect of T-2 toxin on plasma protease enzymes is probably secondary to cytotoxic effects in the vascular endothelium.

Animals↗

The Middle-Norway eye-screening study. I. Epidemiology of the pseudo-exfoliation syndrome.

This is the first population-based PE prevalence study allowing comparison of observations from different geographical areas. The prevalence of the PE syndrome for persons above 64 years of age was found to be 10.2, 21.0 and 19.6% in three municipalities lying distinctly apart. Of 343 married couples the man was PE-positive in 36, the woman in 34, and both in 12 cases. One of the 12 couples was excluded because the spouses were cousins. The observed number of 11 couples is significantly higher (P = 0.022) than expected assuming independent occurrence of PE syndrome. Two homozygote pairs of twins were found in this material, both of them discordant for the presence of PE syndrome. This fact along with the discrepancy between observed and expected numbers of PE positivity in both spouses may indicate environmental influence on the distribution of the syndrome.

Aged↗

Metabolism of T-2 toxin by rat liver carboxylesterase.

The trichothecene T-2 toxin was rapidly hydrolyzed by rat liver microsomal fraction into HT-2 toxin which was the main metabolite. The metabolism was completely blocked by paraoxon, a serine esterase inhibitor, but not affected by EDTA or 4-hydroxy mercury benzoate, inhibitors of arylesterase and esterases containing SH-group in active site, respectively. Among the serine esterases carboxylesterase (EC 3.1.1.1), but not cholinesterase (EC 3.1.1.8) hydrolysed T-2 toxin to HT-2 toxin. Carboxylesterase activity from liver microsomes was separated into at least five different isoenzymes by isoelectric focusing, and only the isoenzyme of pI 5.4 was able to hydrolyse T-2 toxin to HT-2 toxin. The toxicity of T-2 toxin in mice was enhanced by pre-treatment with tri-o-cresyl phosphate (TOCP), a specific carboxylesterase inhibitor. This confirms the importance of carboxylesterase in detoxification of trichothecenes.

Animals↗

Amylase, pancreatic isoamylase and lipase in serum before and after endoscopic pancreatography.

Serum amylase, isoamylase and lipase were determined in 17 patients with pancreatic or biliary diseases before and after endoscopic retrograde pancreatography (ERP). Within 1/2-2 hours after cannulation of the pancreatic duct, serum lipase was increased to approximately 4 times the upper reference level and normalized almost completely at 24 hours. A much smaller increase was found in amylase and isoamylase. The elevation in enzyme activities was less in patients with abnormal than with normal ERP. The results suggest that lipase is a more sensitive indicator of pancreatic injury than amylase and isoamylase.

Amylases↗

Carboxylesterases, importance for detoxification of organophosphorus anticholinesterases and trichothecenes.

Several different types of experiments, including the use of inhibitors, have shown that carboxylesterases are a major factor in the metabolism and therefore detoxification of organophosphorus compounds such as soman and trichothecene toxins. The development of a new assay method for the enzyme has allowed us to separate the carboxylesterases into two major groups. The carboxylesterases can, however, be further separated by gel filtration, affinity chromatography, isoelectric focusing, and chromatofocusing into several isoenzymes. Liver microsomal carboxylesterases can be separated into five or six isoenzymes whereas guinea-pig plasma contains two isoenzymes. The isoenzymes differ in molecular weights, isoelectric points, substrate specificities, and affinity for inhibitors. Intravenous administration of a carboxylesterase preparation lowered the toxicity of soman in young rats. Carboxylesterases from rat and guinea-pig plasma inhibited by soman could be reactivated by DAM, whereas enzymes from porcine liver were not reactivated. Only one of the isoenzymes from rat liver microsomal preparation was responsible for the metabolism of T-2 toxin to HT-2. The further metabolism of HT-2 was performed by esterases from rat liver cytoplasma. Long-term exposure of the bronchial muscle to low concentration of soman modulate the bronchial contraction.

Animals↗

Ascorbic acid determination in serum and aqueous humour by high-performance liquid chromatography.

High-performance liquid chromatography on a Supelcosil LC-HN2 analytical column in weak anion exchange mode has allowed separation of ascorbic acid, in less than 5 min, from other interfering substances in serum and aqueous humour. UV monitoring at 254 nm enables ascorbic acid to be detected at 20 pmol level. A method for determination of ascorbic acid concentration in serum and aqueous humour is described, and values from 10 cataract patients are reported.

Aged↗

Senile cataract and ascorbic acid loading.

Serum, aqueous humour, and lens ascorbic acid levels were determined by high-performance liquid chromatography in cataract-, closed-angle glaucoma-, and aphakic patients. The total number of 108 patients were subdivided into different groups. In several groups the pre-operative serum and aqueous amounts were tested, whereafter patients in some groups were loaded with ascorbic acid orally. Finally, a second test was performed on samples taken during operation. It turned out that the ascorbic acid concentration mechanism in cataractous eyes needed more than 12 h for maximum reaction on the loading stimulus. The slow reaction is surprising compared to other species, and it may reflect an affection of the secretory process itself in this disease.

Aged↗

Gas chromatographic mass spectrometric identification of O-demethylated and mono-hydroxylated metabolites of levomepromazine in blood from psychiatric patients by selected ion recording with high resolution.

An O-demethylated and two mono-hydroxylated metabolites of levomepromazine have previously been identified as conjugates in the urine from psychiatric patients. The three metabolites were identified in hydrolysed and nonhydrolysed plasma and erythrocytes from three patients by selected ion monitoring of the trimethylsilyl derivatives, with a mass spectrometric resolution of 5000. The three metabolites were mainly found as conjugates in the plasma, and smaller amounts were found unconjugated in the plasma and the erythrocytes.

Adult↗

Identification of O-demethylated and ring-hydroxylated metabolites of methotrimeprazine (levomepromazine) in man.

Nonenzymatic FeCl2-catalyzed oxidation of methotrimeprazine (levomepromazine) yielded three ring-hydroxylated derivatives that had different GC retention times but almost identical mass spectra. Two of these, together with O-desmethylmethotrimeprazine, were identified by combined GC/MS in enzymatically hydrolyzed urine from four psychiatric patients, who had been treated with oral doses of methotrimeprazine. The mass chromatograms indicated that the three metabolites were formed in similar amounts. Small amounts of three other metabolites were also found in the urine after enzymatic hydrolysis. These were identified as O-desmethyl-N-monodesmethylmethotrimeprazine and two monohydroxy-N-monodesmethyl derivatives that had different GC retention times. None of those metabolites were found in unconjugated form in the urine.

Adult↗