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Biomedical subjects

A Tangerman

Publications and source records attributed to A Tangerman.

At least 55 records · Page 3Linked to original sources
PubMed1990

Postprandial exocrine pancreatic function during long-term treatment with the somatostatin analogue SMS 201-995 in acromegalic patients.

Long-term treatment with the somatostatin analogue SMS 201-995 (SMS) might impair exocrine pancreatic function, secretion of cholecystokinin (CCK) and pancreatic polypeptide (PP), and pancreatic size. In five acromegalics on chronic treatment with SMS, we investigated postprandial 6-h urinary excretion of p-aminobenzoic acid (PABA) and p-aminosalicylic acid (PAS) after s.c. injection of 100 micrograms SMS or placebo and after ingestion of 2 mmol nBT-PABA and 2 mmol PAS. In the acromegalics, urinary PABA/PAS ratio (reflecting exocrine pancreatic function) after SMS was similar to that after placebo (P greater than 0.10) and higher than in healthy volunteers (n = 8, P = 0.05). The initial inhibition of plasma CCK secretion by SMS was cancelled during the 3rd h after the meal, whereas PP release remained completely abolished. Pancreatic size as measured by ultrasonography, was not reduced in seven acromegalics compared with 14 healthy volunteers. It is concluded that despite a blunted release of the trophic hormone CCK, long-term treatment with SMS 201-995 neither induces an abnormally small pancreas nor deterioration of postprandial exocrine pancreatic function in patients with acromegaly.

4-Aminobenzoic Acid↗
PubMed1990

Pancreatic exocrine and gallbladder function during long-term treatment with octreotide (SMS 201-995).

Since octreotide (SMS 201-995, Sandostatin; Sandoz Pharmaceuticals) is a potent inhibitor of pancreatic exocrine secretion and gallbladder contraction, long-term treatment with this drug may theoretically result in impaired pancreatic function and gallstones. However, we observed excellent pancreatic exocrine function--as assessed by the PABA/PAS test--in acromegalics who received octreotide treatment for more than 6 months. Plasma cholecystokinin showed a significant, although blunted, postprandial response, which exceeded the threshold for gallbladder contraction in healthy controls. Remarkably, postprandial gallbladder contraction was completely abolished for at least 2 h during octreotide treatment. In contrast to other studies, none of 16 acromegalic patients on long-term octreotide treatment developed gallstones. Although the incidence of gallstones in patients on long-term octreotide treatment may be increased, the risk seems to be variable.

4-Aminobenzoic Acid↗
PubMed1989

Cystathionine-synthase-deficient patients do not use the transamination pathway of methionine to reduce hypermethioninemia and homocystinemia.

Methionine is supposed to be degraded via two known routes, the transsulfuration and the transamination pathways. In particular, patients with hypermethioninemia, due to a defect in the transsulfuration pathway, may catabolize significant amounts of methionine via the transamination pathway. In this study the relative amount of methionine degraded via the transamination pathway in 17 patients with homozygous homocystinuria, due to cystathionine synthase deficiency, was compared with 23 normal subjects, and with a patient with hypermethioninemia due to a deficiency in methionine adenosyltransferase. The homocystinuric patients and the normal subjects were studied in the fasting state as well as after methionine loading (0.1 g/kg body weight). It is concluded that in cystathionine synthase deficient patients, the transamination pathway is not quantitatively important in methionine degradation despite elevated methionine levels. This is in contrast to the patient with methionine adenosyltransferase deficiency, who catabolizes at least 20% of his dietary methionine via the transamination pathway.

Adolescent↗
PubMed1989

Transamination of methionine in humans.

1. This study was designed to investigate the transamination pathway of methionine in humans. 2. Evidence is provided that methanethiol and its metabolites are formed via transamination of methionine. 3. Gas-liquid chromatography was used to measure serum and urinary transamination metabolites of methionine: 2-keto-4-methylthiobutyrate, 3-methylthiopropionate and methanethiol, and the metabolites of methanethiol, dimethylsulphide, protein-S-S-CH3 (a mixed disulphide of blood proteins and methanethiol) and X-S-S-CH3 (a mixed disulphide of methanethiol and another thiol with an unknown component X). 4. Methionine and the transamination intermediates were measured in 10 normal subjects, in six normal subjects after L-methionine loading (0.1 g/kg body weight) and in a male patient with hepatic methionine adenosyltransferase (EC 2.5.1.6) deficiency. 5. In the patient with methionine adenosyltransferase deficiency, at least 20% of methionine was degraded via transamination. In normal subjects transamination of methionine did exist but was quantitatively not important in methionine catabolism, not even after methionine loading. 6. The results of this study might be of importance for future studies on the role of methanethiol in hepatic encephalopathy.

Adult↗
PubMed1989

Unconjugated serum bile acids as a marker of small intestinal bacterial overgrowth.

Non-invasive methods to detect small intestinal bacterial overgrowth often lack specificity in patients who have undergone an ileal resection or have an accelerated intestinal transit. Since elevated serum unconjugated bile acid levels have been found in patients with clinical signs of bacterial overgrowth, we studied the clinical value of unconjugated serum bile acids as a marker of small intestinal bacterial overgrowth. Patients with culture-proven bacterial overgrowth had significantly elevated fasting unconjugated serum bile acid levels (median and range: 4.5; 1.4-21.5 mumol l-1) as compared to healthy subjects (0.9; 0.3-1.7 mumol l-1, P less than 0.005), to persons with an accelerated intestinal transit (1.0; 0.3-1.9 mumol l-1, P less than 0.005) and to persons who have undergone an ileal resection (2.1; 0.7-3.6 mumol l-1, P less than 0.005). The same was true 30 and 60 min after ingestion of a Lundh meal. Serum unconjugated bile acid levels above 4 mumol l-1 were found in eight of 10 patients with culture-proven small intestinal bacterial overgrowth whereas serum levels above 4 mumol l-1 were found in none of the patients from the three control groups. These results suggest that determination of unconjugated serum bile acids is of clinical value in the evaluation of patients suspected of small intestine bacterial overgrowth.

Adult↗
PubMed1988

Methanethiol and dimethylsulfide formation from 3-methylthiopropionate in human and rat hepatocytes.

This study was designed to investigate the metabolism of methanethiol, and the involvement of methanethiol and its metabolites in the transamination pathway of methionine. Gaseous methanethiol, methanethiol-mixed disulfides and dimethylsulfide were formed from 3-methylthiopropionate, a metabolite in the transamination pathway of methionine, during incubation with human and rat hepatocytes. An increase of the 3-methylthiopropionate concentration resulted in an increased formation of the products, up to a substrate concentration of 4.4 mM. Higher substrate levels resulted in a decreased methanethiol formation, probably due to poisoning of the system. However, in human hepatocytes the formation of dimethylsulfide increased up to a 3-methylthiopropionate concentration of 12.5 mM. The formation of methanethiol, dimethylsulfide and methanethiol-mixed disulfides from 3-methylthiopropionate in hepatocytes of both human and rat support the hypothesis that methanethiol can be formed from methionine via the transamination pathway.

Animals↗
PubMed1988

Differences between premenopausal women and young men in the transamination pathway of methionine catabolism, and the protection against vascular disease.

Catabolism of methionine is supposed to proceed via two known pathways: transsulphuration and transamination. In 10 premenopausal women and 13 young men we measured methionine, the transsulphuration metabolite homocysteine, and the transamination metabolites 4-methylthio-2-oxo-butryate and methanethiol mixed disulphides in the fasting state as well as after oral administration of 0.1 g L-methionine kg-1 body weight. Both in the fasting state and after methionine loading the concentrations of homocysteine in serum were significantly lower in premenopausal women than in young men. Since there is evidence that even a moderate homocysteinaemia may be a risk factor in the development of vascular disease, the low homocysteine levels could be an additional factor contributing to the lower incidence of vascular disease in premenopausal women. After oral methionine these women showed significantly higher concentrations both in serum and urine of the transamination metabolites than the group of men. This higher methionine transamination in premenopausal women may contribute to keeping the homocysteine levels low and may therefore have an impact on the protection of these women against vascular disease.

Adolescent↗
PubMed1988

Transsulfuration in an adult with hepatic methionine adenosyltransferase deficiency.

We investigated sulfur and methyl group metabolism in a 31-yr-old man with partial hepatic methionine adenosyltransferase (MAT) deficiency. The patient's cultured fibroblasts and erythrocytes had normal MAT activity. Hepatic S-adenosylmethionine (SAM) was slightly decreased. This clinically normal individual lives with a 20-30-fold elevation of plasma methionine (0.72 mM). He excretes in his urine methionine and L-methionine-d-sulfoxide (2.7 mmol/d), a mixed disulfide of methanethiol and a thiol bound to an unidentified group X, which we abbreviate CH3S-SX (2.1 mmol/d), and smaller quantities of 4-methylthio-2-oxobutyrate and 3-methylthiopropionate. His breath contains 17-fold normal concentrations of dimethylsulfide. He converts only 6-7 mmol/d of methionine sulfur to inorganic sulfate. This abnormally low rate is due not to a decreased flux through the primarily defective enzyme, MAT, since SAM is produced at an essentially normal rate of 18 mmol/d, but rather to a rate of homocysteine methylation which is abnormally high in the face of the very elevated methionine concentrations demonstrated in this patient. These findings support the view that SAM (which is marginally low in this patient) is an important regulator that helps to determine the partitioning of homocysteine between degradation via cystathionine and conservation by reformation of methionine. In addition, these studies demonstrate that the methionine transamination pathway operates in the presence of an elevated body load of that amino acid in human beings, but is not sufficient to maintain methionine levels in a normal range.

Adult↗
PubMed1988

Methanethiol metabolism in whole blood.

The metabolism of methanethiol in whole blood has been described. Incubation of carbon 14-labeled or sulfur 35-labeled gaseous methanethiol resulted in complete trapping of methanethiol by whole blood within 30 minutes. After trapping, both labels were found to be equally distributed over plasma and erythrocytes. Eighty to ninety percent of both labels could be extracted from erythrocytes incubated in saline solution. The chemical properties of the 14C and 35S labels in saline solution differed completely. The 14C label was not precipitated by BaCl2, was moderately volatile, and could be extracted by either (pH 1). In contrast, the 35S label was precipitated by BaCl2, was not volatile, and was not extracted by ether. It is concluded that the central carbon-sulfur bond of methanethiol is split by incubation with whole blood. Plasma components are not involved in this process. Most likely, methanethiol becomes largely oxidized by erythrocytes to formic acid and sulfite or sulfate. Only 10% of methanethiol became firmly bound to erythrocytes. One to two percent was transformed to protein--S--S--CH3 and 1% to dimethyl sulfide by the enzyme thiol methyltransferase.

Carbon Radioisotopes↗
PubMed1986

Determination of volatile sulphur compounds in air at the parts per trillion level by Tenax trapping and gas chromatography.

A gas chromatographic technique is described for measuring various volatile sulphur compounds (H2S, COS, CS2, thiols, sulphides, disulphides) in air at the parts per trillion level. The sulphur compounds are trapped and concentrated at -196 degrees C in a small glass tube filled with the porous polymer Tenax GC. The excess of water in the air samples is pretrapped by calcium chloride, which drying agent does not adsorb any of the sulphur volatiles. The Tenax trap tube fits exactly in the injection port of the gas chromatograph, where the adsorbed sulphur compounds are liberated at 200 degrees C directly into the carrier gas stream and are transferred to the gas chromatographic column. The sulphur compounds are then assayed by means of a flame photometric detector. The Tenax trap tubes can be stored at -196 degrees C for more than 1 week without any loss of sulphur volatiles.

Air Pollutants↗
PubMed1986

Analysis of conjugated and unconjugated bile acids in serum and jejunal fluid of normal subjects.

A reliable method is described for the determination of conjugated and unconjugated bile acids in serum and jejunal fluid. Bile acids are extracted using reverse-phase octadecylsilane bonded silica cartridges and are separated into their unconjugated and conjugated fractions using the lipophilic anion exchanger diethylaminohydroxypropyl Sephadex LH-20 (DEAP-LH-20). The conjugated fraction can be separated into a glycine and a taurine fraction, using the same anion exchanger. The bile acids are measured using a hydroxysteroid dehydrogenase-fluorimetric assay for serum and a hydroxysteroid dehydrogenase-photometric assay for jejunal fluid. The normal fasting serum value of total 3 alpha-hydroxy bile acids amounts to 3.5 +/- 2.8 mumol/l (mean +/- SD, range 1.4-10.8, n = 22). The corresponding unconjugated bile acid fraction amounts to 39.9 +/- 11.2% (range 20.7-64.6%) of total bile acids. The concentration of conjugated bile acids became significantly elevated 30, and 60 min after a standard meal, whereas that of unconjugated bile acids remained unchanged. In jejunal fluid only conjugated bile acids are found, as well in fasting subjects as postprandial, 30 or 60 min after a standard meal.

Bile Acids and Salts↗
PubMed1985

New methods for the release of volatile sulfur compounds from human serum: its determination by Tenax trapping and gas chromatography and its application in liver diseases.

New methods are described for the release of sulfur volatiles from human serum or whole blood and for its determination by Tenax trapping and gas chromatography by use of a specific sulfur detector. Methanethiol (MT) is covalently bound in serum in at least two different ways. One fraction of MT is released by addition of acid and is covalently bound to a compound with a mol wt less than 500, probably as methyl-beta-D-thioglucuronide. Another fraction of MT is released by reaction with dithiothreitol and is covalently bound to proteins in a disulfide linkage. No significant differences were observed in the protein-bound MT fraction between normal individuals and patients with cirrhosis. In contrast, the acid-hydrolyzable MT fraction was significantly elevated (P less than 0.0001) in the group with cirrhosis (0.41 +/- 0.19 mumol/L, mean +/- SD, n = 39) compared with the normal group (0.22 +/- 0.04 mumol/L, n = 21). The acid-hydrolyzable MT fraction is excreted in the urine. The concentration in normal persons amounted to 9 to 37 mumol/L. Dimethylsulfide (DMS) was measured in whole blood. There was a close correlation between venous blood DMS concentration and its concentration in breath. Dimethyldisulfide was not present in detectable amounts in the blood of normal individuals. Ethanethiol was absent in the serum and blood of all studied subjects.

Breath Tests↗
PubMed1983

A new sensitive assay for measuring volatile sulphur compounds in human breath by Tenax trapping and gas chromatography and its application in liver cirrhosis.

A new analytical technique is described for measuring volatile sulphur compounds in human breath. The sulphur compounds were trapped and concentrated onto Tenax GC and then assayed by gas chromatography, using a specific sulphur detector. The detection limit amounts to about 0.2 ng/l (0.1 ppb). Among the sulphur volatiles, dimethylsulphide and methanethiol were quantitatively analysed in 100 ml of breath of 20 normal subjects and 35 cirrhotic patients. Dimethylsulphide in the breath of cirrhotics (113.4 +/- 31.9 ng/l, mean +/- SEM) was significantly elevated (p less than 0.05) compared with normals (21.1 +/- 1.7 ng/l). The concentration of methanethiol in the breath of normals and of most cirrhotics was less than 1 ng/l. In only five cirrhotics could methanethiol be detected in 100 ml of breath (3-23 ng/l). Dimethyldisulphide and hydrogen sulphide were not present in detectable amounts in the breath of normals. In cirrhotics, dimethyldisulphide was detected in a few cases. Ethanethiol was absent in the breath of both normals and cirrhotics.

Breath Tests↗
PubMed1982

The development of a new hemoperfusion column: the filmadsorber.

A hemoperfusion system has been developed in which very small charcoal particles (average diameter 40 micrometers) are embedded and immobilized in a collodion film (Filmadsorber). In vitro studies revealed that the absorption of bile acids by these small charcoal particles is superior to that by larger ones (size: 0.5 to 5 mm) as used in commercially available adsorbers. In vivo studies confirmed these results: dogs with ligated bile ducts were subjected to hemoperfusion through different types of charcoal adsorbers. Bile acid clearances of filmadsorbers containing less charcoal than the commercials were significantly higher.

Animals↗
PubMed1981

Is the measurement of blood cimetidine levels useful?

1 Blood cimetidine levels were measured up to 5 h after oral intake of 200 mg cimetidine with breakfast in 13 duodenal, 5 gastric and 15 anastomotic ulcer patients. 2 There were larger inter individual differences in results. The mean peak blood concentrations was 1.14 +/- 0.07 microgram/ml (range 0.54-1.94 microgram/ml), the mean period during which the blood concentration exceeded 0.5 microgram/ml was 141 +/- 11 min (range 23-306 min) and the mean area under the cimetidine blood concentration curve (AUC) was 166 +/- 8 microgram ml-1 min (range 96-280 microgram ml-1 min). Coefficient of variation of these parameters was 33%, 43% and 29% respectively. 3 There were no significant differences in these parameters between non-operated patients and patients with a partial gastrectomy. 4 In 11 patients restudied after 2 to 5 months blood cimetidine levels proved well reproducible; mean coefficient of variation of peak blood levels was 8.5 +/- 2.4%, of time during which blood levels exceeded 0.5 microgram/ml 7.6 +/- 2.5% and of the AUC 5.0 +/- 1.0%. 5 There was no difference in peak blood levels, duration of blood level exceeding 0.5 microgram/ml and blood cimetidine AUC between 24 patients healed after 4 weeks cimetidine therapy and 9 in whom healing took longer. Likewise, there was no evidence of lower blood cimetidine concentrations in 9 patients who relapsed during maintenance cimetidine treatment compared with 24 who did not relapse.

Cimetidine↗
PubMed1981

Acid citrate dextrose reduces platelet retention during in vitro and in vivo dog hemoperfusion: a comparative study of different charcoal adsorbers.

Hemoperfusion through charcoal adsorbers has often been proposed for use in exogenous and endogenous intoxication. A serious drawback of this technique is the often encountered loss of platelets and leucocytes. In vitro hemoperfusion studies with heparinized human blood and in vivo hemoperfusion of heparinized Labrador dogs through different types of charcoal adsorbers (Becton-Dickinson [B-D], Gambro, Haemocol) clearly demonstrated that addition of the anticoagulant acid citrate dextrose (ACD) might reduce the loss of platelets. ACD seemed to have no distinct influence on leucocyte retention.

Adsorption↗