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D Bier

Publications and source records attributed to D Bier.

At least 19 recordsLinked to original sources
PubMed1999

Sympathomimetic effects of MIBG: comparison with tyramine.

UNLABELLED: Because nothing is known about whether metaiodobenzylguanidine (MIBG) has tyramine-like actions, the sympathomimetic effects of MIBG were determined in the isolated rabbit heart and compared with those of tyramine. METHODS: Spontaneously beating rabbit hearts were perfused with Tyrode's solution (Langendorff technique; 37 degrees C; 26 mL/min), and the heart rate as well as the norepinephrine and dopamine overflow into the perfusate was measured before and after doses of MIBG or tyramine (0.03-10 micromol) given as bolus injections (100 microL) into the aortic cannula. Km and Vmax values for the neuronal uptake (uptake1) of 125I-MIBG and 14C-tyramine were obtained in human neuroblastoma (SK-N-SH) cells. The Ki of MIBG for inhibition of the 3H-catecholamine uptake mediated by the vesicular monoamine transporter was determined in membrane vesicles obtained from bovine chromaffin granules and compared with the previously reported Ki value for tyramine determined under identical experimental conditions. RESULTS: By producing increases in heart rate and norepinephrine overflow, both compounds had dose-dependent sympathomimetic effects in the rabbit heart. MIBG was much less effective than tyramine in increasing heart rate (maximum effect 59 versus 156 beats/min) and norepinephrine overflow (maximum effect 35 versus 218 pmol/g). Tyramine also caused increases in dopamine overflow, whereas MIBG was a poor dopamine releaser. At a dose of 10 micromol, the increase in heart rate lasted more than 60 min after MIBG and about 20 min after tyramine injection. Accordingly, the norepinephrine overflow caused by 10 micromol MIBG and tyramine declined with half-lives of 57.8 and 2.2 min, respectively. The effects of both drugs were drastically reduced in hearts exposed to 2 micromol/L desipramine. The kinetic parameters characterizing the saturation of neuronal uptake by 125I-MIBG and 14C-tyramine were similar for the two compounds: Km values of MIBG and tyramine were 1.6 and 1.7 micromol/L, respectively, and Vmax values of MIBG and tyramine were 43 and 37 pmol/mg protein/min, respectively. However, in inhibiting the vesicular 3H-catecholamine uptake, MIBG was eight times less potent than tyramine. CONCLUSION: MIBG is much less effective than tyramine as an indirect sympathomimetic agent. This is probably a result of its relatively low affinity for the vesicular monoamine transporter and explains the relatively poor ability of the drug to mobilize norepinephrine stored in synaptic vesicles. The long duration of MIBG action results primarily from the drug not being metabolized by monoamine oxidase. The sympathomimetic effects of MIBG described here are not likely to come into play in patients given diagnostic or common therapeutic doses of radioiodinated MIBG.

3-Iodobenzylguanidine↗
PubMed1998

Rapid urinary iodide test.

Assessment of iodine deficiency and monitoring of iodine supplementation programs demands rapid, simple and cost-effective methods for the determination of urinary iodide concentrations. We propose a rapid test based on the iodide-catalyzed oxidation of 3,3',5,5'-tetramethylbenzidine by peracetic acid/H2O2 to yield colored products. The color of the chemical reaction is compared with color categories of a pictogram corresponding to three ranges (<10, 10-30, and >>30 microg/100 mL) of iodide concentrations. The test is very easy to perform and does not require any instrumentation or apparatus. Sample preparation is simple and consists in the removal of interfering substances by disposable columns, 65 x 10.5 mm, packed with specifically prepared activated charcoal. For comparison with a reference method for measuring urinary iodide (HPLC), we determined the iodide concentrations of 370 random (untimed) urine samples from consecutive patients by both HPLC and the rapid test. The results obtained by both methods are in close agreement with respect to classification of the samples according to the above three ranges, with a maximum difference of <5% for each range. This rapid test is therefore very well suited to epidemiological surveys of iodine deficiency especially in developing countries.

Benzidines↗
PubMed1998

Methodological and analytical aspects of simple methods for measuring iodine in urine. Comparison with HPLC and Technicon Autoanalyzer II.

This work describes an optimization of a simple photometric determination of iodine concentrations in urine using a modified ceric arsenite method with ammonium persulfate as oxidant. By means of this sensitive method iodine concentrations can be determined in very small specimens (50 microL). Urine samples (105) collected from a mixed population, were analyzed for urine iodine content by the optimized ammonium persulfate method, a Technicon Autoanalyzer II and a paired-ion-RP HPLC. We found that the precision of this optimized ammonium persulfate method yields inter assay CVs of <10% for urinary iodine concentrations >10 microg/dL. Recovery of [123I]iodide added to urine in vitro was 100.9 +/- 2.4%. The detection limit was 0.0029 microg iodine. There was a high correlation between all three methods (r > 0.94 in any case) and the interpretation of the results was consistent. We conclude that this simple, manual ammonium persulfate method is suitable for urinary iodine analysis and can be performed in any routine clinical laboratory.

Ammonium Sulfate↗
PubMed1998

X-ray fluorescence analysis (XFA) of thyroidal iodine content (TIC) with an improved measuring system.

X-ray fluorescence analysis is based on the principal that the electron structure of stable iodine in the thyroid is excited by Americium-241 gamma rays to emit a characteristic fluorescence radiation which is proportional to the amount of iodine present in the gland. A stationary measuring system consisting of a 11.1 GBq Am-241 source and a high-purity Germanium detector with spectrum analyser has been improved by a PC guided method for sonographic definition of the measuring volume. The lower limit of detectibility of the system corresponds to 0.01 mg of Iodine per ml of thyroid volume; the in vivo precision given as coefficient of variation amounts to 15%. The thyroid is exposed with a radiation dose of 6 microSv per measurement. First studies with this improved system carried out in 50 female volunteers between 20 and 40 years of age with normal thyroid volumes resulted in a mean iodine concentration of the thyroid of 0.665 +/- 0.304 mg/ml. The mean iodine excretion in urine was normal with 10.8 +/- 10.4 microg/dl.

Adult↗
PubMed1998

Methods for measuring iodine in urine and serum.

The most important information in the determination of the status of iodine nutrition of a population comes from the measurement of the urinary excretion of iodine. Several methods are available for measuring urinary iodine. The choice among methods depends on the intended application, the number of samples, the cost and the technical capability. Epidemiological field studies demand simple, rapid and cost-effective methods. Suitable for these applications are the rapid urinary iodide test and the ammonium persulfate oxidation method which gives comparable results to the chloric acid method without having the drawbacks of being hazardous and explosive. In research studies however, sophisticated automated technology like the Technicon Autoanalyzer or Paired-Ion Reversed Phase HPLC are used in which the high cost of instrumentation are outweighed by the benefits of processing a large number of samples with high accuracy and minimal technician time. For determining serum inorganic iodide (SII) the HPLC assay is the method of choice, because contaminations from the protein bound iodine fraction do not interfere with the detection process. The clinical relevance of the measurement of SII is limited, but allows the calculation of the absolute iodine uptake which has great value in pathophysiologic studies.

Ammonium Sulfate↗
PubMed1998

Rapid urinary iodide test.

Assessment of iodine deficiency and monitoring of iodine supplementation programs demand rapid, simple, and cost-effective methods for the determination of urinary iodide concentrations. We propose a semiquantitative rapid test, based on the iodide-catalyzed oxidation of 3,3',5,5'-tetramethylbenzidine by peracetic acid/H2O2, to yield colored products. The color of the chemical reaction is compared with color categories of a pictogram corresponding to three ranges: <100, 100-300, and >300 microg/L (<0.79, 0.79-2.36, and >2.36 micromol/L) of iodide concentrations. The test is very easy to perform and does not require any instrumentation or apparatus. Sample preparation is simple and consists of the removal of interfering substances by disposable columns, 65 x 10.5 mm, packed with purified activated charcoal. For comparison with a reference method for measuring urinary iodide, by high-performance liquid chromatography, we determined the iodide concentrations of 370 random (untimed) urine samples from consecutive patients by both high-performance liquid chromatography and the rapid test. The results obtained by both methods are in close agreement, with respect to classification of the samples according to the above three ranges, with a maximum difference of less than 5% for each range. Median (y) values of a given distribution of urinary iodide concentrations can be calculated from the percent (x) of samples below 100 microg/L (0.79 micromol/L) using the regression equation: y = 179.78 - 1.60x. This rapid test, therefore, is suited to epidemiological surveys of iodine deficiency, especially in developing countries.

Chromatography, High Pressure Liquid↗
PubMed1997

Effect of specific activity on cardiac uptake of iodine-123-MIBG.

UNLABELLED: Radioiodinated meta-iodobenzylguanidine (MIBG), an analog of norepinephrine, has been used to assess myocardial sympathetic innervation. Recent in vivo studies predict enhanced cardiac uptake of this radiopharmaceutical with high specific activity. METHODS: To clarify the effect of specific activity on cardiac uptake of radioiodinated MIBG, the distribution and kinetics of no-carrier-added [123I]MIBG (> or = 7.4 TBq/mumol) were compared with those of commercial [123I]MIBG (approximately 74 MBq/mumol) in three healthy volunteers by serial imaging and blood sampling. RESULTS: Higher specific activity result in higher uptake of radioiodinated MIBG in all volunteers in the heart (p < 0.05) and liver (p < 0.05) but not in the lung (p = 0.26). Due to rapid deiodination, a more pronounced accumulation of radioactivity was present in plasma after no-carrier-added MIBG than commercial [123I]MIBG, resulting in higher background and thyroid activity after administration of the former. Calculated heart-to-liver (p = 0.96) and heart-to-lung (p = 0.42) count ratios in all volunteers revealed no significant improvement in cardiac imaging with no-carrier-added [123I]MIBG compared to commercial [123I]MIBG. CONCLUSION: This study highlights the appreciably higher in vivo deiodination of no-carrier-added [123I]MIBG compared to commercial preparation of [123I]MIBG in humans. Cardiac images acquired with no-carrier-added [123I]MIBG do not seem to be superior to those obtained with commercial MIBG.

3-Iodobenzylguanidine↗
PubMed1996

[Somatostatin receptor scintigraphy. Methodology, indications, results].

Somatostatin-receptor scintigraphy has been in clinical use for several years. Most of the experience with somatostatin tumor scintigraphy has been obtained with gastro-enteropathic (GEP) tumors and carcinoids. Clinical applications of somatostatin imaging have been reported in small-cell lung carcinomas, malignant lymphomas, renal-cell carcinomas, breast cancers and medullary thyroid cancers. Somatostatin analogues were initially applicable in larger medical institutions because of the necessity for radioactive labeling with iodine (octreotide to [123I-Tyr3]-octreotide); however, the clinical results with iodinated analogues were worse than the relatively new analogue [111In-DTPA-D-Phe1]octreotide, now available as Octreoscan. This review describes the current status of the clinical application of somatostatin receptor imaging, together with our own experience in carcinoids, GEP tumors and medullary thyroid carcinomas.

Carcinoid Tumor↗
PubMed1996

Radiochemical synthesis of [123I]2-iodo-lisuride for dopamine D2-receptor studies.

By variation of reaction parameters iodination of 3-(9,10-didehydro-6-methyl-8 alpha-ergolinyl)-1,1-diethylurea (lisuride) was performed with the radiohalogen [123I]iodine (t1/2 = 13.3 h). For comparative experiments and stability studies the beta(-)-emitting radioisotope [131I]iodine (t1/2 = 8.04 d) was also used. Reaction occurs at the activated position 2 of the molecule, thus leading to [123I]3-(9,10-didehydro-2-iodo-6-methyl-8 alpha-ergolinyl)-1,1-diethylurea ([123I]2-iodo-lisuride, [123I]ILIS) or the analogous [131I]iodine-labeled compound, respectively. Electrophilic radioactive species were generated by oxidation of no-carrier-added (n.c.a.) iodide with IODOGEN (1,3,4,6-tetrachloro-3 alpha,6 alpha-diphenylglycouril) fixed on the glass wall of the reaction vial prior to iodination. After optimization of reaction parameters [123I]2-iodo-lisuride after HPLC-purification was obtained with radiochemical yields of 70 +/- 5% and a radiochemical purity of > 97%. In n.c.a. syntheses, specific activities of the product were in the range between 4440 and 7400 GBq/mumol (120-200 Ci/mumol) corresponding to 50-85% of the theoretical value.

Cyclotrons↗
PubMed1996

Glutamine and alanine metabolism in NIDDM.

Gluconeogenesis is increased in NIDDM. We therefore examined the metabolism of glutamine and alanine, the most important gluconeogenic amino acids, in 14 postabsorptive NIDDM subjects and 18 nondiabetic volunteers using a combination of isotopic ([6-3H]glucose (20 microCi, 0.2 microCi/min), [U-14C]glutamine (20 microCi, 0.2 microCi/min), [3-13C]alanine (99% 13C, 2 mmol, 20 micromol/min), [ring-2H5]phenylalanine (99% 2H, 2 micromol/kg, 0.03 micromol x kg(-1) x min(-1)), and limb balance techniques. Alanine turnover (4.54 +/- 0.24 vs. 5.64 +/- 0.33 micromol x kg(-1) x min(-1)), de novo synthesis (3.00 +/- 0.25 vs. 4.01 +/- 0.33 micromol x kg(-1) x min(-1)), and conversion to glucose (1.02 +/- 0.09 vs. 1.56 +/- 0.17 micromol x kg(-1) x min(-1)) were increased in NIDDM subjects (all P < 0.01), while its forearm release (0.45 +/- 0.04 vs. 0.39 +/- 0.04 micromol x kg(-1) x min(-1)) was unaltered. Although glutamine turnover (4.81 +/- 0.23 vs. 4.40 +/- 0.31 micromol x kg(-1) x min(-1)) was unaltered in NIDDM, its conversion to glucose (0.57 +/- 0.04 vs. 1.08 +/- 0.10 micromol x kg(-1) x min(-1)) and to alanine (0.10 +/- 0.01 vs. 0.34 +/- 0.04 micromol x kg(-1) x min(-1)) (both P = 0.001) was increased while its oxidation (2.84 +/- 0.27 vs. 1.84 +/- 0.15 micromol x kg(-1) x min(-1), P = 0.03) and forearm release (0.77 +/- 0.05 vs. 0.62 +/- 0.09 micromol x kg(-1) x min(-1), P < 0.008) were both reduced. Our results thus demonstrate that there are substantial alterations of glutamine and alanine metabolism in NIDDM. Conversion of both amino acids to glucose and the proportion of their turnover used for gluconeogenesis are increased; release of both amino acids from tissues other than skeletal muscle seems to be increased. Finally, the reduction in glutamine oxidation, possibly the result of competition with glucose and free fatty acids as fuels, makes more glutamine available for gluconeogenesis without a change in its turnover.

Alanine↗
PubMed1996

Roles of glucose transport and glucose phosphorylation in muscle insulin resistance of NIDDM.

Insulin resistance for glucose metabolism in skeletal muscle is a key feature in NIDDM. The quantitative role of the cellular effectors of glucose metabolism in determining this insulin resistance is still imperfectly known. We assessed transmembrane glucose transport and intracellular glucose phosphorylation in vivo in skeletal muscle in nonobese NIDDM patients. We performed euglycemic insulin clamp studies in combination with the forearm balance technique (brachial artery and deep forearm vein catheterization) in five nonobese NIDDM patients and seven age- and weight-matched control subjects (study 1). D-Mannitol (a nontransportable molecule), 3-O-[14C]methyl-D-glucose (transportable, but not metabolizable) and D[3-3H]glucose (transportable and metabolizable) were simultaneously injected into the brachial artery, and the washout curves were measured in the deep venous effluent blood. In vivo rates of transmembrane transport and intracellular phosphorylation of D-glucose in forearm muscle were determined by analyzing the washout curves with the aid of a multicompartmental model of glucose kinetics in forearm tissues. At similar steady-state concentrations of plasma insulin (approximately 500 pmol/l) and glucose (approximately 5.0 mmol/l), the rates of transmembrane influx (34.3 +/- 9.1 vs. 58.5 +/- 6.5 micromol x min(-1) x kg(-1), P < 0.05) and intracellular phosphorylation (5.4 +/- 1.6 vs. 38.8 +/- 5.1 micromol x min(-1) x kg(-1), P < 0.01) in skeletal muscle were markedly lower in the NIDDM patients than in the control subjects. In the NIDDM patients (study 2), the insulin clamp was repeated at hyperglycemia, (approximately 13 mmol/l) trying to match the rates of transmembrane glucose influx measured during the clamp in the controls. The rate of transmembrane glucose influx (62 +/- 15 micromol x min(-1) x kg(-1)) in the NIDDM patients was similar to the control subjects, but the rate of intracellular glucose phosphorylation (16.6 +/- 7.5 micromol x min(-1) x kg(-1)), although threefold higher than in the patients during study 1 (P < 0.05), was still approximately 60% lower than in the control subjects (P < 0.05). These data suggest that when assessed in vivo, both transmembrane transport and intracellular phosphorylation of glucose are refractory to insulin action and add to each other in determining insulin resistance in skeletal muscle of NIDDM patients. It will be of interest to compare the present results with the in vivo quantitation of the initial rate of muscle glucose transport when methodology to perform this measurement becomes available.

3-O-Methylglucose↗
PubMed1995

Recovery from Wernicke's aphasia: a positron emission tomographic study.

Changes in the organization of the brain after recovery from aphasia were investigated by measuring increases in regional cerebral blood flow (rCBF) during repetition of pseudowords and during verb generation. Six right-handed patients who had recovered from Wernicke's aphasia caused by an infarction destroying the left posterior perisylvian language zone were compared with 6 healthy, right-handed volunteers. In the control subjects, strong rCBF increases were found in the left hemisphere in the posterior part of the superior and middle temporal gyrus (Wernicke's area), and during the generation task in lateral prefrontal cortex (LPFC) and in inferior frontal gyrus (Broca's area). There were some weak right hemisphere increases in superior temporal gyrus and inferior premotor cortex. In the patients, rCBF increases were preserved in the frontal areas. There was clear right hemisphere activation in superior temporal gyrus and inferior premotor and lateral prefrontal cortices, homotopic to the left hemisphere language zones. Increased left frontal and right perisylvian activity in patients with persisting destruction of Wernicke's area emphasizes redistribution of activity within the framework of a preexisting, parallel processing and bilateral network as the central mechanism in functional reorganization of the language system after stroke.

Aged↗
PubMed1995

[Somatostatin receptor scintigraphy in medullary thyroid carcinomas, GEP and carcinoid tumors].

For this study, 24 patients with medullary thyroid cancer (MTC) and 10 with carcinoid-/GEP-tumours underwent scintigraphy with 123I-Tyr3-octreotide or 111In-DTPA-D-Phe1-octreotide (Octreoscan) or 99mTc-V-DMSA. Calcitonin and CEA were elevated in MTC patients, the other had tumour lesions on CT. Octreoscan-scintigraphy was positive in 68% of all suspicious cases. On the other hand, 123I-Tyr3-octreotide showed only rarely positive results. 99mTc-V-DMSA-scans in MTC patients were positive in 23%. Liver metastases could be seen only with Octreoscan in the non-MTC-group. These results showed better sensitivity of 111In-labelled octreotide.

Adult↗
PubMed1993

Transmembrane glucose transport in skeletal muscle of patients with non-insulin-dependent diabetes.

Insulin resistance for glucose metabolism in skeletal muscle is a key feature in non-insulin-dependent diabetes mellitus (NIDDM). Which cellular effectors of glucose metabolism are involved is still unknown. We investigated whether transmembrane glucose transport in vivo is impaired in skeletal muscle in nonobese NIDDM patients. We performed euglycemic insulin clamp studies in combination with the forearm balance technique (brachial artery and deep forearm vein catheterization) in six nonobese NIDDM patients and five age- and weight-matched controls. Unlabeled D-mannitol (a nontransportable molecule) and radioactive 3-O-methyl-D-glucose (the reference molecular probe to assess glucose transport activity) were simultaneously injected into the brachial artery, and the washout curves were measured in the deep venous effluent blood. In vivo transmembrane transport of 3-O-methyl-D-glucose in forearm muscle was determined by computerized analysis of the washout curves. At similar steady-state plasma concentrations of insulin (approximately 500 pmol/liter) and glucose (approximately 5.15 mmol/liter), transmembrane inward transport of 3-O-methyl-D-glucose in skeletal muscle was markedly reduced in the NIDDM patients (6.5 x 10(-2) +/- 0.56 x 10(-2).min-1) compared with controls (12.5 x 10(-2) +/- 1.5 x 10(-2).min-1, P < 0.005). Mean glucose uptake was also reduced in the diabetics both at the whole body level (9.25 +/- 1.84 vs. 28.3 +/- 2.44 mumol/min per kg, P < 0.02) and in the forearm tissues (5.84 +/- 1.51 vs. 37.5 +/- 7.95 mumol/min per kg, P < 0.02). When the latter rates were extrapolated to the whole body level, skeletal muscle accounted for approximately 80% of the defect in insulin action seen in NIDDM patients. We conclude that transmembrane glucose transport, when assessed in vivo in skeletal muscle, is insensitive to insulin in nonobese NIDDM patients, and plays a major role in determining whole body insulin resistance.

Adult↗
PubMed1984

Effects of intravenous glucose on whole body leucine dynamics, studied with 1-13C-leucine, in healthy young and elderly adults.

We examined whole body leucine metabolism in healthy young and elderly adults while in the postabsorptive state and during an intravenous glucose administration at two rates. Leucine flux, incorporation into whole body protein, and oxidation were estimated from a continuous intravenous infusion of L-[1-13C]leucine and determination of 13C enrichment in plasma leucine and expired air. Per unit of body weight, leucine flux and rates of incorporation into protein were similar in young and old men. Old women showed lower rates compared with young women. Rates were similar for both age groups when expressed per unit of total body water and/or of muscle protein mass. Intravenous glucose infusion (4 mg . kg-1 . min-1) reduced plasma leucine levels and flux similarly in both age groups. Thus, age-related differences in muscle mass and sensitivity of peripheral tissues to insulin-mediated glucose uptake and metabolism are not paralleled by alterations in whole body leucine kinetics in the postabsorptive state.

Adult↗
PubMed1982

The use of deuterated phenylalanine for the in vivo assay of phenylalanine hydroxylase activity in children.

Fifteen children, five with phenylketonuria (PKU), five with hyperphenylalaninaemia, and five phenotypically normal but at risk of being carriers for PKU, were given [ring 2H5]phenylalanine orally in amounts ranging from 75 mg/kg to 10 mg/kg. Plasma was assayed for [2H5]phenylalanine and [2H4]tyrosine at hourly intervals, the amino acids being measured as the N-acetyl, n-propyl esters by gas chromatography-mass spectroscopy. The results obtained were calculated as the log of the ratio [2H5]phenylalanine: [2H4]tyrosine in the plasma. The five patients with PKU had ratios of infinity because no [2H4]tyrosine was measured in their plasma during the experimental period. The patients with hyperphenylalaninaemia had log ratios over 2.00 throughout the assay period. Among the five normal children three are considered to be carriers for PKU as the logarithms of the [2H5]phenylalanine: [2H4]tyrosine ratios were 1.77, 1.73, and 1.33 and remained over 1.00 during the assay period. The other children had log ratios of 1.16 and 1.00 at the first hour which dropped below 1.00 subsequently, suggesting normal activity of phenylalanine hydroxylase.

Child↗
PubMed1980

Dynamic aspects of whole body glycine metabolism: influence of protein intake in young adult and elderly males.

The influence of adult age and adequacy of dietary protein intake on whole body glycine metabolism was studied in human subjects. Five healthy young adult males (19-25 yr) and six elderly males (64-78 yr) were given an adequate-protein diet (1.5 g protein/kg/day) for 7 days and a low-protein diet (0.4 g protein/kg/day) for 14 days. At the end of each dietary period, whole body glycine flux and rates of glycine synthesis were estimated with the use of a continuous 60 hr oral administration of 15N-glycine and determination of 15N enrichment of plasma glycine by gas chromatography-mass spectrometry with selected ion monitoring. Mean whole body glycine flux and the rate of endogenous glycine synthesis were 458 and 351 micromole/kg body weight/hr, respectively, for young adults receiving the diet adequate in protein; similar values were obtained in the elderly group. Feeding the diet low in protein resulted in an extensive and significant reduction in both parameters in young adults and also in elderly subjects to a similar extent. Measurement of 15N enrichment in plasma serine gave a constant ratio of 15N enrichment in plasma free serine relative to glycine for both age groups and at the two protein intake levels. It is concluded that aging of adults has little impact on the quantitative aspects of whole body glycine metabolism, but that it responds extensively to changes in protein intake. Thus, it appears that glycine synthesis and flux are integrated with the body's total nitrogen metabolism and requirement for dietary nitrogen.

Adult↗