Infrared-active phonons and the superconducting gap of Tc-reduced double-chain YBa2Cu4O8 superconductors.
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Journal Article↗
Biomedical subjects
C Thomsen
Publications and source records attributed to C Thomsen.
Actions of phenylglycine analogs at subtypes of the metabotropic glutamate receptor family.
The functional effects of phenylglycine analogs on metabotropic glutamate receptor (mGluR) subtypes mGluR1 alpha, mGluR2 and mGluR4 were examined. (S)-4-Carboxyphenylglycine (IC50 = 65 +/- 5 microM), (R,S)-alpha-methyl-4-carboxyphenylglycine (IC50 = 155 +/- 38 microM) and (S)-3-carboxy-4-hydroxyphenylglycine (IC50 = 290 +/- 47 microM) competitively antagonized glutamate-stimulated phosphoinositide hydrolysis in baby hamster kidney (BHK) cells stably expressing mGluR1 alpha. (S)-4-Carboxyphenylglycine and (R,S)-alpha-methyl-4-carboxyphenylglycine competitively antagonized glutamate-induced inhibition of forskolin-stimulated cAMP-formation in BHK cells stably expressing mGluR2 with IC50 values of 577 +/- 74 microM and 340 +/- 59 microM, respectively. (R,S)-4-carboxy-3-hydroxyphenylglycine, (R)-3-hydroxyphenylglycine and (S)-3-carboxy-4-hydroxyphenylglycine were agonists at mGluR2 with EC50 values of 48 +/- 5 microM, 451 +/- 93 and 97 +/- 12 microM, respectively. In parallel experiments, no activities of these phenylglycine analogs at mGluR4 were observed. The present report demonstrates that phenylglycine analogs possess differential functional activities at subtypes of the mGluR family.
Animals↗
Hepatic metabolism during constant infusion of fructose; comparative studies with 31P-magnetic resonance spectroscopy in man and rats.
A protocol of constant infusion of fructose has been carried out both in human volunteers and in the perfused rat liver, aiming at a steady-state blood fructose concentration of 6-8 mM. Localized 31P-NMR spectroscopy and biochemical analyses were used to evaluate the metabolic changes. Comparison of the model experiment and the clinical study allowed an evaluation of this protocol as a clinically relevant assessment of the metabolic function of the liver. The time course of change, as well as the quasi steady-state levels reached during fructose infusion, for phosphomonoesters (PME), ATP and inorganic phosphate (Pi) provided the following results: During fructose infusion, ATP and Pi reached a steady-state level of 74.0 +/- 5.9 and 54.6 +/- 3.3% of control respectively, in the human volunteers. The corresponding data in the rat liver was 71.3 +/- 4.3 and 54.4 +/- 4.3%. Hepatic clearance of fructose was 0.53 and 0.52 ml.g liver-1.min-1 for volunteers and rats, respectively. The time course of intracellular metabolite recovery after fructose could be approximated by a first order kinetic. The rate constants for PME and ATP change were similar during fructose infusion and recovery, while after the discontinuation of fructose infusion, Pi increased with a rate constant significantly greater than during its fructose-induced depletion in human liver (P < 0.005). Thus, this relatively simple clinically applicable protocol seems to be verifiable in the well controlled perfused rat liver model, and it is argued that it may be useful in the clinical evaluation of the metabolic functional capacity of the human liver.
Adult↗
Simultaneous 31P NMR spectroscopy and EMG in exercising and recovering human skeletal muscle: technical aspects.
The bioenergetics of human skeletal muscle can be studied by 31P NMR spectroscopy (31P-MRS) and by surface electromyography (SEMG). Simultaneous 31P-MRS and SEMG permit accurate and noninvasive studies of the correlation between metabolic and electrical changes in exercising and recovering human skeletal muscle, a relationship that is still poorly understood. This study describes the optimization of skeletal muscle 31P-MRS in a whole-body magnet, involving surface coil design, utilization of adiabatic radio frequency pulses and advanced time-domain fitting, to the technical design of SEMG. A nonmagnetic ergometer was used for ankle dorsiflexions that activated only the anterior tibial muscle as verified by post exercise imaging. The coil design and the adiabatic sech/tanh pulse improved sensitivity by 45% and 56% respectively, compared with standard techniques. Simultaneous electromyographic recordings did not deteriorate the NMR spectra. The VARPRO time domain fitting routine was very suitable for estimating 31P muscle spectra. With these methods it was possible to accurately estimate parameters describing metabolic and electrical changes during rest, exercise and the entire recovery period with a 20-s time resolution on a standard 1.5 T whole-body NMR scanner.
Ankle Joint↗
Functional MRI of CO2 induced increase in cerebral perfusion.
The sensitivity of MR gradient echo imaging towards CO2 induced changes in cerebral blood flow was investigated in 10 normal subjects. The subjects were inhaling 5% and 7% CO2 and the experiments were carried out at 1.5 T (n = 6) and 2.0 T (n = 5), allowing a comparison of field strengths. Additional experiments were carried out using a higher spatial resolution. The largest signal increases were noted in areas corresponding to larger vessels, but significant changes were also conspicuous in deeper cortical and central grey matter. The changes appeared linearly related to the arterial CO2 tension, within the range of PaCO2 studied. In white matter, the changes were not statistically significant.
Administration, Inhalation↗
Cerebrospinal fluid flow and production in patients with normal pressure hydrocephalus studied by MRI.
An interleaved velocity-sensitised fast low-angle shot pulse sequence was used to study cerebrospinal fluid (CSF) flow in the cerebral aqueduct, and supratentorial CSF production in 9 patients with normal pressure hydrocephalus (NPH) and 9 healthy volunteers. The peak aqueduct CSF flow, both caudal and rostral, was significantly increased in patients with NPH. No significant difference in the supratentorial CSF production rate was found between patients (mean 0.60 +/- 0.59 ml/min) and healthy volunteers (mean 0.68 +/- 0.31 ml/min). Our method may be useful for investigation and monitoring of patients with NPH before and after ventriculoperitoneal shunt operations.
Adult↗
Assessment of CSF dynamics and venous flow in the superior sagittal sinus by MRI in idiopathic intracranial hypertension: a preliminary study.
A velocity-sensitive magnetic resonance imaging (MRI) phase-mapping method was used for non-invasive study of cerebrospinal fluid (CSF) flow in the cerebral aqueduct, for indirect calculation of supratentorial CSF production, and for measurement of blood flow in the superior sagittal sinus (SSS). We examined 12 patients with idiopathic intracranial hypertension (IIH; pseudotumour cerebri), and 10 healthy volunteers. The peak caudal and rostral CSF flow in the aqueduct during the cardiac cycle did not differ significantly between the patients and the volunteers. A significant correlation was found between the CSF volume flow amplitude and the resistance to cerebrospinal fluid outflow in the patients (p < 0.05). The calculated mean supratentorial CSF production rate was 0.79 ml/min in the patients and 0.70 ml/min in the controls, but this difference was not statistically significant. However, the MRI measurements suggested CSF hypersecretion in three patients, whereas increased transependymal passage of CSF could have been the cause of negative calculated CSF production rates in two others. A tendency towards lower mean blood flow in the SSS (mean 345 ml/min) in the patients than in the controls (mean 457 ml/min) was found, and in two patients showed very low values. We showed that MRI phase-mapping may be used to study the relative importance of the pathophysiological factors thought to play a role in the development of IIH.
Adult↗
Decrease in von Willebrand factor levels after a high-monounsaturated-fat diet in non-insulin-dependent diabetic subjects.
High levels of von Willebrand factor (vWF) have been reported in diabetics with vascular complications, suggesting a role for this protein in the development of cardiovascular complications in non-insulin-dependent diabetes mellitus (NIDDM). Recently, a diet rich in monounsaturated fatty acids (MUFA) has been found to improve glycemic control and decrease diurnal blood pressure as compared with a high-carbohydrate (H-CHO) diet in NIDDM subjects. To study the impact of MUFA on the hemostatic system, we compared the levels of vWF, fibrinogen, fibronectin, and alpha 2-macroglobulin before and after 3 weeks on a high-MUFA (H-MUFA) diet and on an isocaloric H-CHO diet in 15 NIDDM subjects. In a crossover study, the patients were randomly assigned to a H-CHO diet (50% carbohydrate, 30% fat [10% MUFA]) or a H-MUFA diet (30% carbohydrate, 50% fat [30% MUFA]). Before and on the last day of the two diets, vWF, fibrinogen, fibronectin, and alpha 2-macroglobulin levels were measured. The H-MUFA diet caused a decrease in vWF from 1.31 +/- 0.08 to 1.13 +/- 0.08 U/mL (P < .004), whereas an unchanged level was observed after a H-CHO diet (1.19 +/- 0.11 v 1.25 +/- 0.11 U/mL, NS). The relative changes in vWF during 3 weeks on a H-MUFA and on a H-CHO diet attained -12.5% +/- 3.2% versus 5.7% +/- 3.5%, respectively (P < .0001). Furthermore, unchanged levels of fibrinogen, fibronectin, and alpha 2-macroglobulin were seen after usage of the two diets.(ABSTRACT TRUNCATED AT 250 WORDS)
Cross-Over Studies↗
Pulse sequence design for MR velocity mapping of complex flow: notes on the necessity of low echo times.
Lowering of the echo time (TE) has been proposed as a way to reduce effects of phase dispersion in MR velocity mapping, because a low TE reduces sensitivity to higher-order motion terms while first-order velocity sensitivity is maintained. Methods of lowering TE involves the use of extreme gradient ramp times and gradient strengths as well as reduction of the duration of transmit/receive windows, the latter method causing decrements in image resolution. When reducing higher-order sensitivity, however, it is not the overall TE that is the critical parameter, but rather the time pattern of the gradients used in the experiment. Hence, changes in TE without subsequent variations in gradient pattern would, according to theory, not affect quantitative measurements of complex flow and vice versa. In this study, we experimentally demonstrate this relation and utilize the experience to create a sequence robust towards complex flow without sacrifices in image resolution. Our experimental observations show that variations in TE alone while maintaining the time course of the velocity-encoding gradient does not significantly affect measurements of through-plane average complex flow in the studied velocity range. A parameter that cannot be measured as accurately if TE is increased is the peak flow. A phase mapping sequence with prolonged TE from 3 ms to 5 ms but with short duration of the velocity-encoding (section-selective) gradient and improved in-plane resolution was demonstrated in vivo.
Aorta↗
Quantification of liver fat using magnetic resonance spectroscopy.
Localized proton MR spectroscopy using stimulated echoes was used to quantify the liver fat concentration in patients with various degrees of fatty liver due to alcohol abuse. Ten patients underwent a liver biopsy followed by chemical triglyceride estimation of the fatty content. A statistically significant correlation was found between the fat concentration measured in the liver biopsies, and the concentration calculated from the spectroscopic experiments (r = 0.9, p < .001). Quantitative assessment of liver fat concentrations using localized spectroscopy is superior to methods based on differences in relaxation times, and can be used to estimate the fat concentration over the full range of fat content in contrast to the spectroscopic imaging methods. Localized spectroscopy may replace liver biopsy in the diagnosis of diffuse fatty infiltrations, and can be used for follow-up, due to its noninvasive nature.
Adult↗
(S)-4-carboxy-3-hydroxyphenylglycine, an antagonist of metabotropic glutamate receptor (mGluR) 1a and an agonist of mGluR2, protects against audiogenic seizures in DBA/2 mice.
The in vivo anticonvulsant effects and in vitro metabotropic glutamate receptor selectivity of (S)-4-carboxy-3-hydroxy-phenylglycine [(S)-4C3HPG] were examined. Intracerebroventricular injection of (S)-4C3HPG dose-dependently antagonized audiogenic-induced clonic and tonic convulsions in DBA/2 mice with ED50 values of 76 and 110-nmol per mouse, respectively. (S)-4C3HPG dose-dependently inhibited the spontaneously evoked epileptic spikes in a cingulate cortex-corpus callosum slice preparation. (S)-4C3HPG displaced the binding of [3H]glutamate in membranes prepared from baby hamster kidney (BHK) cells expressing the metabotropic glutamate receptor mGluR1a with an EC50 of 5 +/- 1 microM. (S)-4C3HPG dose-dependently antagonized glutamate-stimulated phosphoinositide hydrolysis in BHK cells expressing mGluR1a with an IC50 of 15 +/- 3 microM. (S)-4C3HPG was, however, an agonist at mGluR2 with an EC50 of 21 +/- 4 microM for inhibition of forskolin-stimulated cyclic AMP formation in BHK cells expressing the mGluR2. (S)-4C3HPG had no effects at mGluR4a. These data suggest that the anticonvulsant action of (S)-4C3HPG is mediated by combined antagonism of mGluR1a and agonism of mGluR2. These results suggest the importance of mGluR1a and/or mGluR2 in the control of epileptic activity.
Acoustic Stimulation↗
L-glutamate uptake inhibitors may stimulate phosphoinositide hydrolysis in baby hamster kidney cells expressing mGluR1a via heteroexchange with L-glutamate without direct activation of mGluR1a.
The functional efficacies of inhibitors of L-glutamate uptake for altering second messenger formation in baby hamster kidney cells expressing subtypes mGluR1a, mGluR2, and mGluR4 of the metabotropic glutamate receptor family were examined. L-Serine-O-sulfate was an agonist at mGluR1a (EC50 = 70 microM), mGluR2 (EC50 = 25 microM), and mGluR4 (EC50 = 324 microM). L-Cysteine sulfinate, 1-aminocyclobutane-trans-1,3-dicarboxylate, L-cysteine, and DL-threo-3-methylaspartate stimulated phosphoinositide hydrolysis in mGluR1a cells with EC50 values of 43, 64, 463, and 488 microM, respectively, and displaced L-[3H]glutamate binding from membranes prepared from these cells with respective IC50 values of 48, 44, 79, and 139 microM. However, D-aspartate, L-trans-pyrrolidine-2,4-dicarboxylate, L-threo-3-hydroxyaspartate, and L-aspartate-beta-hydroxamate stimulated phosphoinositide hydrolysis in mGluR1a cells (respective EC50 values of 73, 54, 57, and 430 microM) but did not displace L-[3H]glutamate binding. These compounds inhibited Na(+)-dependent L-glutamate uptake into baby hamster kidney cells with IC50 values similar to those for stimulation of phosphoinositide hydrolysis in mGluR1a cells. Phosphoinositide hydrolysis in mGluR1a cells, as stimulated by inhibitors of (or substrates for) this L-glutamate transporter, was significantly attenuated in the presence of L-glutamate decarboxylase (EC 4.1.1.15) or L-alanine aminotransferase (EC 2.6.1.2). Furthermore, incubation with 1 mM L-trans-pyrrolidine-2,4-dicarboxylate for 30 min increased the basal levels of free glutamate (1.5 +/- 0.2 microM) in the assay buffer four- to fivefold as measured by HPLC analysis. Thus, heteroexchange with endogenous L-glutamate may lead to erroneous estimations of the functional efficacies at mGluR1a.
Alanine Transaminase↗
Effect of alcohol on glucose, insulin, free fatty acid and triacylglycerol responses to a light meal in non-insulin-dependent diabetic subjects.
Alcohol accounts for 4-6% of the average energy intake in most Western countries. Alcohol-induced hypoglycaemia is a well-known and feared complication in insulin-dependent diabetic subjects, but little attention has been paid to the impact of alcohol on carbohydrate metabolism in non-insulin-dependent diabetes. The aim of the present study was to investigate in non-insulin-dependent diabetic subjects the acute metabolic effects of a moderate amount of alcohol taken with a light meal, conditions chosen to mimic an everyday situation. The patients received 500 ml non-alcoholic beer with an alcohol content (ml/l) of 0 (treatment A) and 54 (treatment B) together with a light meal, implying identity of the contents of ingredients except for alcohol. We found similar serum glucose, insulin, free fatty acid and triacylglycerol responses irrespective of addition of a modern amount of alcohol. In conclusion, a moderate amount of alcohol can be taken with a meal without eliciting hypoglycaemia in non-insulin-dependent diabetic subjects.
Blood Glucose↗
Cerebrospinal fluid production and dynamics in normal aging: a MRI phase-mapping study.
Magnetic resonance imaging (MRI) phase mapping was used for non-invasive evaluation of the to-and-fro motion of cerebrospinal fluid (CSF) in the cerebral aqueduct, and to measure the supratentorial CSF production in vivo, in 13 healthy volunteers to determine whether normal aging affects these parameters. Eight young healthy volunteers (mean age 29.8 years) and five elderly healthy volunteers (mean age 69.0 years) were examined, all were normal on conventional MRI. Slightly higher aqueductal CSF peak flow velocities and peak volume flow in both the caudal and rostral directions were found in the group of elderly healthy volunteers, however, this was not statistically significant. The calculated mean supratentorial CSF production rates in the two groups were almost identical, corresponding to approximately 900-1000 ml per 24 h, we suggest that supratentorial CSF production in healthy humans in fact occurs at this relatively high rate. Our study further suggests that the differences found in human CSF production rates are caused by interindividual factors other than age.
Adult↗
The nocturnal increase in human cerebrospinal fluid production is inhibited by a beta 1-receptor antagonist.
A circadian variation in human cerebrospinal fluid (CSF) production has recently been demonstrated using magnetic resonance phase imaging. A nightly peak in CSF production was found at approximately 0200, when production is approximately twice the daytime values. In the present study, we have investigated the effect of a beta 1-receptor antagonist, atenolol, on the production of CSF, specifically the nocturnal production peak. CSF production was measured in fourteen healthy volunteers of both sexes in the time interval 1500-1800, with or without drug administration (100 mg orally) at 1800, and a second measurement was made in the time interval 2300-0200. In the absence of drug administration, all nine volunteers showed a significant increase in CSF production at night, from 0.34 +/- 0.06 ml/min in the time interval 1500-1800 to 0.61 +/- 0.05 (SE) ml/min (P < 0.005), confirming the presence of a circadian variation in these individuals. One week later, the experiment was repeated in five of these volunteers, plus an additional five volunteers, but with the administration of 100 mg atenolol orally immediately after the first measurement (at 1800). In five of the volunteers a decrease in CSF production was seen at midnight compared with daytime production values; in two volunteers CSF production remained unchanged, while three volunteers showed increased production. The average CSF production was 32% lower at night (0.27 +/- 0.10 ml/min) compared with the afternoon (0.40 +/- 0.07 ml/min), after administration of atenolol (P = 0.37).(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenergic beta-Antagonists↗
The glycaemic index of spaghetti and gastric emptying in non-insulin-dependent diabetic patients.
OBJECTIVE: In the dietary treatment of non-insulin-dependent diabetes mellitus (NIDDM) great interest has been focused on foods with low glycaemic indices. Spaghetti has a low glycaemic index, but in NIDDM the underlying mechanism has not been elucidated. We investigated whether the low glycaemic index in spaghetti was the result of a retarded gastric emptying. DESIGN: Randomized study. SETTING: Department of Endocrinology & Metabolism, Aarhus County Hospital. SUBJECTS: Eight NIDDM in-patients participated without drop-outs. INTERVENTIONS: Paracetamol was used as a marker of the gastric emptying. On three different occasions the patients ingested 40 g of carbohydrate as: (1) spaghetti without paracetamol, (2) spaghetti containing 1.5 g paracetamol, and (3) mashed potatoes with 1.5 g paracetamol added. During the 4 h observation periods blood samples were drawn frequently. The spaghettis were industrially manufactured. RESULTS: The spaghetti meals induced similar glucose and insulin responses. The potato meal induced significantly higher glucose and paracetamol areas [607 +/- 108 vs 284 +/- 54 mmol/l*240 min (P = 0.02), and 18,668 +/- 999 vs 4979 +/- 369 mumol/l*240 min (P < 0.02)] as well as lower emptying index (time(peak)/peak concentration ratio of paracetamol) [2.1 +/- 0.3 vs 0.4 +/- 0.1 (P = 0.001)], as compared with the spaghetti meal. CONCLUSIONS: This study shows that the ingestion of spaghetti was associated with a slower gastrointestinal accessibility of the carbohydrates, which accounts for the low glycaemic index of spaghetti in NIDDM subjects.
Acetaminophen↗
Increased self-diffusion of brain water in hydrocephalus measured by MR imaging.
We used MR imaging to measure the apparent brain water self-diffusion in 5 patients with normal pressure hydrocephalus (NPH), in 2 patients with high pressure hydrocephalus (HPH), and in 8 age-matched controls. In all patients with NPH significant elevations of the apparent diffusion coefficients (ADC) of brain water were found within periventricular white matter, in the corpus callosum, in the internal capsule, within cortical gray matter, and in cerebrospinal fluid, whereas normal ADCs were found within the basal ganglia. In 2 patients with HPH elevated ADCs were found most prominently within white matter, and in one patient reexamined one year after surgery, ADCs were unchanged in nearly all brain regions. The increased ADC values in hydrocephalus patients may be caused by factors such as changes in myelin-associated bound water, increased Virchow-Robin spaces, and increased extracellular brain water fraction. For further studies of brain water diffusion in hydrocephalus patients, echo-planar imaging techniques with imaging times of a few seconds may be valuable.
Adult↗
[Magnetic resonance imaging of the cardiovascular system].
Magnetic resonance (MR) is a noninvasive technique to obtain tomographic images in any desired plane of the body. MR offers possibilities not only for morphologic imaging, but also for various physiological measurements, e.g. investigation of blood flow and angiography. This paper summarizes the possibilities of the technique in evaluation of congenital and acquired cardiovascular diseases. The conclusion is that MR may become an important clinical tool for examination of the cardiovascular system providing high accuracy and quantitative measurements.
Angiography↗