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Biomedical subjects

C Thomsen

Publications and source records attributed to C Thomsen.

At least 91 records · Page 5Linked to original sources
PubMed1996

Twelve-hour brain lithium concentration in lithium maintenance treatment of manic-depressive disorder: daily versus alternate-day dosing schedule.

The 12-h brain lithium concentration was measured by lithium-7 magnetic resonance spectroscopy in ten manic-depressive patients receiving daily or alternate-day lithium carbonate treatment. The median dose of lithium carbonate was 800 mg in the daily treatment group and 1200 mg in the alternate-day group. Median 12-h serum lithium concentration in the two groups was 0.86 mmol l-1 and 0.55 mmol l-1, respectively, while the corresponding concentration in brain was 0.67 mmol l-1 and 0.52 mmol l-1, respectively. The 12-h brain lithium concentration was independent of lithium dosing schedule (multiple linear regression), but correlated significantly with the 12-h serum lithium concentration (P = 0.003; B = 0.53, 95% c.l. 0.24-0.82; beta = 0.83). Thus at identical 12-h serum lithium concentrations the 12-h brain lithium concentration is similar with both treatment regimes. As the risk of manic-depressive relapse during alternate-day lithium treatment is in our experience 3-fold greater than with daily treatment (at similar mean 12-h serum lithium concentration), the findings suggest that the difference in the prophylactic efficacy of the two dosing schedules is unrelated to differences in the 12-h brain lithium concentration.

Adult↗
PubMed1996

Metabotropic glutamate receptor subtype 1A activates adenylate cyclase when expressed in baby hamster kidney cells.

1. The coupling of subtype mGluR1a of the metabotropic glutamate receptor family to phosphoinositide hydrolysis, cAMP-formation and arachidonic acid release was characterized when the receptor was expressed in baby hamster kidney (BHK) cells. 2. When measuring cAMP-formation in BHK cells expressing mGluR1a, the rank order of agonist potency as well as the efficacy of mGluR1a antagonists was comparable to what has been observed when measuring mGluR1a-mediated phosphoinositide (PI)-hydrolysis. 3. However, while the presence of extracellular calcium increased the efficacy of quisqualate to stimulate phosphoinositide hydrolysis no significant effects were observed when measuring quisqualate-induced cAMP-formation. 4. Pretreatment of mGluR1a-expressing cells with pertussis toxin increased quisqualate-induced cAMP-formation in contrast to the observed partial inhibition of PI-hydrolysis by pertussis toxin. Cholera toxin increased cAMP-formation in BHK cells but showed no effects on PI-hydrolysis. 5. While quisqualate also stimulated [3H]-arachidonic acid release from BHK cells expressing mGluR1a this effect may be secondary to activation of phospholipase C. 6. These data further suggest that mGluR1a is coupled to PI-hydrolysis as well as cAMP-formation via different G-proteins which can be discriminated by their sensitivity to pertussis toxin.

Adenylate Cyclase Toxin↗
PubMed1996

Development of 123I-labelled NNC 13-8241 as a radioligand for SPECT visualization of benzodiazepine receptor binding.

[125I]- and [123I]NNC 13-8241 were prepared from the trimethyltin precursor and radioactive iodide using the chloramine-T method. The total radiochemical yields of [125I]- and [123I]NNC 13-8241 were 60-70% and 40-50% respectively, with radiochemical purity higher than 98%. In binding studies with [125I]NNC 13-8241 in rats in vitro and in vivo a high uptake of radioactivity was demonstrated in brain regions known to have a high density of benzodiazepine (BZ) receptors such as the occipital and frontal cortex. SPECT examination with [123I]NNC 13-8241 in a Cynomolgus monkey demonstrated a high uptake of radioactivity in the occipital and frontal cortex. After displacement with flumazenil radioactivity in these brain regions was reduced to the level of a central region including the pons. Four hours after injection about 80% of the radioactivity in monkey plasma represented unchanged radioligand. This low degree of metabolism indicates that NNC 13-8241 is metabolically more stable than the radioligands hitherto developed for imaging of BZ-receptors in the primate brain.

Animals↗
PubMed1996

The acute impact of ethanol on glucose, insulin, triacylglycerol,and free fatty acid responses and insulin sensitivity in type 2 diabetes.

The aim of the present study was to evaluate the acute effect of ethanol on insulin sensitivity, and glucose, insulin, free fatty acid (FFA), and triacylglycerol responses in ten patients with non-insulin-dependent (type 2) diabetes. In the test study an oral dose of 0.66 g ethanol/kg followed by continuous intravenous infusion of 0.1 g ethanol/kg per h was given to maintain a constant ethanol level in the blood. In the control study identical volumes of oral water and intravenous saline (9 g NaCl/l) were given. After 90 min insulin sensitivity was determined by the hyperinsulinaemic, euglycaemic clamp technique. Ethanol caused no change in blood glucose or insulin concentrations. The FFA level was suppressed by ethanol while the triacylglycerol level was unaffected. The insulin sensitivity was not affected by ethanol. No major acute effect of ethanol on the glycaemic control in fasting type 2 diabetic patients was found in comparison with what is seen in healthy people. The present study, along with the sparse literature, indicates that the ability of ethanol to induce hypoglycaemia is attenuated or absent in diet-treated type 2 diabetes. Furthermore, we found no change in insulin sensitivity. Consequently, the risk of acute ethanol-induced aberrations in carbohydrate metabolism in diet-treated type 2 diabetes seems to be less than previously expected, when alcohol is not taken as a part of a meal.

Administration, Oral↗
PubMed1996

Differential effects of saturated and monounsaturated fat on blood glucose and insulin responses in subjects with non-insulin-dependent diabetes mellitus.

To compare the metabolic effect of coingestion of saturated and monounsaturated fats with potato, 12 subjects with non-insulin-dependent diabetes mellitus (NIDDM) received 300 g mashed potato alone or in combination with 40 g olive oil, 80 g olive oil, 50 g butter, or 100 g butter, respectively. The blood glucose response area to potatoes with 100 g butter (448 +/- 68 mmol.240 min/L) was significantly lower than after the four other meals: 596 +/- 63 (potato alone), 649 +/- 82 (potato + 40 g olive oil), 587 +/- 80 (potato + 50 g butter), and 604 +/- 81 (potato + 80 g olive oil) nmol.240 min/L, P < 0.05, respectively. The insulin response was significantly increased by adding 50 and 100 g butter, whereas addition of 40 and 80 g olive oil had no effect. The fatty acid concentration was higher when 100 g butter was added to the potato meal than when it was not (0.67 +/- 0.05 compared with 0.48 +/- 0.07 mmol/L, P < 0.05). Fatty acid concentrations were similar to those found for the other meals. The triacylglycerol response increased in a dose-dependent manner with the fat content of the meals irrespective of the type of fat. We conclude that butter increases the insulin response more than does olive oil, and large amounts of butter also increase fatty acid and triacylglycerol concentrations.

Adult↗
PubMed1996

Phenylglycines can evoke quisqualate-primed depolarizations in rat cingulate cortex: an effect associated with [3H]DL-AP4 uptake.

Depolarization could be evoked in slices of rat cingulate cortex by the normally non-excitatory compound L-2-amino-4-phosphonobutyrate (L-AP4) if the slices had been sensitized by exposure to quisqualate. The magnitude of the response to L-AP4 was dependent on the concentrations of both L-AP4 and quisqualate and was inhibited by alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor antagonism. A series of phenylglycine analogues were capable of evoking similar dose-dependent depolarizations in the rat cingulate cortex following quisqualate sensitization, the most potent being (S)-4-carboxy-3-hydroxyphenylglycine. If the superfusate collected during application of (S)-4-carboxy-3-hydroxyphenylglycine to a quisqualate-sensitized slice was administered to a slice not previously exposed to quisqualate, a small depolarization was obtained. All the compounds shown to be capable of evoking the quisqualate-sensitized response showed affinity for the L-AP4 uptake site whilst having no affinity at ionotropic glutamate receptors and different profiles of activity at metabotropic glutamate receptors. None of the compounds was active at the metabotropic glutamate 4a receptor. There was a statistically significant correlation between a compound's effectiveness in inhibiting [3H]DL-AP4 uptake into rat cortical synaptosomes and its potency in evoking quisqualate-sensitized depolarization. It is concluded that this response may be the result of hetero-exchange between L-AP4 ligands and quisqualate.

Aminobutyrates↗
PubMed1996

MR velocity mapping measurement of renal artery blood flow in patients with impaired kidney function.

Renal blood flow (RBF) was measured in 9 patients with chronic impaired kidney function using MR velocity mapping and compared to PAH clearance and 99mTc-DTPA scintigraphy. An image plane suitable for flow measurement perpendicular to the renal arteries was chosen from 2-dimensional MR angiography. MR velocity mapping was performed in both renal arteries using an ECG-triggered gradient echo pulse sequence previously validated in normal volunteers. Effective renal plasma flow was calculated from the clearance rate of PAH during constant infusion and the split of renal function was evaluated by 99mTc-DTPA scintigraphy. A reduction of RBF was found, and there was a significant correlation between PAH clearance multiplied by 1/(1-hematocrit) and RBF determined by MR velocity mapping. Furthermore, a significant correlation between the distribution of renal function and the percent distribution of RBF was found.

Aged↗
PubMed1996

Measurement of blood flow in the superior sagittal sinus in healthy volunteers, and in patients with normal pressure hydrocephalus and idiopathic intracranial hypertension with phase-contrast cine MR imaging.

PURPOSE: To measure blood flow and velocity in the superior sagittal ++sinus. MATERIAL AND METHODS: MR velocity mapping was used to examine 14 healthy volunteers, 15 patients with normal pressure hydrocephalus (NPH), 3 patients with high pressure hydrocephalus (HPH), and 11 patients with idiopathic intracranial hypertension (IIH). RESULTS: Mean blood flow was 443 ml/min in healthy volunteers with a tendency towards reduced blood flow with increasing age. In NPH patients significantly lower superior sagittal sinus blood flow values were found, but this difference was no longer significant when patients and controls were matched for age. In HPH and IIH patients blood flow and velocity were within the normal range. In one patient with thrombosis of the superior sagittal sinus the blood flow was reduced to 40 ml/min. CONCLUSION: MR velocity mapping methods may be of value in the assessment of blood flow in the dural sinuses in various pathologies resulting in dural sinus occlusion, such as dural sinus thrombosis, and for following the progress of these patients while undergoing treatment.

Adult↗
PubMed1996

Quantitative magnetic resonance methods for in vivo investigation of the human liver and spleen. Technical aspects and preliminary clinical results.

This project was initiated with the introduction of magnetic resonance (MR) in Denmark in order to evaluate the possibilities of this technique as a diagnostic aid in non-focal liver and splenic diseases. The signal intensities in the MR image are sensitive to the longitudinal relaxation (T1), the transverse relaxation (T2), flow and chemical shift. All these parameters may be quantified by developing specific pulse sequences sensitive to the parameter in question. Previous studies had indicated that relaxation time measurements might be of value in the diagnosis of liver cirrhosis and haemochromatosis. Measuring relaxation times in these 2 groups of patients posed different challenges. In patients with liver cirrhosis a method had to be developed for simultaneous T1 and T2 relaxation time measurements, which was robust to the respiratory motion of the liver. A combination of multi-echo pulse sequences with different repetition times was chosen, because motion effects were partly refocused. Multi-acquisition was used to improve the signal-to-noise ratio in the heavily saturated experiments with short repetition times, to further reduce the sensitivity to motion. To test the quality of this pulse sequence, phantom experiments were performed, and sensitivity to motion was tested by measuring with and without respiratory synchronization. Respiratory synchronization gave a marked improvement in focal liver diseases, whereas no difference was found in non-focal diseases. Standard imaging sequences with a minimum echo time of 30 ms could not be used to measure the short T2 relaxation times found in patients with increased liver iron. A volume-selective multi-echo spectroscopic pulse was developed with a minimum echo time of 4 ms. Biexponential signal decay could be shown in patients with increased liver iron by using this sequence. Patients with liver cirrhosis, as a group, had increased T1 relaxation times compared to normal volunteers, but an overlap in T1 values was found. No correlation between the degree of fibrosis and the T1 relaxation time was found. Liver iron concentration could be quantified either by using the fast component of the T2 signal decay or by using the decreased signal in spin-echo and gradient echo images. Patients with leukemias and myeloproliferative disorders had prolonged T1 relaxation times in the spleen, but a considerable overlap was found between this group and a group of patients with benign hyperplasia and patients with splenomegaly secondary to portal hypertension. Volume-selective proton spectroscopy was developed and used to quantify the liver fat concentration. The accuracy of the method was about 3 g/100 g. With the implementation of a second generation scanner system it became possible to develop a pulse sequence, using the phase information in the MR signal, to measure portal vein flow during breath-holding. This method made it possible to estimate the portal vein flow during fasting, and the flow increase after eating. Quantitative MR methods may contribute to the diagnosis of non-focal liver diseases by estimation of liver fat and liver iron and by assessment of portal vein blood flow. Increased T1 relaxation time is a sign of a disease process in the liver rather than specific for any liver disease.

Humans↗
PubMed1996

Modulation of seizure activity in mice by metabotropic glutamate receptor ligands.

The anticonvulsant properties of ligands at metabotropic glutamate receptors (mGluRs) were examined in different seizure models by use of intracerebroventricular infusion. The mGluR1a antagonist/mGluR2 agonist, (S)-4-carboxy-3-hydroxyphenylglycine [(S)-4C3HPG] dose-dependently antagonized pentylenetetrazol- and methyl-6,7-dimethoxy-4-ethyl-beta-carboline-2-carboxylate (DMCM)-induced clonic convulsions in mice with ED50 values of 400 and 180 nmol/mice, respectively. A modest increase in electrical seizure threshold was observed in mice injected with (S)-4C3HPG. No effect on seizures induced by systemic administration of N-methyl-D-aspartate was observed by prior intracerebroventricular infusion of (S)-4C3HPG. The more selective (but less potent) mGluR1a antagonist, (S)-4-carboxyphenylglycine, was a weak anticonvulsant in similar seizure models with the exception of convulsions induced by electrical stimulation. (+)-alpha-Methyl-4-carboxyphenylglycine showed no anticonvulsant activity in any of the models examined. Agonists of mGluRs which are particularly potent at mGluR2, (2S,3S,4S)-alpha-(carboxycyclopropyl)glycine and (1S,3R)-1-aminocyclopentane dicarboxylic acid significantly protected against sound-induced convulsions in DBA/2 mice and DMCM-induced seizures in mice but were inactive against seizures induced by administration of pentylenetetrazol or by electrical stimulation. These data suggest that mGluR ligands modulate seizure activity in mice and this effect may be mediated via antagonism of mGluR1a-type as well as via activation of mGluR2-type mGluRs.

Animals↗
PubMed1996

(2S,1'S,2'S,3'R)-2-(2'-carboxy-3'-phenylcyclopropyl)glycine, a potent and selective antagonist of type 2 metabotropic glutamate receptors.

The pharmacological profile of (2S,1'S,2'S,3'R)-2-(2'-Carboxy-3'-phenylcyclopropyl)glycine (PCCG-IV) at metabotropic glutamate receptor (mGluR) subtypes mGluR1a, mGluR2, mGluR4a, and mGluR5 was examined. PCCG-IV potently antagonized glutamate-induced inhibition of forskolin-stimulated cAMP formation in baby hamster kidney cells expressing mGluR2 in a competitive manner (KB = 8.2 +/- 0.4 microM). PCCG-IV was a weak agonist at mGluR4a but inactive at the cloned phosphoinositide-coupled mGluRs (mGluR1a and mGluR5a). PCCG-IV was significantly more potent and selective as an antagonist at mGluR2 compared with previously described mGluR2 antagonists, including alpha-methyl-4-carboxyphenylglycine. In mice cortical neurons, PCCG-IV antagonized the neuroprotective effects of a selective mGluR2 agonist, (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine, at low doses (0.2-20 microM), whereas a higher dose of PCCG-IV (80 microM) was similarly neuroprotective to L-2-amino-4-phosphonobutanoate. The neuroprotective effect of PCCG-IV was blocked by an antagonist of mGluR4a, alpha-methyl-4-phosphonophenylglycine. Thus, PCCG-IV is a novel and useful tool for delineating the physiological roles of group II mGluRs in the central nervous system.

Animals↗
PubMed1995

Plasma levels of von Willebrand factor in non-insulin-dependent diabetes mellitus are influenced by dietary monounsaturated fatty acids.

We have previously demonstrated a lowering effect on von Willebrand Factor (vWF) of a diet rich in monounsaturated fatty acids (MUFA) as compared with a high-carbohydrate diet. In the present study 16 non-insulin dependent diabetic (NIDDM) subjects participated in a cross-over experiment on an out-patient basis comparing the effects on vWF of three weeks treatments with two diets similar in carbohydrate and protein content, one rich in MUFA (30 energy %) and one rich in polyunsaturated fatty acids (PUFA) (30 energy %). Before and on the last day of the two diets, the levels of vWF, fibrinogen, fibronectin and alpha 2-macroglobulin were measured. After 3 weeks diet intervention vWF levels were lower after the MUFA regimen compared with the PUFA diet (mean +/- SD) (1.15 +/- 0.36 vs 1.32 +/- 0.42 U/ml, p = 0.003). Similar and unchanged levels of fibrinogen, fibronectin and alpha 2-macroglobulin were seen. In conclusion, three weeks on a diet rich in MUFA lowers vWF as compared with a PUFA rich diet, suggesting a beneficial effect of MUFA on the endothelium in NIDDM patients.

Cross-Over Studies↗
PubMed1995

Noninvasive MRI thermometry with the proton resonance frequency (PRF) method: in vivo results in human muscle.

The noninvasive thermometry method is based on the temperature dependence of the proton resonance frequency (PRF). High-quality temperature images can be obtained from phase information of standard gradient-echo sequences with an accuracy of 0.2 degrees C in phantoms. This work was focused on the in vivo capabilities of this method. An experimental setup was designed that allows a qualitative in vivo verification. The lower-leg muscles of a volunteer were cooled and afterwards reheated with an external water bolus. The temperature of the bolus water varied between 17 degrees C and 37 degrees C. The in vivo temperature images can be used to extract the temperature in muscle tissue. The data in the fat tissue are difficult to interpret because of the predominance of susceptibility effects. The results confirm the method's potential for hyperthermia control.

Algorithms↗
PubMed1995

Urinary albumin excretion rate and 24-h ambulatory blood pressure in NIDDM with microalbuminuria: effects of a monounsaturated-enriched diet.

Previous studies have shown that unsaturated fat-enriched diets may have a beneficial effect on blood pressure in non-insulin-dependent diabetic (NIDDM) patients, whereas little is known about the effects on albuminuria. In a 3-week cross-over design we compared the effects of a currently recommended high-carbohydrate diet (50% carbohydrate, 30% fat [10% monounsaturated fat]) vs a diet rich in monounsaturated fat (30% carbohydrate, 50% fat [30% monounsaturated fat]) on urinary albumin excretion rate, 24-h ambulatory blood pressure and metabolic control in ten NIDDM patients with persistent microalbuminuria. The 24-h ambulatory blood pressure was similar before and after both the high-carbohydrate diet (mean +/- SD: 145/78 +/- 25/10 vs 143/79 +/- 19/10 mmHg (NS) and the monounsaturated fat diet: 140/78 +/- 16/8 vs 143/79 +/- 15/8 mmHg (NS). No changes were observed in day or night-time blood pressures. Urinary albumin excretion rate was unaffected after 3 weeks' treatment by the diets: from (geometric mean x/divided by tolerance factor) 32.4 x/divided by 2.1 to 36.0 x/divided by 1.9 micrograms/min (NS) vs from 34.2 x/divided by 1.9 to 32.1 x/divided by 2.1 micrograms/min (NS). Fasting plasma glucose, serum fructosamine and HbA1c as well as lipid and lipoprotein concentrations were stable during both diets. Compared to the high-carbohydrate diet a reduction in the LDL/HDL cholesterol ratio was observed during the monounsaturated fat diet (p < 0.03). In conclusion, compared to a high-carbohydrate diet, 3 weeks' treatment with a monounsaturated fat diet did not affect the levels of 24-h ambulatory blood pressure or albuminuria in microalbuminuric NIDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Effects of chronic tiagabine treatment on [3H]GABAA, [3H]GABAB and [3H]tiagabine binding to sections from mice brain.

(R)-N-(4,4-Bis(3-methyl-2-thienyl)but-3-en-1-yl)nipecotic acid (tiagabine) is a potent inhibitor of gamma-aminobutyric acid (GABA) uptake, which maintains its initial anticonvulsant effects when administered to mice for a prolonged period (21 days). In the present study, mice received chronic (21 days) p.o. administration of tiagabine (15 mg/kg, twice daily) or vehicle alone and the densities of GABAA and GABAB receptors and of [3H]tiagabine recognition sites were measured in several brain regions. The following changes were observed following chronic administration of tiagabine as compared to vehicle: significant reduction (18-37%) in [3H]tiagabine binding in the temporal and entorhinal cortex and in the molecular and granular layer of the cerebellar cortex; increases in the number of GABAA sites (22-44%) in various regions of the frontal cortex, in caudate putamen and in the lateral septum; decreases in the numbers of GABAB sites (18-42%) in the motor cortex, the more dorsal parts of cortex, the anteroventral thalamic nucleus, medial geniculate, superior colliculus and the molecular layer of the cerebellar cortex. Such data suggest that the GABAergic system is differentially modulated in a regional specific manner in response to chronic elevation of the extracellular levels of GABA. The significance of these findings in relation to the reported lack of development of tolerance to the anticonvulsant effects of tiagabine is discussed.

Animals↗