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C Chambon

Publications and source records attributed to C Chambon.

At least 37 records · Page 2Linked to original sources

Superparamagnetic iron oxides as positive MR contrast agents: in vitro and in vivo evidence.

The ability of superparamagnetic iron oxides (SPIO) and ultrasmall superparamagnetic iron oxides (USPIO) to act as positive contrast enhancers due to a marked T1 relaxivity was investigated. At low concentrations, an important signal enhancement was observed in vitro, reaching 120% for SPIO and 140% for USPIO in a spin echo 500/22 sequence. The more heavily the sequence was T1-weighted the greater the enhancement. As the concentration increased, the signal dropped. The in vivo study of USPIO in the rat showed that at low doses (14 mumol Fe/kg), the myocardial signal was enhanced by 30%, whereas at high doses (77 mumol Fe/kg), it fell by -50%. These results indicate that in T1-weighted spin echo sequences, the MR signal can be enhanced by low concentrations of superparamagnetic compounds. This effect could be useful in perfusion imaging, and is also important for a better understanding of any possible paradoxical positive enhancement which could occur in perfused organs.

Animals↗

Superparamagnetic iron oxide-enhanced magnetic resonance imaging of experimental liver tumors after mitomycin C administration.

The influence of mitomycin C chemotherapy on superparamagnetic iron oxide (SPIO) uptake by the liver was studied in rats (n = 70). This commonly used antineoplastic drug induces a decrease in the phagocytic function of the macrophage-phagocytic system (MPS). The plasma clearance of SPIO measured by relaxometry followed a biexponential model. The fast component half-life increased from 2.9 minutes in controls to 4.5 minutes in mitomycin C-treated animals. The slow component half-life increased from 11.3 to 36.7 minutes. Nevertheless, the magnetic resonance imaging (MRI) diagnostic efficacy 2 hours after infusion of the superparamagnetic agent AMI 25 (n = 10) was as satisfactory in the treated group as in the untreated one. These MRI results were consistent with the relaxometric T2* liver measurements, which were identical in both groups.

Animals↗

Pharmacokinetic study of gadolinium-DOTA in control and streptozocin diabetic rats.

The pharmacokinetics of gadolinium tetraazacyclododecanetetraacetic acid (Gd-DOTA), a contrast agent used in magnetic resonance imaging, have been evaluated in control and streptozocin-diabetic rats of different ages. In control rats, an age-related decrease in the Gd-DOTA elimination rate was noted, supported by a significantly lower apparent total body clearance and a significantly higher mean residence time. In diabetic rats, a similar but less important age-related change in the mean residence time and the apparent total body clearance was observed. Regardless of age-related differences in the pharmacokinetic parameters, a diabetic state induced several alterations in the Gd-DOTA pharmacokinetic parameters. The apparent total body clearance was significantly higher and the mean residence time significantly lower in diabetic rats indicating a higher elimination rate of Gd-DOTA. An important age-related increase in the volume of distribution at steady-state was noted in diabetic rats.

Animals↗

Sterol pathway in yeast. Identification and properties of mutant strains defective in mevalonate diphosphate decarboxylase and farnesyl diphosphate synthetase.

Yeast mutant strains auxotrophic for ergosterol and blocked in mevalonate diphosphate decarboxylase (erg19) and farnesyl diphosphate (FPP) synthetase (erg20) were isolated. The main feature of the mutants blocked in FPP synthetase is their ability to excrete prenyl alcohols, such as geraniol and farnesol. The isolation of the functional ERG20 gene allowed us to show that farnesyl diphosphate synthetase could be a rate limiting enzyme in ergosterol biosynthesis in yeast.

Acyclic Monoterpenes↗

Liver tumors in cirrhosis: experimental study with SPIO-enhanced MR imaging.

The influence of cirrhosis on superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance (MR) imaging of the liver was studied in 31 rats. Experimental models included carbon tetrachloride-induced cirrhosis and liver engrafting of rhabdomyosarcoma S4T cells. Hepatic uptake of SPIO measured with relaxometry decreased dramatically with histologic grade, while splenic uptake increased; the same results were achieved by calculating K values. Imaging of 13 tumorous cirrhotic rats confirmed these results by showing a muted decrease in liver signal intensity on spin-echo images after injection of SPIO. Nevertheless, all intrahepatic tumors could be visualized, as confirmed by postmortem examination. On gradient-echo images, postinjection contrast between the tumor and the liver was not affected by cirrhosis. Thus, despite strong impairment of hepatic uptake in cirrhosis, the diagnostic efficacy of MR imaging with SPIO did not seem to be significantly affected.

Animals↗

[Isoprenoide pathway and cell proliferation in the yeast Saccharomyces cerevisiae].

Yeast mutants blocked in farnesyl diphosphate (FPP) synthetase have been isolated. Their specific phenotype is likely linked to a lowering in the FPP pool required for protein prenylation. The structural gene of FPP synthetase has been isolated. Complete inactivation of FPP synthetase by gene disruption is letal for the yeast cells.

Cell Division↗

Isolation and properties of yeast mutants affected in farnesyl diphosphate synthetase.

Two yeast mutant strains auxotrophic for ergosterol and blocked in farnesyl diphosphate synthetase (EC 2.5.1.1) were isolated. Genetic analysis has shown that these mutant strains carry additional mutations in the ergosterol pathway besides erg20-1 and erg20-2 which affect FPP synthetase. The novel feature of these mutants is their ability to excrete prenyl alcohols (farnesol and geraniol). As geraniol is toxic for yeast cells, the above leaky mutations in FPP synthetase have to be associated with others in the sterol pathway, in order to slow down geraniol synthesis.

Acyclic Monoterpenes↗

Gd-DOTA. Pharmacokinetics and tolerability after intravenous injection into healthy volunteers.

The pharmacokinetics of Gd-DOTA meglumine in humans were evaluated in six healthy male volunteers. The agent was injected intravenously at 0.1 mmol/kg over approximately 2 minutes. Its behavior was found to be similar to that of urographic and angiographic iodinated contrast media with a plasma elimination half-life of 91 +/- 14 minutes (mean +/- standard deviation [SD]), a small distribution volume of 171.0 +/- 19.7 mL/kg and rapid urinary excretion. The results suggest rapid passive extravascular diffusion of gadolinium (Gd)-DOTA in the interstitial space without intracellular penetration, followed by a rapid urinary excretion via glomerular filtration. Furthermore, the results are consistent with animal data that showed that the compound does not cross the normal blood brain barrier. Its plasma pharmacokinetics appeared to be similar to those reported for Gd-DTPA. No relevant biological effects were seen with Gd-DOTA, especially in regard to serum iron and bilirubin levels.

Adult↗

Comparison of MIBG and monoamines uptake mechanisms: pharmacological animal and blood platelets studies.

The uptake of MIBG, a scintigraphic agent widely used in the detection of APUD tumours, was studied with a pharmacological approach on an in vitro and an in vivo models. MIBG as well as norepinephrine (NE) was taken up by human blood platelets, a model for presynaptic nerve endings amine uptake, with a thermodependant mechanism. MIBG and NE uptake was inhibited by desimipramine and reserpine. However, MIBG but not NE uptake was inhibited by fluvoxamine, a serotonin (5HT) uptake inhibitor. This suggests that MIBG is a NE and also a 5HT uptake tracer which involves uptake one and vesicular storage mechanisms. In rats treated with 6-hydroxydopamine to induce a chemical sympathectomy, we observed an inhibition of uptake similar for MIBG and NE in the heart, the salivary glands and the spleen, but no effect was observed in the liver. Some clinical inferences to best investigate specific monoamine uptake are drawn from these results.

3-Iodobenzylguanidine↗

Therapeutic effectiveness of iodine-131 MIBG metastases of a nonsecreting paraganglioma.

This case report describes the treatment of the bone metastases of a nonfunctioning sympathetic paraganglioma, with [131I]MIBG. After primary tumor excision and unsuccessful external radiotherapy, the patient received three therapeutic doses of [131I]MIBG, resulting in a reduction of the number and volume of metastases, and an improvement of the general condition. At 3 yr following [131I]MIBG therapy, the patient remained in remission. [131I]MIBG appears to be an efficient and safe agent for treating malignant sympathetic paraganglioma.

3-Iodobenzylguanidine↗

Meta-iodobenzylguanidine adrenal medulla localization: autoradiographic and pharmacologic studies.

In order to investigate the mechanism of uptake of meta-iodobenzylguanidine (mIBG) by the adrenal glands, autoradiographic and pharmacologic studies were performed in mice and dogs receiving radioiodinated mIBG. In mice, on macroautoradiography of whole body sections 48 h after 125I-mIBG, most of the radioactivity was focused in the adrenal glands. On microautoradiography, silver grains were exclusively located in the adrenal medulla. Tissue counting after phenoxybenzamine, cocaine, and desipramine treatment resulted in 45%, 35%, and 0% inhibition of mIBG uptake, respectively. Tissue counting and scintigraphic studies demonstrated a more than 50% mIBG release from the adrenal glands after reserpine. These data indicate the high affinity of mIBG for adrenal medulla and suggest that the mIBG and catecholamine uptake mechanisms are only partially the same.

3-Iodobenzylguanidine↗

First-pass evaluation of renal perfusion with TurboFLASH MR imaging and superparamagnetic iron oxide particles.

First-pass intrarenal hemodynamics were studied with superparamagnetic iron oxide particles and a T2-weighted TurboFLASH (fast low-angle shot) magnetic resonance (MR) imaging sequence. Four groups of five rabbits each were imaged after bolus injection of 40, 100, 140, and 200 mumol/kg iron, respectively. Images were acquired every 1.2 seconds, with an acquisition time of 700 msec. The signal intensity was measured in the cortex, outer medulla, inner medulla, and globally. In preliminary pathologic applications, two rabbits were imaged after ligation of the lumbar ureter and two after embolization of the renal artery. The reproducibility of the normal dynamics was evaluated with a cross-correlation test. On the images, the intravascular progression of the iron particles could be visualized within the cortex and the two compartments of the medulla in all cases. The maximal reduction in signal intensity in the cortex and medulla increased with the dose. The relationship between signal intensity decrease and dose was not linear, and the reproducibility of the signal intensity versus time plots was acceptable only at the 140 and 200 mumol/kg doses. The decrease in signal intensity was reduced and delayed in the embolized and hydronephrotic kidneys.

Animals↗