Social and emotional cognition in patients with severe migraine consulting in a tertiary headache center: A preliminary study.

Twenty-three severe migraine participants were studied to investigate social and emotional cognition features and explore their relationship with depression, anxiety and alexithymia. In comparison to normative data, 74% were under the norm for the Faux Pas subtest, 13% for the facial emotion recognition subtest and 52% for the overall composite score of the mini-SEA. Factor 1, Factor 3, and the total score of the TAS-20 were negatively correlated with the Faux Pas subtest. Our preliminary study shows that severe migraine patients present difficulties in inferring mental states, which could be related to alexithymia. It would be useful to identify these impairments in order to improve the quality of care provided. Clinical Trials registration number: NCT03577548.

Ultrasonic depolymerization of an exopolysaccharide produced by a bacterium isolated from a deep-sea hydrothermal vent polychaete annelid.

Low frequency ultrasound was used to depolymerize a high-molecular-weight exopolysaccharide (EPS) produced by a deep-sea hydrothermal bacterium Alteromonas macleodii subsp. fijiensis biovar deepsane. The influence of several parameters was examined including the duration of ultrasonic irradiation, EPS concentration, reaction temperature and volume of the sonicated solution. With the aim of optimizing the depolymerization, the native EPS was simultaneously treated with hydrogen peroxide and ultrasound. This study identified the sonication conditions that produce low-molecular-weight derivatives from the native EPS (>10(6)Da) with good reproducibility.

Description and technical pitfalls of a hepatoma model and of intra-arterial injection of radiolabelled lipiodol in the rat.

Intra-arterial metabolic radiotherapy (using lipiodol labelled with iodine-131 or rhenium-188) is a therapeutic approach that can be used for the treatment of hepatocellular carcinomas (HCC). We propose a detailed description of the tumoral model using the N1-S1 cell line as well as a technique for intra-arterial injection of radiolabelled lipiodol in order to undertake preclinical studies necessary for the evaluation of a new molecule. We also report the principal technical pitfalls that were faced. The speed of injection of the tumoral cells is a key factor in the tumoral induction since slow injections lead to a tumoral induction rate of 36.3% compared with 76.6% (P<0.01) when using very slow injections. This parameter should thus be controlled carefully during the subcapsular injection of the tumoral cells. In addition, when injecting radiolabelled lipiodol, anaesthesia should not be performed with isoflurane since this leads to a reduction in tumoral uptake. Indeed, we found a 'tumour/healthy liver' uptake ratio of only 2.1+/-0.7 with isoflurane as against 4.4+/-2.6 (P<0.05) when anaesthesia was carried out by intraperitoneal injection of ketamine. Lastly, we show that the tumour size has an influence on the tumoral uptake of radiolabelled lipiodol; therefore, this parameter must also be carefully controlled.

Regio- and enantioselective oxidation of thiaoleic acids by an algal delta 12-desaturase.

In a non aerated incubation medium, the oxidation of the tested thiaoleic acids by C. vulgaris was regioselective. Moreover the non oxidised 14-thiaoleic acid had no influence on the endogenous fatty acid pattern whereas the 13-thiaoleic acid, readily oxidised by the microalgae, caused a significant 18:1 accumulation in phospholipids. Examination of the 13-thiaoleic acid metabolism revealed that up to 15% of the substrate was specifically oxidised in the phospholipids before being transferred into the neutral lipids class of C. vulgaris. Confirmation of the monooxygenase-like delta 12-desaturase intervention in this biotransformation was obtained by the stereochemical analysis of the optically active sulfoxide isolated from the endoplasmic phospholipids.

Rhenium-188 and technetium-99m nitridobis(N-ethoxy-N-ethyldithiocarbamate) leucocyte labelling radiopharmaceuticals: [188ReN(NOET)2] and [99mTcN(NOET)2], NOET = Et(EtO)NCS2: their in vitro localization and chemical behaviour.

In this study, we have investigated the preparation of rhenium-188 nitridobis(N-ethoxy-N-ethyldithiocarbamate) [188ReN(NOET)2] (NOET = Et(EtO)NCS2), analogous to the known technetium-99m radiopharmaceutical. The new 188Re complex was synthesized in good yield with a satisfactory radiochemical purity, using a kit method. The subcellular localization of both radiopharmaceuticals in granulocytes was observed by microautoradiography. The uptake was independent of the radionuclide and predominantly nuclear. Furthermore, HPLC was used to characterize the 99mTc complex before and after blood cell labelling and revealed that the intact radiopharmaceutical was involved.

New bis(dithiocarboxylato) nitridotechnetium-99m radiopharmaceuticals for leucocyte labelling: in vitro and in vivo studies.

Dithiocarboxylate ligands were synthesized and characterised. New nitrido 99m-technetium complexes were obtained with these ligands and identified by thin layer chromatography. The nitrido complexes were tested in vitro in whole blood for leucocyte labelling and the design of the ligand was optimized. Best results were obtained with aliphatic linear ligands, containing 9 to 11 atoms of carbon. The in vivo experiment failed because an inflammated area could not be visualized by gamma imaging, the cell labelling mechanism being probably different.

Studies of technetium-99m nitridobisdithiocarboxylate leucocyte specific radiopharmaceutical: [99mTcN(DTCX)2], DTCX = CH3(CH2)8CS2. The cellular and subcellular distribution in human blood cells, and chemical behaviour. Synthesis of the analogous rhenium-188 radiopharmaceutical.

The distribution of the radiopharmaceutical ([99mTcN(DTCX)2], DTCX = CH3(CH2)8CS2) in the leucocyte population determined by a density separation with double gradient Polymorphprep was studied. Microautoradiographic analysis showed a subcellular distribution of the radiomarker in human blood cells. This technique confirmed the observed lymphocyte selectivity (69%) and revealed that the uptake was predominantly cytoplasmic around the nucleus. A labeling mechanism by passive endocytosis could be proposed involving a required lipophilicity of the radiopharmaceutical for lymphocyte targeting. Finally, we describe the new synthesis with an efficient yield and radiochemical purity of the analogous radiopharmaceutical [188ReN(DTCX)2].

Mixed-ligand complexes of yttrium-90 dialkyldithiocarbamates with 1,10-phenanthroline as a possible agent for therapy of hepatocellular carcinoma.

Yttrium-90 is a radioelement which has found wide use in targeted radionuclide therapy because of its attractive physical and chemical properties. Radioembolisation of hepatocellular carcinoma with radiolabelled Lipiodol is a method of choice. We have synthesised a series of alkyldithiocarbamate yttrium complexes, easily extracted into Lipiodol due to their high lipophilicity. Among the prepared series, a new radioconjugate, which is stable over an extended period of time, has been prepared, and could represent a potential treatment procedure for hepatocellular carcinoma.

188Re-loaded lipid nanocapsules as a promising radiopharmaceutical carrier for internal radiotherapy of malignant gliomas.

PURPOSE: Lipid nanocapsules (LNC) entrapping lipophilic complexes of (188)Re ((188)Re(S(3)CPh)(2)(S(2)CPh) [(188)Re-SSS]) were investigated as a novel radiopharmaceutical carrier for internal radiation therapy of malignant gliomas. The present study was designed to evaluate the efficacy of intra-cerebral administration of (188)Re-SSS LNC by means of convection-enhanced delivery (CED) on a 9L rat brain tumour model. METHODS: Female Fischer rats with 9L glioma were treated with a single injection of (188)Re-SSS LNC by CED 6 days after cell implantation. Rats were put into random groups according to the dose infused: 12, 10, 8 and 3 Gy in comparison with blank LNC, perrhenate solution (4 Gy) and non-treated animals. The radionuclide brain retention level was evaluated by measuring (188)Re elimination in faeces and urine over 72 h after the CED injection. The therapeutic effect of (188)Re-SSS LNC was assessed based on animal survival. RESULTS: CED of (188)Re perrhenate solution resulted in rapid drug clearance with a brain T (1/2) of 7h. In contrast, when administered in LNC, (188)Re tissue retention was greatly prolonged, with only 10% of the injected dose being eliminated at 72 h. Rat median survival was significantly improved for the group treated with 8 Gy (188)Re-SSS LNC compared to the control group and blank LNC-treated animals. The increase in the median survival time was about 80% compared to the control group; 33% of the animals were long-term survivors. The dose of 8 Gy proved to be a very effective dose, between toxic (10-12 Gy) and ineffective (3-4 Gy) doses. CONCLUSIONS: These findings show that CED of (188)Re-loaded LNC is a safe and potent anti-tumour system for treating malignant gliomas. Our data are the first to show the in vivo efficacy of (188)Re internal radiotherapy for the treatment of brain malignancy.

Development and biodistribution of 188Re-SSS lipiodol following injection into the hepatic artery of healthy pigs.

Although intra-arterial radiotherapy with (131)I-labelled lipiodol is a useful therapeutic approach in the treatment of hepatocellular carcinomas, various disadvantages limit its use. Here we describe the development of (188)Re-SSS lipiodol, as well as its biodistribution in the healthy pig after injection into the hepatic artery. The (188)Re-SSS lipiodol was obtained after dissolving a chelating agent, previously labelled with (188)Re, in cold lipiodol. The radiochemical purity (RCP) of the labelling was checked immediately and at 24 and 48 h. The (188)Re-SSS lipiodol was injected into the hepatic artery of six healthy pigs. They were killed 1, 24 and 48 h post injection, for ex vivo counting. An autoradiographic study was performed in three cases. (188)Re-SSS lipiodol was obtained with a yield of 87%+/-9.1%. The immediate RCP was 93%+/-3.4%. This radiolabelling was reproducible and stable at 48 h in plasma: 90.6%+/-1.5% of the activity remained in the lipiodol with an RCP of 91%+/-4%. Ex vivo counting confirmed the predominantly hepatic uptake and revealed weak lung and intestinal uptake. There was very weak urinary elimination (2.3%+/-0.5% at 48 h) and a slightly higher level of intestinal elimination (4.8%+/-1.9% at 48 h). The autoradiographic studies showed (188)Re-SSS lipiodol to be located mainly in sinusoids, like (131)I-lipiodol. By using the method described here, (188)Re-SSS lipiodol can be obtained with a very high yield and a satisfactory RCP. Its biodistribution in the healthy pig is in agreement with data published elsewhere concerning other types of radiolabelling used for lipiodol, except for the very weak urinary and intestinal elimination, which probably indicates better stability of (188)Re-SSS labelling.