Solvent extraction of rare earths elements from nitrate media in DMDOHEMA/ionic liquid systems: performance and mechanism studies.

Extraction of La(iii), Eu(iii) and Fe(iii) was compared in n-dodecane and two ionic liquids (ILs) (1-ethyl-1-butylpiperidinium bis (trifluoromethylsulfonyl)imide [EBPip+] [NTf2 -] and 1-ethyl-1-octylpiperidinium bis (trifluoromethylsulfonyl)imide [EOPip+] [NTf2 -]). Using the extractant N,N'-dimethyl-N,N'-dioctylhexylethoxymalonamide (DMDOHEMA), the effect of pH was investigated in detail to recover extraction mechanisms. The use of ILs as the organic solvent instead of n-dodecane, greatly enhances extraction efficiency, and an ionic liquid with a shorter alkyl chain [EBPip+] [NTf2 -] provides higher extraction than [EOPip+] [NTf2 -]. The mechanistic study points out that for low nitric acid concentrations ([HNO3] ≤ 0.01 M), metal is extracted via a cation of the ionic liquids, while for higher nitric acid concentrations ([HNO3] ≥ 1.0 M), extraction occurs through pure solvation mechanism of DMDOHEMA as in conventional diluents. This latter case is of high interest for applications, as higher extraction can be obtained without any loss of ILs by ion exchange mechanisms.

An ionic liquid-based extraction system using diglycolamide functionalized macrocyclic platforms for the extraction and recovery of lanthanides.

Solvent extraction of lanthanides Ln(iii) (La, Eu and Yb) with resorcin[4]arene cavitand-triazole-DODGA (CR4-TZ-DODGA) and t-butylcalix[4]arene-triazole-DODGA (C4-TZ-DODGA) has been studied in a room temperature ionic liquid (RTIL), N-octyl-N-ethylpiperidinium bis(trifluoromethylsulfonyl)imide ([EOPip]NTf2). The two macrocyclic platforms were functionalized with four diglycolamide (DGA) moieties thanks to a click reaction and fully characterized by NMR and MS analysis. The effects of acidity as well as the concentration of the ligands were investigated on the extraction and separation properties. The parameters of the extraction processes were determined by the slope method and thermodynamic studies. For both ligands, the extraction efficiency changes along the lanthanoid series with selectivity toward Yb(iii) in regard to La(iii) and Eu(iii). The selective extraction and recovery of lanthanides from a simulated leaching solution of a Nd/Fe/B/Dy magnet has also been investigated.

Thermodynamic Description of Synergy in Solvent Extraction: II Thermodynamic Balance of Driving Forces Implied in Synergistic Extraction.

In the second part of this study, we analyze the free energy of transfer in the case of synergistic solvent extraction. This free energy of the transfer of an ion in dynamic equilibrium between two coexisting phases is decomposed into four driving forces combining long-range interactions with the classical complexation free energy associated with the nearest neighbors. We demonstrate how the organometallic complexation is counterbalanced by the cost in free energy related to structural change on the colloidal scale in the solvent phase. These molecular forces of synergistic extraction are driven not only by the entropic term associated with the tight packing of electrolytes in the solvent and by the free energy cost of coextracting water toward the hydrophilic core of the reverse aggregates present but also by the entropic costs in the formation of the reverse aggregate and by the interfacial bending energy of the extractant molecules packed around the extracted species. Considering the sum of the terms, we can rationalize the synergy observed, which cannot be explained by classical extraction modeling. We show an industrial synergistic mixture combining an amide and a phosphate complexing site, where the most efficient/selective mixture is observed for a minimal bending energy and maximal complexation energy.

[Misuse and dependence on prescription opioids: Prevention, identification and treatment]. / Mésusage et dépendance aux opioïdes de prescription : prévention, repérage et prise en charge.

Since the 1990s, the use of prescription opioids has largely spread, which has brought a real progress in the treatment of pain. The long-term use of prescription opioid is sometimes required, and may lead to pharmacological tolerance and withdrawal symptoms, i.e. pharmacological dependence on prescription opioids. Occasionally, this may also lead to misuse of prescription opioids (MPO). MPO preferentially occurs in vulnerable individuals, i.e., those with a young age, history of other addictive or psychiatric disorders, especially anxious and depressive disorders. MPO is associated with numerous complications, including an increased risk of fatal overdose. Prevention of MPO begins before the opioid prescription, with the identification of potential vulnerability factors. A planned and personalized monitoring should be systematically implemented. In vulnerable patients, contractualizing the prescription is warranted. During follow-up, the relevance of the prescription should be regularly reconsidered, according to the benefit observed on pain and the potential underlying signs of MPO. Patients with suspected MPO should be referred early to pain or addiction centers. The treatment of MPO should be based on multidisciplinary strategies, involving both the addiction and pain aspects: progressive opioid withdrawal, non-pharmacological measures against pain, or switching to medication-assisted treatment of addiction (i.e., buprenorphine or methadone).

Thermodynamic Description of Synergy in Solvent Extraction: I. Enthalpy of Mixing at the Origin of Synergistic Aggregation.

Revisiting aggregation of extractant molecules into water-poor mixed reverse micelles, we propose in this paper to identify the thermodynamic origins of synergy in solvent extraction. Considering that synergistic extraction properties of a mixture of extractants is related to synergistic aggregation of this mixture, we identify here the elements at the origin of synergy by independently investigating the effect of water, acid, and extracted cations. Thermodynamic equations are proposed to describe synergistic aggregation in the peculiar case of synergistic solvent extraction by evaluating critical aggregation concentration (CAC) as well as specific interactions between extractants due to the presence of water, acid and cations. Distribution of two extractant molecules in the free extractants and in reverse micelles was assessed, leading to an estimation of the in-plane interaction parameter between extractants in the aggregates as introduced by Bergström and Eriksson ( Bergström, M.; Eriksson, J. C. A Theoretical Analysis of Synergistic Effects in Mixed Surfactant Systems . Langmuir 2000 , 16 , 7173 - 7181 ). Based on this model, we study the N,N'-dimethyl-N,N'-dioctylhexylethoxymalonamide (DMDOHEMA) and di(2-ethylexyl) phosphoric acid (HDEHP) mixture and show that adding nitric acid enhances synergistic aggregation at the equimolar ratio of the two extractants and that this configuration can be related to a favored enthalpy of mixing.

Synergism in a HDEHP/TOPO Liquid-Liquid Extraction System: An Intrinsic Ligands Property?

Among the proposed mechanisms to predict and understand synergism in solvent extraction, the possibility of a preorganization of the mixture of extractant molecules has never been considered. Whether involving synergistic aggregation as for solubilization enhancement with reverse micelles or favored molecular interaction between the extractant molecules, evaluation of this hypothesis requires characterization of the aggregates formed by the extractant molecules at different scales. We investigate here the HDEHP/TOPO couple of extractant with methods ranging from vibrational spectroscopy and ESI-MS spectrometry to vapor pressure osmometry and neutron and X-ray scattering to cover both molecular and supramolecular scales. These experimental methods are subjected to DFT calculations and molecular dynamics calculations, allowing a rationalization of the results through the different scales. Performed in the absence of any cation, this original study allows a decorrelation of the mechanisms at the origin of synergy: it appears that no clear preorganization of the extractants can explain the synergy and therefore that the synergistic aggregation observed in the presence of cations is rather due to the chelation mechanisms than to intrinsic properties of the extractant molecules.

Performances and mechanistic investigations of a triphosphine trioxide/ionic liquid system for rare earth extraction.

The extraction of rare earth elements (REEs) from nitric acid solution with a triphosphine trioxide (TPO) is presented. Performances of such a ligand in ionic liquids vs. a classical solvent (benzyl ether) are compared. TPO seems to be 10 to 100 times more efficient when it is dissolved in ionic media whatever the concentration of nitric acid involved. Mechanistic investigations reveal that cation exchange classically observed in ionic liquids is not consistent with the experimental data. Moreover, clear differences in the TPO/Ln complexes between classical and ionic media are highlighted. A stable complex of 1 lanthanide for 3 TPO is formed in an ionic liquid whereas a complex of 1 lanthanide for 6 to 9 TPO is formed in benzyl ether. Back extraction is also studied and good recovery of REEs could be obtained. The TPO/ionic liquid system shows remarkable performances i.e. efficiency and selectivity towards lanthanides in a simulated leaching solution of a Nd/Fe/B/Dy magnet.

Ionic liquids as diluents in solvent extraction: first evidence of supramolecular aggregation of a couple of extractant molecules.

Ionic liquids have many favorable properties over conventional diluents in solvent extraction. They provide an environmentally benign feature, adjustable polarity and, in some cases, higher extraction performances that remain however not predictable. As it may have a major role in extraction mechanisms, we evidence the supramolecular aggregation of HDEHP/TOPO extractant molecules in the [OMim][NTf2] ionic liquid.

Synergy in Extraction System Chemistry: Combining Configurational Entropy, Film Bending, and Perturbation of Complexation.

Iron-uranium selectivity in liquid-liquid extraction depends not only on the mole fraction of extractants, but also on the nature of the diluent used, even if the diluent has no complexation interaction with the extracted ions. Modeling strong nonlinearity is difficult to parametrize without a large number of parameters, interpreted as "apparent constants". We determine in this paper the synergy curve versus mole fraction of HDEHP-TOPO (di(2-ethylexyl) phosphoric acid/tri-n-octyl phosphine oxide) and compare the free energy of aggregation to the free energy of extraction in various diluents. There is always a concomitant maximum of the two quantities, but with a gradual influence on intensity. The diluent is wetting the chains of the reverse aggregates responsible of the extraction. We show here that the intensity of the unexplained synergy peak is strongly dependent on the "penetrating" or "nonpenetrating" nature of the diluent. This experimental determination allows us to attribute the synergy to a combination of entropic effects favoring extraction, opposed to perturbation of the first coordination sphere by penetration as well as surfactant film bending energy.

Self-assembly of condensable "bola-amphiphiles" in water/tetraethoxysilane mixtures for the elaboration of mesostructured hybrid materials.

The self-assembly of condensable amphiphile molecules in water is an attractive approach for the synthesis of mesostructured hybrid materials. In this article, we focus on aminoundecyltriethoxysilane (AUT), a condensable "bola-amphiphile", i.e., an amphiphilic molecule possessing two polar heads on both sides of an aliphatic chain. In the present case, one side is a condensable triethoxysilane, and the other side is an amino group. We report on the self-assembly of AUT in mixtures of water and tetraethoxysilane (TEOS). In situ small-angle X-ray scattering (SAXS) measurements allowed us to follow the evolution of the structure from the liquid state up to the solid material formed upon catalytic polycondensation. Depending on the medium composition, hexagonal or lamellar structures can be observed in the final material. These observations allowed us to propose a model for the self-assembly of AUT in water/TEOS mixtures that we were able to validate by simulations of the SAXS profiles. By taking advantage of the modularity of such a system, it proves possible to prepare in a simple way various structured hybrid materials possessing a high number of available organic functions without using sacrificial surfactant molecules.

Synergism by coassembly at the origin of ion selectivity in liquid-liquid extraction.

In liquid-liquid extraction, synergism emerges when for a defined formulation of the solvent phase, there is an increase of distribution coefficients for some cations in a mixture. To characterize the synergistic mechanisms, we determine the free energy of mixed coassembly in aggregates. Aggregation in any point of a phase diagram can be followed not only structurally by SANS, SAXS, and SLS, but also thermodynamically by determining the concentration of monomers coexisting with reverse aggregates. Using the industrially used couple HDEHP/TOPO forming mixed reverse aggregates, and the representative couple U/Fe, we show that there is no peculiarity in the aggregates microstructure at the maximum of synergism. Nevertheless, the free energy of aggregation necessary to form mixed aggregates containing extracted ions in their polar core is comparable to the transfer free energy difference between target and nontarget ions, as deduced from the synergistic selectivity peak.

Motor cortex stimulation in the treatment of central and neuropathic pain.

BACKGROUND: Motor cortex stimulation has been proposed for the treatment of central pain. METHODS: Thirty-two patients with refractory central and neuropathic pain of peripheral origin were treated by chronic stimulation of the motor cortex between May 1993 and January 1997. The mean follow-up was 27.3 months. The first 24 patients were operated on according to the technique described by Tsubokawa. The last 13 cases (8 new patients and 5 reinterventions) were operated on by a technique including localization by superficial CT reconstruction of the central region and neuronavigator guidance. The position of the central sulcus was confirmed by the use of intraoperative somatosensory evoked potentials. The somatotopic organization of the motor cortex was established preoperatively by studying the motor responses at stimulation of the motor cortex through the dura. RESULTS: Ten of the 13 patients with central pain (77%) and 10 of the 12 patients with neuropathic facial pain experienced substantial pain relief (83.3%). One of the three patients with post-paraplegia pain was clearly improved. A satisfactory result was obtained in one patient with pain related to plexus avulsion and in one patient with pain related to intercostal herpes zoster. None of the patients developed epileptic seizures. CONCLUSIONS: Our results confirm that chronic stimulation of the motor cortex is an effective method in treating certain forms of refractory pain.

MRI-stereotactical approach for neural grafting in basal ganglia disorders.

Optimization of the procedures for neural grafting is a timely issue, as this technique has proven beneficial for a few patients with late-stage Parkinson's disease in pilot studies and therefore may expand to become a more widely available therapeutic. In this research, one major issue is that of the placement of the cell deposits in the right target areas within the striatum. Although it is widely accepted that these suitable regions are the sensorimotor regions of the putamen, reliable delineation of these areas using classical stereotactical mapping techniques remains difficult. Along the course of a 5-year-long clinical transplantation program, we have developed an original procedure based on magnetic resonance imaging of the striatum on parasagittal views. This technique allowed us to identify precisely, and reproducibly in each patient, three subregions of the putamen (precommissural, commissural, and postcommissural) to be implanted. On the basis of the literature defining the sensorimotor putaminal regions in nonhuman primates, it was subsequently possible to extrapolate and localize these regions in each patient, thus providing a basis for the placement of cell deposits. Examples taken from our series of grafted patients demonstrate the value of this procedure that, in addition, minimizes interference of interindividual variability in the interpretation of clinical results.

[Cephalic cancer pain controlled by intraventricular administration of morphine and clonidine]. / Douleurs céphaliques néoplasiques contrôlées par administration intraventriculaire de morphine et de clonidine.

A 47-year-old woman suffered from a pharyngeal cancer causing pain only poorly relieved by high doses of oral morphine. Oral administration was switched to the intracerebroventricular (ICV) route but pain relief was only transient despite a daily dosage up to 1.5 mg of morphine. Finally an effective pain relief was achieved with increasing doses of clonidine (5 to 30 micrograms) in combination with morphine (1.5 mg) by ICV route. Neither arterial hypotension nor sedation occurred and the patient recovered transiently a better quality of life.

Effect of epidural clonidine on analgesia and pharmacokinetics of epidural fentanyl in postoperative patients.

Epidural clonidine produces postoperative analgesia in patients and potentiates opioid analgesia in animals. The aim of the current study was to assess the effect of epidural clonidine on the plasma concentrations and analgesic effect of fentanyl after epidural administration. Twenty ASA physical status 2 or 3 patients recovering from abdominal surgery were allocated randomly to receive either epidural fentanyl (100 micrograms in 10 ml isotonic saline; EF group) or epidural fentanyl (same dose) plus epidural clonidine (150 micrograms; EF + C group) in isotonic saline solution. Analgesia was assessed over a period of 12 h after epidural injection. Venous samples were obtained until 360 min after epidural injection for radioimmunoassay determination of plasma fentanyl concentration. Onset of analgesia was similar in the two groups of patients (13 +/- 6 and 13 +/- 3 min, respectively, after injection), but duration was more than doubled in the patients receiving clonidine (543 +/- 183 vs. 250 +/- 64 min). Peak plasma fentanyl concentrations (Fmax) and the time to reach Cmax (Tmax) were comparable in the two groups (0.29 +/- 0.15 ng.ml-1 at 16.2 +/- 14.8 min in the EF group and 0.27 +/- 0.11 ng.ml-1 at 8.3 +/- 5.5 min in the EF + C group), as were plasma concentrations at each definite time of measurement. Drowsiness and hypotension were noticed in the EF + C group. Thus, epidural clonidine appears to prolong epidural fentanyl analgesia without affecting its plasma concentration.

[Intracerebral hematoma surgically treated under x-ray computed tomography with Backlund's needle. A series of 15 cases]. / Hématomes intracérébraux opérés sous contrôle scanographique à l'aide du trocart de Backlund. Une série de 15 cas.

15 cases of supratentorial intracerebral hematomas (12 cases of primary hematomas and 3 post-traumatic cases) were operated under C.T. scan control, using the screw and suction technique (Backlund's needle). 10 cases of primary hematomas were operated early, before the 24th hour. The patients were selected for intervention on the following criteria: 1) Patients aged less than 70 years old; 2) initial Glasgow coma scale between 6 and 10; 3) cases with involvement of the mesencephalon by the hematoma were excluded. In the 3 cases of post-traumatic hematomas, intervention was decided in reference to the clinical course. The volume of the hematomas ranged from 40 to 160 cc. Putaminal or thalamic hematomas were observed in 9 cases. The percentage of aspirated hematoma volume ranged from 50 to 91%, the average being 70.5%. Dramatic improvement of the consciousness was observed in all cases. Improvement of the motor deficit was incomplete, for the most part. 1 patient rebled and 1 patient died (6.6% mortality). In 26% of the cases (4 patients) the development of a brain oedema, in the surrounding of the residual hematoma site, was observed during the post operative follow up. There was no post operative infection. Intervention under direct C.T. control allows an accurate guidance of the needle. Efficacity of the evacuation is attested by an immediate improvement of the mass effect on C.T. scan. Under C.T. control the risk to aspirate the adjacent brain is avoided. The technique proposed here has been easily performed in emergency condition.

Clonidine-induced analgesia in postoperative patients: epidural versus intramuscular administration.

To compare the analgesic efficacy and plasma concentration of intramuscular (IM) versus epidural (EP) clonidine, 20 patients recovering from orthopedic or perineal surgery were randomly divided into two groups of ten. Clonidine (2 micrograms/kg) was administered epidurally in group 1 and intramuscularly in group 2. Analgesia was assessed using a visual analog scale (VAS) over a period of 6 h following clonidine administration. Venous blood samples were obtained at specific intervals for radioimmunoassay determination of plasma clonidine concentrations. The maximum reduction in VAS pain score was 78.5 +/- 20.6% in the EP group and 68.1 +/- 31.5% in the IM group (NS). Onset of analgesia was similar (within 15 min of injection), but duration tended to be longer after epidural than intramuscular administration (208 +/- 87 min vs. 168 +/- 95 min, mean +/- SD, P greater than 0.05). The peak plasma clonidine concentration after EP injection was 0.82 +/- 0.22 ng/ml and 1.02 +/- 0.76 ng/ml after IM injection. Hypotension, bradycardia, and drowsiness occurred with both methods of administration. None of these effects required treatment. Thus, in postoperative patients clonidine produces similar analgesia and side effects after parenteral or EP administration.

Postoperative analgesia with extradural clonidine.

The analgesic effect of extradural clonidine was evaluated in a double-blind study. In the recovery room, following orthopaedic or perineal surgery 20 ASA I and II patients were allocated randomly to two groups. The extradural clonidine (EC) group received clonidine 2 micrograms kg-1 in isotonic saline solution 15 micrograms ml-1. The extradural saline (ES) group received the equivalent volume of plain isotonic saline solution. Pain was evaluated by a visual analogue scale (VAS) at 15-min intervals for the first 2 h and subsequently at 30-min intervals for the following 4 h. Morphine 5 mg was given s.c. when patients complained of pain after extradural saline or clonidine. In the EC group, the mean (SD) maximum pain relief was 68.2 (24.1)% of the initial VAS score, but it was only 14.7 (25.2)% in the ES group. The mean duration of analgesia, before injection of morphine, was significantly longer in the EC group (210 (87) min) compared with the ES group (45 (27) min) (P less than 0.001). Drowsiness and moderate hypotension were observed in the EC group.

Dose-related prolongation of hyperbaric tetracaine spinal anesthesia by clonidine in humans.

The effect of clonidine, an alpha 2 agonist, on sensory and motor blockade during spinal anesthesia was studied in 44 ASA physical status I II patients scheduled for orthopedic surgery. The patients were randomly allocated into three groups given 15 mg of 0.5% hyperbaric tetracaine (HT), within group I (N = 14) 1 ml isotonic saline, in group II (N = 15) 0.5 ml saline solution and 0.5 ml clonidine (75 micrograms), and in group III (N = 15) 1 ml clonidine (150 micrograms). Sensory blockade (SB) was evaluated by pinprick and motor blockade (MB) according to Bromage's scale. The level of SB was comparable in the three groups but the duration was different. The 75 micrograms clonidine was associated with 25% prolongation of SB at L2 and 29% prolongation of grade 3 MB Clonidine 150 micrograms prolonged the time of SB at L2 by 72% and grade 3 MB by 96%. Colloid infusion and the decrease in diastolic blood pressure were significantly greater in the clonidine 150 micrograms group compared to group I. A dose related prolongation of spinal anesthesia is demonstrated with clonidine.