Intelligence and Executive Functions: A Comprehensive Assessment of Intellectually Gifted Children.

OBJECTIVE: Executive functions (EFs) play a key role in cognitive and behavioral functioning. Their multiple forms and implications for daily life behaviors mean they are sometimes equated with intelligence. Several elements even suggest that intellectually gifted children (IGC) may present better executive functioning than typical developing children (TDC, children with intelligence in the average range). However, no study has ever completely tested this hypothesis by a comprehensive assessment of EFs in IGC. METHOD: Results of 30 IGC and 35 TDC aged from 6 to 16 years old were compared through a comprehensive assessment of EFs (inhibition, flexibility, and planning), comprising performance-based and daily life measures. RESULTS: IGC did not differ from TDC in EF performance-based measures. However, they scored higher in parents' and some teachers' ratings, suggesting higher indicators of difficulties in daily life. CONCLUSIONS: Contrary to expectations, high intellectual level does not appear to be associated with superior EFs. Surprisingly, parents and teachers of IGC reported more complaints about their executive functioning in everyday life. We put forward different hypotheses to explain this contrast. Further research is needed to better understand this phenomenon, in which neuropsychology has a fundamental role to play.

Achievement of effective cardiopulmonary trauma surgical skills training throughout the incorporation of a low-cost and easy to implement pulsatile simulation model.

OBJECTIVES: . In the last decade, concern regarding the preparedness of general surgery graduates to effectively manage thoracic trauma cases has been raised. However, due to limited availability and elevated costs, access to cardiopulmonary trauma simulation models is limited. This article describes our experience implementing a low-cost blended ex vivo tissue-based simulation model using animal by-products that incorporates pump perfusion and ventilation. DESIGN: . Firstly, for validation purposes 8 junior residents, 8 recently graduated general surgeons, and 3 cardiothoracic surgery attendings from Pontificia Universidad Católica de Chile Clinical Hospital were recruited. Proficiency in performing a pulmonary tractotomy and a myocardial injury repair was assessed with global and specific rating scales. Secondly, to evaluate the effectiveness of the model as a learning tool, 16 general surgery residents from different programs across the country were recruited receiving intensive, personalized training on the models. Proficiency was measured before and after the training. RESULTS: . For the validation phase, significant differences among groups according to the previous level of expertise were shown, and therefore construct validity was established. The results of the second phase showed a significant overall improvement in participant's performance. CONCLUSION: . Effective training and assessment for advanced surgical skills in cardiothoracic trauma can be achieved using a low-cost pulsatile simulation model.

Gestural apraxia.

Gestural apraxia was first described in 1905 by Hugo Karl Liepmann. While his description is still used, the actual terms are often confusing. The cognitive approach using models proposes thinking of the condition in terms of production and conceptual knowledge. The underlying cognitive processes are still being debated, as are also the optimal ways to assess them. Several neuroimaging studies have revealed the involvement of a left-lateralized frontoparietal network, with preferential activation of the superior parietal lobe, intraparietal sulcus and inferior parietal cortex. The presence of apraxia after a stroke is prevalent, and the incidence is sufficient to propose rehabilitation.

Enantioselective synthesis of 2- and 3-substituted 2,3-dihydro[1,4]dioxino[2,3-b]pyridine derivatives and enantiomeric purity control by capillary electrophoresis.

A rapid and simple procedure for enantioselective preparation of 2- and 3-substituted 2,3-dihydro[1,4]dioxino[2,3-b]pyridine derivatives (A and B, respectively) is described. The enantiomeric purity of each isomer was determined by capillary electrophoresis using a dual-cyclodextrin system (S-beta-CD/beta-CD) dissolved in formic acid-ammonia buffer (pH 4, ionic strength 50 mM).

Direct injection HPLC micro method for the determination of voriconazole in plasma using an internal surface reversed-phase column.

A direct plasma injection liquid chromatographic method has been developed for the determination of a new triazole antifungal agent, voriconazole, using an internal surface reversed phase column. Therapeutic drug monitoring of voriconazole is relevant for patient management, especially in the case of drug-drug interaction. The method is easy to perform and requires 10 microL of a plasma sample. The chromatographic run time is less than 9 min using a mobile phase of 17:83 v/v acetonitrile-potassium dihydrogen phosphate buffer, 100 mM, pH 6.0 and UV detection at 255 nm. The fl ow rate was 1 microL/min. A linear response was observed over the concentration range 0.5-10 microg/mL (r2 = 0.977). A good accuracy (bias < or = 7.5%) was achieved for all quality controls, with intra-day and inter-day variation coefficients inferior to 6.7%. The lower limit of quantitation was 0.2 microg/mL, without interference of endogenous components. The stability of voriconazole in plasma stored at different temperatures was checked. Finally, the possibility of direct injection of plasma samples into the column permits a reduction in reagent consumption and in analytical steps, and hence in analytical error.

HPLC microdetermination of flurbiprofen enantiomers in plasma with a glycopeptide-type chiral stationary phase column.

A rapid and stereospecific HPLC micromethod to quantify flurbiprofen enantiomers was developed. Both flurbiprofen enantiomers and indomethacin, used as internal standard, were extracted with methylene chloride from 100 microL of acidified plasma. The resolution of the R- and S-forms was performed on a bonded vancomycin chiral stationary phase (Chirobiotic V) with 20% of tetrahydrofuran in ammonium nitrate (100 mM, pH 5) as mobile phase. Calibration curves were linear in the range 0.5-10 microg/mL for both enantiomers. A good accuracy (< or = 5%) was obtained for all quality controls, with intra-day and inter-day variation coefficients equal or less than 7.7%. Recovery of both enantiomers was found in the range 77.4-86.3%. The lower limit of quantitation was 0.25 microg/mL for both enantiomers, without interference of endogenous components. This validated micromethod has been successfully applied for quantifying R- flurbiprofen and S- flurbiprofen in rat plasma.

Simultaneous determination of four antipsychotic drugs in plasma by high-performance liquid chromatography. Application to management of acute intoxications.

A specific reversed phase-high pressure liquid chromatography (RP-HPLC) method has been developed for the simultaneous determination of clozapine (CZP), loxapine (LXP), zuclopenthixol (ZPT) and flupenthixol (FPT) in plasma. These four antipsychotic drugs are frequently used for the treatment of schizophrenia and other neuropsychiatric diseases. Carpipramine, a dihydrodibenzazepine, was used as an internal standard (I.S.). A liquid-liquid procedure was used to extract the drugs from human plasma. The analysis was performed on a XTerra MS C18 column with UV detection. Calibration curves were linear in the range 50-1000 microg/l. The limit of quantification (LOQ) was 15 microg/l for clozapine and loxapine and 20 microg/l for zuclopenthixol and flupenthixol. The coefficient of variation (CV) for intra- and inter-day precision was 7.2% or less with accuracies within 10% for the three concentrations.This isocratic and rapid method (run time<10 min) is useful for the management of acute intoxication.

Synthesis and anti-histaminic evaluation of N-phenyl-(alkyl)-5-(dialkylamino)methyl-2-amino-2-oxazolines.

New N-phenyl(alkyl)-5-(dialkylamino)methyl-2-amino-2-oxazolines, 5a-e, have been synthesized from the corresponding 3-phenyl(alkyl)carbamoyl-2-iminooxazolidines 2. A two-stage hydrolysis reaction led finally to the corresponding ring-opened N-phenyl(alkyl)-N'-[1-(3-(dialkylamino)-propan-2-ol)]ureas 4. The oxazoline ring was regenerated through an intramolecular nucleophilic substitution involving an halogen atom introduced by the reaction of thionyl chloride on 4. Pharmacological properties of 5a-e were evaluated on histaminic and adrenergic receptors in guinea-pig trachea and rat aorta. Compounds 5b and 5e showed a selective anti-histaminic effect on guinea-pig airways, but a significant response was obtained for a concentration >10(-6) M. No pharmacological activity was obtained with oxazoline 5c whereas oxazolines 5a and 5d seemed to present a non-selective effect on the contractile mechanism of the smooth muscle cell.

Determination of pKa values of 2-amino-2-oxazolines by capillary electrophoresis.

The dissociation constants of new 2-amino-2-oxazolines were determined by capillary electrophoresis (CE) as a new technique. A method based on a linear model has been used in the CE determination. A series of eight 2-amino-2-oxazolines are investigated to determine their ionization constant. Among them, three new oxazolines synthesized are presented. The Ka values were obtained from the plots of reciprocal effective mobility against inverse concentrations of protons. The potentiometric method (PM) was performed as a comparative method. No significant differences were observed between the determined dissociation constants using both methods. Thus, the pKa values have been found to vary between 8.55 and 8.68.

Rapid HPLC measurement of buflomedil in plasma in poisoning cases.

A rapid high-performance liquid chromatographic method for the determination of buflomedil in human plasma is described. It requires a single liquid-liquid extraction step from 1 mL of plasma with diethyl ether followed by chromatography on a Nova Pak C(18) reversed-phase column and detection by ultaviolet light. Metoclopramide was used as internal standard. The method is sensitive with a quantification limit at 500 ng/mL. It was used for the determination of buflomedil in biological fluids in poisoning cases.

Determination of mirtazapine and its demethyl metabolite in plasma by high-performance liquid chromatography with ultraviolet detection. Application to management of acute intoxication.

Mirtazapine is a new centrally acting noradrenergic and specific serotonin antidepressant, with an active demethyl metabolite. For toxicological purposes, a specific and accurate RP-HPLC assay was developed for the simultaneous plasma determination of these compounds. A linear response was observed over the concentration range 50-500 ng/ml. A good accuracy (bias <10%) was achieved for all quality controls, with intra-day and inter-day variation coefficients less than 8.3%. The lower limit of quantification was 20 ng/ml, without interferences with endogenous or exogenous components. This rapid method (run time <12 min) was used to manage three intoxications involving mirtazapine.

[Porphyria and drugs]. / Porphyries et médicaments.

Porphyrias are the result of inherited enzymatic defects of the heme's biosynthesis chain. A porphyria crisis with abdominal pain and neurological or psychiatric signs may be precipitated by drugs. Our purpose is to list the main drugs which may precipitate phorphyria crisis, specifying which are contraindicated such as cefalosporins, anaesthetics, anti epileptic and anti tubercular drugs, and which are doubtful because of conflicting results published in literature. In any case it is necessary to verify any prescription before giving a drug to a patient with porphyria.

[Risk medications in case of glucose-6-phosphate dehydrogenase deficiency]. / Médicaments à risque en cas de déficit en glucose-6-phosphate deshydrogénase (G-6PD).

The best known morbid effect of glucosephosphate dehydrogenase (G-6PD) deficiency is hemolysis induced by oxidative drugs. When prescribing drugs for G-6PD deficient subjects, two points should be kept in mind: different genetic variants of G-6PD deficiency entail different susceptibility to the hemolytic risk from drugs; thus a drug found to be safe in some G-6PD deficient subjects may not be equally safe in others; the risk and severity of hemolysis is almost always dose-related. The purpose of this paper is to underline the main drugs that cannot be safely administrated to G-6PD deficient subjects. They can be separated in drugs that must be avoided by G-6PD deficient subjects (such as sulphonamides, quinolones, nitrofurantoin), and drugs that do not systematically precipitate hemolysis but must nevertheless be prescribed with caution.

Synthesis and preliminary behavioural evaluation in mice of new 3-aryl-3-pyrrol-1-ylpropanamides, analogues of FGIN-1-27 and FGIN-1-43.

The 2-aryl-3-indoleacetamides FGIN-1-27 and FGIN-1-43 have already been characterized in-vitro as potent and specific ligands for the mitochondrial DBI receptor. This affinity was associated with psychotropic properties in several rodent behavioural tasks (in particular anxiolytic action) via enhancement of GABA transmission through neurosteroid production. The synthesis of new 3-aryl-3-pyrrol-1-ylpropanamides 1a-i, analogues of FGIN-1-27 and FGIN-1-43, is described in four steps starting from the corresponding arylaldehydes. Preliminary evaluation of these compounds in behavioural studies (spontaneous locomotor activity and anxiolytic activity) in mice was also undertaken.

Rapid high-performance liquid chromatographic measurement of venlafaxine and O-desmethylvenlafaxine in human plasma. Application to management of acute intoxications.

Venlafaxine, a second-generation antidepressant, acts by inhibition of the reuptake of presynaptic noradrenaline and serotonin. The main metabolite, O-desmethylvenlafaxine was found biologically active. For toxicological purpose, a rapid specific and accurate RP-HPLC assay was developed for the simultaneous determination of venlafaxine and O-desmethylvenlafaxine in human plasma. A linear response was observed over the concentration range 0.2-4 microg/ml. A good accuracy (<8%) was achieved for all quality controls, with intra-day and inter-day variation coefficient less than 10%. Finally, no interference was observed with other psychotic drugs encountered in acute poisoning. This rapid method (run time <10 min) was used to manage four voluntary intoxications involving venlafaxine.

Synthesis and pharmacological evaluation of 5-dialkylaminomethyl-2-amino-2-oxazolines as H1-antagonists.

New 5-dialkylaminomethyl-2-amino-2-oxazolines have been synthezised in two steps from the corresponding dialkylamines. They were evaluated in-vitro as H1-antagonists. Compounds 1c, 1d and 1j significantly antagonized histamine-induced contraction of guinea-pig trachea with a rightward shift of the concentration-response curve to histamine. Compound 1f, 5-[(4-benzyl-1-piperidinyl)methyl]-2-amino-2-oxazoline, induced an increase in acetylcholine Emax (the maximal response to acetylcholine 10(-3) M) and a shift to the left of the concentration-response curve. The lack of effect of this compound on histamine-induced contraction rules out a non-selective potentiation of the contraction mechanisms. Preliminary structure-activity results were reported partly based on physicochemical results.

Chiral resolution of flurbiprofen and ketoprofen enantiomers by HPLC on a glycopeptide-type column chiral stationary phase.

Vancomycin is an amphoteric, glycopeptide, macrocyclic antibiotic. When attached to 5 microspherical silica gel, vancomycin proved to be an effective chromatographic chiral stationary phase that could be used in the reversed-phase mode. In this study, a bonded vancomycin chiral stationary phase (Chirobiotic Vtrade mark) was investigated for the chiral liquid chromatography analysis of ketoprofen and flurbiprofen. The selectivity factor (alpha) and the chiral resolution factor (RS) of Chirobiotic Vtrade mark were evaluated first as a function of the buffer pH and molarity, and second as a function of organic modifier type and composition of the mobile phase. Four organic modifiers (tetrahydrofuran, 2-propanol, 1,4-dioxane and methanol) have been tested for their selectivity. Optimized conditions using 20% of tetrahydrofuran in ammonium nitrate (100 mM, pH 5) were selected for the enantioseparation of flurbiprofen and ketoprofen from their racemic forms. At pH 5, these acidic compounds are almost negatively charged, while the chiral selector possesses a positive charge allowing it to interact electrostatistically with the analytes. Using these chromatographic conditions, the column stability was excellent over several months of experiments.

Respective contributions of alpha-adrenergic and non-adrenergic mechanisms in the hypotensive effect of imidazoline-like drugs.

The hypotensive effect of imidazoline-like drugs, such as clonidine, was first attributed to the exclusive stimulation of central alpha2-adrenoceptors (alpha2ARs). However, a body of evidence suggests that non-adrenergic mechanisms may also account for this hypotension. This work aims (i) to check whether imidazoline-like drugs with no alpha2-adrenergic agonist activity may alter blood pressure (BP) and (ii) to seek a possible interaction between such a drug and an alpha2ARs agonist alpha-methylnoradrenaline (alpha-MNA). We selected S23515 and S23757, two imidazoline-like drugs with negligible affinities and activities at alpha2ARs but with high affinities for non-adrenergic imidazoline binding sites (IBS). S23515 decreased BP dose-dependently (-27+/-5% maximal effect) when administered intracisternally (i.c.) to anaesthetized rabbits. The hypotension induced by S23515 (100 microg kg(-1) i.c.) was prevented by S23757 (1 mg kg(-1) i.c.) and efaroxan (10 microg kg(-1) i.c.), while these compounds, devoid of haemodynamic action by themselves, did not alter the hypotensive effect of alpha-MNA (3 and 30 microg kg(-1) i.c.). Moreover, the alpha2ARs antagonist rauwolscine (3 microg kg(-1) i.c.) did not prevent the effect of S23515. Finally, whilst 3 microg kg(-1) of S23515 or 0.5 microg kg(-1) of alpha-MNA had weak hypotensive effects, the sequential i.c. administration of these two drugs induced a marked hypotension (-23+/-2%). These results indicate that an imidazoline-like drug with no alpha2-adrenergic properties lowers BP and interacts synergistically with an alpha(ARs agonist.

Effects of steam sterilization on thermogelling chitosan-based gels.

A new thermogelling chitosan-glycerophosphate system has been recently proposed for biomedical applications such as drug and cell delivery. The objectives of this work were to characterize the effect of steam sterilization on the in vitro and in vivo end performances of the gel and to develop a filtration-based method to assess its sterility. Autoclaving 2% (w/v) chitosan solutions for as short as 10 min resulted in a 30% decrease in molecular weight, 3-5-fold decrease in dynamic viscosity, and substantial loss of mechanical properties of the resulting gel. However, sterilization did not impair the ability of the system to form a gel at 37 degrees C. The antimicrobial activity of chitosan against several microorganisms was evaluated after inoculation of chitosan solutions and removal of the cells by filtration. It was found that, although chitosan was bacteriostatic against the heat sterilization bioindicator Bacillus stearothermophilus, the bacteria could rapidly grow after separation from the chitosan solution by filtration. This indicated that B. stearothermophilus is an adequate strain to validate a heat sterilization method on chitosan preparations, and accordingly this strain was used to assess the sterility of chitosan solution following a 10 min autoclaving time.

Interactions between imidazoline binding sites and dopamine levels in the rat nucleus accumbens.

Imidazoline binding sites are present in the striatal complex and in the extended amygdala and have been implicated in mood disorders. In this report we analysed the influence of these sites on the functional activity of the mesolimbic dopaminergic transmission, one of the major brain systems involved in the regulation of motivation and reward. We studied the effects of two imidazoline ligands, S23229 and S23230 (respectively S(+) and R(-) enantiomers of the S22687 or (5-[2-methyl phenoxy methyl] 1,3-oxazolin-2-yl) amine), on extracellular dopamine in the nucleus accumbens using microdialysis in freely moving rats. We compared these imidazoline ligands to cocaine, a dopamine uptake blocker known to increase extracellular dopamine concentrations. S23229 dose-dependently increased extracellular dopamine and locomotor activity. S23230 dose-dependently increased extracellular dopamine and produced a near-significant dose-effect on locomotor activity. S23229 had a stronger efficacy than S23230 and increased dopamine levels in the nucleus accumbens at an extent similar to the one of cocaine. These results suggest that central imidazoline binding sites could contribute to the functional regulation of the mesolimbic dopaminergic system.