Dye-Sensitized Nanostructured Crystalline Mesoporous Tin-doped Indium Oxide Films with Tunable Thickness for Photoelectrochemical Applications.

A simple route towards nanostructured mesoporous Indium-Tin Oxide (templated nano-ITO) electrodes exhibiting both high conductivities and optimized bicontinuous pore-solid network is reported. The ITO films are first produced as an X-ray-amorphous, high surface area material, by adapting recently established template-directed sol-gel methods using Sn(IV) and In(III) salts. Carefully controlled temperature/atmosphere treatments convert the as-synthesized ITO films into nano-crystalline coatings with the cubic bixbyite structure. Specially, a multi-layered synthesis was successfully undertaken for tuning the film thickness. In order to evaluate the performances of templated nano-ITO as an electrode substrate for photoelectrochemical applications, photoelectrodes were prepared by covalent grafting of a redox-active dye, the complex [Ru(bpy)2(4,4'-(CH2PO3H2)2-bpy)]Cl21 (bpy=bipyridine). Surface coverage was shown to increase with the film thickness, from 0.7 × 10-9 mol.cm-2 (one layer, 45 nm) to 3.5 × 10-9 mol.cm-2 (ten layers, 470 nm), the latter value being ~ 100 times larger than that for commercially available planar ITO. In the presence of an electron mediator, photocurrents up to 50 µA.cm-2 have been measured under visible light irradiation, demonstrating the potential of this new templated nano-ITO preparation for the construction of efficient photoelectrochemical devices.

Influence of social isolation and 6-OHDA lesion on the effects of quinelorane.

The sensitivity of the response to the preferential dopaminergic D3 (DAD3) receptor agonist, quinelorane, was compared in mice housed socially and in mice isolated for 4 weeks. Quinelorane (1, 5, 10, 50 and 100 microg/kg) was administered intraperitoneally. Motor activity was measured for 60 min posttreatment. Rectal temperature was measured prior to and 1 h following the administration of quinelorane (10, 50 and 100 microg/kg i.p.). Quinelorane significantly and dose-dependently decreased locomotor activity in social and in isolated mice. The locomotor activity of isolated mice was significantly lower than that of social mice, but isolation had no effect on quinelorane-induced hypomotility. Quinelorane decreased dose-dependently rectal temperature in isolated and social mice, but isolation had no effect on quinelorane-induced decrease in rectal temperature. The lesions of dopaminergic terminals with intracerebroventricular administration of 6-OHDA decreased the dopamine (DA) level by 93% in the nucleus accumbens and by 91% in the corpus striatum; these lesions impaired neither the hypolocomotion nor the hypothermia induced by quinelorane. Thus, it may be concluded that social isolation has no influence on the quinelorane-induced decreases in rectal temperature and in locomotor activity and that the DA receptors involved in these effects of quinelorane are located postsynaptically.

Evolution of plasma homovanillic acid (HVA) in chronic schizophrenic patients treated with haloperidol.

In a 4-week study of 14 drug-free schizophrenic patients (according to DSM-III-R), free and conjugated fractions of plasma homovanillic acid (pHVA) were repeatedly measured. Free HVA levels decreased during the first 2 h of haloperidol intake (P < 0.03). Conjugated HVA levels slowly decreased during the following weeks (P < 0.05), while free HVA levels remained stable. After 4 weeks, free HVA levels remained unchanged 2 h after morning haloperidol intake, but conjugated HVA levels tended to increase. In haloperidol responders, at baseline the free/total HVA ratio was significantly higher than that in non-responders (P < 0.01). Tolerant patients, i.e. those whose post-treatment free HVA levels decreased below pre-treatment levels, were not found to respond better to haloperidol than non-tolerant patients. The balance between free and conjugated pHVA may be a better reflection of the action of haloperidol than free pHVA levels and it may be of prognostic value in terms of drug response.

Neuroleptic-resistant schizophrenic patients treated by clozapine: clinical evolution, plasma and red blood cell clozapine and desmethylclozapine levels.

The aim of this open study was to determine a more rational therapeutic approach for psychotic patients treated with clozapine for several months, using measurement of plasma and red blood cell levels (P, RBC) of clozapine (cloza) and N-desmethylclozapine (descloza), the major metabolite of clozapine, which has been reported to be less active but more toxic (agranulocytosis) than clozapine itself. The RBC concentration may be considered as more representative of the free fraction drug. The study concerned 7 patients suffering from chronic paranoid schizophrenia according to the DSM-IV criteria. All of them were treatment-refractory schizophrenic inpatients (4 men, 3 women, mean age +/- SD: 38.2 +/- 8.4 years; mean duration of illness +/- SD: 14.4 +/- 5.1 years). They had received at least two different neuroleptics, for 6 weeks, before entering the study. Treatment started in our hospitalization unit with clozapine 25 mg up to a maximum of 900 mg/d (mean stabilized daily dose +/- SD: 507 +/- 211 mg and mean daily dose per kg: 6.91 +/- 3.08 mg). Clinical evaluations (Quality of Life Scale: QLS), regular blood monitoring and biological samples were conducted at the same time, weekly for 18 weeks and then monthly (duration of the study: 4 to 38 months; mean +/- SD: 12.9 +/- 11.5 months). Plasma and RBC (after lysis) levels were determined by reversed phase HPLC and UV detection after extraction with hexane. All the patients improved very quickly after the first week of treatment and six were able to leave the hospitalization unit and start outpatient care such as daily hospitalization, returning home or in sheltered accommodation. With the following plasma (P) and RBC levels: mean cloza +/- SD: (P = 294 +/- 146 ng/ml; RBC = 110 +/- 82 ng/ml) and mean descloza +/- SD: (P = 173 +/- 106 ng/ml; RBC = 76 +/- 54 ng/ml); none of the seven patients developed agranulocytosis. The blood levels, ensuring better surveillance, have a predictive value for clinical improvement. A linear pharmacoclinical correlation was only found between RBC cloza concentrations and the evolution of the QLS scores. Clozapine fulfils the criteria for therapeutic drug monitoring, and determination of plasma, and more particularly RBC, cloza and descloza levels may help to find the lowest effective dose with the fewest side effects.

[Pharmaco-clinical correlations during fluoxetine administration in patients with depressive schizophrenia treated with haloperidol decanoate]. / Corrélations pharmacocliniques lors de l'administration de fluoxétine chez des patients schizophrènes déprimés traités par halopéridol décanoate.

The study concerned 7 patients suffering from schizophrenic disorder according to the DSM III R criteria, treated with a stable dose of haloperidol decanoate (Haldol décanoas) added with fluoxetine (Prozac) from 20 mg to 40 mg/day because of major depression. Patients were assessed at baseline and weekly during the first cycle, and then once a month before each haloperidol decanoate injection, using the brief psychiatric rating scale (BPRS), the general clinical impression scale (CGI) and the Montgomery and Asberg depression rating scale (MADRS). Extrapyramidal and anticholinergic side-effects, blood pressure and pulse were noted. Determinations of plasma and red blood cells concentrations of haloperidol and reduced haloperidol, and of fluoxetine and norfluoxetine, were conducted at the same time than clinical evaluations. For all patients, we observed an improvement by the end of the first week, which became significant at the end of the second week, and continued in subsequent weeks (more than 30 per cent). Two weeks after the addition of fluoxetine, a very significant increase in haloperidol concentrations (more than 100 per cent) was noted; fluoxetine seems to have pharmacokinetic interactions with haloperidol, either by inhibiting its hepatic metabolism (inhibition of cytochrome P450 isoenzyme) or/and by displacing it from protein binding sites.

Brain catecholamines, serotonin and their metabolites in mice selected for low (MGL) and high (MGH) blood magnesium levels.

Brain noradrenaline, dopamine, DOPAC (3-4 dihydroxyphenylacetic acid), HVA (homovanillic acid), serotonin and 5-HIAA (5-hydroxyindolacetic acid) were determined by high performance liquid chromatography with amperimetric detection in adult male mice from three different strains : mice with genetically low (MGL) or high (MGH) blood magnesium levels, obtained by selective breeding and outbred Swiss albino mice. Noradrenaline levels were significantly higher (P < or = 0.001) in MGL than in MGH and Swiss mice : DOPAC levels were lower (P < or = 0.001) in MGL than in MGH and Swiss. Little or no differences were found for these variables between MGH and Swiss mice. MGL and MGH animals had similar brain dopamine, HVA and serotonin contents. These results suggest that the mere selection for genetic traits inducing low blood magnesium levels increases the synthesis of noradrenaline or decreases its catabolism. The above data together with the higher urinary noradrenalin excretion previously observed in the MGL line might account for the higher sensitivity and/or reactivity of MGL animals to stress. Swiss mice had significantly lower (P < or = 0.001) brain dopamine and serotonin contents than both MGL and MGH lines; indeed Swiss mice and MGL/MGH mice were issued from very different populations and had vastly different stocks of genes. Brain 5-HIAA content was also found higher (P < or = 0.01) in MGH than in MGL and Swiss mice; this latter result needs to be confirmed by further research.

Brain weight and noradrenaline content in mice selected for low (MGL) and high (MGH) blood magnesium.

Brain noradrenaline content was determined by high performance liquid chromatography in adult male mice from three different strains: 40 mice with genetically low (MGL) or high (MGH) blood magnesium levels, obtained by selective breeding and 20 outbred Swiss albino mice. Brain wet weight and noradrenaline levels were significantly higher in MGL than in MGH and Swiss mice. Few or no differences were found between MGH and Swiss mice. MGL and MGH animals had a similar mean body weight, were raised in identical conditions, and were fed with a normal diet, rich in magnesium. These results together with the higher urinary noradrenaline excretion previously observed in the MGL line, indicate that the mere selection for genetic traits inducing low blood magnesium levels entails an increased catecholamine production. This phenomenon most probably accounts for the higher sensitivity and/or reactivity of MGL animals to stress. The possible role of magnesium-controlling genetic factors in the regulation of brain growth is also suggested.