Mesoporous solids functionalized with anion-binding groups have proved to be suitable anion hosts and have been used in selective colorimetric displacement assays. The material UVM-7, a mesoporous MCM41-type support characterized by the presence of nanometric mesoporous particle conglomerates, was selected as inorganic scaffolding. Reaction of the template-free UVM-7 solid with 3-aminopropyltriethoxysilane (1) yielded solid S1, from which the derivatives S2 and S3 were obtained by reaction with 2-methylthio-2-imidazoline hydroiodide (2) and butyl isocyanate (3), respectively. Solids S4 and S5 were prepared by reaction of the starting mesoporous UVM-7 scaffolding with N-methyl-N'-propyltrimethoxysilyl imidazolium chloride (4) and with 3-(trimethoxysilyl)propyl-N,N,N-trimethylammonium chloride (5), respectively. The solids synthesized contain mesoporous binding pockets that can interact with anions through electrostatic attractive forces (S1, S2, S4, S5) and hydrogen-bonding interactions (S1, S2, S3, S4). These functionalized solids were loaded with a dye (d) capable of interacting coordinatively with the anchored binding sites, in our case 5-carboxyfluorescein, to yield the hybrid materials S1d, S2d, S3d, S4d and S5d. These dye-containing solids are the signaling reporters. Their sensing ability towards a family of carboxylates, namely acetate, citrate, lactate, succinate, oxalate, tartrate, malate, mandelate, glutamate and certain nucleotides, has been studied in pure water at pH 7.5 (Hepes, 0.01 mol dm(-3)). In the sensing protocol, a particular analyte may be bonded preferentially by the nanoscopic functionalized pocket, leading to delivery of the dye to the solution and resulting in colorimetric detection of the guest. The response to a given anion depends on the characteristics of the binding pockets and the specific interaction of the anion with the binding groups in the mesopores. We believe that the possibility of using a wide variety of mesoporous supports that can easily be functionalized with anion-binding sites, combined with suitable dyes as indicators, make this approach significant for opening new perspectives in the design of chromogenic assays for anion detection in pure water.

Objectives: A number of studies have now shown that subjects with bipolar disorder (BD) have significant psychosocial impairment during interepisode intervals. This study was carried out to assess the level of functioning as well as to identify potential predictors of functioning in a well-defined, euthymic bipolar sample. Methods: The study included 71 euthymic bipolar patients and 61 healthy controls. The Functioning Assessment Short Test (FAST) was used to assess multiple areas of functioning such as autonomy, occupational functioning, cognitive functioning, interpersonal relationships, financial issues, and leisure time. Multivariate analysis was used to determine the global and specific clinical predictors of outcome. Results: Sixty percent (n = 42) of the patients had overall functional impairment (defined as a FAST total score > 11) compared to 13.1%(n = 8) of the control group (p = 0.001). Bipolar patients showed a worse functioning in all the areas of the FAST. Only four variables-older age, depressive symptoms, number of previous mixed episodes, and number of previous hospitalizations-were associated with poor functioning, on a linear regression model, which accounted for 44% of the variance (F = 12.54, df = 58, p < 0.001). Conclusions: A substantial proportion of bipolar patients experience unfavorable functioning, suggesting that there is a significant degree of morbidity and dysfunction associated with BD, even during remission periods. Previous mixed episodes, current subclinical depressive symptoms, previous hospitalizations, and older age were identified as significant potential clinical predictors of functional impairment.

Ziprasidone was the fifth atypical antipsychotic approved by Food and Drug Administration (FDA) for use in bipolar mania and mixed episodes. This atypical antipsychotic has a unique profile, as it acts primarily through serotonergic and dopaminergic receptor antagonism, but also exerts effects as an inhibitor of norepinephrine reuptake. Moreover, one of the advantages of ziprasidone is its safety profile as it is not associated with clinically significant metabolic side effects and little or no effect on prolactin level or anticholinergic side effects. Most of the studies evaluating ziprasidone's efficacy and safety are short-term double-blind, placebo-controlled studies in acute mania and mixed episodes. In two of them, ziprasidone was associated to significant improvement in the primary measures assessed. However, an add-on study, lithium plus ziprasidone showed similar results than lithium monotherapy, although there was a significant advantage for the combination within the first week. In a more recent trial, ziprasidone was compared with placebo and haloperidol as monotherapies, again beating placebo. In that trial, ziprasidone appeared to be safer and better tolerated, although less likely efficacious than haloperidol. Particularly, subjects treated with ziprasidone were less likely to switch to depression. Despite the well-studied efficacy of ziprasidone in the first weeks of treatment, there are no controlled trials that evaluate the role and efficacy of ziprasidone in long-term treatment of bipolar disorder (BD). Overall, in the open-label extension studies, there was a global improvement at all visits compared with baseline scores. Furthermore, ziprasidone appears to offer some antidepressant effect in patients with major depressive episode and resistant to treatment, as demonstrated in add-on open-label studies with ziprasidone plus selective serotonin reuptake inhibitor (SSRI).

Dual-function hybrid material U 1 was designed for simultaneous chromofluorogenic detection and removal of Hg(2+) in an aqueous environment. Mesoporous material UVM-7 (MCM41 type) with homogeneously distributed pores of about 2-3 nm in size, a large specific surface area exceeding 1000 m(2) g(-1), and nanoscale particles was used as an inorganic support. The mesoporous solid is decorated with thiol groups that were treated with squaraine dye III to give a 2,4-bis(4-dialkylaminophenyl)-3-hydroxy-4-alkylsulfanylcyclobut-2-enone (APC) derivative that is covalently anchored to the inorganic silica matrix. The solid was characterised by various techniques including X-ray diffraction, transmission electron microscopy, Raman spectroscopy, and nitrogen adsorption. This hybrid solid is the chemodosimeter for Hg(2+) detection. Hg(2+) reacts with the APC fragment in U 1 with release of the squaraine dye into the solution, which turns deep blue and fluoresces strongly. Naked-eye Hg(2+) detection is thus accomplished in an easy-to-use procedure. In contrast, U 1 remains silent in the presence of other thiophilic transition metal ions, alkali and alkaline earth metal ions, or anions ubiquitously present in water such as chloride, carbonate, sulfate, and phosphate. Material U 1 acts not only as chemodosimeter that signals the presence of Hg(2+) down to parts-per-billion concentrations, but at the same time is also an excellent adsorbent for the removal of mercury cations from aqueous solutions. The amount of adsorbed mercury ranges from 0.7 to 1.7 mmol g(-1), depending on the degree of functionalisation. In addition, hybrid material U 1 can be regenerated for both sensing and removal purposes. As far as we know, U 1 is the first example of a promising new class of polyfunctional hybrid supports that can be used as both remediation and alarm systems by selective signalling and removal of target species of environmental importance. Model compounds based on silica gel (G 1), fumed silica (F 1), and micrometre-sized MCM-41 scaffolds (M 1) were also prepared and studied for comparative purposes.

Mesoporous amino-functionalised solids containing certain dyes have been used as suitable anion hosts in displacement assays for the colorimetric signalling of phosphate in water.

Objective: The aim of this paper was to review the association of most commonly used psychopharmacological drugs with weight gain in bipolar disorder. Method: Information was retrieved from a PubMed/Medline literature search reviewing weight gain in pharmacological studies in bipolar disorder. Results: Obesity and overweight in bipolar disorder are partly related to prescribed drugs with a strong effect of clozapine and olanzapine. Lesser but still relevant weight gain is caused by quetiapine, risperidone, lithium, valproate, gabapentin and by some antidepressants. Ziprasidone, aripiprazole, carbamazepine and lamotrigine do not seem to cause significant overweight. Conclusion: Careful monitoring of weight changes in patients before and after drug prescription should be implemented in the clinical routine and drugs which potentially cause weight gain should be avoided in overweight patients with bipolar disorder. Furthermore, eating habits and daily activities should be targeted as they may also have a significant impact on overall health and weight-related issues.

Objective: Although there are some randomized controlled trials that highlight the positive role of family-focused treatment added to pharmacotherapy in bipolar disorder, no trials using contemporary methodologies have analyzed the specific effect of working with caregiver-only groups. The aim of this study was to assess the efficacy of a psychoeducational group intervention focused on caregivers of euthymic bipolar patients. Method: A total of 113 medicated euthymic bipolar outpatients who lived with their caregivers were randomized into an experimental and a control group. Caregivers in the experimental group received twelve 90-min group psychoeducation sessions focused on knowledge of bipolar disorder and training in coping skills. The patients did not attend the groups. Caregivers assigned to the control group did not receive any specific intervention. Patients were assessed monthly during both the intervention and the 12 months of follow-up. The primary outcome was time to any mood recurrence. Results: Psychoeducation group intervention focused on the caregivers of bipolar patients carried a reduction of the percentage of patients with any mood recurrence (chi(2)= 6.53; p = 0.011) and longer relapse-free intervals (log-rank chi(2)= 4.04; p = 0.044). When different types of episodes were analyzed separately, the effect was significant for both the number of patients who experienced a hypomanic/manic recurrence (chi(2)= 5.65; p = 0.017) and the time to such an episode (log-rank chi(2)= 5.84; p = 0.015). The differences in preventing depressive and mixed episodes were not significant. Conclusions: A psychoeducation group intervention for the caregivers of bipolar patients is a useful adjunct to usual treatment for the patients in reducing the risk of recurrences, particularly mania and hypomania, in bipolar disorder.

We evaluated the prophylactic efficacy and the long-term tolerability of oxcarbazepine administration in the treatment of bipolar I and II disorder as an adjunctive therapy to lithium. We conducted a 52-wk, double-blind, randomized, placebo-controlled, parallel-group, multicentre, clinical trial. Bipolar I and II DSM-IV outpatients, having had two or more episodes in the last year, but currently being in remission, were randomly assigned on a 1:1 ratio to oxcarbazepine (n=26) or placebo (n=29) as adjuncts to ongoing treatment with lithium. The primary efficacy variable was the length of the remission period assessed by means of the Young Mania Rating Scale (YMRS) and Montgomery-Asberg Depression Rating Scale (MADRS). Other assessments were the Clinical Global Impression (CGI-BP-M), functional activity (GAF), anxiety (HAMA) and impulsiveness (BIS-11). The average time until first recurrence of any type was 19.2+/-13.9 wk and 18.6+/-17.0 wk for oxcarbazepine and placebo respectively (p=0.315). Ten (38.46%) patients had a recurrence of any kind in the oxcarbazepine group vs. 17 (58.62%) in the placebo group (p=0.1354). There was a trend for depressive episodes being less likely in the oxcarbazepine group compared to the placebo group (11.54% and 31.03% respectively, p=0.085), and for better functionality with the GAF (p=0.074). Impulsivity was significantly better prevented by oxcarbazepine (p=0.0443). Overall, oxcarbazepine was well tolerated. This pilot, randomized clinical trial, suggests that oxcarbazepine might have some prophylactic efficacy with regards to impulsivity and perhaps mood episodes in patients taking lithium, although further, adequately powered controlled trials are needed to confirm these findings.

OBJECTIVES: To evaluate the baseline characteristics and follow-up outcomes of rapid-cycling (RC) bipolar I patients in a large, prospective, observational study. METHODS: EMBLEM (European Mania in Bipolar Longitudinal Evaluation of Medication) is a long-term prospective observational study of in- and outpatients with an acute mania/mixed episode conducted in 14 European countries. Demographic and clinical variables were collected at baseline, including the presence or absence of DSM-IV rapid-cycling during the past year. Outcome measures included the 5-item Hamilton Depression Rating Scale (HAMD-5) and Young Mania Rating Scale (YMRS) over 12 weeks, as well as the Clinical Global Impressions-Bipolar Disorder Scale (CGI-BP overall, mania and depression) over 12 months. RESULTS: Of 3684 patients enrolled, 3089 patients provided reliable data to qualify for either RC (N=535, 17.3%) or non-RC (NRC, N=2554), according to DSM-IV. RC prevalence varied across countries (p<0.001). Baseline and 12 week outcomes on the YMRS and HAMD-5, 12 month ratings on the CGI-BP subscales and work impairment at 12 months were significantly different (p<0.001) between groups, being worse in RC. RC patients were more likely to receive antidepressants and lamotrigine (p<0.001). Using logistic regression, RC was associated to country (p<0.001), female sex (p=0.029), outpatients (p=0.035), more history of attempted suicide (p<0.001) and alcohol abuse (p<0.001). CONCLUSIONS: The EMBLEM results suggest that in naturalistic settings, patients with mania and RC differ from NRC in socio-demographic characteristics, treatment prescriptions and clinical outcome measures with a consistently worse occupational outcome and comorbidities. RC represents a longitudinally severe form of bipolar disorder, with poorly evidence-based diagnostic and therapeutic tools.

BACKGROUND: To evaluate the 12-week outcomes (effectiveness, tolerability, and patterns of medication use) of olanzapine (either in antimanic monotherapy or in combination with other antipsychotics, anticonvulsants, and/or lithium) in patients with bipolar mania or mixed mania. METHOD: EMBLEM (European Mania in Bipolar Longitudinal Evaluation of Medication) is a 24-month prospective observational study of in- and outpatients with acute mania/mixed mania conducted in 14 European countries. Primary outcome measures included Clinical Global Impressions-Bipolar Disorder scale (overall, mania, and depression); 5-item Hamilton Depression Rating Scale; and Young Mania Rating Scale. Tolerability measures included a questionnaire to assess patients' symptomatic complaints. RESULTS: Overall, 2004 patients received olanzapine (olanzapine monotherapy, n=673; olanzapine combination, n=1331). Concomitant therapy with antidepressants and/or anxiolytics was possible in both groups. The countries significantly differed in the use of olanzapine monotherapy versus olanzapine combination (p<.0001). Baseline-to-endpoint changes on the CGI-BP subscales, YMRS, and HAMD-5 were significant within both treatment groups (p<.0001). Olanzapine monotherapy was generally better tolerated than olanzapine combination, particularly with regard to sedation (12% vs 17%; p<.001), tremor (2% vs 5%; p<.001), and akathisia (3% vs 6%; p<.001). DISCUSSION: The acute-phase EMBLEM results suggest that in naturalistic settings, olanzapine (both as monotherapy and combination) may be effective in treating patients with bipolar mania. The use of olanzapine monotherapy or combination varies significantly across countries, but combination is generally the rule, rather than the exception.