Significant cell uptake of Gd(III)-diphenylphosphoryl-diphenylphosphonium complexes: evidence for a new conformationally-dependent tumour cell targeting vector.

The synthesis, characterisation, and tumour cell uptake of six novel Gd(III)-diphenylphosphoryl-diphenylphosphonium complexes are reported. The propyl-linked Gd(III) complexes can accumulate inside human glioma cells at prodigious levels, approaching 1200%, over the parent triphenylphosphonium salts. DFT and quantum chemical topology analyses support a new type of conformationally-dependent tumour cell targeting vector.

Selective delivery of remarkably high levels of gadolinium to tumour cells using an arsonium salt.

The use of a triphenylarsonium vector for tumour cell-targeting leads to a dramatic increase in Gd uptake in human glioblastoma multiforme cells by up to an order of magnitude over the isosteric triarylphosphonium analogue, with significant implications for 'theranostic' applications involving delivery of this important lanthanoid metal ion to tumour cells.

Salivary levels of total huntingtin are elevated in Huntington's disease patients.

Patients with Huntington's disease (HD), an autosomal-dominant neurodegenerative disease, show substantial variability in age-of-onset, symptom severity and course of illness, warranting the need for biomarkers to anticipate and monitor these features. The HD gene encodes the disease protein huntingtin (Htt), a potentially useful biomarker for this disease. In the current study, we determined whether total Htt protein (normal plus mutant; "tHtt") could be reliably measured in human saliva, a body fluid that is much more accessible compared to cerebral spinal fluid or even blood, and whether salivary levels of tHtt were clinically meaningful.

Clozapine and risperidone in moderately refractory schizophrenia: a 6-month randomized double-blind comparison.

Objective: Clozapine remains the only medication indicated for refractory schizophrenia. As new antipsychotic drugs become available, their efficacy compared to clozapine, particularly in moderately ill patients, is of great clinical interest. We compared risperidone, the first of these, to clozapine in partially responsive patients.

Polymerizable cationic micelles form cylinders at intermediate conversions.

The structural evolution of micelles of the polymerizable surfactant omega-methacryloyloxyundecyltrimethylammonium bromide (MUTAB) during UV-initiated polymerization in aqueous micellar solution has been followed by small-angle neutron scattering. Although the micelles are short spheroids both before and after polymerization, a significant, distinct population of rodlike micelles develops during the reaction, which accounts for as much as 40 vol % of the micellized surfactant and coexists with the spheroids and dissolved monomer. These coexisting micelle populations are shown to remain in dynamic equilibrium throughout the reaction and can be understood by treating it as a ternary mixture of surfactant, amphiphilic polyelectrolyte, and water.

Case reports of postmarketing adverse event experiences with olanzapine intramuscular treatment in patients with agitation.

Objective: Agitation is a medical emergency with increased risk for poor outcome. Successful treatment often requires intramuscular (IM) psychotropics. Safety data from the first 21 months of olanzapine IM, approved in the United States for the treatment of agitation associated with schizophrenia and bipolar disorder, are presented.

Structure changes in micelles and adsorbed layers during surfactant polymerization.

We have studied the self-assembled structures formed by the cationic surfactant 11-(methacryloyloxy)undecyltrimethylammonium bromide (MUTAB) using small angle neutron scattering as it undergoes UV-initiated polymerization in bulk solution, and the subsequent adsorbed structures at the mica/solution interface using atomic force microscopy. MUTAB forms spheroidal aggregates in aqueous solution with an axial ratio of 2-3 both before and after polymerization, as previously reported in numerous studies. However, at intermediate conversions the micelles surprisingly form elongated structures up to 200 A long.

ATRMec1 phosphorylation-independent activation of Chk1 in vivo.

The conserved protein kinase Chk1 is a player in the defense against DNA damage and replication blocks. The current model is that after DNA damage or replication blocks, ATR(Mec1) phosphorylates Chk1 on the non-catalytic C-terminal domain. However, the mechanism of activation of Chk1 and the function of the Chk1 C terminus in vivo remains largely unknown.

Clinical, functional, and economic ramifications of early nonresponse to antipsychotics in the naturalistic treatment of schizophrenia.

Objective: Early nonresponse to antipsychotics appears to predict subsequent nonresponse to treatment when assessed in randomized controlled trials of predominately acute inpatients treated for schizophrenia. This study assessed the predictive accuracy of early nonresponse to treatment and its clinical, functional, and economic ramifications in the naturalistic treatment of predominately chronic outpatients treated for schizophrenia.

Methods: This post hoc analysis used data from a 1-year, randomized, open-label study of olanzapine, risperidone, and typical antipsychotics in the treatment of schizophrenia.

Outcomes for Latin American versus White patients suffering from acute mania in a randomized, double-blind trial comparing olanzapine and haloperidol.

Data from a published double-blind randomized trial comparing olanzapine versus haloperidol in acute mania were used to address the response and tolerability of Latin American patients. Primary efficacy end point was the remission rate (Young Mania Rating Scale score View Article and Find Full Text PDF

Olanzapine versus risperidone in the treatment of manic or mixed States in bipolar I disorder: a randomized, double-blind trial.

Objective: To compare olanzapine and risperidone in the treatment of nonpsychotic acute manic or mixed episodes.

Method: This 3-week, randomized, controlled, double-blind, parallel multicenter study compared olanzapine (5-20 mg/day; N = 165) and risperidone (1-6 mg/day; N = 164) among hospital inpatients who met DSM-IV criteria for bipolar I disorder, manic or mixed episode, without psychotic features. The study was conducted at 30 sites in the United States between July 2001 and June 2002.

Clinical relevance of depressive symptom improvement in bipolar I depressed patients.

Background: Gaps remain between rating scale changes obtained in a clinical trial and what those results mean in clinical practice.

Objective: To better understand the relevance of results from a clinical trial we examined the relationship between rating scale measures and the clinicians' assessment of illness severity.

Methods: Data from a randomized double-blind 8-week study of bipolar I depression were examined post hoc in patients who received placebo (PLA, n = 355), olanzapine (n = 351) (OLZ, 5 to 20 mg/d), or olanzapine-fluoxetine combination (n = 82) (OFC, 6 and 25, 6 and 50, or 12 and 50 mg/d).

Randomized, placebo-controlled trial of olanzapine as maintenance therapy in patients with bipolar I disorder responding to acute treatment with olanzapine.

Objective: In a placebo-controlled, double-blind study, the authors investigated the efficacy and safety of olanzapine as monotherapy in relapse prevention in bipolar I disorder.

Method: Patients achieving symptomatic remission from a manic or mixed episode of bipolar I disorder (Young Mania Rating Scale [YMRS] total score < or =12 and 21-item Hamilton Depression Rating Scale [HAM-D] score or =15, HAM-D score > or =15, or hospitalization).

Clinical features of bipolar depression versus major depressive disorder in large multicenter trials.

Objective: Failure to recognize bipolar disorder in patients who experience a major depressive episode may lead to inappropriate treatment and poorer outcomes. Clinical features that could distinguish bipolar from unipolar depression would facilitate more appropriate treatment selection.

Method: The authors used data from nonpsychotic outpatients participating in three large multicenter clinical trials conducted in the United States for the treatment of major depressive episodes to compare 477 subjects with a diagnosis of bipolar disorder and 1,074 with major depressive disorder.

Retrospective analysis of diabetes risk in elderly patients with dementia in olanzapine clinical trials.

Objective: The objective of this study was to evaluate the association of established risk factors for treatment-emergent diabetes (TED) among patients over 65 years of age with dementia who received treatment with olanzapine.

Methods: This was a post hoc analysis of data pooled from seven olanzapine clinical trials, which included patients over 65 years of age with dementia. The association of established risk factors for TED was evaluated using categorical and time-to-event analysis.

Rapid versus non-rapid cycling as a predictor of response to olanzapine and divalproex sodium for bipolar mania and maintenance of remission: post hoc analyses of 47-week data.

Background: Rapid cycling in bipolar disorder has been associated with greater morbidity. We examine whether rapid cycling affects treatment response to olanzapine or divalproex in acute mania.

Methods: A post hoc analysis of a 47-week, randomized, double-blind study compared olanzapine (5-20 mg/day) to divalproex sodium (500-2500 mg/day) for bipolar manic or mixed episodes (N=251).

Olanzapine does not enhance cognition in non-agitated and non-psychotic patients with mild to moderate Alzheimer's dementia.

Objective: This was an exploratory study of olanzapine as potential treatment for improvement in cognition in patients with Alzheimer's disease without prominent psychobehavioral symptoms.

Methods: Non-psychotic/non-agitated patients (n = 268) with Alzheimer's disease, who had baseline Mini-Mental State Examination (MMSE) scores of 14-26 were randomized to treatment with olanzapine (2.5 to 7.

Initial symptoms of manic relapse in manic or mixed-manic bipolar disorder: post hoc analysis of patients treated with olanzapine or lithium.

Unlabelled: A post hoc analysis of Young Mania Rating Scale (YMRS) item scores was conducted to identify symptoms that may predict impending relapse using prospectively collected data from a double-blind, randomized relapse prevention study of patients treated with olanzapine (N=200, 5-20 mg/d) versus lithium (N=201, 300-1800 mg/d).

Methods: Relapses (YMRS > or = 15, or hospitalization) included in this analysis occurred 3-52 weeks after randomization. Repeated measures logistic regression of increases (> or = 1) in YMRS item scores prior to the visit that preceded relapse was used to estimate the odds of relapse.

Olanzapine versus lithium in the maintenance treatment of bipolar disorder: a 12-month, randomized, double-blind, controlled clinical trial.

Objective: The authors compared the efficacy of olanzapine and lithium in the prevention of mood episode relapse/recurrence.

Method: Patients with a diagnosis of bipolar disorder (manic/mixed), a history of two or more manic or mixed episodes within 6 years, and a Young Mania Rating Scale total score > or =20 entered the study and received open-label co-treatment with olanzapine and lithium for 6-12 weeks. Those meeting symptomatic remission criteria (Young Mania Rating Scale score < or =12; 21-item Hamilton depression scale score < or =8) were randomly assigned to 52 weeks of double-blind monotherapy with olanzapine, 5-20 mg/day (N=217), or lithium (target blood level: 0.

Service utilization and costs of olanzapine versus divalproex treatment for acute mania: results from a randomized, 47-week clinical trial.

Objective: This study examined direct treatment costs based on medication and service use data collected in a 47-week multi-center, double-blind, randomized clinical trial of olanzapine versus divalproex for patients with bipolar disorder and and experiencing acute mania.

Research Design And Methods: Patients who completed the 3-week acute phase and entered into the 44-week maintenance phase (n = 147) of the trial were included. Service use data were collected at weeks 3, 7, 15, 23, 31, 39 and 47 of the maintenance phase.

Longitudinal effect of olanzapine on fasting serum lipids: a randomized, prospective, 4-month study.

Our objective was to compare lipid profiles of schizophrenic patients treated with conventional antipsychotics or risperidone to those of patients switched to olanzapine. Our results indicate that in patients switched to olanzapine, fasting serum lipids initially increased then returned to pretreatment levels, and endpoint lipid levels were not significantly different from those in patients remaining on conventional antipsychotics or risperidone.

Recovery and functional outcomes following olanzapine treatment for bipolar I mania.

Background: Typical experimental categorizations of treatment responses in bipolar disorder (BPD) patients may have limited relationship to clinical recovery or functional status, and there is inadequate research on such clinically important outcomes.

Methods: We analyzed data from a study of open continuation of olanzapine treatment following a 3-week placebo-controlled trial involving initially hospitalized adult subjects with DSM-IV BP-I mania to estimate rates and times to symptomatic remission (low scores on standardized symptomatic assessments) and clinical recovery (remission sustained>or=8 weeks), associated clinical factors, and functional outcomes.

Results: During treatment with olanzapine for 27.

Efficacy of olanzapine combined with valproate or lithium in the treatment of dysphoric mania.

Background: Few controlled studies examine the treatment of depressive features in mania.

Aims: To evaluate the efficacy of olanzapine, in combination with lithium or valproate, for treating depressive symptoms associated with mania.

Method: Secondary analysis of a 6-week, double-blind, randomised study of olanzapine (5-20 mg/day) or placebo combined with ongoing valproate or lithium open treatment for 344 patients in mixed or manic episodes.

Naltrexone does not prevent acquisition or expression of flavor preferences conditioned by fructose in rats.

The effects of the general opioid antagonist, naltrexone, on the acquisition and expression of flavor preferences conditioned by the sweet taste of fructose were examined. Food-restricted rats were trained over eight daily alternating one-bottle sessions (2 h) to drink an 8% fructose solution containing one novel flavor (CS+/F) and a less preferred 0.2% saccharin solution containing a different flavor (CS-/S).