Development of a highly sensitive method based on QuEChERS and GC-MS/MS for the determination of polycyclic aromatic hydrocarbons in infant foods.

Polycyclic aromatic hydrocarbons (PAHs) are environmental contaminants that can be found in various food products, including those intended for infants. Due to their potential health risks, it is crucial to develop sensitive analytical methods for the accurate determination of PAHs in infant foods. This study describes the development and validation of a highly sensitive method for the quantification of European PAH markers, namely benzo[a]pyrene, benzo[a]anthracene, chrysene, and benzo[b]fluoranthene, using gas chromatography-tandem mass spectrometry (GC-MS/MS), in baby food samples. The first step was the optimization of the sample preparation procedure, performed using different methods based on the QuEChERS approach, also testing different extraction solvents. Several factors such as extraction efficiency, selectivity, and recovery were evaluated to choose the most effective procedure for sample preparation. Furthermore, the GC-MS/MS method was optimized, evaluating parameters such as linearity, sensitivity, accuracy, and robustness using spiked infant food samples. The method demonstrated excellent linearities with a correlation coefficient higher than 0.999 over a wide concentration range, and limits of detection and limits of quantification in the range 0.019-0.036 µg/kg and 0.06-0.11 µg/kg, respectively. Extraction recoveries were between 73.1 and 110.7%, with relative standard deviations always lower than 8%. These findings are compliant with the indications of the European Commission (Reg. 836/2011). To assess the applicability of the method to official control activities, a survey was conducted on commercially available infant food products. Four markers were determined in commercial samples belonging to different food categories for infants and young children. The outcome of this monitoring showed that PAH contamination, in all samples, was below the quantification limits. In conclusion, the developed GC-MS/MS method provides a highly sensitive and reliable approach for the determination of PAHs in baby foods. The optimized sample preparation, instrumental parameters, and validation results ensure accurate quantification of 4 PAHs even at trace levels. This method could contribute to the assessment of PAH exposure in infants and it could support regulatory efforts to ensure the safety and quality of infant food products with regular monitoring.

Development of a screening analytical method for the determination of non-dioxin-like polychlorinated biphenyls in chicken eggs by gaschromatography and electron capture detection.

A sensitive and reproducible screening analytical method is here proposed for the determination of six non dioxin-like polychlorinated biphenyls (NDL-PCBs, congener 28, 52, 101, 138, 153, 180) in chicken eggs based on accelerated solvent extraction (ASE) procedure for the fat extraction and determination, a solid phase extraction (SPE) sample clean-up process, and a gas chromatography - electron capture detection (GC-ECD) analysis. The optimized chromatographic separation, in less than 25 min, returned good responses for the six NDL-PCBs in the range of 2.5-60.0 µg L-1, with correlation coefficients always higher than 0.9995. Instrumental limits of detection were between 0.08-0.35 µg L-1, corresponding to 0.05 and 0.23 ng g-1 fat in the matrix, while method detection limits, calculated on spiked egg samples, ranged from 1.6 to 3.5 ng g-1 fat. The method has been extensively validated in terms of selectivity, sensitivity, recovery, precision, ruggedness and measurement uncertainty, following the European Directives.

Sensitive Screening Method for Determination of Pyrethroids in Chicken Eggs and Various Meat Samples by Gas Chromatography and Electron Capture Detection.

A sensitive and reproducible screening analytical method is described for the determination of six pyrethroids (phenothrin, permethrin, cyfluthrin, cypermethrin, deltamethrin, fenvalerate) in egg and meat samples by gas chromatography and electron capture detection (GC-ECD). A fast cleanup procedure, based on solid-phase extraction has been used, ensuring reduced solvent consumption and time and allowing the simultaneous preparation of multiple sample extracts. Under the optimal chromatographic conditions, an efficient separation was obtained with a total analysis time of less than 60 min, including the extraction-purification steps. Good responses for the six pyrethroids were obtained in a range of 50-500 µg L-1, with linear coefficients higher than 0.9992. Instrumental limits of detection were between 0.22 and 0.63 µg L-1, corresponding to 0.04 and 0.13 µg kg-1 in the matrix. Detection limits in chicken eggs and various meat samples, calculated on spiked samples, were in the range 0.05-0.25 µg kg-1 and 0.07-0.23 µg kg-1, respectively. The validation results confirmed that the proposed GC-ECD method can be used as a reliable screening tool for the determination of pyrethroids in official check analyses. The method was extensively validated following the European directives, demonstrating its conformity in terms of selectivity, sensitivity, recovery, precision, and measurement uncertainty.

Pharmacotherapy of binge-eating disorder: a review.

OBJECTIVES: The purpose of this article is to provide a comprehensive review of pharmacotherapy for binge eating disorder, including new therapeutic approaches such as centrally acting sympathomimetics, nootropics, lisdexamfetamine, and substance abuse treatment agents such as acamprosate, sodium oxybate, baclofen, and naltrexone. METHODS: The study was conducted by searching the MEDLINE database using the keywords "binge eating disorder," "obesity," and "pharmacological therapy."All available studies on each drug dating from 1988 to the present were considered, focusing mainly on randomized controlled trials (RCTs). Other types of studies were considered when no RCTs were found. We drafted separate tables for open-label studies (), RCT (), and retrospective studies (). Each study is detailed by the number of subjects, additional design considerations, doses, results, additional main comparators, and study limitations. RESULTS: The data emerging from this study seem to show that, at least in the short term, some specific medications within the classes of antidepressants, anticonvulsants, and antiobesity agents may prove promising in achieving the main objectives in the treatment of binge eating disorder: reducing the frequency of binge eating, reducing weight, and improving the associated psychopathology. The major limitation in interpreting these results is the short duration of the studies and the lack of adequately sized trials, or trials including patients with medical comorbidities.Good results are being obtained with new combinations of drugs and with substance abuse treatment agents. Although the precise nature of the relationship between substance use disorders and binge eating disorder remains to be clarified, the evidence suggests that treatments recognized as effective for substance use disorders may be useful as novel treatments for binge eating disorder. This field of research remains open to future studies with more precise methodological approaches and more detailed parameter assessment; a multidisciplinary approach is also essential to better understand such a complex disease.

Binge eating disorder: from clinical research to clinical practice.

This case report describes the clinical course of a young woman suffering from binge eating disorder (BED) associated with obesity. It illustrates the efficacy of different medications in the treatment of BED and related conditions and is followed by the comments and clinical observations of 2 practicing psychiatrists. The issues described in this paper have important clinical implications and are topical, given that BED is now recognized as a specific disorder in the new Diagnostic and Statistical Manual of Mental Disorders, fifth edition classification system, but neither the US Food and Drug Administration nor any other regulatory agency has yet approved a drug for treatment of this disease, despite its very prevalent and disabling nature. Growing evidence from the fields of psychopathology and neurobiology, including preclinical and clinical studies, converges to support the idea that "overeating" has much in common with other behavioral addictions, and substance abuse treatment agents may show promise for the treatment of BED.

Ziprasidone as adjunctive therapy in severe bipolar patients treated with clozapine.

Aim. To confirm the efficacy and tolerability of ziprasidone as adjunctive therapy in bipolar patients partially responding to clozapine or with persisting negative symptoms, overweight, or with metabolic syndrome. Methods. Eight patients with psychotic bipolar disorder were tested with the BPRS, the HAM-D, and the CGI at T0 and retested after 2 weeks (T1). Plasma clozapine and norclozapine levels and BMI were tested at T0 and T1. Results. Ziprasidone was well tolerated by all the patients. BPRS and HAM-D scores were reduced in all patients. BMI was reduced in patients with a BMI at T0 higher than 25. Plasma levels of clozapine and norclozapine showed an irregular course.

Asenapine for the treatment of manic and mixed episodes associated with bipolar I disorder: from clinical research to clinical practice.

INTRODUCTION: Asenapine is a sublingually administered second-generation antipsychotic with proven efficacy for the treatment of moderate to severe manic episodes associated with bipolar I disorder in adults. Its relatively favorable weight and metabolic profile, as well as the lack of appreciable activity at muscarinic cholinergic receptors and the sublingual administration are of clinical interest. AREAS COVERED: This paper comprises a review and commentary regarding the use of sublingual asenapine in the treatment of acute manic and mixed episodes of bipolar disorder. Basic principles in dosing, switching, management of side effects and co-administration with other medications are provided. EXPERT OPINION: Asenapine displays quick and reliable effects on manic symptoms, very low risk of depressive switches, efficacy on depressive symptoms during manic and mixed episodes, usually good tolerability and continued longer-term efficacy on residual and subthreshold symptoms. The fast-dissolving sublingual route of administration may favor those who have difficulties in swallowing medications. Also, the sublingual administration reduces the risk of overdose when more than the prescribed tablets are swallowed. The relatively low metabolic risk and the lack of anticholinergic side effects contribute to making this medication a useful tool for the treatment of patients with bipolar disorder.

Catatonia and neuroleptic malignant syndrome: two disorders on a same spectrum? Four case reports.

We present the history of four bipolar patients who developed neuroleptic malignant syndrome (NMS) after antipsychotic treatment, focusing on the relationship between NMS and catatonia. In all cases, the administration of antipsychotics has been suspended as soon as fever and autonomic disturbances occurred. A supportive therapy was initiated to stabilize general conditions, then every patient started electroconvulsive therapy (ECT) in combination with benzodiazepines (BDZ). The risk of complications was reduced by the quick adoption of supportive care, whereas the combination of ECT and BDZ was effective in resolving the clinical picture. These cases may provide further support to the hypothesis that catatonia and NMS are disorders pertaining to the same spectrum of illness because the onset or exacerbation of catatonic symptoms coincided with the administration of antipsychotics. Our experience confirms the efficacy and safety of ECT in combination with BDZ as treatment of NMS and residual catatonia.

[Catatonia and neuroleptic malignant syndrome: two disorders on a same spectrum? Three case reports]. / Catatonia e sindrome maligna da neurolettici: condizioni cliniche diverse di uno stesso spettro? Descrizione di tre casi.

AIM: The authors present the cases of three bipolar patients who developed Neuroleptic Malignant Syndrome (NMS) after antipsychotic treatment, both typical and atypical, focusing on relationship between NMS and catatonia. METHODS: In all three cases, administration of antipsychotics has been stopped at once, when fever and autonomic disturbances occurred. A supportive therapy (including rehydration, electrolyte restoration and blood pressure aids, together with antipyretics, antibiotics and anticoagulants) was prescribed in order to stabilize general conditions. Every patient started then Electroconvulsive Therapy (ECT) in combination with benzodiazepines. RESULTS: High risk of complications and lethal outcome, associated with NMS, were successfully reduced by the tempestive adoption of a supportive care, while combination between ECT and BDZ was effective in resolution of clinical picture. DISCUSSIONS; These cases may provide further evidences about hypothesis of catatonia and NMS as disorders on the same spectrum. In one patient, NMS occurred overlapping with a previous catatonic state, while two others exhibited catatonic features after resolution of NMS. However, catatonic symptoms arose or worsened with administration of antipsychotics, supporting hypothesis of neuroleptic-induced catatonia as a step of progressive development of NMS. Our experience also confirms efficacy and safety of ECT in combination with BDZ as treatment of NMS and residual catatonia.

Aripiprazole for the treatment of bipolar disorder: a review of current evidence.

INTRODUCTION: several medications are available for the treatment of different phases of bipolar disorder, yet many of the drugs that are currently approved carry a substantial burden of side effects or do not lead all treated patients to remission. AREAS COVERED: this paper comprises a review and commentary regarding the use of oral and intramuscular aripiprazole in the acute and maintenance phases of bipolar disorder. Basic principles in dosing, switching, management of side effects and co-administration of aripiprazole with other medications are provided. This paper presents practical strategies to translate the data from clinical research into clinical practice. EXPERT OPINION: aripiprazole has proven to be an effective medication for the acute treatment of manic and mixed episodes, as well as for the prophylactic-maintenance phase of bipolar disorder in patients recovering from a manic/mixed episode. Choosing the appropriate dosing and tapering strategy, addressing the side effects, controlling withdrawal symptoms from previous medications and using adjunctive medications when necessary are key to successful treatment with aripiprazole.

L-type calcium channels and psychiatric disorders: A brief review.

Emerging evidence from genome-wide association studies (GWAS) support the association of polymorphisms in the alpha 1C subunit of the L-type voltage-gated calcium channel gene (CACNA1C) with bipolar disorder. These studies extend a rich prior literature implicating dysfunction of L-type calcium channels (LTCCs) in the pathophysiology of neuropsychiatric disorders. Moreover, calcium channel blockers reduce Ca(2+) flux by binding to the α1 subunit of the LTCC and are used extensively for treating hypertension, preventing angina, cardiac arrhythmias and stroke. Calcium channel blockers have also been studied clinically in psychiatric conditions such as mood disorders and substance abuse/dependence, yielding conflicting results. In this review, we begin with a summary of LTCC pharmacology. For each category of disorder, this article then provides a review of animal and human data. In particular, we extensively focus on animal models of depression and clinical trials in mood disorders and substance abuse/dependence. Through examining rationale and study design of published clinical trials, we provide some of the possible reasons why we still do not have definitive evidence of efficacy of calcium-channel antagonists for mood disorders. Refinement of genetic results and target phenotypes, enrollment of adequate sample sizes in clinical trials and progress in physiologic and pharmacologic studies to synthesize tissue and isoform specific calcium channel antagonists, are all future challenges of research in this promising field. © 2010 Wiley-Liss, Inc.

Neuroleptic malignant syndrome: further lessons from a case report.

BACKGROUND: Neuroleptic malignant syndrome (NMS) represents an iatrogenic form of malignant catatonia, and simple catatonia has been shown to predispose to NMS. OBJECTIVE: The authors present the case of a bipolar patient with catatonic features who developed NMS after receiving haloperidol. METHOD: Supportive therapy, including rehydration, electrolyte restoration, and blood pressure aids were given, together with antipyretics, antibiotics, and anticoagulants. The patient was also started on bromocriptine and diazepam. RESULTS: Supportive care, diazepam, and dopamine agonists yielded only partial benefit. However, switching from diazepam to lorazepam, in combination with electroconvulsive therapy (ECT) and a long-acting dopamine agonist led to the resolution of NMS. CONCLUSION: This case sheds further light on the relationship between catatonia and NMS. As noted in the literature, ECT in combination with lorazepam proved to be safe and effective for NMS.

Augmentation of clozapine with aripiprazole in severe psychotic bipolar and schizoaffective disorders: a pilot study.

AIM: To evaluate the efficacy and safety of the augmentation of clozapine with aripiprazole in patients with treatment-resistant schizoaffective and psychotic bipolar disorders in a retrospective manner. Pharmacodynamic and pharmacokinetic interactions between the two drugs were also investigated. PATIENTS: Three men and 4 women (median age 36 and 40 years, respectively) who had mean scores at BPRS and CGI-Severity of 59.1+/-12.0 and 5.4+/-0.5, respectively, were treated with clozapine (mean dose 292.9+/-220.7 mg/day). Patients received an adjunctive treatment with aripiprazole (mean dose 6.8 +/- 3.7 mg/day). Clozapine, norclozapine and aripiprazole plasma levels were measured by means of a high performance liquid chromatograpy with UV detection. RESULTS: Total scores at BPRS decreased significantly (from 59.1+/-12.0 to 51.1+/-15.6, p=0.007) after aripirazole augmentation. In particular, the factors "thought disorder" (from 10.4+/-4.4 to 9.0+/-4.5, p=.047) and "anergia" (from 10.0+/-2.7 to 8.0+/-2.4, p=.018) significantly improved. Concomitant administration of aripiprazole and clozapine did not result in an increase in side effects over the period of treatment. Dose-normalized plasma levels of both clozapine and norclozapine and the clozapine/norclozapine metabolic ratio in all patients did not vary as well. CONCLUSION: The augmentation of clozapine with aripirazole was safe and effective in severe psychotic schizoaffective and bipolar disorders which failed to respond to atypical antipsychotics. A possible pharmacokinetic interaction between clozapine and aripiprazole does not account for the improved clinical benefit obtained after aripiprazole augmentation.

Risperidone long-acting injection as monotherapy and adjunctive therapy in the maintenance treatment of bipolar I disorder.

IMPORTANCE OF THE FIELD: It is very rare for patients with bipolar disorder to have a single episode of mania or depression over a lifetime and the vast majority of these individuals need long-term prophylactic/maintenance treatment. However, treatment nonadherence is a major issue for close to half of subjects with bipolar disorder who are prescribed medications. Risperidone long-acting injection (LAI) has proven efficacious for the maintenance phase of bipolar disorder and may mitigate the problem of nonadherence in the substantial group of patients for whom this is a significant concern. AREAS COVERED IN THIS REVIEW: This paper comprises a review and commentary regarding the use of risperidone LAI in bipolar disorder. WHAT THE READER WILL GAIN: The reader will gain an understanding regarding the risks and benefits of risperidone LAI in bipolar disorder. We review the available evidence and discuss the strengths and weaknesses of published studies, providing an opinion about the clinical usefulness of risperidone LAI as well as suggestions for future research. TAKE HOME MESSAGE: The use of risperidone LAI, through improved adherence, has the potential to ameliorate the course of bipolar disorder.

Phenotypic effects of a bipolar liability gene among individuals with major depressive disorder.

Variations in voltage-dependent calcium channel L-type, alpha 1C subunit (CACNA1C) gene have been associated with bipolar disorder in a recent meta-analysis of genome-wide association studies [Ferreira et al., 2008]. The impact of these variations on other psychiatric disorders has not been yet investigated. Caucasian non-Hispanic participants in the STAR*D study of treatment for depression for whom DNA was available (N = 1213) were genotyped at two single-nucleotide polymorphisms (SNPs) (rs10848635 and rs1006737) in the CACNA1C gene. We examined putative phenotypic indicators of bipolarity among patients with major depression and elements of longitudinal course suggestive of latent bipolarity. We also considered remission and depression severity following citalopram treatment. The rs10848635 risk allele was significantly associated with lower levels of baseline agitation (P = 0.03; beta = -0.09). The rs1006737 risk allele was significantly associated with lesser baseline depression severity (P = 0.04; beta = -0.4) and decreased likelihood of insomnia (P = 0.047; beta = -0.22). Both markers were associated with an increased risk of citalopram-emergent suicidality (rs10848635: OR = 1.29, P = 0.04; rs1006737: OR = 1.34, P = 0.02). In this exploratory analysis, treatment-emergent suicidality was associated with two risk alleles in a putative bipolar liability gene.

Stability of symptoms across major depressive episodes in bipolar disorder.

OBJECTIVE: Some studies suggest that depressive subtypes, defined by groups of symptoms, have predictive or diagnostic utility. These studies make the implicit assumption of stability of symptoms across episodes in mood disorders, which has rarely been investigated. METHODS: We examined prospective data from a cohort of 3,750 individuals with bipolar I or II disorder participating in the Systematic Treatment Enhancement Program for Bipolar Disorder study, selecting a subset of individuals who experienced two depressive episodes during up to two years of follow-up. Across-episode association of individual depressive or hypomanic/mixed symptoms was examined using the weighted kappa measure of agreement as well as logistic regression. RESULTS: A total of 583 subjects experienced two prospectively observed depressive episodes, with 149 of those subjects experiencing a third. Greatest evidence of stability was observed for neurovegetative features, suicidality, and guilt/rumination. Loss of interest and fatigue were not consistent across episodes. Structural equation modeling suggested that the dimensional structure of symptoms was not invariant across episodes. CONCLUSION: While the overall dimensional structure of depressive symptoms lacks temporal stability, individual symptoms including suicidality, mood, psychomotor, and neurovegetative symptoms are stable across major depressive episodes in bipolar disorder and should be considered in future investigations of course and pathophysiology in bipolar disorder.

Efficacy of electroconvulsive therapy in Fahr disease associated with bipolar psychotic disorder: a case report.

We report a case of a patient with Fahr disease affected by bipolar disorder type I with psychotic symptoms. The complex clinical picture, characterized by both neurological and psychiatric symptoms, proved to be partially or completely resistant to several pharmacological trials. On the contrary, a marked improvement of clinical picture occurred after a cycle of 10 sessions of electroconvulsive therapy, followed by a complete and sustained resolution of mood, cognitive, motor, and behavioral symptoms during the next 4 years.

Bipolar disorder in late life: clinical characteristics in a sample of older adults admitted for manic episode.

BACKGROUND: Although manic episodes in older adults are not rare, little published data exist on late-life manic episodes. Resistance to treatment and concomitant neurological lesions are frequent correlates of elderly mania. The aim of this study was to investigate the prevalence of hospitalizations due to mania in patients older than 64 years through a period of 5 years in an Italian public psychiatric ward. Moreover, we aimed at describing clinical presentation of elderly manic episodes. METHODS: A retrospective chart review was conducted in order to describe clinical presentation of 20 elderly patients hospitalized for manic episode; moreover, we compared age at onset, the presence of family history for mood disorders, psychosis and irritability between the elderly group and a matched group of 20 younger manic inpatients. RESULTS: Seven percent of the whole inpatient elderly people suffered from mania. Half of those patients had a mood disorder age at onset after 50 years and 5 patients were at their first manic episode. Geriatric- and adulthood mania showed similar clinical presentation but younger people had more frequently a mood disorders family history. CONCLUSION: Half of our older manic inpatients consisted of "classic" bipolar patients with an extension of clinical manifestations into later life; the other half of our sample was heterogeneous, even though it was not possible to identify clearly which patients may have had vascular lesions related to the onset of mania.

Gender differences in bipolar disorder type 1: a 48-week prospective follow-up of 72 patients treated in an Italian tertiary care center.

To explore gender differences in bipolar I disorder, we compared the longitudinal treatment outcome and baseline demographic and clinical characteristics of 27 male and 45 female adult subjects who were treated for an acute affective episode and longitudinally followed for a period of up to 48 weeks. Females were more likely to report a history of suicidal gestures and a comorbid panic disorder; males were more likely to present with a comorbid obsessive-compulsive disorder, and there was a trend for a more frequent history of alcohol or substance abuse. No significant differences were found between the genders for the time to remission from the index episode, number of recurrences, and time spent with any clinical or subclinical mood symptom during the 48 weeks of maintenance treatment. Although differences may exist between bipolar I male and female subjects, prospective course does not seem to reveal differences in a 48-week period, at least when similar treatment strategies are adopted.