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2.
Schizophr Bull ; 44(1): 75-83, 2018 01 13.
Article in English | MEDLINE | ID: mdl-28338954

ABSTRACT

INTRODUCTION: Schizophrenia, bipolar disorder, and major depressive disorder (MDD) have all been associated with immune system dysfunction, including aberrant cerebrospinal fluid (CSF) levels of cytokines and tryptophan catabolites; however, the pattern of alterations has not been compared across disorders. We performed a meta-analysis of CSF cytokine and tryptophan catabolites in patients with these major psychiatric disorders. METHODS: Articles were identified by searching Pub Med, PsycInfo, and Web of Science, and the reference lists of these studies. RESULTS: Twenty-eight studies met the inclusion criteria (16 schizophrenia, 4 bipolar disorder, and 9 MDD). CSF levels of IL-1ß and kynurenic acid were significantly increased in patients with schizophrenia and bipolar disorder compared to healthy controls (P < .001). CSF levels of IL-6 and IL-8 were significantly increased in patients with schizophrenia and MDD compared to healthy controls (P ≤ .013). DISCUSSION: There is preliminary evidence for similarities in the pattern of CSF cytokine and tryptophan catabolite alterations across major psychiatric disorders, although findings must be interpreted with caution in light of small numbers of studies/subjects. Many CSF alterations are also concordant with those in the peripheral blood, particularly for schizophrenia. Findings have important implications for our understanding of the pathophysiology and treatment of major psychiatric disorders.


Subject(s)
Bipolar Disorder/cerebrospinal fluid , Cytokines/cerebrospinal fluid , Depressive Disorder, Major/cerebrospinal fluid , Inflammation/cerebrospinal fluid , Schizophrenia/cerebrospinal fluid , Tryptophan/cerebrospinal fluid , Humans
3.
Ann Clin Psychiatry ; 29(1): 4-10, 2017 02.
Article in English | MEDLINE | ID: mdl-27901521

ABSTRACT

BACKGROUND: Smoking is highly prevalent in patients with schizophrenia. Electronic cigarettes (e-cigarettes) are becoming increasingly popular among smokers. Surveys indicate overall favorable attitudes toward the use of e-cigarettes to reduce or quit smoking, relieve withdrawal symptoms, and with respect to perceived health risks; however, less is known about their use in patients with schizophrenia. In the present study, we investigated the prevalence of and attitudes toward e-cigarettes in patients with schizophrenia. METHODS: Sixty inpatients and outpatients age 18 to 70 with schizophrenia completed a brief survey on e-cigarette use. RESULTS: Thirty-seven percent of participants reported having tried e-cigarettes, 24% of never-users were considering use, and 7% were current users. Thirty-four percent of surveyed patients believed that the health effects of e-cigarettes were less harmful than regular cigarettes. Health benefits (39%), cutting down (37%), and quitting smoking (37%) were the most frequently cited potential advantages, whereas cost (33%) was the most common potential disadvantage of e-cigarettes. Participants who were ever-users reported that regular cigarettes were significantly more helpful with reducing symptoms such as depression/anxiety, impaired concentration, and paranoia, than e-cigarettes (P < .05 for each). CONCLUSIONS: These preliminary findings should be investigated in larger samples, but suggest that e-cigarettes have, at best, modest relevance to smoking cessation in patients with schizophrenia.


Subject(s)
Electronic Nicotine Delivery Systems/statistics & numerical data , Health Knowledge, Attitudes, Practice , Schizophrenia , Female , Humans , Male , Middle Aged , Prevalence , Smoking/epidemiology , Smoking/psychology , Smoking Cessation/methods , Surveys and Questionnaires
5.
Psychoneuroendocrinology ; 63: 144-54, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26444588

ABSTRACT

OBJECTIVE: Leptin may play a role in the pathophysiology of schizophrenia and it remains unclear if levels are raised compared to controls. Therefore, we performed a systematic review and meta-analysis comparing leptin levels among people with schizophrenia and controls. METHOD: Two authors independently searched major electronic databases from inception until June 2015 for studies measuring blood leptin levels among people with schizophrenia and controls. Random effects meta-analysis calculating hedges g and 95% confidence intervals (CI) and meta-regression analyses were conducted. RESULTS: Twenty-seven articles representing 1674 individuals with schizophrenia (34.6 ± 6.8 years, 55% male (0-100%), BMI 25.2 ± 3.1) and 2033 controls (33.9 ± 7.0 years, 51% male (0-100%), BMI=24.1 ± 2.1) were included. Across all studies, leptin levels may be marginally higher in schizophrenia (g=0.164, 95% CI -0.014-0.341, p=0.07, Q=217, p<0.01), particularly when one outlier was removed (g=0.196, 95% CI 0.210-0.370, p=0.02) and when we included the smallest effect size from studies with multiple comparisons (g=0.318, 95% CI 0.125-0.510, p=0.001). Leptin levels were higher in multi-episode schizophrenia (g=0.245, 95% CI 0.058-0.433, p=0.01) and females (g=0.557 95% CI 0.16-0.954, p=0.006). Subgroup analyses revealed leptin levels may be higher in participants taking second-generation antipsychotics compared to controls. Multivariate meta-regression demonstrated a lower percentage of males (ß=-0.0064, 95% CI -0.0129 to -0.0002, p=0.05), but not BMI, moderated the results. CONCLUSION: Our results suggest that schizophrenia is associated with increased blood leptin levels compared to controls, which may not be entirely attributable to antipsychotic medication or BMI. Other illness related and lifestyle choices may play a pivotal role.


Subject(s)
Leptin/blood , Schizophrenia/blood , Antipsychotic Agents/therapeutic use , Case-Control Studies , Female , Humans , Male , Schizophrenia/drug therapy , Sex Factors , Time Factors
6.
Biochemistry ; 51(46): 9354-63, 2012 Nov 20.
Article in English | MEDLINE | ID: mdl-23088292

ABSTRACT

Osmolytes are common constituents of bacteria that may be produced or accumulate at high concentrations, up to 1 M, when cells are subjected to stresses like ionic strength and temperature. However, the effects of osmolytes on the allosteric properties of bacterial enzymes have rarely been examined. We have studied the effects of osmolytes and hydrostatic pressure on the allosteric equilibria of Salmonella typhimurium tryptophan (Trp) synthase. Trp synthase is a well-studied multienzyme complex with activity tightly regulated by allosteric interactions between the α- and ß-subunits. Trp synthase activity is affected by a wide range of physical parameters, including monovalent cations, pH, ligands, solvents, and hydrostatic pressure. Osmolytes, including betaine, taurine, sucrose, and polyethylene glycol, activate Trp synthase 2-3-fold in the absence of monovalent cations, indicating that osmolytes can stabilize the active closed conformation. However, in the presence of monovalent cations, osmolytes have only minor effects on activity and allosteric equilibria, but 1 M betaine stabilizes the Trp synthase-Ser-indoline complex against apparent pressure-induced subunit dissociation. Na(+) and K(+) are more effective at shifting the α-aminoacrylate-indoline quinonoid equilibrium toward the quinonoid side, with a K(Q) of 8-10, than NH(4)(+)(K(Q) ~ 2). Furthermore, pressure-jump experiments show that the mechanism of indoline reaction to form a quinonoid complex may be different for the NH(4)(+) enzyme than the Na(+) and K(+) forms. These results show that osmolytes have subtle but significant effects on the allosteric properties of Trp synthase, and these effects may be important in vivo.


Subject(s)
Salmonella typhimurium/enzymology , Tryptophan Synthase/metabolism , Allosteric Regulation , Hydrogen-Ion Concentration , Pressure , Spectrometry, Fluorescence
7.
Rapid Commun Mass Spectrom ; 23(7): 1029-34, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19253910

ABSTRACT

A simple and specific method using reversed-phase liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) was investigated, which allowed the determination of residues of glyphosate and its metabolite, aminomethylphosphonic acid (AMPA), in soybean samples. An aqueous extraction with liquid-liquid partition followed by protein precipitation was performed before the LC/MS/MS determination. The quantitation of glyphosate and AMPA was performed in positive and negative ESI mode, respectively, using the multiple reaction monitoring (MRM) mode with three transitions for each analyte to enhance the specificity of the method and avoid false positives. The methodology reported in this work is capable of detecting residues of glyphosate and AMPA in soybean samples with limits of quantification of 0.30 and 0.34 mg kg(-1), respectively. This alternative method has throughput advantages such as simpler sample preparation and faster chromatographic analysis.


Subject(s)
Food Contamination/analysis , Glycine max/chemistry , Glycine/analogs & derivatives , Herbicides/analysis , Organophosphonates/analysis , Spectrometry, Mass, Electrospray Ionization/methods , Chromatography, High Pressure Liquid , Glycine/analysis , Isoxazoles , Reproducibility of Results , Tandem Mass Spectrometry , Tetrazoles , Glyphosate
8.
Forensic Sci Int ; 173(2-3): 130-6, 2007 Dec 20.
Article in English | MEDLINE | ID: mdl-17376619

ABSTRACT

The consumption of synthetic drugs, generally known as designer drugs, has increased drastically in all parts of the world. Typical constituents of designer synthetic drugs are chemical substances derived from amphetamine but significant differences in effects caused and duration may result. In May, 2005, the civil state police of Sao Paulo seized thirty-one gelatinous capsules containing a very small quantity of a white powder inside (approximately 1.5 mg per capsule). This paper describes the analytical assays that were used to identify the seized material. Preliminary assays using colorimetric tests and high performance thin-layer chromatography indicated that the capsules content could be an amphetamine derivative. In the capillary zone electrophoresis assay, it was possible to observe that the analyzed material had basic characteristics. Mass spectrometry analysis revealed that the compound had the same molecular mass as 2,5-dimethoxy-4-bromoamphetamine (DOB) and its identity was confirmed through collision-induced dissociation (CID) experiments. Finally, the comparison of infrared sample spectrum with a spectra library provided further evidence of the DOB presence in the seized material. Although a reference standard material was not available, the information gathered from the different assays allowed the conclusion that the substance was, in fact, DOB, a substance with a powerful hallucinogenic action of proscribed use in the country and which was seized and identified for the first time in Brazil.

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