Quetiapine affects neuropeptide Y and corticotropin-releasing hormone in cerebrospinal fluid from schizophrenia patients: relationship to depression and anxiety symptoms and to treatment response.

Cumulative evidence indicates that neuropeptides play a role in the pathophysiology of schizophrenia. Early data showed increased neuropeptide Y (NPY) in cerebrospinal fluid (CSF) from schizophrenia patients and data from rodents show that antipsychotic drugs modulate NPY levels in and release from selected rat brain regions. In view of these findings we investigated whether the atypical antipsychotic quetiapine, originally used as an antipsychotic but subsequently shown to be efficient also in major depressive disorder and in both poles of bipolar disorder, would affect NPY-like immunoreactivity (-LI), and corticotropin-releasing hormone (CRH)-LI levels in CSF of schizophrenia patients. NPY-LI and CRH-LI in CSF were determined in 22 patients with schizophrenia. Lumbar puncture was performed at baseline and again after 4 wk of quetiapine treatment (600 mg/d). Patients were assessed with the Positive and Negative Syndrome Scale (PANSS) at baseline and at weekly intervals. Quetiapine treatment was associated with a significant increase in NPY-LI (p<0.001) and decrease in CRH-LI (p<0.01). Stepwise multiple regression analysis revealed that ΔNPY-LI and ΔCRH-LI levels predicted 63% (p<0.001) of the variability of the ΔPANSS total score, ΔNPY-LI 42% (p<0.05) of the ΔPANSS anxiety items (G2) and ΔCRH-LI 40% (p=0.05) of the ΔPANSS depression items (G6). These results suggest that while quetiapine's effects on monoamines are probably related to its antipsychotic properties, the modulation of NPY and CRH accounts for its antidepressant and anxiolytic effects and can be markers of response.

Quetiapine and norquetiapine in plasma and cerebrospinal fluid of schizophrenic patients treated with quetiapine: correlations to clinical outcome and HVA, 5-HIAA, and MHPG in CSF.

This study investigated concentrations of quetiapine and norquetiapine in plasma and cerebrospinal fluid (CSF) in 22 schizophrenic patients after 4-week treatment with quetiapine (600 mg/d), which was preceded by a 3-week washout period. Blood and CSF samples were obtained on days 1 and 28, and CSF levels of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations were measured at baseline and after 4 weeks of quetiapine, allowing calculations of differences in HVA (ΔHVA), 5-HIAA (Δ5-HIAA), and MHPG (ΔMHPG) concentrations. Patients were assessed clinically, using the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression Scale at baseline and then at weekly intervals. Plasma levels of quetiapine and norquetiapine were 1110 ± 608 and 444 ± 226 ng/mL, and the corresponding CSF levels were 29 ± 18 and 5 ± 2 ng/mL, respectively. After the treatment, the levels of HVA, 5-HIAA, and MHPG were increased by 33%, 35%, and 33%, respectively (P < 0.001). A negative correlation was found between the decrease in PANSS positive subscale scores and CSF ΔHVA (r(rho) = -0.690, P < 0.01), and the decrease in PANSS negative subscale scores both with CSF Δ5-HIAA (r(rho) = -0.619, P = 0.02) and ΔMHPG (r(rho) = -0.484, P = 0.038). Because, unfortunately, schizophrenic patients experience relapses even with the best available treatments, monitoring of CSF drug and metabolite levels might prove to be useful in tailoring individually adjusted treatments.

Grec 2370

ANTHEMIUS Trallianus. De admirabilibus machinis

Grado de impacto en el suelo y la vegetación en áreas de uso público del Parque Nacional de Tierra del Fuego (Argentina)

En los últimos años, el uso turístico de las áreas protegidas ha aumentado considerablemente, y con él, el grado de impacto. Es por este motivo que se requieren medidas de gestión adecuadas para identificar, conocer y evaluar estos impactos potenciales y así poder actuar ofreciendo un uso recreativo de estas áreas a la vez que se asegura su conservación. El objetivo del presente trabajo fue establecer el grado de impacto que sufre la vegetaciòn y el suelo del Parque Nacional de Tierra del Fuego en las zonas de acampada y compararlas con las áreas adyacentes, como controles. Asimismo, se buscó establecer cuales son los indicadores de impacto de mayor relevancia para poder ser usados como herramientas de gestión. La evaluación se efectuó mediante el muestreo de 40 parcelas, transectas y intertransectas en donde se analizaron variables vegetacionales (cobertura arbórea, arbustiva y herbácea, porcentaje de suelo desnudo, daño en árboles y arbustos, y presencia de raíces expuestas) y del suelo (pH, materia orgánica, densidad aparente y humedad). El grado de impacto se estableció numéricamente con una fórmula matemática en donde se seleccionaron los parámetros evaluados y se corrigieron con factores de correción, dando un impacto clasificado como “compatible” en el área de Río Pipo y “moderado” en el área de Laguna Verde. También se formularon propuestas de manejo para prevenir y/o minimizar los impactos producidos en las zonas de camping.

Assessment of driving capability through the use of clinical and psychomotor tests in relation to blood cannabinoids levels following oral administration of 20 mg dronabinol or of a cannabis decoction made with 20 or 60 mg Delta9-THC.

Delta(9)-Tetrahydrocannabinol (THC) is frequently found in the blood of drivers suspected of driving under the influence of cannabis or involved in traffic crashes. The present study used a double-blind crossover design to compare the effects of medium (16.5 mg THC) and high doses (45.7 mg THC) of hemp milk decoctions or of a medium dose of dronabinol (20 mg synthetic THC, Marinol on several skills required for safe driving. Forensic interpretation of cannabinoids blood concentrations were attempted using the models proposed by Daldrup (cannabis influencing factor or CIF) and Huestis and coworkers. First, the time concentration-profiles of THC, 11-hydroxy-Delta(9)-tetrahydrocannabinol (11-OH-THC) (active metabolite of THC), and 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THCCOOH) in whole blood were determined by gas chromatography-mass spectrometry-negative ion chemical ionization. Compared to smoking studies, relatively low concentrations were measured in blood. The highest mean THC concentration (8.4 ng/mL) was achieved 1 h after ingestion of the strongest decoction. Mean maximum 11-OH-THC level (12.3 ng/mL) slightly exceeded that of THC. THCCOOH reached its highest mean concentration (66.2 ng/mL) 2.5-5.5 h after intake. Individual blood levels showed considerable intersubject variability. The willingness to drive was influenced by the importance of the requested task. Under significant cannabinoids influence, the participants refused to drive when they were asked whether they would agree to accomplish several unimportant tasks, (e.g., driving a friend to a party). Most of the participants reported a significant feeling of intoxication and did not appreciate the effects, notably those felt after drinking the strongest decoction. Road sign and tracking testing revealed obvious and statistically significant differences between placebo and treatments. A marked impairment was detected after ingestion of the strongest decoction. A CIF value, which relies on the molar ratio of main active to inactive cannabinoids, greater than 10 was found to correlate with a strong feeling of intoxication. It also matched with a significant decrease in the willingness to drive, and it matched also with a significant impairment in tracking performances. The mathematic model II proposed by Huestis et al. (1992) provided at best a rough estimate of the time of oral administration with 27% of actual values being out of range of the 95% confidence interval. The sum of THC and 11-OH-THC blood concentrations provided a better estimate of impairment than THC alone. This controlled clinical study points out the negative influence on fitness to drive after medium or high dose oral THC or dronabinol.

Vestibulo-ocular reflex characteristics in patients with unilateral Ménière's disease.

OBJECTIVE: The pathophysiologic concept of Ménière's disease assumes that endolymphatic hydrops is the cause of the symptoms via increased pressure in the endolymphatic space and/or ionic disorder due to ruptured membrane. The goal of this study was to assess whether the vestibulo-ocular reflex (VOR) properties in patients with Ménière's disease were consistent with the classical theory. MATERIAL AND METHODS: We studied 34 patients (19 women, 15 men) presenting with unilateral Ménière's disease divided into 2 groups according to the duration of the disease: 18 were in the early stage (< 12 mo), and 16 were in the late stage (> or = 12 mo). Nineteen patients were examined during an attack. Eight of them and the 15 other patients were tested during the interval between attacks. Their characteristics were compared with those of a group of 22 normal subjects. The VOR function was evaluated via standard caloric and impulse rotatory tests (velocity step). A mathematic model of vestibular function was used to characterize the VOR response to rotational stimulation. Dynamic VOR parameters (sensitivity coefficient, time constant, gain, and asymmetries between the 2 directions of rotation) were statistically compared between the 2 groups of patients during and between attacks and between the patients and controls. RESULTS: All dynamic VOR parameters showed no statistically significant difference both with normal controls and among the patients during and between attacks (p > 0.05) except for gain asymmetry (p < or = 0.008). During attacks, patients with early Ménière's disease displayed a higher gain in rotation toward the affected ear, the opposite being observed in patients with late disease. Caloric test revealed a moderate canal paresis on the affected side during the crisis and a slight asymmetry between attacks. CONCLUSION: During attacks in patients with early Ménière's disease, the VOR gain toward the affected side is higher than that toward the intact side, supporting the fact that that the sensitivity of the cupuloendolymphatic system on the affected ear is increased. This observation is in agreement with a mechanical pressure effect of hydrops on the vestibular organs.

Cytochrome P450 and ABCB1 genetics: association with quetiapine and norquetiapine plasma and cerebrospinal fluid concentrations and with clinical response in patients suffering from schizophrenia. A pilot study.

Variability in response to atypical antipsychotic drugs is due to genetic and environmental factors. Cytochrome P450 (CYP) isoforms are implicated in the metabolism of drugs, while the P-glycoprotein transporter (P-gp), encoded by the ABCB1 gene, may influence both the blood and brain drug concentrations. This study aimed to identify the possible associations of CYP and ABCB1 genetic polymorphisms with quetiapine and norquetiapine plasma and cerebrospinal fluid (CSF) concentrations and with response to treatment. Twenty-two patients with schizophrenia receiving 600 mg of quetiapine daily were genotyped for four CYP isoforms and ABCB1 polymorphisms. Quetiapine and norquetiapine peak plasma and CSF concentrations were measured after 4 weeks of treatment. Stepwise multiple regression analysis revealed that ABCB1 3435C > T (rs1045642), 2677G > T (rs2032582) and 1236C > T (rs1128503) polymorphisms predicted plasma quetiapine concentrations, explaining 41% of the variability (p = 0.001). Furthermore, the ABCB1 polymorphisms predicted 48% (p = 0.024) of the variability of the Δ PANSS total score, with the non-carriers of the 3435TT showing higher changes in the score. These results suggest that ABCB1 genetic polymorphisms may be a predictive marker of quetiapine treatment in schizophrenia.

Biblioteca digital: a experiência do Impa

Relato da experiência do Impa na informatização de sua biblioteca, utilizando o software Horizon, e na construção de um servidor de preprints (dissertações de mestrado, teses de doutorado e artigos ainda não publicados) através da participação no projeto internacional Math-Net.

A Spanish version of the short Mathematics Anxiety Rating Scale (sMARS)

The aim of this studywas to adapt and assess the psychometric properties of the Spanish version of the sMARS in terms of evidence of validity and reliability of scores. The sMARS was administered to 342 students and, in order to assess convergent and discriminant validity, several subsamples completed a series of related tests. The factorial structure of the sMARSwas analyzed by means of a confirmatory factor analysis and results showed that the three-factor structure reported in the original test fits well with the data. Thus, three dimensions were established in the test: math test, numerical task and math course anxiety. The results of this study provide sound evidence that demonstrates the good psychometric properties of the scores of the Spanish version of the sMARS: strong internal consistency, high 7-week testretest reliability and good convergent/discriminant validity were evident. Overall, this study provides an instrument that allows us to obtain valid and reliable math anxiety measurements. This instrument may be a useful tool for educators and psychologists interested in identifying individuals that may have a low level of math mastery because of their anxiety.

WISE: Women in Science and Engineering, Fall 2006

Women in Science and Engineering (WISE) Program is to expand and improve educational and professional opportunities for women in all fields of science, technology, engineering and math (STEM) by facilitating individual, institutional, and social change.

WISE: Women in Science and Engineering, Spring 2007

Women in Science and Engineering (WISE) Program is to expand and improve educational and professional opportunities for women in all fields of science, technology, engineering and math (STEM) by facilitating individual, institutional, and social change.