Molecular docking study of conformational polymorph: building block of crystal chemistry.

Two conformational polymorphs of novel 2-[2-(3-cyano-4,6-dimethyl-2-oxo-2H-pyridin-1-yl)-ethoxy]-4,6-dimethyl nicotinonitrile have been developed. The crystal structure of both polymorphs (1a and 1b) seems to be stabilized by weak interactions. A difference was observed in the packing of both polymorphs. Polymorph 1b has a better binding affinity with the cyclooxygenase (COX-2) receptor than the standard (Nimesulide).

Features and prevalence of patients with probable adult attention deficit hyperactivity disorder who request treatment for cocaine use disorders.

To characterize those patients with probable adult attention deficit hyperactivity disorder (ADHD) who ask for treatment of cocaine use disorders; to estimate the prevalence of probable adult ADHD among these patients. This is a cross-sectional and multi-center study performed at outpatient resources of 12 addiction treatment centers in Spain. Participants were treatment-seeking primary cocaine abusers recruited consecutively at one center and through convenience sampling at the other centers. Assessments included semi-structured clinical interview focused on Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) ADHD criteria adapted to adulthood, and the Wender-Utah Rating Scale (WURS) for screening childhood history of ADHD according to patients. Probable adult ADHD was diagnosed when patients met DSM-IV criteria of ADHD in adulthood and scored WURS>32. All participants were diagnosed with current cocaine dependence (n=190) or abuse (n=15). Patients with probable adult ADHD, compared with patients having no lifetime ADHD, were more frequently male, reported higher impulsivity, and began to use nicotine, alcohol, cannabis, or cocaine earlier. Before starting the current treatment, patients with probable adult ADHD also showed higher cocaine craving for the previous day, less frequent cocaine abstinence throughout the previous week, and higher use of cocaine and tobacco during the previous month. Impulsivity and male gender were the only independent risk factors of probable adult ADHD in a logistic regression analysis. The prevalence of probable adult ADHD was 20.5% in the sub-sample of patients consecutively recruited (n=78). A diagnosis of probable adult ADHD strongly distinguishes among treatment-seeking cocaine primary abusers regarding past and current key aspects of their addictive disorder; one-fifth of these patients present with probable adult ADHD.

Assessing gender disparities in excess mortality of heroin or cocaine users compared to the general population.

BACKGROUND: Previous analyses of excess mortality in drug users compared with the general population have almost always been based on mortality ratios, reporting much higher figures in women than men. This study tests the hypothesis that being a heroin or cocaine user adds more death risk in women than men in Spain. METHODS: A retrospective cohort of 15,305 heroin users (HUs) and 11,905 cocaine users (CUs) aged 15-49 starting drug treatment in 1997-2007 was recruited in Spain and followed until December 2008 to determine vital status and cause of death. Excess mortality in men and women compared to the general population was assessed with directly age-standardized rate ratios (SRRs) and differences (SRDs). RESULTS: SRR was significantly higher in women than men for all causes (14.7 vs. 9.4), natural causes (8.7 vs. 6.2), overdose (331.6 vs. 163.9) and other external causes (46.9 vs. 11.8) among HUs; and for overdose (170.8 vs. 40.5) and other external causes (21.0 vs. 4.7) among CUs. However, the opposite happened with SRD for all causes (1294 vs. 1845 deaths/100,000 person-years), natural causes (675 vs. 1016 deaths/100,000 person-years) and overdose (331 vs. 619 deaths/100,000 person-years) among HUs, while no significant SRD gender disparities were observed among CUs. CONCLUSION: Compared with the general population, being a heroin user adds greater absolute risk in men than women, but this does not happen with cocaine users. Similar results would likely have been found in most published cohort studies if this indicator had been used; the exclusive use of relative indices of disparity as in previous meta-analysis can be extremely misleading.

Rolipram impairs NF-kappaB activity and MMP-9 expression in experimental autoimmune encephalomyelitis.

Rolipram suppresses experimental autoimmune encephalomyelitis (EAE) and diminishes cell infiltration of the central nervous system (CNS). In Lewis rats with EAE, rolipram reduced matrix metalloproteinase-9 (MMP-9) gene expression in lymph node cells (LNCs) and spinal cord, decreased basal levels of nuclear (p50/p65) NF-kappaB in LNCs from treated rats, and impaired CD3 mediated NF-kappaB translocation. Rolipram reduced the luciferase activity directed by the NF-kappaB binding site of the MMP-9 gene in lymphocytes. It also diminished NF-kappaB activity and the ability of a myelin basic protein (MBP) specific cell line to migrate across artificial basement membranes. IL-2 induced MMP-9 proteolytic activity was only slightly reduced indicating that additional factors contribute to inhibit cell migration mediated by rolipram.

Importance of weak interactions in developing 1,3-bis(4,6-dimethyl-1H-nicotinonitrile-1-yl)1,3-dioxy propane polymorphs.

The structure of 1,3-bis(4,6-dimethyl-1H-nicotinonitrile-1-yl)1,3-dioxy propane polymorphs has been characterized by X-ray diffraction, FT-IR, 1H and 13C NMR spectroscopies. The influence of intra and intermolecular weak interactions is thoroughly studied in solid state using single crystal X-ray diffraction and FT-IR. These polymorphs belong to monoclinic space group 'P2(1/n)' and 'P2(1/c)'. These polymorphs have C-H⋯n (lone pair), hydrogen bonds, C-N⋯π, C-H⋯π and π⋯π intermolecular non-covalent interactions. These polymorphs are the result of weak interactions and solvent used in crystallization. The FT-IR spectra have been recorded in the solid phase and NMR has been recorded in solvent. The optimized geometry has been calculated by B3LYP methods using different basis sets. The FT-IR and NMR spectra of 1st polymorphs has been calculated at B3LYP/6-31G (d) level. The scaled theoretical wave number showed good agreement with the experimental values. These two polymorphs as well as other stereomers are studied by DFT calculations.

Versión española del Cuestionario Disejecutivo (DEX-Sp): propiedades psicométricas en adictos y población no clínica / Spanish version of the Dysexecutive Questionnaire (DEX-Sp): psychometric properties in addicts and non-clinical sample

Objetivo: Diversos estudios han evidenciado el deterioro de las funciones ejecutivas asociado al abuso de sustancias. Este hecho sugiere la conveniencia de contar con algún instrumento de cribado que sirva para establecer una línea base sobre los déficits que presentan los sujetos que inician tratamiento. El Cuestionario Disejecutivo (DEX) es un test ampliamente utilizado para estimar disfunción ejecutiva. El principal objetivo del presente trabajo se centra en estudiar las propiedades de la versión española del Cuestionario Disejecutivo (DEX-Sp). Complementariamente se pretende estudiar su potencial utilidad como instrumento de cribado en adictos en tratamiento. Método: 131 sujetos de población no clínica y 127 adictos (con criterios DSM-IVTR para abuso o dependencia). Resultados: Se estudia la consistencia interna (¬ de Cronbach = 0,91) entre otros indicadores de fiabilidad. El análisis factorial exploratorio y confirmatorio ofrece soluciones de 4 y 5 factores. Se estudió la dimensionalidad y el modelo estructural de base, así como la validez convergente y discriminante. Se estudiaron las diferencias apreciadas entre adictos y población no clínica. Conclusiones: Los datos sugieren que la versión española del DEX es un instrumento útil para evaluar síntomas disejecutivos generales, con la suficiente fiabilidad y validez para explorar deterioro cognitivo asociado al abuso desustancias (AU)

Objective: Several studies have shown evidence of executive function impairment associated with substance abuse. This suggests the potential usefulness of a baseline assessment measure to screen for dysexecutive impairments in individuals beginning treatment. The Dysexecutive Questionnaire (DEX) is a test widely used to estimate executive dysfunction. The main objective of this work is to study the psychometric properties of the Spanish version of the Dysexecutive Questionnaire (DEX-Sp). A complementary goal is to study its potential utility for initial screening in addicted individuals seeking treatment. Method: A sample of 131 non-clinical and 127 clinical individuals meeting the DSM-IV-TR substance abuse or dependence criteria were recruited. Results: Internal consistency of the questionnaire was assessed (Cronbach’s ¬ =0.91), as well as other reliability indicators. Exploratory and confirmatory factor analysis offers four- and five-factor solutions. Also tested were the dimensionality and structural model and its convergent and discriminant validity with other instruments. Differences between clinical and non-clinical individuals and total scores were also analyzed. Conclusions: The data suggest that the Spanish version of the DEX is a useful measure for assessing general symptoms of dysexecutive syndrome, and a valid, reliable and adequate screening test for estimating cognitive impairment associated with substance abuse (AU)