Mesoporous bioactive glasses. I. Synthesis and structural characterization

Highly ordered mesoporous bioactive glasses (MBGs) with different compositions have been synthesized by a combination of surfactant templating, sol-gel method and evaporation-induced self-assembly (EISA) processes. The texture properties and compositional homogeneity of MBGs have been characterized and compared with conventional bioactive glasses (BGs) synthesized in the absence of surfactants by evaporation method. The formation mechanism (pore - composition dependence) and compositional homogeneity in the case of MBG materials are different from those in conventional BGs. Unlike conventional sol-gel-derived BGs that shows a direct correlation between their composition and pore architecture, MBGs with different compositions may possess similar pore volume and uniformly distributed pore size when the same structure-directing agent is utilized. The framework of MBG is homogeneously distributed in composition at the nanoscale and the inorganic species generally exists in the form of amorphous phase. MBGs calcined at temperatures

The in-vitro bioactivity of mesoporous bioactive glasses

Ordered mesoporous bioactive glasses (MBGs) with different compositions were prepared by using nonionic block copolymer surfactants as structure-directing agents through an evaporation-induced self-assembly process. Their in-vitro bioactivities were studied in detail by electron microscopy, Fourier-transform infrared spectroscopy, and inductively coupled plasma (ICP) atomic emission spectroscopy. The ICP element analysis results were further calculated in terms of the total consumption of Ca and P, Delta[Ca]/Delta[P] ratios, and ionic activity product (IP) of hydroxyapatite. Through the above analysis, it is clear that MBGs show a different structure-bioactivity correlation compared to conventional sol-gel-derivcd BGs. The in vitro bioactivity of MBGs is dependent on the Si/Ca ratio in the network when the other material parameters such as the mesostructure and texture properties (pore size, pore volume) are controlled. MBG 80S15C with relatively lower calcium content exhibits the best in vitro bioactivity, in contrast to conventional sol-gel-derived BGs where usually higher calcium percentage BGs (e.g. 60S35C) show better bioactivity. Calcination temperature is another important factor that influences the in vitro bioactivity. According to our results, MBGs calcined at 973 K may possess the best in vitro bioactivity. The influences of the composition and calcination temperature upon bioactivity are explained in terms of the unique structures of MBGs. (c) 2006 Elsevier Ltd. All rights reserved.

The empirical basis of substance use disorders diagnosis: research recommendations for the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V)

Aims This paper presents the recommendations, developed from a 3-year consultation process, for a program of research to underpin the development of diagnostic concepts and criteria in the Substance Use Disorders section of the Diagnostic and Statistical Manual of Mental Disorders (DSM) and potentially the relevant section of the next revision of the International Classification of Diseases (ICD). Methods A preliminary list of research topics was developed at the DSM-V Launch Conference in 2004. This led to the presentation of articles on these topics at a specific Substance Use Disorders Conference in February 2005, at the end of which a preliminary list of research questions was developed. This was further refined through an iterative process involving conference participants over the following year. Results Research questions have been placed into four categories: (1) questions that could be addressed immediately through secondary analyses of existing data sets; (2) items likely to require position papers to propose criteria or more focused questions with a view to subsequent analyses of existing data sets; (3) issues that could be proposed for literature reviews, but with a lower probability that these might progress to a data analytic phase; and (4) suggestions or comments that might not require immediate action, but that could be considered by the DSM-V and ICD 11 revision committees as part of their deliberations. Conclusions A broadly based research agenda for the development of diagnostic concepts and criteria for substance use disorders is presented.

The development of a research agenda for substance use disorders diagnosis in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V)

Aims paper describes the background to the establishment of the Substance Use Disorders Workgroup, which was charged with developing the research agenda for the development of the next edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM). It summarizes 18 articles that were commissioned to inform that process. Methods A preliminary list of research topics, developed at the DSM-V Launch Conference in 2004, led to the identification of subjects that were subject to formal presentations and detailed discussion at the Substance Use Disorders Conference in February 2005. Results The 18 articles presented in this supplement examine: (1) categorical versus dimensional diagnoses; (2) the neurobiological basis of substance use disorders; (3) social and cultural perspectives; (4) the crosswalk between DSM-IV and the International Classification of Diseases Tenth Revision (ICD-10); (5) comorbidity of substance use disorders and mental health disorders; (6) subtypes of disorders; (7) issues in adolescence; (8) substance-specific criteria; (9) the place of non-substance addictive disorders; and (10) the available research resources. Conclusions In the final paper a broadly based research agenda for the development of diagnostic concepts and criteria for substance use disorders is presented.

Course of substance misuse and daily tobacco use in first-episode psychosis

Background: Study of the course of substance misuse and daily tobacco use in first-episode psychosis may enhance detection and treatment of these substance-related problems. Methods: This 15-month follow-up study examined the course of substance misuse and daily tobacco use in 103 individuals treated for first-episode psychosis. Results: Three-quarters (72.6%) of patients with lifetime substance misuse, or half (51.5%) of all patients, continued substance misuse (primarily cannabis) during the 15-month follow-up period. There was a significant reduction in the rate of any substance misuse (70.9% versus 53.4%) but not daily tobacco use (76.7% versus 75.7%) between baseline and 15-month follow-up. Patients who continued substance misuse showed a significant reduction in the severity and frequency of substance use between baseline and follow-up. Patients who continued substance misuse were more likely to be younger, male and single, less likely to have completed secondary school, and more likely to have had more severe cannabis use prior to entry to treatment compared to patients who ceased substance misuse. Discussion: A significant proportion of young patients treated for first-episode psychosis are at risk of mental and physical health problems associated with substance misuse and/or regular tobacco use. (c) 2005 Elsevier B.V. All rights reserved.

Evidence for conservation and selection of upstream open reading frames suggests probable encoding of bioactive peptides

Background: Approximately 40% of mammalian mRNA sequences contain AUG trinucleotides upstream of the main coding sequence, with a quarter of these AUGs demarcating open reading frames of 20 or more codons. In order to investigate whether these open reading frames may encode functional peptides, we have carried out a comparative genomic analysis of human and mouse mRNA 'untranslated regions' using sequences from the RefSeq mRNA sequence database. Results: We have identified over 200 upstream open reading frames which are strongly conserved between the human and mouse genomes. Consensus sequences associated with efficient initiation of translation are overrepresented at the AUG trinucleotides of these upstream open reading frames, while comparative analysis of their DNA and putative peptide sequences shows evidence of purifying selection. Conclusion: The occurrence of a large number of conserved upstream open reading frames, in association with features consistent with protein translation, strongly suggests evolutionary maintenance of the coding sequence and indicates probable functional expression of the peptides encoded within these upstream open reading frames.

Substance misuse in first-episode psychosis: 15-month prospective follow-up study

Background Well-designed prospective studies of substance misuse in first-episode psychosis can improve our understanding of the risks associated with comorbid substance misuse and psychosis. Aims To examine the potential effects of substance misuse on in-patient admission and remission and relapse of positive symptoms in first-episode psychosis. Method The study was a prospective 15-month follow-up investigation of 103 patients with first-episode psychosis recruited from three mental health services. Results Substance misuse was independently associated with increased risk of in-patient admission, relapse of positive symptoms and shorter time to relapse of positive symptoms after controlling for potential confounding factors, Substance misuse was not associated with remission or time to remission of positive symptoms. Heavy substance misuse was associated with increased risk of in-patient admission, relapse and shorter time to relapse. Conclusions Substance misuse is an independent risk factor for a problematic recovery from first-episode psychosis.

Substance P preferentially inhibits large conductance nicotinic ACh receptor channels in rat intracardiac ganglion neurons

The effects of substance P (SP) on nicotinic acetylcholine (ACh)-evoked currents were investigated in parasympathetic neurons dissociated from neonatal rat intracardiac ganglia using standard whole cell, perforated patch, and outside-out recording configurations of the patch-clamp technique. Focal application of SP onto the soma reversibly decreased the peak amplitude of the ACh-evoked current with half-maximal inhibition occurring at 45 mu M and complete block at 300 mu M SP. Whole cell current-voltage (I-V) relationships obtained in the absence and presence of SP indicate that the block of ACh-evoked currents by SP is voltage independent. The rate of decay of ACh-evoked currents was increased sixfold in the presence of SP (100 mu M), suggesting that SP may increase the rate of receptor desensitization. SP-induced inhibition of ACh-evoked currents was observed following cell dialysis and in the presence of either 1 mM 8-Br-cAMP, a membrane-permeant cAMP analogue, 5 mu M H-7, a protein kinase C inhibitor, or 2 mM intracellular AMP-PNP, a nonhydrolyzable ATP analogue. These data suggest that a diffusible cytosolic second messenger is unlikely to mediate SP inhibition of neuronal nicotinic ACh receptor (nAChR) channels. Activation of nAChR channels in outside-out membrane patches by either ACh (3 mu M) or cytisine (3 mu M) indicates the presence of at least three distinct conductances (20, 35, and 47 pS) in rat intracardiac neurons. In the presence of 3 mu M SP, the large conductance nAChR channels are preferentially inhibited. The open probabilities of the large conductance classes activated by either ACh or cytisine were reversibly decreased by 10- to 30-fold in the presence of SP. The single-channel conductances were unchanged, and mean apparent channel open times for the large conductance nAChR channels only were slightly decreased by SP. Given that individual parasympathetic neurons of rat intracardiac ganglia express a heterogeneous population of nAChR subunits represented by the different conductance levels, SP appears to preferentially inhibit those combinations of nAChR subunits that form the large conductance nAChR channels. Since ACh is the principal neurotransmitter of extrinsic (vagal) innervation of the mammalian heart, SP may play an important role in modulating autonomic control of the heart.