A review of pharmacokinetic parameters of metabolites and prodrugs

In drug discovery and development, the kinetic study of active metabolites plays an important role, helping to define the time course of the drug in the body and its activity or toxicity. After a pharmacokinetics assessment of a drug and its metabolite or a prodrug and its parent-drug, several parameters can be calculated. In some cases, achieving the objective of the study does not require all possible parameters to be calculated. When parameters are calculated, it is essential that their denotations are widely accepted and used. However, some parameters undergo a certain variability of denotation, which may confuse some readers. Thus, this review summarizes the current published data for experimental pharmacokinetic parameters of metabolites and the calculations involved in simple metabolite pharmacokinetic studies. It also evaluates the most common pharmacokinetic parameters in the literature and suggests metabolite parameters that could be determined to help advance metabolite kinetic models.

Relation between bruxism and dental implants

OBJECTIVE: The aim of this study was to gather information and discuss the predictability of implant-supported prostheses in patients with bruxism by performing a literature review. METHODS: In order to select the studies included in this review, a detailed search was performed in PubMed and Medline databases, using the following key words: bruxism, dental implants, implant supported prosthesis, and dental restoration failure. Items that were included are: case reports, randomized controlled trials, in vitro studies, literature and systematic reviews, with or without meta-analysis, of the last 20 years that addressed the theme. Articles without abstracts, animal studies, articles in languages other than English and articles from journals unrelated to the dental field were excluded. RESULTS: after analysis according to inclusion and exclusion criteria, 28 articles were selected from a total of 54. It is known from the array of scientific articles which have assessed, either through retrospective, prospective or experimental studies, that the biomechanical and biological impact of bruxism on implant-supported prostheses is small, and that the literature has contributed little to exemplify the prosthetic limits of safety for the specialist from a clinical point of view. CONCLUSION: Although there is still no general consensus on this matter, most of the literature review articles do provide clinical guidelines that contribute to implant supported prostheses longevity and stability in patients with bruxism.

A novel and rapid microbiological assay for ciprofloxacin hydrochloride

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Green training supporting eco-innovation in three Brazilian companies: practices and levels of integration

Purpose – The purpose of this paper is to show results from the relationship between green/environmental training and the development of three projects of low-carbon eco-innovations in top Brazilian companies. Design/methodology/approach – This study includes three organizational projects for low-carbon eco-innovations in products (A, B and C) with the objective of reducing their impact on GHG emissions, the so-called low-carbon products. Data were collected from several sources of evidence, including in-depth interviews, document analyses and direct observations. Findings – The authors verified that the environmental training interface for mitigating climate change is relevant for the systematic development of low-carbon products in most of the cases studied. Originality/value – Low-carbon eco-innovations are a trend in the corporate world; however, there is not enough literature and practical evidence on this subject. Thus, this paper adds new evidence to the literature.

Hamlet's Ophelia: The Changing Perceptions of Suicide, Death, and Madness in the Elizabethan and Victorian Periods

William Shakespeare's Hamlet, Prince of Denmark has been the source of question, debate, and research since its theatrical debut. In the midst of readings performances and one particular question has remained open and unresolved: was Ophelia's death an accident or a suicide? Some see Ophelia's death as an accident; others see it as a suicide resulting from the accumulation of a series of unfortunate events: her rejection by her boyfriend, her father’s murder, and her possible pregnancy. This paper will explore that age-old question from the perspectives of two historically different audiences: those of sixteenth-century and nineteenth-century England. I will argue that, despite the 300-year expanse between these two audiences, both emerged with the same conclusion: Ophelia's death was accidental. However, cultural and scientific changes affected the reasons why each came to that conclusion.

Review of Global Warming in the 21st Century. Volume 1: Our Evolving Climate Crisis; Volume 2: Melting Ice and Warming Seas; Volume 3: Plants and Animals in Peril by Bruce E. Johansen

There is compelling evidence that Planet Earth is on the path to an era of global warming that has serious implications for the well-being of both people and nature. This three-volume synthesis of literature will be a marvelous place for both the public and new scholars interested in global warming to begin their pursuit of the subject. The author captures the best of the scientific literature and press materials appearing in recent years. The utility of these volumes as a resource for gaining a broad background or pursuing a particular aspect of global warming is enhanced by Johansen's talent for explaining with clarity a vast and rapidly growing subject.

Women in Wisdom Tradition: Review of Carol Fontaine, Smooth Words: Women, Proverbs and Performance in Biblical Wisdom

Smooth Words is a well-researched and entertaining, if somewhat uneven, book on women in the Wisdom tradition in ancient Israel. Fontaine, a faculty member at a small Protestant seminary in Newton, MA, writes with her students constantly in mind, her interactions with them informing her scholarship throughout the book. She is also in dialogue with other scholars in the fields of Wisdom literature and feminist scholarship, a dialogue that gives the book academic rigor and depth.

Synaptolaemus latofasciatus, a new combination for Leporinus latofasciatus Steindachner, 1910 and its junior synonym Synaptolaemus cingulatus Myers and Fernandez-Yepez, 1950 (Characiformes: Anostomidae)

Leporinus latofasciatus was described by Steindachner (1910) on the basis of a single specimen collected in the rio Orinoco, Venezuela. Since then, no other specimen of the species was mentioned in the literature, and the species was only listed in catalogues, eventually mentioned and treated as a ""poorly known"" species, or even omitted in checklists of fishes from Venezuela. During a visit to the fish collection at the Naturhistorisches Museum at Vienna (NMW) to examine all the type specimens of Leporinus, we were able to study the holotype of Leporinus latofasciatus and recognize that the specimen corresponds to the species described by Myers and Fernandez-Yepez (in Myers, 1950) as Synaptolaemus cingulatus. Thus, the latter is a junior synonym of Leporinus latofasciatus and, based on that, Synaptolaemus latofasciatus (Steindachner, 1910) should be the name applied for this taxon, as a new combination. Herein new data on the holotype of Synaptolaemus latofasciatus are presented and compared with previously data from other authors. In addition, illustrations of live specimens are presented as well as new distribution records for the species.

Screening, immobilization and utilization of whole cell biocatalysts to mediate the ethanolysis of babassu oil

The screening. biomass growth of lipase-producing fungus isolated from different sources and available at URM (University Recife Mycologia). as well as, the immobilization and utilization of the whole cells for the transesterification of babassu oil were investigated. Rhizopus oryzae (URM 3231, 4692), Mucor circinelloides (URM 4140, 4182) and Penicillium citrinum URM 4216 were considered to be good intracellular lipase producers whereas those from Mucor hiemalis URM 4144 and Mucor piriformis URM 4145 were weaker. Fungi biomass containing high lipase activities was immobilized on different biomass support particles (BSPs) and with the exception of Penicillium citrinum URM 4216 all the other fungi strains exhibited high lipase activity (20-50 Ug(-1)) when immobilized in situ using polyurethane foam particles. Transesterification activities of the immobilized whole cells were evaluated in the ethanolysis reaction with babassu oil and the highest performance was attained by M. circinelloides URM 4182 giving 83.22 +/- 3.68% ester yield in less than 96 h reaction. The biocatalyst operational stability was also assessed and an inactivation profile was found to follow the Arrhenius model, revealing values of 26 days and 2.6 x 10(-2)day(-1), for half-life and a deactivation coefficient, respectively. The purified product (biodiesel) exhibited viscosity (6.63 cSt) close to the value to attend specifications by the ASTM 06751 to be used as biofuel. Results are favorable compared with data already reported in the literature and demonstrated that M. circinelloides URM 4182 whole cells is a cheaper biocatalyst that can be used in the biodiesel synthesis. (C) 2012 Elsevier B.V. All rights reserved.

Positron scattering from the cyclic ethers oxirane, 1,4-dioxane, and tetrahydropyran

In this paper we report original measurements of total cross sections (TCSs) for positron scattering from the cyclic ethers oxirane (C2H4O), 1,4-dioxane (C4H8O2), and tetrahydropyran (C5H10O). The present experiments focus on the low energy range from similar to 0.2 to 50 eV, with an energy resolution smaller than 300 meV. This study concludes our systematic investigation into TCSs for a class of organic compounds that can be thought of as sub-units or moieties to the nucleotides in living matter, and which as a consequence have become topical for scientists seeking to simulate particle tracks in matter. Note that as TCSs specify the mean free path between collisions in such simulations, they have enjoyed something of a recent renaissance in interest because of that application. For oxirane, we also report original Schwinger multichannel elastic integral cross section (ICS) calculations at the static and static plus polarisation levels, and with and without Born-closure that attempts to account for the permanent dipole moment of C2H4O. Those elastic ICSs are computed for the energy range 0.5-10 eV. To the best of our knowledge, there are no other experimental results or theoretical calculations against which we can compare the present positron TCSs. However, electron TCSs for oxirane (also known as ethylene oxide) and tetrahydropyran do currently exist in the literature and a comparison to them for each species will be presented. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.3696378]

Ab initio studies of pristine and oxidized Cu3Au(100) and (111) surfaces

We review the previous literature and our recent work on first-principles studies of Cu3Au(100) and (111) surfaces, with focus on the segregation of atomic species to the surface at pristine conditions and in the presence of oxygen. In particular, the combined use of experimental and theoretical tools to achieve chemical identification at an atomic level of the surface species is emphasized and discussed.

Genetic analyses of smoking initiation, persistence, quantity, and age-at-onset of regular cigarette use in Brazilian families: the Baependi Heart Study

Background: The purpose of this study was to estimate the genetic influences on the initiation of cigarette smoking, the persistence, quantity and age-at-onset of regular cigarette use in Brazilian families. Methods: The data set consisted of 1,694 individuals enrolled in the Baependi Heart Study. The heritability and the heterogeneity in genetic and environmental variance components by gender were estimated from variance components approaches, using the SOLAR (Sequential Oligogenic Linkage Analysis Routines) computer package. The mixed-effects Cox model was used for the genetic analysis of the age-at onset of regular cigarette use. Results: The heritability estimates were high (> 50%) for smoking initiation and were intermediate, ranging from 23.4 to 31.9%, for smoking persistence and quantity. Significant evidence for heterogeneity in variance components by gender was observed for smoking initiation and age-at-onset of regular cigarette use. Genetic factors play an important role in the interindividual variation of these phenotypes in females, while in males there is a predominant environmental component, which could be explained by greater social influences in the initiation of tobacco use. Conclusions: Significant heritabilities were observed in smoking phenotypes for both males and females from the Brazilian population. These data add to the literature and are concordant with the notion of significant biological determination in smoking behavior. Samples from the Baependi Heart Study may be valuable for the mapping of genetic loci that modulate this complex biological trait.

Evidence-based guidelines for interpreting change scores for the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30

Aim: To use published literature and experts' opinion to investigate the clinical meaning and magnitude of changes in the Quality of Life (QOL) of groups of patients measured with the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). Methods: An innovative method combining systematic review of published studies, expert opinions and meta-analysis was used to estimate large, medium, and small mean changes over time for QLQ-C30 scores. Results: Nine hundred and eleven papers were identified, leading to 118 relevant papers. One thousand two hundred and thirty two mean changes in QOL over time were combined in the meta-analysis, with timescales ranging from four days to five years. Guidelines were produced for trivial, small, and medium size classes, for each subscale and for improving and declining scores separately. Estimates for improvements were smaller than respective estimates for declines. Conclusions: These guidelines can be used to aid sample size calculations and interpretation of mean changes over time from groups of patients. Observed mean changes in the QLQ-C30 scores are generally small in most clinical situations, possibly due to response shift. Careful consideration is needed when planning studies where QOL changes over time are of primary interest; the timing of follow up, sample attrition, direction of QOL changes, and subscales of primary interest are key considerations. (C) 2012 Elsevier Ltd. All rights reserved.

Rationale and knowledge for the universal implementation of sanitation in areas of social vulnerability

The adoption of principles of equality and universality stipulated in legislation for the sanitation sector requires discussions on innovation. The existing model was able to meet sanitary demands, but was unable to attend all areas causing disparities in vulnerable areas. The universal implementation of sanitation requires identification of the know-how that promotes it and analysis of the model adopted today to establish a new method. Analysis of how different viewpoints on the restructuring process is necessary for the definition of public policy, especially in health, and understanding its complexities and importance in confirming social practices and organizational designs. These are discussed to contribute to universal implementation of sanitation in urban areas by means of a review of the literature and practices in the industry. By way of conclusion, it is considered that accepting a particular concept or idea in sanitation means choosing some effective interventions in the network and on the lives of individual users, and implies a redefinition of the space in which it exercises control and management of sewerage networks, such that connected users are perceived as groups with different interests.

Using Prior Information from the Medical Literature in GWAS of Oral Cancer Identifies Novel Susceptibility Variant on Chromosome 4-the AdAPT Method

Background: Genome-wide association studies (GWAS) require large sample sizes to obtain adequate statistical power, but it may be possible to increase the power by incorporating complementary data. In this study we investigated the feasibility of automatically retrieving information from the medical literature and leveraging this information in GWAS. Methods: We developed a method that searches through PubMed abstracts for pre-assigned keywords and key concepts, and uses this information to assign prior probabilities of association for each single nucleotide polymorphism (SNP) with the phenotype of interest - the Adjusting Association Priors with Text (AdAPT) method. Association results from a GWAS can subsequently be ranked in the context of these priors using the Bayes False Discovery Probability (BFDP) framework. We initially tested AdAPT by comparing rankings of known susceptibility alleles in a previous lung cancer GWAS, and subsequently applied it in a two-phase GWAS of oral cancer. Results: Known lung cancer susceptibility SNPs were consistently ranked higher by AdAPT BFDPs than by p-values. In the oral cancer GWAS, we sought to replicate the top five SNPs as ranked by AdAPT BFDPs, of which rs991316, located in the ADH gene region of 4q23, displayed a statistically significant association with oral cancer risk in the replication phase (per-rare-allele log additive p-value [p(trend)] = 2.5 x 10(-3)). The combined OR for having one additional rare allele was 0.83 (95% CI: 0.76-0.90), and this association was independent of previously identified susceptibility SNPs that are associated with overall UADT cancer in this gene region. We also investigated if rs991316 was associated with other cancers of the upper aerodigestive tract (UADT), but no additional association signal was found. Conclusion: This study highlights the potential utility of systematically incorporating prior knowledge from the medical literature in genome-wide analyses using the AdAPT methodology. AdAPT is available online (url: http://services.gate.ac.uk/lld/gwas/service/config).