49 research outputs found

    Exploring and anticipating supramolecular synthons: from fundamental science to practical applications

    Get PDF
    Doctor of PhilosophyDepartment of ChemistryChrister B. AakeröyFour different methods; molecular electrostatic potentials (MEPs), hydrogen-bond energies (HBE), hydrogen-bond propensities (HBP) and hydrogen-bond coordination (HBC) were used for mapping out the structural landscape of twelve pyrazole and twelve thiazole based molecules. In seven out of eight crystal structures obtained in pyrazoles, a combination of HBE and HBP predicted the experimentally observed synthons correctly. In all eight crystal structures obtained in thiazoles, the synthons were predicted correctly using all four methods. A series of co-crystallizations between twelve pyrazole with twenty carboxylic acids (240 experiments), and twelve thiazole with twenty carboxylic acids (240 experiments) were carried out to build an experimental library that could be used for evaluating the ability of electrostatics, energies, propensities and molecular complementarity methods to rationalize the observed intermolecular interactions. The results suggested that a combination of electrostatics and molecular complementarity are essential for identifying the predominant molecular recognition events in the pyrazole based study, and methods such as MEPs, HBE, and HBP all predicted the observed synthons in co-crystals of the thiazole-based molecules. In order to examine competition between hydrogen and halogen bonds, and to synthesize ternary co-crystals, four thiazole based molecules were co-crystallized with 15 hydrogen-bond donors and one halogen bond donor resulting in new co-crystals in 44 out of 60 experiments, and the crystal structures of two ternary co-crystals were obtained. A series of eight unactivated and activated amide functionalized molecules were synthesized to establish a supramolecular halogen-bond hierarchy. The positive electrostatic potential on the halogen atoms was enhanced through an sp-hybridized carbon and electron-withdrawing fluoro group(s) next to amide group. Tetraflourinated and iodoethynyl based molecules were identified as the most effective halogen-bond donors and were therefore least successful for co-crystal synthesis. In order to predict crystallizability of 83 drug-like molecules a molecule, logistic regression approach was employed using molecular descriptors such as molecular weight, rotatable bond, surface area, heteroatom, melting temperature, glass transition temperature, and molecular shape/volume. Four different models were developed, and the success rate was above 85% (using experimental DSC data for the crystallization classification). Finally, the solid-form landscape of urea was explored using full interaction maps (FIMs), and data from the CSD to develop optimum protocols for synthesizing co-crystals of this compound. As a result, 49 of 60 attempted reactions produced new co-crystals. Moreover, the goal of reducing solubility and lowering hygroscopicity of the parent compound was achieved, which, in turn, offers new opportunities for a slow-release fertilizer with limited hygroscopicity thereby reducing many current problems of transport, handling, and storage of urea

    Probiotics for gastrointestinal disorders: Proposed Recommendations for children of the Asia-Pacific region

    Get PDF
    Recommendations for probiotics are available in several regions. This paper proposes recommendations for probiotics in pediatric gastrointestinal diseases in the Asia-Pacific region. Epidemiology and clinical patterns of intestinal diseases in Asia-Pacific countries were discussed. Evidence-based recommendations and randomized controlled trials in the region were revised. Cultural aspects, health management issues and economic factors were also considered. Final recommendations were approved by applying the Likert scale and rated using the GRADE system. Saccharomyces boulardii CNCM I-745 (Sb) and Lactobacillus rhamnosus GG (LGG) were strongly recommended as adjunct treatment to oral rehydration therapy for gastroenteritis. Lactobacillus reuteri could also be considered. Probiotics may be considered for prevention of (with the indicated strains): antibiotic-associated diarrhea (LGG or Sb); Clostridium difficile-induced diarrhea (Sb); nosocomial diarrhea (LGG); infantile colic (L reuteri) and as adjunct treatment of Helicobacter pylori (Sb and others). Specific probiotics with a history of safe use in preterm and term infants may be considered in infants for prevention of necrotizing enterocolitis. There is insufficient evidence for recommendations in other conditions. Despite a diversity of epidemiological, socioeconomical and health system conditions, similar recommendations apply well to Asia pacific countries. These need to be validated with local randomized-controlled trials

    The Impact of E-Learning on Adherence to Guidelines for Acute Gastroenteritis: A Single-Arm Intervention Study

    Get PDF
    Objective E-learning is a candidate tool for clinical practice guidelines (CPG) implementation due to its versatility, universal access and low costs. We aimed to assess the impact of a five-module e-learning course about CPG for acute gastroenteritis (AGE) on physicians' knowledge and clinical practice. Study design This work was conceived as a pre/post single-arm intervention study. Physicians from 11 European countries registered for the online course. Personal data, pre- and post-course questionnaires and clinical data about 3 to 5 children with AGE managed by each physician before and after the course were collected. Primary outcome measures included the proportion of participants fully adherent to CPG and number of patients managed with full adherence. Results Among the 149 physicians who signed up for the e-learning course, 59 took the course and reported on their case management of 519 children <5 years of age who were referred to their practice because of AGE (281 and 264 children seen before and after the course, respectively). The course improved knowledge scores (pre-course 8.6 +/- 2.7 versus post-course 12.8 +/- 2.1, P < 0.001),average adherence (from 87.0 +/- 7.7% to 90.6 +/- 7.1%,P = 0.001) and the number of patients managed in full adherence with the guidelines (from 33.6 +/- 31.7% to 43.9 +/- 36.1%,P = 0.037). Conclusions E-learning is effective in increasing knowledge and improving clinical practice in paediatric AGE and is an effective tool for implementing clinical practice guidelines

    Irritable bowel syndrome in children: Pathogenesis, diagnosis and evidence-based treatment

    No full text

    Digestion and absorption

    No full text
    Improved understanding of gastrointestinal tract physiology has led to major progress in the treatment of gastrointestinal disorders. For example, the development of oral rehydration therapy based on understanding of sodium transport across the enterocyte has helped to save thousands of lives each year. Digestion and absorption of nutrients involves a series of complex processes, some of which may be defective from birth (primary disorders), and others may malfunction because of diseased states (secondary disorders). © 2004 Elsevier Ltd. All rights reserved

    The investigation of chronic diarrhoea

    No full text
    Chronic diarrhoea can present a major diagnostic and management problem, particularly in infants. It is an important cause of anxiety and frustration for the parents of affected children. In this article, we set out a logical approach to the investigation of chronic diarrhoea, from basic first-line investigations to more specialized tests. There is a wide range of aetiologies, from the harmless toddler diarrhoea, the most common cause of chronic diarrhoea in more developed countries, to severe protracted diarrhoea of infancy. In this latter group, several new diarrhoeal syndromes have been identified, although in a significant number of cases (up to 30%), no specific cause may be identified and the prognosis may be poor. © 2003 Elsevier Science Ltd
    corecore