bluuebunny/crossref_metadata_2025_split huggingface dataset:
A QSAR analysis to explain the analgesic properties of Aconitum alkaloids
Authors: Bello‐Ramírez Angélica M. , Buendía‐Orozco Jacob , Nava‐Ocampo Alejandro A. 
Published: September 2003

Abstract Aconitum roots are traditionally prescribed for the management of different types of painful affections in Asiatic countries. A quantitative structure‐activity relationship (QSAR) analysis was performed to study the effect of chemical substitutes in the analgesic potency of alkaloids available in Chinese Aconitum roots. Using the CAChe program package for biomolecules, molecular modelling was performed in 12 alkaloids previously tested in a model of acetic acid‐induced writhing in rats. The ED50 (μmol/kg) was used as the activity parameter. Structural parameters were compared between alkaloids with an aroyl/aroyloxy group at R14 and alkaloids with the aroyloxy group at R4. Single linear regression analyses were performed in order to find the parameters explaining activity. Alkaloids with an aroyl/aroyloxy group at R14 exhibited the highest potency (significantly less ED50). The stability parameters were different between groups, e.g. total energy was −8.0 ± 0.4 in the potent analgesic alkaloids and −6.7 ± 0.3 in the weak analgesic alkaloids (P = 0.001). The reactivity index of C2′, C3′ and C5′ of the aromatic ring was also different between groups, e.g. the reactivity index of C5′ was 40.8 ± 0.6 in potent analgesic alkaloids and 48.1 ± 0.6 in weaker analgesic alkaloids (P < 0.001). Several structural parameters explained analgesic activity of alkaloids, being the reactivity index of C5′ on the aromatic group the most important factor (r = 0.89; P < 0.001).
Cough after inhalation of corticosteroids delivered from spacer devices in children with asthma
Authors: Dubus Jean‐Christophe , Mély Laurent , Huiart Laetitia , Marguet Christophe , Roux Pascal Le ,   on behalf of the ‘Réseau de Recherche Clinique en Pneumologie Pédiatrique’
Published: September 2003

AbstractChildren using a spacer device rather than another device for delivering inhaled corticosteroids (ICS) has been identified as a risk factor for cough immediately after inhalation. The aim of this study was to point out the different factors influencing the occurrence of such lateral side‐effects. We studied this local side‐effect in 402 asthmatic children (55.6 ± 34.9 months; 65.6% boys) treated for at least 1 month with beclomethasone dipropionate (n = 331), budesonide (n = 47) or fluticasone propionate (n = 24) delivered from pressurized metered‐dose inhalers and small (75.1%) or large volume (24.8%) spacer devices mainly used with face mask (90.7%). A total of 219 patients (54.5%), treated with either high doses of ICS or ICS and long‐acting β2‐agonist, were considered as having severe asthma. Cough was reported after each inhalation of corticosteroids in 216 patients (53.7%). Among them, about 30% also complained of cough with β2‐agonists. Despite different propellants and dispersants, all corticosteroids induced cough similarly. Cough was not linked with asthma severity, but was significantly related to therapy duration and use of long‐acting β2‐agonist. Type and volume of the spacer device, use of a face mask or mouthpiece were not influencing factors. Cough after inhalation of corticosteroids delivered from spacer devices is a frequent local side‐effect in children with asthma. This side effect can greatly alter compliance. A practitioner must be sought at each visit.
Sequential methods and group sequential designs for comparative clinical trials
Authors: Sébille Véronique , Bellissant Eric 
Published: September 2003

AbstractComparative clinical trials are performed to assess whether a new treatment has superior efficacy than a placebo or a standard treatment (one‐sided formulation) or whether two active treatments have different efficacies (two‐sided formulation) in a given population. The reference approach is the single‐stage design and the statistical test is performed after inclusion and evaluation of a predetermined sample size. In practice, the single‐stage design is sometimes difficult to implement because of ethical concerns and/or economic reasons. Thus, specific early termination procedures have been developed to allow repeated statistical analyses to be performed on accumulating data and stop the trial as soon as the information is sufficient to conclude.Two main different approaches can be used. The first one is derived from strictly sequential methods and includes the sequential probability ratio test and the triangular test. The second one is derived from group sequential designs and includes Peto, Pocock, and O'Brien and Fleming methods, α and β spending functions, and one‐parameter boundaries. We review all these methods and describe the bases on which they rely as well as their statistical properties. We also compare these methods and comment on their advantages and drawbacks. We present software packages which are available for the planning, monitoring and analysis of comparative clinical trials with these methods and discuss the practical problems encountered when using them.The latest versions of all these methods can offer substantial sample size reductions when compared with the single‐stage design not only in the case of clear efficacy but also in the case of complete lack of efficacy of the new treatment. The software packages make their use quite simple. However, it has to be stressed that using these methods requires efficient logistics with real‐time data monitoring and, apart from survival studies or long‐term clinical trials with censored endpoints, is most appropriate when the endpoint is obtained quickly when compared with the recruitment rate.
Metabolic drug interactions with new psychotropic agents
Authors: Spina Edoardo , Scordo Maria Gabriella , D'Arrigo Concetta 
Published: September 2003

AbstractNew psychotropic drugs introduced in clinical practice in recent years include new antidepressants, such as selective serotonin reuptake inhibitors (SSRI) and ‘third generation’ antidepressants, and atypical antipsychotics, i.e. clozapine, risperidone, olanzapine, quetiapine, ziprasidone and amisulpride. These agents are extensively metabolized in the liver by cytochrome P450 (CYP) enzymes and are therefore susceptible to metabolically based drug interactions with other psychotropic medications or with compounds used for the treatment of concomitant somatic illnesses. New antidepressants differ in their potential for metabolic drug interactions. Fluoxetine and paroxetine are potent inhibitors of CYP2D6, fluvoxamine markedly inhibits CYP1A2 and CYP2C19, while nefazodone is a potent inhibitor of CYP3A4. These antidepressants may be involved in clinically significant interactions when coadministered with substrates of these isoforms, especially those with a narrow therapeutic index. Other new antidepressants including sertraline, citalopram, venlafaxine, mirtazapine and reboxetine are weak in vitro inhibitors of the different CYP isoforms and appear to have less propensity for important metabolic interactions. The new atypical antipsychotics do not affect significantly the activity of CYP isoenzymes and are not expected to impair the elimination of other medications. Conversely, coadministration of inhibitors or inducers of the CYP isoenzymes involved in metabolism of the various antipsychotic compounds may alter their plasma concentrations, possibly leading to clinically significant effects. The potential for metabolically based drug interactions of any new psychotropic agent may be anticipated on the basis of knowledge about the CYP enzymes responsible for its metabolism and about its effect on the activity of these enzymes. This information is essential for rational prescribing and may guide selection of an appropriate compound which is less likely to interact with already taken medication(s).
Structure and pharmacology of swelling‐sensitive chloride channels, ICl,swell
Authors: D'Anglemont De Tassigny Alexandra , Souktani Rachid , Ghaleh Bijan , Henry Patrick , Berdeaux Alain 
Published: September 2003

AbstractSince several years, the interest for chloride channels and more particularly for the enigmatic swelling‐activated chloride channel (ICl,swell) is increasing. Despite its well‐characterized electrophysiological properties, the ICl,swell structure and pharmacology are not totally elucidated. These channels are involved in a variety of cell functions, such as cardiac rhythm, cell proliferation and differentiation, cell volume regulation and cell death through apoptosis. This review will consider different aspects regarding structure, electrophysiological properties, pharmacology, modulation and functions of these swelling‐activated chloride channels.
Tumour necrosis factor‐alpha‐ vs. growth factor deprivation‐promoted cell death: distinct converging pathways
Authors: Macdonald Nancy J. , Delderfield Susan M. , Zhang Wenru , Taglialatela Giulio 
Published: September 2003

SummaryPerturbations of neuronal physiological homeostasis are likely to underscore neuronal demise/impairments that are reportedly associated with aging of the central nervous system and age‐related neurodegenerative diseases such as Alzheimer's disease (AD). A number of age‐ and/or disease‐associated neurotoxic events has been described. These include abnormally modified proteins such as beta amyloid and hyper‐phosphorylated Tau, cytokines such as tumour necrosis factor‐alpha (TNFα), high levels of free radicals conducive to oxidative stress, and impaired/decreased neuronal trophic support by neurotrophic factors. Overall, it could be argued that toxic events in the aged brain are either active, such as those due to a direct action of cytokines, or passive, such as those due to lack of growth factor support. It is therefore conceivable that cellular responses to such diverse toxic stimuli are different, suggesting that interventions should be targeted accordingly. In order to begin answering this question, we determined in PC12 cells the time course of activity, in response to TNFα (active) or growth factor withdrawal (passive), of protein kinase c‐zeta (PKCζ), nuclear factor kappa B (NFκB), caspases 3 and 8, and poly (ADP‐ribose) polymerase (PARP), key signal transduction elements associated with modulation of cell death/survival in PC12 cells. We found that the overall activity of PKCζ, NFκB and caspase 8 was significantly different depending on the apoptotic initiator. The pattern of caspase 3 and PARP activity, however, was not statistically different between serum‐free‐ and TNFα‐induced cell death conditions. This suggests that two distinct cell responses are elicited that converge at caspase 3, which then induces downstream events involved in the execution of a common apoptotic programme. These results contribute to the aim of differentially targeting neuronal death in the aged brain (characterized by neurotrophic factor impairments) or in the diseased brain (e.g. AD, characterized by elevated levels of pro‐inflammatory cytokines).
Delayed behavioural aging and altered mortality in Drosophilaβ integrin mutants
Authors: Goddeeris M. M. , Cook‐Wiens E. , Horton W. J. , Wolf H. , Stoltzfus J. R. , Borrusch M. , Grotewiel M. S. 
Published: September 2003

SummaryThe genetic basis for aging is being intensely investigated in a variety of model systems. Much of the focus in Drosophila has been on the molecular–genetic determinants of lifespan, whereas the molecular–genetic basis for age‐related functional declines has been less vigorously explored. We evaluated behavioural aging and lifespan in flies harbouring loss‐of‐function mutations in myospheroid, the gene that encodes βPS, a β integrin. Integrins are adhesion molecules that regulate a number of cellular processes and developmental events. Their role in aging, however, has received limited attention. We report here that age‐related declines in locomotor activity are ameliorated and that mean lifespan is increased in myospheroid mutants. The delayed functional senescence and altered mortality in myospheroid flies are independent of changes in body size, reproduction or stress resistance. Our data indicate that functional senescence and age‐dependent mortality are influenced by β integrins in Drosophila.
Age‐related changes in the metabolism and body composition of three dog breeds and their relationship to life expectancy
Authors: Speakman J. R. , Van Acker A. , Harper E. J. 
Published: September 2003

SummaryWe measured body composition and resting metabolic rates (RMR) of three dog breeds (Papillons, mean body mass 3.0 kg (n = 35), Labrador retrievers, mean body mass 29.8 kg (n = 35) and Great Danes, mean body mass 62.8 kg (n = 35)) that varied between 0.6 and 14.3 years of age. In Papillons, lean body mass (LBM) increased with age but fat mass (FBM) was constant; in Labradors, both LBM and FBM were constant with age, and in Great Danes, FBM increased with age but LBM was constant. FBM averaged 14.8% and 15.7% of body mass in Papillons and Labradors, respectively. Great Danes were leaner and averaged only 10.5% FBM. Pooling the data for all individuals, the RMR was significantly and positively associated with LBM and FBM and negatively associated with age. Once these factors had been taken into account there was still a significant breed effect on RMR, which was significantly lower in Labradors than in the other two breeds. Using the predictive multiple regression equation for RMR and the temporal trends in body composition, we modelled the expenditure of energy (at rest) over the first 8 years of life, and over the entire lifespan for each breed. Over the first 8 years of life the average expenditure of energy per kg LBM were 0.985, 0.675 and 0.662 GJ for Papillons, Labradors and Great Danes, respectively. This energy expenditure was almost 60% greater for the smallest compared with the largest breed. On average, however, the life expectancy for the smallest breed was a further 6 years (i.e. 14 years in total), whereas for the largest breed it was only another 6 months (i.e. 8.5 years in total). Total lifetime expenditure of energy at rest per kg LBM averaged 1.584, 0.918 and 0.691 GJ for Papillons, Labradors and Great Danes, respectively. In Labradors, total daily energy expenditure, measured by the doubly labelled water method in eight animals, was only 16% greater than the observed RMR. High energy expenditure in dogs appears positively linked to increased life expectancy, contrary to the finding across mammal species and within exotherms, yet resembling observations in other intraspecific studies. These contrasting correlations suggest that metabolism is affecting life expectancy in different ways at these different levels of enquiry.
Mitochondrial oxidative stress causes chromosomal instability of mouse embryonic fibroblasts
Authors: Samper E. , Nicholls D. G. , Melov S. 
Published: September 2003

SummaryReactive oxygen species are an inevitable by‐product of mitochondrial respiration. It has been estimated that between 0.4 and 4% of molecular oxygen is converted to the radical superoxide () and this level is significantly influenced by the functional status of the mitochondria. It is well established that exogenous oxidative stress and high doses of mitochondrial poisons such as paraquat and carbonyl cyanide 4 (trifluoromethoxy) phenylhydrazone (FCCP) can lead to genomic instability. In this report we show for the first time that endogenous mitochondrial oxidative stress in standard cell culture conditions results in nuclear genomic instability in primary mouse embryonic fibroblasts (MEFs). We show that lack of mitochondrial superoxide dismutase in MEFs leads to a severe increase of double strand breaks, end‐to‐end fusions, chromosomal translocations, and loss of cell viability and proliferative capacity. Our results predict that endogenous mitochondrial oxidative stress can induce genomic instability, and therefore may have a profound effect in cancer and aging.
Systemische Therapie des kutanen Lupus erythematodes
Authors: Wenzel Joerg , Bieber Thomas , Uerlich Manfred , Tüting Thomas 
Published: September 2003

ZusammenfassungDie Behandlung des kutanen Lupus erythematodes (CLE) stellt oft eine therapeutische Herausforderung dar, vor allem bei Patienten, die auf eine rein topische Therapie nicht ansprechen oder zusätzliche systemische Manifestationen zeigen. Hier muß vielfach auf eine systemische Therapie zurückgegriffen werden. Zwar werden einige Substanzen erfolgreich in der systemischen Therapie des CLE eingesetzt, diese sind jedoch häufig nicht für diese Indikation zugelassen.Wir geben im folgenden eine Übersicht über die eingesetzten Substanzen und stellen den Wirkmechanismus sowie mögliche Indikationen, Zulassung und wichtige Punkte für das praktische Vorgehen dar.Berücksichtigt werden die Einsatzmöglichkeiten von Kortikosteroiden, Antimalariamedikamenten, Dapson, Azathioprin, Cyclophosphamid, Methotrexat, Retinoiden, Ciclosporin A, Mycophenolat Mofetil, Sulfasalazin, Thalidomid, Clofazimin, Tacrolimus, Immunglobulinen, monoklonalen Antikörper, Plasmapherese, Etanercept, Infliximab, Leflunomid, Gold und Interferon‐α.
Die Behandlung der Psoriasis capillitii mit Dithranol
Authors: Haas Norbert , Wulff‐Woesten Andrea , Sterry Wolfram , Meffert Hans 
Published: September 2003

ZusammenfassungDithranol kann in den gebräuchlichen Fettgrundlagen am behaarten Kopf nicht angewendet werden und ist in abwaschbaren Zubereitungen zumindest in Deutschland wenig im Gebrauch. Mögliche Gründe dafür könnten sein, daß die Anwendung zu wenig bekannt ist, die Wirkung unterschätzt und Nebenwirkungen überschätzt werden. Wir haben deshalb die Fachliteratur zunächst nach Studien, dann nach Rezepturvorschlägen und Anwendungsempfehlungen und schließlich nach Berichten über Nebenwirkungen durchgesehen. Wir listen auf, welche dithranolhaltigen Fertigpräparate zur Kopfbehandlung in den europäischen Nachbarländern verfügbar sind, dazu die Empfehlungen für den Gebrauch und Warnhinweise für Nebenwirkungen.Weil das Dithranolmolekül sowohl hydrophile als auch lipophile Anteile aufweist, kann es auch leicht in Seifen inkorporiert werden. Die Stabilität solcher Zubereitungen ist zwar limitiert, in der Praxis ist die Wirksamkeit aber belegt, denn Dithranol in einem Detergens ist in der Hautklinik der Charité seit 20 Jahren in Gebrauch. Das spezielle, hier verwendete Vehikel, Biowaschöl, ist eine ölige flüssige Seife, die zur Reinigung stark verschmutzter Hände in der Industrie konzipiert wurde. Es ist am behaarten Kopf ebenso leicht aufzutragen wie ohne Seife auswaschbar. Wir berichten hier von der 1979 publizierten, ursprünglichen Studie von Meffert et al. mit Dithranol‐Biowaschöl, von den seither gemachten Erfahrungen und einer neuen, vergleichenden Studie, insbesondere über aufgetretene Nebenwirkungen, praktische Hinweise, Patientenkomfort und ‐urteil, die heute wichtige Kriterien darstellen.
Wertigkeit des externen Hautexpanders (ETE®) beim sekundären Verschluß von Hautdefekten
Authors: Zutt Markus , Beckmann Iris , Kretschmer Lutz 
Published: September 2003

Zusammenfassung Hintergrund: Beim Verschluß großer Hautdefekte, bei denen erhebliche Spannung auf den Wundrändern lasten kann, bedient man sich plastischer Methoden bis hin zum Einsatz von subkutanen Ballonexpandern. Wir machen mit dieser Arbeit auf die sehr einfache Methode der Sekundärnaht aufmerksam. Patienten und Methodik: Es wird ein verbessertes System zur sekundären Hautnaht, ein sog. External Tissue Extender (ETE™) vorgestellt. Dieser Hautexpander besteht im wesentlichen aus Silikonbändern und Stoppern, die eine gute Druckverteilung gewährleisten. Es werden mögliche Anwendungen in der operativen Dermatologie und unsere Erfahrungen beschrieben. Ergebnisse: Die Implantation und die Handhabung des Expanders sind ausgesprochen einfach und wenig zeitaufwendig. Die funktionellen Ergebnisse sind gut, die kosmetischen Ergebnisse zufriedenstellend. Invasivere chirurgische Maßnahmen können durch die Verwendung dieses Verfahrens vermieden werden. Der auffälligste Nachteil der Methode ist die mögliche Entwicklung von Drucknekrosen unter den Stoppern. Schlußfolgerung: Nach unseren Erfahrungen ist der Gebrauch eines externen Expanders bei bestimmten dermatochirurgischen Indikationen eine sinnvolle Alternative zu aufwendigeren Verfahren des Hautverschlusses.
Behandlung von Pruritus als Symptom von Hauterkrankungen mit dem Serotonin‐Rezeptorantagonisten Ondansetron
Authors: Zenker Sabine , Schuh Theda , Degitz Klaus 
Published: September 2003

Zusammenfassung Hintergrund: Pruritus ist ein subjektiv häufig sehr belastendes Symptom und stellt nicht selten eine therapeutische Herausforderung dar. Wir berichten über unsere Erfahrungen mit dem Serotonin‐Rezeptorantagonisten Ondansetron bei der Behandlung von Pruritus bei verschiedenen Hauterkrankungen. Patienten und Methodik: Es wurde der Einfluß von Ondansetron (8 – 12 mg p. o. täglich) auf den Juckreiz bei zwölf Patienten mit unterschiedlichen Hauterkrankungen untersucht. Die subjektive Juckreizintensität wurde täglich mit Hilfe einer visuellen Analogskala im Zeitraum von einer Woche vor, während und einer Woche nach der Behandlung bewertet. Ergebnisse: Unter Ondansetron war eine Besserung der Pruritussymptomatik bei Prurigo simplex subacuta (vier Patienten), Exsikkationsekzematid (zwei Patienten), Parapsoriasis en plaques und Pruritus sine materia (jeweils ein Patient) festzustellen. Einer von zwei Patienten mit atopischem Ekzem erfuhr eine Besserung seiner Juckreizsymptomatik, keine Besserung zeigt sich bei Patienten mit Urticaria factitia und Notalgia paraesthetica (jeweils ein Patient). Schlußfolgerung: Bei einigen dermatologischen Erkrankungen kann der begleitende Juckreiz durch Ondansetron günstig beeinflußt werden.
A review of Clinical Terms Version 3 (Read Codes) for speech and language record keeping
Authors: M. Cowie J. , Wanger K. M. , Cartwright A. , Bailey H. , Millar J. A. , Price S. , Henry M. 
Published: September 2003

AbstractThere may be bugs, there may be viruses, but computers are here to stay. Access to computers may vary greatly from ‘seen one once’ to daily usage. However, with an increasing dependence on electronic records, even the most remote therapist will ultimately be faced with computerization. To make this process as painless as possible some commonality in approach is logical. A common vocabulary, for instance, would ensure that dysphasia in Cape Town is the same as dysphasia in Dundee. This is great in theory but is Clinical Terms Version 3 (Read Codes) (CTV3) sufficient to encode records in clinical practice? It is to this end that the Speech and Language Therapy Department at Burton Hospital took part in a multidisciplinary project with the NHS Centre for Coding and Classification (NHS CCC). (NHS CCC became the NHS Information Authority, Coding and Classification on 1 April 1999.) Their CTV3 offers a standardized clinical terminology. An audit of patient case‐notes found that 78% of the terms used by therapists were available in CTV3. Although there are many issues raised concerning electronic patient records, CTV3 presented as a potential vocabulary for recording patient information in this acute setting.