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1.
Ann R Coll Surg Engl ; 105(3): 278-282, 2023 Mar.
Article de Anglais | MEDLINE | ID: mdl-36260293

RÉSUMÉ

INTRODUCTION: Since the Montgomery ruling in 2015 surgeons have been tasked with identifying material risk when taking informed consent. Despite this, there has been limited uptake of technological aids to supplement the consent process although such aids are shown to improve patient knowledge and satisfaction. ConsentPLUS is a free-to-access website with bite-sized educational videos designed to clearly explain lower limb arthroplasty procedures to patients and aid their consent. METHODS: The authors performed a prospective cost-consequence analysis, outlining any costs associated with the intervention and any quantitative or qualitative impacts the intervention may have on patients. RESULTS: A total of 3,143 consecutive patients were identified who were undergoing total knee or hip replacement in 25 elective NHS orthopaedic units. The total cost of development and projected 10-year running fees for ConsentPLUS total £75,000. Health Foundation support means the service is free-to-access for centres throughout the UK. Mean exposure time per patient was 10min 29s, equivalent to £185,437 of additional contact time according to the National Tariff. Mean clinic time was reduced by 17min owing to the earlier identification of material risk. Patient knowledge on pre- and post-video quizzes increased from 7.01 to 9.08 following eLearning (paired t-test = 0.998). The process had an overall satisfaction rate of 97%. CONCLUSION: Educational eLearning videos are an accessible and digestible way to supplement the consent process. This enables earlier identification of material risk in clinics owing to improved patient knowledge, leading to increased patient satisfaction with arthroplasty consenting.


Sujet(s)
Arthroplastie prothétique de hanche , Enseignement assisté par ordinateur , Humains , Études prospectives , Consentement libre et éclairé , Membre inférieur
2.
Rev Mal Respir ; 38(7): 773-779, 2021 Sep.
Article de Français | MEDLINE | ID: mdl-34045087

RÉSUMÉ

INTRODUCTION: Secondary spontaneous pneumothoraces account for 35% of all pneumothoraces after the age of 50. Their management is still debated and can be challenging due to the underlying respiratory condition. In our observation, the use of small-bore chest tubes allowed prolonged ambulatory care in a palliative setting. CASE REPORT: We report the case of a 54-year-old woman suffering from a leiomyosarcoma with multiple pulmonary metastases who had repeated episodes of pneumothorax, one of which was bilateral. Treatment involved the bilateral insertion of 8.5F pigtail catheters connected to Heimlich valves that allowed management as an outpatient. Recurrences were treated similarly, in association with oncological management, providing great additional benefits for patient comfort in this palliative context. CONCLUSION: Altogether, this case report confirms the applicability of outpatient management for drained spontaneous secondary pneumothoraces, even bilateral, especially in a palliative-care setting.


Sujet(s)
Pneumothorax , Soins ambulatoires , Drains thoraciques , Femelle , Humains , Adulte d'âge moyen , Récidive tumorale locale , Soins palliatifs , Pneumothorax/étiologie , Pneumothorax/thérapie , Études rétrospectives , Résultat thérapeutique
5.
Respir Med Res ; 77: 72-78, 2020 Mar.
Article de Anglais | MEDLINE | ID: mdl-32416587

RÉSUMÉ

INTRODUCTION: The new 2018 international guidelines for diagnosing usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF) by CT scan split the old pattern possible UIP (2011 IPF guidelines) into two new patterns: probable UIP and indeterminate for UIP. However, the proportions and prognoses of these new CT-scan patterns are not clear. METHODS: We used a monocentric retrospective cohort of 322 patients suspected of having IPF (University Hospital of Rennes; Competence Center for Rare Lung Diseases; 1 January 2012-31 December 2017). All patients initially diagnosed by CT scan as possible UIP were included. The chest CT-scans were then reclassified according to the new 2018 international guidelines by 3 observers. These data were then subjected to survival analysis with multivariate Cox regression using a composite endpoint of death, lung transplantation, a decline of≥10% in forced vital capacity (FVC), or hospitalization. RESULTS: Of the 89 possible UIP patients included, 74 (83%) were reclassified as probable UIP and 15 (17%) as indeterminate for UIP. Probable UIP patients were more likely to meet the composite endpoint (56/74 [75.7%] vs. 5/15 [33%] patients; HR [IC 95%] =3.12 [1.24; 7.83], P=0.015). Multivariate analysis indicated that the probable UIP pattern was associated with significantly increased risk of reaching the composite endpoint (HR [95% CI]=2.85[1.00; 8.10], P=0.049). CONCLUSION: The majority of possible UIP diagnoses corresponded to probable UIP, which was associated with a significantly worse prognosis than indeterminate for UIP. This distinction between these two CT patterns emphasizes the relevance of the new international guidelines for the diagnosis of IPF.


Sujet(s)
Techniques de diagnostic respiratoire/normes , Fibrose pulmonaire idiopathique/classification , Fibrose pulmonaire idiopathique/diagnostic , Sujet âgé , Sujet âgé de 80 ans ou plus , Études de cohortes , Femelle , France/épidémiologie , Humains , Fibrose pulmonaire idiopathique/traitement médicamenteux , Fibrose pulmonaire idiopathique/épidémiologie , Indoles/usage thérapeutique , Internationalité , Mâle , Adulte d'âge moyen , Guides de bonnes pratiques cliniques comme sujet , Pronostic , Pyridones/usage thérapeutique , Études rétrospectives , Tomodensitométrie , Résultat thérapeutique
6.
Acta Chim Slov ; 67(3): 904-915, 2020 Sep.
Article de Anglais | MEDLINE | ID: mdl-33533437

RÉSUMÉ

This paper aims to identify differences in the justification of the selection of 3D dynamic submicroscopic-representation (SMR) of the solid and liquid states of water, as well as the freezing of water presented in selected authentic tasks. According to students' achievements in solving these tasks at different levels of education, their explanations were identified. To explain in greater detail how students attempted to solve the authentic tasks, an eye-tracking method was used to identify the differences in the total fixation durations on specific areas of interest at the specific SMRs between successful and unsuccessful students in three age groups. A total of 79 students participated in this research. The data were collected with a structured interview conducted with students when solving three authentic tasks displayed on the computer screen. The tasks comprise text (as problem and questions), macro-images (photos of the phenomena) and SMRs of the phenomena. The eye-tracker was also used to measure the students' gaze fixations at the particular area of interest. The results show that successful students' justifications for a correct SMR include macroscopic and sub-microscopic representations of the chosen concepts. Along different stages of education, the selection success increases and sufficient justifications comprise the sub-microscopic level. It could be concluded that there are mostly no significant differences between successful and unsuccessful students within the same age group in the total fixation duration at the correct SMR. Further studies are needed to investigate the information-processing strategies between high and low achievers in solving various authentic tasks comprising SMRs and those that integrate all three levels of the representation of chemical concepts.

7.
Rev Mal Respir ; 36(5): 638-642, 2019 May.
Article de Français | MEDLINE | ID: mdl-31202604

RÉSUMÉ

INTRODUCTION: Lung volume reduction can be effective in appropriately selected patients with severe emphysema and is associated with reduced breathlessness and improved survival. Spontaneous resolution of emphysematous bullae can also sometimes occur. CASE REPORT: We report a case of severe smoking-related emphysema in a 60-year-old patient, who presented in October 2013 with a right upper lobe acute community-acquired pneumonia on the background of previously undocumented emphysema. The patient improved following treatment with co-amoxiclav and serial radiology showed progressive cicatricial retraction. Nine months later there had been a major functional improvement characterized by a complete normalization of the patient's ventilatory parameters, specifically a 45% improvement in FEV1. In the literature, the average FEV1 improvement obtained by surgical or endoscopic lung volume reduction techniques does not exceed 28%. CONCLUSION: Rarely, emphysematous bullae resolve following infections. Further studies of the mechanisms involved in these natural regressions may be of interest in the development of new therapeutics.


Sujet(s)
Pneumonie associée aux soins/complications , Pneumonie associée aux soins/anatomopathologie , Poumon/anatomopathologie , Emphysème pulmonaire/complications , Emphysème pulmonaire/anatomopathologie , Maladie aigüe , Bronchoscopie/méthodes , Volume expiratoire maximal par seconde , Pneumonie associée aux soins/diagnostic , Pneumonie associée aux soins/chirurgie , Humains , Poumon/imagerie diagnostique , Poumon/chirurgie , Mâle , Adulte d'âge moyen , Taille d'organe , Pneumonectomie , Emphysème pulmonaire/diagnostic , Emphysème pulmonaire/chirurgie , Tests de la fonction respiratoire , Fumeurs
8.
Diabet Med ; 36(12): 1652-1658, 2019 12.
Article de Anglais | MEDLINE | ID: mdl-31162713

RÉSUMÉ

AIM: To investigate potential cost savings associated with the use of real-time continuous glucose monitoring (RT-CGM) throughout pregnancy in women with Type 1 diabetes. METHODS: A budget impact model was developed to estimate, from the perspective of National Health Service England, the total costs of managing pregnancy and delivery in women with Type 1 diabetes using self-monitoring of blood glucose (SMBG) with and without RT-CGM. It was assumed that the entire modelled cohort (n = 1441) would use RT-CGM from 10 to 38 weeks' gestation (7 months). Data on pregnancy and neonatal complication rates and related costs were derived from published literature, national tariffs, and device manufacturers. RESULTS: The cost of glucose monitoring was £588 with SMBG alone and £1820 with RT-CGM. The total annual costs of managing pregnancy and delivery in women with Type 1 diabetes were £23 725 648 with SMBG alone, and £14 165 187 with SMBG and RT-CGM; indicating potential cost savings of approximately £9 560 461 from using RT-CGM. The principal drivers of cost savings were the daily cost of neonatal intensive care unit (NICU) admissions (£3743) and the shorter duration of NICU stay (mean 6.6 vs. 9.1 days respectively). Sensitivity analyses showed that RT-CGM remained cost saving, albeit to lesser extents, across a range of NICU costs and durations of hospital stay, and with varying numbers of daily SMBG measurements. CONCLUSIONS: Routine use of RT-CGM by pregnant women with Type 1 diabetes, would result in substantial cost savings, mainly through reductions in NICU admissions and shorter duration of NICU care.


Sujet(s)
Autosurveillance glycémique/économie , Économies , Diabète de type 1/sang , Grossesse chez les diabétiques/sang , Glycémie/analyse , Autosurveillance glycémique/méthodes , Diabète de type 1/complications , Angleterre , Femelle , Humains , Hyperbilirubinémie/thérapie , Hypoglycémie/thérapie , Nouveau-né , Unités de soins intensifs néonatals/économie , Unités de soins intensifs néonatals/statistiques et données numériques , Soins intensifs néonatals/économie , Durée du séjour/économie , Grossesse , Naissance prématurée/thérapie
9.
Rev Mal Respir ; 35(1): 78-82, 2018 Jan.
Article de Français | MEDLINE | ID: mdl-29398155

RÉSUMÉ

INTRODUCTION: Pancreatic cancer is often not diagnosed until at a metastatic stage at which point the prognosis is very poor. Pulmonary metastases are pleomorphic, often present at the time of diagnosis and can lead to the discovery of an asymptomatic primary disease. CASE REPORT: We describe two cases aged 60 and 74 years, where imaging identified what was thought to be an interstitial lung disease but which was actually metastasis from pancreatic cancer. In the first case, CT showed multiple excavated pulmonary nodules but the presentation with medullary compression led rapidly to pathological diagnosis on bone lesions. In the second patient, a history of rheumatoid arthritis and the lack of abdominal symptoms led to an initial search for disease related to the rheumatoid disease. Histopathology, from lung and bone biopsies, enabled a correct diagnosis to be achieved. CONCLUSION: Where atypical interstitial lung disease occurs, biopsy should be considered in order not to delay a diagnosis of cancer, especially pancreatic cancer.


Sujet(s)
Carcinome du canal pancréatique/anatomopathologie , Pneumopathies interstitielles/diagnostic , Tumeurs du poumon/diagnostic , Tumeurs du poumon/secondaire , Tumeurs du pancréas/anatomopathologie , Sujet âgé , Carcinome du canal pancréatique/complications , Diagnostic différentiel , Issue fatale , Femelle , Humains , Pneumopathies interstitielles/étiologie , Pneumopathies interstitielles/anatomopathologie , Tumeurs du poumon/complications , Adulte d'âge moyen , Tumeurs du pancréas/complications , Pronostic , Études rétrospectives
10.
Sci Rep ; 5: 12517, 2015 Jul 24.
Article de Anglais | MEDLINE | ID: mdl-26205348

RÉSUMÉ

The scarce functional recovery of the adult CNS following injuries or diseases is largely due to its reduced potential for plasticity, the ability to reorganize neural connections as a function of experience. Recently, some new strategies restoring high levels of plasticity in the adult brain have been identified, especially in the paradigmatic model of the visual system. A chronic treatment with the anti-depressant fluoxetine reinstates plasticity in the adult rat primary visual cortex, inducing recovery of vision in amblyopic animals. The molecular mechanisms underlying this effect remain largely unknown. Here, we explored fluoxetine effects on mouse visual cortical plasticity, and exploited a proteomic approach to identify possible candidates mediating the outcome of the antidepressant treatment on adult cortical plasticity. We showed that fluoxetine restores ocular dominance plasticity in the adult mouse visual cortex, and identified 31 differentially expressed protein spots in fluoxetine-treated animals vs. controls. MALDITOF/TOF mass spectrometry identification followed by bioinformatics analysis revealed that these proteins are involved in the control of cytoskeleton organization, endocytosis, molecular transport, intracellular signaling, redox cellular state, metabolism and protein degradation. Altogether, these results indicate a complex effect of fluoxetine on neuronal signaling mechanisms potentially involved in restoring plasticity in the adult brain.


Sujet(s)
Fluoxétine/pharmacologie , Protéines de tissu nerveux/métabolisme , Plasticité neuronale/effets des médicaments et des substances chimiques , Protéomique , Cortex visuel/métabolisme , Animaux , Souris , Rats
11.
Psychol Med ; 42(4): 769-80, 2012 Apr.
Article de Anglais | MEDLINE | ID: mdl-21995856

RÉSUMÉ

BACKGROUND. This paper examined the hypothesis that males with first-episode psychosis (FEP) experience lower pre-morbid adjustment, greater social disability and more self-perceived needs at illness onset than females(by controlling for duration of untreated psychosis, diagnosis, age and symptoms at onset). Results disconfirming this hypothesis were thought to suggest the potentially mediating role of social context in determining the impact of symptoms and disability on the everyday lives of male patients in the early phase of psychosis. METHOD. A large epidemiologically representative cohort of FEP patients (n=517) was assessed within the Psychosis Incident Cohort Outcome Study (PICOS) framework ­ a multi-site research project examining incident cases of psychosis in Italy's Veneto region. RESULTS. Despite poorer pre-morbid functioning and higher social disability at illness onset, males reported fewer unmet needs in the functioning domain than females did. An analysis of help provided by informal care givers showed that males received more help from their families than females did. This finding led us to disconfirm the second part of the hypothesis and suggest that the impact of poorer social performance and unmet needs on everyday life observed in male patients might be hampered by higher tolerance and more support within the family context.CONCLUSIONS. These findings shed new light on rarely investigated sociocultural and contextual factors that may account for the observed discrepancy between social disability and needs for care in FEP patients. They also point to a need for further research on gender differences, with the ultimate aim of delivering gender-sensitive effective mental health care.


Sujet(s)
Besoins et demandes de services de santé , Troubles psychotiques/épidémiologie , Schizophrénie/épidémiologie , Psychologie des schizophrènes , Caractères sexuels , Adaptation sociale , Adolescent , Adulte , Analyse de variance , Enfant , Études de cohortes , Études transversales , Famille , Femelle , Humains , Incidence , Italie/épidémiologie , Mâle , Services de santé mentale/organisation et administration , Adulte d'âge moyen , Échelles d'évaluation en psychiatrie , Troubles psychotiques/psychologie , Indice de gravité de la maladie , Facteurs sexuels , Environnement social , Médecine d'État , Jeune adulte
12.
Neuroscience ; 172: 219-25, 2011 Jan 13.
Article de Anglais | MEDLINE | ID: mdl-21056088

RÉSUMÉ

Increasing evidence suggests that plastic changes underlying skill learning may occur at early stages of neural processing. However, whether visual perceptual learning (PL) is accompanied by neuronal plasticity phenomena in the primary visual cortex (V1) is yet unknown. Here, we provide the first evidence that practice with specific visual stimuli (gratings) induces long-term potentiation (LTP) of synaptic responses in the rat V1. We report that in rats which have improved through practice their ability to discriminate between two gratings of different spatial frequency, the input/output curves of field potentials evoked in layers II-III of V1 slices by stimulation of either vertical and horizontal connections are shifted leftward compared to controls. Thus, visual PL is followed by potentiation of synaptic transmission both in vertical and horizontal connections (mimicry). We next show that this increase in intracortical connectivity gain is paralleled by LTP-like phenomena caused by the learning process: indeed, visual PL occludes further LTP (occlusion). Mimicry and occlusion are not present in the primary somatosensory cortex of rats trained with PL. These results demonstrate that LTP accompanies PL and highlight the notion that learning can occur at processing stages as early as the primary sensory cortices.


Sujet(s)
Apprentissage/physiologie , Potentialisation à long terme/physiologie , Cortex visuel/physiologie , Perception visuelle/physiologie , Animaux , Électrophysiologie/méthodes , Techniques de culture d'organes , Stimulation lumineuse/méthodes , Rats , Rat Long-Evans
13.
Cell Death Differ ; 17(7): 1092-103, 2010 Jul.
Article de Anglais | MEDLINE | ID: mdl-20019745

RÉSUMÉ

Environmental enrichment (EE) is known to profoundly affect the central nervous system (CNS) at the functional, anatomical and molecular level, both during the critical period and during adulthood. Recent studies focusing on the visual system have shown that these effects are associated with the recruitment of previously unsuspected neural plasticity processes. At early stages of brain development, EE triggers a marked acceleration in the maturation of the visual system, with maternal behaviour acting as a fundamental mediator of the enriched experience in both the foetus and the newborn. In adult brain, EE enhances plasticity in the cerebral cortex, allowing the recovery of visual functions in amblyopic animals. The molecular substrate of the effects of EE on brain plasticity is multi-factorial, with reduced intracerebral inhibition, enhanced neurotrophin expression and epigenetic changes at the level of chromatin structure. These findings shed new light on the potential of EE as a non-invasive strategy to ameliorate deficits in the development of the CNS and to treat neurological disorders.


Sujet(s)
Encéphale/physiologie , Environnement , Plasticité neuronale/physiologie , Animaux , Encéphale/cytologie , Système nerveux central/physiologie , Cortex cérébral/physiologie , Humains
14.
FASEB J ; 21(1): 130-9, 2007 Jan.
Article de Anglais | MEDLINE | ID: mdl-17135370

RÉSUMÉ

Retina has long been considered less plastic than cortex or hippocampus, the very sites of experience-dependent plasticity. Now, we show that retinal development is responsive to the experience provided by an enriched environment (EE): the maturation of retinal acuity, which is a sensitive index of retinal circuitry development, is strongly accelerated in EE rats. This effect is present also in rats exposed to EE up to P10, that is before eye opening, suggesting that factors sufficient to trigger retinal acuity development are affected by EE during the first days of life. Brain derived neurotrophic factor (BDNF) is precociously expressed in the ganglion cell layer of EE with respect to non-EE rats and reduction of BDNF expression in EE animals counteracts EE effects on retinal acuity. Thus, EE controls the development of retinal circuitry, and this action depends on retinal BDNF expression.


Sujet(s)
Facteur neurotrophique dérivé du cerveau/physiologie , Rétine/croissance et développement , Animaux , Séquence nucléotidique , Amorces ADN , Électrorétinographie , Test ELISA , Potentiels évoqués visuels , Femelle , Immunohistochimie , Mâle , Grossesse , Rats , Rat Long-Evans , Rétine/physiologie , Acuité visuelle
15.
Proc Biol Sci ; 270 Suppl 2: S129-32, 2003 Nov 07.
Article de Anglais | MEDLINE | ID: mdl-14667360

RÉSUMÉ

While the long-distance movements of pelagic vertebrates are becoming known thanks to satellite telemetry, the factors determining their courses have hardly been investigated. We have analysed the effects of oceanographic factors on the post-nesting movements of three satellite-tracked leatherback turtles (Dermochelys coriacea) moving in the southwest Indian Ocean. By superimposing the turtle tracks on contemporaneous images of sea-surface temperatures and sea height anomalies, we show that currentrelated features dominate the shape of the reconstructed routes. After an initial offshore movement, turtles moved along straight routes when in the core of the current, or executed loops within eddies. Large parts of the routes were strikingly similar to those of surface drifters tracked in the same region. These findings document that long-lasting oceanic movements of marine turtles may be shaped by oceanic currents.


Sujet(s)
Migration animale/physiologie , Géographie , Mouvement/physiologie , Tortues/physiologie , Mouvements de l'eau , Animaux , Océan Indien , Océanographie , Communications par satellite
16.
Boll Chim Farm ; 130(10): 402-8, 1991 Nov.
Article de Italien | MEDLINE | ID: mdl-1805875

RÉSUMÉ

Three industrial batches of a 10% (w/v) amino acid solution have been checked for particulate contamination. The batches differed in preparative technology and/or type of additives. In particular, one batch was prepared under nitrogen, filled under vacuum and with the addition of sodium metabisulfite and cysteine. The other two batches were simply prepared under nitrogen and differed in the presence or not of cysteine and sodium metabisulfite. Accelerated stability tests were performed (40, 50, e 60 degrees C) and controls were effected both at room (25 degrees C) and refrigerator (6 degrees C) temperature. The results show that the preparation under nitrogen and the presence of cysteine result in an improved chemical stability and allow the particulate contamination level to be maintained within the limits of the Italian Pharmacopoeia. In particular, the batch prepared under nitrogen and filled under vacuum is characterized by a particulate contamination level which remains within the more restrictive limits of the British Pharmacopoeia for the entire period of the stability studies. Moreover, the particulate contamination control performed at 6 degrees C has proved to be a useful predictive tool with regards to batch quality evaluation.


Sujet(s)
Acides aminés/administration et posologie , Contamination de médicament , Perfusions parentérales , Acides aminés/composition chimique , Solutions , Température
17.
Farmaco Sci ; 43(6): 489-99, 1988 Jun.
Article de Anglais | MEDLINE | ID: mdl-3208891

RÉSUMÉ

Twelve new fluoroquinolones, structurally related to norfloxacin, have been synthesized in order to investigate the effect of substituents at the secondary nitrogen of the piperazine ring on antimicrobial activity. The new substances (carbamates, isoureas, guanidines, ureas and cyanamides) tested on a variety of gram-positive and gram-negative organisms showed lower activity than the model compound.


Sujet(s)
Antibactériens/synthèse chimique , Norfloxacine/analogues et dérivés , Antibactériens/pharmacologie , Bactéries/effets des médicaments et des substances chimiques , Phénomènes chimiques , Chimie , Ciprofloxacine/pharmacologie , Tests de sensibilité microbienne , Norfloxacine/synthèse chimique
18.
Xenobiotica ; 14(6): 429-43, 1984 Jun.
Article de Anglais | MEDLINE | ID: mdl-6475103

RÉSUMÉ

The metabolic pathways of the non-hormonal anti-fertility agent 3-(2-ethylphenyl)-5-(3-methoxyphenyl)-1H-1,2,4-triazole (DL 111-IT) were studied in rats given the 14C-labelled compound intramuscularly. The diaryltriazole, once absorbed, was metabolized rapidly by three phase I reactions: (a) hydroxylation at the C-4 of the methoxyphenyl ring, (b) hydroxylation at the alpha-C of the ethyl chain, and (c) demethylation of the methoxyl function. Seven free metabolites and three conjugates have been isolated and characterized by u.v., i.r., n.m.r. and mass spectroscopy. The products of the first step of metabolism of the diaryltriazole were tested for their pregnancy-terminating activity in the rat. They were only 5-9% as effective as the parent compound, indicating that the unchanged drug is the active molecule.


Sujet(s)
Abortifs/métabolisme , Triazoles/métabolisme , Animaux , Bile/analyse , Phénomènes chimiques , Chimie , Fèces/analyse , Femelle , Spectroscopie par résonance magnétique , Grossesse , Rats , Lignées consanguines de rats , Spectrophotométrie IR , Spectrophotométrie UV , Triazoles/sang , Triazoles/urine
19.
Farmaco Sci ; 39(5): 450-62, 1984 May.
Article de Italien | MEDLINE | ID: mdl-6734819

RÉSUMÉ

The synthesis and activity on the central nervous system of a series of 2-aryl or 2-alkyl-7-phenylhexahydroimidazo[1,5-a] pyrazin-3(2H)-ones (II a-f) are reported. The intermediate 3-carbomethoxy-1-phenylpiperazine (X) was prepared in six steps from aniline and methyl-2-chloroacrylate. Compared with that of derivatives of Zetidoline, the depressant activity of (II a-f) is markedly reduced.


Sujet(s)
Dépresseurs du système nerveux central/synthèse chimique , Pyrazines/synthèse chimique , Animaux , Comportement animal/effets des médicaments et des substances chimiques , Souris , Pyrazines/pharmacologie , Rats
20.
J Med Chem ; 26(8): 1187-92, 1983 Aug.
Article de Anglais | MEDLINE | ID: mdl-6876087

RÉSUMÉ

A series of 3,5-diaryl-s-triazoles were synthesized and evaluated as postimplantation contragestational agents. The introduction of various substituents (e.g., an o-alkyl chain on one phenyl and a m-alkoxy group on the other) was found to increase the potency. Several compounds with very high pregnancy-terminating activity in both hamsters and rats were obtained. One of these, 3-(2-ethylphenyl)-5-(3-methoxyphenyl)-s-triazole, DL 111 (36), was selected for detailed evaluation in various animal species. A synthetic scheme for the preparation of these compounds and preliminary structure-activity relationships are presented.


Sujet(s)
Abortifs non stéroïdiens/synthèse chimique , Abortifs/synthèse chimique , Triazoles/synthèse chimique , Animaux , Cricetinae , Femelle , Grossesse , Rats , Relation structure-activité , Triazoles/pharmacologie
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