HEDRINE (un nouvel outil d aide à la décision pour les interactions plante-médicament)

Lors de ce travail de thèse un nouvel outil a été mis en place pour l aide à la détection des interactions plante-médicament. Une base de données est dorénavant disponible sur le net à l adresse https://hedrine.ujf-grenoble.fr/. A ce jour, elle recense les interactions potentielles (via des interactions pharmacocinétiques ou pharmacodynamiques) ou démontrées lors d études cliniques ou de case reports entre des plantes médicinales et les médicaments anticancéreux listés dans la classe L du classement (ATC). Les interactions répertoriées sont toutes issues de la bibliographie internationale.GRENOBLE1-BU Médecine pharm. (385162101) / SudocSudocFranceF

Interactions Plantes et Médicaments post-greffe (participation à HEDRINE)

Ce travail de thèse a permis d enrichir HEDRINE, base de données créée par Florence SOUARD, en s intéressant aux interactions entre les plantes et les médicaments utilisés après des greffes hépatique et rénale surtout. Les patients greffés sont particulièrement à risque du fait de leur état affaibli et des médicaments qu ils prennent, des médicaments dits à marge thérapeutique étroite. Il faut donc être très vigilant par rapport à ce qu ils consomment sachant que les médecines complémentaires et alternatives dont la phytothérapie sont de plus en plus utilisées et que tout n est pas sans risque.The work for this thesis has contributed to develop HEDRINE, the database created by Florence SOUARD. The main aim has been to study the interactions between plants and the drugs used especially after liver and kidney transplants. The transplanted patients are particularly at risk because of their lower immunity level and of the medicines they take, drugs with a narrow therapeutic range. Great vigilance is required to ensure that whatever they consume is carefully controlled since the use of complementary and alternative medicines including herbal therapy is rapidly growing with all the risks that can be involved.GRENOBLE1-BU Médecine pharm. (385162101) / SudocSudocFranceF

Cooperation with local administrations of primary school principals in solving economic problems of schoolOkulun ekonomik sorunlarının çözümünde ilkokul müdürlerinin yerel yönetimler ile işbirliği

In this research, it is aimed to find out whether being in cooperation with local administrations of the primary schools affects the solution of economic problems of the school, and if so, what kind of contribution it has. Survey design model was used in the research. Interview technique from qualitative research methods, was used in the collection of data. Determination of the study group of research, easily accessible sampling method of purpose sampling model is used. The study group subject to the research is determined as the primary school principals who can give information in a willing manner to understand the study problem and limited to 20 primary school principals, serve in different socio-economic regions within the province of Ankara, where the researcher could easily access it. Local governments within the scope of the research have been limited to municipalities, because the schools in the survey are schools located in the central districts and removal of the Ankara Special Provincial Administration through Law No:6360. The collection of data was carried out “Interview Form for the Primary School Administrators on Cooperation with Local Governments” created by the researcher. Descriptive analysis was performed in the analysis of data.As a result of the research, it is concluded that the primary schools are in cooperation with the local administrations; however this cooperation is not completely helpful in solving economic problems of the school. In addition, either local administrations or other institutions that the schools cooperate with can only support the schools in certain expenditure items. This situation can only help to solve the limited problem, or not at all. It has been determined that all of the school principals want to cooperate with the Provincial and District National Education Directorate in solving the economic problems of the school and that the school principals also want to cooperate with the Ministry of National Education, the parents and the local administrations. In this context, it may be suggested to increase cooperation with the Provincial and District Directorates of National Education, to give schools a budget, and to increase the cooperation of schools with local administrations can be suggested to solve their own economic problems.Extended English abstract is in the end of Full Text PDF (TURKISH) file. ÖzetBu araştırmada ilkokulların yerel yönetimlerle işbirliği içerisinde olmalarının okulun ekonomik sorunlarının çözümüne katkılarının olup olmadığı, katkıları oluyor ise ne tür katkılarının olduğunun çözümlenmesi amaçlanmıştır. Araştırmanın modeli tarama modelidir.  Verilerin toplanmasında nitel araştırma yöntemlerinden görüşme tekniği kullanılmıştır. Araştırmanın çalışma grubunun oluşturulmasında, amaçlı örnekleme yöntemlerinden kolay ulaşılabilir örnekleme yöntemi kullanılmıştır. Çalışma grubu çalışma probleminin anlaşılmasına yönelik istekli olarak bilgiler verebilecek olan ve araştırmacının kolay ulaşabileceği Ankara ili içerisindeki farklı sosyo ekonomik bölgelerde görev yapan 20 ilkokul müdürü ile sınırlandırılmıştır. Araştırmada Ankara il merkezinde bulunan ilkokul müdürleri ile görüşülmesi ve 6360 sayılı yasa ile Ankara İl Özel İdaresi’nin kaldırılmış olması nedeniyle araştırma kapsamında yerel yönetimler olarak belediyeler ifade edilmiştir. Verilerin toplanması, araştırmacı tarafından oluşturulan “Yerel Yönetimler ile İşbirliği Konusunda İlkokul Müdürü Görüşme Formu” aracılığı ile gerçekleştirilmiştir. Verilerin çözümlenmesinde betimsel analiz yapılmıştır.Bu araştırmada, ilkokulların belediyeler ile işbirliği içerisinde olduğu ancak bu işbirliğinin okulun ekonomik sorunlarını çözmeye tam olarak yardımcı olmadığı sonucuna ulaşılmıştır. Ayrıca okulların işbirliği yaptığı gerek belediyeler gerekse diğer kurumlar okullara yalnızca belirli gider kalemlerinde destek olabildiğinden yapılan destekler sınırlı çözümler sağlamakta ya da hiç çözüm olamamaktadır. Araştırmada okul müdürlerinin tamamının okulun ekonomik sorunlarının çözümünde İl ve İlçe Milli Eğitim Müdürlüğü ile işbirliği yapmak istedikleri, bunun yanı sıra Milli Eğitim Bakanlığı, veliler ve yerel yönetimlerle de işbirliği yapmayı istedikleri belirlenmiştir. Bu kapsamda okulların ekonomik sorunlarının çözümünde öncelikli olarak İl ve İlçe Milli Eğitim Müdürlükleri ile işbirliğini artıracak, okullara bir bütçe verilmesini sağlayacak, okulların yerel yönetimler ile işbirliğini artıracak yasal düzenlemeler yapılması önerilebilir

Pro-oxidant properties of indolone-N-oxides in relation to their antimalarial properties

Indolone-N-oxides (INODs) are bioreducible and possess remarkable anti-malarial activities in the low nanomolar range in vitro against different Plasmodium falciparum (P. falciparum) strains and in vivo. INODs have an original mechanism of action: they damage the host cell membrane without affecting non-parasitized erythrocytes. These molecules produce a redox signal which activates SYK tyrosine kinases and induces a hyperphosphorylation of AE1 (band 3, erythrocyte membrane protein). The present work aimed to understand the early stages of the biochemical interactions of these compounds with some erythrocyte components from which the redox signal could originate. The interactions were studied in a biomimetic model and compared with those of chloroquine and artemisinin. The results showed that INODs i) do not enter the coordination sphere of the metal in the heme iron complex as does chloroquine; ii) do not generate iron-dependent radicals as does artemisinin; iii) generate stable free radical adducts after reduction at one electron; iv) cannot trap free radicals after reduction. These results confirm that the bioactivity of INODs does not lie in their spin-trapping properties but rather in their pro-oxidant character. This property may be the initiator of the redox signal which activates SYK tyrosine kinases

A novel chalcone derivative which acts as a microtubule depolymerising agent and an inhibitor of P-gp and BCRP in in-vitro and in-vivo glioblastoma models

<p>Abstract</p> <p>Background</p> <p>Over the past decades, in spite of intensive search, no significant increase in the survival of patients with glioblastoma has been obtained. The role of the blood-brain barrier (BBB) and especially the activity of efflux pumps belonging to the ATP Binding Cassette (ABC) family may, in part, explain this defect.</p> <p>Methods</p> <p>The <it>in-vitro </it>activities of JAI-51 on cell proliferation were assessed by various experimental approaches in four human and a murine glioblastoma cell lines. Using drug exclusion assays and flow-cytometry, potential inhibitory effects of JAI-51 on P-gp and BCRP were evaluated in sensitive or resistant cell lines. JAI-51 activity on <it>in-vitro </it>microtubule polymerization was assessed by tubulin polymerization assay and direct binding measurements by analytical ultracentrifugation. Finally, a model of C57BL/6 mice bearing subcutaneous GL26 glioblastoma xenografts was used to assess the activity of the title compound <it>in vivo</it>. An HPLC method was designed to detect JAI-51 in the brain and other target organs of the treated animals, as well as in the tumours.</p> <p>Results</p> <p>In the four human and the murine glioblastoma cell lines tested, 10 μM JAI-51 inhibited proliferation and blocked cells in the M phase of the cell cycle, via its activity as a microtubule depolymerising agent. This ligand binds to tubulin with an association constant of 2 × 10⁵M^-1, overlapping the colchicine binding site. JAI-51 also inhibited the activity of P-gp and BCRP, without being a substrate of these efflux pumps. These <it>in vitro </it>studies were reinforced by our <it>in vivo </it>investigations of C57BL/6 mice bearing GL26 glioblastoma xenografts, in which JAI-51 induced a delay in tumour onset and a tumour growth inhibition, following intraperitoneal administration of 96 mg/kg once a week. In accordance with these results, JAI-51 was detected by HPLC in the tumours of the treated animals. Moreover, JAI-51 was detected in the brain, showing that the molecule is also able to cross the BBB.</p> <p>Conclusion</p> <p>These <it>in vitro </it>and <it>in vivo </it>data suggest that JAI-51 could be a good candidate for a new treatment of tumours of the CNS. Further investigations are in progress to associate the title compound chemotherapy to radiotherapy in a rat model.</p

HEDRINE : outil d’aide à la décision pour les interactions plante–médicament

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Procédé de transformation d'une huile essentielle

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MEDITRINE-PHYTO: pour un usage validité et responsable de la phytothérapie

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Aromatherapy and cystic fibrosis: real-life, but many questions remain. Aromatherapy in cystic fibrosis: real-life

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Les compléments alimentaires solaires

Le bronzage, phénomène de mode de ces dernières décennies, encourage la population occidentale à arborer un teint halé toute l'année. Pourtant l'exposition solaire, bien que synonyme de synthèse de la vitamine D, n'est pas sans risque pour la peau. Elle peut engendrer de nombreuses modifications cutanées, à l'origine de pathologies telles que l'érythème actinique, la lucite estivale, voire dans les cas les plus graves, des cancers cutanés. Il parait donc essentiel de contribuer à la protection de la peau en stimulant ses défenses endogènes. Pour cela les laboratoires pharmaceutiques et de parapharmacies ont mis au point un panel de compléments alimentaires solaires accessibles aux patients en officine. Un de nos rôles de pharmacien d'officine est de garantir la sécurité des produits présents en libre accès et de pouvoir apporter tous les conseils nécessaires à leur bonne utilisation. Ce travail de recherche et d'analyse sur la composition de la majorité des compléments alimentaires solaires présents sur le marché pharmaceutique français permet de faire le point sur les données des études scientifiques relatées dans la littérature. D'autre part ce travail a permis de classer les compléments alimentaires solaires en catégories, afin que cela puisse servir de support aux pharmaciens officinaux dans le conseil des compléments alimentaires solaires.Tanning has been popular amongst western culture over the past decades. However, although solar exposure is proven to encourage synthesis of D vitamin, it is not risk-free for the skin. It can provoke numerous cutaneous modifications such as actinic erythema, summer lucitis, or even in some severe cases, skin cancer. It appears therefore essential to help stimulate skin protection by activating its endogenous defence protection mechanisms. Pharmaceutical companies have created a range of supplements readily available for general public. Part of our role as pharmacists is not only to make sure products sold are safe, but to be able to provide clients with appropriate advice regarding their safe use. In this work, we analysed the composition of most of the supplements currently on the French market in order to summarise data related in the literature. Furthermore, this study aims to provide support to pharmacists for clients advice.GRENOBLE1-BU Médecine pharm. (385162101) / SudocSudocFranceF