A nanoparticle comprising a micelle formed by an amphiphilic block copolymer and encapsulating a gadolinium complex

Publication number: WO2011/113616The present invention relates to a nanoparticle comprising a micelle formed by an amphophilic block-copolymer and an agent encapsulated within said micelle. The present invention also relates to a composition comprising such nanoparticle and to the use of such nanoparticle and/or of such composition. More particularly, in one embodiment, the invention describes a new class of polymeric nanoparticles as smart Tl contrast agent for MR imaging for breast cancer early detection. These nanoparticles contrast agents have the capability to remain switched off during circulation and then switch on their imaging capacity upon arrival at the target sites (tissue of interest). These smart nanoparticles contrast agent are self-assembled from pH sensitive amphiphilic polymer, loaded with Gadolinium (Gd3+) complex based Tl agent and then fitted with targeting biomolecules such as antibody, small molecules or DNA to increase its specificity toward the target of interest

Iliac artery false aneurysm twelve years after allograft nephrectomy

We report a case of a non-infected right external iliac artery false aneurysm. The patient was a 44 year-old woman on chronic peritoneal dialysis had had an allograft nephrectomy 12 years before and who presented with acute abdominal pain. Ultrasound and CT-scan showed a saccular aneurysm arising from the right external iliac artery. A large false aneurysm was identified during surgery, from donor arterial vessel remaining in situ after graft nephrectomy. Resection of the false aneurysm, with ligation of the right external iliac artery and interposition of a femorofemoral graft was successfully performed, with an uneventful post-operative recovery. False aneurysms after renal allograft nephrectomy are very rare. To our knowledge, this is the longest reported period of time between na nephrectomy and clinical evidence of a false aneurysm.info:eu-repo/semantics/publishedVersio

Case Report

We report a case of a cerebral venous thrombosis (CVT) in a chronic kidney disease patient with three CVT predisposing conditions. A 53 year-old woman on chronic peritoneal dialysis presented to the emergency department with acute headache and vertigo. The neurological examination and head CT scan performed at the emergency department were normal but, three days later, a lateral gait deviation and a horizontal nystagmus were identified. A brain MRI and MRI-venogram confirmed a left lateral sinus thrombosis. Hormonal replacement therapy (HRT), a positive lupus anticoagulante and a homozygous mutation on the methylenetetrahydrofolate reductase gene, with hyperhomocysteinaemia, were the three well-known prothrombotic conditions identified in this patient. HRT was discontinued, the patient started anticoagulation with warfarin and folic acid supplementation and was discharged, 10 days after admission, complaining of a mild vertigo. After six months of therapy the patient had vertigo improvement and maintained a positive lupus anticoagulant. The head MRI and MRI-venography showed a thrombus reduction.info:eu-repo/semantics/publishedVersio

Cytokeratin 7/19 expression inN-diethylnitrosamine-induced mouse hepatocellular lesions: implications for histogenesis International

Hepatocellular carcinoma (HCC) is a common malignancy with poor clinical outcome, whose histogenesis is the subject of intense debate. Specifically, expression ofcytokeratins (CKs) 7 and 19, associated with aggressive biological behaviour, is proposed to reflect a possible progenitor cell origin or tumour dedifferentiation towardsa primitive phenotype. This work addresses that problem by studying CKs 7 and 19expression in N-diethylnitrosamine (DEN)-induced mouse HCCs. ICR mice weredivided into six DEN-exposed and six matched control groups. Samples were takenfrom each group at consecutive time points. Hyperplastic foci (13 lesions) occurredat 29-40 weeks (groups 8, 10 and 12) with diffuse dysplastic areas (19 lesions) andwith one hepatocellular adenoma (HCA) (at 29 weeks). HCCs (4 lesions) wereobserved 40 weeks after the first DEN administration (group 12). CKs 7 and 19showed identical expression patterns and located to large, mature hepatocytes, isolated or in small clusters. Hyperplastic foci and the single HCA were consistentlynegative for both markers, while dysplastic areas and HCCs were positive. Theseresults support the hypothesis that CKs 7 and 19 expression in hepatocellular malignancies results from a dedifferentiation process rather than from a possible progenitor cell origin

Embedding of Cortical Representations by the Superficial Patch System

Pyramidal cells in layers 2 and 3 of the neocortex of many species collectively form a clustered system of lateral axonal projections (the superficial patch system—Lund JS, Angelucci A, Bressloff PC. 2003. Anatomical substrates for functional columns in macaque monkey primary visual cortex. Cereb Cortex. 13:15-24. or daisy architecture—Douglas RJ, Martin KAC. 2004. Neuronal circuits of the neocortex. Annu Rev Neurosci. 27:419-451.), but the function performed by this general feature of the cortical architecture remains obscure. By comparing the spatial configuration of labeled patches with the configuration of responses to drifting grating stimuli, we found the spatial organizations both of the patch system and of the cortical response to be highly conserved between cat and monkey primary visual cortex. More importantly, the configuration of the superficial patch system is directly reflected in the arrangement of function across monkey primary visual cortex. Our results indicate a close relationship between the structure of the superficial patch system and cortical responses encoding a single value across the surface of visual cortex (self-consistent states). This relationship is consistent with the spontaneous emergence of orientation response-like activity patterns during ongoing cortical activity (Kenet T, Bibitchkov D, Tsodyks M, Grinvald A, Arieli A. 2003. Spontaneously emerging cortical representations of visual attributes. Nature. 425:954-956.). We conclude that the superficial patch system is the physical encoding of self-consistent cortical states, and that a set of concurrently labeled patches participate in a network of mutually consistent representations of cortical inpu

Self-assembled polymeric nanoparticles as new, smart contrast agents for cancer early detection using magnetic resonance imaging

Early cancer detection is a major factor in the reduction of mortality and cancer management cost. Here we developed a smart and targeted micelle-based contrast agent for magnetic resonance imaging (MRI), able to turn on its imaging capability in the presence of acidic cancer tissues. This smart contrast agent consists of pH-sensitive polymeric micelles formed by self-assembly of a diblock copolymer (poly(ethyleneglycol-b-trimethylsilyl methacrylate)), loaded with a gadolinium hydrophobic complex ((t)BuBipyGd) and exploits the acidic pH in cancer tissues. In vitro MRI experiments showed that (t)BuBipyGd-loaded micelles were pH-sensitive, as they turned on their imaging capability only in an acidic microenvironment. The micelle-targeting ability toward cancer cells was enhanced by conjugation with an antibody against the MUC1 protein. The ability of our antibody-decorated micelles to be switched on in acidic microenvironments and to target cancer cells expressing specific antigens, together with its high Gd(III) content and its small size (35-40 nm) reveals their potential use for early cancer detection by MRI

Induction of human mesenchymal stem cells osteogenesis by bioactive agent-releasing liposomes

Stem cell therapy is a rapidly evolving area of research in regenerative medicine. Mesenchymal stem cells (MSCs) have received considerable attention by the scientific community because of their potential of expansion and the ability to differentiate into various mesodermal tissues. Liposomes are well-established non-viral carrier systems, presenting significant advantages over other nanoparticle-based drug delivery systems, namely a high load carrying capacity, a relative safety and an ease of large-scale production, as well as a versatile nature in terms of possible formulation and functionalization. The objectives of the present study were to evaluate the efficacy of growth differentiation factor-releasing liposomes on the induction of MSCs osteogenesis. For that, dexamethasone (Dex) was encapsulated within the liposome bilayer at different lipid formulations. The obtained liposomes showed a monodisperse distribution of particles size, and an increased ζ- potential for the PEGylated liposomes. Dex encapsulation studies demonstrate that the presence of cholesterol (Chol) decreases the Dex loading capacity of the liposome bilayer. The different stabilizing effect of Chol and Dex on the liposomes is due to differences in their interaction with phospholipid molecules. Highly lipophilic Chol gets incorporated between the acyl chains and reduces chain movement increasing rigidity and stabilization the membrane. Dex, being more hydrophilic, interacts differently with phospholipid acyl chains and head groups and destabilizes the membrane. In vitro release study demonstrated an initial burst release within an initial timeframe of 24 hours. Following the initial release, a slower release was observed until 6 days. Afterwards, Dex continues to be released at a slower but steady rate until day 21. The effect of Dex-loaded liposomes on viability, proliferation and osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) was assessed. The results of the biological activity showed that the Dex-loaded liposomes do not have any cytotoxic effect and, more importantly, were able to promote an earlier induction of hBMSCs differentiation into the osteogenic lineage, as demonstrated by the expression of osteoblastic markers at the phenotypic and the genotypic levels. Concluding, Dex-loaded liposomes represent a novel biological or nature-inspired nanoparticle strategy for tissue engineering and regenerative medicine applications

Patient and Public Involvement in Youth Mental Health Research: Protocol for a Systematic Review of Practices and Impact

Various health settings have advocated for involving patients and members of the public (PPI) in research as a means to increase quality and relevance of the produced knowledge. However, youth PPI has been an understudied area. This protocol paper describes a new project that aims to summarize what is known about PPI with young people in mental health research. In line with the Preferred Reporting Items for Systematic reviews and Meta-Analyses Statement guidelines we will identify and appraise suitable articles and extract and synthesize relevant information including at least two reviewers at each stage of the process. Results will be presented in two systematic reviews that will describe (a) how youth PPI has been conducted (Review1) and (b) what impact youth PPI had on the subsequent research and on stakeholders (Review2). To our knowledge, this is the first set of reviews that uses a critical appraisal tool, which is co-developed with children and young people. Findings from this project will provide valuable insights and set out the key steps to adopting adequate PPI methods when involving children and young people in mental health research

Stress ocupacional no ensino : um estudo com professores dos 3º ciclo e ensino secundário

Este trabalho foi realizado com 689 professores portugueses, a leccionarem nos terceiro ciclo e ensino secundário. Foram avaliados indicadores de stress, “burnout”, saúde física e satisfação profissional. Observaram-se valores significativos de stress ocupacional (perto de 40%), e de “burnout” (10% na exaustão emocional, 3% na baixa realização pessoal e 1% na despersonalização), vários problemas de saúde física e valores de insatisfação profissional perto dos 20%. As análises de regressão múltipla apontaram diferentes variáveis preditoras para as três dimensões do “burnout” (62% de variância explicada na exaustão emocional, 16% na realização pessoal e 13% na despersonalização). As análises discriminantes e “t-test” para amostras independentes demonstraram maior stress ocupacional nas mulheres, nos professores mais velhos, nos profissionais com vínculos profissionais mais precários, nos professores com mais horas de trabalho e com mais alunos em sala de aula. No final, apresentam-se as limitações do estudo e as implicações para a investigação futura.(undefined