Paramagnetic and fluorescent liposomes for target-specific imaging and therapy of tumor angiogenesis

Angiogenesis is essential for tumor growth and metastatic potential and for that reason considered an important target for tumor treatment. Noninvasive imaging technologies, capable of visualizing tumor angiogenesis and evaluating the efficacy of angiostatic therapies, are therefore becoming increasingly important. Among the various imaging modalities, magnetic resonance imaging (MRI) is characterized by a superb spatial resolution and anatomical soft-tissue contrast. Revolutionary advances in contrast agent chemistry have delivered versatile angiogenesis-specific molecular MRI contrast agents. In this paper, we review recent advances in the preclinical application of paramagnetic and fluorescent liposomes for noninvasive visualization of the molecular processes involved in tumor angiogenesis. This liposomal contrast agent platform can be prepared with a high payload of contrast generating material, thereby facilitating its detection, and is equipped with one or more types of targeting ligands for binding to specific molecules expressed at the angiogenic site. Multimodal liposomes endowed with contrast material for complementary imaging technologies, e.g., MRI and optical, can be exploited to gain important preclinical insights into the mechanisms of binding and accumulation at angiogenic vascular endothelium and to corroborate the in vivo findings. Interestingly, liposomes can be designed to contain angiostatic therapeutics, allowing for image-supervised drug delivery and subsequent monitoring of therapeutic efficacy

Differential Deployment of REST and CoREST Promotes Glial Subtype Specification and Oligodendrocyte Lineage Maturation

The repressor element-1 (RE1) silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) is a master transcriptional regulator that binds to numerous genomic RE1 sites where it acts as a molecular scaffold for dynamic recruitment of modulatory and epigenetic cofactors, including corepressor for element-1-silencing transcription factor (CoREST). CoREST also acts as a hub for various cofactors that play important roles in epigenetic remodeling and transcriptional regulation. While REST can recruit CoREST to its macromolecular complex, CoREST complexes also function at genomic sites independently of REST. REST and CoREST perform a broad array of context-specific functions, which include repression of neuronal differentiation genes in neural stem cells (NSCs) and other non-neuronal cells as well as promotion of neurogenesis. Despite their involvement in multiple aspects of neuronal development, REST and CoREST are not believed to have any direct modulatory roles in glial cell maturation.We challenged this view by performing the first study of REST and CoREST in NSC-mediated glial lineage specification and differentiation. Utilizing ChIP on chip (ChIP-chip) assays, we identified distinct but overlapping developmental stage-specific profiles for REST and CoREST target genes during astrocyte (AS) and oligodendrocyte (OL) lineage specification and OL lineage maturation and myelination, including many genes not previously implicated in glial cell biology or linked to REST and CoREST regulation. Amongst these factors are those implicated in macroglial (AS and OL) cell identity, maturation, and maintenance, such as members of key developmental signaling pathways and combinatorial transcription factor codes.Our results imply that REST and CoREST modulate not only neuronal but also glial lineage elaboration. These factors may therefore mediate critical developmental processes including the coupling of neurogenesis and gliogenesis and neuronal-glial interactions that underlie synaptic and neural network plasticity and homeostasis in health and in specific neurological disease states

Avaliação dos efeitos adversos clínicos e alterações laboratoriais em pacientes com acne vulgar tratados com isotretinoína oral Evaluation of clinical adverse effects and laboratory alterations in patients with acne vulgaris treated with oral isotretinoin

FUNDAMENTOS: A isotretinoína oral revolucionou o manejo da acne. Os efeitos adversos observados, durante o tratamento, são divididos em dois grupos: mucocutâneos e sistêmicos. Anormalidades laboratoriais, principalmente, as dislipidemias e aumento das enzimas hepáticas são relatados. OBJETIVO: Avaliar a tolerabilidade da isotretinoína oral, com atenção, no metabolismo lipídico, função hepática e reações adversas clínicas. MÉTODOS: Foram incluídos 150 pacientes com diagnóstico clínico de acne submetidos a tratamento com isotretinoína oral. Avaliações clínicas e laboratoriais foram feitas, após um mês e a cada três meses, até completar o tratamento. RESULTADOS: Dos 150 pacientes 48% eram do sexo feminino e 52% do sexo masculino. A idade variou de 15 a 32 anos. Quanto aos efeitos adversos cutâneos e mucosos da isotretinoína, queilite foi o mais frequente, ocorrendo em 94% pacientes. Efeitos clínicos sistêmicos foram bem menos comuns. Os níveis de colesterol, triglicerídeos, transaminases, foram avaliados e não mostraram alterações significativas, ao longo do tratamento. CONCLUSÃO: Os pacientes apresentaram efeitos adversos, compatíveis com os da literatura, e, em sua maioria, controlados com medicações sintomáticas. Podemos concluir que a isotretinoína é uma droga segura, em relação a seus efeitos adversos, tanto clínicos como laboratoriais.<br>BACKGROUND: Oral isotretinoin therapy has completely changed the treatment of acne. The clinical adverse effects of isotretinoin are classified into two groups: mucocutaneous and systemic toxic. Laboratory alterations such as dyslipidemia and increase of hepatic enzymes are reported. OBJECTIVES: To evaluate the tolerability of oral isotretinoin with special attention to lipid metabolism, hepatic function, and clinical adverse reactions. METHODS: 150 patients clinically diagnosed with acne being treated with oral isotretinoin were included in the study. Clinical and laboratory evaluations were conducted before the start of therapy, one month after, and every three months thereafter until the completion of treatment. RESULTS: Of the 150 patients evaluated, 48% were female and 52%, male. They were aged from 15 to 32 years. The most prevalent mucocutaneous adverse reaction associated with isotretinoin therapy was cheilitis, reported by 94% of the patients. Systemic clinical effects were much less common. Cholesterol, triglyceride, and transaminase levels were assessed and significant changes were not observed during treatment. CONCLUSION: Patients showed adverse effects compatible to those described in the literature, which are mostly controlled with symptomatic medication. Isotretinoin is a safe drug and adverse and laboratory effects are well tolerated