Influência da forma farmacêutica (emulsão múltipla A/O/A, emulsão O/A e pomada) sobre a permeação e retenção cutânea da paromomicina

Pomadas contendo paromomicina (PA) são utilizadas no tratamento tópico da leishmaniose cutânea. Embora a influência do veículo seja crucial para otimização de formulações contendo PA, este aspecto não tem sido investigado experimentalmente. Neste estudo, nós avaliamos a influência do tipo de formulação [emulsões óleo-em-água (o/a), múltipla água-em-óleo-em-água (a/o/a) e pomadas] sobre a liberação e permeação cutânea in vitro da PA e os experimentos foram conduzidos sobre membranas de acetato de celulose e biópsias de pele de camundongos glabros, respectivamente. A liberação de PA a partir da emulsão o/a (51,7% da dose aplicada) foi mais rápida do que aquela observada a partir da emulsão múltipla a/o/a (3,0% da dose aplicada). A permeação cutânea da PA a partir da emulsão o/a (87,1% ± 3,9), através da pele sem estrato córneo, foi 5 a 6 vezes mais alta do que aquela observada para a emulsão múltipla a/o/a (14,7% ± 0,5) e pomada (16,6% ± 0.1), respectivamente. A permeação da PA através da pele normal foi desprezível para todas as formulações avaliadas. Nesta condição, a retenção cutânea a partir da emulsão o/a (0,9% ± 0,1) foi maior do que aquela observada para a emulsão múltipla (0,3% ± 0.1) e pomada. Esses resultados sugerem que um veículo hidrofílico seria uma alternativa interessante para aumentar o transporte e a permeação cutânea da PA.Ointments containing paromomycin (PA) have been used for topical treatment of cutaneous leishmaniasis. Although influence of the vehicle on skin permeation is crucial for optimization of formulations containing PA, this aspect has not been investigated experimentally. In this study, we have evaluated the influence of the formulation type [oil-in-water (o/w), water-in-oil-in-water (w/o/w) emulsions and ointment] on in vitro release and skin permeation of PA and experiments were carried out on cellulose acetate membrane and skin biopsies from hairless mice, respectively. PA release from o/w emulsion (51.7% ± 0.9 of dose applied) was faster than that observed for w/o/w emulsion (3.0% ± 0.5). PA absorption from o/w emulsion (87.1% ± 3.9) through stripped skin was 5 to 6 times higher than that observed for w/o/w multiple emulsion (14.7% ± 0.5) and ointment (16.6% ± 0.1). PA permeation through intact (normal) skin was negligible for all tested formulations. Skin uptake from o/w emulsion (0.9% ± 0.1) was greater than that observed for w/o/w multiple emulsion (0.3% ± 0.1) and ointment (0.1% ± 0.1). These results suggest that a hydrophilic vehicle (o/w emulsion) could be an interesting alternative to improve topical delivery of PA

Hyaluronic acid-coated nanoemulsions loaded with a hydrophobic ion pair of all-trans retinoic acid for improving the anticancer activity

All-trans retinoic acid (ATRA) has been studied for the treatment of cancer, including leukemia and breast cancer. This work aims to develop nanoemulsions (NE) loaded with a hydrophobic ion pair (HIP) of all-trans retinoic acid (ATRA) and a lipophilic amine, stearylamine (SA), and coated with hyaluronic acid (HA) to enhance anticancer activity and reducing toxicity. Blank NE was prepared by spontaneous emulsification and optimized prior to HIP incorporation. NE-ATRA was electrostatically coated with different concentrations of HA. Incorporation of ATRA-SA led to monodisperse NE with small size (129 ± 2 nm; IP 0.18 ± 0.005) and positive zeta potential (35.7 ± 1.0 mV). After coating with 0.5 mg/mL HA solution, the mean diameter slightly increased to 158 ± 5 nm and zeta potential became negative (-19.7 ± 1.2 mV). As expected, high encapsulation efficiency (near 100%) was obtained, confirmed by polarized light microscopy and infrared analysis. Formulations remained stable over 60 days and release of ATRA from NE was delayed after the hydrophilic HA-coating. HA-coated NE-ATRA was more cytotoxic than free ATRA for MDA-MB-231 and MCF-7 breast cancer cell lines, especially in the CD44 overexpressing cells. Blank coated formulations showed no cytotoxicity. These findings suggest that this easily-made HA-coated NE-ATRA formulation is a promising alternative for parenteral administration, thus improving the breast cancer therapy with this drug

Effect of a hydrophilic formulation of topical paromomycin on cutaneous leishmaniasis among patients with contraindications for treatment with pentavalent antimonials

Descrevem-se o efeito terapêutico e os eventos adversos associados com o uso tópico de paromomicina 10% em gel na leishmaniose cutânea. Quinze pacientes com leishmaniose cutânea cumpriram os critérios de inclusão descritos a seguir: contra-indicação para o uso de antimoniato de meglumina, intradermorreação de Montenegro positiva e até quatro lesões ulceradas. A fórmula foi prescrita duas vezes ao dia por 20 dias. Quatorze pacientes estiveram disponíveis para a avaliação do desfecho terapêutico e a proporção de cura foi de 21,4% (3/14), 50% melhoraram até a epitelização completa e a proporção de falha foi de 28,6%. Nove pacientes que não apresentaram cura inicialmente foram re-tratados. Oito receberam uma nova série de paromomicina tópica e um foi tratado com antimoniato de meglumina. Dois pacientes não receberam novo tratamento e tiveram melhora lenta e contínua. Cinco de oito pacientes retratados com paromomicina tópica alcançaram a cura clínica, e três apresentaram falha, incluindo um paciente que tinha apresentado melhora com o primeiro tratamento. Os eventos adversos foram leves e locais em 53,3% dos pacientes e nunca levaram à suspensão do tratamento.The therapeutic effect of and adverse events associated with topical use of 10% paromomycin gel on cutaneous leishmaniasis are described. Fifteen patients with cutaneous leishmaniasis fulfilled the following inclusion criteria: contraindication for the use of meglumine antimoniate, positive Montenegro skin test and up to four ulcerated lesions. The formula was prescribed twice a day for 20 days. Fourteen patients were available for the therapeutic outcome evaluation. The cure rate was 21.4% (3/14); 50% improved as far as complete epithelialization; and the failure rate was 28.6%. Nine patients who did not initially present cure were retreated. Eight received a new series of topical paromomycin and one was treated with meglumine antimoniate. Two patients did not receive any new treatment and had continuous slow improvement. Five out of the eight patients retreated with topical paromomycin achieved clinical cure, and three presented failure, including one patient who had shown any improvement with the first treatment. For 53.3% of the patients, the adverse events were mild and local and never led to treatment suspension

Nanostructured lipid carriers as a novel tool to deliver sclareol: physicochemical characterisation and evaluation in human cancer cell lines

Sclareol (SC) is arousing great interest due to its cytostatic and cytotoxic activities in several cancer cell lines. However, its hydrophobicity is a limiting factor for its in vivo administration. One way to solve this problem is through nanoencapsulation. Therefore, solid lipid nanoparticles (SLN-SC) and nanostructured lipid carriers (NLC-SC) loaded with SC were produced and compared regarding their physicochemical properties. NLC-SC showed better SC encapsulation than SLN-SC and was chosen to be compared with free SC in human cancer cell lines (MDA-MB-231 and HCT-116). Free SC had slightly higher cytotoxicity than NLC-SC and produced subdiploid DNA content in both cell lines. On the other hand, NLC-SC led to subdiploid content in MDA-MB-231 cells and G2/M checkpoint arrest in HCT-116 cells. These findings suggest that SC encapsulation in NLC is a way to allow the in vivo administration of SC and might alter its biological properties

ENTEROPARASITOSES EM ESCOLARES DA CIDADE DE CAMPOS SALES, CE: APLICAÇÃO DO PROJETO PARASITOLOGIA NA ESCOLA

Infecções intestinais causadas por helmintos e protozoários atingem principalmente crianças em idade escolar pela falta de medidas básicas de higiene e sanitárias da sociedade. Com isso em mente o objetivo do Projeto Parasitologia na Escola foi a integração da comunidade acadêmica do curso de Ciências no enfrentamento de parasitoses intestinais e determinar a incidência em crianças de escolas públicas do município de Campos Sales, CE. O Projeto Parasitologia na Escola está dividido na fase de apresentação de atividades lúdicas com apresentação de paródias, peças teatrais e de fantoche. Na fase seguinte, foi realizado aplicação de questionários socioeconômico e de avaliação das condições sanitárias e hábitos de higiene das crianças juntamente a coleta de material parasitológico para análise no método de Hoffman. Nas análises parasitológicas o parasita mais encontrado nas amostras fecais foi Entamoeba hystolitica (45%) escola A e (40%) escola B. Quanto a análise do questionário pode-se ver que as crianças e suas famílias em sua maioria possuem hábitos adequados apesar da falta de saneamento básico, e a dificuldade em certas épocas do ano quanto ao abastecimento de água. E as crianças são tratadas quanto às parasitoses, por isso, o baixo índice de infectados na amostra pesquisada e que os seus pais e a rede pública buscam melhorar a qualidade de vida das suas crianças

Diagnóstico diferencial da Síndrome de Takotsubo e infarto agudo do miocárdio: uma revisão sistemática: Differential diagnosis of Takotsubo Syndrome and acute myocardial infarction: a systematic review

A cardiomiopatia de Takotsubo e o infarto agudo do miocárdio compartilham apresentação clínica e risco de morte semelhantes, embora uma das diferenças mais importantes seja a ausência de doença coronariana obstrutiva na cardiomiopatia de Takotsubo. Neste estudo, tem-se como objetivo analisar a literatura disponível avaliando o diagnóstico diferencial entre pacientes com CTT em comparação com pacientes com infarto agudo do miocárdio. Para isso, foi realizada uma revisão sistemática, utilizando-se a Pubmed e a Medline como base de dados. A partir da análise dos estudos e interpretação de suas principais descobertas, concluiu-se que para pacientes com CTT, outras condições e comorbidades, em vez de apenas dislipidemia e/ou outros fatores de risco estabelecidos, sejam responsáveis por um risco de morte comparável ao de IAM. No entanto, as conclusões desse estudo têm várias limitaçõe

ATLANTIC-PRIMATES: a dataset of communities and occurrences of primates in the Atlantic Forests of South America

Primates play an important role in ecosystem functioning and offer critical insights into human evolution, biology, behavior, and emerging infectious diseases. There are 26 primate species in the Atlantic Forests of South America, 19 of them endemic. We compiled a dataset of 5,472 georeferenced locations of 26 native and 1 introduced primate species, as hybrids in the genera Callithrix and Alouatta. The dataset includes 700 primate communities, 8,121 single species occurrences and 714 estimates of primate population sizes, covering most natural forest types of the tropical and subtropical Atlantic Forest of Brazil, Paraguay and Argentina and some other biomes. On average, primate communities of the Atlantic Forest harbor 2 ± 1 species (range = 1–6). However, about 40% of primate communities contain only one species. Alouatta guariba (N = 2,188 records) and Sapajus nigritus (N = 1,127) were the species with the most records. Callicebus barbarabrownae (N = 35), Leontopithecus caissara (N = 38), and Sapajus libidinosus (N = 41) were the species with the least records. Recorded primate densities varied from 0.004 individuals/km 2 (Alouatta guariba at Fragmento do Bugre, Paraná, Brazil) to 400 individuals/km 2 (Alouatta caraya in Santiago, Rio Grande do Sul, Brazil). Our dataset reflects disparity between the numerous primate census conducted in the Atlantic Forest, in contrast to the scarcity of estimates of population sizes and densities. With these data, researchers can develop different macroecological and regional level studies, focusing on communities, populations, species co-occurrence and distribution patterns. Moreover, the data can also be used to assess the consequences of fragmentation, defaunation, and disease outbreaks on different ecological processes, such as trophic cascades, species invasion or extinction, and community dynamics. There are no copyright restrictions. Please cite this Data Paper when the data are used in publications. We also request that researchers and teachers inform us of how they are using the data. © 2018 by the The Authors. Ecology © 2018 The Ecological Society of Americ

ATLANTIC EPIPHYTES: a data set of vascular and non-vascular epiphyte plants and lichens from the Atlantic Forest

Epiphytes are hyper-diverse and one of the frequently undervalued life forms in plant surveys and biodiversity inventories. Epiphytes of the Atlantic Forest, one of the most endangered ecosystems in the world, have high endemism and radiated recently in the Pliocene. We aimed to (1) compile an extensive Atlantic Forest data set on vascular, non-vascular plants (including hemiepiphytes), and lichen epiphyte species occurrence and abundance; (2) describe the epiphyte distribution in the Atlantic Forest, in order to indicate future sampling efforts. Our work presents the first epiphyte data set with information on abundance and occurrence of epiphyte phorophyte species. All data compiled here come from three main sources provided by the authors: published sources (comprising peer-reviewed articles, books, and theses), unpublished data, and herbarium data. We compiled a data set composed of 2,095 species, from 89,270 holo/hemiepiphyte records, in the Atlantic Forest of Brazil, Argentina, Paraguay, and Uruguay, recorded from 1824 to early 2018. Most of the records were from qualitative data (occurrence only, 88%), well distributed throughout the Atlantic Forest. For quantitative records, the most common sampling method was individual trees (71%), followed by plot sampling (19%), and transect sampling (10%). Angiosperms (81%) were the most frequently registered group, and Bromeliaceae and Orchidaceae were the families with the greatest number of records (27,272 and 21,945, respectively). Ferns and Lycophytes presented fewer records than Angiosperms, and Polypodiaceae were the most recorded family, and more concentrated in the Southern and Southeastern regions. Data on non-vascular plants and lichens were scarce, with a few disjunct records concentrated in the Northeastern region of the Atlantic Forest. For all non-vascular plant records, Lejeuneaceae, a family of liverworts, was the most recorded family. We hope that our effort to organize scattered epiphyte data help advance the knowledge of epiphyte ecology, as well as our understanding of macroecological and biogeographical patterns in the Atlantic Forest. No copyright restrictions are associated with the data set. Please cite this Ecology Data Paper if the data are used in publication and teaching events. © 2019 The Authors. Ecology © 2019 The Ecological Society of Americ

Nanomedicine in Oncocardiology: Contribution and Perspectives of Preclinical Studies

International audienceCancer and cardiovascular diseases are the leading causes of death and morbidity worldwide. Strikingly, cardiovascular disorders are more common and more severe in cancer patients than in the general population, increasing incidence rates. In this context, it is vital to consider the anticancer efficacy of a treatment and the devastating heart complications it could potentially cause. Oncocardiology has emerged as a promising medical and scientific field addressing these aspects from different angles. Interestingly, nanomedicine appears to have great promise in reducing the cardiotoxicity of anticancer drugs, maintaining or even enhancing their efficacy. Several studies have shown the benefits of nanocarriers, although with some flaws when considering the concept of oncocardiology. Herein, we discuss how preclinical studies should be designed as closely as possible to clinical protocols, considering various parameters intrinsic to the animal models used and the experimental protocols. The sex and age of the animals, the size and location of the tumors, the doses of the nanoformulations administered, and the acute vs. the long-term effects of treatments are essential aspects. We also discuss the perspectives offered by non-invasive imaging techniques to simultaneously assess both the anticancer effects of treatment and its potential impact on the heart. The overall objective is to accelerate the development and validation of nanoformulations through high-quality preclinical studies reproducing the clinical conditions