Curzerene antileishmania activity: Effects on Leishmania amazonensis and possible action mechanisms.

Leishmaniasis is a set of infectious diseases with high rates of morbidity and mortality, it affects millions of people around the world. Treatment, mainly with pentavalent antimonials, presents significant toxicity and many cases of resistance. In previous works we have demonstrated the effective and selective antileishmanial activity of Eugenia uniflora L. essential oil, being constituted (47.3%) by the sesquiterpene curzerene. Considering the high rate of parasite inhibition demonstrated for E. uniflora essential oil, and the significant presence of curzerene in the oil, this study aimed to evaluate its antileishmania activity and possible mechanisms of action. Curzerene was effective in inhibiting the growth of promastigotes (IC50 3.09 ± 0.14 µM) and axenic amastigotes (EC50 2.56 ± 0.12 µM), with low cytotoxicity to RAW 264.7 macrophages (CC50 83.87 ± 4.63 µM). It was observed that curzerene has direct effects on the parasite, inducing cell death by apoptosis with secondary necrotic effects (producing pores in the plasma membrane). Curzerene proved to be even more effective against intra-macrophage amastigote forms, with an EC50 of 0.46 ± 0.02 µM. The selectivity index demonstrated by curzerene on these parasite forms was 182.32, being respectively 44.15 and 8.47 times more selective than meglumine antimoniate and amphotericin B. The antiamastigote activity of curzerene was associated with immunomodulatory activity, as it increased TNF-α, IL-12, and NO levels, and lysosomal activity, and decreased IL-10 and IL-6 cytokine levels detected in macrophages infected and treated. In conclusion, our results demonstrate that curzerene is an effective and selective antileishmanial agent, a candidate for in vivo investigation in models of antileishmanial activity.

Macroscopic Evaluation of Atherosclerosis in the Arteries: An Autopsy Assessment Tool. / Avaliação Macroscópica da Aterosclerose nas Artérias: Uma Ferramenta de Avaliação na Autópsia.

BACKGROUND: Atherosclerosis, in some cases, is an asymptomatic condition, and it is important to know the degree of arterial impairment caused by plaques and its association with risk factors. Autopsy examination provides understanding of basic disease processes and assessment to data about macroscopic characteristic of atherosclerotic involvement. OBJECTIVE: To macroscopically assess and standardize atherosclerotic involvement of aorta, carotid and iliac arteries and compare with age, gender and causes of death. METHODS: We collected 53 aortic arteries, 53 right carotid arteries, 53 left carotid arteries, 53 right iliac arteries and 53 left iliac arteries. For this assessment, the extension of fatty streaks, atheromatous plaques, fibrosis and calcification were considered, being the reference to score the degree of atherosclerotic involvement. Many degrees of atherosclerosis and accurate values were observed for mild, moderate and severe classification. For statistical analysis, data were analyzed using the software GraphPad Prism® 7.0. Differences were considered statistically significant if p-value was less than 5% (p <0.05). RESULTS: Carotid arteries had greater atherosclerotic involvement compared to the other arteries (K = 15.73, p = 0.0004). Atherosclerosis was progressive and significant with increasing age (carotid arteries: t = 6.321; p <0.0001; aorta: U = 83.5; p <0.0001; iliac: U = 306; p <0.0001) and as cause of cardiovascular death (carotids: t = 5.047; p <0.0001; aorta: U = 98.5; p = 0.0068; iliac: U = 467.5; p = 0.0012). CONCLUSION: Macroscopic assessment of atherosclerosis is an innovative and low-cost way of direct visualization of atherosclerotic plaques, enabling an association with risk factors such as increasing age and cardiovascular diseases, providing important data for clinical practice.

FUNDAMENTO: A aterosclerose, em alguns casos, é uma condição assintomática, sendo necessário conhecer o grau de comprometimento arterial provocado pelas placas e sua associação com os fatores de risco. O exame de autópsia permite a compreensão dos processos básicos de doenças, assim como a avaliação e fornecimento de dados sobre a característica macroscópica do acometimento aterosclerótico. OBJETIVO: Avaliar macroscopicamente e padronizar o acometimento aterosclerótico das artérias aorta, carótidas e ilíacas e comparar com a idade, o sexo e a causa de morte. MÉTODOS: Foram coletados 53 artérias aorta, 53 artérias carótida direita, 53 artérias carótida esquerda, 53 artérias ilíaca direita e 53 artérias ilíaca esquerda. Para essa avaliação, foi considerada a extensão de estrias lipídicas, de placas ateromatosas, de fibrose e de calcificação, as quais serviram de referência para pontuar a intensidade do acometimento aterosclerótico. Foram observados vários graus da aterosclerose e valores acurados para a classificação discreta, moderada e acentuada. Para a análise estatística, os dados foram analisados utilizando-se o software GraphPad Prism ® 7.0. As diferenças foram consideradas estatisticamente significativas quando "p" foi menor que 5% (p<0,05). RESULTADOS: As artérias carótidas apresentaram maior acometimento aterosclerótico em comparação às outras artérias avaliadas (K=15,73, p=0,0004). A ocorrência da aterosclerose se mostrou progressiva e significativa com o decorrer da idade (carótidas: t=6,321; p<0,0001; aortas: U=83,5; p<0,0001; ilíacas: U=306; p<0,0001) e na causa de morte cardiovascular (carótidas: t=5,047; p<0,0001; aortas: U=98,5; p=0,0068; ilíacas: U=467,5; p=0,0012). CONCLUSÃO: A avaliação macroscópica da aterosclerose trata-se de uma forma inovadora e de baixo custo de avaliação através da visualização direta das placas ateroscleróticas, possibilitando uma associação com fatores de risco como idade avançada e doenças cardiovasculares, fornecendo dados importantes para a prática clínica.

Avaliação Macroscópica da Aterosclerose nas Artérias: Uma Ferramenta de Avaliação na Autópsia / Macroscopic Evaluation of Atherosclerosis in the Arteries: An Autopsy Assessment Tool

Resumo Fundamento A aterosclerose, em alguns casos, é uma condição assintomática, sendo necessário conhecer o grau de comprometimento arterial provocado pelas placas e sua associação com os fatores de risco. O exame de autópsia permite a compreensão dos processos básicos de doenças, assim como a avaliação e fornecimento de dados sobre a característica macroscópica do acometimento aterosclerótico. Objetivo Avaliar macroscopicamente e padronizar o acometimento aterosclerótico das artérias aorta, carótidas e ilíacas e comparar com a idade, o sexo e a causa de morte. Métodos Foram coletados 53 artérias aorta, 53 artérias carótida direita, 53 artérias carótida esquerda, 53 artérias ilíaca direita e 53 artérias ilíaca esquerda. Para essa avaliação, foi considerada a extensão de estrias lipídicas, de placas ateromatosas, de fibrose e de calcificação, as quais serviram de referência para pontuar a intensidade do acometimento aterosclerótico. Foram observados vários graus da aterosclerose e valores acurados para a classificação discreta, moderada e acentuada. Para a análise estatística, os dados foram analisados utilizando-se o software GraphPad Prism ® 7.0. As diferenças foram consideradas estatisticamente significativas quando "p" foi menor que 5% (p<0,05). Resultados As artérias carótidas apresentaram maior acometimento aterosclerótico em comparação às outras artérias avaliadas (K=15,73, p=0,0004). A ocorrência da aterosclerose se mostrou progressiva e significativa com o decorrer da idade (carótidas: t=6,321; p<0,0001; aortas: U=83,5; p<0,0001; ilíacas: U=306; p<0,0001) e na causa de morte cardiovascular (carótidas: t=5,047; p<0,0001; aortas: U=98,5; p=0,0068; ilíacas: U=467,5; p=0,0012). Conclusão A avaliação macroscópica da aterosclerose trata-se de uma forma inovadora e de baixo custo de avaliação através da visualização direta das placas ateroscleróticas, possibilitando uma associação com fatores de risco como idade avançada e doenças cardiovasculares, fornecendo dados importantes para a prática clínica.

Abstract Background Atherosclerosis, in some cases, is an asymptomatic condition, and it is important to know the degree of arterial impairment caused by plaques and its association with risk factors. Autopsy examination provides understanding of basic disease processes and assessment to data about macroscopic characteristic of atherosclerotic involvement. Objective To macroscopically assess and standardize atherosclerotic involvement of aorta, carotid and iliac arteries and compare with age, gender and causes of death. Methods We collected 53 aortic arteries, 53 right carotid arteries, 53 left carotid arteries, 53 right iliac arteries and 53 left iliac arteries. For this assessment, the extension of fatty streaks, atheromatous plaques, fibrosis and calcification were considered, being the reference to score the degree of atherosclerotic involvement. Many degrees of atherosclerosis and accurate values were observed for mild, moderate and severe classification. For statistical analysis, data were analyzed using the software GraphPad Prism® 7.0. Differences were considered statistically significant if p-value was less than 5% (p <0.05). Results Carotid arteries had greater atherosclerotic involvement compared to the other arteries (K = 15.73, p = 0.0004). Atherosclerosis was progressive and significant with increasing age (carotid arteries: t = 6.321; p <0.0001; aorta: U = 83.5; p <0.0001; iliac: U = 306; p <0.0001) and as cause of cardiovascular death (carotids: t = 5.047; p <0.0001; aorta: U = 98.5; p = 0.0068; iliac: U = 467.5; p = 0.0012). Conclusion Macroscopic assessment of atherosclerosis is an innovative and low-cost way of direct visualization of atherosclerotic plaques, enabling an association with risk factors such as increasing age and cardiovascular diseases, providing important data for clinical practice.

Morphological and Histopathological Study of Autopsied Patients with Atherosclerosis and HIV.

BACKGROUND: Chronic infection by HIV evolves with a vascular inflammatory action causing endothelial dysfunction. The action of the virus, as well as the side effects of antiretroviral drugs, contribute to the progression of cardiovascular diseases. The present study aimed to evaluate the percentage of collagen fibers and the density of mast cells, chymase and tryptase, in aortas of patients with and without HIV, and also patients with and without atherosclerosis. METHODS: Aortic fragments were obtained from autopsied patients aged 22-69 years and selected regardless of the cause of death or underlying disease. The samples were divided into four groups, (1) Group with HIV and with atherosclerosis; (2) Group with HIV and without atherosclerosis; (3) Group without HIV and with atherosclerosis; (4) Group without HIV and without atherosclerosis (Control). The percentage of collagen fibers was analyzed in the intima-media layer and the density of mast cells was analyzed in all aortic layers. Graphpad Prism 5.0® software was used for statistical analysis. RESULTS: There were more collagen fibers in HIV patients, with or without atherosclerosis. The group with HIV and atherosclerosis presented a higher density of chymase and tryptase mast cells. The correlation between collagen fibers and age was negative in the non-HIV group and with atherosclerosis. CONCLUSION: The inflammatory process resulting from HIV infection may be relevant in the alteration of aortic collagen fibers and in triggering or accelerating atherosclerosis. The study is important because HIV patients have increased risks for the development of cardiovascular diseases, and follow-up is necessary to prevent such diseases.

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

Analysis of mast cells and myocardial fibrosis in autopsied patients with hypertensive heart disease.

OBJECTIVE: To analyze the percentage of collagen fibers and mast cell density in the left ventricular myocardium of autopsied patients with and without hypertensive heart disease. METHODS: Thirty fragments of left ventricular myocardium were obtained from individuals autopsied at the Clinical Hospital of the Federal University of Triângulo Mineiro (UFTM) in the period from 1987 to 2017. Individuals were divided into two groups: those with hypertensive heart disease (HD) and those with no heart disease (ND). Subjects were also assessed according to age, gender and race (white and non-white). Collagen fibers were quantified by computed morphometry and mast cell density was assessed by immunohistochemical methods. RESULTS: There were significantly more collagen fibers in the left ventricle in the HD group than in the ND group (p<0.001). Mast cell density was significantly higher in the left ventricle of individuals with HD immunolabeled with anti-chymase and anti-tryptase antibodies (p=0.02) and also of those immunolabeled only with anti-tryptase antibodies (p=0.03). Analyzing the HD group, there was a significant positive correlation between the percentage of collagen fibers in the left ventricle and mast cell density immunolabeled by anti-chymase and anti-tryptase antibodies (p=0.04) and also mast cell density immunolabeled only with anti-tryptase antibodies (p=0.02). CONCLUSIONS: Mast cells are involved in the development of hypertensive heart disease, contributing to the remodeling of collagen fibers in this disease.

Morphological and histopathological evaluation of autopsied patients with hypertensive cardiopathy.

BACKGROUND: Physiopathological processes in hypertensive heart disease are controlled by complex interactions between cardiomyocytes, extracellular matrix, microvasculature and other cells present in the myocardium. OBJECTIVE: To analyze morphological changes in hypertensive cardiopathy and to describe and compare findings in order to help clarify determinant factors. METHODS: 42 fragments of the left ventricular myocardium and circumflex branch of the left coronary artery were obtained from individuals autopsied at the Clinical Hospital of the Federal University of Triângulo Mineiro (UFTM) in the period ranging from 1984 to 2018. Groups were split into individuals with hypertensive heart disease (HD) and individuals without heart disease (ND). Wall thickness was measured with a digital caliper and Computed Tomography. Quantification of collagen fibers was conducted by computerized morphometry and mast cell density was assessed by immunohistochemical methods. RESULTS: There was a significant increase of heart weight in the HD group compared to the ND group, (p = 0.0002). There was a significant increase of thickness of the middle third of the free wall in the HD group compared to the ND group, (p = 0.04). There was a significant increase of collagen fibers in the left ventricle in the HD group compared to the ND group, (p < 0.0001). Concerning mast cell density, there was a significant increase in the left ventricle of individuals with HD immuno-labeled by the set anti-chymase/anti-tryptase (p < 0.0001). There was a significant increase of mast cell density in the circumflex branch of the left coronary artery of individuals with HD immuno-labeled by the set anti-chymase/anti-tryptase (p = 0.01). CONCLUSIONS: Mast cells are involved in the development of hypertensive heart disease, contributing to the remodeling of collagen fibers in this disease.

Analysis of the collagen fibers on autopsied patients' uterus with the Acquired Immunodeficiency Syndrome / Análise das fibras colágenas do útero de pacientes autopsiadas com a Síndrome da Imunodeficiência Adquirida

Abstract Objectives: to compare the percentage of collagen fibers in the autopsied women's uterine body and cervix with and without the Acquired Immunodeficiency Syndrome (Aids). Methods: 30 autopsied women's medical files were selected from 1988 to 2013. 30 fragments of the uterine body and 30 cervix were collected and then divided into two groups, 15 with Aids and 15 without, The quantification of the collagen fibers of the uterine body and cervix was performed on slides stained with picrosirius, using the KS-300® system. Results: the percentage of collagen fibers was lower for cervix (U=336544; p=0.001) and higher for the uterine body (U=308726,5; p=0.004) in the retroviral group when compared to the group without the disease. The percentage was higher for cervix than the uterine body in the group with Aids (t=0,4793; p=0.0031). the same result was found in the group without Aids (t=2,397; p=0.0637). Conclusions: the increase in the percentage of collagen fibers in the uterine body of women with Aids' indicates an immune response for viral infection and reveals a failure in keeping the infection restricted to the cervix. The interpretation of the histochemical and morphometric parameters can be useful in the diagnosis associated to HIV infection, contributing for clinical improvement and life expectancy.

Resumo Objetivos: comparar a porcentagem de fibras colágenas no corpo e colo uterino de mulheres autopsiadas com e sem a Síndrome da Imunodeficiência Adquirida (Aids). Métodos: foram selecionados 30 prontuários de mulheres autopsiadas no período de 1988 a 2013. Foram coletados 30 fragmentos do corpo uterino e 30 do colo uterino, dividido em dois grupos, 15 com Aids e 15 sem. A quantificação das fibras colágenas do corpo e colo uterino foi feita nas lâminas coradas por picrosirius, utilizando-se o sistema KS-300®. Resultados: a porcentagem de fibras colágenas foi menor no colo (U=336544; p=0,001) e maior no corpo uterino (U=308 726,5; p=0,004) no grupo com a retrovirose quando comparado ao grupo sem a doença. A porcentagem no grupo com Aids foi maior no colo uterino do que no corpo (t=0,4793; p=0,0031). Sendo o mesmo resultado encontrado para o grupo sem Aids (t=2.397; p=0,0637). Conclusões: um aumento da porcentagem de fibras colágenas no corpo uterino das mulheres com Aids indica uma resposta imune frente a infecção viral e revela uma falha em manter a infecção restrita ao colo. A interpretação dos parâmetros histoquímicos e morfométricos podem ser úteis no diagnóstico das condições associadas à infecção pelo HIV, contribuindo para a melhora clínica e expectativa de vida.

Improved Cytotoxic Effect of Doxorubicin by Its Combination with Sclareol in Solid Lipid Nanoparticle Suspension.

This work aims to develop, characterize, and evaluate the anticancer activity of solid lipid nanoparticles (SLN) containing doxorubicin (DOX), an antitumoral from the antracycline class, and sclareol (SC), a lipophilic labdene diterpene (SLN-DOX-SC). The SLN were characterized by Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD), Small Angle X-ray Diffraction (SAXS), in vitro release, transmission electron microscopy, and polarized light microscopy. Evaluation of cell viability was performed in two cell cultures: MCF-7 (human breast cancer) and 4T1 (murine breast cancer). The SLN showed a size in the range of 128 nm, negative zeta potential, DOX encapsulation efficiency (EE) of 99%, and drug loading (DL) of 66 mg/g. Characterization of the formulation by DSC, XRD, and SAXS revealed the presence of DOX inside the nanoparticles of SLN and suggested increased expulsion/release of this drug when associated with SC. The release profiles revealed that the SLN-DOX-SC showed controlled release of DOX at pH 7.4 with enhanced drug release at low pH, useful for cancer treatment. The SLN-DOX-SC demonstrated to be more effective than the free DOX against 4T1 cells. So, the developed SLN efficiently encapsulate DOX and SC and show good potential as an alternative for cancer treatment.

Implications of alcoholic cirrhosis in atherosclerosis of autopsied patients.

INTRODUCTION:: Alcoholism is a major public health problem, which has a high social cost and affects many aspects of human activity. Liver disease is one of the first consequences of alcohol abuse, and steatosis, liver cirrhosis and hepatitis may occur. Other organs are also affected with pathological changes, such as pancreatitis, cardiomyopathies, dyslipidemias and atherosclerosis. OBJECTIVE:: To identify the occurrence and degree of atherosclerosis in alcohol-dependent individuals with liver cirrhosis, observing macroscopic and microscopic changes in lipid and collagen deposits and in the liver. We also aimed to verify the association of lipid and collagen fiber deposits with gender, age and body mass index, and to relate alcoholism, liver cirrhosis and atherosclerosis. METHOD:: We performed a study based on autopsy reports of patients with alcoholic liver cirrhosis, with analysis of aorta and liver fragments to verify the occurrence and degree of atherosclerosis, as well as collagen contents. RESULTS:: Microscopic atherosclerosis was higher in young subjects (early injury) and in patients with alcoholic liver cirrhosis. The macroscopic analysis of atherosclerosis in aortas showed that patients in more advanced age groups presented more severe classifications. Atherosclerosis, both micro and macroscopically, and the percentage of fibrosis in the liver and aorta were more expressive in females. CONCLUSION:: Cirrhotic patients presented a higher percentage of fibrosis and lipidosis, and may represent a group susceptible to the accelerated progression of cardiovascular diseases. Investigative studies contribute to targeting health-promoting interventions, reducing the mortality and costs of treating cardiovascular disease.

Implications of alcoholic cirrhosis in atherosclerosis of autopsied patients / Implicações da doença hepática alcoólica na aterosclerose de pacientes autopsiados

Summary Introduction: Alcoholism is a major public health problem, which has a high social cost and affects many aspects of human activity. Liver disease is one of the first consequences of alcohol abuse, and steatosis, liver cirrhosis and hepatitis may occur. Other organs are also affected with pathological changes, such as pancreatitis, cardiomyopathies, dyslipidemias and atherosclerosis. Objective: To identify the occurrence and degree of atherosclerosis in alcohol-dependent individuals with liver cirrhosis, observing macroscopic and microscopic changes in lipid and collagen deposits and in the liver. We also aimed to verify the association of lipid and collagen fiber deposits with gender, age and body mass index, and to relate alcoholism, liver cirrhosis and atherosclerosis. Method: We performed a study based on autopsy reports of patients with alcoholic liver cirrhosis, with analysis of aorta and liver fragments to verify the occurrence and degree of atherosclerosis, as well as collagen contents. Results: Microscopic atherosclerosis was higher in young subjects (early injury) and in patients with alcoholic liver cirrhosis. The macroscopic analysis of atherosclerosis in aortas showed that patients in more advanced age groups presented more severe classifications. Atherosclerosis, both micro and macroscopically, and the percentage of fibrosis in the liver and aorta were more expressive in females. Conclusion: Cirrhotic patients presented a higher percentage of fibrosis and lipidosis, and may represent a group susceptible to the accelerated progression of cardiovascular diseases. Investigative studies contribute to targeting health-promoting interventions, reducing the mortality and costs of treating cardiovascular disease.

Resumo Introdução: O alcoolismo é um grande problema de saúde pública, de elevado custo social e que afeta vários aspectos da atividade humana. Hepatopatia é uma das primeiras consequências do abuso de álcool, podendo ocorrer esteatose, cirrose hepática e hepatite. Outros órgãos, porém, também são afetados, ocorrendo alterações patológicas, como pancreatite, cardiomiopatias, dislipidemias e aterosclerose. Objetivo: Identificar a ocorrência e a intensidade de aterosclerose em alcoolistas com cirrose hepática, observando alterações macro e microscópicas do depósito lipídico e de fibras colágenas e fígado. Verificar a associação de depósito lipídico e de fibras colágenas com gênero, idade e índice de massa corporal (IMC). Relacionar alcoolismo, cirrose hepática e aterosclerose. Método: Foi realizado estudo com base em laudos de autópsias de pacientes com cirrose hepática alcoólica, sendo estudados aortas e fígados para verificar a ocorrência e a intensidade de aterosclerose, bem como a quantidade de colágeno encontrada. Resultados: A aterosclerose microscópica foi maior em jovens (lesão inicial) e em pacientes com cirrose hepática alcoólica. A análise macroscópica da aterosclerose nas aortas mostrou que pacientes com faixas etárias mais avançadas apresentaram classificações mais intensas. A aterosclerose, tanto micro quanto macroscopicamente, e a porcentagem de fibrose no fígado e na aorta foram mais expressivas no gênero feminino. Conclusão: Os pacientes cirróticos apresentaram maior porcentagem de fibrose e lipidose, e podem representar um grupo susceptível à acelerada progressão de doenças cardiovasculares. Estudos investigativos contribuem para o direcionamento das intervenções promotoras da saúde, reduzindo a mortalidade e os custos no tratamento das doenças cardiovasculares.

Hydrophobic ion pairing as a strategy to improve drug encapsulation into lipid nanocarriers for the cancer treatment.

INTRODUCTION: Incorporation of anticancer drugs with low lipophilicity in lipid nanocarriers is usually low, which limits the utilization of this strategy in cancer therapy. However, the complexation of these drugs with lipophilic ion pairs containing ionizable groups has been reported to improve their incorporation in nanocarriers such as solid lipid nanoparticles (SLNs), nanostructured lipid nanocarriers (NLCs), and nanoemulsions (NEs). Therefore, those nanocarriers have shown an increase in efficacy and lower toxicity compared with the free drugs, particularly if the counter ion utilized has anticancer activity. Areas covered: This review covers, from 1999 to the present, the utilization of the hydrophobic ion pair (HIP) approach to enhance the encapsulation of anticancer drugs in lipid nanostructured delivery systems, SLN, NLC, and NE; the benefits achieved; and challenges to improve the anticancer therapy. Expert opinion: The HIP strategy has consistently demonstrated enhancement of the encapsulation efficiency in NLCs associated with increased anticancer activity of drugs such as doxorubicin, all-trans retinoic acid, methotrexate, vincristine and others. From this point on, conducting further physicochemical characterization studies of the formed ion pair as well as proceeding with the in vivo efficacy, toxicity and pharmacokinetics studies are expected.

Liposomes Containing Gadodiamide: Preparation, Physicochemical Characterization, and In Vitro Cytotoxic Evaluation.

BACKGROUND: The aim of this study was to develop, characterize and assess the cytotoxic activity of pHsensitive (pHL-Gd), stealth pH-sensitive (SpHL-Gd), and conventional (convL-Gd) liposomes containing gadodiamide (Gd-DTPA-BMA). METHODS: Formulations were prepared by reverse-phase evaporation method and their physicochemical properties were evaluated by means of particle size, zeta potential, and Gd-DTPA-BMA entrapment. SpHL-Gd was considered being the most promising liposome, since it combines stealth and fusogenic characteristics that might contribute to achieve higher therapeutic efficiency. Their drug encapsulation percentages have been optimized satisfactorily. The addition of Gd-DTPA-BMA at 125 µmol/mL in the SpHL-Gd preparation allowed obtaining liposomes with appropriate encapsulation percentage (20.3 ± 0.1%) and entrapment (25.4 ± 0.1 µmol/mL). RESULTS: The cytotoxic studies on the 4T1 breast cancer cell line demonstrated that liposomes-loaded with Gd-DTPA-BMA inhibited cancer cell. pHL-Gd and SpHL-Gd liposomes showed higher activity than convL-Gd and free Gd-DTPA-BMA, indicating that the pH-sensitive characteristic was important to improve intracellular delivery. CONCLUSION: The presence of polyethylene glycol (PEG) in the SpHL-Gd formulation did not affect the pH-sensitivity and internalization. Therefore, the results of this study suggest the feasibility of liposomes containing Gd-DTPA-BMA as a new promising controlled delivery system.

Significado de vivenciar um grupo terapêutico junto a um projeto de extensão: relato de ex-periência / Significado de experimentar un grupo terapéutico junto con un proyecto de extensión: relato de experiencia / The meaning of participating in group therapy within an outreach project: an experience re-port

O trabalho objetivou descrever o significado de vivenciar um grupo terapêutico como formade capacitação junto a um projeto de extensão. Trata-se de um relato da experiência devivenciar um grupo terapêutico realizado com 11 pessoas dentre elas graduandas, mestrandase docentes do Curso de Enfermagem, integrantes de um Projeto de Extensão da UniversidadeFederal do Triângulo Mineiro. O intuito foi possibilitar ao grupo o conhecimento dessatécnica como forma de assistência de enfermagem, por meio da capacitação da equipe parautilização dessa estratégia, após refletirem seus benefícios enquanto integrantes do grupo.Para avaliar os resultados utilizou-se uma questãonorteadora contemplando o significado departicipar do treinamento. A análise dos dados decorreu segundo análise de conteúdo propostapor Minayo. Foram observadas como resultados as seguintes categorias: I - Compartilharexperiências; II - Identificação; III - Auto avaliação. A partir da experiência foi possívelevidenciar crescimento pessoal e profissional dos integrantes .

The objective of this study was to describe the meaning of participating in group therapytraining as part of an outreach project. This is anexperience report of 11 people, includingnursing undergraduate and graduate students and faculty, all of which were members of anOutreach Project by Universidade Federal do Triângulo Mineiro. The purpose was to allowthe group to learn about group therapy as a nursingcare approach and to train the team to usethis strategy after reflecting, as a group, about the benefits of the strategy. The results wereevaluated using a guiding question that contemplated the meaning of participating in thetraining program. Data analysis was performed usingcontent analysis as proposed by Minayo. The following categories were found: I – Sharing experiences; II - Identification; III – Self-evaluation. The experience revealed the personal and professional growth of the participants .

Se objetivó describir el significado de experimentar un grupo terapéutico como modo decapacitación conjuntamente con un proyecto de extensión. Relato de experiencia de compartircon un grupo terapéutico de 11 personas, entre ellas alumnas de grado, de maestría y docentesdel Curso de Enfermería, integrantes de un Proyectode Extensión de la Universidad Federaldel Triángulo Mineiro. El objetivo fue ofrecer al grupo el conocimiento de esa técnica comoforma de atención de enfermería, mediante capacitación del equipo para utilizar la estrategia,luego de reflexionar sobre sus beneficios en su carácter de miembros del grupo. Para evaluarlos resultados se utilizó una pregunta orientadora,considerando el significado de participardel entrenamiento. Análisis de datos realizado según análisis de contenido de Minayo.Surgieron tres categorías: I- Compartir experiencias; II- Identificación; III- Autoevaluación. Apartir de la experiencia, fue posible evidenciar crecimiento personal y profesional de losparticipantes .