Desenvolvimento de organogel injetável subcutâneo de Pluronic®-F127 e lecitina de soja (OPL) contendo meloxicam para uso veterinário / Development of a veterinary organogel formulation containing soy lecithin, Pluronic® F-127 and meloxicam for the treatment of acute and chronic pain in small animals

O organogel é formado por uma matriz tridimensional composta de filamentos que se auto-organizam em uma rede entrelaçada e que, por seu tipo de estrutura, pode ser utilizado com o objetivo de atuar como um implante que se forma in situ, sendo capaz de se comportar como uma forma farmacêutica de liberação prolongada. Esse trabalho tem, por tanto, o objetivo desse trabalho foi desenvolver, caracterizar, quantificar e traçar perfis de dissolução para formulações de organogel contendo meloxicam como principio ativo. O material está dividido em quatro capítulos, sendo apresentada inicialmente (I) revisão da literatura a respeito da lecitina de origem vegetal, com suas principais fontes de obtenção, como soja, girassol e colza, e também seu uso farmacêutico na obtenção de formulações como organogéis, microemulsões e lipossomas. Os demais capítulos abordam (II) desenvolvimento e otimização de uma formulação de organogel contendo lecitina de soja e Pluronic® F-127 como formadores da matriz tridimensional e meloxicam como principio ativo. (III) Desenvolvimento e validação de um método de quantificação do teor de meloxicam por cromatografia líquida de alta eficiência (CLAE). (IV) Desenvolvimento de um método de dissolução para formulações de organogel, que fosse capaz de ser utilizado na caracterização do perfil de dissolução de diferentes formulações. Com os resultados obtidos, foi possível desenvolver formulações de organogel contendo lecitina de soja, Pluronic® F-127 e meloxicam, assim como um método analítico validado para as analises de teor. Por fim, foram obtidos também os perfis de dissolução de duas formulações mais promissoras

Organogels are formed by a three-dimensional matrix composed of filaments that selforganize in an interlaced network and that, due to its type of structure, can be used with the objective of acting as an implant that forms in situ, being able to behave as an extendedrelease dosage form. This work has, therefore, the objective of this work was to develop, characterize, quantify and trace dissolution profiles for organogel formulations containing meloxicam as active ingredient. The material is divided into four chapters, initially presented (I) review of the literature on lecithin of plant origin, with its main sources of production, such as soybean, sunflower and rapeseed, and also its pharmaceutical use in obtaining formulations such as organogels , microemulsions and liposomes. The remaining chapters address (II) development and optimization of an organogel formulation containing soy lecithin and Pluronic® F-127 as three-dimensional matrix formers and meloxicam as an active ingredient. (III) Development and validation of a method for quantification of meloxicam content by high performance liquid chromatography (HPLC). (IV) Development of a dissolution method for organogel formulations, capable of being used to characterize the dissolution profile of different formulations. With the results obtained, it was possible to develop organogel formulations containing soy lecithin, Pluronic® F-127 and meloxicam, as well as a validated analytical method for content analysis. Finally, the dissolution profiles of two more promising formulations were also obtained

LECISAN® y sus potencialidades terapéuticas para el abordaje farmacológico de la obesidad / LECISAN® and its therapeutic potentialities for the pharmacological approach to obesity

Introducción: La obesidad se ha identificado como un estado crónico de inflamación sistémica conocido como lipoinflamación. En los últimos tiempos ha cobrado relevancia el descubrimiento de moléculas clave que actúan como blancos terapéuticos, así como sus conexiones y mecanismos existentes. Por otra parte, es sabido lo difícil que es la obtención de nuevos fármacos naturales como alternativas o terapias complementarias en enfermedades crónicas no transmisibles como la obesidad y las dislipemias. El LECISAN® destaca como candidato por sus potencialidades. Objetivos: Valorar los resultados de investigaciones preclínicas y clínicas que avalan el uso del LECISAN®. Métodos: Se realizó una revisión sistemática y crítica de las evidencias de impacto de los efectos de la lecitina de soya. Se consultaron artículos publicados preferentemente en los últimos diez años en las bases de datos EBSCO, Google Scholar, Latindex, Redalyc, DOAJ, Dialnet, WorldCat, LILACS, SciELO y OATD. Conclusiones: El LECISAN® es un producto natural que rebasa el contexto de su empleo como suplemento nutricional, pero requiere nuevas investigaciones en el campo de la farmacología. Resultan contradictorios y poco concluyentes los resultados referentes a sus posibles efectos y usos(AU)

Introduction: Obesity has been identified as a chronic state of systemic inflammation known as lipoinflammation. In recent times, the discovery of key molecules acting as therapeutic targets, as well as their connections and existing mechanisms, has gained relevance. On the other hand, it is known how difficult it is to obtain new natural drugs as alternatives or complementary therapies in chronic noncommunicable diseases such as obesity and dyslipidemias. LECISAN® stands out as a candidate, for its potentialities. Objective: To assess the results of preclinical and clinical investigations that support the use of LECISAN®. Methods: A systematic and critical review of evidence about the impact of the effects of soy lecithin was carried out. Articles published preferably in the last ten years were consulted, from the EBSCO, Google Scholar, Latindex, Redalyc, DOAJ, Dialnet, WorldCat, LILACS, SciELO and OATD databases. Conclusions: LECISAN® is a natural product that goes beyond the context of its use as a nutritional supplement, but requires new research in the field of pharmacology. The results regarding its possible effects and uses are contradictory and inconclusive, based on hypotheses that relate an emulsifying action with the phospholipids present in the mixture, the antioxidant effects with isoflavones, the anti-inflammatory effects with the polyunsaturated fatty acids that regulate lipid metabolism, as well as the activation of the phospholipase A2 system with the consequent production of inflammatory cytosines(AU)

Utilization of agroindustrial byproducts for the production of lipase by a new strain of Pseudomonas sp / Utilização de subprodutos agroindustriais para a produção de lipase por uma nova cepa de Pseudomonas sp

This study aimed to evaluate the production of lipases by a new strain of Pseudomonas sp. using fermentation medium containing byproducts of poultry meat or soybean oil industry. The results indicate that chicken fat and soybean gum induced 48.3 U/mL and 93.3 of lipase activity, respectively. However, the higher lipase production was obtained when the crude lecithin gum was used, archiving 272.6 U/ml of activity after 24 hours. The partial biochemical characterization of the enzyme showed that the optimum reaction conditions were pH 9.0 and 35 °C. The enzyme was stable at temperatures between 25 to 75 °C and at pH from 6 to 9. The enzyme also showed good stability in organic solvents, such as acetronitrile, hexane, ethanol and isopropanol. This study indicates that the byproducts tested are promising for the production of lipase and can contribute to the reduction of enzymatic production costs on a large scale, increase the value of these byproducts and reduce potential environmental impacts caused by its accumulation in nature.(AU)

Este estudo teve como objetivo avaliar a produção de lipases por uma nova cepa de Pseudomonas sp. utilizando meio de fermentação contendo subprodutos de industrialização de carne de frango e óleo de soja. Os resultados indicaram que a gordura de frango e a goma de soja induziram 48,3 U/mL e 93,3 U/ml de atividade lipásica, respectivamente. No entanto, a produção de lipase mais elevada foi obtida quando a goma de lecitina bruta foi utilizada, induzindo 272,6 U/ml de atividade após 24 horas. A caracterização bioquímica parcial da enzima mostrou que as condições de reação ótimas foram de pH 9,0 e 35 °C. A enzima foi estável nas temperaturas entre 25 a 75 °C e pH de 6 a 9. A enzima mostrou boa estabilidade em solventes orgânicos, tais como acetonitrila, hexano, etanol e isopropanol. Este estudo indicou que os subprodutos testados são promissores para a produção de lipase e podem contribuir para a redução dos custos de produção enzimática em larga escala, aumentar o valor desses subprodutos e reduzir potenciais impactos ambientais causados por sua acumulação na natureza.(AU)

Tableta masticable de lecitina de soya: de subproducto a producto farmacéutico / Chewable pill of soy phosphatidylcholine: from by-product to pharmaceutical product

En el Laboratorio Farmacéutico Oriente de Santiago de Cuba se acometió el desarrollo de una tableta masticable de lecitina de soya con fines de registro y ulterior producción, lo cual se realizó durante el bienio 2011-2013. Se utilizaron excipientes de calidad farmacéutica, los métodos analíticos de la Farmacopea de los Estados Unidos, edición 35/Formulario Nacional, edición 30 del 2012, así como la tecnología de granulación húmeda y compresión directa. La lecitina fue caracterizada como materia prima farmacéutica y la tableta desarrollada cumplió con los atributos de calidad establecidos, por lo cual se registró con estabilidad comprobada de 2 años. Se suministró valor agregado a esta sustancia, con riesgo potencial de acumulación para el medio ambiente, como producto farmacéutico nuevo en Cuba

The development of a chewable pill of soy phosphatidylcholilne was undertaken in Oriente Pharmaceutical Laboratory from Santiago de Cuba with registration ends and subsequent production, that was carried out during the biennium 2011-2013. Excipients of pharmaceutical quality, the analytic methods of the United States Pharmacopoeia, edition 35/National Form, 2012 30th edition, as well as the technology of humid granulation and direct compression were used. Phosphatidylcholine was characterized as pharmaceutical raw material and the developed pill fulfilled the established quality attributes, reason why it was registered with 2 years proven stability. Added value was given to this substance, with potential risk of accumulation for the environment, as new pharmaceutical product in Cuba

Aspectos farmacológicos de la lecitina de soya y sus posibles aplicaciones médicas / Pharmacological aspects of soy phosphatidylcholine and its possible medical uses

La lecitina de soya, producto natural empleado como suplemento nutricional, presenta múltiples acciones biológicas demostradas, por lo cual resulta muy beneficiosa para tratar a pacientes con distintas afecciones. Teniendo en cuenta lo anterior se realizó la presente investigación donde se exponen algunos aspectos de interés, con vistas a difundir aún más lo relacionado con esta temática

The soy phosphatidylcholine, natural product used as nutritional supplement, presents multiple demonstrated biological actions, reason why it is very beneficial to treat patients with different disorders. Taking into account the above-mentioned the present investigation was carried out where some aspects of interest are exposed, aimed at diffusing even more everything related to this thematic

Comparative evaluation of propofol in nanoemulsion with solutol and soy lecithin for general anesthesia / Avaliação comparativa do propofol em nanoemulsão com solutol e com lecitina de soja para anestesia geral

ABSTRACT INTRODUCTION: The vehicle for propofol in 1 and 2% solutions is soybean oil emulsion 10%, which may cause pain on injection, instability of the solution and bacterial contamination. Formulations have been proposed aiming to change the vehicle and reduce these adverse reactions. OBJECTIVES: To compare the incidence of pain caused by the injection of propofol, with a hypothesis of reduction associated with nanoemulsion and the occurrence of local and systemic adverse effects with both formulations. METHOD: After approval by the CEP, patients undergoing gynecological procedures were included in this prospective study: control (n = 25) and nanoemulsion (n = 25) groups. Heart rate, noninvasive blood pressure and peripheral oxygen saturation were monitored. Demographics and physical condition were analyzed; surgical time and total volume used of propofol; local or systemic adverse effects; changes in variables monitored. A value of p < 0.05 was considered significant. RESULTS: There was no difference between groups regarding demographic data, surgical times, total volume of propofol used, arm withdrawal, pain during injection and variables monitored. There was a statistically significant difference in pain intensity at the time of induction of anesthesia, with less pain intensity in the nanoemulsion group. CONCLUSIONS: Both lipid and nanoemulsion formulations of propofol elicited pain on intravenous injection; however, the nanoemulsion solution elicited a less intense pain. Lipid and nanoemulsion propofol formulations showed neither hemodynamic changes nor adverse effects of clinical relevance.

RESUMO INTRODUÇÃO: O veículo do propofol em soluções a 1 e 2% é a emulsão de óleo de soja a 10%, que pode provocar dor à injeção, instabilidade da solução e contaminação bacteriana. Formulações foram propostas com o objetivo de alterar o veículo e reduzir essas reações adversas. OBJETIVOS: Comparar a incidência de dor à injeção do propofol com a hipótese de redução associada à nanoemulsão e a ocorrência de efeitos adversos locais e sistêmicos com as duas formulações. MÉTODO: Após aprovação pelo Conselho de Ética em Pesquisa, foram incluídos neste estudo prospectivo pacientes submetidas a procedimentos cirúrgicos ginecológicos: grupos controle (n = 25) e nanoemulsão (n = 25). Foram monitorados frequência cardíaca, pressão arterial não invasiva e saturação periférica de oxigênio. Foram analisados dados demográficos e estado físico; tempo cirúrgico e volume total usado de propofol; efeitos adversos locais ou sistêmicos; alterações nas variáveis de monitoramento. Considerou-se significativo valor de p < 0,05. RESULTADOS: Não houve diferença entre os grupos em relação a: dados demográficos, tempos cirúrgicos, volume total usado de propofol, retirada do braço, presença de dor durante a injeção e variáveis de monitoramento. Verificou-se diferença estatística significativa na intensidade da dor no momento da indução da anestesia, com menor intensidade no grupo nanoemulsão. CONCLUSÕES: Ambas as formulações de propofol, lipídica e em nanoemulsão, elicitaram dor à injeção venosa, porém a solução de nanoemulsão promoveu dor em menor intensidade. O propofol lipídico e o propofol em nanoemulsão não apresentaram alterações hemodinâmicas e efeitos adversos de relevância clínica.

Effect of lecithin on oxidative stress in an experimental model of rats colitis induced by acetic acid / Efeito da lecitina sobre o estresse oxidativo no modelo experimental de colite induzida por ácido acético em ratos

Ulcerative colitis (UC) is an inflammatory disease that affects the bowels. Reactive oxygen species (ROS) are involved in the progress of UC. Objective: Evaluate the antioxidant effect of lecithin in an experimental model of acute UC induced by administration of acetic acid (AA) in rats. Methods: Lecithin (0.5 mL/kg/day) administered orally 2 days before and after induction of colitis with 4% AA in a volume of 4 mL. Twenty-five male Wistar rats were divided in 5 groups: control (CO); control + lecithin (CO + LE); colitis (CL); colitis + lecithin (CL + LE); lecithin + colitis (LE + CL). Anal sphincter pressure, LPO (TBARS), and antioxidant activity of enzymes superoxide dismutase (SOD) and catalase (CAT) were measured, and a histological analysis with H&E was performed. Results and discussion: Anal sphincter pressure was significantly smaller in the CO group, lecithin treatment increased it in pre- and post-treated groups. LPO and SOD activity were increased in the CO group and decreased in the lecithin-treated groups. CAT activity was increased in CO group and decreased in lecithin groups. The histological analysis showed damage to the bowels with destruction of crypts, edema, and inflammatory infiltrate. Use of lecithin preserved the crypts and decreased the edema. Conclusion: Ulcerative colitis increased lipid peroxidation, and the use of lecithin was effective reducing damage to the bowels in the model of experimental colitis.

A retocolite ulcerativa (RCUI) é uma doença intestinal inflamatória. Espécies reativas de oxigênio (ERO) estão envolvidas no progresso da RCUI. Objetivo: Avaliar o efeito antioxidante de lecitina em modelo experimental de RCUI induzida pela administração de ácido acético (AA) em ratos. Métodos: A Lecitina (0,5 mL/kg/dia) foi administrada por via oral 2 dias antes e após a indução de colite com AA. Vinte e cinco ratos Wistar machos foram divididos em 5 grupos: controle (CO); controle + lecitina (CO + LE); colite (CL); colite + lecitina (CL + LE); lecitina + colite (LE + CL). Foram avaliadas: pressão do esfíncter anal, lipoperoxidação (LPO), atividade antioxidante das enzimas superóxido dismutase (SOD) e catalase (CAT), e foi realizada uma análise histológica com H&E. Resultados e discussão: A pressão do esfíncter anal foi significativamente menor no grupo CL, o tratamento com lecitina aumentou a pressão nos grupos pré e pós tratados. A LPO e atividade da SOD aumentaram no grupo CL e diminuíram nos grupos tratados com lecitina. A atividade da CAT foi aumentada no grupo CL e diminuiu nos grupos com lecitina. A análise histológica mostrou danos ao intestino com destruição das criptas, edema e infiltrado inflamatório. O uso de lecitina proporcionou uma preservação das criptas e diminuição do edema. Conclusão: A RCUI aumenta a LPO, a utilização de lecitina foi eficaz na redução dos danos ao intestino induzido por AA no modelo de colite experimental.

High-Density Lipoprotein, Lecithin: Cholesterol Acyltransferase, and Atherosclerosis

Epidemiological data clearly show the existence of a strong inverse correlation between plasma high-density lipoprotein cholesterol (HDL-C) concentrations and the incidence of coronary heart disease. This relation is explained by a number of atheroprotective properties of HDL, first of all the ability to promote macrophage cholesterol transport. HDL are highly heterogeneous and are continuously remodeled in plasma thanks to the action of a number of proteins and enzymes. Among them, lecithin:cholesterol acyltransferase (LCAT) plays a crucial role, being the only enzyme able to esterify cholesterol within lipoproteins. LCAT is synthetized by the liver and it has been thought to play a major role in reverse cholesterol transport and in atheroprotection. However, data from animal studies, as well as human studies, have shown contradictory results. Increased LCAT concentrations are associated with increased HDL-C levels but not necessarily with atheroprotection. On the other side, decreased LCAT concentration and activity are associated with decreased HDL-C levels but not with increased atherosclerosis. These contradictory results confirm that HDL-C levels per se do not represent the functionality of the HDL system.

Expressed sequence tags in venomous tissue of Scorpaena plumieri (Scorpaeniformes: Scorpaenidae)

Species of the family Scorpaenidae are responsible for accidents and sporadic casualties by the shore they inhabit. The species Scorpaena plumieri from this family populate the Northeastern and Eastern coast of Brazil causing human envenomation characterized by local and systemic symptoms. In experimental animals the venom induces cardiotoxic, hypotensive, and airway respiratory effects. As first step to identify the venom components we isolated gland mRNA to produce a cDNA library from the fish gland. This report describes the partial sequencing of 356 gland transcripts from S. plumieri. BLAST analysis of transcripts showed that 30% were unknown sequences, 17% hypothetical proteins, 17% related to metabolic enzymes, 14% belonged to signal transducing functions and the remaining groups (7-8%) composed by gene related with expressing proteins, regulatory proteins and structural proteins. A considerable number of these EST were not found in available databases suggesting the existence of new proteins and/or functions yet to be discovered. By screening the library with antibodies against a lectin fraction from S. plumieri venom we identified several clones whose DNA sequence showed similarities with lectins found in fish. In silico analysis of these clones confirm the identity of these molecules in the venom gland of S. plumieri. .

Espécies da família Scorpaenidae são responsáveis por acidentes e mortes esporádicas ao longo da costa que habitam. A espécie Scorpaena plumieri desta família povoam a costa Leste e Nordeste do Brasil, causando envenenamento humano caracterizado por sintomas locais e sistêmicos. Em modelos experimentais animais a peçonha induz cardiotoxicidade, efeitos hipotensivos e alterações nas vias aéreas respiratórias. Como primeiro passo para identificar os componentes da peçonha foram isolados os mRNA das glândulas do peixe para produzir uma biblioteca de cDNAs. Esse artigo descreve o sequenciamento parcial de 356 transcritos das glândulas de S. plumieri. Análises em bancos de dados (BLAST) dos transcritos demonstraram que 30% eram sequências desconhecidas, 17% proteínas hipotéticas, 17% relacionadas às enzimas do metabolismo, 14% pertenciam a funções de transdução de sinais e os demais grupos (7-8%) formados por genes relacionados com a expressão de proteínas, proteínas regulatórias e estruturais. Um número considerável destes EST não foi encontrado em bases de dados disponíveis, sugerindo a existência de novas proteínas e/ou funções ainda a serem descobertas. Ao fazer um barrido da biblioteca com anticorpos produzidos contra uma fração das lectinas do veneno de S. plumieri, identificamos vários clones, cuja sequência de DNA mostram semelhanças com lectinas encontradas em peixes. A análise in silico destes clones confirmam a identidade destas moléculas na glândula de peçonha de S. plumieri.

Medication and Diet in Gallstone Diseases / 대한췌담도학회지

Gallstone disease represents one of the most common gastroenterological disorders. Several risk factors for cholesterol gallstone formation in the general population have been identified. There is a strongly increased risk of gallstone disease during prolonged fasting, rapid weight loss, total parenteral nutrition, and somatostatin analogue treatment. Cholecystectomy is the most frequently recommended conventional treatment for symptomatic gallstones. In asymptomatic and symptomatic gallstone carriers, treatment with the hydrophilic bile salt ursodeoxycholic acid (UDCA) has been claimed to reduce the risk of biliary colic and gallstone complications such as acute cholecystitis and acute pancreatitis. However, randomized, double-blind, placebo-controlled trials are lacking. There is evidence that dietary factors influence the risk of developing cholesterol gallstones. Dietary factors that may increase risk include cholesterol, saturated fat, trans-fatty acids, refined sugar, and possibly legumes. Obesity is also a risk factor for gallstones. Dietary factors that may prevent the development of gallstones include polyunsaturated fat, monounsaturated fat, fiber, and caffeine. Consuming a vegetarian diet is also associated with decreased risk. In addition, identification and avoidance of allergenic foods frequently relieves symptoms of gallbladder disease, although it does not dissolve gallstones. Nutritional supplements that might help prevent gallstones include vitamin C, soy lecithin, and iron. In addition, a mixture of plant terpenes (Rowachol(R)) has been used with some success to dissolve radiolucent gallstones.

Lecithin: Cholesterol Acyltransferase and Na(+)-K(+)-ATPase Activity in Patients with Breast Cancer / 한국유방암학회지

PURPOSE: The aim of this study was to determine whether plasma lecithin:cholesterol acyltransferase (pLCAT) and erythrocyte membrane Na(+)-K(+)-ATPase ase (emNaKATPs) activity have a correlation in breast cancer. This study compared these parameters at time points before and after treatment with radiotherapy. METHODS: The levels of pLCAT and emNaKATPs were assessed in 30 patients with breast carcinoma and 20 control subjects. While emNaKATPs was measured with spectrophotometric method, pLCAT levels was measured using a specific enzyme-linked immunosorbent assay. RESULTS: pLCAT levels, both before and after radiotherapy, were found to be decreased in breast cancer patients than in the controls groups (p0.05). CONCLUSION: The results of the present study demonstrated that decreased pLCAT and emNaKATPs activity levels in breast cancer patients after/before RT than control group. In addition, decreased emNaKATPs activity in breast cancer patients receiving radiotherapy may be due to decreased pLCAT concentrations and RT beam. In our opinion, altered activities of pLCAT and emNaKATPs are linked to the treatment effect of radiotherapy. These data may clarify the development of cell membrane dysfunction and lipid metabolism in breast cancer patients receiving radiotherapy.

Solubility of amphotericin B in water-lecithin-dispersions and lecithin-based submicron emulsions

The aim of this work was to evaluate water-lecithin-dispersions [WLDs] as carriers for Amphotericin B [AmB] and to compare the drug solubility in WLDs and O/W lecithin-based submicron emulsions [SMEs] in order to evaluate the influence of lecithin content on the dosage form solubilization of the active compound. WLDs and different SMEs with either 1.2 or 2.4% of lecithin were prepared. WLD with 2.4% lecithin show a 10-fold increase in solubilization of AmB compared with 1.2% lecithin WLD. SMEs with 1.2% lecithin show an increase of over 400 times in solubilization compared with WLD containing the same concentration of lecithin, whereas SMEs with 2.4% lecithin show an increase of over 40 times compared with the corresponding WLD. Drug solubilization in SMEs with 2.4% lecithin is not significantly greater than in those containing 1.2% lecithin. The content of surfactant Brij 97 had a significant influence on drug solubilization in SMEs [P<0.05]. Results indicate that indicate that SMEs are proper systems to solubilize AmB. It can be assumed that solubilization is due to the formulation microstructure and not to the separate components themselves

Efeito da utilização de diferentes diluidores para a produção in vitro de embriões bovinos / Effect of different bovine semen extenders on in vitro development of bovine embryos

Objetivou-se avaliar as características morfológica e funcional do sêmen bovino congelado comparando-se a eficácia de dois diferentes diluidores. O ejaculado de quatro touros foi dividido em duas partes iguais, uma submetida ao diluidor Tris e gema de ovo (A) e outra ao diluidor à base de lecitina de soja (Andromed®) (B). No experimento I, cinco palhetas dos diluidores A e B de cada touro foram descongeladas e avaliadas quanto à motilidade, vigor, concentração, morfologia espermática e teste de termor-resistência lento. Foram feitas, ainda, avaliação da integridade de membranas, por meio da associação das sondas iodeto de propídio, isotiocionato de fluoresceína - Pisum sativum e carbocianina catiônica lipofílica, e avaliação funcional da membrana plasmática com teste hiposmótico. A avaliação da integridade da cromatina foi realizada pelo método de coloração com laranja de acridina. No experimento II, o sêmen com os diferentes diluidores foi utilizado na fecundação in vitro, sendo observadas taxas de clivagem e desenvolvimento embrionário in vitro. Em relação aos resultados obtidos, apenas a porcentagem de espermatozoides no sêmen congelado foi discretamente maior com o diluidor A, concluindo-se que o diluidor composto por lecitina de soja pode substituir o composto por Tris e gema de ovo, respeitando-se as variações individuais de cada touro utilizado no presente experimento.

The goal of this study was to evaluate the protective effect of egg yolk compared with a soybean lecithin-based extender on morphologic and functional characteristics of frozen bovine semen. The ejaculate of four bulls was divided into two equal parts, one diluted with egg-yolk-Tris extender (A) and the other with a soy-lecithin based extender (Andromed®) (B). In experiment I, five straws of extender A and B from each bull were thawed and assessed regarding motility (subjective and computerized analysis), vigor, concentration, sperm morphology and slow thermoresistance (STR), evaluation of membrane integrity through association of propidium iodite probes (PI), fluorescein isotiocianate - Pisum sativum (FITC-PSA) and lipophilic cationic carbocyanine (JC-1) and functional evaluation of the plasmatic membrane through Hyposmotic Swelling Test (HOST). An evaluation of chromatin integrity was performed with the acridine orange staining procedure. In experiment II, the frozen semen with different extenders was used for in vitro fertilization (IVF), analyzing cleavage rates and in vitro embryo development. No statistical difference between extenders was identified, suggesting that the soy lecithin extender may substitute egg-yolk-Tris extender, considering the individual variations of each bull used in this experiment.

Estudo comparativo entre propofol em nanoemulsão não lipídica com solutol e em emulsão com lecitina / A comparative study of non-lipid nanoemulsion of propofol with solutol and propofol emulsion with lecithin / Estudio comparativo entre el propofol en la nanoemulsión no lipídica con solutol y en la emulsión con lecitina

JUSTIFICATIVA E OBJETIVOS: Formulações têm sido propostas com o objetivo de reduzir as reações adversas decorrentes da emulsão lipídica de óleo de soja utilizada como veículo do propofol. O objetivo deste estudo foi avaliar comparativamente, em sedação para endoscopia, a segurança, eficácia e efeitos adversos do uso do propofol em nanoemulsão em relação ao propofol comercializado atualmente. MÉTODO: Foram incluídos neste estudo prospectivo 150 pacientes submetidos a procedimentos endoscópicos digestivos altos, divididos em grupo-controle (Grupo CONT; n = 75) e grupo nanoemulsão (Grupo NE; n = 75). Foram monitorados FC, PAS, PAD, SpO2 e BIS (considerado apropriado entre 65 e 75, durante o procedimento). Foram analisados: gênero, idade, peso, altura, IMC, estado físico ASA; tempos e doses utilizadas; efeitos adversos (sinais flogísticos e dor à injeção, apneia, náuseas/vômitos) e alterações nas variáveis de monitoramento. Considerou-se significativo p < 0,05. RESULTADOS: Os grupos foram homogêneos quanto aos dados antropométricos e estado físico. Nenhum paciente apresentou apneia nem sinais flogísticos no local da injeção. A incidência de dor à injeção no grupo CONT foi 82,7% e 53,3% no grupo NE (p < 0,001) e de náuseas e vômitos foi 10,7% no grupo CONT e 2,7% no grupo NE (p > 0,05). Os tempos, as doses de indução e os valores das PAS e PAD ao final do exame e no momento da alta da SRPA foram menores no grupo NE (p < 0,05). CONCLUSÕES: O propofol lipídico e o propofol em nanoemulsão, nas doses utilizadas, foram equivalentes em relação a eficácia, segurança e efeitos adversos, ressaltando-se a menor incidência de dor à injeção da formulação em nanoemulsão.

BACKGROUND AND OBJECTIVES: Some formulations have been proposed to reduce the adverse reactions due to the lipid emulsion containing soybean oil used as propofol carrier. This study for endoscopy sedation was aimed at evaluating and comparing the safety, effectiveness and adverse effects of the use of propofol nanoemulsion compared to propofol currently commercialized. METHOD: In this prospective study, 150 patients were submitted to upper digestive endoscopy. These patients were allocated into two groups: the control group (CONT Group; n = 75) and the nanoemulsion group (NE Group; n = 75). HR, SBP, DBP, SpO2 and BIS (which is considered to be appropriate between 65 and 75 during procedure) were monitored. Gender, age, weight, height, BMI, ASA physical status, times and doses were analyzed, as well as adverse effects (phlogistic signs and pain on injection, apnea, nausea/vomiting) and alterations in monitoring variables. A p-value < 0.05 was considered significant. RESULTS: The groups had similar results concerning anthropometric data and physical status. None of the patients developed apnea or presented phlogistic signs in the injection site. The incidence of pain on injection in the CONT Group was 82.7% and 53.3% in the NE Group (p < 0.001), and the incidence of nausea and vomiting was 10.7% in the CONT Group and 2.7% in the NE Group (p > 0.05). The times, induction doses and the SBP and DBP values at the end of examination and at the moment of discharge from the PACU were lower in the NE Group (p < 0.05). CONCLUSIONS: Lipid propofol and propofol nanoemulsion were equivalent concerning effectiveness, safety and adverse effects in the doses used. There was a lower incidence of pain on injection in the nanoemulsion formulation.

JUSTIFICATIVA Y OBJETIVOS: Las formulaciones han sido propuestas con el objetivo de reducir las reacciones adversas provenientes de la emulsión lipídica de aceite de soja utilizada como vehículo del propofol. El objetivo de este estudio, fue la evaluación comparativa en la sedación para la endoscopia, la seguridad, la eficacia y los efectos adversos del uso del propofol en la nanoemulsión con relación al propofol actualmente comercializado. MÉTODO: En este estudio prospectivo se incluyeron 150 pacientes sometidos a procedimientos endoscópicos digestivos altos, divididos en grupo control (Grupo CONT; n = 75) y grupo nanoemulsión (Grupo NE; n = 75). Se monitorizaron FC, PAS, PAD, SpO2 y BIS (considerado apropiado entre 65 y 75, durante el procedimiento). Fueron analizados el sexo, la edad, el peso, la altura, el IMC, el estado físico ASA; tiempos y dosis utilizados; efectos adversos (signos flogísticos y dolor a la inyección, apnea, náuseas/vómitos) y las alteraciones en las variables de monitorización. Se consideró como significativo p < 0,05. RESULTADOS: Los grupos fueron homogéneos en cuanto a los datos antropométricos y al estado físico. Ningún paciente presentó apnea ni signos flogísticos en la región de la inyección. La incidencia de dolor a la inyección en el grupo CONT fue de 82,7% y 53,3% en el grupo NE (p < 0,001) y de náuseas y vómitos fue 10,7% en el grupo CONT y 2,7% en el grupo NE (p > 0,05). Los tiempos, las dosis de inducción y los valores de las PAS y PAD al final del examen y en el momento del alta de la SRPA fueron menores en el grupo NE (p < 0,05). CONCLUSIONES: El propofol lipídico y el propofol en nanoemulsión en las dosis utilizadas, fueron equivalentes con relación a la eficacia, seguridad y efectos adversos, destacando la menor incidencia de dolor a la inyección de la formulación en nanoemulsión.

Efeito da Lecitina de Soja sobre os Lipídeos e Proteína C reativa e na prevenção da Hipertrofia Ventricular Esquerda de Camundongos Hiperlipidêmicos / Effect of soy lecithin on lipids and C-reactive protein and the prevention of Left Ventricular Hypertrophy in hyperlipidemic mice

A regulação do metabolismo lipídico com drogas ou alimentos naturais é um alvo importante para diminuir o risco de doenças cardiovasculares. O objetivo deste estudo foi verificar o efeito da lecitina de soja na dislipidemia e na hipertrofia ventricular de camundongos hipercolesterolêmicos. Utilizaram-se quatro grupos de camundongos LDLr-/- com 3 meses de idade que receberam a seguintes dietas: Grupo S- ração padrão; Grupo S+Lec- ração padrão e lecitina de soja; Grupo HL- ração hiperlipídica; e Grupo HL+Lec- ração hiperlipídica e lecitina de soja. Após 15 dias, o sangue foi coletado para análise sérica dos lipídeos e da proteína C reativa. O ventrículo esquerdo foi separado, a proporção peso ventricular (mg) pelo peso do animal (g) foi calculada e, em seguida, processado histologicamente. Cortes histológicos foram corados com hematoxilina/eosina e picrosírius red para avaliar alterações morfológicas e morfométricas ventriculares. A lecitina de soja apresentou efeito antidislipidêmico e aumentou os níveis séricos de HDL nos camundongos do grupo S+Lec. Entretanto, nos camundongos do grupo HL+lec, a lecitina de soja não preveniu a dislipidemia, apenas aumentou o nível sérico do HDL. Este efeito nestes animais influenciou no processo inflamatório cardiovascular, reduzindo o nível sérico de proteína C reativa; e prevenindo a hipertrofia ventricular esquerda. A utilização da lecitina de soja representa um tratamento e/ou uma prevenção alternativa de baixo custo para as dislipidemias não associadas com dieta hiperlipídica. Contudo, a lecitina de soja aumenta os níveis séricos do HDL prevenindo o desenvolvimento da HVE mesmo em dislipidemias associadas com dieta hiperlipídica.

The regulation of lipid metabolism with drugs or natural foods is an important target for reducing the risk of cardiovascular disease. The aim of this study was to investigate the effects of soy lecithin on left ventricular hypertrophy (LVH) and dyslipidemia in hypercholesterolemic mice. We used four experimental groups of LDLr-/- mice (aged 3 months), which received the following diets: Group S: standard diet, Group S+Lec: standard diet and soy lecithin; Group HL: hyperlipidic diet and Group HL+Lec: hyperlipidic diet and soy lecithin. After 15 days on these diets, blood was collected for analysis of serum lipids and C-reactive protein. The left ventricle was dissected out and weighed and the ratio of its weight to the body weight of the animal was calculated, after which it was processed histologically. Sections were stained with hematoxylin-eosin and picrosirius red, to assess morphological and morphometric changes in the ventricle. In Group S+Lec, the soy lecithin had an antidyslipidemic effect and enhanced the serum levels of HDL. However, in the mice in group HL+Lec, soy lecithin did not prevent dyslipidemia, only increasing the serum level of HDL. These effects in these animals influenced the cardiovascular inflammatory process, reducing the level of serum C-reactive protein and preventing LVH. Soy lecithin could thus be used as a treatment or a low-cost alternative preventative measure against dyslipidemia associated with a non-fat diet. However, soy lecithin increases the serum level of HDL, reducing the risk of LVH even in dyslipidemia associated with a high-fat diet.

Effect of Nanoparticle with VEGF in Mouse Ischemic Hindlimb Model

PURPOSE: Vascular endothelial growth factor (VEGF) is one of the factors regulating angiogenesis. For angiogenesis, the local concentration of VEGF has to be maintained. Because of its short half-life, VEGF has been conjugated with nanoparticles. Some nanoparticles, such as poly (lactic-co-glycolic acid (PLGA)) or polyethylenimine (PEI) are commonly used in this field, but have weak points such as faster release than expected and cell toxicity. We investigated the effect of core/shell nanoparticles including lecithin lipid cores in the ischemic hindlimb model. METHODS: Mice were anesthetized and a region of the common femoral artery and vein was ligated and excised. Hindlimb ischemic mice (n=28) were divided randomly into four groups: Control group (normal saline, n=7), mouse VEGF group (mVEGF, n=7), nanoparticle including mVEGF group (N-mVEGF, n=7), and nanoparticle/hydrogel mouse VEGF group (NH-mVEGF, n=7). The drug was injected postoperatively into the thigh muscle of the ischemic limb. Perfusion, capillary number and H&E stain were assessed 28 d after treatment. RESULTS: The capillary number increased in N-mVEGF and mVEGF group (P=0.026). Improvements of ischemic limb perfusion were inferior in N-mVEGF, NH-mVEGF groups (P=0.006) compared to other groups. Mice received N-mVEGF, NH-mVEGF treatment showed significant inflammation in the H&E staining. CONCLUSION: Sustained VEGF delivery via core/shell nanoparticle with lecithin core did not show improved perfusion rate despite an increase in capillary number. Furthermore, vacuolization and induction of inflammation requiring a different composition of nanoparticle should be tested.

Cholesterol oxides inhibit cholesterol esterification by lecithin: cholesterol acyl transferase / Óxidos de colesterol por inibir a esterificação do colesterol lecitina: colesterol acil transferase

Cholesterol oxides are atherogenic and can affect the activity of diverse important enzymes for the lipidic metabolism. The effect of 7β-hydroxycholesterol, 7-ketocholesterol, 25-hydroxycholesterol, cholestan-3β,5α,6β-triol,5,6β-epoxycholesterol, 5,6α-epoxycholesterol and 7α-hydroxycholesterol on esterification of cholesterol by lecithin:cholesterol acyl transferase (LCAT, EC 2.3.1.43) and the transfer of esters of cholesterol oxides from high density lipoprotein (HDL) to low density lipoproteins (LDL) and very low density lipoproteins (VLDL) by cholesteryl ester transfer protein (CETP) was investigated. HDL enriched with increasing concentrations of cholesterol oxides was incubated with fresh plasma as source of LCAT. Cholesterol and cholesterol oxides esterification was followed by measuring the consumption of respective free sterol and oxysterols. Measurements of cholesterol and cholesterol oxides were done by gas-chromatography. 14C-cholesterol oxides were incorporated into HDL2 and HDL3 subfractions and then incubated with fresh plasma containing LCAT and CETP. The transfer of cholesterol oxide esters was followed by measuring the 14C-cholesterol oxide-derived esters transferred to LDL and VLDL. All the cholesterol oxides studied were esterified by LCAT after incorporation into HDL particles, competing with cholesterol by LCAT. Cholesterol esterification by LCAT was inversely related to the cholesterol oxide concentration. The esterification of 14C-cholesterol oxides was higher in HDL3 and the transfer of the derived esters was greater from HDL2 to LDL and VLDL. The results suggest that cholesterol esterification by LCAT is inhibited in cholesterol oxide-enriched HDL particles. Moreover, the cholesterol oxides-derived esters are efficiently transferred to LDL and VLDL. Therefore, we suggest that cholesterol oxides may exert part of their atherogenic effect by inhibiting cholesterol esterification...

Os óxidos de colesterol são aterogênicos e podem afetar a atividade de diversas enzimas importantes para o metabolismo lipídico. Este estudo investigou o efeito dos óxidos 7β-hidroxicolesterol, 7-cetocolesterol, 25-hidroxicolesterol, colestan-3β,5α,6β-triol, 5,6β-epoxicolesterol, 5,6α-epoxicolesterol e 7α-hidroxicolesterol na esterificação do colesterol por ação da lecitina colesterol aciltransferase (LCAT, EC 2.3.1.43) e a posterior transferência dos óxidos esterificados da lipoproteína de alta densidade (HDL) para as lipoproteínas de baixa densidade (LDL) e muito baixa densidade (VLDL) mediada pela proteína de transporte de éster de colesterol (CETP). Para atingir os objetivos, HDL enriquecida com concentrações crescentes de óxidos de colesterol foi incubada com plasma fresco pobre em lipoproteínas, como fonte de LCAT; posteriormente a esterificação do colesterol e dos óxidos de colesterol foi medida pelo consumo do colesterol livre e dos óxidos livres presentes na HDL. As determinações de colesterol e dos óxidos de colesterol foram realizadas por cromatografia gasosa. 14C-óxidos de colesterol foram incorporados nas subfrações HDL2 e HDL3 e posteriormente incubados com plasma fresco, contendo LCAT e CETP. A transferência dos ésteres de óxidos de colesterol foi medida e quantificada pela presença desses ésteres na LDL e VLDL. Todos os óxidos de colesterol estudados foram esterificados pela LCAT após incorporação nas partículas de HDL e competiram com a esterificação do colesterol nativo. A esterificação do colesterol pela LCAT foi inversamente relacionada à concentração de óxidos de colesterol. A esterificação dos óxidos de colesterol foi maior na HDL3 e a transferência desses ésteres foi maior a partir da HDL2 para a LDL e VLDL. Estes resultados indicam que a esterificação do colesterol pela LCAT é inibida nas partículas de HDL enriquecidas com óxidos de colesterol e que os ésteres de óxidos de colesterol...

Preparation of self-assemble nobiletin proliposomes and its pharmacokinetics in rats / 药学学报

To prepare self-assemble nobiletin proliposomes and study its pharmacokinetic behavior in rats after ig administration, and nobiletin suspension was used as control, self-assemble nobiletin proliposomes were prepared by a new proliposome preparation method, their physicochemical properties including encapsulation efficiency, particle size and stability of formed liposome were determined. Plasma concentration of nobiletin was determined by HPLC taking nimodipine as internal standard. The pharmacokinetic parameters were calculated by Kinetica 4.4 software. The encapsulation efficiency of nobiletin liposomes was more than 80%, with an average particle size of 212.1 nm and very good stability. Compared to nobiletin suspension, nobiletin liposomes possessed higher absorptive rate and longer MRT, and the relative bioavailability was 264.3% in rats. It could be concluded that self-assemble nobiletin proliposome was a simple and feasible preparation, and showed greater absorption compared with nobiletin suspension.