Synthesis of triheptanoin and formulation as a solid diet for rodents

Triheptanoin-enriched diets have been successfully used in the experimental treatment of various metabolic disorders. Maximal therapeutic effect is achieved in the context of a ketogenic diet where triheptanoin oil provides 30-40% of the daily caloric intake. However, pre-clinical studies using triheptanoin-rich diets are hindered by the difficulty of administering to laboratory animals as a solid foodstuff. In the present study, we successfully synthesized triheptanoin to the highest standards of purity from glycerol and heptanoic acid, using sulfonated charcoal as a catalyst. Triheptanoin oil was then formulated as a solid, stable and palatable preparation using a ketogenic base and a combination of four commercially available formulation agents: hydrophilic fumed silica, hydrophobic fumed silica, microcrystalline cellulose, and talc. Diet compliance and safety was tested on C57Bl/6 mice over a 15-week period, comparing overall status and body weight change. Practical applications: This work provides a complete description of (i) an efficient and cost-effective synthesis of triheptanoin and (ii) its formulation as a solid, stable, and palatable ketogenic diet (triheptanoin-rich; 39% of the caloric intake) for rodents. Triheptanoin-rich diets will be helpful on pre-clinical experiments testing the therapeutic efficacy of triheptanoin in different rodent models of human diseases. In addition, using the same solidification procedure, other oils could be incorporated into rodent ketogenic diet to study their dosage and long-term effects on mammal health and development. This approach could be extremely valuable as ketogenic diet is widely used clinically for epilepsy treatment.

Synthesis of triheptanoin and formulation as a solid diet for rodents

Triheptanoin-enriched diets have been successfully used in the experimental treatment of various metabolic disorders. Maximal therapeutic effect is achieved in the context of a ketogenic diet where triheptanoin oil provides 30-40% of the daily caloric intake. However, pre-clinical studies using triheptanoin-rich diets are hindered by the difficulty of administering to laboratory animals as a solid foodstuff. In the present study, we successfully synthesized triheptanoin to the highest standards of purity from glycerol and heptanoic acid, using sulfonated charcoal as a catalyst. Triheptanoin oil was then formulated as a solid, stable and palatable preparation using a ketogenic base and a combination of four commercially available formulation agents: hydrophilic fumed silica, hydrophobic fumed silica, microcrystalline cellulose, and talc. Diet compliance and safety was tested on C57Bl/6 mice over a 15-week period, comparing overall status and body weight change. Practical applications: This work provides a complete description of (i) an efficient and cost-effective synthesis of triheptanoin and (ii) its formulation as a solid, stable, and palatable ketogenic diet (triheptanoin-rich; 39% of the caloric intake) for rodents. Triheptanoin-rich diets will be helpful on pre-clinical experiments testing the therapeutic efficacy of triheptanoin in different rodent models of human diseases. In addition, using the same solidification procedure, other oils could be incorporated into rodent ketogenic diet to study their dosage and long-term effects on mammal health and development. This approach could be extremely valuable as ketogenic diet is widely used clinically for epilepsy treatment.

Produção de mudas de baru (Dipteryx alata Vog.) sob três níveis de sombreamento e quatro classes texturais de solo

Foi avaliado o desenvolvimento de mudas de baru (Dipteryx alata Vog.) em vasos, sob três níveis de sombreamento e quatro classes texturais do solo, no período de março a outubro de 2010, em Campo Grande-MS. Os tratamentos consistiram em 0%, 30% e 50% de sombreamento e solos de textura arenosa, média, argilosa e muito argilosa. O delineamento experimental foi em blocos ao acaso, em parcelas subdivididas, com medidas repetidas no tempo. Foram utilizadas três repetições e dez plantas por subparcela. Os níveis de sombreamento corresponderam aos tratamentos, e as diferentes classes texturais do solo, aos subtratamentos. As plantas foram avaliadas em intervalos de 15 dias após a emergência (DAE) até 195 DAE, sendo avaliadas quanto à altura (cm) de plantas, número de folhas e diâmetro do coleto (mm). Aos 195 DAE, também foram avaliadas a percentagem de sobrevivência, a área foliar e a massa seca de folha, caule e das raízes das plantas. Sob sombreamento, foram observados maiores valores de altura e área foliar. A altura de plantas foi de 32,09 cm e 31,21 cm planta-1 , e a área foliar foi de 639,24 cm² e 580,49 cm² planta-1 para os níveis de sombreamento de 50% e 30%, respectivamente. No solo de textura argilosa, os valores foram superiores na maioria das características avaliadas, seguido do solo com textura muito argilosa. A maior produção de massa seca de folha foi no solo com textura argilosa, com média de 7,28 g planta-1. A percentagem de sobrevivência das mudas no solo com textura arenosa foi inferior aos demais. Houve interação entre níveis de sombreamento e classes texturais do solo na massa seca de raízes, que foi maior (1,43 g kg-1 de solo) no solo de textura muito argilosa, no nível de 50% de sombreamento. As mudas de baru atingiram medidas de altura e diâmetro de coleto adequadas em todos os níveis de sombreamento e classes texturais do solo.

Crescimento de mudas de Campomanesia adamantium (Cambess.) O. Berg (guavira), submetidas a três níveis de sombreamento e substratos

O experimento foi desenvolvido em Campo Grande - MS, no período de março de 2008 a janeiro de 2009. O objetivo foi avaliar o desenvolvimento das mudas da Campomanesia adamantium (Cambess.) O. Berg. sob três condições de sombreamento e seis substratos. Os tratamentos foram três níveis de sombreamento (0%, 30% e 50% de sombra) e seis substratos [100% de solo Latossolo Vermelho distrófico textura argilosa - LVd (ta); 100% de solo de Latossolo Vermelho distrófico textura média LVd (tm); 75% de LVd (ta) + 15% de areia + 10% de cama de frango semidecomposta - LVd (ta) + CF; 75% de LVd(tm) + 15% de areia + 10 % de cama de frango semidecomposta - LVd (tm) + CF; 75% de LVd(ta) + 15% de areia + 10 % Organosuper® - LVd (ta) + OR; 75% de LVd (tm) + 15% de areia + 10% de Organosuper® - LVd (tm) + OR]. O delineamento experimental foi em blocos ao acaso, arranjado em parcelas subdivididas com medidas repetidas no tempo. Foram utilizadas três repetições e dez plantas por subparcela. Os níveis de sombreamento interferiram do desenvolvimento das mudas nas características de diâmetro do coleto (maior sob sol), área foliar (maior sob 50% de sombra) e massa seca de raízes (maior sob sol). Considerando o desenvolvimento da parte aérea das mudas, a observação de que sob sol pleno há necessidade de utilização de maior volume de irrigação e que houve menor sobrevivência de plantas, considera-se o nível de sombreamento de 50% como mais adequado para produção de mudas de guavira. Dos substratos testados, o LVd (ta) foi considerado o mais adequado ao desenvolvimento das mudas pela percentagem de plantas vivas (95,55%) sem diferir do LVd (tm) (98,88%), maior altura de plantas observada no desenvolvimento e na altura final, maior massa seca de raízes, diferindo estatisticamente dos demais substratos e maior IQD (2,62), sem diferir de LVd (tm) (1,50).

Enxertia de fruteira-pão em função da idade do porta-enxerto

A fruteira-pão (Artocarpus altilis var. apyrena) é uma Moraceae de alto valor nutritivo, com ampla distribuição no Brasil. O tipo sem sementes é comumente propagado por estaca de raiz, processo geralmente lento. O trabalho objetivou avaliar o método da enxertia para propagação de fruteira-pão em função da idade do porta-enxerto. Os porta-enxertos foram obtidos de fruteira-pão A. altilis com sementes, e o método de enxertia empregado foi o de garfagem de topo em fenda cheia. O delineamento experimental foi o inteiramente casualizado, com quatro tratamentos (constituídos por porta-enxertos de dois, quatro, seis e oito meses de idade), cinco repetições e 10 plantas por parcela. Foram avaliados o crescimento dos porta-enxertos, a partir do diâmetro do caule, e a altura da planta, e, após a enxertia, as porcentagens de pegamento aos 30 dias e de sobrevivência dos enxertos, número de brotos e de folhas do enxerto e o comprimento do maior broto, aos 90 dias após a enxertia. A enxertia por garfagem no topo em fenda cheia é viável para produção de mudas de fruteira-pão, proporcionando porcentagem de pegamento entre 76% e 92%, independentemente da idade do porta-enxerto. No entanto, verificou-se que o percentual de sobrevivência do enxerto (72%) com os porta-enxertos com quatro meses e o diâmetro médio do caule de 10,52 mm foram superiores aos das demais idades. Houve pouca influência da idade do porta-enxerto para o número de brotos e de folhas, porém porta-enxertos com oito meses proporcionaram maior comprimento de broto.

Hierarchical linear models in Psychiatry: A bibliometric study

Development of research methods requires a systematic review of their status. This study focuses on the use of Hierarchical Linear Modeling methods in psychiatric research. Evaluation includes 207 documents published until 2007, included and indexed in the ISI Web of Knowledge databases; analyses focuses on the 194 articles in the sample. Bibliometric methods are used to describe the publications patterns. Results indicate a growing interest in applying the models and an establishment of methods after 2000. Both Lotka"s and Bradford"s distributions are adjusted to the data.

Análisis de sistemas bucoadhesivos

[spa]Objetivo: El objetivo de este estudio es el diseño de un parche bucoadhesivo para la administración transbucal de clorhidrato de doxepina utilizando diferentes polímeros así como la caracterización de dichos sistemas en cuanto al análisis calorimétrico y la capacidad de hinchamiento.Materiales y métodos: Se ha utilizado clorhidrato de doxepina y diferentes polímeros, carboximetilcelulosa sódica, hidroxipropilmetilcelulosa y chitosan. La calorimetría diferencial de barrido (DSC) se ha realizado en un dispositivo Mettler FP 80 equipado con un horno FP 85 y la capacidad de hinchamiento utilizando placas de agar.Resultados: Se obtienen termogramas de los parches y las mezclas físicas donde se observan transiciones endotérmicas entre 30 y 120º C y el pico endotérmico del principio activo en las mezclas físicas binarias. La entalpía de deshidratación es similar en los polímeros de carboximetilcelulosa sódica y chitosan (281 J/g) siendo menor en la película de hidroxipropilmetilcelulosa (251 J/g), al igual que el porcentaje de hidratación donde se demuestra que los parches elaborados con hidroxipropilmetilcelulosa presenta menor tendencia a captar agua (55,91 %) frente al 67,04 % y 67,30 % de la carboximetilcelulosa sódica y chitosan, respectivamente.Conclusión: Los resultados obtenidos muestran que existe compatibilidad entre los componentes de la formulación y los datos de entalpía se correlacionan con los datos obtenidos en el ensayo de hinchamiento.[eng]The aim of this study is to design a bucoadhesive patch for the transbuccal administration of doxepin hydrochloride using different polymers as well as the characterization of these systems for calorimetric analysis and the swelling capacity. Materials and methods: Doxepin hydrochloride was used as well as various polymers; carboxymethylcellulose sodium, hydroxypropylmethyl cellulose and chitosan. Differential scanning calorimetry (DSC) was carried out using a Mettler FP 80 device equipped with a FP 85 oven and the swelling capacity using agar plates. Results: Thermograms obtained patches and physical mixtures where there are endothermic transitions between 30 and 120º C and the endothermic peak of the active principle in binary physical mixtures. Dehydration enthalpy is similar in polymers of carboxymethylcellulose sodium and chitosan (281 J/g), the film having less hydroxypropylmethylcellulose (251 J/g), the percentage of moisture shows that the patches prepared with hydroxypropylmethylcellulose have less tendency to collect water (55.91 %) compared to 67.04 % and 67.30 % with sodium carboxymethylcellulose and chitosan, respectively. Conclusion: The results show that there is compatibility between the components of the formulation and the enthalpy data correlate

Design and physicochemical stability studies of paediatric oral formulations of sildenafil

Abstract Personalized medicine is a challenging research area in paediatric treatments. Elaborating new paediatric formulations when no commercial forms are available is a common practice in pharmacy laboratories; among these, oral liquid formulations are the most common. But due to the lack of specialized equipment, frequently studies to assure the efficiency and safety of the final medicine cannot be carried out. Thus the purpose of this work was the development, characterization and stability evaluation of two oral formulations of sildenafil for the treatment of neonatal persistent pulmonary hypertension. After the establishment of a standard operating procedure (SOP) and elaboration, the physicochemical stability parameters appearance, pH, particle size, rheological behaviour and drug content of formulations were evaluated at three different temperatures for 90 days. Equally, prediction of long term stability, as well as, microbiological stability was performed. Formulations resulted in a suspension and a solution slightly coloured exhibiting fruity odour. Formulation I (suspension) exhibited the best physicochemical properties including Newtonian behaviour and uniformity of API content above 90% to assure an exact dosification process.

Development, physical-chemical stability and release studies of four alcohol-free spironolactone suspensions for use in pediatrics

Dissolution studies have become of great significance because, in most cases, drug dissolution is the rate-limiting step in the absorption process. As occurs with solid oral dosage forms, heterogeneous disperse systems (suspensions) could also have some problems with their in vitro dissolution. The objective of this study was to evaluate influence of the excipients on the release of spironolactone from four alcohol free suspensions (pharmaceutical compounding) of spironolactone 5 mg/mL suitable for pediatric use. Also the comparison of the physical and chemical stability of the suspensions stored at 4, 25 and 40 ºC over a 60- day period has been studied. Rheological behavior, particle size, a prediction of long-term physical stability, pH and assay of spironolactone by HPLC were assessed at prefixed times. The dissolution profile of each suspension was determined and compared with that of the commercial tablets. A microbiological study of the best formula was also performed. Chemically, the four spironolactone suspensions were stable for 60 days stored at three temperatures; Suspension IV had optimum pH values and the highest recovery percentage. In terms of physical stability, sedimentation occurred in Suspension IV and flotation of spironolactone in Suspensions I, II and III. Suspension III had the highest viscosity and the slowest drug release. Suspension IV was also microbiologically stable for 60 days. In conclusion, Suspension IV had the best properties and the least suitable form was Suspension III, as its high viscosity made it difficult to achieve homogeneous redispersion, and it had the slowest dissolution profile.

Dificuldades diagnósticas no osteoma osteoide do cotovelo: estudo clínico, radiológico e histopatológico

OBJETIVO: Descrever os aspectos clínicos e de imagem que podem auxiliar no diagnóstico correto do osteoma osteoide no cotovelo. MATERIAIS E MÉTODOS: Realizado estudo retrospectivo de sete pacientes com diagnóstico de osteoma osteoide no cotovelo confirmado histologicamente por biópsia óssea. Eles tiveram seus prontuários médicos e exames de imagem revisados. RESULTADOS: Do total de 142 pacientes identificados em nossos arquivos, 4,9% apresentavam a lesão no cotovelo, com predomínio no sexo masculino (2,5:1) e idade média de 25 anos. Dor e limitação de movimento foram os sintomas mais comuns. Cinco pacientes (71,4%) receberam outro diagnóstico clínico prévio. A duração média dos sintomas foi de 21 meses. As radiografias não demonstraram o nidus em 42,8% dos casos. A tomografia computadorizada e a ressonância magnética mostraram claramente o nidus. Derrame articular foi um achado constante. O aspecto histológico observado foi o usual. A ressecção cirúrgica promoveu alívio dos sintomas e/ou melhora funcional em todos os casos. CONCLUSÃO: É importante considerar a possibilidade de osteoma osteoide em paciente adulto jovem com dor, limitação do movimento e sinais de sinovite no cotovelo, refratária ao tratamento conservador. Esclerose óssea, espessamento cortical e/ou reação periosteal detectados na radiografia permitem direcionar a tomografia computadorizada para a visualização precisa do nidus.

Detecção de adulterações em produtos alimentares contendo leite e/ou proteínas lácteas

A critical review of the most relevant analytical methodologies for quality and authenticity control of dairy products and foods containing milk proteins is presented. Chromatographic, electrophoretic and immunological methods are used for: detection of cow's milk in ewe and goat milks, detection of whey added to milk, detection of caseins and/or whey proteins in non-lactic foods and study compounds resulting from milk proteins degradation. Techniques based on polimerase chain reaction are also suitable for detection of cow's milk on cheeses of ewe and goat milks.

Validated spectrofluorometric method for determination of gemfibrozil in self nanoemulsifying drug delivery systems (SNEDDS)

A spectrofluorometric method has been developed and validated for the determination of gemfibrozil. The method is based on the excitation and emission capacities of gemfibrozil with excitation and emission wavelengths of 276 and 304 nm respectively. This method allows de determination of the drug in a self-nanoemulsifying drug delivery system (SNEDDS) for improve its intestinal absorption. Results obtained showed linear relationships with good correlation coefficients (r(2)>0.999) and low limits of detection and quantification (LOD of 0.075 μg mL(-1) and LOQ of 0.226 μg mL(-1)) in the range of 0.2-5 μg mL(-1), equally this method showed a good robustness and stability. Thus the amounts of gemfibrozil released from SNEDDS contained in gastro resistant hard gelatine capsules were analysed, and release studies could be performed satisfactorily.

Design and physicochemical stability studies of paediatric oral formulations of sildenafil

Personalized medicine is a challenging research area in paediatric treatments. Elaborating new paediatric formulations when no commercial forms are available is a common practice in pharmacy laboratories; among these, oral liquid formulations are the most common. But due to the lack of specialized equipment, frequently studies to assure the efficiency and safety of the final medicine cannot be carried out. Thus the purpose of this work was the development, characterization and stability evaluation of two oral formulations of sildenafil for the treatment of neonatal persistent pulmonary hypertension. After the establishment of a standard operating procedure (SOP) and elaboration, the physicochemical stability parameters appearance, pH, particle size, rheological behaviour and drug content of formulations were evaluated at three different temperatures for 90 days. Equally, prediction of long term stability, as well as, microbiological stability was performed. Formulations resulted in a suspension and a solution slightly coloured exhibiting fruity odour. Formulation I (suspension) exhibited the best physicochemical properties including Newtonian behaviour and uniformity of API content above 90% to assure an exact dosification process.

Isolamento do alcalóide ricinina das folhas de Ricinus communis (Euphorbiaceae) através de cromatografias em contracorrente

Droplet counter-current chromatography, rotation locular counter-current chromatography and high-speed counter-current chromatography were applied to the preparative separation of the alkaloid ricinine from the dichloromethane extracts of Ricinus communis leaves. The solvent system used was composed of dichloromethane-methanol-water (93:35:72 v/v/v) and all techniques led to the isolation of large amounts of the alkaloid. The best result was obtained through HSCCC, since the ricinine yield was respectively 50% and 30% higher than when using RLCCC or DCCC.

Avaliação do óleo essencial de Aloysia sellowii (Briquet) moldenke (Verbenaceae) do Sul do Brasil

This work was performed with the aim of evaluating the chemical variability among samples of Aloysia sellowii (Verbenaceae) collected in different geographical regions as well as the application of supercritical CO2 for obtaining essential oil. Thus, samples were collected in different localities and oils were isolated by hydrodistillation and supercritical CO2. Results showed existence of two chimiotypes in the species (cineole and sabinene). The supercritical CO2 extraction process was appropriate for extraction of A. sellowii essential oil at 40 ºC, 110 bar, 2 mL/min of flow and 10 min of extraction time.