Crystallization transformation of amorphous extracts of traditional Chinese medicine and its effect on dissolution behavior — Taking total flavonoids from Pueraria lobata as an example / 中国药科大学学报

@#In order to guarantee the quality of traditional Chinese medicines (TCMs), the crystallization transformation of complex extracts of TCMs and the influence of solid form on their physicochemical properties were studied.The extract of total flavonoids from Pueraria lobata was taken as a model.Crystallization transformation happened when lofting under different conditions, and the intrinsic dissolution tests were carried out.It was found that humidity was the key factor to induce crystallization of total flavonoids from Pueraria lobata.The greater the wettability was, the more the crystallization was.The dissolution rate of total flavonoids from Pueraria lobata with the most crystallization amount significantly decreased by 96.51% compared to the sample without crystallization.After further simulating the preparation process of total flavonoids from Pueraria lobata, it was found that the wet granulation process with introduced water would also lead to crystallization and reduced dissolution rate.As for all crystallization samples, there was an inversely proportional relationship between the dissolution rates and the amount of crystallization.The risk of crystallization existed both in the storage and preparation process of TCM extracts.Crystallization would significantly affect the dissolution rate, and thus the quality of TCM products.In this study, the crystallization transformation of amorphous complex TCM extracts was discovered, and the effect of the crystallization transformation on its dissolution behavior was systematically studied, which provides a new research idea for assuring the quality of TCM products and promoting the improvement of TCM preparation level.

Evaluation of the remineralizing capacity of silver diamine fluoride on demineralized dentin under pH-cycling conditions

Abstract Objective (1) to determine the effects of the silver diamine fluoride (SDF) and sodium fluoride (NaF) in demineralized dentin exposed to an acid challenge by pH-cycling, (2) to evaluate the remineralizing capacity of SDF/NaF products based on the physicochemical and mechanical properties of the treated dentin surfaces. Methodology In total, 57 human molars were evaluated in different stages of the experimental period: sound dentin - negative control (Stage 1), demineralized dentin - positive control (Stage 2), and dentin treated with SDF/NaF products + pH-c (Stage 3). Several commercial products were used for the SDF treatment: Saforide, RivaStar, and Cariestop. The mineral composition and crystalline and morphological characteristics of the dentin samples from each experimental stage were evaluated by infrared spectroscopy (ATR-FTIR), X-ray diffraction, and electron microscopy (SEM-EDX) analytical techniques. Moreover, the mechanical response of the samples was analyzed by means of the three-point bending test. Statistics were estimated for ATR-FTIR variables by Wilcoxon test, while the mechanical data analyses were performed using Kruskal-Wallis and Mann Whitney U tests. Results Regarding the chemical composition, we observed a higher mineral/organic content in the SDF/NaF treated dentin + pH-c groups (Stage 3) than in the positive control groups (Saforide p=0.03; Cariestop p=0.008; RivaStar p=0.013; NaF p=0.04). The XRD results showed that the crystallite size of hydroxyapatite increased in the SDF/NaF treated dentin + pH-c groups (between +63% in RivaStar to +108% in Saforide), regarding the positive control. SEM images showed that after application of the SDF/NaF products a crystalline precipitate formed on the dentin surface and partially filled the dentin tubules. The flexural strength (MPa) values were higher in the dentin treated with SDF/NaF + pH-c (Stage 3) compared to the positive control groups (Saforide p=0.002; Cariestop p=0.04; RivaStar p=0.04; NaF p=0.02). Conclusions The application of SDF/NaF affected the physicochemical and mechanical properties of demineralized dentin. According to the results, the use of SFD/NaF had a remineralizing effect on the dentin surface even under acid challenge.

Influence of solvent choice and operating conditions on Chlorzoxazone crystal shape and size

Abstract Solubility of pharmaceutical drugs in organic solvents is one of the important parameters to understand the equilibrium concentration of solute-solvent, which helps optimize and design crystallization conditions to obtain the desired product crystals. In the present study, Chlorzoxazone (CHZ) is used as a model pharmaceutical compound to investigate the equilibrium solubility, the influence of solvent and the operating conditions on the shape, and the size distribution. The solubility of CHZ is determined in organic solvents like Isopropanol, Ethanol, and 2-Ethoxyethylacetate, Ethylacetate and Ethyllactate using shake flask method from -5ºC to 60ºC. The solubility of CHZ in these solvents shows an increasing trend as the temperature increases in the following order: ethyllactate + water (0.5+0.5) < ethylacetate < isopropanol < ethanol < 2-ethoxyethylacetate < ethyllactate + water (0.75+0.25). The solvents, isopropanol, ethanol, and ethyl lactate, produce needle-shaped crystals, while 2-ethoxyethylacetate and ethyl acetate tend to produce plate shaped crystals. CHZ crystals obtained from 2-ethoxyethylacetate tend to have plate shaped crystals with a lower aspect ratio and are selected for batch cooling crystallization experiments performed at different cooling rates, and agitation. It is found that the agitation at 300 rpm and the cooling rate 0.2ºC/min produce more uniform crystal size distribution

Diagnóstico molecular indirecto en estudio de familias con hemofilia en Pinar del Río / Indirect molecular diagnosis in a study of families with hemophilia in Pinar del Río

RESUMEN Introducción: la hemofilia es una enfermedad hereditaria que se transmite con un patrón recesivo ligado al cromosoma X. Su expresión clínica está dada por el déficit o la ausencia de actividad de factores de la coagulación (factor VIII para la Hemofilia A y factor IX para la Hemofilia B) Se caracteriza por una marcada heterogeneidad genética, lo que hace complejo su diagnóstico por métodos moleculares directos. En Cuba, se dispone de estudios indirectos por técnica de ligamiento para la caracterización de familias que conviven con hemofilia. Objetivo: describir los resultados de estudios moleculares indirectos en familias con antecedentes de hemofilia en Pinar del Río. Métodos: se realizó una investigación observacional, descriptiva y transversal en el universo de nueve familias que agrupan 10 pacientes en edad pediátrica con diagnóstico de hemofilia en Pinar del Río. La muestra se conformó con cinco familias, cuatro con hemofilia A y una con hemofilia B, a las que se realizó estudio molecular indirecto para diagnóstico de portadoras y diagnóstico prenatal. Resultados: las cinco familias resultaron informativas para los marcadores disponibles. Se identificaron nueve mujeres portadoras y se realizó diagnóstico prenatal de cuatro fetos, de ellos dos enfermos, uno sano y el otro pendiente de resultado. El marcador St14 resultó el más informativo para hemofilia A. Conclusiones: la posibilidad de estudio molecular indirecto contribuye al diagnóstico, asesoramiento y manejo del riesgo de recurrencia de la hemofilia en cada genealogía de manera particular y se presenta como alternativa útil, aunque elemental, para la caracterización genotípica de las familias afectadas.

ABSTRACT Introduction: hemophilia is a hereditary disease transmitted with an X-linked recessive pattern. Its clinical expression is given by the deficit or absence of coagulation factor activity (factor VIII for Hemophilia A and factor IX for Hemophilia B). It is characterized by a marked genetic heterogeneity, which makes its diagnosis by direct molecular methods complex. In Cuba, indirect studies by linkage technique are available for the characterization of families living with hemophilia. Objective: to describe the results of indirect molecular studies in families with a history of hemophilia in Pinar del Río. Methods: an observational, descriptive and transversal research was carried out in the universe of nine families grouping 10 pediatric patients with a diagnosis of hemophilia in Pinar del Río. The sample consisted of five families, four with hemophilia A and one with hemophilia B, which underwent an indirect molecular study for the diagnosis of carriers and prenatal diagnosis. Results: the five families were informative for the available markers. Nine carrier women were identified and prenatal diagnosis was performed in four fetuses, two of which were diseased, one healthy and the other pending results. The St14 marker proved to be the most informative for hemophilia A. Conclusions: the possibility of indirect molecular study contributes to the diagnosis, counseling and management of the risk of recurrence of hemophilia in each genealogy in a particular way and is presented as a useful, although elementary, alternative for the genotypic characterization of affected families.

Series of experiments performed with the droplet evaporation method on low potencies

Homeopathic preparations in low potencies, containing still measurable quantities of the starting substance, constitute a unique research field in homeopathic basic research. Here a series of experiments is presented carried out by means of the droplet evaporation method (DEM), investigating the specificity of the method, and presumed effects of the succussion procedure applied in the production of homeopathic preparations. Methods:DEM analysis consisted in the evaporation of droplets of the potencies perse placed on microscope slides. Resulting patterns were photographed. Images were evaluated by means of ImageJ software, by measuring grey level distribution, texture, and fractality. The experimentation consisted of four series: (i) screening (1x­6x potencies from 19 substances), (ii) differentiation experiments (2x­6x potencies of Echinacea, Baptisia, Luffa, and Spongia), (iii) differentiation between succussed (100 or 10 times) and unsuccussed samples (Echinacea 2x, Baptisia 3x, Baptisia 4x, Luffa 4x, and Spongia 6x). (iv) investigation of the influence upon the patterns of single compounds present in a remedy complex. The experimental set-up stability was examined by systematic positive control experiments. Results:(i) Homeopathic preparations of mineral origin showed the greatest form variety, whereas those of vegetal origin created fractal patterns in the potency range 2x­4x. (ii) Differentiation of potencies of different origin at the same dilution level was possible from 2x to 4x. (iii) In all potency levels, succussed (100 and 10 times) and unsuccussed variants could be significantly differentiated. Significant differences between all variants were found in some cases in potency levels 4x and higher. In general, application of succussion reduced size, homogeneity, and complexity of the DEM patterns. (iv) Patterns of a remedy complex Luffa 4x -Mercurius bijodatum 9x showed a clear predominance of the Luffa 4x; however also the second component, present in a much lower concentration, influenced significantly the pattern of the remedy complex as also differed significantly from the pattern of succussed water control. Conclusions:The results suggest that DEM is a suitable tool for scientific investigation of homeopathic preparations in the low potency range. DEM might be applied to assess further research questions, such different potentization procedures (vessel shape, overhead volume, material), storing time, and difference between batches.

Recent progress on dissolution and absorption of amorphous solid dispersions / 药学学报

The amorphous solid dispersion is one of the most effective formulation approaches to enhance the oral bioavailability of poorly water-soluble drugs. However, the amorphous drugs tend to crystallize during storage or dissolution due to inadequate formulations, preparation techniques, storage and dissolution conditions, thus negating their advantages. Meanwhile, it is often difficult to establish in vitro-in vivo correlation for amorphous solid dispersions owing to the difference between dissolution media and physiological environments and between the apparent concentration and membrane transport flux, the dynamic process of the in vivo absorption, which put great challenges to the development of amorphous solid dispersion products. This review covers the recent progress on the mechanistic study of the in vitro dissolution and in vivo absorption of amorphous solid dispersions, aiming to provide guidance for the formulation development of poorly soluble drugs.

The Influence of Different Extraction Methods/Solvents on Composition, Biological Activities and ADMET Predictions of Phenolics in Tribulus terrestris

Abstract Tribulus terrestris is a plant that has medical importance in treating diseases such as cancer, urinary tract infections, kidney stones, rheumatism, and hypertension. The aim of this study is to examine the effects of extraction methods/solvents on the biological activity and chemical content of the plant and then to determine ADMET predictions of phenolics that were analysed quantitatively using HPLC-DAD in the plant. Maceration methanol (IC50:0.277 mg/mL) and chloroform (0.263 mMFeSO4/mg extract) extracts were found to have the strongest DPPH radical scavenging and iron (III) ion reducing activity, respectively. It was determined that Soxhlet methanol (0.0225 mMTE/mg extract) and Soxhlet chloroform (1.360 mMTE/mg extract) extracts exhibited stronger radical cation (ABTS.+) scavenging and cupric ion reducing activity compared to other extracts, respectively. It was found that ultrasonic bath methanol extracts showed the highest anti-urease (21.47%) and calcium oxalate anti-crystallization (71.54%, 80.52%) activity. It was also found that Soxhlet methanol extract (66.763%) has strong acetylcholinesterase enzyme inhibition capacity compared to other extracts. Pyrocatechol, vanillic acid, vanillin, rutin and rosmarinic acid were analysed by HPLC-DAD in the plant. Moreover, it was determined that methanol extracts obtained using soxhlet, ultrasonic bath, and maceration contained the highest amount of rutin, pyrocatechol, and rutin, respectively. ADMET predictions of phenolics show that these compounds are easily absorbed and do not have toxic effects, suggesting that this species may be used as a natural medicinal and nutritional source in the future after detailed analysis tests.

Study of crystallization, microstructure and mechanical properties of lithium disilicate glass-ceramics as a function of the sintering temperature / Estudo da cristalização, microestrutura e propriedades mecânicas de uma vitrocerâmica de dissilicato de lítio em função da temperatura de sinterização

Objective: The purpose of the present study was to synthesize and characterize lithium disilicate glass-ceramics through the Li2O-SiO2system for determining the most satisfactory sintering parameter by evaluating the crystalline composition, microstructure and mechanical properties. Material and methods: The glass-ceramics were prepared from a glass precursor by means of the melting/cooling technique with a composition of 33.33 Li2O and 66.67 SiO2 (mol.%). The specimens were compressed by the uniaxial pressing technique and three different thermal treatments were used for sintering: 850 °C (Group 1), 900 °C (Group 2), and 950 °C (Group 3), which were determined based on the differential scanning calorimetry (DSC) result. The glass-ceramics were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), Archimedes method, microhardness and biaxial flexural strength analyses. Results: The results regarding XRD predominantly showed lithium disilicate phase for all the heat treatments performed. Moreover, grains with a needle form were more predominantly observed in the SEM images for Group 3, as well as a higher densification and consequently higher mechanical properties. In contrast, Group 1 presented the lowest mechanical properties and densification, as well as the highest porosity. Conclusion: The present study demonstrated how extremely important it is to follow the heat treatment recommended by the manufacturers of ceramics, including time and temperature, which possess direct effects in the crystalline phase formation, as well as in the material's microstructure and mechanical properties (AU)

Objetivo: O presente estudo teve como objetivo sintetizar e caracterizar uma vitrocerâmica de dissilicato de lítio através do sistema Li2O-SiO2para determinar o parâmetro de sinterização mais satisfatório através da avaliação da composição cristalina, microestrutura e propriedades mecânicas. Material e Métodos: As vitrocerâmicas foram preparadas a partir de um vidro precursor pelo método fusão/resfriamento utilizando a composição de 33.33 Li2O e 66.67 SiO2 (mol.%). As amostras foram prensadas utilizando uma técnica de prensagem uniaxial e três tratamentos térmicos diferentes foram utilizadas para sinterização: 850 °C (Grupo 1), 900 °C (Grupo 2), e 950 °C (Grupo 3), que foram determinados através do resultado da análise diferencial de calorimetria. As vitrocerâmicas foram caracterizadas através das análises de difração de raios X (DRX), microscopia eletrônica de varredura (MEV), métodos de Arquimedes, microdureza e ensaio de flexão biaxial. Resultados: Os resultados de DRX mostraram predominantemente a fase de dissilicato de lítio para todos os tratamentos realizados. Além disso, grãos com forma agulhada foram mais predominantemente observados por MEV no grupo 3, assim como uma densificação maior e consequentemente valores maiores das propriedades mecânicas. Em contraste, o grupo 1 apresentou os menores valores de propriedades mecânicas e densificação, e também a maior porosidade. Conclusão: O presente estudo demonstrou como é extremamente importante seguir o tratamento térmico recomendado pelos fabricantes de cerâmica, incluindo tempo e temperatura, que possuem efeitos diretos na formação da fase cristalina, assim como na microestrutura do material e propriedades mecânicas. (AU)

Pharmaceutical cocrystals: A review of preparations, physicochemical properties and applications

Pharmaceutical cocrystals are multicomponent systems in which at least one component is an active pharmaceutical ingredient and the others are pharmaceutically acceptable ingredients. Cocrystallization of a drug substance with a coformer is a promising and emerging approach to improve the performance of pharmaceuticals, such as solubility, dissolution profile, pharmacokinetics and stability. This review article presents a comprehensive overview of pharmaceutical cocrystals, including preparation methods, physicochemical properties, and applications. Furthermore, some examples of drug cocrystals are highlighted to illustrate the effect of crystal structures on the various aspects of active pharmaceutical ingredients, such as physical stability, chemical stability, mechanical properties, optical properties, bioavailability, sustained release and therapeutic effect. This review will provide guidance for more efficient design and manufacture of pharmaceutical cocrystals with desired physicochemical properties and applications.

Research advances in methods of cyclezation mechanism of sesquiterpenes / 中国中药杂志

Terpenes are the largest group of natural products and contain the widest assortment of structural types. Terpene cyclization is also the most complex reaction found in nature. For a long time, terpenoids with diverse structures have attracted natural product chemists to explore their biosynthesis mechanism. Such a large number of terpene skeletons are catalyzed by enzymes called terpene synthase. Sesquiterpene synthase is a kind of terpene synthase, which can catalyze the cyclization of linear precursor farnesyl pyrophosphate(FPP) to sesquiterpene skeletons. Sesquiterpene synthase cyclize a single precursor FPP into many sesquiterpene skeletons. With the continuous discovery of sesquiterpene synthase, the cyclization mechanism of sesquiterpene synthase has been studied deeply. In recent years, with the development and improvement of isotope labeling of substrate FPP and structural analysis of sesquiterpene synthase, the structure and cyclization mechanism of sesquiterpene synthase have been studied more systematically and accurately. In this review, we reviewed the progress of the research methods on the mechanism of sesquiterpene cyclization by substrate isotope labeling and protein structure, as well as the summary and prospect of sesquiterpene synthase research.

An insight into crystallization test: A neoteric approach for screening premalignant and malignant lesions

Introduction: Crystallization test is based on the principle that, when a salt crystallizes out of an aqueous solution, the crystal growth is influenced by the presence of other substances in the solution, such as blood or plant extracts. If a mixture of copper chloride solution with a small amount of whole blood is allowed to crystallize under controlled experimental conditions, an aggregate of crystals forms. Crystallization method can be used as a diagnostic aid to provide information about the systemic conditions and general health of the patient. Aim: This study aims to study the patterns of crystallization and to further determine the efficacy of crystallization test as a screening modality in premalignant lesions and oral squamous cell carcinoma (OSCC). Materials and Methods: Fifty patients of OSCC, 50 patients of premalignant lesions, and 50 healthy individuals were selected. One drop of blood was collected from the study groups to perform crystallization using cupric chloride. Statistical Analysis Used: Statistical analysis was performed using Chi-square test, Student's t-test (two-tailed), and analysis of variance. Results: The different patterns of crystals formed were studied and statistically analyzed. Conclusion:Based on the study, it was concluded that Crystallization test can be used as an effective screening modality for detection of premalignant lesions and OSCC

Pharmaceutical polymorphism of a 5´-O-oxalatoyl prodrug of zidovudine (azidothymidine)

The importance of polymorphism in pharmaceuticals makes its study relevant. The aim of this study was to investigatethe solid-state forms in which 3´-azido-2´, 3´-dideoxi-5´-O-oxalatoyl-thymidinic acid (AZT-Ac), a zidovudine (AZT)prodrug with improved pharmacokinetic properties, may exist. Samples were prepared using different crystallizationconditions and characterized using powder X-ray diffraction, solid-state nuclear magnetic resonance, differentialscanning calorimetry, thermogravimetry, and hot-stage microscopy. Pharmaceutical relevant properties such assolid-state stability and intrinsic dissolution rate (IDR) at 37°C in simulated gastric fluid (SGF) were also evaluated.AZT-Ac was found to able to exist as a crystalline polymorph (AZT-Ac-C) and an amorphous phase (AZT-Ac-A),which were thoroughly characterized. At 40°C/75% relative humidity (RH), AZT-Ac-A, in part, devitrified toAZT-Ac-C and partially hydrolyzed to AZT after 7 and 14 days of storage, respectively. AZT-Ac-C was physicallystable at 40°C/75% RH but partly hydrolyzed to AZT after 14 days of storage. In SGF, AZT-Ac-C exhibited a linearID profile and provided an ID rate of 0.494 mg/min/cm2, whereas AZT-Ac-A exhibited a nonlinear profile. Therefore,the crystalline form demonstrated the advantages over the amorphous one in terms of solid-state stability and IDR, butthe approaches to enhance its stability should be considered for further formulation of this prodrug.

Effect of systemic administration of phytosterol on lacrimal quality of dogs / Efeito da administração sistêmica de fitoesterol na qualidade lacrimal de cães

The tear lipid layer (oily outer layer) reduces evaporation and prevents tear overflow. In dogs, reductions in the lipid components of this layer (cholesterol, triglycerides and phospholipids) can cause eye serious diseases. In this way, the tear crystallization test analyzes the lacrimal quality, however, it is less used in veterinary. As phytosterol reduces blood cholesterol, the objective of this study was to investigate, through the tear crystallization test, whether the systemic administration of this drug influences the lacrimal quality of healthy dogs and, in addition, to verify differences in the interpretation of the ophthalmic test between different evaluators. Eight beagles, healthy, of both sexes, young and adults, without clinical ophthalmic signs apparent were selected. Basal lacrimal samples (D0) were collected from the right and left eye of all animals with glass capillary tube and arranged on a glass slide for scanning the images and subsequent microscopic analysis. Subsequently, all were medicated with the phytosterol (Collestra® 650 mg: 1 capsule, orally, every 12 hours, for 15 days). After seven (D7) and fifteen (D15) days of this systemic administration, the tear crystallization test in both eyes of all dogs was again performed for statistical comparison with the baseline results. The photographs of the slides were classified by four evaluators (AV1 and AV2 with professional experience in ophthalmology and AV3 and AV4 without previous professional experience in ophthalmology), following standards established by Rolando (1984). The results were statistically verified by analysis of simple variance (ANOVA One-Way). There was no statistical difference in the tear crystallization test between the established periods and in relation to the different ophthalmic test evaluators (p≤0.05). Although phytosterols reduce blood cholesterol levels, it was observed in the present study that these drugs when administered systemically did not interfere in the tear lipid layer and, consequently, in the lacrimal quality of healthy dogs, and may be prescribed as lipid-lowering agents for patients with ocular diseases, especially the lacrimal ones.

A camada lipídica lacrimal (camada externa oleosa) reduz a evaporação e previne o transbordamento lacrimal. Em cães, reduções nos componentes lipídicos desta camada (colesterol, triglicérides e fosfolipídios) podem causar doenças graves nos olhos. Desta forma, o teste de cristalização lacrimal analisa a qualidade lacrimal, no entanto, é menos utilizado em veterinária. Como o fitoesterol reduz o colesterol sanguíneo, o objetivo deste estudo foi investigar, através do teste de cristalização lacrimal, se a administração sistêmica deste fármaco influencia na qualidade lacrimal de cães hígidos e, além disso, verificar diferenças na interpretação do teste oftalmológico entre diferentes avaliadores. Oito beagles, saudáveis, de ambos os sexos, jovens e adultos, sem sinais oftalmológicos clínicos aparentes foram selecionados. Amostras lacrimais basais (D0) foram coletadas do olho direito e esquerdo de todos os animais, com tubo capilar de vidro e, dispostas em lâmina de vidro para escaneamento das imagens e posterior análise microscópica. Ato contínuo todos foram medicados com o fitoesterol (Collestra® 650 mg: 1 cápsula, por via oral, a cada 12 horas, durante 15 dias). Após sete (D7) e quinze (D15) dias desta administração sistêmica, o teste de cristalização lacrimal em ambos os olhos de todos os cães foi novamente realizado para comparação estatística com os resultados basais. As fotografias das lâminas foram classificadas por quatro avaliadores (AV1 e AV2 com experiência profissional em oftalmologia e AV3 e AV4 sem experiência profissional prévia em oftalmologia), seguindo padrões estabelecidos por Rolando (1984). Os resultados foram estatisticamente verificados pela análise de variância simples (ANOVA One-Way). Não houve diferença estatística no teste de cristalização lacrimal entre os períodos estabelecidos e em relação aos diferentes avaliadores de teste oftalmológico (p≤0,05). Embora os fitoesteróis reduzam os níveis de colesterol no sangue, observou-se no presente estudo que esses fármacos quando administrados sistemicamente não interferiram na camada lipídica da lágrima e, consequentemente, na qualidade lacrimal de cães hígidos, podendo ser prescritos como agentes hipolipemiantes para pacientes com doenças oculares, especialmente as lacrimais.

Fractalidad en un patrón de cristalización de moco cervical humano obtenido en período periovulatorio / Fractality in a pattern of crystallization of human cervical mucus obtained at periovulatory period

Introducción: La secreción cervical cumple una función importante en el proceso reproductivo humano y algunas sus características (e.g., el cristalizar) cambian dependiendo de las variaciones en los niveles de hormonas esteroidales sexuales. Objetivo: Reportar la fractalidad observada en un patrón de cristalización de moco cervical humano. Métodos: El moco fue obtenido de una paciente en período periovulatorio. La imagen de un patrón cristalino de moco cervical fue transformada a blanco y negro y analizada mediante Fractalyse v. 2.4, el cual determina la dimensión fractal (DF) para cada imagen estudiada. Se analizaron tres zonas para la imagen seleccionada. Resultados: Se encontró, para la Zona 1, DF (± desviación estándar) = 1,36 ± 0,02 (r² = 0,9985); para la Zona 2, DF = 1,35 ± 0,02 (r² = 0,9979); y para la Zona 3, DF = 1,36 ± 0,03 (r² = 0,9958). Las DF encontradas para las zonas estudiadas fueron estadísticamente iguales entre sí. Conclusiones: El moco cervical humano en período periovulatorio puede seguir un patrón de cristalización tipo fractal, especialmente en lo referente a la semejanza de sus componentes estructurales (criterio de autosimilitud) (AU)

Introduction: Cervical secretion plays an important role in the human reproductive process and its characteristics (e.g., crystallization) change depending on variations in the levels of sex steroid hormones. Objective: The purpose of this brief communication is to report the fractality observed in a crystallization pattern of human cervical mucus. Methods: Mucus samples were obtained from a patient in the periovulatory period and an image of the crystalline pattern of cervical mucus was transformed to black and white and analysed by Fractalyse v. 2.4, which determines the fractal dimension (FD) for each studied image. Three zones were analysed for the selected image. Results: It was found that, for Zone 1, FD (± standard deviation) = 1.36 ± 0.02 (r² = 0.9985); for Zone 2, FD = 1.35 ± 0.02 (r² = 0.9979); and for Zone 3, FD = 1.36 ± 0.03 (r² = 0.9958). Zones studied were statistically equal to each other regarding their FD. Conclusions: Human cervical mucus obtained at periovulatory period can follow a fractal-like pattern of crystallization, especially in relation to the similarity of its structural components (criterion of self-similarity) (AU)

Modificações estruturais e reológicas em chocolate amargo devido à alteração do tipo de gordura utilizada / Structural and rheological changes in bitter chocolate due to the change in the type of fat used

O chocolate é conhecido mundialmente, proveniente do fruto do cacaueiro (Theobroma cacao) normalmente consumido em forma de barra, mas também podendo ser usado de inúmeras formas como coberturas, recheios dentre outras. Um importante componente na produção do chocolate é a gordura utilizada, uma vez que esta é responsável pela textura, brilho e características organolépticas do produto. O objetivo deste trabalho foi utilizar a manteiga de cupuaçu (proveniente do fruto da Theobroma grandiflorum) na elaboração de chocolate amargo. Para tanto a manteiga de cacau foi substituída de forma parcial e total. Foram desenvolvidas duas formulações de chocolate padrão com liquor de cacau (P1) e com cacau em pó (P2), e quatro formulações com substituição parcial da manteiga de cacau por manteiga de cupuaçu a partir de P2(F1 e F2) e de P1 (F3 e F4). As amostras elaboradas e os ingredientes (líquor de cacau, cacau em pó, manteiga de cacau e manteiga de cupuaçu) foram avaliadas por análise térmica (DSC-Differential Scanning Calorimetry), reologia, tamanho de partícula, composição em ácidos graxos e em triacilgliceróis, índice de temperagem e índice de resfriamento, bem como testes de acompanhamento de 112 dias como cor, atividade de água e textura. A manteiga de cupuaçu apresentou maior quantidade de ácido oleico quando comparada com a manteiga de cacau, aproximadamente 11,5%, e também características reológicas diferentes dos padrões: tensões iniciais variaram de 3,4 ± 0,3 a 7,9 ± 2,0 Pa para as amostras e 2,9 ± 1,4 a 6,2 ± 0,7 Pa para os padrões; viscosidade de 1,6 ± 0,1 a 2,9 ± 0,4 Pa*s para as amostras e 1,9 ± 0,8 a 2,9 ± 0,9 Pa*s para os padrões; tamanho de partícula das amostras de 21 ± 2 a 22 ± 2 µm, padrões de 20 ± 2 a 34 ± 4 µm. Durante os 112 dias de estudo de prateleira: Aw variou de 0,405 ± 0,03 a 0,424 ± 0,02 nas amostras e 0,399 ± 0,03 no padrão; textura variou de 16,3 ± 1,2 a 31,6 ± 2,0 N para as amostras e 25,9 ± 3,0 a 28,6 ± 7,2 N para os padrões; WI variou de 24,1 ± 0,6 a 25,4 ± 0,3 para as amostras e 23,0 ± 0,4 a 23,9 ± 0,8 para os padrões; ΔE variou de 0,4 a 2,2 para as amostras e de 0,5 a 1,2 para os padrões. Concluiu-se que: A variação do líquor de cacau para cacau em pó acarretou aumentando do tempo total de processo em aproximadamente 15 min. Os chocolates com maior teor de manteiga de cupuaçu apresentaram aumento em triacilglicerol C54, com redução de POP e POS. A faixa de fusão dos chocolates com maiores porcentagens de manteiga de cupuaçu (F3 e F4) foi maior do que para chocolates formulados apenas com manteiga de cacau (P1 e P2). A manteiga de cupuaçu tem relação direta com a queda da tensão inicial e da viscosidade (sem diferença significativa, p<0,05) nos chocolates produzidos. O baixo ponto de fusão do ácido oleico contido na manteiga de cupuaçu alterou a temperatura final e o valor do índice de temperagem nas amostras com maior teor de manteiga de cupuaçu (F3 e F4)

The chocolate is known worldwide, coming from the fruit of the cacao (Theobroma cacao) normally consumed in the form of a bar, but also can be used in countless ways like coverings, fillings among others. An important component in the production of chocolate is the fat used, since it is responsible for the texture, brightness and organoleptic characteristics of the product. The objective of this work was to use cupuassu butter (from the fruit of Theobroma grandiflorum) in elaboration of bitter chocolate. For this purpose, the cocoa butter was partially and totally replaced. Two formulations of standard chocolate with cocoa liquor (P1) and with cocoa powder (P2) were developed, and four formulations with partial replacement of cocoa butter by cupuassu butter from P2 (F1 and F2) and P1 (F3 and F4). The elaborated samples and the ingredients (cocoa liquor, cocoa powder, cocoa butter and cupuassu butter) were evaluated by DSC, rheology, particle size, fatty acid composition and triacylglycerol, temperature index and cooling index, as well as follow-up tests of 112 days such as color, water activity and texture. The cupuassu butter presented a higher amount of oleic acid when compared to cocoa butter, approximately 11.5%, and also different rheological characteristics of the standards: initial tensions ranged from 3.4 ± 0.3 to 7.9 ± 2, 0 Pa for the samples and 2.9 ± 1.4 to 6.2 ± 0.7 Pa for the standards; viscosity of 1.6 ± 0.1 to 2.9 ± 0.4 Pa*s for the samples and 1.9 ± 0.8 to 2.9 ± 0.9 Pa*s for the standards; sample particle size from 21 ± 2 to 22 ± 2 µm, patterns from 20 ± 2 to 34 ± 4 µm. During the 112 days of shelf study: Aw ranged from 0.405 ± 0.03 to 0.424 ± 0.02 in the samples and 0.399 ± 0.03 in the standard; texture ranged from 16.3 ± 1.2 to 31.6 ± 2.0 N for the samples and 25.9 ± 3.0 to 28.6 ± 7.2 N for the standards; WI ranged from 24.1 ± 0.6 to 25.4 ± 0.3 for the samples and 23.0 ± 0.4 to 23.9 ± 0.8 for the standards; ΔE ranged from 0.4 to 2.2 for the samples and from 0.5 to 1.2 for the standards. It was concluded that: The variation of cocoa liquor to cocoa powder increased the total process time by approximately 15 min. The chocolates with higher content of cupuassu butter presented increase in triacylglycerol C54, with reduction of POP and POS. The melting range of chocolates with higher percentages of cupuassu butter (F3 and F4) was higher than for chocolates formulated with cocoa butter alone (P1 and P2). Cupuassu butter is directly related to the drop in initial tension and viscosity (without significant difference, p <0.05) in the chocolates produced. The low melting point of the oleic acid contained in the cupuassu butter altered the final temperature and the temperature index value in the samples with the highest cupuassu butter content (F3 and F4)

Detection of monosodium urate crystals with dual-energy CT in gout patients / 中华全科医师杂志

Objective To evaluate the application of the dual-energy CT (DECT) in detection of monosodium urate (MSU) crystals in gout patients.Methods The imaging and clinical data of 101 patients with suspected gout were retrospectively analyzed,including 64 cases of clinically diagnosed gout (gout group) and 37 non-gout cases (non-gout group).The DECT examination was performed for 85 joints in gout group and 42 joints in non-joint group.The value of DECT in detection of MSU crystals was evaluated with receiver operating characteristic (ROC) curve.Results There were significant differences in gender (x2=5.32,P=0.03) and blood uric acid levels (t=1.95,P=0.04) between gout and non-gout groups.The detection rate of MSU in gout group was significantly higher than that of non-gout group (x2=30.52,P＜0.001).The area under the ROC curve (AUC) of DECT in detection of was 0.74±0.05 (Mean±SE),95％CI:0.64-0.85.The sensitivity,specificity,positive predictive value and negative predictive value of the DECT in detection of gouty stone was 0.844,0.703,83.1％ and 72.2％,respectively.Conclusion The dual-energy CT has high sensitivity,specificity and reliability for the detection and diagnosis of monosodium urate crystals in joints of gout patients.

Effectiveness of crystallization test in screening of potentially malignant oral disorders and oral cancer

This study aims to determine the effectiveness of crystallization test in screening of oral potentially malignant disorders (PMDs) and oral cancer. Materials and Methods: Thirty patients of oral PMD, 30 patients of oral cancer and 40 normal healthy people were selected. One drop of blood was collected and added to 1 cc of double-distilled water at room temperature to get a final dilution of 6% hemolyzed blood. 0.1–0.2 cc of this blood sample is added to 10 cc of 20% cupric chloride solution and further is subjected to crystallization test. Results: In the normal healthy group, the pattern was typical with an eccentrically placed center of gravity with needles arranged in radiating fashion. Whereas in oral PMD and cancer groups, there was “transverse form” formation. This test had sensitivity and specificity of about 83.33% and 86.84% for PMDs group and 96.30% and 86.84% for oral cancer group respectively. Conclusion: Crystallization test was found to be sensitive, reliable, economical and less-invasive procedure for screening of oral PMDs and oral cancer.

Prokaryotic expression， purification and crystallization of CYP71AV1, key enzyme in artemisinin biosynthesis / 中国中药杂志

Malaria is a worldwide epidemic that extensively endangers health of human beings. Before artemisinin was developed to treat with malaria, about 400 million person-time of malaria infections and at least 1 million deaths from malaria were reported in the world every year. Thus malaria has been listed as one of the world's three major death diseases by the WHO. The discovery of artemisinin by Chinese scientists created a novel therapy approach to treat with malaria effectively. Amorpha-4,11-diene oxidase is a plant cytochrome P450 enzymes, i.e. CYP71AV1, which catalyzes each of the three oxidation steps from amorpha-4,11-diene to form artemisinic acid, the intermediate of artemisinin. CYP71AV1 is the key enzyme in artemisinin biosynthesis. By constructing the prokaryotic expression vector pCWOri(+)-CYP71AV1, functional expression and purification of complementary CYP71AV1 were performed. The enzyme activity was monitored by CO differential spectrum assay and the heme-based activity analysis. The preliminary crystallization condition was obtained by crystallization screening. These studies provide basis for resolving the crystal structure of CYP71AV1 and for producing artemisinin in large scale through biosynthetic biology approach, and will provide references for over expression, purification and crystallization of other plant P450 enzymes.

The effects of sinter temperature on the crystalline phase and microstructural evolution of lithium disilicate glass-ceramic / 实用口腔医学杂志

Objective:To investigate the influence of sinter temperature alteration on the crystalline phase and microstructure of lithium disilicate glass-ceramic.Methods:Samples of lithium disilicate glass-ceramic were heated using the standard two stage heating-schedule at different final temperatures.All samples were observed by X-ray diffractometer (XRD),field emission scanning electron microscope(FESEM) and energy-dispersive X-ray spectroscopy(FE-SEM-EDS) for the evaluation of crystalline phase and microstructural evolution.Results:Crystalline phase and microstructure of ceramic samples showed significant changes during processing at different temperatures,especially at 800 ℃.Samples sintered at 840 ℃ displayed higher crystallinity(P<0.05) and denser microstructure.Conclusion:Temperature control is important in ceramic sintering.800 ℃ and 840 ℃ are the critical temperature points in the crystalline phase and microstructural evolution of lithium disilicate glass-ceramic.

Properties and in vitro dissolution of indomethacin Co-PVP amorphous preparation / 中国药学杂志

OBJECTIVE: To prepare indomethacin amorphous preparation with Co-PVP as carrier, characterize it for exploring the interaction between indomethacin and Co-PVP, and investigate the difference of dissolution between indomethacin crystalline and amorphous preparations. METHODS: The inhibitory effect of Co-PVP on the crystallization of indomethacin supersaturated solution was studied. The indomethacin amorphous preparation was prepared by solvent evaporation method and characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared spectroscopy (FT-IR). In addition, the dissolution behavior in vitro was investigated. RESULTS: Co-PVP had an inhibitory effect on the crystallization of indomethacin supersaturated solution evidently. Indomethacin existed in amorphous state in Co-PVP as hydrogen bonds formed between them. The amorphous preparation of indomethacin-Co-PVP improved the dissolution rate and extent obviously. CONCLUSION: The indomethacin amorphous preparation with Co-PVP as carrier can improve the dissolution in vitro significantly, which providing a reference for obtaining stable amorphous preparation.