Molecular engineering of transketolase from Escherichia coli and tartaric semialdehyde biosynthesis / 生物工程学报

Transketolase (EC 2.2.1.1, TK) is a thiamine diphosphate-dependent enzyme that catalyzes the transfer of a two-carbon hydroxyacetyl unit with reversible C-C bond cleavage and formation. It is widely used in the production of chemicals, drug precursors, and asymmetric synthesis by cascade enzyme catalysis. In this paper, the activity of transketolase TKTA from Escherichia coli K12 on non-phosphorylated substrates was enhanced through site-directed saturation mutation and combined mutation. On this basis, the synthesis of tartaric semialdehyde was explored. The results showed that the optimal reaction temperature and pH of TKTA_M (R358I/H461S/R520Q) were 32 ℃ and 7.0, respectively. The specific activity on d-glyceraldehyde was (6.57±0.14) U/mg, which was 9.25 times higher than that of the wild type ((0.71±0.02) U/mg). Based on the characterization of TKTA_M, tartaric acid semialdehyde was synthesized with 50 mmol/L 5-keto-d-gluconate and 50 mmol/L non-phosphorylated ethanolaldehyde. The final yield of tartaric acid semialdehyde was 3.71 g with a molar conversion rate of 55.34%. Hence, the results may facilitate the preparation of l-(+)-tartaric acid from biomass, and provide an example for transketolase-catalyzed non-phosphorylated substrates.

Isolation of Penicillium expansum WH-3 for the production of L(+)-tartaric acid / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The L(+)-form of tartaric acid (L(+)-TA) exists extensively in nature, and is widely used in the food, chemical, textile, building, and pharmaceutical industries (Su et al., 2001). The main method for L(+)-TA production is microbial transformation by cis-epoxysuccinate hydrolase (CESH), which can catalyze the asymmetric hydrolysis of cis-epoxysuccinic acid or its salts to TA or tartrate (Bao et al., 2019). Seventeen species containing CESH have been isolated so far. However, most species for L(+)-TA production have been reported from bacteria (Xuan and Feng, 2019). The only fungus isolated from soil by our lab recently, that could be used as catalyst for the process under acidic condition, is Aspergillus niger WH-2 (Bao et al., 2020). In order to find strains with new characteristics, this study attempted to isolate a new CESH source from fungi and investigate its application value.

Electrochemical fingerprint of traditional Chinese medicines based on BrO⁻₃-Ce⁴⁺-H⁺-malonic acid/tartaric acid chemical oscillating system / 中国中药杂志

A new composite organic oscillating reaction system based on BrO₃-Ce(SO₄)₂-H₂SO₄-malonic acid/tartaric acid was proposed in this paper. On the basis of the influence of the concentration of each component on the stability and characteristic parameters of the blank system, the electrochemical fingerprints of 30 kinds of traditional Chinese medicines (TCM) were obtained. The results showed that the electrochemical fingerprint can be used for the identification of TCMs, the distinguishment of different parts and the appraisal of genuineness, which is fast, sensitive and accurate. At the same time, we explored and verified the mechanism of oscillation and the formation mechanism of TCM fingerprint.

Sugars, organic acids, and phenolic compounds of ancient grape cultivars (Vitis vinifera L.) from Igdir province of Eastern Turkey

BACKGROUND: The Eurasian grapevine (Vitis vinifera L.) is the most widely cultivated and economically important horticultural crop in the world. As a one of the origin area, Anatolia played an important role in the diversification and spread of the cultivated form V. vinifera ssp. vinifera cultivars and also the wild form V. vinifera ssp. sylvestris ecotypes. Although several biodiversity studies have been conducted with local cultivars in different regions of Anatolia, no information has been reported so far on the biochemical (organic acids, sugars, phenolic acids, vitamin C) and antioxidant diversity of local historical table V. vinifera cultivars grown in Igdir province. In this work, we studied these traits in nine local table grape cultivars viz. 'Beyaz Kismis' (synonym name of Sultanina or Thompson seedless), 'Askeri', 'El Hakki', 'Kirmizi Kismis', 'Inek Emcegi', 'Hacabas', 'Kerim Gandi', 'Yazen Dayi', and 'Miskali' spread in the Igdir province of Eastern part of Turkey. RESULTS: Variability of all studied parameters is strongly influenced by cultivars (P < 0.01). Among the cultivars investigated, 'Miskali' showed the highest citric acid content (0.959 g/l) while 'Kirmizi Kismis' produced predominant contents in tartaric acid (12.71 g/l). The highest glucose (16.47 g/100 g) and fructose (15.55 g/100 g) contents were provided with 'Beyaz Kismis'. 'Kirmizi Kismis' cultivar had also the highest quercetin (0.55 mg/l), o-coumaric acid (1.90 mg/l), and caffeic acid (2.73 mg/l) content. The highest ferulic acid (0.94 mg/l), and syringic acid (2.00 mg/l) contents were observed with 'Beyaz Kismis' cultivar. The highest antioxidant capacity was obtained as 9.09 μmol TE g-1 from 'Inek Emcegi' in TEAC (Trolox equivalent Antioxidant Capacity) assay. 'Hacabas' cultivar had the highest vitamin C content of 35.74 mg/100 g. CONCLUSIONS: Present results illustrated that the historical table grape cultivars grown in Igdir province of Eastern part of Turkey contained diverse and valuable sugars, organic acids, phenolic acids, Vitamin C values and demonstrated important antioxidant capacity for human health benefits. Further preservation and use of this gene pool will be helpful to avoid genetic erosion and to promote continued agriculture in the region.

Relationship between the climbing up and climbing down stairs domain scores on the FES-DMD, the score on the Vignos Scale, age and timed performance of functional activities in boys with Duchenne muscular dystrophy / Relação entre escore FES-DMD-subir e descer escada com escore Escala Vignos, idade e tempo de realização das atividades em meninos com Distrofia Muscular de Duchenne

BACKGROUND: Knowing the potential for and limitations of information generated using different evaluation instruments favors the development of more accurate functional diagnoses and therapeutic decision-making. OBJECTIVE: To investigate the relationship between the number of compensatory movements when climbing up and going down stairs, age, functional classification and time taken to perform a tested activity (TA) of going up and down stairs in boys with Duchenne muscular dystrophy (DMD). METHOD: A bank of movies featuring 30 boys with DMD performing functional activities was evaluated. Compensatory movements were assessed using the climbing up and going down stairs domain of the Functional Evaluation Scale for Duchenne Muscular Dystrophy (FES-DMD); age in years; functional classification using the Vignos Scale (VS), and TA using a timer. Statistical analyses were performed using the Spearman correlation test. RESULTS: There is a moderate relationship between the climbing up stairs domain of the FES-DMD and age (r=0.53, p=0.004) and strong relationships with VS (r=0.72, p=0.001) and TA for this task (r=0.83, p<0.001). There were weak relationships between the going down stairs domain of the FES-DMD-going down stairs with age (r=0.40, p=0.032), VS (r=0.65, p=0.002) and TA for this task (r=0.40, p=0.034). CONCLUSION: These findings indicate that the evaluation of compensatory movements used when climbing up stairs can provide more relevant information about the evolution of the disease, although the activity of going down stairs should be investigated, with the aim of enriching guidance and strengthening accident prevention. Data from the FES-DMD, age, VS and TA can be used in a complementary way to formulate functional diagnoses. Longitudinal studies and with broader age groups may supplement this information. .

CONTEXTUALIZAÇÃO: Conhecer as potencialidades e limitações das informações geradas por diferentes instrumentos de avaliação favorece o desenvolvimento mais preciso do diagnóstico funcional e da tomada de decisão terapêutica. OBJETIVO : Investigar a relação entre o número de movimentos compensatórios ao subir e descer escadas, idade, classificação funcional e tempo de realização de atividade (TA) em meninos com Distrofia Muscular de Duchenne (DMD). MÉTODO : Foi utilizado banco de filmes de 30 meninos com DMD realizando atividades funcionais. Os movimentos compensatórios foram avaliados pela Escala de Avaliação Funcional para Distrofia Muscular de Duchenne (FES-DMD), domínio subir e descer escada; a idade, mensurada em anos; a classificação funcional foi pesquisada pela Escala de Vignos (EV), e o TA foi cronometrado. Foi utilizado o teste de correlação de Spearman. RESULTADOS : Existe moderada relação entre a FES-DMD-subir escada e a idade (r=0,53, p=0,004) e forte relação com a EV (r=0,72, p=0,001) e TA dessa tarefa (r=0,83, p<0,001). Houve fraca relação entre a FES-DMD-descer escada e a idade (r=0,40, p=0,032), EV (r=0,65, p=0,002) e o TA dessa tarefa (r=0,40, p=0,034). CONCLUSÃO : Esses achados indicam que a avaliação da tarefa de subir escada pode trazer informações mais relevantes sobre a evolução da doença, embora a atividade de descer escada deva ser pesquisada visando à orientação e prevenção de acidentes. A utilização conjunta de dados provenientes da FES-DMD, da idade e do TA pode se complementar para formulação do diagnóstico funcional. Estudos longitudinais e com outras faixas etárias mais amplas podem complementar tal informação. .

Optimization of the fermentation conditions for 5-keto-D-gluconic acid production / 生物工程学报

Gluconobacter oxydans converts glucose to gluconic acid and subsequently to 5-keto-D-gluconic acid (5-KGA), a precursor of industrially important L(+)-tartaric acid. To increase the yield of 5-KGA, fermentation conditions of 5-KGA production was optimized. Under the optimum medium and culture conditions in the shake flask, the highest 5-KGA production reached 19.7 g/L, increased by 43.8% after optimization. In a 5-L bioreactor, the pH was controlled at 5.5 and dissolved oxygen (DO) at 15%, 5-KGA production reached 46.0 g/L, raised at least 1.3 times than in the shake flask. Glucose feeding fermentation process was further developed, and the highest 5-KGA production of 75.5 g/L with 70% of yield was obtained, 32.0% higher than the highest reported value. Therefore, this newly developed fermentation process provided a practical and effective alternative for the commercial production of 5-KGA, and further of L(+)-tartaric acid.

Production of L(+)-tartaric acid by immobilized Rhizobium strain BK-20 / 生物工程学报

The cis-epoxysuccinate hydrolase (CESH) from Rhizobium strain BK-20 is the key enzyme for L(+)-tartaric acid production. To establish a highly efficient and stable production process, we first optimized the enzyme production from Rhizobium strain BK-20, and then developed an immobilized cell-culture process for sustained production of L(+)-tartaric acid. The enzyme activity of free cells reached (3 498.0 +/- 142.6) U/g, and increased by 643% after optimization. The enzyme activity of immobilized cells reached (2 817.2 +/- 226.7) U/g, under the optimal condition with sodium alginate as carrier, cell concentration at 10% (W/V) and gel concentration at 1.5% (W/V). The immobilized cells preserved high enzyme activity and normal structure after 10 repeated batches. The conversion rate of the substrate was more than 98%, indicating its excellent production stability.

Diet of the Fuscous Flycatcher Cnemotriccus fuscatus (Wied, 1831) Aves, Tyrannidae - in three habitats of the northern Pantanal, Mato Grosso, Brazil / Dieta de Cnemotriccus fuscatus (Wied, 1831) - Aves, Tyrannidae - em três habitats do Pantanal norte, Mato Grosso, Brasil

The Fuscous Flycatcher (Cnemotriccus fuscatus) is a medium-sized Tyrannidae widespread in South America. Despite its large distribution, there have been very few studies on its diet, especially in different habitats. This study presents data on diet variation in three habitats in the Pantanal wetlands in the state of Mato Grosso, Brazil. The specimens were captured through a mist-netting programme between February 2000 and May 2010, in the Retiro Novo Farm, in the Poconé municipality. Birds were captured in three vegetation types: Landizal, Cambarazal and Cordilheira. Tartar emetic was used to obtain the regurgitation samples identified at order level. We captured 61 individuals (21, 26 and 14 in the above described habitats, respectively). Diet of C. fuscatus differed between the three habitats. Ants and beetles were the most relevant prey items either in numerical frequency (NF) or in frequency of occurrence (OF), in terms of the overall diet (NF = 27.34% and 37.89%; OF = 36.06% and 75.4%, respectively). However, in Cordilheira, seeds and beetles dominated the NF (21.8% and 38.1%, respectively) and OF (28.5% and 85.7%, respectively). Cnemotriccus fuscatus was found to have an omnivorous diet, although in Cambarazal, individuals preyed exclusively on arthropods. The present study provides an important contribution to the knowledge of the diet of a poorly studied Neotropical bird.

O Guaracavuçu (Cnemotriccus fuscatus) é um tyranídeo de tamanho médio, bem distribuído na América do Sul. Apesar de sua ampla distribuição, existem poucos estudos sobre a sua dieta, especialmente em diferentes habitats. Este estudo apresenta dados sobre a variação da dieta de C. fuscatus, em três diferentes fitofisionomias do Pantanal norte, Mato Grosso, Brasil. As aves foram capturadas em redes de neblina entre fevereiro de 2000 e maio de 2010, na fazenda Retiro Novo no município de Poconé. Os espécimes foram amostradas em três diferentes tipos de vegetação: Cambarazal, Landizal e Cordilheira. O tartarato emético foi usado para obtenção das amostras de regurgito que foram identificadas ao menor nível taxonômico possível. Foram capturados 61 indivíduos (26, 21 e 14 indivíduos nos habitats descritos acima, respectivamente). A dieta de C. fuscatus foi diferente entre as três fitofisionomias. Em geral, Formicidae e Coleoptera foram os itens alimentares mais relevantes tanto nas frequências numérica (FN) (FN 27,34% e 37,89%, respectivamente) quanto na frequência de ocorrência (FO) (FO = 36,06% e 75,4%, respectivamente). Entretanto, na Cordilheira as sementes (ou frutos) e os Coleoptera dominaram a FN (21,8% e 38,1%, respectivamente) e a FO (28,5% e 85,7%, respectivamente). Cnemotriccus fuscatus apresentou uma dieta onívora, porém no Cambarazal a espécie consumiu apenas artrópodes. O presente estudo fornece uma importante contribuição para o conhecimento da dieta de uma ave Neotropical tão pouco estudada.

Crystal structures and biochemical studies of human lysophosphatidic acid phosphatase type 6

Lysophosphatidic acid (LPA) is an important bioactive phospholipid involved in cell signaling through Gprotein-coupled receptors pathways. It is also involved in balancing the lipid composition inside the cell, and modulates the function of lipid rafts as an intermediate in phospholipid metabolism. Because of its involvement in these important processes, LPA degradation needs to be regulated as precisely as its production. Lysophosphatidic acid phosphatase type 6 (ACP6) is an LPA-specific acid phosphatase that hydrolyzes LPA to monoacylglycerol (MAG) and phosphate. Here, we report three crystal structures of human ACP6 in complex with malonate, L-(+)-tartrate and tris, respectively. Our analyses revealed that ACP6 possesses a highly conserved Rossmann-foldlike body domain as well as a less conserved cap domain. The vast hydrophobic substrate-binding pocket, which is located between those two domains, is suitable for accommodating LPA, and its shape is different from that of other histidine acid phosphatases, a fact that is consistent with the observed difference in substrate preferences. Our analysis of the binding of three molecules in the active site reveals the involvement of six conserved and crucial residues in binding of the LPA phosphate group and its catalysis. The structure also indicates a water-supplying channel for substrate hydrolysis. Our structural data are consistent with the fact that the enzyme is active as a monomer. In combination with additional mutagenesis and enzyme activity studies, our structural data provide important insights into substrate recognition and the mechanism for catalytic activity of ACP6.

Formulation and in vitro evaluation of fast dissolving tablets of metoprolol tartrate

The demand for fast dissolving tablets has been growing during the last decade, especially for elderly and children who have swallowing difficulties. In the present work, fast dissolving tablets of metoprolol tartrate, were prepared using sodium starch glycolate, sodium croscarmellose and crospovidone as superdisintegrants, by the direct compression method. The tablets prepared were evaluated for various parameters including weight variation, hardness, friability, in vitro dispersion time, drug-polymer interaction, drug content water absorption ratio, wetting time, in vitro drug release, FTIR and DSC studies. The tablets prepared by the direct compression method had a weight variation in the range of 145 mg to 152 mg, which is below ± 7.5%, a hardness of 3.6 kg/cm² to 4.5 kg/cm², percentage friability of 0.46% to 0.73%, in vitro dispersion time of 18 s to 125 s, drug content uniformity of between 98.12% and 100.03%, a water absorption ratio of 67% to 87%, wetting time of 32 sec. to 64 sec., and an in vitro drug release of 53.92% - 98.82% within 15 min. The IR spectral analysis and DSC study showed no drug interaction with formulation additives of the tablet, and the formulations indicated no significant changes in hardness, friability, drug content or in vitro drug release. Fast dissolving tablets of metoprolol tartrate have enhanced dissolution and will lead to improved bioavailability and more effective therapy.

A exigência por comprimidos de dissolução rápida aumentou durante a última década, especialmente para idosos e crianças, com dificuldades de deglutição . No presente trabalho prepararam-se, pelo método de compressão direta, comprimidos de tartarato de metoprolol de rápida dissolução, utilizando glicolato sódico de amido, croscarmellose sódica e crospovidona como superdisintegrantes. Os comprimidos preparados foram avaliados em relação a diferentes parâmetros, como variação de peso, dureza, friabilidade, tempo de dispersão in vitro, interação fármaco-polímero, taxa de absorção de água pelo fármaco, tempo de umedecimento, liberação do fármaco in vitro,, FTIR e estudos de DSC. Os comprimidos preparados por compressão direta apresentaram variação de peso de 145 mg a 152 mg, abaixo de ±7,5%, dureza de 3,6 kg/cm² a 4,5 kg/cm² , porcentagem de friabilidade de 0,46% a 0,73%, tempo de dispersão in vitro de 18 s a 125 s, uniformidade de conteúdo de fármaco entre 98,12% e 100,03%, taxa de absorção de água de 67% a 87%, tempo de umidificaçãode 32 s a 64 s liberação do fármaco in vitro entre 53,92% e 98,82%, em 15 min. A análise no IV e de DSC mostrou que não houve interação de fármacos com os aditivos de formulação do comprimido e as formulações indicaram que não houve mudança significativa na dureza, friabilidade, s uniformidade de conteúdo de fármaco e na liberação do fármaco in vitro. Os comprimidos de liberação rápida apresentaram aumento na dissolução de tartarato metoprolol e conduzem à melhoria dabiodisponibilidade e à terapia eficaz.

Cross-linking mechanism of the matrix of hydrogel patch / 药学学报

In this study, we prepared various matrices of hydrogel patches and studied their cross-linking mechanism by observing their rheological properties, which could provide theoretical basis and deep technical support for further industrial development of hydrogel patch. Rheology method was used to do the amplitude scanning and single-frequency scanning for various hydrogel matrix, under the condition of oscillation mode of the rheometer. Then the linear viscoelastic region, composite modulus value, as well as changes in slope with time of the composite modulus and phase angle of various hydrogel matrix were analyzed in detail. The results showed that the stability of matrix was mainly determined by hydrogel frame; only in acidic environment, the cross-linking reaction between cross-linker and hydrogel frame can occur; elasticity of matrix can be decreased by organic acid and the effect level was related to the ratio of the number of carboxyl and hydroxyl (-COO(-)/-OH) in adjusters: if the ratio was not equal, the higher -COO(-)/-OH in adjusters would be the less elasticity of matrix decreased; the cross-linking speed of matrix was determined by adjuster, the cross-linking speed of matrix contain different adjusters was ranged in following order: matrix containing tartaric acid > matrix containing lactic acid > matrix containing malic acid > matrix containing citric acid; the cross-linking speed of matrix was not uniform in the whole cross-linking process.

Ischemic Stroke in Rats Enhances Bone Resorption in Vitro

We hypothesized that the formation and differentialtion of osteoclasts are accelerated and the potential of bone resorption is increased in the hemiplegic bone marrow in the early stage of stroke. We randomly divided white female Sprague-Dawley (SD) rats (n = 30) into two groups, stroke (n = 15) and sham group (n = 15). On the 7th day after stroke, after cutting away the epiphyses of the femurs and tibias, diaphyseal channels were flushed using alpha-minimum essential medium (alpha-MEM) and bone marrow cells were collected. Bone marrow stem cells, which were extracted from the femur and tibia, were cultured on the 7th day after middle cerebral artery occlusion. We then estimated the ratio of non-adherent cells to total bone marrow cells that included osteoclast precursor cells. After culturing these cells separately, cells that tested positive on the tartrate resistant acid phosphatase (TRAP) were counted and bone resorption was evaluated by using the OAAS(TM) plate. In comparison to the control group, the stroke group showed a higher increase of non-adherent cells in the hemiplegic side bone marrow. In addition, after the primary culture, the stroke group showed an increased number of TRAP positive cells and a higher degree of bone resorption estimated by OAAS(TM) plate. As a result, osteoclastogenesis and osteoclast differentiation are accelerated and the potential of bone resorption is increased in the hemiplegic bone marrow and these changes are detected as early as within the first week after middle cerebral artery occlusion in SD rats.

Serum total and bone alkaline phosphatase and tartrate-resistant acid phosphatase activities for the assessment of bone fracture healing in dogs / Fosfatase alcalina total, isoenzima óssea da fosfatase alcalina e fosfatase ácida resistente ao tartarato na monitorização da cicatrização de fraturas ósseas

O objetivo deste trabalho foi estudar o padrão de variação da atividade sérica da fosfatase alcalina total (tALP), da isoenzima óssea da fosfatase alcalina (BALP) e da fosfatase ácida resistente ao tartarato (TRAP), assim como a variação da concentração dos minerais séricos durante o processo de cicatrização de fraturas ósseas no cão. A variação sérica destes marcadores do metabolismo ósseo foi avaliada em nove cães com fraturas diafisárias fechadas de ossos longos, submetidas a tratamento cirúrgico para osteosíntese. Durante o período pós-operatório, sete animais evoluíram no sentido de uma normal união óssea, sendo que dois deles desenvolveram um processo de não união óssea. Foram observados, relativamente à BALP, valores de actividade sérica mais elevados e com diferença estatística (P<0,05) no grupo de animais que evoluiu no sentido de uma normal união óssea, comparativamente ao grupo de animais que evoluiu no sentido do processo de não união. No grupo de animais que evoluiu para a completa união óssea foram, adicionalmente, observados valores diminuidos (P<0,05) da atividade sérica da TRAP, até ao dia 60 do período pós-operatório seguido de uma elevação estatisticamente significativa após este período. Em conclusão, os biomarcadores do metabolismo ósseo poderão vir a constituir um método auxiliar de diagnóstico na monitorização do processo de cicatrização de fracturas ósseas, possibilitando, a detecção precoce de complicações pós-operatórias.

Tumor shrinkage by cyclopamine tartrate through inhibiting hedgehog signaling / 癌症

The link of hedgehog (Hh) signaling activation to human cancer and synthesis of a variety of Hh signaling inhibitors raise great expectation that inhibiting Hh signaling may be effective in human cancer treatment. Cyclopamine (Cyc), an alkaloid from the Veratrum plant, is a specific natural product inhibitor of the Hh pathway that acts by targeting smoothened (SMO) protein. However, its poor solubility, acid sensitivity, and weak potency relative to other Hh antagonists prevent the clinical development of Cyc as a therapeutic agent. Here, we report properties of cyclopamine tartrate salt (CycT) and its activities in Hh signaling-mediated cancer in vitro and in vivo. Unlike Cyc, CycT is water soluble (5-10 mg/mL). The median lethal dose (LD50) of CycT was 62.5 mg/kg body weight compared to 43.5 mg/kg for Cyc, and the plasma half-life (T1/2) of CycT was not significantly different from that of Cyc. We showed that CycT had a higher inhibitory activity for Hh signaling-dependent motor neuron differentiation than did Cyc (IC50 = 50 nmol/L for CycT vs. 300 nmol/L for Cyc). We also tested the antitumor effectiveness of these Hh inhibitors using two mouse models of basal cell carcinomas (K14cre:Ptch1(neo/neo) and K14cre:SmoM2(YFP)). After topical application of CycT or Cyc daily for 21 days, we found that all CycT-treated mice had tumor shrinkage and decreased expression of Hh target genes. Taken together, we found that CycT is an effective inhibitor of Hh signaling-mediated carcinogenesis.

Characterization of vinflunine tartrate liposomes in vitro and in vivo / 药学学报

Vinflunine tartrate-loaded liposomes (VT-L) with two drug-to-lipid ratios were prepared by pH gradient method. Vesicle size and zeta potential were determined by the Zetasizer Nano ZS. Entrapment efficiency was evaluated by cation exchange resin centrifugalization method. The toxicity and tumor inhibition to nude mouse administrated by VT-L with different drug-to-lipid ratios were investigated and compared with the vinflunine tartrate injection (VT-I). The results showed that the mean particle size, zeta potential and entrapment efficiency of the VT-L with drug-to-lipid ratios of 1 : 5 and 1 : 10 were 124.6 nm and 128.3 nm, -25.3 mV and -22.8 mV, 94.46% and 97.31%, respectively. The VT-L with two different drug-to-lipid ratios has significantly higher anti-tumor effect to nude mouse transplanted human non-small cell lung carcinoma A549 and lower toxicity than VT-I. While there were no significant differences in anti-tumor effect and toxicity between VT-L with two different drug-to-lipid ratios.

Effects of Liriopis Tuber Water Extract on RANKL-induced Osteoclast Differentiation / 체질인류학회지

Increased formation and activation of osteoclast lead to unwanted bone resorption. Several natural products which have inhibitory effects on osteoclast differentiation and function are under investigation to prevent and treat the osteoporotic bone disease. Liriopis tuber has been used in Oriental medicine for the suppression of cough, expectoration, thirst, and has been used for sthenia, diuresis, blood glucose regulation, treatment of xerostomia, and constipation. Also, recently it has been reported that Liriopsis tuber has anti-inflammatory, anti-thrombic, anti-adhesive activities. The purpose of this study was to evaluate the effects of Liriopis tuber on osteoclast differentiation and was to evaluate of its mechanism. Water extract of Liriopis tuber significantly inhibited receptor activator of nuclear factor-kappaB ligand (RANKL)-induced osteoclast differentiation in bone marrow macrophages (BMMs) in a dose dependent manner. However, water extract of Liriopis tuber did not affect cytotoxicity when compared with control. The mRNA expression of c-Fos, NFATc1, tartrate resistant-acid phosphatase (TRAP), and cathepsin K induced by RANKL was inhibited by water extract of Liriopis tuber treatment. Also, water extract of Liriopis tuber inhibited the protein expression of c-Fos and NFATc1 expression in BMMs treated with RANKL. Among the signal pathways, water extract of Liriopis tuber suppressed the phosphorylation of p38 induced by RANKL. In summary, Liriopis tuber exerted inhibitory effects on osteoclast diffentiation via suppression of c-Fos and NFATc1 which are essential gene to osteoclastogenesis. Taken together, these results suggest that Liriopis tuber may be a useful candidate in the treatment of osteoporosis without special toxicity.

Removal of heavy metals from a contaminated soil using organic chelating acids

Changes in heavy metal speciation and uptake by maize in a soil before and after washing with chelating organic acids, citric acid, tartaric acid and ethylenediaminetetraacetic acid were assessed. A sandy loam was collected from the vicinity of the Benue industrial layout, Makurdi, Nigeria and spiked with a quinternary mixture of nickel, copper, zinc, cadmium and lead nitrates to achieve higher levels of contamination. Batch soil washing experiments performed on 1.0 g portions of the spiked soil using 0.05 M chelating agents at a solid:liquid ratio of 1:25 showed that washing efficiencies varied in the order: ethylenediaminetetraacetic acid>citric acid>tartaric acid with metal extraction yields typically following the sequence, copper>nickel>zinc>cadmium>lead. Sequential extractions proposed by the European Communities Bureau of Reference method used to assess the redistribution of heavy metal forms in the soil showed that apparent metal mobilities were reduced upon soil washing. Citric acid removed most of the metals hitherto associated with the exchangeable and reducible fractions; tartaric acid, the exchangeable metal pools; and ethylenediaminetetraacetic acid, the non-residual metal pools. Heavy metal assay of harvested biomass of maize grown on unwashed and washed soil samples indicated that metal transfer coefficients, decreased in the order of treatment: ethylenediaminetetraacetic acid

pH-independent release of propranolol hydrochloride from HPMC-based matrices using organic acids

Propranolol HC1, a widely used drug in the treatment of cardiac arrhythmias and hypertension, is a weak basic drug with pH-dependent solubility that may show release problems from sustained release dosage forms at higher pH of small intestine. This might decrease drug bioavailability and cause variable oral absorption. Preparation of a sustained release matrix system with a pH-independent release profile was the aim of the present study. Three types of organic acids namely tartaric, citric and fumaric acid in the concentrations of 5, 10 and 15% were added to the matrices prepared by hydroxypropyl methylcellulose [HPMC] and dicalcium phosphate. The drug release studies were carried out at pH 1.2 and pH 6.8 separately and mean dissolution time [MDT] as well as similarity factor [f[2]] were calculated for all formulations. It was found that incorporation of 5 and 10% tartaric acid in tablet formulations with 30% HPMC resulted in a suitable pH-independent release profiles with significant higher f[2] values [89.9 and 87.6 respectively] compared to acid free tablet [58.03]. The other two acids did not show the desirable effects. It seems that lower pK[a] of tartaric acid accompanied by its higher solubility were the main factors in the achievement of pH-independent release profiles

Changes in urinary compositions among children after consuming prepared oral doses of aloe (Aloe vera Linn).

OBJECTIVES: 1) To investigate the amount of citrate and tartrate in aloe gel, and in the urine of healthy normal children, before and after consuming fresh aloe gel. 2) To evaluate the changes in the chemical composition of urine among subjects after taking aloe gel. 3) To determine the value of consuming aloe gel for prevention of renal stone formation. DESIGN: Experimental study. MATERIAL AND METHOD: Thirteen healthy boys between 9 and 13 years of age were enrolled (with informed permission) in the clinical trial. Subjects ingested 100 g of fresh prepared aloe gel twice a day for seven consecutive days. The 24-hour urine was collected one day prior to taking the gel (Day 0), Days 2 and 5 of consumption, and Day 8 (one day after completion). The authors determined the urine volume, osmolality, potassium, sodium, phosphate, calcium, magnesium, uric acid, citrate, tartrate, oxalate, Permissible Increment in Calcium (PI Ca), Permissible Increment in Oxalate (PI Ox), Concentration Product Ratio of Calcium Phosphate (CPR CaPO4) and the citrate per creatinine ratio. RESULTS: The citrate and tartrate concentration in 100 g of fresh aloe gel was 96.3 and 158.9 mg, respectively. The 24-hr urine volume and urinary citrate excretion were significantly increased (p < 0.05). The PI Ca and the PI Ox were also significantly increased (p < 0.05). The other measurements were unremarkable. CONCLUSION: One hundred grams of fresh Aloe vera gel contains 96.3 milligrams of citrate and 158.9 milligrams of tartrate and were in the mid-range among Thai fruits. Changes in chemical compositions of urine after aloe gel consumption shows potential for preventing kidney stone formation among children.

Effect of aloe (Aloe vera Linn.) on healthy adult volunteers: changes in urinary composition.

OBJECTIVE: 1. To investigate the amount of citrate and tartrate in aloe gel, and in the urine of healthy normal volunteers, before and after consuming fresh aloe gel. 2. To evaluate the changes in the chemical composition of urine among subjects after taking aloe gel. 3. To determine the value of consuming aloe gel for prevention of renal stone formation. DESIGNS: Experimental study; before and after experiment with no control group MATERIAL AND METHOD: Thirty one healthy male medical students between 18 and 23 years of age were enrolled (with informed consent) in the clinical trial. Subjects ingested 100 g of fresh aloe gel twice a day for seven consecutive days. The 24-hr urine was collected one day prior to taking the gel (Day 0), Days 2 and 5 of consumption, and Day 8 (one day after completion). The authors determined the urine volume, osmolality, potassium, sodium, phosphate, calcium, magnesium, uric acid, citrate, tartrate, oxalate, Permissible Increment in calcium (PI in calcium), Permissible Increment in oxalate (PI in oxalate), Concentration product ratio of calcium phosphate (CPR of CaPO4) and the citrate per creatinine ratio. RESULTS: The citrate and tartrate concentration in 100 g of fresh aloe gel was 96.3 and 158.9 mg, respectively. The urinary excretion of oxalate was significantly decreased (p < 0.05). The PI in calcium was significantly increased (p < 0.05), while the citrate excretion and PI in oxalate were consistently, albeit non-significantly, increased. The mean CPR values of CaPO4 were decreased non-significantly. The other measurements were unremarkable. CONCLUSION: Fresh Aloe vera gel (100 g) contains 96.3 mg of citrate and 158.9 mg of tartrate. This is mid-range for Thai fruits. Changes in chemical compositions of urine after aloe consumption shows its potential for preventing kidney stone formation among adults.