WorldWideScience

Sample records for alpha-glucosidases

  1. Alpha glucosidase inhibitors.

    Science.gov (United States)

    Kalra, Sanjay

    2014-04-01

    Alpha glucosidase inhibitors (AGIs) are a unique class of anti-diabetic drugs. Derived from bacteria, these oral drugs are enzyme inhibitors which do not have a pancreato -centred mechanism of action. Working to delay carbohydrate absorption in the gastrointestinal tract, they control postprandial hyperglycaemia and provide unquestioned cardiovascular benefit. Specially suited for a traditional Pakistani carbohydrate-rich diet, AGIs have been termed the 'untapped diamonds' of diabetology. The use of these oral antidiabetic drugs (OADs) that target pathophysiology in the early stages of type 2 diabetes, notably to reduce postprandial hyperglycaemia and hyperinsulinaemia will inevitably increase with time. This review describes the history of their development, mechanism of action, basic and clinical pharmacology, and suggests practical, evidence-based guidance for their optimal use. PMID:24864650

  2. Miglitol, a new alpha-glucosidase inhibitor

    NARCIS (Netherlands)

    Sels, J P; Huijberts, M S; Wolffenbuttel, B H

    1999-01-01

    Miglitol (Bay m 1099, Bayer) is a second generation alpha-glucosidase inhibitor. It is a derivative of 1-desoxynojirimycin, and binds reversibly to the brushborder alpha-glucosidase enzymes. In contrast to its parent drug (acarbose, Bay g 5421, Bayer), miglitol is almost completely absorbed in the s

  3. Macroalage as a source of alpha-glucosidase inhibitors

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Alpha-glucosidase inhibitors were screened from organic solvent extracts of macroalgae by a spectrophotometrical method with p-nitrophenyl-D-glucopyranosidase as the substrate. The result indicates that organic crude extracts from some macroalgae such as Rhodomela confervoides (Huds.) Silva, Gracilaria textorii (Suringar) DeToni, Plocamium telfairiae Harv., Dictyopteris divaricata (Okam.) Okam, Ulval pertusa and Enteromorpha intestinalis (L.) Link et al. show strong inhibitory activity of alpha-glucosidase at concentration of 79.6 μg/ml.

  4. The Role of alpha-Glucosidase in Germinating Barley Grains

    DEFF Research Database (Denmark)

    Stanley, Duncan; Rejzek, Martin; Næsted, Henrik;

    2011-01-01

    The importance of alpha-glucosidase in the endosperm starch metabolism of barley (Hordeum vulgare) seedlings is poorly understood. The enzyme converts maltose to glucose (Glc), but in vitro studies indicate that it can also attack starch granules. To discover its role in vivo, we took complementa...

  5. The role of alpha-glucosidase in germinating barley grains.

    Science.gov (United States)

    Stanley, Duncan; Rejzek, Martin; Naested, Henrik; Smedley, Mark; Otero, Sofía; Fahy, Brendan; Thorpe, Frazer; Nash, Robert J; Harwood, Wendy; Svensson, Birte; Denyer, Kay; Field, Robert A; Smith, Alison M

    2011-02-01

    The importance of α-glucosidase in the endosperm starch metabolism of barley (Hordeum vulgare) seedlings is poorly understood. The enzyme converts maltose to glucose (Glc), but in vitro studies indicate that it can also attack starch granules. To discover its role in vivo, we took complementary chemical-genetic and reverse-genetic approaches. We identified iminosugar inhibitors of a recombinant form of an α-glucosidase previously discovered in barley endosperm (ALPHA-GLUCOSIDASE97 [HvAGL97]), and applied four of them to germinating grains. All four decreased the Glc-to-maltose ratio in the endosperm 10 d after imbibition, implying inhibition of maltase activity. Three of the four inhibitors also reduced starch degradation and seedling growth, but the fourth did not affect these parameters. Inhibition of starch degradation was apparently not due to inhibition of amylases. Inhibition of seedling growth was primarily a direct effect of the inhibitors on roots and coleoptiles rather than an indirect effect of the inhibition of endosperm metabolism. It may reflect inhibition of glycoprotein-processing glucosidases in these organs. In transgenic seedlings carrying an RNA interference silencing cassette for HvAgl97, α-glucosidase activity was reduced by up to 50%. There was a large decrease in the Glc-to-maltose ratio in these lines but no effect on starch degradation or seedling growth. Our results suggest that the α-glucosidase HvAGL97 is the major endosperm enzyme catalyzing the conversion of maltose to Glc but is not required for starch degradation. However, the effects of three glucosidase inhibitors on starch degradation in the endosperm indicate the existence of unidentified glucosidase(s) required for this process.

  6. Unexpected high digestion rate of cooked starch by the Ct-Maltase-Glucoamylase small intestine mucosal alpha-glucosidase subunit

    Science.gov (United States)

    For starch digestion to glucose, two luminal alpha-amylases and four gut mucosal alpha-glucosidase subunits are employed. The aim of this research was to investigate, for the first time, direct digestion capability of individual mucosal alpha-glucosidases on cooked (gelatinized) starch. Gelatinized ...

  7. A specific acid [alpha]-glucosidase in lamellar bodies of the human lung

    NARCIS (Netherlands)

    Vries, A.C.J. de; Schram, A.W.; Tager, J.M.; Batenburg, J.J.

    2006-01-01

    In the present investigation, we have demonstrated that three lysosomal-type hydrolases, alpha-glucosidase, alpha-mannosidase and a phosphatase, are present in lamellar bodies isolated from adult human lung. The hydrolase activities that were studied, all showed an acidic pH optimum, which is charac

  8. Different polyphenolic components of soft fruits inhibit alpha-amylase and alpha-glucosidase.

    Science.gov (United States)

    McDougall, Gordon J; Shpiro, Faina; Dobson, Patricia; Smith, Pauline; Blake, Alison; Stewart, Derek

    2005-04-01

    Polyphenol-rich extracts from soft fruits were tested for their ability to inhibit alpha-amylase and alpha-glucosidase. All extracts tested caused some inhibition of alpha-amylase, but there was a 10-fold difference between the least and most effective extracts. Strawberry and raspberry extracts were more effective alpha-amylase inhibitors than blueberry, blackcurrant, or red cabbage. Conversely, alpha-glucosidase was more readily inhibited by blueberry and blackcurrant extracts. The extent of inhibition of alpha-glucosidase was related to their anthocyanin content. For example, blueberry and blackcurrant extracts, which have the highest anthocyanin content, were the most effective inhibitors of alpha-glucosidase. The extracts most effective in inhibiting alpha-amylase (strawberry and raspberry) contain appreciable amounts of soluble tannins. Other tannin-rich extracts (red grape, red wine, and green tea) were also effective inhibitors of alpha-amylase. Indeed, removing tannins from strawberry extracts with gelatin also removed inhibition. Fractionation of raspberry extracts on Sephadex LH-20 produced an unbound fraction enriched in anthocyanins and a bound fraction enriched in tannin-like polyphenols. The unbound anthocyanin-enriched fraction was more effective against alpha-glucosidase than the original extract, whereas the alpha-amylase inhibitors were concentrated in the bound fraction. The LH-20 bound sample was separated by preparative HPLC, and fractions were assayed for inhibition of alpha-amylase. The inhibitory components were identified as ellagitannins using LC-MS-MS. This study suggests that different polyphenolic components of fruits may influence different steps in starch digestion in a synergistic manner. PMID:15796622

  9. Purification and partial characterization of three forms of alpha-glucosidase from the fruit fly Drosophila melanogaster.

    Science.gov (United States)

    Tanimura, T; Kitamura, K; Fukuda, T; Kikuchi, T

    1979-01-01

    Three forms of alpha-glucosidase, I, II, and III, have been purified from the whole body extract of adult flies of Drosophila melanogaster in yields of 2.1, 5.3, and 6.7%, respectively. The purification procedures involved ammonium sulfate fractionation, Con A-Sepharose 4B affinity chromatography, DEAE-Sepharose CL-6B ion exchange chromatography, Sephacryl S-200 gel filtration, and preparative gel electrophoresis. Each purified enzyme showed a single band on polyacrylamide gel on both protein and enzyme activity staining. The molecular weights of alpha-glucosidases I, II, and III were estimated to be 200,000, 56,000, and 76,000, respectively, by gel filtration. SDS gels indicated that alpha-glucosidases II and III were each composed of a single polypeptide chain, whereas alpha-glucosidase I was composed of two identical subunits. Both alpha-glucosidases II and III hydrolyzed sucrose and p-nitrophenyl-alpha-D-glucoside (PNPG), but alpha-glucosidase I hydrolyzed PNPG to a much lesser extent than sucrose. For sucrose the pH optima of alpha-glucosidases I, II, and III were pH 6.0, 5.0, and 6.0 and the Km values were 13.1, 8.9, and 10 mM, respectively. For PNPG the pH optima of alpha-glucosidases II and III were pH 5.5 and 6.5 and the Km values were 0.77 and 0.21 mM, respectively.

  10. Antidiabetic property of Symplocos cochinchinensis is mediated by inhibition of alpha glucosidase and enhanced insulin sensitivity.

    Directory of Open Access Journals (Sweden)

    Kalathookunnel Antony Antu

    Full Text Available The study is designed to find out the biochemical basis of antidiabetic property of Symplocos cochinchinensis (SC, the main ingredient of 'Nisakathakadi' an Ayurvedic decoction for diabetes. Since diabetes is a multifactorial disease, ethanolic extract of the bark (SCE and its fractions (hexane, dichloromethane, ethyl acetate and 90% ethanol were evaluated by in vitro methods against multiple targets relevant to diabetes such as the alpha glucosidase inhibition, glucose uptake, adipogenic potential, oxidative stress, pancreatic beta cell proliferation, inhibition of protein glycation, protein tyrosine phosphatase-1B (PTP-1B and dipeptidyl peptidase-IV (DPP-IV. Among the extracts, SCE exhibited comparatively better activity like alpha glucosidase inhibition (IC50 value-82.07 ± 2.10 µg/mL, insulin dependent glucose uptake (3 fold increase in L6 myotubes, pancreatic beta cell regeneration in RIN-m5F (3.5 fold increase and reduced triglyceride accumulation (22% decrease in 3T3L1 cells, protection from hyperglycemia induced generation of reactive oxygen species in HepG2 cells (59.57% decrease with moderate antiglycation and PTP-1B inhibition. Chemical characterization by HPLC revealed the superiority of SCE over other extracts due to presence and quantity of bioactives (beta-sitosterol, phloretin 2'glucoside, oleanolic acid in addition to minerals like magnesium, calcium, potassium, sodium, zinc and manganese. So SCE has been subjected to oral sucrose tolerance test to evaluate its antihyperglycemic property in mild diabetic and diabetic animal models. SCE showed significant antihyperglycemic activity in in vivo diabetic models. We conclude that SC mediates the antidiabetic activity mainly via alpha glucosidase inhibition, improved insulin sensitivity, with moderate antiglycation and antioxidant activity.

  11. Transformation of maltose into prebiotic isomaltooligosaccharides by a novel alpha-glucosidase from Xantophyllomyces dendrorhous

    OpenAIRE

    Fernández Arrojo, Lucía; Marín Alberdi, Dolores; Gómez de Segura, María Aránzazu; Linde López, Dolores; Alcalde Galeote, Miguel; Gutiérrez Alonso, Patricia; Ghazi, Iraj; Plou Gasca, Francisco José; Fernández Lobato, María; Ballesteros Olmo, Antonio

    2007-01-01

    The transglycosylation activity of a novel alpha-glucosidase from the basidiomycetous yeast Xanthophyllomyces dendrorhous (formerly Phaffia rhodozyma) was studied using maltose as glucosyl donor. The enzyme synthesized oligosaccharides with alpha-(1-2), alpha-(1-4) and alpha-(1-6) bonds. Using 200 g/l maltose, the yield of oligosaccharides was 53.8 g/l, with prebiotic oligosaccharides containing at least one alpha-(1-6) linkage (panose, 6-O-alpha-glucosyl-maltotriose and 6-O-alpha-isomaltosyl...

  12. An alpha-glucosidase inhibitor from an endophytic Cladosporium sp. with potential as a biocontrol agent.

    Science.gov (United States)

    Singh, Bahaderjeet; Kaur, Tamanreet; Kaur, Sanehdeep; Manhas, Rajesh K; Kaur, Amarjeet

    2015-02-01

    This study highlights the importance of alpha-glucosidase inhibitors as mechanisms for endophyte-mediated resistance to insect pests. One of the major benefits which endophytes confer on plants is providing resistance against insect pests. This built-in defense mechanism of the plant can be used for exploring ecofriendly strategies for pest control. In the present study, 34 endophytic fungi were isolated from Tinospora cordifolia and screened for their ability to produce alpha-glucosidase inhibitors. Maximum inhibitory activity was observed in an isolate from T. cordifolia (TN-9S), identified to be Cladosporium sp. The inhibitor was purified using chromatographic techniques. The insecticidal activity of the purified inhibitor was evaluated against Spodoptera litura. The inhibitor induced a significant mortality in the larvae of S. litura and adversely affected its survival and development. It also inhibited the activity of α-glycosidases in vivo in the gut of the larvae. The purified inhibitor was determined to be a phenolic compound with amine groups, demonstrating a noncompetitive type of inhibition in vitro. The production of the inhibitor was optimized. Response surface methodology (RSM) analysis revealed a significant interaction between dextrose and malt extract, with first-order effect of pH.

  13. An alpha-glucosidase inhibitor from an endophytic Cladosporium sp. with potential as a biocontrol agent.

    Science.gov (United States)

    Singh, Bahaderjeet; Kaur, Tamanreet; Kaur, Sanehdeep; Manhas, Rajesh K; Kaur, Amarjeet

    2015-02-01

    This study highlights the importance of alpha-glucosidase inhibitors as mechanisms for endophyte-mediated resistance to insect pests. One of the major benefits which endophytes confer on plants is providing resistance against insect pests. This built-in defense mechanism of the plant can be used for exploring ecofriendly strategies for pest control. In the present study, 34 endophytic fungi were isolated from Tinospora cordifolia and screened for their ability to produce alpha-glucosidase inhibitors. Maximum inhibitory activity was observed in an isolate from T. cordifolia (TN-9S), identified to be Cladosporium sp. The inhibitor was purified using chromatographic techniques. The insecticidal activity of the purified inhibitor was evaluated against Spodoptera litura. The inhibitor induced a significant mortality in the larvae of S. litura and adversely affected its survival and development. It also inhibited the activity of α-glycosidases in vivo in the gut of the larvae. The purified inhibitor was determined to be a phenolic compound with amine groups, demonstrating a noncompetitive type of inhibition in vitro. The production of the inhibitor was optimized. Response surface methodology (RSM) analysis revealed a significant interaction between dextrose and malt extract, with first-order effect of pH. PMID:25432333

  14. Isolation, characterization and chemobiological quantification of alpha-glucosidase enzyme inhibitory and free radical scavenging constituents from Derris scandens Benth.

    Science.gov (United States)

    Rao, Sridhar A; Srinivas, Pullela V; Tiwari, Ashok K; Vanka, Uma Maheswara S; Rao, Rama V Subba; Dasari, Krishna R; Rao, Madhusudana J

    2007-08-15

    The hexane and chloroform extracts of Derris scandens have displayed potent alpha-glucosidase inhibitory and moderate free radical scavenging activities. Phytochemical investigation of the active extracts led to the isolation of three new prenylated isoflavones, isoscandinone, scandenin A and scandenin B in addition to scandenone, scandinone and 4', 5', 7-trihydroxybiprenylisoflavone as the main constituents, having alpha-glucosidase enzyme inhibitory and free radical scavenging properties. A reversed-phase HPLC method is developed to quantify these active principles in the plant material, which can serve as an effective quality control method for standardization of D. scandens. PMID:17537687

  15. Terpenoids with alpha-glucosidase inhibitory activity from the submerged culture of Inonotus obliquus.

    Science.gov (United States)

    Ying, You-Min; Zhang, Lin-Yan; Zhang, Xia; Bai, Hai-Bo; Liang, Dong-E; Ma, Lie-Feng; Shan, Wei-Guang; Zhan, Zha-Jun

    2014-12-01

    Lanostane-type triterpenoids, inotolactones A and B, a drimane-type sesquiterpenoid, inotolactone C, and five known terpenoids 6β-hydroxy-trans-dihydroconfertifolin, inotodiol, 3β,22-dihydroxyanosta-7,9(11),24-triene, 3β-hydroxycinnamolide, and 17-hydroxy-ent-atisan-19-oic acid, were isolated from the submerged culture of chaga mushroom, Inonotus obliquus. Their structures were characterized by spectroscopic methods, including MS and NMR (1D and 2D) spectroscopic techniques. Inotolactones A and B, examples of lanostane-type triterpenoids bearing α,β-dimethyl, α,β-unsaturated δ-lactone side chains, exhibited more potent alpha-glucosidase inhibitory activities than the positive control acarbose. This finding might be related to the anti-hyperglycemic properties of the fungus and to its popular role as a diabetes treatment. In addition, a drimane-type sesquiterpenoid and an atisane-type diterpenoid were isolated from I. obliquus. PMID:25446238

  16. AGI, a previously unreported D. melanogaster {alpha}-glucosidase: Partial purification, characterization, and cytogenetic mapping

    Energy Technology Data Exchange (ETDEWEB)

    Parker, G.F.; Roberts, D.B. [Univ. of Oxford (United Kingdom)

    1996-04-01

    Inbred Drosophila melanogaster stocks were surveyed for {alpha}-glucosidases with nondenaturing gel electrophoresis using a fluorogenic substrate to stain the gels. The glucosidase most active under these conditions is polymorphic. We established that the polymorphism is genetic in origin and that the glucosidase was not likely to be a previously characterized enzyme. The gene encoding the enzyme was mapped cytogenetically to 33 A1-2- 33A8-B1, confirming that this is an enzyme not yet reported in D. melanogaster. The enzyme was partially purified by elution from nondenaturing gels, which enable us to establish that it has optimal activity at pH 6 and interacts most strongly with {alpha}- 1 -4 glucosides. A developmental and tissue survey suggested that this enzyme could have a purely digestive role or be involved in carbohydrate metabolism inside the organism. We propose that this enzyme is involved in either starch digestion or glycogen metabolism. 37 refs., 6 figs., 1 tab.

  17. AGI, a previously unreported D. melanogaster alpha-glucosidase: partial purification, characterization, and cytogenetic mapping.

    Science.gov (United States)

    Parker, G F; Roberts, D B

    1996-04-01

    Inbred Drosophila melanogaster stocks were surveyed for alpha-glucosidases with nondenaturing gel electrophoresis using a fluorogenic substrate to stain the gels. The glucosidase most active under these conditions is polymorphic. We established that the polymorphism is genetic in origin and that the glucosidase was not likely to be a previously characterized enzyme. The gene encoding the enzyme was mapped cytogenetically to 33 A1-2- 33A8-B1, confirming that this is an enzyme not yet reported in D. melanogaster. The enzyme was partially purified by elution from nondenaturing gels, which enabled us to establish that it has optimal activity at pH 6 and interacts most strongly with alpha-1-4 glucosides. A developmental and tissue survey suggested that this enzyme could have a purely digestive role or be involved in carbohydrate metabolism inside the organism. We propose that this enzyme is involved in either starch digestion or glycogen metabolism.

  18. Optimization and Modeling of Ultrasound-assisted Extraction of Polysaccharides from Cynomorium songaricum and &alpha-glucosidase Inhibitory Activity

    Directory of Open Access Journals (Sweden)

    Tao Guo

    2015-01-01

    Full Text Available In the study, the extraction processing of polysaccharides from Cynomorium songaricum was optimized by Response Surface Methodology (RSM and projected by a computer-stimulated Artificial Neural Network (ANN. The optimal process conditions were obtained as follows: extraction temperature 55C, solid-liquid ratio 1:10, power 175 W. Under optimized conditions, The R2 value of 0.99391 and an MSE value of 0.0495 suggested a good generalization of the network and showed a good agreement between the experimental and predicted values. On the other hand, the results also suggested that polysaccharides from Cynomorium songaricum had &alpha-glucosidase inhibitory activity with an IC50 of 8.316 &mug/mL and may be a potential &alpha-glucosidase inhibitory.

  19. Alpha-glucosidase inhibitory activity of Syzygium cumini (Linn.) Skeels seed kernel in vitro and in Goto-Kakizaki (GK) rats.

    Science.gov (United States)

    Shinde, Jayantrao; Taldone, Tony; Barletta, Michael; Kunaparaju, Naveen; Hu, Bo; Kumar, Sunil; Placido, Jessica; Zito, S William

    2008-05-19

    Syzygium cumini seed kernel extracts were evaluated for the inhibition of alpha-glucosidase from mammalian (rat intestine), bacterial (Bacillus stearothermophilus), and yeast (Saccharomyces cerevisiae, baker's yeast). In vitro studies using the mammalian alpha-glucosidase from rat intestine showed the extracts to be more effective in inhibiting maltase when compared to the acarbose control. Since acarbose is inactive against both the bacterial and the yeast enzymes, the extracts were compared to 1-deoxynojirimycin. We found all extracts to be more potent against alpha-glucosidase derived from B. stearothermophilus than that against the enzymes from either baker's yeast or rat intestine. In an in vivo study using Goto-Kakizaki (GK) rats, the acetone extract was found to be a potent inhibitor of alpha-glucosidase hydrolysis of maltose when compared to untreated control animals. Therefore, these results point to the inhibition of alpha-glucosidase as a possible mechanism by which this herb acts as an anti-diabetic agent. PMID:18374320

  20. In vitro potential of Ascophyllum nodosum phenolic antioxidant-mediated alpha-glucosidase and alpha-amylase inhibition.

    Science.gov (United States)

    Apostolidis, E; Lee, C M

    2010-04-01

    Ascophyllum nodosum is a brown seaweed that grows abundantly in the Northeast coastal region. In this study, the potential of A. nodosum for type 2 diabetes management through antioxidant-mediated alpha-glucosidase and alpha-amylase inhibition was investigated. After the initial screening of 4 locally harvested seaweeds, A. nodosum was chosen for its highest phenolic content and was subjected to water extraction. Among extraction ratios of 50 g to 100 to 1000 mL at room temperature, 50 g/400 mL yielded the highest phenolic content of 4.5 mg/g wet weight. For evaluation of extraction temperature ranging from 20 to 80 degrees C, 50 g/400 mL was chosen as a minimum amount of extractant. Among temperatures studied, extraction at 80 degrees C resulted in the highest total phenolic contents (4.2 mg/g wet weight). All extracts had similar levels of antioxidant activity in the range of 60% to 70% in terms of 1, 1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity. The 80 degrees C extract had the highest alpha-glucosidase and alpha-amylase inhibitory activity with IC(50) of 0.24 and 1.34 microg phenolics, respectively, compared to the IC(50) of acarbose, reference inhibitor, being 0.37 and 0.68 microg. The results show that fresh A. nodosum has strong alpha-glucosidase and mild alpha-amylase inhibitory activities that correlated with phenolic contents. This study suggests a nutraceutical potential of A. nodosum based on phytochemical antioxidant and antihyperglycemia activities. PMID:20492300

  1. In vitro alpha glucosidase inhibition and free-radical scavenging activity of propolis from Thai stingless bees in mangosteen orchard

    Directory of Open Access Journals (Sweden)

    Boonyadist Vongsak

    2015-10-01

    Full Text Available ABSTRACTThe chemical component and biological activity of propolis depend on flora area of bee collection and bee species. In the study, the propolis from three stingless bee species, Lepidotrigona ventralis Smith, Lepidotrigona terminata Smith, and Tetragonula pagdeni Schwarz, was collected in the same region of mangosteen garden from Thailand. Total phenolic content, alpha glucosidase inhibitory effect, and free-radical scavenging activity using FRAP, ABTS, DPPH assays were determined. The most potent activity of propolis extract was investigated for bioactive compounds and their quantity. The ethanol extract of T. pagdeni propolis had the highest total phenolic content 12.83 ± 0.72 g of gallic acid equivalents in 100 g of the extract, and the strongest alpha glucosidase inhibitory effect with the IC50 of 70.79 ± 6.44 µg/ml. The free-radical scavenging activity evaluated by FRAP, ABTS, DPPH assays showed the FRAP value of 279.70 ± 20.55 µmol FeSO4 equivalent/g extract and the IC50 of 59.52 ± 10.76 and 122.71 ± 11.76 µg/ml, respectively. Gamma- and alpha-mangostin from T. pagdeni propolis extract were isolated and determined for the biological activity. Gamma-mangostin exhibited the strongest activity for both alpha glucosidase inhibitory effect and free-radical scavenging activity. Using HPLC quantitative analysis method, the content of gamma- and alpha-mangostin in the extract was found to be 0.94 ± 0.01 and 2.77 ± 0.08% (w/w, respectively. These findings suggested that T. pagdeni propolis may be used as a more suitable raw material for nutraceutical and pharmaceutical products and these mangostin derivatives as markers.

  2. Punica granatum flower extract, a potent alpha-glucosidase inhibitor, improves postprandial hyperglycemia in Zucker diabetic fatty rats.

    Science.gov (United States)

    Li, Yuhao; Wen, Suping; Kota, Bhavani Prasad; Peng, Gang; Li, George Qian; Yamahara, Johji; Roufogalis, Basil D

    2005-06-01

    Postprandial hyperglycemia plays an important role in the development of type 2 diabetes and has been proposed as an independent risk factor for cardiovascular diseases. The flowering part of Punica granatum Linn. (Punicaceae) (PGF) has been recommended in Unani literature as a remedy for diabetes. We investigated the effect and action mechanism of a methanolic extract from PGF on hyperglycemia in vivo and in vitro. Oral administration of PGF extract markedly lowered plasma glucose levels in non-fasted Zucker diabetic fatty rats (a genetic model of obesity and type 2 diabetes), whereas it had little effect in the fasted animals, suggesting it affected postprandial hyperglycemia in type 2 diabetes. In support of this conclusion the extract was found to markedly inhibit the increase of plasma glucose levels after sucrose loading, but not after glucose loading in mice, and it had no effect on glucose levels in normal mice. In vitro, PGF extract demonstrated a potent inhibitory effect on alpha-glucosidase activity (IC50: 1.8 microg/ml). The inhibition is dependent on the concentration of enzyme and substrate, as well as on the length of pretreatment with the enzyme. These findings strongly suggest that PGF extract improves postprandial hyperglycemia in type 2 diabetes and obesity, at least in part, by inhibiting intestinal alpha-glucosidase activity. PMID:15894133

  3. Functional significance of amylase polymorphism in Drosophila melanogaster. III. Ontogeny of amylase and some alpha-glucosidases.

    Science.gov (United States)

    Hoorn, A J; Scharloo, W

    1980-02-01

    Changes in amylase (E.C. 3.2.1.1), maltase (E.C. 3.2.1.20), sucrase, and PNPGase activities in relation to changes in wet weight and protein content were studied during the development of larvae and adult flies from two strains of Drosophila melanogaster, homozygous for different amylase alleles. All alpha-glucosidase activities increase exponentially during a large part of larval development, parallel to the increase in weight, and drop at the end of the third instar. Amylase activity of the Amy1 strain follows the same pattern. In contrast, amylase activity of the Amy4,6 strain continues its exponential increase longer. In the third larval instar amylase activity in the Amy4,6 strain becomes much higher than in the Amy1 strain. During the first hours of adult life amylase activity of the two strains does not differ. Then Amy4,6 activity starts to rise and becomes much higher (4-5 times) than Amy1 amylase activity, which remains approximately constant. All adult enzyme activities are much higher than in larvae. Comparison of enzyme activity of amylase and alpha-glucosidases in larvae and adults confirms that differences in amylase activities can become important only when starch is a limiting factor in the food.

  4. Transcriptional regulation of the human acid alpha-glucosidase gene. Identification of a repressor element and its transcription factors Hes-1 and YY1.

    Science.gov (United States)

    Yan, B; Heus, J; Lu, N; Nichols, R C; Raben, N; Plotz, P H

    2001-01-19

    Acid alpha-glucosidase, the product of a housekeeping gene, is a lysosomal enzyme that degrades glycogen. A deficiency of this enzyme is responsible for a recessively inherited myopathy and cardiomyopathy, glycogenesis type II. We have previously demonstrated that the human acid alpha-glucosidase gene expression is regulated by a silencer within intron 1, which is located in the 5'-untranslated region. In this study, we have used deletion analysis, electrophoretic mobility shift assay, and footprint analysis to further localize the silencer to a 25-base pair element. The repressive effect on the TK promoter was about 50% in both orientations in expression plasmid, and two transcriptional factors were identified with antibodies binding specifically to the element. Mutagenesis and functional analyses of the element demonstrated that the mammalian homologue 1 of Drosophila hairy and Enhancer of split (Hes-1) binding to an E box (CACGCG) and global transcription factor-YY1 binding to its core site function as a transcriptional repressor. Furthermore, the overexpression of Hes-1 significantly enhanced the repressive effect of the silencer element. The data should be helpful in understanding the expression and regulation of the human acid alpha-glucosidase gene as well as other lysosomal enzyme genes.

  5. Alpha-glucosidase inhibitors and hepatotoxicity in type 2 diabetes: a systematic review and meta-analysis

    Science.gov (United States)

    Zhang, Longhao; Chen, Qiyan; Li, Ling; Kwong, Joey S. W.; Jia, Pengli; Zhao, Pujing; Wang, Wen; Zhou, Xu; Zhang, Mingming; Sun, Xin

    2016-01-01

    Alpha-glucosidase inhibitors (AGIs) was reported to be associated with several rare adverse hepatic events, but with inconsistent results. We aimed to investigate the risk of hepatotoxicity associated with the use of AGIs in patients with type 2 diabetes mellitus (T2DM), and performed a systematic review and meta-analysis. Fourteen studies (n = 2881) were eligible, all of which were RCTs. Meta-analysis of data regarding elevation of more than 3-fold the upper limit of normal (ULN) of AST and ALT showed statistically significant differences between AGIs treatment versus control (OR 6.86, 95% CI 2.50 to 18.80; OR 6.48, 95% CI 2.40 to 17.49). Subgroup analyses of elevation of more than 1.8-fold ULN of AST and ALT by dose of AGIs showed differential effects on AST and ALT (AST: OR 0.38 vs 7.31, interaction P = 0.003; ALT: OR 0.32 vs 4.55, interaction p = 0.02). Meta-analysis showed that AGIs might increase the risk of hepatotoxicity, and higher dose appeared to be associated with higher risk of hepatotoxicity. However, the evidence is limited with surrogate measures (i.e. ALT and AST), and no clinically important adverse events were observed. PMID:27596383

  6. Purification, enzymatic characterization, and nucleotide sequence of a high-isoelectric-point alpha-glucosidase from barley malt

    DEFF Research Database (Denmark)

    Frandsen, T P; Lok, F; Mirgorodskaya, E;

    2000-01-01

    .5, and catalyzed the hydrolysis by a retaining mechanism, as shown by nuclear magnetic resonance. Acarbose was a strong inhibitor (K(i) = 1.5 microM). Molecular recognition revealed that all OH-groups in the non-reducing ring and OH-3 in the reducing ring of maltose formed important hydrogen bonds to the...... enzyme in the transition state complex. Mass spectrometry of tryptic fragments assigned the 92-kD protein to a barley cDNA (GenBank accession no. U22450) that appears to encode an alpha-glucosidase. A corresponding sequence (HvAgl97; GenBank accession no. AF118226) was isolated from a genomic phage...... library using a cDNA fragment from a barley cDNA library. HvAgl97 encodes a putative 96.6-kD protein of 879 amino acids with 93.8% identity to the protein deduced from U22450. The sequence contains two active site motifs of glycoside hydrolase family 31. Three introns of 86 to 4,286 bp interrupt the...

  7. Alpha-glucosidase inhibitors and hepatotoxicity in type 2 diabetes: a systematic review and meta-analysis

    Science.gov (United States)

    Zhang, Longhao; Chen, Qiyan; Li, Ling; Kwong, Joey S. W.; Jia, Pengli; Zhao, Pujing; Wang, Wen; Zhou, Xu; Zhang, Mingming; Sun, Xin

    2016-09-01

    Alpha-glucosidase inhibitors (AGIs) was reported to be associated with several rare adverse hepatic events, but with inconsistent results. We aimed to investigate the risk of hepatotoxicity associated with the use of AGIs in patients with type 2 diabetes mellitus (T2DM), and performed a systematic review and meta-analysis. Fourteen studies (n = 2881) were eligible, all of which were RCTs. Meta-analysis of data regarding elevation of more than 3-fold the upper limit of normal (ULN) of AST and ALT showed statistically significant differences between AGIs treatment versus control (OR 6.86, 95% CI 2.50 to 18.80; OR 6.48, 95% CI 2.40 to 17.49). Subgroup analyses of elevation of more than 1.8-fold ULN of AST and ALT by dose of AGIs showed differential effects on AST and ALT (AST: OR 0.38 vs 7.31, interaction P = 0.003 ALT: OR 0.32 vs 4.55, interaction p = 0.02). Meta-analysis showed that AGIs might increase the risk of hepatotoxicity, and higher dose appeared to be associated with higher risk of hepatotoxicity. However, the evidence is limited with surrogate measures (i.e. ALT and AST), and no clinically important adverse events were observed.

  8. Pneumatosis cystoides intestinalis following alpha-glucosidase inhibitor treatment: A case report and review of the literature

    Institute of Scientific and Technical Information of China (English)

    Tatsuhiro Tsujimoto; Hiroshi Fukui; Erika Shioyama; Kei Moriya; Hideto Kawaratani; Yasuyo Shirai; Masahisa Toyohara; Akira Mitoro; Jun-ichi Yarnao; Hisao Fujii

    2008-01-01

    A 69-year-old man was diagnosed as having myasthenia gravis (MG) in September 2004, and treated with thymectomy and prednisolone. He was then diagnosed as having steroid-induced diabetes mellitus, and received sulfonylurea (SU) therapy in May 2005. An alpha-glucosidase inhibitor (αGI) was added in March 2006, resulting in good glycemic control. He experienced symptoms of abdominal distention, increased flatus, and constipation in October 2007, and was admitted into our hospital in late November with hematochezia. Plain abdominal radiography revealed small linear radiolucent clusters in the wall of the colon. Computed tomography (CT) showed intramural air in the sigmoid colon. Colonoscopy revealed multiple smooth surfaced hemispherical protrusions in the sigmoid colon. The diagnosis of pneumatosis cystoides intestinalis (PCI) was made on the basis of these findings. As the αGI voglibose was suspected as the cause of this patient's PCI, treatment was conservative, ceasing voglibose, with fasting and fluid supplementation. The patient progressed well, and was discharged 2 wk later. Recently, several reports of PCI associated with αGI therapy have been published, predominantly in Japan where αGIs are commonly used. If the use of αGIs becomes more widespread, we can expect more reports of this condition on a global scale. The possibility of PCI should be considered in diabetic patients complaining of gastrointestinal symptoms, and the gastrointestinal tract should be thoroughly investigated in these patients.

  9. Miconia sp. Increases mRNA Levels of PPAR Gamma and Inhibits Alpha Amylase and Alpha Glucosidase

    Directory of Open Access Journals (Sweden)

    David Mizael Ortíz-Martinez

    2016-01-01

    Full Text Available Diabetes mellitus is a public health problem worldwide. For this reason, ethanolic extract of Miconia sp. from Oaxaca, Mexico, was selected in search of an alternative against this disease. The effect of Miconia sp. on mRNA expression of PPARγ on cell line 3T3-L1, its effect on alpha amylase and alpha glucosidase, lipid accumulation during adipogenesis, and cell viability on VERO cells were evaluated. The mRNA levels of PPARγ increased on 1.393±0.008 folds, lipid accumulation was increased by 29.55% with Miconia sp. extract and 34.57% with rosiglitazone, and α-amylase and α-glycosidase were inhibited with IC50 values from 28.23±2.15 μg/mL and 1.95±0.15 μg/mL, respectively; the IC50 on antiproliferative activity on VERO cells was 314.54±45.40 μg/mL. In case of α-amylase and α-glycosidase assays, IC50 (inhibitory concentration 50 refers to necessary extract amounts to inhibit 50% of enzymatic activity. On the other hand, on antiproliferative activity, IC50 (inhibitory concentration 50 refers to necessary extract amounts to inhibit 50% of cell proliferation. It was concluded that the compounds present in Miconia sp. ethanolic extract increase mRNA expression of PPARγ, inhibit α-amylase and α-glucosidase, and increase lipid accumulation. It constitutes an alternative as adjuvant in diabetes mellitus treatment; therefore, we recommend continuing identifying the compounds responsible for its promising in vivo antidiabetic activity.

  10. Miconia sp. Increases mRNA Levels of PPAR Gamma and Inhibits Alpha Amylase and Alpha Glucosidase

    Science.gov (United States)

    Ortíz-Martinez, David Mizael; Rivas-Morales, Catalina; de la Garza-Ramos, Myriam Angelica; Verde-Star, Maria Julia; Nuñez-Gonzalez, Maria Adriana

    2016-01-01

    Diabetes mellitus is a public health problem worldwide. For this reason, ethanolic extract of Miconia sp. from Oaxaca, Mexico, was selected in search of an alternative against this disease. The effect of Miconia sp. on mRNA expression of PPARγ on cell line 3T3-L1, its effect on alpha amylase and alpha glucosidase, lipid accumulation during adipogenesis, and cell viability on VERO cells were evaluated. The mRNA levels of PPARγ increased on 1.393 ± 0.008 folds, lipid accumulation was increased by 29.55% with Miconia sp. extract and 34.57% with rosiglitazone, and α-amylase and α-glycosidase were inhibited with IC50 values from 28.23 ± 2.15 μg/mL and 1.95 ± 0.15 μg/mL, respectively; the IC50 on antiproliferative activity on VERO cells was 314.54 ± 45.40 μg/mL. In case of α-amylase and α-glycosidase assays, IC50 (inhibitory concentration 50) refers to necessary extract amounts to inhibit 50% of enzymatic activity. On the other hand, on antiproliferative activity, IC50 (inhibitory concentration 50) refers to necessary extract amounts to inhibit 50% of cell proliferation. It was concluded that the compounds present in Miconia sp. ethanolic extract increase mRNA expression of PPARγ, inhibit α-amylase and α-glucosidase, and increase lipid accumulation. It constitutes an alternative as adjuvant in diabetes mellitus treatment; therefore, we recommend continuing identifying the compounds responsible for its promising in vivo antidiabetic activity. PMID:27478477

  11. Purification and characterization of alpha-glucosidase I from Japanese honeybee (Apis cerana japonica) and molecular cloning of its cDNA.

    Science.gov (United States)

    Wongchawalit, Jintanart; Yamamoto, Takeshi; Nakai, Hiroyuki; Kim, Young-Min; Sato, Natsuko; Nishimoto, Mamoru; Okuyama, Masayuki; Mori, Haruhide; Saji, Osamu; Chanchao, Chanpen; Wongsiri, Siriwat; Surarit, Rudee; Svasti, Jisnuson; Chiba, Seiya; Kimura, Atsuo

    2006-12-01

    alpha-Glucosidase (JHGase I) was purified from a Japanese subspecies of eastern honeybee (Apis cerana japonica) as an electrophoretically homogeneous protein. Enzyme activity of the crude extract was mainly separated into two fractions (component I and II) by salting-out chromatography. JHGase I was isolated from component I by further purification procedure using CM-Toyopearl 650M and Sephacryl S-100. JHGase I was a monomeric glycoprotein (containing 15% carbohydrate), of which the molecular weight was 82,000. Enzyme displayed the highest activity at pH 5.0, and was stable up to 40 degrees C and in a pH-range of 4.5-10.5. JHGase I showed unusual kinetic features: the negative cooperative behavior on the intrinsic reaction on cleavage of sucrose, maltose, and p-nitrophenyl alpha-glucoside, and the positive cooperative behavior on turanose. We isolated cDNA (1,930 bp) of JHGase I, of which the deduced amino-acid sequence (577 residues) confirmed that JHGase I was a member of alpha-amylase family enzymes. Western honeybees (Apis mellifera) had three alpha-glucosidase isoenzymes (WHGase I, II, and III), in which JHGase I was considered to correspond to WHGase I. PMID:17151473

  12. Alternative Agents in Type 1 Diabetes in Addition to Insulin Therapy: Metformin, Alpha-Glucosidase Inhibitors, Pioglitazone, GLP-1 Agonists, DPP-IV Inhibitors, and SGLT-2 Inhibitors.

    Science.gov (United States)

    DeGeeter, Michelle; Williamson, Bobbie

    2016-04-01

    Insulin is the mainstay of current treatment for patients with type 1 diabetes mellitus (T1DM). Due to increasing insulin resistance, insulin doses are often continually increased, which may result in weight gain for patients. Medications currently approved for the treatment of type 2 diabetes offer varying mechanisms of action that can help to reduce insulin resistance and prevent or deter weight gain. A MEDLINE search was conducted to review literature evaluating the use of metformin, alpha-glucosidase inhibitors, pioglitazone, glucagon-like peptide 1 agonists, dipeptidyl peptidase, and sodium-dependent glucose transporter 2 inhibitors, in patients with T1DM. Varying results were found with some benefits including reductions in hemoglobin A1c, decreased insulin doses, and favorable effects on weight. Of significance, a common fear of utilizing multiple therapies for diabetes treatment is the risk of hypoglycemia, and this review displayed limited evidence of hypoglycemia with multiple agents. PMID:25312263

  13. Enzyme-assisted extraction of phenolics from winemaking by-products: Antioxidant potential and inhibition of alpha-glucosidase and lipase activities.

    Science.gov (United States)

    de Camargo, Adriano Costa; Regitano-d'Arce, Marisa Aparecida Bismara; Biasoto, Aline Camarão Telles; Shahidi, Fereidoon

    2016-12-01

    Phenolics in food and agricultural processing by-products exist in the soluble and insoluble-bound forms. The ability of selected enzymes in improving the extraction of insoluble-bound phenolics from the starting material (experiment I) or the residues containing insoluble-bound phenolics (experiment II) were evaluated. Pronase and Viscozyme improved the extraction of insoluble-bound phenolics as evaluated by total phenolic content, antioxidant potential as determined by ABTS and DPPH assays, and hydroxyl radical scavenging capacity, reducing power as well as evaluation of inhibition of alpha-glucosidase and lipase activities. Viscozyme released higher amounts of gallic acid, catechin, and prodelphinidin dimer A compared to Pronase treatment. Furthermore, p-coumaric and caffeic acids, as well as procyanidin dimer B, were extracted with Viscozyme but not with Pronase treatment. Solubility plays an important role in the bioavailability of phenolic compounds, hence this study may assist in better exploitation of phenolics from winemaking by-products as functional food ingredients and/or supplements.

  14. Alpha-glucosidase inhibitor, acarbose, improves glycamic control and reduces body weight in type 2 diabetes: Findings on indian patients from the pooled data analysis

    Directory of Open Access Journals (Sweden)

    Sanjay Kalra

    2013-01-01

    Full Text Available Alpha-glucosidase inhibitors are widely used especially in Asian countries as a treatment option for type 2 diabetes patients with high postprandial glycemia (PPG. The higher carbohydrate in the Indian diets lead to greater prandial glycemic excursion, increased glucosidase, and incretin activity in the gut and may need special therapeutic strategies to tackle these glucose peaks. This is the subgroup analysis of Indian subjects who participated in the GlucoVIP study that investigated the effectiveness and tolerability of acarbose as add-on or monotherapy in a range of patients with type 2 diabetes mellitus. A total of 1996 Indian patients were included in the effectiveness analysis. After 12.5 weeks (mean, the mean change in 2-hour PPG from baseline was −74.4 mg/dl, mean HbA1c decreased by -1.0%, and mean fasting blood glucose decreased by -37.9 mg/dl. The efficacy of acarbose was rated "very good" or "good" in 91.1% of patients, and tolerability as "very good" or "good" in 88.0% of patients. The results of this observational study suggest that acarbose was effective and well tolerated in the Indian patients with T2DM.

  15. Hes-1, a known transcriptional repressor, acts as a transcriptional activator for the human acid alpha-glucosidase gene in human fibroblast cells.

    Science.gov (United States)

    Yan, Bo; Raben, Nina; Plotz, Paul H

    2002-03-01

    Hes-1, the mammalian homologue 1 of Drosophila hairy and Enhancer of split proteins, belongs to a family of basic helix-loop-helix proteins that are essential to neurogenesis, myogenesis, hematopoiesis, and sex determination. Hes-1 is a transcriptional repressor for a number of known genes including the human acid alpha-glucosidase (GAA) gene as we have previously shown in Hep G2 cells. The human GAA gene encodes the enzyme for glycogen breakdown in lysosomes, deficiency of which results in Glycogen Storage Disease type II (Pompe syndrome). Using constructs containing the DNA element that demonstrates repressive activity in Hep G2 cells and conditions in which the same transcription factors, Hes-1 and YY1, bind, we have shown that this element functions as an enhancer in human fibroblasts. Site-directed mutagenesis and overexpression of Hes-1 showed that Hes-1 functions as a transcriptional activator. The dual function of Hes-1 we have found is likely to contribute to the subtle tissue-specific control of this housekeeping gene.

  16. Enzyme-assisted extraction of phenolics from winemaking by-products: Antioxidant potential and inhibition of alpha-glucosidase and lipase activities.

    Science.gov (United States)

    de Camargo, Adriano Costa; Regitano-d'Arce, Marisa Aparecida Bismara; Biasoto, Aline Camarão Telles; Shahidi, Fereidoon

    2016-12-01

    Phenolics in food and agricultural processing by-products exist in the soluble and insoluble-bound forms. The ability of selected enzymes in improving the extraction of insoluble-bound phenolics from the starting material (experiment I) or the residues containing insoluble-bound phenolics (experiment II) were evaluated. Pronase and Viscozyme improved the extraction of insoluble-bound phenolics as evaluated by total phenolic content, antioxidant potential as determined by ABTS and DPPH assays, and hydroxyl radical scavenging capacity, reducing power as well as evaluation of inhibition of alpha-glucosidase and lipase activities. Viscozyme released higher amounts of gallic acid, catechin, and prodelphinidin dimer A compared to Pronase treatment. Furthermore, p-coumaric and caffeic acids, as well as procyanidin dimer B, were extracted with Viscozyme but not with Pronase treatment. Solubility plays an important role in the bioavailability of phenolic compounds, hence this study may assist in better exploitation of phenolics from winemaking by-products as functional food ingredients and/or supplements. PMID:27374548

  17. KAPASITAS ANTIOKSIDAN DAN INHIBITOR ALFA GLUKOSIDASE EKSTRAK UMBI BAWANG DAYAK [Antioxidant and Alpha-Glucosidase Inhibitory Properties of Bawang Dayak Bulb Extracts

    Directory of Open Access Journals (Sweden)

    Andi Early Febrinda*

    2013-12-01

    Full Text Available Bawang dayak (Eleutherine palmifolia is an indigenous plant in Borneo traditionally used by Dayak tribes to treat any kind of degenerative deseases including diabetes mellitus. The purpose of this research was to measure antioxidant and antidiabetic capacities of water and ethanolic extracts of bawang dayak bulb. Parameters evaluated in this research were phytochemical screening, total phenolics, flavonoid content, DPPH free-radical scavenging activity, and alpha glucosidase inhibiting (AGI activity. The result showed that the total phenolics and flavonoid content in bawang dayak ethanolic extract (217.71 mg GAE/g and 65.35 mg QE/g were higher than that of the water extract (139.93 mg GAE/g and 16.95 mg QE/g. The ethanolic extract also had higher antioxidant and AGI activities (IC50 112 and 241 ppm than that of the water extract (IC50 526 and 505 ppm. In addition, the IC50 values for AGI in bawang dayak ethanolic extract was lower than acarbose which is known as a commercial antidiabetic agent.

  18. Production of enzymatically active recombinant full-length barley high pI alpha-glucosidase of glycoside family 31 by high cell-density fermentation of Pichia pastoris and affinity purification

    DEFF Research Database (Denmark)

    Næsted, Henrik; Kramhøft, Birte; Lok, F.;

    2006-01-01

    Recombinant barley high pI alpha-glucosidase was produced by high cell-density fermentation of Pichia pastoris expressing the cloned full-length gene. The gene was amplified from a genomic clone and exons (coding regions) were assembled by overlap PCR. The resulting cDNA was expressed under control...... of the alcohol oxidase 1 promoter using methanol induction of P. pastoris fermentation in a Biostat B 5 L reactor. Forty-two milligrams a-glucosidase was purified from 3.5 L culture in four steps applying an N-terminal hexa-histidine tag. The apparent molecular mass of the recombinant alpha-glucosidase was 100 k......Da compared to 92 kDa of the native barley enzyme. The secreted recombinant enzyme was highly stabile during the 5-day fermentation and had significantly superior specific activity of the enzyme purified previously from barley malt. The kinetic parameters K-m, V-max, and k(cat) were determined to 1.7 mM, 139...

  19. alpha-Glucosidase inhibition (acarbose) fails to enhance secretion of glucagon-like peptide 1 (7-36 amide) and to delay gastric emptying in Type 2 diabetic patients

    DEFF Research Database (Denmark)

    Hücking, K; Kostic, Z; Pox, C;

    2005-01-01

    AIM: Acarbose is able to enhance GLP-1 release and delay gastric emptying in normal subjects. The effect of alpha-glucosidase inhibition on GLP-1 has been less evident in Type 2 diabetic patients. The aim of this study was to investigate the possible influence of acarbose on GLP-1 release...... and gastric emptying in Type 2 diabetic patients after a mixed test meal. PATIENTS AND METHODS: Ten Type 2 diabetic patients were tested with 100 mg acarbose or placebo served with a mixed meal that was labelled with 100 mg 13C-octanoic acid. Plasma concentrations of glucose, insulin, C-peptide, glucagon, GLP......-1 and GIP were determined over 6 h. Gastric emptying was measured by determining breath 13CO2 using infrared absorptiometry. Statistics repeated-measures anova. RESULTS: Gastric emptying rates (t1/2: 162 +/- 45 vs. 163 +/- 62 min, P = 0.65) and plasma concentrations (increasing from approximately 12...

  20. 地骨皮提取物对α-葡萄糖苷酶的抑制作用及其降血糖作用机制探讨%Inhibititory effect of Cortex Lycii extract on alpha-glucosidase and its hypoglycemic mechanism

    Institute of Scientific and Technical Information of China (English)

    张丽; 邝少轶; 刘辰鹏; 黄凌

    2012-01-01

    Objective: To study the inhibitory effect of Cortex Lycii extract (CLE) on alpha-gluco-sidase by pharmacodynamic experiments in vitro , and to discuss the mechanism of its hypoglycemic activity. Methods:The alpha-glucosidase was extracted form the small intestine of rats, and the activity of α-glucosidase was determined by glucose kit. The concentration of glucose and the optical density value of starch in the reaction system were determined by the inhibitory experiment in vitro and the in vivo experiment, and the inhibitory rate of drug were detected respectively. The reciprocal of concentration of substrate was used as abscissa, and the reciprocal of reaction rate as ordinate, the Lineweaver-Burk plot was applied to determine the type of inhibited alpha-glucosidase activity. Results; The activity of crglucosidase in rat small intestine was 77.4 μmol · L-1 min-1. The low, moderate, high dose CLE inhibited the activity of alpha-glucosidase comparing with normal control group (P<0. 05, P<0. 05, P<0. 01) , and they also inhibited the hydrolytic effect of amylase (P<0. 01, P<0. 01, P<0. 01). The inhibitory curve experiment showed that the maximum reaction rate changed as concentration of CLE changed, but Michaelis constant(Km) remained the same. Conclusion: CLE has superior inhibition on crglucosidase.%目的:研究地骨皮提取物(CLE)对α-葡萄糖苷酶的抑制作用,并对其降血糖的作用机制进行探讨.方法:提取大鼠小肠中α-葡萄糖苷酶,采用葡萄糖试剂盒测定酶活力;通过体外抑制实验和离体器官实验测定反应体系中葡萄糖浓度和淀粉光密度值,分别计算药物对蔗糖酶和淀粉酶的抑制率;以底物浓度的倒数作为横坐标,以反映速率的倒数作为纵坐标,双倒数作图判断CLE对α-葡萄糖苷酶抑制作用类型.结果:大鼠小肠酶活力值为77.4个活力单位;与正常对照比较,CLE低、中、高剂量组对蔗糖酶的抑制率明显增加(P<0.05,P<0.05,P

  1. Relato do primeiro paciente brasileiro com a forma infantil da doença de Pompe tratado com alfa-glicosidase recombinante humana Report of the first Brazilian infantile Pompe disease patient to be treated with recombinant human acid alpha-glucosidase

    Directory of Open Access Journals (Sweden)

    Sandra J. Pereira

    2008-06-01

    Full Text Available Objetivo: Relatar o primeiro caso de forma infantil da doença de Pompe tratado no Brasil. Descrição: Trata-se de doença de depósito lisossomal que se caracteriza por defeitos da enzima alfa-glicosidase ácida, com acúmulo intracelular de glicogênio, principalmente nos músculos. São descritas a forma infantil e tardia. Desde 2006, está disponível tratamento com enzima recombinante humana. Descreve-se o primeiro caso de forma infantil da doença tratado no Brasil. Trata-se de menina com 2,5 meses de idade e progressão rápida da doença, com perda dos movimentos dos membros, miocardiopatia hipertrófica e insuficiência respiratória aos 7 meses de idade. Após 10 meses de tratamento, apresentou boa resposta clínica, com remissão da insuficiência respiratória, recuperação parcial dos movimentos dos membros e melhora importante do quadro cardiológico. Comentários: Apesar de pouco freqüente, a forma infantil da doença de Pompe é letal. A disponibilidade de tratamento eficaz aumenta a necessidade de conhecimento e diagnóstico precoce da doença.Objective: To describe the first case of infantile Pompe disease to be treated in Brazil. Description: Pompe disease is a glycogen storage disease related to defects in the acid alpha-glucosidase enzyme, leading to an intracellular accumulation of glycogen, mainly in muscles. Two forms are described: infantile and juvenile. Since 2006, treatment with recombinant human acid alpha-glucosidase has been available. This article describes the first case of infantile Pompe disease treated in Brazil. A girl presented at 2.5 months of age with rapid disease progression, exhibiting severe hypotonia, loss of movements in both upper and lower limbs and hypertrophic cardiomyopathy, progressing to respiratory failure by the age of 7 months. After 10 months of treatment, she exhibited a good clinical response, with remission of the respiratory failure, partial recovery of arm and leg movements and

  2. Optimization of Inhibitory Reaction System of Folium Mori Extracts on Alpha-glucosidase Activity and Enzyme Kinetics%桑叶提取物抑制α-葡萄糖苷酶活性体系的优化及动力学研究

    Institute of Scientific and Technical Information of China (English)

    吕欢; 罗明琍; 方飞; 吴新荣

    2012-01-01

    Objective To establish an optimized inhibitory reaction system for the research of Folium Mori extracts in inhibiting alpha-glucosidase activity and to investigate the enzyme kinetics. Methods We studied the inhibitive effects of Folium Mori extracts on alpha-glucosidase by using enzyme-inhibitor model and optimized the reaction system by optimizing the substrate concentration, the amount of enzyme and the reaction time. We also investigated the inhibitory kinetic characteristics of extracts by using Lineweaver-Burk method. Results The optimized reaction system consisted of 40 mg/mL of the substrate concentration, 0.2 mL of enzyme and 25 min for reaction time. Inhibitory kinetic results indicated that the extracts were mixed competitive inhibitors, but the positive drug was noncompetitive inhibitor. Conclusion Folium Mori extracts have inhibitory effect on a- glucosidase activity, and the inhibitory type is in mixed competitive inhibition, which are expected to be used to develop as anti-diabetes drugs.%目的 研究桑叶提取物抑制α-葡萄糖苷酶活性反应体系的条件优化及酶动力学.方法 采用酶-抑制剂模型法,优化底物浓度、酶用量和反应时间,确定最佳反应体系,研究桑叶提取物对α-葡萄糖苷酶的抑制作用,并采用双倒数作图法研究桑叶提取物的酶抑制动力学特性.结果 当蔗糖浓度为40 mg/mL,酶用量为0.2mL(约1.6 U/mL),反应时间为25 min时为最佳反应体系;酶抑制动力学实验表明,桑叶提取物的抑制类型为混合型竞争性抑制,阳性对照为非竞争性抑制.结论 桑叶提取物对α-葡萄糖苷酶活性有抑制作用;桑叶提取物对α-葡萄糖苷酶抑制活性为混合性竞争性抑制,可以用于开发降糖药物.

  3. Biogenesis of lysosomal enzymes in the alpha-glucosidase II-deficient modA mutant of Dictyostelium discoideum: retention of alpha-1,3-linked glucose on N-linked oligosaccharides delays intracellular transport but does not alter sorting of alpha-mannosidase or beta-glucosidase.

    Science.gov (United States)

    Ebert, D L; Bush, J M; Dimond, R L; Cardelli, J A

    1989-09-01

    The endoplasmic reticulum-localized enzyme alpha-glucosidase II is responsible for removing the two alpha-1,3-linked glucose residues from N-linked oligosaccharides of glycoproteins. This activity is missing in the modA mutant strain, M31, of Dictyostelium discoideum. Results from both radiolabeled pulse-chase and subcellular fractionation experiments indicate that this deficiency did not prevent intracellular transport and proteolytic processing of the lysosomal enzymes, alpha-mannosidase and beta-glucosidase. However, the rate at which the glucosylated precursors left the rough endoplasmic reticulum was several-fold slower than the rate at which the wild-type precursors left this compartment. Retention of glucose residues did not disrupt the binding of the precursor forms of the enzymes with intracellular membranes, indicating that the delay in movement of proteins from the ER did not result from lack of association with membranes. However, the mutant alpha-mannosidase precursor contained more trypsin-sensitive sites than did the wild-type precursor, suggesting that improper folding of precursor molecules might account for the slow rate of transport to the Golgi complex. Percoll density gradient fractionation of extracts prepared from M31 cells indicated that the proteolytically processed mature forms of alpha-mannosidase and beta-glucosidase were localized to lysosomes. Finally, the mutation in M31 may have other, more dramatic, effects on the lysosomal system since two enzymes, N-acetylglucosaminidase and acid phosphatase, were secreted much less efficiently from lysosomal compartments by the mutant strain.

  4. Study on the Optimum Proportion of Radix Astragalus with Flos Carthami on alpha - Glucosidase and Antioxidant Activities%黄芪与红花抑制α-葡萄糖苷酶及抗氧化活性的最佳配比研究

    Institute of Scientific and Technical Information of China (English)

    廖晖; 王孝敏

    2015-01-01

    目的:依照国家食品药品监督管理总局(CFDA)制定的黄芪注射液与红花注射液的制备方法,分别对黄芪与红花进行相关提取。研究黄芪、红花提取物抑制α-葡萄糖苷酶及抗氧化活性的最佳配比。方法液相色谱仪测定黄芪中黄芪甲苷的含量,以山奈酚为标准品测定红花中总黄酮的含量。以4-甲基-伞形酮-β- D -半乳糖苷(4- MUG)为反应底物,测定样品对酵母α-葡萄糖苷酶活性的影响,阿卡波糖为阳性对照。以氧自由基清除能( Oxygen Radical Absorbance Capacity, ORAC)法测定样品的抗氧化活性,维生素 C 为阳性对照。结果每1 ml 黄芪提取液中含有0.127 mg黄芪甲苷,每1 ml 红花提取液中含0.57 mg 总黄酮,均符合 CFDA 有关活性成分的含量要求。红花抑制α-葡萄糖苷酶活性的半数抑制浓度(IC50)为(32.8±5.7)μg/ ml,显著低于黄芪[(1686±810)μg/ ml,P <0.01];黄芪与红花生药比为10:1、5:1、2:1时的 IC50值均显著低于20:1时(P <0.01)。红花的 ORAC 值为(1090±161)μmol TE/ g,显著高于黄芪[(205±32)μmol TE/ g,P <0.01];生药比为5:1及2:1时的 ORAC 值分别显著高于20:1及 10:1时(P <0.01)。结论黄芪与红花均具有抑制酵母α-葡萄糖苷酶活性的作用及一定的抗氧化活性,在同时改善以上两项指标方面,生药比为5:1及2:1时较20:1时作用显著(P <0.01)。%Objective To prepare radix astragalus injection and flos carthami injection according to the method of the China Food and Drug Administration(CFDA)and extract them respectively so as to study the optimum proportion of them on alpha - glucosidase and antioxidant activities. Methods The liquid chro-matograph was used to determine the content of astragaloside in radix astragalus. Kaempferol was used as the standard to determine the content of general flavone in flos carthami. 4 - MUG was as the

  5. Alpha-Glucosidase Enzyme Biosensor for the Electrochemical Measurement of Antidiabetic Potential of Medicinal Plants

    OpenAIRE

    Mohiuddin, M.; D. Arbain; Islam, A. K. M. Shafiqul; M. S. Ahmad; Ahmad, M.N.

    2016-01-01

    A biosensor for measuring the antidiabetic potential of medicinal plants was developed by covalent immobilization of α-glucosidase (AG) enzyme onto amine-functionalized multi-walled carbon nanotubes (MWCNTs-NH2). The immobilized enzyme was entrapped in freeze-thawed polyvinyl alcohol (PVA) together with p-nitrophenyl-α-d-glucopyranoside (PNPG) on the screen-printed carbon electrode at low pH to prevent the premature reaction between PNPG and AG enzyme. The enzymatic reaction within the biosen...

  6. Alpha-glucosidase inhibitory effect and inorganic constituents of Phyllanthus amarus Schum. & Thonn. ash

    Directory of Open Access Journals (Sweden)

    Malinee Wongnawa

    2014-10-01

    Full Text Available This study investigated the -glucosidase inhibitory effect and determined the concentration of some inorganic constituents in P. amarus ash. Oral glucose and sucrose tolerance test were performed on normal mice. In vitro -glucosidase inhibitory activity was evaluated by using yeast a-glucosidase. The element concentrations were measured by inductively coupled plasma (ICP spectroscopy. Single oral administration of P. amarus ash did not show antihyperglycemic effect after glucose administration, but decreased blood glucose level after sucrose administration. The ash showed -glucosidase inhibitory activity in vitro with IC50 of 982 mg/mL. The concentrations of K, Ca, Mg, Mn, Fe, Zn, Cu, Pb, Cr, Ni and Co in P. amarus ash were 35049.80±340.64, 3337.24±52.10, 1368.52±13.29, 90.81±1.34, 87.68±1.15, 18.28±0.22, 4.69±0.07, 1.07±0.15, 0.29±0.03, 0.20±0.04 and 0.10±0.02 mg/g, respectively. These results indicate that the antihyperglycemic effect of P. amarus ash might be partly due to the -glucosidase inhibitory activity of the inorganic constituents.

  7. Alpha-Glucosidase Enzyme Biosensor for the Electrochemical Measurement of Antidiabetic Potential of Medicinal Plants.

    Science.gov (United States)

    Mohiuddin, M; Arbain, D; Islam, A K M Shafiqul; Ahmad, M S; Ahmad, M N

    2016-12-01

    A biosensor for measuring the antidiabetic potential of medicinal plants was developed by covalent immobilization of α-glucosidase (AG) enzyme onto amine-functionalized multi-walled carbon nanotubes (MWCNTs-NH2). The immobilized enzyme was entrapped in freeze-thawed polyvinyl alcohol (PVA) together with p-nitrophenyl-α-D-glucopyranoside (PNPG) on the screen-printed carbon electrode at low pH to prevent the premature reaction between PNPG and AG enzyme. The enzymatic reaction within the biosensor is inhibited by bioactive compounds in the medicinal plant extracts. The capability of medicinal plants to inhibit the AG enzyme on the electrode correlates to the potential of the medicinal plants to inhibit the production of glucose from the carbohydrate in the human body. Thus, the inhibition indicates the antidiabetic potential of the medicinal plants. The performance of the biosensor was evaluated to measure the antidiabetic potential of three medicinal plants such as Tebengau (Ehretis laevis), Cemumar (Micromelum pubescens), and Kedondong (Spondias dulcis) and acarbose (commercial antidiabetic drug) via cyclic voltammetry, amperometry, and spectrophotometry. The cyclic voltammetry (CV) response for the inhibition of the AG enzyme activity by Tebengau plant extracts showed a linear relation in the range from 0.423-8.29 μA, and the inhibition detection limit was 0.253 μA. The biosensor exhibited good sensitivity (0.422 μA/mg Tebengau plant extracts) and rapid response (22 s). The biosensor retains approximately 82.16 % of its initial activity even after 30 days of storage at 4 °C. PMID:26887579

  8. Long-term intravenous treatment of Pompe disease with recombinant human alpha-glucosidase from milk

    NARCIS (Netherlands)

    J.M.P. van den Hout (Johanna); B. Sibbles (Barbara); J.P. Brakenhoff (Just); A.H. Cromme-Dijkhuis (Adri); N. Weisglas-Kuperus (Nynke); A.J.J. Reuser (Arnold); M.A. Boer (Marijke); J.A.M. Smeitink (Jan); O.P. van Diggelen (Otto); E. Voort (Edwin); E.J.J.M. van Corven (Emiel); H. van Hirtum (Hans); J.H.J. Kamphoven (Joep); A.T. van der Ploeg (Ans); J. van Hove (Johan); W.F.M. Arts (Willem Frans); P.A. van Doorn (Pieter); J.B.C. de Klerk (Johannes); M.C.B. Loonen (Christa); A.G. Vulto (Arnold); M.A. Kroos (Marian); W.C.J. Hop (Wim); L.P.F. Winkel (Léon); G. de Jong (Gerard)

    2004-01-01

    textabstractOBJECTIVE: Recent reports warn that the worldwide cell culture capacity is insufficient to fulfill the increasing demand for human protein drugs. Production in milk of transgenic animals is an attractive alternative. Kilogram quantities of product per year can be obtain

  9. Competitive inhibitor of cellular alpha-glucosidases protects mice from lethal dengue virus infection

    OpenAIRE

    Chang, Jinhong; Schul, Wouter; Yip, Andy; Xu, Xiaodong; Guo, Ju-Tao; Block, Timothy M.

    2011-01-01

    Dengue virus infection causes diseases in people, ranging from the acute febrile illness Dengue fever, to life-threatening Dengue Hemorrhagic Fever/Dengue Shock Syndrome. We previously reported that a host cellular α-glucosidases I and II inhibitor, imino sugar CM-10-18, potently inhibited dengue virus replication in cultured cells, and significantly reduced viremia in dengue virus infected AG129 mice. In this report we show that CM-10-18 also significantly protects mice from death and/or dis...

  10. Alpha-Glucosidase Inhibition and Hypoglycemic Activities of Sweitenia mahagoni Seed Extract

    OpenAIRE

    Tutik Wresdiyat; Siti Sa’diah; Adi Winarto; Venny Febriyani

    2015-01-01

    Inhibition of α-glucosidase and hypoglycemic activity are two effects commonly used to identify bioactive compounds with potential to treat diabetes. The objectives of this study were to analyse and compare the bioactive compounds and α-glucosidase inhibitory effect of four different types of Swietenia mahagoni seed extract, and to analyse the hypoglycemic activity of the greatest inhibition of α-glucosidase-extract in rats. The extracts were obtained using two different solvents (aqueous and...

  11. Alpha-Glucosidase Enzyme Biosensor for the Electrochemical Measurement of Antidiabetic Potential of Medicinal Plants

    Science.gov (United States)

    Mohiuddin, M.; Arbain, D.; Islam, A. K. M. Shafiqul; Ahmad, M. S.; Ahmad, M. N.

    2016-02-01

    A biosensor for measuring the antidiabetic potential of medicinal plants was developed by covalent immobilization of α-glucosidase (AG) enzyme onto amine-functionalized multi-walled carbon nanotubes (MWCNTs-NH2). The immobilized enzyme was entrapped in freeze-thawed polyvinyl alcohol (PVA) together with p-nitrophenyl-α- d-glucopyranoside (PNPG) on the screen-printed carbon electrode at low pH to prevent the premature reaction between PNPG and AG enzyme. The enzymatic reaction within the biosensor is inhibited by bioactive compounds in the medicinal plant extracts. The capability of medicinal plants to inhibit the AG enzyme on the electrode correlates to the potential of the medicinal plants to inhibit the production of glucose from the carbohydrate in the human body. Thus, the inhibition indicates the antidiabetic potential of the medicinal plants. The performance of the biosensor was evaluated to measure the antidiabetic potential of three medicinal plants such as Tebengau ( Ehretis laevis), Cemumar ( Micromelum pubescens), and Kedondong ( Spondias dulcis) and acarbose (commercial antidiabetic drug) via cyclic voltammetry, amperometry, and spectrophotometry. The cyclic voltammetry (CV) response for the inhibition of the AG enzyme activity by Tebengau plant extracts showed a linear relation in the range from 0.423-8.29 μA, and the inhibition detection limit was 0.253 μA. The biosensor exhibited good sensitivity (0.422 μA/mg Tebengau plant extracts) and rapid response (22 s). The biosensor retains approximately 82.16 % of its initial activity even after 30 days of storage at 4 °C.

  12. Alpha-Glucosidase Inhibition and Hypoglycemic Activities of Sweitenia mahagoni Seed Extract

    Directory of Open Access Journals (Sweden)

    Tutik Wresdiyat

    2015-04-01

    Full Text Available Inhibition of α-glucosidase and hypoglycemic activity are two effects commonly used to identify bioactive compounds with potential to treat diabetes. The objectives of this study were to analyse and compare the bioactive compounds and α-glucosidase inhibitory effect of four different types of Swietenia mahagoni seed extract, and to analyse the hypoglycemic activity of the greatest inhibition of α-glucosidase-extract in rats. The extracts were obtained using two different solvents (aqueous and ethanol and two different methods: maceration and reflux methods. This resulted in four types of extract varying by solvent and extraction method. Testing of these extracts for α-glucosidase inhibitory effect was carried out in vitro using spectrophotometer. Testing for hypoglycemic activity was carried out in vivo using rats. A total of 40 male Sprague-Dawley rats were divided into eight groups: (1 the negative control group, received an oral dose of aquadest only, (2 the positive control group, was given 90% sucrose orally without S. mahagoni seed extract, and five treated groups (3-7, were given 90% sucrose followed by the best extract-ethanolic S. mahagoni seed extract in doses of 100, 200, 300, 400, and 500 mg/kgBW, and (8 the acarbose group, was given 90% sucrose orally followed by acarbose. Glucose levels in each animal were measured at 0, 30, 60, 90, and 120 min after treatment. The results showed the greatest inhibition of α-glucosidase in ethanolic extract, using maceration methods. This ethanolic-maceration S. mahagoni seed extract also showed hypoglycemic effects in hyperglycemic rats at dose from 100 to 500 mg/kgBW. Ethanolic extract of S. mahagoni seed, using maceration method, can be proposed as potential antidiabetic agent.

  13. Structure of the Sulfolobus solfataricus alpha-glucosidase: Implications for domain conservation and substrate recognition in GH31

    DEFF Research Database (Denmark)

    Ernst, Heidi Asschenfeldt; Lo Leggio, Leila; Willemoes, M.;

    2006-01-01

    glycogen degradation and glycoprotein processing. The structure of MalA shows clear differences from the only other structure known from GH31, a-xylosidase YicI. MalA and YicI share only 23% sequence identity. Although the two enzymes display a similar domain structure and both form hexamers, their......), whereas YicI prefers isoprimeverose (Xyl-a1,6-Glc). The structural origin of this difference occurs in the -1 subsite where MalA residues Asp251 and Trp284 could interact with OH6 of the substrate. The structure of MalA in complex with ß-octyl-glucopyranoside has been determined. It reveals Arg400, Asp87...

  14. Alpha-amylase and alpha-glucosidase inhibition is differentially modulated by fucoidan obtained from Fucus vesiculosus and Ascophyllum nodosum.

    Science.gov (United States)

    Kim, Kyung-Tae; Rioux, Laurie-Eve; Turgeon, Sylvie L

    2014-02-01

    Fucoidan is a water-soluble, negatively charged, biologically active polysaccharide found in great abundance in brown marine algae. However, the inhibition of α-amylase and α-glucosidase by fucoidan derived from two algal species (Ascophyllum nodosum and Fucus vesiculosus) harvested at different periods (accounting for seasonal and yearly variations) has never been investigated. It was found that fucoidans inhibited α-glucosidase differently, depending on the algal species from which it was extracted and the algae's season of harvest. Fucoidan extracted from A. nodosum was a more potent inhibitor of α-glucosidase, with an IC50 ranging from 0.013 to 0.047 mg/mL, than the inhibition by fucoidan extracted from F. vesiculosus (IC50=0.049 mg/mL). In contrast, fucoidan extracted from F. vesiculosus did not inhibit α-amylase activity, while fucoidan from A. nodosum decreased α-amylase activity by 7-100% at 5 mg/mL depending upon the algae harvest period. An IC50 of 0.12-4.64 mg/mL for fucoidan from A. nodosum was found for the α-amylase inhibition. The ability of fucoidan to inhibit α-amylase and α-glucosidase thus varies according to the algae species and harvest period. A. nodosum is more suitable than F. vesiculosus as a source of fucoidan to inhibit α-amylase and α-glucosidase activities. Their potential benefits towards Type 2 diabetes management should be further investigated. PMID:24388677

  15. Optimization and Modeling of Ultrasound-assisted Extraction of Polysaccharides from Cynomorium songaricum and &alpha-glucosidase Inhibitory Activity

    OpenAIRE

    Tao Guo; Jun-qing Wei; Ya Wang; Dan Su; Zhen Zhang; Yu-long Yao

    2015-01-01

    In the study, the extraction processing of polysaccharides from Cynomorium songaricum was optimized by Response Surface Methodology (RSM) and projected by a computer-stimulated Artificial Neural Network (ANN). The optimal process conditions were obtained as follows: extraction temperature 55C, solid-liquid ratio 1:10, power 175 W. Under optimized conditions, The R2 value of 0.99391 and an MSE value of 0.0495 suggested a good generalization of the network and showed a good agreement between t...

  16. [Constituents relating to anti-oxidative and alpha-glucosidase inhibitory activities in Yacon aerial part extract].

    Science.gov (United States)

    Terada, Sumio; Ito, Kikuo; Yoshimura, Akira; Noguchi, Naoto; Ishida, Takashi

    2006-08-01

    Hot water extract of the aerial part of Yacon (Smallanthus sonchifolia, Compositae) showed potent free radical-scavenging activity and inhibitory effects on lipid peroxidation in rat brain homogenate. The most potent antioxidative activity focused on the 50% MeOH-eluted fraction on DIAION HP-20 column chromatography. The structure of the major component in the fraction was identified as 2,3,5-tricaffeoylaltraric acid (TCAA) based on spectroscopic evidence. The antioxidative activity of TCAA is superior to that of natural antioxidants such as (+/-)-catechin, alpha-tocopherol, and ellagic acid, and TCAA also showed selective maltase-inhibitory activity (IC(50) 49 microg/ml). As the hypoglycemic activity of Yacon extract was described in a previous report, the present results showing that the aerial part of Yacon has strong antioxidative activity may encourage its potential use as a food supplement to prevent type II diabetes. PMID:16880725

  17. EVALUATION OF ALPHA-AMYLASE AND ALPHA-GLUCOSIDASE INHIBITORY PROPERTIES OF SELECTED SEAWEEDS FROM GULF OF MANNAR

    Directory of Open Access Journals (Sweden)

    Palanisamy SenthilKumar

    2012-08-01

    Full Text Available Aqueous extracts of four seaweeds collected from Gulf of Mannar coastal waters were tested for α-amylase and α-glucosidase inhibition properties. The aqueous extracts of seaweeds in the order of Gracilaria edulis, Sargassum polycystum, Ulva lactuca and Gracilaria corticata showed significant inhibitory activity against α-amylase and α-glucosidase enzymes. G. edulis was found to be a potent inhibitor of α-glucosidase with an IC50 value of 46μg/mL. The aqueous extract of S. polycystum at a concentration of 10-100 µg/ml showed maximum α-amylase inhibitory activity with an IC50 value of 60μg/mL. This study warrants further investigation on the antidiabetic activity and identifies the hyperglycemic principle to elucidate their mode of action.

  18. Synthesis and Characterization of New Chromogenic Substrates for Exoglycosidases : alpha-Glucosidase, alpha-Mannosidase, and beta-Galactosidase

    OpenAIRE

    Iga, Dumitru Petru; Schmidt, Richard; Iga, Silvia; Hotoleanu, Corina Loredana; Duica, Florentina; Nicolescu, Alina; Gitman, Silvia Stefania

    2013-01-01

    Glycosides of 4-nitrocatechol (1,2-dihydroxy 4-nitrobenzene) with α-D-glucopyranose and α-D-mannopyranose were synthesized by the glycosylation of phenol with peracetylated sugars in the presence of BF3·OBu2 . The glycoside of 4-nitrocatechol with β-D-galactopyranose was prepared by the glycosylation of this phenol as sodium phenoxide with tetra-O-benzoyl-α-D-galactopyranosyl bromide. The structure of the reaction products was confirmed by 1H and 13C NMR spectra and by chemical analysis. The ...

  19. Anti-inflammatory, free radical scavenging and alpha-glucosidase inhibitory activities of Hamelia patens and its chemical constituents.

    Science.gov (United States)

    Jiménez-Suárez, Verónica; Nieto-Camacho, Antonio; Jiménez-Estrada, Manuel; Alvarado Sánchez, Brenda

    2016-09-01

    Context Hamelia patens Jacq. (Rubiaceae) is traditionally used to treat wounds, inflammation and diabetes. However, there is still a lack of scientific evidence to support these applications. Objective The objective of this study is to evaluate the anti-inflammatory, antioxidant and antidiabetic activities of Hamelia patens, and identify its bioactive compounds. Materials and methods Four extracts were obtained by maceration and liquid-liquid extraction: HEX, DCM-EtOAc, MeOH-EtOAc and MeOH-Aq. The anti-inflammatory effect was evaluated orally on rat paw carrageenan-induced oedema over 6 h (50, 200 and 500 mg/kg), and topically in mouse ear oedema induced by 12-tetradecanoylphorbol-13-acetate (TPA) after 4 h (0.5 and 1 mg/ear). We also evaluated myeloperoxidase levels in ear tissue, 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging ability, and in vitro α-glucosidase inhibition. The chemical compounds were separated by column chromatography and identified by spectroscopic analysis. Results We found that the oral administration of the HEX extract at 500 and 200 mg/kg significantly decreased the carrageenan-induced inflammation after 1 and 3 h, respectively. The MeOH-EtOAc extract significantly inhibited myeloperoxidase activity (83.5%), followed by the DCM-EtOAc extract (76%), β-sitosterol/stigmasterol (72.7%) and the HEX extract (55%), which significantly decreased oedema induced by TPA at both doses, giving a similar effect to indomethacin. We also found that the MeOH-EtOAc, MeOH-Aq and DCM-EtOAc extracts showed good DPPH scavenging activity (IC50 values of 18.6, 93.9 and 158.2 μg/mL, respectively). The HEX extract showed the lowest α-glucosidase inhibition (an IC50 value of 26.07 μg/mL), followed by the MeOH-EtOAc extract (an IC50 value of 30.18 μg/mL), β-sitosterol/stigmasterol (IC50 34.6 μg/mL) and compound A ((6E,10E,14E,18E)-2,6,10,14,18,23-hexamethyl-2,6,10,14,18,22-tetracosahexaene, an IC50 value of 114.6 μg/mL), which were isolated for the first time from Hamelia patens. Discussion and conclusion Hamelia patens possesses anti-inflammatory, antioxidant and α-glucosidase inhibitory activities, which support its traditional use. These effects can be attributed to the identified compounds.

  20. In vitro evaluation and determination of responsible fraction of coffee beans and dried sugar beet leaves for alpha-glucosidase inhibition.

    Directory of Open Access Journals (Sweden)

    K. Singh

    2013-10-01

    Full Text Available Summary. Recent studies have identified that hydrophobic phenolic phytochemicals and hydrophilic Amadori compounds have potential for type 2 diabetes management via inhibition of carbohydrate hydrolysis enzymes. Here, we determined the phenolic content, α-glucosidase inhibitory activity, and pancreatic α-amylase inhibitory activity of water extracts of roasted and unroasted coffee beans and dried sugar beet leaves. Sugar beet leaves appeared to have the lowest total phenolic content while unroasted and roasted coffee beans had similar phenolic contents (1.49 and 1.40 mg/mL GAE DW respectively. All tested samples resulted to a dose-dependent α-glucosidase inhibitory activity. Sugar beet leaves had significant inhibitory activity (78% at the highest dose and after C18 extraction this activity appeared to be both hydrophilic and hydrophobic compound dependent.  Roasted coffee beans had significantly higher α-glucosidase inhibitory activity when compared to green coffee beans at all tested doses. Roasted coffee beans were subjected to C18 extraction and the α-glucosidase inhibitory activity was evaluated and determined to be solely hydrophobic compound dependent. When the α-amylase inhibitory activity was evaluated, no inhibition was observed with all tested samples. Our findings indicate that the observed bioactivities in coffee beans is hydrophobic compound dependent, while in sugar beet leaves the observed effect is possibly due to the synergistic effect of both hydrophobic and hydrophilic fractions. This is the first report on the carbohydrate hydrolyzing enzyme inhibition of roasted coffee beans and sugar beet leaves.Industrial Relevance. Sugar beets are widely cultivated in Europe and Northern Asia for the production of table sugar. After the harvesting of sugar beets large quantities of sugar beet leaves remain on the field and are either left to become fertilizer or appropriately disposed. Identification of appropriate strategies to utilize this by-product of sugar production, could possibly result to a sustainable utilization of this by-product. Taking into consideration that sugar is one of the reasons for the increase in the incidence of type 2 diabetes, possibly utilization of sugar-production by-products for the management of type 2 diabetes will be of extreme importance. Coffee is an important commodity and popular beverage. Over 2.25 billion cups of coffee are consumed in the world every day. Taking the above into consideration, identification of potential glucose lowering compounds in coffee can lead to the development of coffee beverages designed to prevent type 2 diabetes.Keywords: sugar beet leaves; green coffee beans; roasted coffee beans; type 2 diabetes; α-glucosidase inhibition; phenolic phytochemicals; Amadori compounds

  1. Bean cultivars (Phaseolus vulgaris L.) have similar high antioxidant capacity, in vitro inhibition of alpha-amylase and alpha-glucosidase while diverse phenolic composition and concentration

    Science.gov (United States)

    Common beans are a good source of essential nutrients such as protein, fiber, vitamins, and minerals; they also contain phenolic compounds and other phytochemicals. Phenolic compounds exhibit high antioxidant capacity that promotes health benefits by reducing oxidative stress. The objective was to c...

  2. Effect of storage time on metabolite profile and alpha-glucosidase inhibitory activity of Cosmos caudatus leaves – GCMS based metabolomics approach

    Directory of Open Access Journals (Sweden)

    Neda Javadi

    2015-09-01

    Full Text Available Cosmos caudatus, which is a commonly consumed vegetable in Malaysia, is locally known as “Ulam Raja”. It is a local Malaysian herb traditionally used as a food and medicinal herb to treat several maladies. Its bioactive or nutritional constituents consist of a wide range of metabolites, including glucosinolates, phenolics, amino acids, organic acids, and sugars. However, many of these metabolites are not stable and easily degraded or modified during storage. In order to investigate the metabolomics changes occurring during post-harvest storage, C. caudatus samples were subjected to seven different storage times (0 hours, 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, and 12 hours at room temperature. As the model experiment, the metabolites identified by gas chromatography-mass spectrometry (GC-MS were correlated with α-glucosidase inhibitory activity analyzed with multivariate data analysis (MVDA to find out the variation among samples and metabolites contributing to the activity. Orthogonal partial least squares (OPLS analysis was applied to investigate the metabolomics changes. A profound chemical alteration, both in primary and secondary metabolites, was observed. The α-tocopherol, catechin, cyclohexen-1-carboxylic acid, benzoic acid, myo-inositol, stigmasterol, and lycopene compounds were found to be the discriminating metabolites at early storage; however, sugars such as sucrose, α-d-galactopyranose, and turanose were detected, which was attributed to the discriminating metabolites for late storage. The result shows that the MVDA method is a promising technique to identify biomarker compounds relative to storage at different times.

  3. In vitro evaluation and determination of responsible fraction of coffee beans and dried sugar beet leaves for alpha-glucosidase inhibition.

    OpenAIRE

    Singh, K; Kafka, A.; B-H Kang; R. Goundra; Y-I Kwon; E Apostolidis

    2013-01-01

    Summary. Recent studies have identified that hydrophobic phenolic phytochemicals and hydrophilic Amadori compounds have potential for type 2 diabetes management via inhibition of carbohydrate hydrolysis enzymes. Here, we determined the phenolic content, α-glucosidase inhibitory activity, and pancreatic α-amylase inhibitory activity of water extracts of roasted and unroasted coffee beans and dried sugar beet leaves. Sugar beet leaves appeared to have the lowest total phenolic content while unr...

  4. The pharmacological chaperone AT2220 increases the specific activity and lysosomal delivery of mutant acid alpha-glucosidase, and promotes glycogen reduction in a transgenic mouse model of Pompe disease.

    Directory of Open Access Journals (Sweden)

    Richie Khanna

    Full Text Available Pompe disease is an inherited lysosomal storage disorder that results from a deficiency in acid α-glucosidase (GAA activity due to mutations in the GAA gene. Pompe disease is characterized by accumulation of lysosomal glycogen primarily in heart and skeletal muscles, which leads to progressive muscle weakness. We have shown previously that the small molecule pharmacological chaperone AT2220 (1-deoxynojirimycin hydrochloride, duvoglustat hydrochloride binds and stabilizes wild-type as well as multiple mutant forms of GAA, and can lead to higher cellular levels of GAA. In this study, we examined the effect of AT2220 on mutant GAA, in vitro and in vivo, with a primary focus on the endoplasmic reticulum (ER-retained P545L mutant form of human GAA (P545L GAA. AT2220 increased the specific activity of P545L GAA toward both natural (glycogen and artificial substrates in vitro. Incubation with AT2220 also increased the ER export, lysosomal delivery, proteolytic processing, and stability of P545L GAA. In a new transgenic mouse model of Pompe disease that expresses human P545L on a Gaa knockout background (Tg/KO and is characterized by reduced GAA activity and elevated glycogen levels in disease-relevant tissues, daily oral administration of AT2220 for 4 weeks resulted in significant and dose-dependent increases in mature lysosomal GAA isoforms and GAA activity in heart and skeletal muscles. Importantly, oral administration of AT2220 also resulted in significant glycogen reduction in disease-relevant tissues. Compared to daily administration, less-frequent AT2220 administration, including repeated cycles of 4 or 5 days with AT2220 followed by 3 or 2 days without drug, respectively, resulted in even greater glycogen reductions. Collectively, these data indicate that AT2220 increases the specific activity, trafficking, and lysosomal stability of P545L GAA, leads to increased levels of mature GAA in lysosomes, and promotes glycogen reduction in situ. As such, AT2220 may warrant further evaluation as a treatment for Pompe disease.

  5. Synthèses enzymatiques de néoglucoconjugués catalysées par l'alpha-glucosidase purifiée de la blatte Periplaneta americana (Linnaeus

    Directory of Open Access Journals (Sweden)

    Kamenan A.

    2005-01-01

    Full Text Available Enzymatic synthesis of neoglucoconjugates by purified α-glucosidase from cockroach Periplaneta americana (Linnaeus. Cockroach Periplaneta americana (Linnaeus contains in his digestive tract an acid (pH 5,0 and mesophile (50°C α-glucosidase. This enzyme, purified to homogeneity, hydrolyses highly maltose, sucrose and p-nitrophenyl-α-Dglucopyranoside. The ability of α-glucosidase from cockroach purified to homogeneity to catalyse transglucosylation reactions was tested using maltose and saccharose as glucosyl donors and 2-phenylethanol and phenol as acceptors. The experimental conditions were optimized in relation to the time course of the reaction, pH and concentrations of glucosyl donors and acceptors. The yields in transglucosylation reactions at 37 °C were very high and could attain 67% and 48% with 2-phenylethanol and phenol respectively as glucosyl acceptors. This α-glucosidase hydrolyzed the products formed. It seems that the products formed were the phenylethyl-α-D-glucoside and phenyl-α-D-glucoside. These results suggest that α- glucosidase from cockroach is an exoglucosidase which catalyse the splitting of the α-glucosyl residue from the non reducing terminal of the substrate to liberate α-glucose. This comportment indicates that this enzyme operated by a mechanism involving the retention of the anomeric configuration. On the basis of this work, α-glucosidase from P. americana appears to be a valuable tool for the preparation of α-neoglucoconjugates.

  6. 不同干酪乳杆菌菌株对α-葡萄糖苷酶抑制作用的比较%Comparison of Alpha -glucosidase Inhibitory Effect of Different Lactobacillus casei Strains

    Institute of Scientific and Technical Information of China (English)

    范文娅; 吴正钧; 季红; 郭本恒

    2012-01-01

    The α-glucosidase inhibitory activity of whey from fermented skim milk by 11 strains with milk curding ability which were selected from 14 Lactobacillus casei strains, assayed in vitro enrolling maltase ( EC 3.2.1.20) as the targeting enzyme. It was showed that the c~-glucosidase inhibitory activity of Lb. casei was strain specific, with a significant increase in inhibitory intensity with the fermentation elongated for those strains demonstrated α-glucosidase inhibitory activity. Among the tested Lb. casei strains, Lb. casei LC2W (CGMCC0828) demonstrated the strongest α- glucosidase inhibitory activity, with an inhibitory percentage of 37.36% for whey derived of 10% (w/w) skim milk fermented at 37C for 96 hours. These results suggested Lb. casei LC2W has the potentials of antihyperglycemia as well as anti-diabetes.%从14株干酪乳杆菌中筛选出11株具有凝乳作用的菌株,采用以麦芽糖酶为靶向酶的α-葡萄糖苷酶抑制剂体外筛选模型,分析了不同干酪乳杆菌发酵脱脂乳上清对α-葡萄糖苷酶的抑制作用。结果表明,不同菌株发酵脱脂乳上清对麦芽糖酶的抑制活性具有明显的菌株特异性,且随着发酵时间延长,α-葡萄糖苷酶抑制活性呈现上升趋势。其中,干酪乳杆菌LC2W在37℃发酵10%(w/w)脱脂乳96 h后所得的上清液对麦芽糖酶抑制活性最高,达37.36%,明显高于其它被测试的干酪乳杆菌菌株,表明该菌株具有潜在的抗高血糖作用。

  7. Alpha-glucosidase Inhibitors from Fermented Soybean Milk and Steamed Soybean by Lactobacillus plantarum ST-Ⅲ%植物乳酸菌ST-Ⅲ产α-糖苷酶抑制剂作用的研究

    Institute of Scientific and Technical Information of China (English)

    韩瑨; 季红; 周方方; 吴正钧

    2014-01-01

    以改良的体外模型为测定手段,评价了植物乳杆菌ST-Ⅲ(Lactobacillus plantarum ST-Ⅲ)以蒸煮大豆为培养基料时,其接种量、发酵温度对发酵产物抑制麦芽糖酶的影响,同时,通过对植物乳杆菌ST-Ⅲ在最优条件下发酵大豆豆浆和蒸煮大豆的产物对麦芽糖酶的抑制效果及其相应粗提物对麦芽糖酶的半数抑制浓度IC50的比较,评价了植物乳杆菌ST-Ⅲ在不同形式的大豆基料中产-葡萄糖苷酶抑制剂的能力,结果表明:植物乳杆菌ST-Ⅲ发酵蒸煮大豆产生麦芽糖酶抑制物的最适条件分别为接种量2%(v/w)、发酵温度37℃。在优化条件下,植物乳杆菌ST-Ⅲ发酵大豆豆浆10 h的产物对麦芽糖酶的抑制效果可达80%左右,而发酵蒸煮大豆时达到相同抑制效果需发酵10 d以上。发酵两种不同形式大豆基料制得的粗提物对麦芽糖酶的半数抑制浓度IC50分别为2.989 mg/mL和2.597 mg/mL。因此,液体状态的大豆豆浆是植物乳杆菌ST-Ⅲ发酵产-葡萄糖苷酶抑制剂的优选基料形式。%The optimum condition for Lactobacillus plantarum ST-Ⅲto biosynthesize maltase (EC 3.2.1.20) inhibitors in fermented steamed soybean was assayed via a modified model in vitro , and the optimized condition was found to be a combination of inoculation ratio of 2%(v/w), fermentation temperature of 37℃, respectively. Under the optimized conditions, inhibitory effect on maltase of soybean milk fermented 10 h reached 80%, and the time for the fermented steamed soybean reaching the same inhibitory effect on maltase is at least 10 d. The IC 50 of crude extract prepared from soybean milk and steamed soybean fermented by Lactobacillus plantarum ST-Ⅲwas 2.989 mg/mL and 2.597 mg/mL. Therefore, soybean milk was the more suitable form for Lactobacillus plantarum ST-Ⅲto produceα-glucosidase inhibitors.

  8. Serviceberry [Amerlanchier alnifolia (Nutt.) Nutt. ex. M. Roem(Rosaceae)] leaf exhibits mammalian alpha glucosidase activity and suppresses postprandial glycemic response in a mouse model of diet induced obesity/hyperglycemia

    Science.gov (United States)

    Several plant-based remedies offer cost-effective management of diabetes, but few plant species adapted to North America have been validated for their antidiabetic properties. One such species is serviceberry (Amelanchier alnifolia), found in Browning, MT, which has been traditionally used by the Am...

  9. SwissProt search result: AK102309 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK102309 J033090B18 (P10253) Lysosomal alpha-glucosidase precursor (EC 3.2.1.20) (Acid maltase) (Aglucosidas...e alfa) [Contains: 76 kDa lysosomal alpha-glucosidase; 70 kDa lysosomal alpha-glucosidase] LYAG_HUMAN 1e-145 ...

  10. SwissProt search result: AK066051 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK066051 J013051B02 (P10253) Lysosomal alpha-glucosidase precursor (EC 3.2.1.20) (Acid maltase) (Aglucosidas...e alfa) [Contains: 76 kDa lysosomal alpha-glucosidase; 70 kDa lysosomal alpha-glucosidase] LYAG_HUMAN 1e-89 ...

  11. Effect of enzyme therapy in juvenile patients with Pompe disease: a three-year open-label study.

    NARCIS (Netherlands)

    Capelle, C.I. van; Beek, N.A. van der; Hagemans, M.L.; Arts, W.F.M.; Hop, W.C.J.; Lee, P.; Jaeken, J.; Frohn-Mulder, I.M.; Merkus, P.J.F.M.; Corzo, D.; Puga, A.C.; Reuser, A.J.J.; Ploeg, A.T. van der

    2010-01-01

    Pompe disease is a rare neuromuscular disorder caused by deficiency of acid alpha-glucosidase. Treatment with recombinant human alpha-glucosidase recently received marketing approval based on prolonged survival of affected infants. The current open-label study was performed to evaluate the response

  12. Sequence Classification: 407438 [

    Lifescience Database Archive (English)

    Full Text Available TMB Non-TMH TMB TMB TMB Non-TMB >gi|15828934|ref|NP_326294.1| GLUCAN 1,6-ALPHA-GLUCOSIDASE (DEXTRAN GLUCOSID...ASE) (EXO-1,6-ALPHA-GLUCOSIDASE) (GLUCODEXTRANASE) || http://www.ncbi.nlm.nih.gov/protein/15828934 ...

  13. NCBI nr-aa BLAST: CBRC-CINT-01-0028 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-CINT-01-0028 gb|EAW83988.1| maltase-glucoamylase (alpha-glucosidase), isoform ...CRA_a [Homo sapiens] gb|EAW83989.1| maltase-glucoamylase (alpha-glucosidase), isoform CRA_a [Homo sapiens] EAW83988.1 4.3 29% ...

  14. In vitro inhibition activity of polyphenol-rich extracts from Syzygium aromaticum (L.) Merr. & Perry (Clove) buds against carbohydrate hydrolyzing enzymes linked to type 2 diabetes and Fe2+-induced lipid peroxidation in rat pancreas

    Institute of Scientific and Technical Information of China (English)

    Stephen Adeniyi Adefegha; Ganiyu Oboh

    2012-01-01

    To investigate and compare the inhibitory properties of free and bound phenolic extracts of clove bud against carbohydrate hydrolyzing enzymes (alpha-amylase & alpha-glucosidase) and Fe2+-induced lipid peroxidation in rat pancreas in vitro. Methods: The free phenolics were extracted with 80% (v/v) acetone, while bound phenolics were extracted from the alkaline and acid hydrolyzed residue with ethyl acetate. Then, the interaction of the extracts with alpha-amylase and alpha-glucosidase was subsequently assessed. Thereafter, the total phenolic contents and antioxidant activities of the extracts were determined. Results: The result revealed that both extracts inhibited alpha-amylase and alpha-glucosidase in a dose-dependent manner. However, the alpha-glucosidase inhibitory activity of the extracts were significantly (P<0.05) higher than their alpha-amylase inhibitory activity. The free phenolics (31.67 mg/g) and flavonoid (17.28 mg/g) contents were significantly (P<0.05) higher than bound phenolic (23.52 mg/g) and flavonoid (13.70 mg/g) contents. Both extracts also exhibited high antioxidant activities as typified by their high reducing power, 1,1 diphenyl-2- picrylhydrazyl (DPPH) and 2, 2-azinobis-3-ethylbenzo-thiazoline-6-sulfonate (ABTS) radical scavenging abilities, as well as inhibition of Fe2+-induced lipid peroxidation in rat pancreas in vitro. Conclusions: This study provides a biochemical rationale by which clove elicits therapeutic effect on type 2 diabetes.

  15. Effect of Mouse Maltase-glucoamylase (Mgam) Knockout on Starch Digestion to Glucose

    Science.gov (United States)

    Digestion of starch requires activities provided by six different alpha-glucosidase enzymes. Two activities are luminal alpha-amylases (AMY). Four activities are mucosal activities described as maltases. Two of the activities are associated with sucrase-isomaltase (Si) activities. Two activities ...

  16. Inhibition of recombinant human maltase glucoamylase by salacinol and derivatives.

    Science.gov (United States)

    Rossi, Elena J; Sim, Lyann; Kuntz, Douglas A; Hahn, Dagmar; Johnston, Blair D; Ghavami, Ahmad; Szczepina, Monica G; Kumar, Nag S; Sterchi, Erwin E; Nichols, Buford L; Pinto, B M; Rose, David R

    2006-06-01

    Inhibitors targeting pancreatic alpha-amylase and intestinal alpha-glucosidases delay glucose production following digestion and are currently used in the treatment of Type II diabetes. Maltase-glucoamylase (MGA), a family 31 glycoside hydrolase, is an alpha-glucosidase anchored in the membrane of small intestinal epithelial cells responsible for the final step of mammalian starch digestion leading to the release of glucose. This paper reports the production and purification of active human recombinant MGA amino terminal catalytic domain (MGAnt) from two different eukaryotic cell culture systems. MGAnt overexpressed in Drosophila cells was of quality and quantity suitable for kinetic and inhibition studies as well as future structural studies. Inhibition of MGAnt was tested with a group of prospective alpha-glucosidase inhibitors modeled after salacinol, a naturally occurring alpha-glucosidase inhibitor, and acarbose, a currently prescribed antidiabetic agent. Four synthetic inhibitors that bind and inhibit MGAnt activity better than acarbose, and at comparable levels to salacinol, were found. The inhibitors are derivatives of salacinol that contain either a selenium atom in place of sulfur in the five-membered ring, or a longer polyhydroxylated, sulfated chain than salacinol. Six-membered ring derivatives of salacinol and compounds modeled after miglitol were much less effective as MGAnt inhibitors. These results provide information on the inhibitory profile of MGAnt that will guide the development of new compounds having antidiabetic activity.

  17. Pompe disease is a differential diagnosis in case of reduced physical capacity and abnormal muscular fatigue

    DEFF Research Database (Denmark)

    Hansen, Julie Schjødtz; Ellingsen, Anne R; Andreasen, Caroline M;

    2014-01-01

    Late-onset Pompe disease is an inherited metabolic myopathy with low activity of alpha glucosidase and variable clinical symptoms. In this case report we describe a woman with long standing muscular fatigue and malaise with the diagnosis initially established by pathologic findings in the muscle...

  18. InterProScan Result: BP124820 [KAIKOcDNA[Archive

    Lifescience Database Archive (English)

    Full Text Available BP124820 BP124820_3_ORF2 35CD3B2AD11B04C6 PANTHER PTHR22762:SF7 NEUTRAL ALPHA-GLUCOSIDA...SE AB PRECURSOR (GLUCOSIDASE II ALPHA SUBUNIT) (ALPHA GLUCOSIDASE 2) NA ? IPR000322 unintegrated ...

  19. InterProScan Result: BP124820 [KAIKOcDNA[Archive

    Lifescience Database Archive (English)

    Full Text Available BP124820 BP124820_5_ORF1 DC1B7DDE14643E5E PANTHER PTHR22762:SF7 NEUTRAL ALPHA-GLUCOSIDA...SE AB PRECURSOR (GLUCOSIDASE II ALPHA SUBUNIT) (ALPHA GLUCOSIDASE 2) NA ? IPR000322 unintegrated ...

  20. InterProScan Result: FS830859 [KAIKOcDNA[Archive

    Lifescience Database Archive (English)

    Full Text Available FS830859 FS830859_4_ORF1 D905399DCEA8EB3E PANTHER PTHR22762:SF7 NEUTRAL ALPHA-GLUCOSIDA...SE AB PRECURSOR (GLUCOSIDASE II ALPHA SUBUNIT) (ALPHA GLUCOSIDASE 2) NA ? IPR000322 unintegrated Biological Process: carbohydrate metabolic process (GO:0005975) ...

  1. InterProScan Result: BP124820 [KAIKOcDNA[Archive

    Lifescience Database Archive (English)

    Full Text Available BP124820 BP124820_2_ORF1 DFD3D5A0B4996BA2 PANTHER PTHR22762:SF7 NEUTRAL ALPHA-GLUCOSIDA...SE AB PRECURSOR (GLUCOSIDASE II ALPHA SUBUNIT) (ALPHA GLUCOSIDASE 2) 3.9e-72 T IPR000322 unintegrated Biological Process: carbohydrate metabolic process (GO:0005975) ...

  2. InterProScan Result: FS830859 [KAIKOcDNA[Archive

    Lifescience Database Archive (English)

    Full Text Available FS830859 FS830859_4_ORF1 D905399DCEA8EB3E PANTHER PTHR22762:SF7 NEUTRAL ALPHA-GLUCOSIDA...SE AB PRECURSOR (GLUCOSIDASE II ALPHA SUBUNIT) (ALPHA GLUCOSIDASE 2) 9.9e-21 T IPR000322 unintegrated Biological Process: carbohydrate metabolic process (GO:0005975) ...

  3. InterProScan Result: CK495917 [KAIKOcDNA[Archive

    Lifescience Database Archive (English)

    Full Text Available CK495917 CK495917_5_ORF1 7F944B343AFB57FA PANTHER PTHR22762:SF7 NEUTRAL ALPHA-GLUCOSIDA...SE AB PRECURSOR (GLUCOSIDASE II ALPHA SUBUNIT) (ALPHA GLUCOSIDASE 2) 6.1e-18 T IPR000322 unintegrated Biological Process: carbohydrate metabolic process (GO:0005975) ...

  4. InterProScan Result: BP124820 [KAIKOcDNA[Archive

    Lifescience Database Archive (English)

    Full Text Available BP124820 BP124820_6_ORF2 8E9FAE9903327F4B PANTHER PTHR22762:SF7 NEUTRAL ALPHA-GLUCOSIDA...SE AB PRECURSOR (GLUCOSIDASE II ALPHA SUBUNIT) (ALPHA GLUCOSIDASE 2) NA ? IPR000322 unintegrated ...

  5. Disposition kinetics and bioavailability of the glucosidase inhibitor N-benzyl-1-deoxynojirimycin after various routes of administration in mice

    NARCIS (Netherlands)

    Faber, ED; Delbressine, LPC; vandeVorstenbosch, CG; vandenBroek, LAGM; Meijer, DKF; Stok, B.P.

    1997-01-01

    Pharmacokinetics, biodistribution, and excretion of the alpha-glucosidase inhibitor and antiviral compound N-benzyl-1-deoxynojirimycin (BndNM) were studied in mice, after intravenous, subcutaneous, and oral administration of a single radiolabeled dose, No metabolites were detected in plasma, urine,

  6. Enzymic synthesis of alpha- and beta-D-glucosides of 1-deoxynojirimycin and their glycosidase inhibitory activities.

    Science.gov (United States)

    Asano, N; Oseki, K; Kaneko, E; Matsui, K

    1994-05-20

    1-Deoxynojirimycin (1) is a potent inhibitor of mammalian and rice alpha-glucosidase. Several glucosides of 1 were synthesized by use of the native and immobilized enzyme and their effect on various enzymes was investigated. Transglucosylation reactions using rice alpha-glucosidase, yeast alpha- and beta-glucosidases purified from Rhodotorula lactosa were performed with maltose or cellobiose as a glucose donor and N-(benzyloxycarbonyl)-1-deoxynojirimycin (2) as an acceptor. The transglucosylation reaction using native rice alpha-glucosidase afforded 3-O-alpha-D-glucopyranosyl-N-(benzyloxycarbonyl)-1-deoxynojirimycin (4), 4-O-alpha-D-glucopyranosyl-N-(benzyloxycarbonyl)-1-deoxynojirimycin (5), and 2-O-alpha-D-glucopyranosyl-N-(benzyloxycarbonyl)-1-deoxynojirimycin (3) in yields of 40, 13, and 2%, respectively, after 30 min. The transglucosylation reaction using immobilized rice alpha-glucosidase was similar to that using the native enzyme. In the system using native yeast alpha-glucosidase, 3, 5, and 4 were formed in yields of 34, 13, and 6%, respectively, after 15 h. The immobilization of yeast alpha-glucosidase caused a significant decrease in transglucosylation activity. Yeast beta-glucosidase showed a high transglucosylation activity and incubation with the reaction system afforded 2-O-beta-D-glucopyranosyl-N-(benzyloxycarbonyl)-1-deoxynojirimycin (6) and 4-O-beta-D-glucopyranosyl-N-(benzyloxycarbonyl)-1-deoxynojirimycin (7) in yields of 69 and 3%, respectively, after 3 h. The transglucosylation reaction using immobilized yeast beta-glucosidase preferentially afforded 6 in a yield of 73% after 3 h. After removal of N-benzyloxycarbonyl group from the product glucosides, their glycosidase inhibitory activities were measured. 3-O-alpha-D-Glucopyranosyl-1-deoxynojirimycin (9) retained the potent inhibition of 1 against rat intestinal sucrase activity and was more effective than 1 against rice alpha-glucosidase. 4-O-alpha-D-Glucopyranosyl-1-deoxynojirimycin (10

  7. Comparison of two chromogenic media and evaluation of two molecular based identification systems for Enterobacter sakazakii detection

    Directory of Open Access Journals (Sweden)

    Diep Benjamin

    2006-02-01

    Full Text Available Abstract Background Enterobacter sakazakii is a foodborne pathogen that has been associated with sporadic cases and outbreaks causing meningitis, necrotizing enterocolitis and sepsis especially in neonates. The current FDA detection method includes two enrichment steps, the subculturing of the second enrichment broth on a selective agar (VRBG, a further subculturing of selected grown colonies on TSA and the subsequent biochemical identification of yellow-pigmented colonies by API20E. However, there is a strong need for simplified methods for isolation and identification of E. sakazakii. In this study, two chromogenic media, which allow to indicate presumptive E. sakazakii colonies by the alpha glucosidase activity, as well as a newly developed 1,6-alpha-glucosidase based conventional PCR assay and a rRNA oligonucleotide probe based commercial test system for identification of presumptive E. sakazakii were evaluated on 98 target and non-target strains. The methods were compared with respect to specificity aspects. Results A total of 75 presumptive E. sakazakii and 23 non-target strains were analysed by using chromogenic media, alpha-glucosidase based PCR assay, and the VIT assay. For most presumptive E. sakazakii strains on the chromogenic media, the PCR and VIT assay confirmed the identification. However, for a number of presumptive E. sakazakii isolates from fruit powder, the alpha-glucosidase PCR and VIT assay did not correspond to the typical E. sakazakii colonies on DFI and ESIA. Further characterization by API32E identification, phylogenetic analysis of partial 16S rRNA sequences and ribotyping strongly suggested, that these strains did not belong to the species E. sakazakii. The newly developed alpha-glucosidase based PCR assay as well as the commercially available VIT Enterobacter sakazakii identification test showed an excellent correlation with the 16S rRNA data, and are thus well suited for identification of E. sakazakii. Conclusion

  8. A RARE METABOLIC DISORDER: POMPE’S DISEASE

    Directory of Open Access Journals (Sweden)

    Nazeer Ahmed

    2015-10-01

    Full Text Available Pompe disease is an autosomal recessive metabolic disorder caused by the buildup of a sugar called glycogen in the body’s cells.1,2 It is caused by an accumulation of glycogen in the lysosome due to deficiency or absence of the enzyme acid alpha-glucosidase (GAA. The enzyme GAA is used to breakdown glycogen into a simpler sugar, glucose.3 It is characterised by progressive weakness in the muscles used for mobility and breathing. In infants with Pompe disease, the heart muscles are often severely affected as well.4,7 The cells of the heart and skeletal muscles are affected the most.It is caused by a mutation in a gene (Acid alpha-glucosidase: also known as acid maltase on long arm of chromosome 17 at 17q25.2-q25.3.. Without treatment the disease is particularly lethal in infants and young children.8

  9. 天然α-葡萄糖苷酶抑制剂的分离与生理活性研究进展%Research Advancement of Separation and Physiological Activity of Natural α -glucosidase Inhibitor

    Institute of Scientific and Technical Information of China (English)

    贾光锋; 邸幼军

    2012-01-01

    Alpha-glucosidase inhibitor is an important substance to improve the postprandial hyperglycemia since binding between inhibitor and glucosidase prevents carbohydrate turning into glucose. Four kinds of chemical compositions including polysaccharides, alkaloid, flavones and saponins were extracted and isolated from natural plant. They could competively or noncompetitively inhibit the activity of alpha glucosidase. Compared with inhibitors from chemical synthesis, alpha-glucosidase inhibitors from natural herb had some predominance including many sorts, obvious effect and lower side effect. Furthermore, their synergistic effect could be shown in the inhibition to alpha-glucosidase through scientific combination.%α-葡萄糖苷酶抑制剂通过结合α-葡萄糖苷酶的位点来阻断碳水化合物降解为葡萄糖,是一种重要的降低餐后血糖水平的物质。从天然产物中提取分离出多糖类、生物碱类、黄酮类和皂苷类等化学成分,可以竞争性或非竞争性地抑制α-葡萄糖苷酶的活性。相比于化学合成糖苷酶抑制剂,天然产物中的α-葡萄糖苷酶抑制剂具有品种多、效果明显、副作用小的优势,可以通过科学组方,发挥其协同增效作用。

  10. A new prenylated isoflavone from Derris scandens Benth.

    Science.gov (United States)

    Babu, Tatipaka Hari; Tiwari, Ashok K; Rao, Vidadala Rama Subba; Ali, Amtul Z; Rao, Janaswamy Madhusudana; Babu, Katragadda Suresh

    2010-07-01

    The phytochemical study of the whole plant of Derris scandens (Leguminosae) has resulted in the isolation of a new isoflavone derivative, scandinone A (11), together with 11 known compounds (1-10, 12). Structural elucidations of these compounds were performed using spectroscopic methods especially 1D, 2D NMR, and mass spectral analyses. The alpha-glucosidase-inhibitory activity of the isolates was also evaluated. PMID:20628945

  11. Organ culture of fetal rat small intestine for testing gluten toxicity: a reappraisal.

    OpenAIRE

    Wood, G. M.; Howdle, P. D.; Losowsky, M. S.

    1987-01-01

    Jejunal segments from fetal rats of 18 days gestation were maintained in an organ culture system for up to 72 h. During this period, villi developed within the intestinal lumen and the epithelium changed from stratified to simple columnar. Peristaltic activity was observed during in-vitro culture. Alkaline phosphatase specific activity of the bowel segments fell after 48 hours culture, compared with pre-culture values (P less than 0.05), but that of alpha-glucosidase increased. The addition o...

  12. Lack of robust satellite cell activation and muscle regeneration during the progression of Pompe disease

    OpenAIRE

    Schaaf, Gerben J.; van Gestel, Tom JM; Brusse, Esther; Verdijk, Robert M.; de Coo, Irenaeus FM; Doorn Van, Pieter A; Ploeg, Ans T van der; Pijnappel, WWM Pim

    2015-01-01

    Introduction Muscle stem cells termed satellite cells are essential for muscle regeneration. A central question in many neuromuscular disorders is why satellite cells are unable to prevent progressive muscle wasting. We have analyzed muscle fiber pathology and the satellite cell response in Pompe disease, a metabolic myopathy caused by acid alpha-glucosidase deficiency and lysosomal glycogen accumulation. Pathology included muscle fiber vacuolization, loss of cross striation, and immune cell ...

  13. REDUCTION OF CARDIOVASCULAR COMPLICATIONS OF MODERN HYPOGLYCEMIC THERAPY OF DIABETES MELLITUS TYPE 2: "FLORENTINE HERESY"

    OpenAIRE

    Aleksandrov, A. A.

    2016-01-01

    The classic hypoglycemic agents include biguanides, sulfonylurea drugs, meglitinides, glitazones and alpha-glucosidase inhibitors. Modern algorithm of hypoglycemic therapy in the first step considers lifestyle modification and metformin monotherapy, the second step — the combined therapy. However, the effect of combined hypoglycemic therapy on long-term cardiovascular prognosis in patients with type 2 diabetes mellitus is studied insufficiently. Combined therapy with glibenclamide and metform...

  14. 薬物治療について

    OpenAIRE

    藤中, 雄一; Fujinaka, Yuichi

    2006-01-01

    Pharmacological therapy in diabetes mellitus has been changing in the last decade. Because conventional therapy for type 2 diabetes patients using sulfonylurea often caused secondary failure during long-term glycemic control, it was recognized that alpha-glucosidase inhibitors, metformin and thiazolidinedione which had hypoglycemic effects without exhaustion of beta cell function were beneficial. These drugs have efficacy not only for lowing plasma glucose concentration but for ...

  15. Trends in Antihyperglycemic Medication Prescriptions and Hypoglycemia in Older Adults: 2002-2013

    OpenAIRE

    Clemens, Kristin K.; Salimah Shariff; Kuan Liu; Irene Hramiak; Jeffrey L Mahon; Eric McArthur; Garg, Amit X

    2015-01-01

    Background Over the last decade, several new antihyperglycemic medications have been introduced including those associated with a lower hypoglycemia risk. We aimed to investigate how these medications are being prescribed to older adults in our region. Methods We conducted population-based cross-sectional analyses of older adults (mean age 75 years) with treated diabetes in Ontario, Canada from 2002 until 2013, to examine the percentage prescribed insulin, sulphonylureas, alpha-glucosidase in...

  16. Pompe disease gene therapy

    OpenAIRE

    Barry J Byrne; Falk, Darin J.; Pacak, Christina A; Nayak, Sushrusha; Herzog, Roland W; Elder, Melissa E.; Collins, Shelley W.; Conlon, Thomas J.; Clement, Nathalie; Cleaver, Brian D.; Cloutier, Denise A.; Porvasnik, Stacy L; Islam, Saleem; ElMallah, Mai K; Martin, Anatole

    2011-01-01

    Pompe disease is an autosomal recessive metabolic myopathy caused by the deficiency of the lysosomal enzyme acid alpha-glucosidase and results in cellular lysosomal and cytoplasmic glycogen accumulation. A wide spectrum of disease exists from hypotonia and severe cardiac hypertrophy in the first few months of life due to severe mutations to a milder form with the onset of symptoms in adulthood. In either condition, the involvement of several systems leads to progressive weakness and disabilit...

  17. Progress in Enzyme Replacement Therapy in Glycogen Storage Disease Type II

    OpenAIRE

    Angelini, Corrado; SEMPLICINI, CLAUDIO; Tonin, Paola; Filosto, Massimiliano; Pegoraro, Elena; Sorarù, Gianni; Fanin, Marina

    2009-01-01

    Glycogen storage disease type II (GSDII) is an autosomal recessive lysosomal disorder caused by mutations in the gene encoding alpha-glucosidase (GAA). The disease can be clinically classified into three types: a severe infantile form, a juvenile and an adultonset form. Cases with juvenile or adult onset GSDII mimic limb-girdle muscular dystrophy or polymyositis and are often characterized by respiratory involvement. GSDII patients are diagnosed by biochemical assay and by m...

  18. Pompe disease: literature review and case series.

    Science.gov (United States)

    Dasouki, Majed; Jawdat, Omar; Almadhoun, Osama; Pasnoor, Mamatha; McVey, April L; Abuzinadah, Ahmad; Herbelin, Laura; Barohn, Richard J; Dimachkie, Mazen M

    2014-08-01

    Pompe disease is a rare multi-systemic metabolic myopathy caused by autosomal recessive mutations in the acidic alpha glucosidase (GAA) gene. Significant progress had been made in the diagnosis and management of patients with Pompe disease. Here, we describe our experience with 12 patients with various forms of Pompe disease including 4 potentially pathogenic, novel GAA variants. We also review the recent the recent advances in the pathogenesis, diagnosis, and treatment of individuals with Pompe disease.

  19. The receptor of Bacillus sphaericus binary toxin in Culex pipiens (Diptera: Culicidae) midgut: molecular cloning and expression.

    Science.gov (United States)

    Darboux, I; Nielsen-LeRoux, C; Charles, J F; Pauron, D

    2001-09-01

    Culex pipiens larval midgut is the primary target of the binary toxin (Bin) present in parasporal inclusions of Bacillus sphaericus. Cpm1, a 60-kDa protein purified from brush border membranes, has been proposed as the receptor of the Bin toxin in the midgut epithelial cells of mosquitoes. We have cloned and characterized the corresponding cDNA from midgut of Culex pipiens larvae. The open reading frame predicted a 580 amino-acid protein with a putative signal peptide at the N-terminus and a putative GPI-anchoring signal at the C-terminus. The amino acid sequence of the cloned Cpm1 exhibited 39-43% identities with insect maltases (alpha-glucosidases and alpha-amylases). Recombinant Cpm1 expressed in E. coli specifically bound to the Bin toxin and had a significant alpha-glucosidase activity but no alpha-amylase activity. These results support the view that Cpm1 is an alpha-glucosidase expressed in Culex midgut where it constitutes the receptor for the Bin toxin. To date, this is the first component involved in the mosquitocidal activity of the Bacillus sphaericus Bin toxin to be characterized. Its identification provides a key step to elucidate the mode of action of the Bin toxin and the mechanisms of resistance developed against it by some mosquito strains. PMID:11483434

  20. N-alkylated nitrogen-in-the-ring sugars: conformational basis of inhibition of glycosidases and HIV-1 replication.

    Science.gov (United States)

    Asano, N; Kizu, H; Oseki, K; Tomioka, E; Matsui, K; Okamoto, M; Baba, M

    1995-06-23

    The conformations of nitrogen-in-the-ring sugars and their N-alkyl derivatives were studied from 1H NMR analyses, mainly using 3J(H,H) coupling constants and quantitative NOE experiments. No significant difference was seen in the ring conformation of 1-deoxynojirimycin (1), N-methyl-1-deoxynojirimycin (2), and N-butyl-1-deoxynojirimycin (3). However, it was shown that the C6 OH group in 1 is predominantly equatorial to the piperidine ring, while that in 2 or 3 is predominantly axial, and its N-alkyl group is oriented equatorially. In the furanose analogues 1,4-dideoxy-1,4-imino-D-arabinitol (4) and its N-methyl (5) and N-butyl (6) derivatives, the five-membered ring conformation differed significantly by the presence or absence of the N-substituted group and the length of the N-alkyl chain. Compound 3 reduced its inhibitory effect on almost all glycosidases, resulting in an extremely specific inhibitor for processing alpha-glucosidase I since N-alkylation of 1 is known to enhance both the potency and specificity of this enzyme in vitro and in vivo. This preferred (C6 OH axial) conformation in 2 and 3 appears to be responsible for their strong alpha-glucosidase I activity. Compound 4 is a good inhibitor of intestinal alpha-glucohydrolases, alpha-glucosidase II, and Golgi alpha-mannosidases I and II, but its N-alkyl derivatives 5 and 6 markedly decreased inhibitory potential for all enzymes tested. In the case of 2,5-dideoxy-2,5-imino-D-mannitol (DMDP, 7), which is a potent beta-galactosidase inhibitor, its N-methyl (8) and N-butyl (9) derivatives completely lost potency toward beta-galactosidase as well. N-Alkylation of compounds 4 and 7, known well as potent yeast alpha-glucosidase inhibitors, resulted in a serious loss of inhibitory activity toward yeast alpha-glucohydrolases. Activity of these nine analogues against HIV-1 replication was determined, based on the inhibition of virus-induced cytopathogenicity in MT-4 and MOLT-4 cells. Compounds 2 and 3, which are

  1. A cross-sectional single-centre study on the spectrum of Pompe disease, German patients: molecular analysis of the GAA gene, manifestation and genotype-phenotype correlations

    Directory of Open Access Journals (Sweden)

    Herzog Andreas

    2012-06-01

    Full Text Available Abstract Background Pompe disease (Glycogen storage disease type II, GSD II, acid alpha-glucosidase deficiency, acid maltase deficiency, OMIM # 232300 is an autosomal-recessive lysosomal storage disorder due to a deficiency of acid alpha-glucosidase (GAA, acid maltase, EC 3.2.1.20, Swiss-Prot P10253. Clinical manifestations are dominated by progressive weakness of skeletal muscle throughout the clinical spectrum. In addition, the classic infantile form is characterised by hypertrophic cardiomyopathy. Methods In a cross-sectional single-centre study we clinically assessed 3 patients with classic infantile Pompe disease and 39 patients with non-classic presentations, measured their acid alpha-glucosidase activities and analysed their GAA genes. Results Classic infantile patients had nearly absent residual enzyme activities and a typical clinical course with hypertrophic cardiomyopathy until the beginning of therapy. The disease manifestations in non-classic patients were heterogeneous. There was a broad variability in the decline of locomotive and respiratory function. The age of onset ranged from birth to late adulthood and correlated with enzyme activities. Molecular analysis revealed as many as 33 different mutations, 14 of which are novel. All classic infantile patients had two severe mutations. The most common mutation in the non-classic group was c.-32-13 T > G. It was associated with a milder course in this subgroup. Conclusions Disease manifestation strongly correlates with the nature of the GAA mutations, while the variable progression in non-classic Pompe disease is likely to be explained by yet unknown modifying factors. This study provides the first comprehensive dataset on the clinical course and the mutational spectrum of Pompe disease in Germany.

  2. Nitrogen-in-the-ring pyranoses and furanoses: structural basis of inhibition of mammalian glycosidases.

    Science.gov (United States)

    Asano, N; Oseki, K; Kizu, H; Matsui, K

    1994-10-28

    Seven pyranoses and three furanoses with a nitrogen in the ring were prepared by chemical synthesis, microbial conversion, and isolation from plants to investigate the contribution of epimerization, deoxygenation, and conformation to the potency of inhibition and specificity of mammalian glycosidases. The seven pyranoses are 1-deoxynojirimycin (1), the D-manno (2), D-allo (3), and D-galacto (4) isomers of 1, fagomine (1,2-dideoxynojirimycin, 5), and the D-allo (6) and D-galacto (7) isomers of 5, while the three furanoses are 2,5-dideoxy-2,5-imino-D-mannitol (8), 1,4-dideoxy-1,4-imino-D-arabinitol (9), and 1,4-dideoxy-1,4-imino-D-ribitol (10). The 2-deoxygenation and/or 3-epimerization of 1 enhanced the potency for rat intestinal lactase and bovine liver cytosolic beta-galactosidase. Especially compound 6 showed a potent inhibitory activity against both enzymes, and compound 8, a mimic of beta-D-fructofuranose, was a potent inhibitor of both beta-galactosidases as well. Compound 4, which has been known as a powerful alpha-galactosidase inhibitor, exhibited no significant inhibitory activity for most of mammalian beta-galactosidases. In addition, compound 6 fairly retained a potency of 1 toward rat intestinal isomaltase. In this study, compound 8, known as a processing alpha-glucosidase I inhibitor in cell culture, has been found to have no effect on processing alpha-glucosidase II, whereas 9 has been shown to be a good nonspecific inhibitor of intestinal isomaltase, processing alpha-glucosidase II, Golgi alpha-mannosidases I and II, and porcine kidney trehalase. It has been speculated that glycosidase inhibitors have structures which resemble those of the respective glycosyl cations. This Broad inhibitory activity of 9 toward various glycosidases suggest that it superimposes well on the various glycosyl cations.

  3. In vitro inhibition activity of polyphenol-rich extracts from Syzygium aromaticum(L.)Merr.& Perry(Clove)buds against carbohydrate hydrolyzing enzymes linked to type 2 diabetes and Fe2+-induced lipid peroxidation in rat pancreas

    Institute of Scientific and Technical Information of China (English)

    Stephen; Adeniyi; Adefegha; Ganiyu; Oboh

    2012-01-01

    Objective:To investigate and compare the inhibitor)’properties)of free and bound phenolic extracts of clove bud against carbohydrate hydrolyzing enzymes(alpha-amylase&alphaglucosidase)and Fe2+-induced lipid peroxidation in rat pancreas in vitro.Methods:The free phenolics were extracted with 80%.(v/v)acetone,while bound phenolics were extracted from the alkaline and acid hydrolyzed residue with ethyl acetate.Then,the interaction of the extracts with alpha-amylase and alpha-glucosidase was subsequently assessed.Thereafter,the total phenolic contents and antioxidant activities of the extracts were determined.Results:The result revealed that both extracts inhibited alpha-amylase and alpha-glucosidase in a dose-dependent manner.However,the alpha-glucosidase inhibitory activity of the extracts were significantly(P<0.05)higher than their alpha-amylase inhibitory activity.The free phenolics(31.67 mg/g)and flavonoid(17.28 mg/g)contents were significantly(P<0.05)higher than bound phenolic(23.52 mg/g)and flavonoid(13.70 mg/g)contents.Both extracts also exhibited high antioxidant activities as typified by their high reducing power,LI diphenyl-2-picrylhydrazyl(DPPH)and 2,2-azinobis-3-ethylbenzo-thiazoline-6-sulfonate(ABTS)radical scavenging abilities,as well as inhibition of Fe2+-induced lipid peroxidation in rat pancreas in vitro.Conclusions:This study provides a biochemical rationale by which clove elicits therapeutic effect on type 2 diabetes.

  4. Concurrent Therapy with a Low-carbohydrate Diet and Miglitol Remarkably Improved the Postprandial Blood Glucose and Insulin Levels in a Patient with Reactive Hypoglycemia due to Late Dumping Syndrome.

    Science.gov (United States)

    Hirose, Sachie; Iwahashi, Yasuyuki; Seo, Akane; Sumiyoshi, Michitaka; Takahashi, Tetsuya; Tamori, Yoshikazu

    2016-01-01

    Reactive hypoglycemia induced by late dumping syndrome is often observed after gastrectomy. However, no effective therapy has yet been fully established. We herein describe a case in which concurrent therapy with a low-carbohydrate diet using low-glycemic-index food and an alpha-glucosidase inhibitor, miglitol, very effectively ameliorated the postprandial fluctuations in the blood glucose and plasma insulin levels in a patient with reactive hypoglycemia due to late dumping syndrome following total gastrectomy. The administration of miglitol under a low-carbohydrate diet using low-glycemic-index food may therefore be an ideal treatment for reactive hypoglycemia due to late dumping syndrome. PMID:27150868

  5. Infantile Onset Glycogen Storage Disease Type 2: Case Report

    Directory of Open Access Journals (Sweden)

    Serkan Bilge Koca

    2014-08-01

    Full Text Available Glycogen storage disease type 2 (Pompe’s disease is an autosomal recessive, fatal glycogen storage disease presenting with hypotonia and muscle weakness. It is known that deficiency of lysosomal acid alpha-glucosidase (acid maltase leads to progressive generalised myopathy, cardiomyopathy and death in early infancy because of respiratory muscle weakness. Excessive undegradable intracellular glycogen deposition plays a role in the pathogenesis of the disease. Here we report a 3.5 month-old girl presenting with respiratory failure due to pneumonia and hypotonia, who was later diagnosed as Pompe disease.

  6. Adult onset glycogen storage disease type II (adult onset Pompe disease): report and magnetic resonance images of two cases

    Energy Technology Data Exchange (ETDEWEB)

    Del Gaizo, Andrew [Emory University School of Medicine, Radiology Resident, Atlanta, GA (United States); Banerjee, Sima [Emory University School of Medicine, Musculoskeletal Radiology Department, Atlanta, GA (United States); Terk, Michael [Emory University School of Medicine, Radiology, Division of Musculoskeletal Imaging, Atlanta, GA (United States)

    2009-12-15

    Glycogen storage disease type II (GSDII), also referred to as Pompe disease or acid maltase deficiency, is a rare inherited condition caused by a deficiency in acid alpha-glucosidase (GAA) enzyme activity. The condition is often classified by age of presentation, with infantile and late onset variants (Laforet et al. J Neurology 55:1122-8, 2000). Late onset tends to present with progressive proximal muscle weakness and respiratory insufficiency (Winkel et al. J Neurology 252:875-84, 2005). We report two cases of biopsy confirmed adult onset GSDII, along with key Magnetic Resonance (MR) images. (orig.)

  7. REDUCTION OF CARDIOVASCULAR COMPLICATIONS OF MODERN HYPOGLYCEMIC THERAPY OF DIABETES MELLITUS TYPE 2: "FLORENTINE HERESY"

    Directory of Open Access Journals (Sweden)

    A. A. Aleksandrov

    2010-01-01

    Full Text Available The classic hypoglycemic agents include biguanides, sulfonylurea drugs, meglitinides, glitazones and alpha-glucosidase inhibitors. Modern algorithm of hypoglycemic therapy in the first step considers lifestyle modification and metformin monotherapy, the second step — the combined therapy. However, the effect of combined hypoglycemic therapy on long-term cardiovascular prognosis in patients with type 2 diabetes mellitus is studied insufficiently. Combined therapy with glibenclamide and metformin can result in adverse cardiovascular effects, so that long term therapy should be avoided in patients with coronary heart disease. Adequate pharmacological approaches to hyperglycemia correction should be elaborated.

  8. Testudinibacter aquarius gen. nov., sp nov., a member of the family Pasteurellaceae isolated from the oral cavity of freshwater turtles

    DEFF Research Database (Denmark)

    Hansen, Mie Johanne; Pennanen, Elin Anna Erica; Bojesen, Anders Miki;

    2016-01-01

    Pasteurellaceae. However, they could be separated from existing genera of the Pasteurellaceae by the following test results: indole, ornithine decarboxylase and Voges-Proskauer positive; and methyl red, urease and PNPG (alpha-glucosidase) negative. No X- or V-factor requirement was observed. A zone of beta....... nov., sp. nov. The type strain of Testudinibacter aquarius is ELNT2x(T) (=CCUG 65146(T)=DSM 28140(T)), which was isolated from the oral cavity of a captive eastern long-necked turtle (Chelodina longicollis) in Denmark in 2012....

  9. A complex craniovertebral junction malformation in a patient with late onset glycogenosis 2

    Directory of Open Access Journals (Sweden)

    Mariasofia Cotelli

    2014-01-01

    Full Text Available Glycogenosis II (GSDII is an autosomal recessive lysosomal storage disorder resulting from deficiency of acid alpha-glucosidase and subsequent lysosomal accumulation of glycogen in skeletal, cardiac and smooth muscles. The late-onset form is characterized by wide variability of the phenotypical spectrum. Clinical findings may include muscle weakness, respiratory insufficiency, vascular abnormalities, low bone mineral density and higher risk of developing osteoporosis. Craniovertebral junction (CVJ malformations have never been described so far. We here report on a GSDII 43-year-old woman who harbored the mutations IVS1-13T>G and c.2237G>A in the acid alpha-glucosidase gene. She recurrently suffered from headache, neck pain and dizziness. Brain MRI and CT scan showed the presence of a very rare complex CVJ malformation composed of basilar invagination, basiocciput hypoplasia, partial C1 assimilation, C1 posterior arch aplasia and C1 lateral mass hypoplasia and offset. Although we cannot rule out their coincidental occurrence, the rarity of multiple CVJ malformations in the general population as well as the well-known GSDII multisystem involvement should suggest to study the CVJ in the diagnostic process of GSDII patients in order to assess the CVJ malformation frequency in GSDII population and verify a possible relationship between these two conditions.

  10. Evaluation of antihyperglycemia and antihypertension potential of native Peruvian fruits using in vitro models.

    Science.gov (United States)

    Pinto, Marcia Da Silva; Ranilla, Lena Galvez; Apostolidis, Emmanouil; Lajolo, Franco Maria; Genovese, Maria Inés; Shetty, Kalidas

    2009-04-01

    Local food diversity and traditional crops are essential for cost-effective management of the global epidemic of type 2 diabetes and associated complications of hypertension. Water and 12% ethanol extracts of native Peruvian fruits such as Lucuma (Pouteria lucuma), Pacae (Inga feuille), Papayita arequipeña (Carica pubescens), Capuli (Prunus capuli), Aguaymanto (Physalis peruviana), and Algarrobo (Prosopis pallida) were evaluated for total phenolics, antioxidant activity based on 2, 2-diphenyl-1-picrylhydrazyl radical scavenging assay, and functionality such as in vitro inhibition of alpha-amylase, alpha-glucosidase, and angiotensin I-converting enzyme (ACE) relevant for potential management of hyperglycemia and hypertension linked to type 2 diabetes. The total phenolic content ranged from 3.2 (Aguaymanto) to 11.4 (Lucuma fruit) mg/g of sample dry weight. A significant positive correlation was found between total phenolic content and antioxidant activity for the ethanolic extracts. No phenolic compound was detected in Lucuma (fruit and powder) and Pacae. Aqueous extracts from Lucuma and Algarrobo had the highest alpha-glucosidase inhibitory activities. Papayita arequipeña and Algarrobo had significant ACE inhibitory activities reflecting antihypertensive potential. These in vitro results point to the excellent potential of Peruvian fruits for food-based strategies for complementing effective antidiabetes and antihypertension solutions based on further animal and clinical studies. PMID:19459727

  11. Physicochemical and biofunctional properties of crab chitosan nanoparticles.

    Science.gov (United States)

    Nguyen, The Han; Kwak, Hae Soo; Kim, Sang Moo

    2013-08-01

    The physicochemical and biofunctional properties of crab chitosan nanoparticles of two different sizes (Nano A and B) manufactured by dry milling method were evaluated for commercialization. The deacetylation degrees (DD) of Nano A, B and the control chitosan were 90.9, 93.0, and 92.7% respectively whereas their molecular weights (M(w)) were 43.9, 44.7 and 208.8 kDa. The average sizes of the dispersed Nano A, B and the control chitosan in cetyltrimethylammonium chloride were 735.9, 849.4 and 2,382.4 nm, respectively, which were lower than 1441.7, 2935.6 and 6832.9 nm of the intact chitosans. Chitosan nanoparticles had mild tyrosinase, antioxidant and angiotensin I converting enzyme (ACE), but weak collagenase, elastase and beta-glucuronidase inhibitory activity. However, Nano A had strong alpha-glucosidase inhibitory activity, which was comparable to that of acarbose, a commercial alpha-glucosidase inhibitor. In addition, the minimum inhibitory concentrations (MICs) of chitosan and its nanoparticles ranged from 30 to > 200 microg/mL against each four gram-positive and gram-negative bacteria. Therefore, crab chitosan nanoparticles could be used as a nutraceutical, cosmeceutical or pharmaceutical product.

  12. 6,7-diepicastanospermine, a tetrahydroxyindolizidine alkaloid inhibitor of amyloglucosidase

    Energy Technology Data Exchange (ETDEWEB)

    Molyneux, R.J.; Benson, M. (Dept. of Agriculture, Albany, CA (United States)); Pan, Y.T.; Tropea, J.E.; Kaushal, G.P.; Elbein, A.D. (Univ. of Texas, San Antonio (United States))

    1991-10-15

    A tetrahydroxyindolizidine alkaloid, 6,7-diepicastanospermine, was isolated from the seeds of Castanospermum australe by extraction with methanol and purified to homogeneity using ion-exchange, preparative thin-layer, and radial chromatography. A very low yield of a pyrrolidine alkaloid, N-(hydroxyethyl)-2-(hydroxymethyl)-3-hydroxypyrrolidine, was also obtained by analogous methods. The purity of both alkaloids was established by gas chromatography of their trimethylsilyl (TMS) derivatives as better than 99%. The molecular weight of each alkaloid was established as 189 and 161, respectively, by mass spectrometry, and the structure of each was deduced from their {sup 1}H and {sup 13}C NMR spectra. The structure of the pyrrolidine alkaloids which co-occur in C. australe. 6,7-Diepicastanospermine was found to be a moderately good inhibitor of the fungal {alpha}-glucosidase, amyloglucosidase and a relatively weak inhibitor of {beta}-glucosidase. It failed to inhibit {alpha}-glucosidase. It failed to inhibit {alpha}- or {beta}-galactosidase, {alpha}- or {beta}-mannosidase, or {alpha}-L-fucosidase. Comparison of its inhibitory activity toward amyloglucosidase with those of its isomers, castanospermine and 6-epicastanospermine, demonstrated that epimerization of a single hydroxyl group can produce significant alteration of such inhibitory properties.

  13. Pompe disease: A case report

    Directory of Open Access Journals (Sweden)

    Abdullah Çim

    2015-12-01

    Full Text Available Pompe disease is inherited in an autosomal recessive manner, and is usually observed in the children of asymptomatic carriers. Pompe disease, known as Glycogen Storage Disorder type II, is caused by pathogenic mutations in the gene encoding lysosomal acid alpha-glucosidase (GAA. There are three types of Pompe disease: classical infantile form, non-classical infantile form and late-onset Pompe disease. Age of onset and severity of the disease determine the type of Pompe disease. We aimed to identify a mutation in GAA gene in parents who were first cousins and their baby girl was passed away due to the Pompe disease. The baby girl had reduced acid alpha-glucosidase activity, but genetic analysis had not been performed. Mutation analysis of parents was performed using high-throughput DNA sequencing method. Heterozygous mutation of c.896 T>C in exon 5 was found in parents, and prenatal diagnosis was performed for their next pregnancy. In conclusion, c.896 T>C substitution in GAA gene may lead to the severe type of Pompe disease. Using a relatively fast and reliable molecular genetic analysis method to confirm the early diagnosis of the Pompe disease is important for the management of the disease.

  14. Stability of Culex quinquefasciatus resistance to Bacillus sphaericus evaluated by molecular tools.

    Science.gov (United States)

    Amorim, Liliane Barbosa; de Barros, Rosineide Arruda; Chalegre, Karlos Diogo de Melo; de Oliveira, Cláudia Maria Fontes; Regis, Lêda Narcisa; Silva-Filha, Maria Helena Neves Lobo

    2010-04-01

    Bacillus sphaericus binary toxin action on Culex quinquefasciatus larvae relies on the binding to Cqm1alpha-glucosidases, which act as midgut receptors. Resistance of two laboratory-selected colonies is associated with the allele cqm1(REC) that prevents Cqm1 expression as membrane-bound molecules. This study evaluated stability of resistance after the interruption of selection pressure and introduction of susceptible individuals in these colonies. Bioassays showed that frequency of resistant larvae did not decrease throughout 11 generations, under these conditions, and it was associated to a similar frequency of larvae lacking the Cqm1alpha-glucosidase receptor, detected by in gel enzymatic assays. Direct screening of the cqm1(REC) allele, by specific PCR, showed that its frequency remained stable throughout 11 generations. Parental resistant colony did not display biological costs regarding fecundity, fertility and pupal weight and data from susceptibility assays, enzymatic assays and PCR screening showed that cqm1(REC) was not disfavored in competition with the susceptible allele and persisted in the progenies, in the lack of selection pressure. Characterization of molecular basis of resistance is essential for developing diagnostic tools and data have relevant implication for the establishment of strategies for resistance management. PMID:20211258

  15. Ultrastructural analysis of midgut cells from Culex quinquefasciatus (Diptera: Culicidae) larvae resistant to Bacillus sphaericus.

    Science.gov (United States)

    de Melo, Janaina Viana; Vasconcelos, Romero Henrique Teixeira; Furtado, André Freire; Peixoto, Christina Alves; Silva-Filha, Maria Helena Neves Lobo

    2008-12-01

    The larvicidal action of the entomopathogen Bacillus sphaericus towards Culex quinquefasciatus is due to the binary (Bin) toxin present in crystals, which are produced during bacterial sporulation. The Bin toxin needs to recognize and bind specifically to a single class of receptors, named Cqm1, which are 60-kDa alpha-glucosidases attached to the apical membrane of midgut cells by a glycosylphosphatidylinositol anchor. C. quinquefasciatus resistance to B. sphaericus has been often associated with the absence of the alpha-glucosidase Cqm1 in larvae midgut microvilli. In this work, we aimed to investigate, at the ultrastructural level, the midgut cells from C. quinquefasciatus larvae whose resistance relies on the lack of the Cqm1 receptor. The morphological analysis showed that midgut columnar cells from the resistant larvae are characterized by a pronounced production of lipid inclusions, throughout the 4th instar. At the end of this stage, resistant larvae had an increased size and number of these inclusions in the midgut cells, while only a small number were observed in the cells from susceptible larvae. The morphological differences in the midgut cells of resistant larvae found in this work suggested that the lack of the Cqm1 receptor, which also has a physiological role as being an alpha-glucosidase, can be related to changes in the cell metabolism. The ultrastructural effects of Bin toxin on midgut epithelial cells from susceptible and resistant larvae were also investigated. The cytopathological alterations observed in susceptible larvae treated with a lethal concentration of toxin included breakdown of the endoplasmic reticulum, mitochondrial swelling, microvillar disruption and vacuolization. Some effects were observed in cells from resistant larvae, although those alterations did not lead to larval death, indicating that the receptor Cqm1 is essential to mediate the larvicidal action of the toxin. This is the first ultrastructural study to show differences

  16. Expanded bed chromatography of proteins in small-diameter columns. II. Methods development and scale up.

    Science.gov (United States)

    Ghose, S; Chase, H

    2000-01-01

    The scaled down system developed in Part I of this series was further validated by using a 1-cm diameter column for method development studies for the separation of two model proteins, alcohol dehydrogenase and alpha-glucosidase, from unclarified yeast homogenate by hydrophobic interaction expanded bed chromatography based on the STREAMLINE matrix. The efficacy of solids removal and establishment of optimal binding and separation condition by stepwise elution were investigated. Equilibration of the EBA column and loading at high salt strengths affected the subsequent recovery of the two target proteins. Although good resolution between the target proteins could be achieved, peak tailing was found to be a consistent problem. The optimised separation protocol was scaled up 25-fold to a column diameter of 5.0 cm. The results were in good agreement with the run conducted in the 1-cm column, indicating the potential of using the small columns as an viable approach for method scouting and development studies.

  17. Dapagliflozin: a new adjunct in the treatment of Type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Mamta Sachdeva

    2014-08-01

    Full Text Available Diabetes mellitus (DM Type 2 is a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. The classic symptoms are excess thirst, frequent urination, and constant hunger. Management of Type 2 diabetes focuses on lifestyle interventions, lowering other cardiovascular risk factors, and maintaining blood glucose levels in the normal range. There are several classes of anti-diabetic medications available and these include sulfonylureas, nonsulfonylurea secretagogues, alpha glucosidase inhibitors, thiazolidinediones, glucagon-like peptide-1 analog, and dipeptidyl peptidase-4 inhibitors. Recently, dapagliflozin (Farxiga and trade;, a sodium-glucose cotransporter 2 inhibitor has been approved by Food and Drug Administration as an adjunct to diet and exercises to improve glycemic control in adults with Type 2 DM. [Int J Basic Clin Pharmacol 2014; 3(4.000: 741-747

  18. Anti-diabetes constituents in leaves of Smallanthus sonchifolius.

    Science.gov (United States)

    Xiang, Zheng; He, Fan; Kang, Ting-Guo; Dou, De-Qiang; Gai, Kuo; Shi, Yu-Yuan; Kim, Young-Ho; Dong, Feng

    2010-01-01

    The inhibitory effect of smallanthaditerpenic acids A, B, C and D previously isolated from leaves of Smallanthus sonchifolius (yacon) on alpha-glucosidase were examined and their IC50 were determined to be 0.48 mg/mL, 0.59 mg/mL, 1.00 mg/mL, and 1.17 mg/mL respectively. In addition, a rapid, reliable RP-HPLC method for the analysis of chlorogenic acid, caffeic acid, and smallanthaditerpenic acids A and C in yacon leaves was established, and the variation in their contents in leaves from plants cultivated in different places and collected at different times of the year were compared. The established analytical method for determining smallanthaditerpenic acids A and C, chlorogenic acid and caffeic acid presented good results and could be used as a method for the quality control of S. sonchifolius leaves. PMID:20184030

  19. Oleanolic acid and related derivatives as medicinally important compounds.

    Science.gov (United States)

    Sultana, Nighat; Ata, Athar

    2008-12-01

    Oleanolic acid has been isolated from chloroform extract of Olea ferruginea Royle after removal of organic bases and free acids. The literature survey revealed it to be biologically very important. In this review the biological significance of oleanolic acid and its derivatives has been discussed. The aim of this review is to update current knowledge on oleanolic acid and its natural and semisynthetic analogs, focussing on its cytotoxic, antitumer, antioxidant, anti-inflamatory, anti-HIV, acetyl cholinesterase, alpha-glucosidase, antimicrobial, hepatoprotective, anti-inflammatory, antipruritic, spasmolytic activity, anti-angiogenic, antiallergic, antiviral and immunomodulatory activities. We present in this review, for the first time, a compilation of the most relevant scientific papers and technical reports of the chemical, pre-clinical and clinical research on the properties of oleanolic acid and its derivatives.

  20. Bacterial and enzymatic bioassays for toxicity testing in the environment

    Energy Technology Data Exchange (ETDEWEB)

    Bitton, G.; Koopman, B. (Department of Environmental Engineering Sciences, University of Florida, Gainesville (United States))

    1992-01-01

    Microbioassays using bacteria or enzymes are increasingly applied to measure chemical toxicity in the environment. Attractive features of these assays may include low cost, rapid response to toxicants, high sample throughput, modest laboratory equipment and space requirements, low sample volume, portability, and reproducible responses. Enzymatic tests rely on measurement of either enzyme activity or enzyme biosynthesis. Dehydrogenases are the enzymes most used in toxicity testing. Assay of dehydrogenase activity is conveniently carried out using oxidoreduction dyes such as tetrazolium salts. Other enzyme activity tests utilize ATPases, esterases, phosphatases, urease, luciferase, beta-galactosidase, protease, amylase, or beta-glucosidase. Recently, the inhibition of enzyme (beta-galactosidase, tryptophanase, alpha-glucosidase) biosynthesis has been explored as a basis for toxicity testing. Enzyme biosynthesis was found to be generally more sensitive to organic chemicals than enzyme activity.107 references.

  1. Newer Approaches In The Treatment of Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Kamlesh Patel

    2013-01-01

    Full Text Available Diabetes Mellitus is a public health problem worldwide. The most effective anti-diabetic drugs currently available include insulin and newer insulin preparations, sulphonylureas, biguanides, meglitinides, thiazolidinediones, alpha- glucosidase inhibitors, incretins, guargum and glucomannan. However, the future therapies will need to focus on those patents who do not respond well to these treatments and who account for 50% of the health care costs of diabetes mellitus. Drug development for diabetes mellitus has been directed at improving currently available drugs and findings new compounds. In this review article, we will review the role of future new chemical entities able to target the metabolic disorder. Some of these new anti-diabetic treatment strategies may in the future not only control symptoms and modify the natural course of diabetes, but also potentially prevent or cure the disease.

  2. Opposing effects of dietary protein and sugar regulate a transcriptional target of Drosophila insulin-like peptide signaling.

    Science.gov (United States)

    Buch, Susanne; Melcher, Christoph; Bauer, Matthias; Katzenberger, Joerg; Pankratz, Michael J

    2008-04-01

    Specific neurosecretory cells of the Drosophila brain express insulin-like peptides (dilps), which regulate growth, glucose homeostasis, and aging. Through microarray analysis of flies in which the insulin-producing cells (IPCs) were ablated, we identified a target gene, target of brain insulin (tobi), that encodes an evolutionarily conserved alpha-glucosidase. Flies with lowered tobi levels are viable, whereas tobi overexpression causes severe growth defects and a decrease in body glycogen. Interestingly, tobi expression is increased by dietary protein and decreased by dietary sugar. This pattern is reminiscent of mammalian glucagon secretion, which is increased by protein intake and decreased by sugar intake, suggesting that tobi is regulated by a glucagon analog. tobi expression is also eliminated upon ablation of neuroendocrine cells that produce adipokinetic hormone (AKH), an analog of glucagon. tobi is thus a target of the insulin- and glucagon-like signaling system that responds oppositely to dietary protein and sugar.

  3. Guidelines for the diagnosis, treatment and clinical monitoring of patients with juvenile and adult Pompe disease

    Directory of Open Access Journals (Sweden)

    Juan Clinton Llerena Junior

    2015-01-01

    Full Text Available ABSTRACT Pompe disease (PD is a potentially lethal illness involving irreversible muscle damage resulting from glycogen storage in muscle fiber and activation of autophagic pathways. A promising therapeutic perspective for PD is enzyme replacement therapy (ERT with the human recombinant enzyme acid alpha-glucosidase (Myozyme®. The need to organize a diagnostic flowchart, systematize clinical follow-up, and establish new therapeutic recommendations has become vital, as ERT ensures greater patient longevity. A task force of experienced clinicians outlined a protocol for diagnosis, monitoring, treatment, genetic counseling, and rehabilitation for PD patients. The study was conducted under the coordination of REBREPOM, the Brazilian Network for Studies of PD. The meeting of these experts took place in October 2013, at L’Hotel Port Bay in São Paulo, Brazil. In August 2014, the text was reassessed and updated. Given the rarity of PD and limited high-impact publications, experts submitted their views.

  4. Oleanolic acid and related derivatives as medicinally important compounds.

    Science.gov (United States)

    Sultana, Nighat; Ata, Athar

    2008-12-01

    Oleanolic acid has been isolated from chloroform extract of Olea ferruginea Royle after removal of organic bases and free acids. The literature survey revealed it to be biologically very important. In this review the biological significance of oleanolic acid and its derivatives has been discussed. The aim of this review is to update current knowledge on oleanolic acid and its natural and semisynthetic analogs, focussing on its cytotoxic, antitumer, antioxidant, anti-inflamatory, anti-HIV, acetyl cholinesterase, alpha-glucosidase, antimicrobial, hepatoprotective, anti-inflammatory, antipruritic, spasmolytic activity, anti-angiogenic, antiallergic, antiviral and immunomodulatory activities. We present in this review, for the first time, a compilation of the most relevant scientific papers and technical reports of the chemical, pre-clinical and clinical research on the properties of oleanolic acid and its derivatives. PMID:18618318

  5. An enzymatic method for the determination of fructans in foods and food products - Comparison of the results by high performance anion exchange chromatography with pulsed amperemetric detection

    DEFF Research Database (Denmark)

    Andersen, Rikke; Sørensen, A.

    1999-01-01

    effects than the fructanase reported as normally used. The method is tested on ten standard substances and five fructan products, and nine foods and food products are also analysed. The enzymatic measurement of the released sugars is confirmed by measurements done by high performance anion exchange......We report a new and non-equipment demanding method of measuring the content of fructans as well as the contents of free glucose, free fructose and sucrose in foods and food products enzymatically. This method comprises hydrolysis of fructans into D-glucose and D-fructose enzymatically...... and measurement of the released sugars enzymatically. Sucrose is hydrolysed by alpha-glucosidase instead of beta-fructosidase, which is normally used. In addition, sucrose is measured in the form of D-fructose instead of the typical D-glucose form, and the fructanase used to hydrolyse the fructans has fewer side...

  6. SGLT 2 Inhibitors: A New Therapeutic Target And Its Role In Current Clinical Practice

    Directory of Open Access Journals (Sweden)

    PV Shiji

    2015-10-01

    Full Text Available Diabetes, one of the major life style diseases, is associated with high morbidity and mortality owing to its microvascular and macrovascular complications. The chance of development of various complications can be effectively prevented by tight glycemic control. We have various groups of drugs like Biguanides, Sulfonyl ureas, Glitazones, Alpha-glucosidase inhibitors, Incretin based therapy, Insulin and Insulin analogues in the armamentarium to treat diabetes. But still, the number of patients attaining glycemic targets are relatively low and various adverse effect limit the use of some of these drugs, especially in special groups. Hence there is ongoing research to develop newer and newer drugs which provide sustained blood glucose reduction with minimal adverse effects. SGLT-2 inhibitors are a new group of drugs recently approved by FDA to treat Diabetes. In this review we discuss about mechanism of action, various adverse effects and the clinical role of various SGLT-2 Inhibitors.

  7. [Adult form of Pompe disease].

    Science.gov (United States)

    Ziółkowska-Graca, Bozena; Kania, Aleksander; Zwolińska, Grazyna; Nizankowska-Mogilnicka, Ewa

    2008-01-01

    Pompe disease (glycogen-storage disease type II) is an autosomal recessive disorder caused by a deficiency of lysosomal acid alpha-glucosidase (GAA), leading to the accumulation of glycogen in the lysosomes primarily in muscle cells. In the adult form of the disease, proximal muscle weakness is noted and muscle volume is decreased. The infantile form is usually fatal. In the adult form of the disease the prognosis is relatively good. Muscle weakness may, however, interfere with normal daily activities, and respiratory insufficiency may be associated with obstructive sleep apnea. Death usually results from respiratory failure. Effective specific treatment is not available. Enzyme replacement therapy with recombinant human GAA (rh-GAA) still remains a research area. We report the case of a 24-year-old student admitted to the Department of Pulmonary Diseases because of severe respiratory insufficiency. Clinical symptoms such as dyspnea, muscular weakness and increased daytime sleepiness had been progressing for 2 years. Clinical examination and increased blood levels of CK suggested muscle pathology. Histopathological analysis of muscle biopsy, performed under electron microscope, confirmed the presence of vacuoles containing glycogen. Specific enzymatic activity of alpha-glucosidase was analyzed confirming Pompe disease. The only effective method to treat respiratory insufficiency was bi-level positive pressure ventilation. Respiratory rehabilitation was instituted and is still continued by the patient at home. A high-protein, low-sugar diet was proposed for the patient. Because of poliglobulia low molecular weight heparin was prescribed. The patient is eligible for experimental replacement therapy with rh-GAA. PMID:19003770

  8. Disruption of Brewers' yeast by hydrodynamic cavitation: Process variables and their influence on selective release.

    Science.gov (United States)

    Balasundaram, B; Harrison, S T L

    2006-06-01

    Intracellular products, not secreted from the microbial cell, are released by breaking the cell envelope consisting of cytoplasmic membrane and an outer cell wall. Hydrodynamic cavitation has been reported to cause microbial cell disruption. By manipulating the operating variables involved, a wide range of intensity of cavitation can be achieved resulting in a varying extent of disruption. The effect of the process variables including cavitation number, initial cell concentration of the suspension and the number of passes across the cavitation zone on the release of enzymes from various locations of the Brewers' yeast was studied. The release profile of the enzymes studied include alpha-glucosidase (periplasmic), invertase (cell wall bound), alcohol dehydrogenase (ADH; cytoplasmic) and glucose-6-phosphate dehydrogenase (G6PDH; cytoplasmic). An optimum cavitation number Cv of 0.13 for maximum disruption was observed across the range Cv 0.09-0.99. The optimum cell concentration was found to be 0.5% (w/v, wet wt) when varying over the range 0.1%-5%. The sustained effect of cavitation on the yeast cell wall when re-circulating the suspension across the cavitation zone was found to release the cell wall bound enzyme invertase (86%) to a greater extent than the enzymes from other locations of the cell (e.g. periplasmic alpha-glucosidase at 17%). Localised damage to the cell wall could be observed using transmission electron microscopy (TEM) of cells subjected to less intense cavitation conditions. Absence of the release of cytoplasmic enzymes to a significant extent, absence of micronisation as observed by TEM and presence of a lower number of proteins bands in the culture supernatant on SDS-PAGE analysis following hydrodynamic cavitation compared to disruption by high-pressure homogenisation confirmed the selective release offered by hydrodynamic cavitation.

  9. New treatments for patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Wolffenbuttel, B H; Graal, M B

    1996-11-01

    In subjects with type 2 diabetes, both defects of insulin secretion and insulin resistance contribute to the development of hyperglycaemia. The major goals of treatment are to optimise blood glucose control, and normalise the associated lipid disturbances and elevated blood pressure. Pharmacologic treatment is often necessary. This paper discusses new forms of oral treatment for subjects with type 2 diabetes. These include a new sulphonylurea compound glimepiride (Amaryl), which binds to a different protein of the putative sulphonylurea receptor than glibenclamide, and seems to have a lower risk of hypoglycaemia. A new class of drugs with insulin secretory capacity, of which repaglinide (NovoNorm) is the leading compound, is now in phase III clinical trials. Alpha-glucosidase inhibitors reversibly inhibit alpha-glucosidase enzymes in the small intestine, which delays cleavage of oligo- and disaccharides to monosaccharides. This leads to a delayed and reduced blood glucose rise after a meal. Two compounds are in development or have been marketed, ie, miglitol and acarbose (Glucobay). Another new class of drugs is the thiazolidine-diones, which seem to work by enhancing insulin action. The 'insulin sensitising' effects of the leading compounds, troglitazone and BRL 49653C, do not involve any effect on insulin secretion. These drugs also seem to beneficially influence serum cholesterol and triglyceride levels. Oral antihyperglycaemic agents can be used only during a limited period of time in most patients, after which the diabetic state 'worsens' and insulin therapy has to be started. In this light, two new forms of treatment which require subcutaneous injections are also discussed: the synthetic human amylin analogue AC137 (pramlintide) and glucagon-like peptide-1 (7-36)-amide, a strong glucose-dependent stimulator of insulin secretion. It remains to be seen whether these compounds can be developed further for clinical use in patients with diabetes.

  10. Impaired Organization and Function of Myofilaments in Single Muscle Fibers from a Mouse Model of Pompe Disease

    Energy Technology Data Exchange (ETDEWEB)

    Xu, S.; Galperin, M; Melvin, G; Horowits, R; Raben, N; Plotz, P; Yu, L

    2010-01-01

    Pompe disease, a deficiency of lysosomal acid {alpha}-glucosidase, is a disorder of glycogen metabolism that can affect infants, children, or adults. In all forms of the disease, there is progressive muscle pathology leading to premature death. The pathology is characterized by accumulation of glycogen in lysosomes, autophagic buildup, and muscle atrophy. The purpose of the present investigation was to determine if myofibrillar dysfunction in Pompe disease contributes to muscle weakness beyond that attributed to atrophy. The study was performed on isolated myofibers dissected from severely affected fast glycolytic muscle in the {alpha}-glucosidase knockout mouse model. Psoas muscle fibers were first permeabilized, so that the contractile proteins could be directly relaxed or activated by control of the composition of the bathing solution. When normalized by cross-sectional area, single fibers from knockout mice produced 6.3 N/cm{sup 2} of maximum Ca{sup 2+}-activated tension compared with 12.0 N/cm{sup 2} produced by wild-type fibers. The total protein concentration was slightly higher in the knockout mice, but concentrations of the contractile proteins myosin and actin remained unchanged. Structurally, X-ray diffraction showed that the actin and myosin filaments, normally arranged in hexagonal arrays, were disordered in the knockout muscle, and a lower fraction of myosin cross bridges was near the actin filaments in the relaxed muscle. The results are consistent with a disruption of actin and myosin interactions in the knockout muscles, demonstrating that impaired myofibrillar function contributes to weakness in the diseased muscle fibers.

  11. Effects of xylitol on carbohydrate digesting enzymes activity, intestinal glucose absorption and muscle glucose uptake: a multi-mode study.

    Science.gov (United States)

    Chukwuma, Chika Ifeanyi; Islam, Md Shahidul

    2015-03-01

    The present study investigated the possible mechanism(s) behind the effects of xylitol on carbohydrate digesting enzymes activity, muscle glucose uptake and intestinal glucose absorption using in vitro, ex vivo and in vivo experimental models. The effects of increasing concentrations of xylitol (2.5%-40% or 164.31 mM-2628.99 mM) on alpha amylase and alpha glucosidase activity in vitro and intestinal glucose absorption and muscle glucose uptake were investigated under ex vivo conditions. Additionally, the effects of an oral bolus dose of xylitol (1 g per kg BW) on gastric emptying and intestinal glucose absorption and digesta transit in the different segments of the intestinal tract were investigated in normal and type 2 diabetic rats at 1 hour after dose administration, when phenol red was used as a recovery marker. Xylitol exhibited concentration-dependent inhibition of alpha amylase (IC₅₀ = 1364.04 mM) and alpha glucosidase (IC₅₀ = 1127.52 mM) activity in vitro and small intestinal glucose absorption under ex vivo condition. Xylitol also increased dose dependent muscle glucose uptake with and without insulin, although the uptake was not significantly affected by the addition of insulin. Oral single bolus dose of xylitol significantly delayed gastric emptying, inhibited intestinal glucose absorption but increased the intestinal digesta transit rate in both normal and diabetic rats compared to their respective controls. The data of this study suggest that xylitol reduces intestinal glucose absorption via inhibiting major carbohydrate digesting enzymes, slowing gastric emptying and fastening the intestinal transit rate, but increases muscle glucose uptake in normal and type 2 diabetic rats. PMID:25656339

  12. Glucose Supply and Insulin Demand Dynamics of Antidiabetic Agents

    Science.gov (United States)

    Monte, Scott V.; Schentag, Jerome J.; Adelman, Martin H.; Paladino, Joseph A.

    2010-01-01

    Background For microvascular outcomes, there is compelling historical and contemporary evidence for intensive blood glucose reduction in patients with either type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM). There is also strong evidence to support macrovascular benefit with intensive blood glucose reduction in T1DM. Similar evidence remains elusive for T2DM. Because cardiovascular outcome trials utilizing conventional algorithms to attain intensive blood glucose reduction have not demonstrated superiority to less aggressive blood glucose reduction (Action to Control Cardiovascular Risk in Diabetes; Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation; and Veterans Affairs Diabetes Trial), it should be considered that the means by which the blood glucose is reduced may be as important as the actual blood glucose. Methods By identifying quantitative differences between antidiabetic agents on carbohydrate exposure (CE), hepatic glucose uptake (HGU), hepatic gluconeogenesis (GNG), insulin resistance (IR), peripheral glucose uptake (PGU), and peripheral insulin exposure (PIE), we created a pharmacokinetic/pharmacodynamic model to characterize the effect of the agents on the glucose supply and insulin demand dynamic. Glucose supply was defined as the cumulative percentage decrease in CE, increase in HGU, decrease in GNG, and decrease in IR, while insulin demand was defined as the cumulative percentage increase in PIE and PGU. With the glucose supply and insulin demand effects of each antidiabetic agent summated, the glucose supply (numerator) was divided by the insulin demand (denominator) to create a value representative of the glucose supply and insulin demand dynamic (SD ratio). Results Alpha-glucosidase inhibitors (1.25), metformin (2.20), and thiazolidinediones (TZDs; 1.25–1.32) demonstrate a greater effect on glucose supply (SD ratio >1), while secretagogues (0.69–0.81), basal insulins (0.77

  13. Conversion of cassava starch to biomass, carbohydrates, and acids by Aspergillus niger.

    Science.gov (United States)

    Tan, K H; Ferguson, L B; Carlton, C

    1984-01-01

    The filamentous fungus, Aspergillus niger, efficiently converted cassava polysaccharides to mycelial mass, simple sugars, and acids during the course of its growth. A typical 70-ml culture broth containing 2% cassava polysaccharides yielded 0.38 g dry mycelial mass, 1.14 mmol reducing sugars, and 1.17 meq acids at the end of 42 h. About 70% of the initial total carbohydrate in the medium was degraded during the same period. The sugars and acids in the culture broths were analyzed by HPLC on a single Aminex HPX-87 column at 55 degrees C, using 0.013 N H2SO4 as the eluting solvent. Cassava polysaccharides were degraded to oligosaccharides, maltotriose, maltose, and glucose beyond the 20-h growth periods, with maltotriose emerging as the major simple sugar. The appearance of citric, malic, gluconic, succinic, and fumaric acids accounted mostly for the decreasing pH in the growth media. Formation of carbohydrate species in the culture broths was closely related to the biosynthesis and secretion of several carbohydrases by A. niger. The extracellular carbohydrases were separated and identified by chromatofocusing and polyacrylamide gel electrophoresis to be amyloglucosidase (EC 3.1.2.3), alpha-amylase (EC 3.2.1.1), and alpha-glucosidase (EC 3.2.1.20), respectively.

  14. Progress in Enzyme Replacement Therapy in Glycogen Storage Disease Type II.

    Science.gov (United States)

    Angelini, Corrado; Semplicini, Claudio; Tonin, Paola; Filosto, Massimiliano; Pegoraro, Elena; Sorarù, Gianni; Fanin, Marina

    2009-05-01

    Glycogen storage disease type II (GSDII) is an autosomal recessive lysosomal disorder caused by mutations in the gene encoding alpha-glucosidase (GAA). The disease can be clinically classified into three types: a severe infantile form, a juvenile and an adultonset form. Cases with juvenile or adult onset GSDII mimic limb-girdle muscular dystrophy or polymyositis and are often characterized by respiratory involvement. GSDII patients are diagnosed by biochemical assay and by molecular characterization of the GAA gene. Ascertaining a natural history of patients with heterogeneous late-onset GSDII is useful for evaluating their progressive functional disability. A significant decline is observed over the years in skeletal and respiratory muscle function. Enzyme replacement therapy (ERT) has provided encouraging results in the infantile form. It is not yet known if ERT is effective in late-onset GSDII. We examined a series of 11 patients before and after ERT evaluating muscle strength by MRC, timed and graded functional tests, 6-minute walk test (6MWT), respiratory function by spirometric parameters and quality of life. We observed a partial improvement during a prolonged follow-up from 3 to 18 months. The use of different clinical parameters in the proposed protocol seems crucial to determine the efficacy of ERT, since not all late-onset patients respond similarly to ERT. PMID:21179524

  15. Effect of experimental varicocele on structure and function of epididymis in adolescent rats

    Institute of Scientific and Technical Information of China (English)

    Qiu-YangZHANG; Shu-DongQIU; Xiao-NianMA; He-MingYU; Yan-WanWU

    2003-01-01

    Aim: To study the effect of experimental left varicocele (ELV) on epididymal structure and function in adolescent Sprague-Dawley rats. Methods: ELV was induced by partial ligation of the left renal vein. Sham-operated animals served as the controls. Four and 8 weeks after the operation, the histological, ultrastructural and biochemical(alpha-glucosidase activity and camitine content) changes in different segments of the epididymis were observed.Results: In the treated animals, there were degeneration of the epididymal epithelium and edema of the interstitial tissue; numerous shedding cells, residual bodies, deformed sperm and macrophages appeared in the epididymal lumen.Morphometric measurement indicated a significant reduction in the epididymal tubular diameter (P<0.05) and a significant increase in the epididymal interstitial area (P<0.05) compared with the controls. Ultrastructural study showed sparse microvilli of the columnar epithelium, increased and enlarged lysosomes in the principal cells with defected organelles and the presence of large cytoplasmic vacuoles. The protein and carnitine contents and the alpha-glucosi-dase activity in the caput, corpus and cauda epididymis of the ELV rats were lower than those of the controls (P<0.05). Conclusion: There were structural and functional changes in the epididymis of adolescent ELV rats, which may contribute to the infertility caused by varicocele. (Asian J Androl 2003 Jun; 5: 108-112)

  16. Recent Trends in Therapeutic Approaches for Diabetes Management: A Comprehensive Update.

    Science.gov (United States)

    Tiwari, Pragya

    2015-01-01

    Diabetes highlights a growing epidemic imposing serious social economic crisis to the countries around the globe. Despite scientific breakthroughs, better healthcare facilities, and improved literacy rate, the disease continues to burden several sections, especially middle and low income countries. The present trends indicate the rise in premature death, posing a major threat to global development. Scientific and technological advances have witnessed the development of newer generation of drugs like sulphonylureas, biguanides, alpha glucosidase inhibitors, and thiazolidinediones with significant efficacy in reducing hyperglycemia. Recent approaches in drug discovery have contributed to the development of new class of therapeutics like Incretin mimetics, Amylin analogues, GIP analogs, Peroxisome proliferator activated receptors, and dipeptidyl peptidase-4 inhibitor as targets for potential drugs in diabetes treatment. Subsequently, the identification and clinical investigation of bioactive substances from plants have revolutionized the research on drug discovery and lead identification for diabetes management. With a focus on the emerging trends, the review article explores the current statistical prevalence of the disease, discussing the benefits and limitations of the commercially available drugs. Additionally, the critical areas in clinical diabetology are discussed, with respect to prospects of statins, nanotechnology, and stem cell technology as next generation therapeutics and why the herbal formulations are consistently popular choice for diabetes medication and management.

  17. Starch Degradation Metabolism towards Sucrose Synthesis in Germinating Araucaria araucana Seeds.

    Science.gov (United States)

    Cardemil, L; Varner, J E

    1984-12-01

    As starch is the main seed reserve material in both species of Araucaria of South America, A. araucana and A. angustifolia, it is important to understand starch breakdown in both embryo and megagametophyte tissues of Araucaria seeds. Sugar analysis by thin layer chromatography indicates that sucrose is the main sugar produced in both tissues. Enzyme reactions coupled to benzidine oxidation indicate that sucrose is the main sugar moved from the megagametophyte to the growing regions of the embryo via the cotyledons.Phosphorylase was detected in both embryo and megagametophyte tissues by the formation of [(32)P]glucose-1-P and by formation of [(14)C] amylopectin from [(14)C]glucose-1-P. The enzyme activity increases 5-fold in both embryo and gametophyte to a peak 18 hours after the start of imbibition. Debranching enzyme, alpha-glucosidase, and hexokinase are also present in both embryonic and megagametophytic tissues.Branched glucan oligosaccharides accumulate during this time, reaching a maximum 40 hours after imbibition starts, and decline after germination occurs.The pattern of activity of the enzymes studied in this work suggests that starch degradation is initiated by alpha-amylase and phosphorylase in the embryo and by phosphorylase mainly in the megagametophyte. Sucrose-P synthase seems to be the enzyme responsible for sucrose synthesis in both tissues. PMID:16663947

  18. Evaluation of the toxic effects of arsenite, chromate, cadmium, and copper using a battery of four bioassays

    Energy Technology Data Exchange (ETDEWEB)

    Ko, Kyung-Seok; Lee, Pyeong-Koo [Korea Institute of Geoscience and Mineral Resources (KIGAM), Daejeon (Korea, Republic of). Geologic Environment Div.; Kong, In Chul [Yeungnam Univ., Kyungbuk (Korea, Republic of). Dept. of Environmental Engineering

    2012-09-15

    The sensitivities of four different kinds of bioassays to the toxicities of arsenite, chromate, cadmium, and copper were compared. The different bioassays exhibited different sensitivities, i.e., they responded to different levels of toxicity of each of the different metals. However, with the exception of the {alpha}-glucosidase enzyme activity, arsenite was the most toxic compound towards all the tested organisms, exhibiting the highest toxic effect on the seeds of Lactuca, with an EC{sub 50} value of 0.63 mg/L. The sensitivities of Lactuca and Raphanus were greater than the sensitivities of two other kinds of seeds tested. Therefore, these were the seeds appropriate for use in a seed germination assay. A high revertant mutagenic ratio (5:1) of Salmonella typhimurium was observed with an arsenite concentration of 0.1 {mu}g/plate, indicative of a high possibility of mutagenicity. These different results suggested that a battery of bioassays, rather than one bioassay alone, is needed as a more accurate and better tool for the bioassessment of environmental pollutants. (orig.)

  19. New α-Glucosidase Inhibitory Triterpenic Acid from Marine Macro Green Alga Codium dwarkense Boergs

    Directory of Open Access Journals (Sweden)

    Liaqat Ali

    2015-07-01

    Full Text Available The marine ecosystem has been a key resource for secondary metabolites with promising biological roles. In the current study, bioassay-guided phytochemical investigations were carried out to assess the presence of enzyme inhibitory chemical constituents from the methanolic extract of marine green alga—Codium dwarkense. The bioactive fractions were further subjected to chromatographic separations, which resulted in the isolation of a new triterpenic acid; dwarkenoic acid (1 and the known sterols; androst-5-en-3β-ol (2, stigmasta-5,25-dien-3β,7α-diol (3, ergosta-5,25-dien-3β-ol (4, 7-hydroxystigmasta-4,25-dien-3-one-7-O-β-d-fucopyranoside (5, 7-hydroxystigmasta-4,25-dien-3-one (6, and stigmasta-5,25-dien-3β-ol (7. The structure elucidation of the new compound was carried out by combined mass spectrometry and 1D (1H and 13C and 2D (HSQC, HMBC, COSY, and NOESY NMR spectroscopic data. The sub-fractions and pure constituents were assayed for enzymatic inhibition of alpha-glucosidase. Compound 1 showed significant inhibition at all concentrations. Compounds 2, 3, 5, and 7 exhibited a dose-dependent response, whereas compounds 4–6 showed moderate inhibition. Utilizing such marine-derived biological resources could lead to drug discoveries related to anti-diabetics.

  20. Fractures in children with Pompe disease: a potentiallong-term complication

    Energy Technology Data Exchange (ETDEWEB)

    Case, Laura E. [Duke University Medical Center, Division of Physical Therapy, Department of Community and Family Medicine, Durham, NC (United States); Hanna, Rabi; DeArmey, Stephanie; Mackey, Joanne; Boney, Anne; Chen, Yuan-Tsong; Kishnani, Priya S. [Duke University Medical Center, Department of Pediatrics, Durham, NC (United States); Frush, Donald P. [Duke University Medical Center, Department of Radiology, Durham, NC (United States); Krishnamurthy, Vidya [Duke University Medical Center, Department of Pediatrics and Department of Medicine, Durham, NC (United States); Morgan, Claire; Bouchard, Susan [Genzyme Corporation, Pharmacovigilance, Cambridge, MA (United States); Corzo, Deyanira [Genzyme Corporation, Cambridge, MA (United States); Weber, Thomas J. [Duke University Medical Center, Department of Medicine, Durham, NC (United States)

    2007-05-15

    Pompe disease (glycogen storage disease type II or acid maltase deficiency) is an autosomal recessive disorder caused by deficiency of the lysosomal enzyme acid {alpha}-glucosidase (GAA). Classic infantile-onset disease, characterized by cardiomegaly and profound weakness, leads to death in the first year of life from cardiorespiratory failure. Reversal of cardiomyopathy and improved motor function have been shown in clinical trials of rhGAA enzyme replacement therapy (ERT) with alglucosidase alfa (Myozyme), recently approved for clinical use. Increased survival potentially unmasks long-term complications of this previously lethal disease, including risk of skeletal fracture, recently identified at our institution and not previously reported in children with Pompe disease. To report the risk of fracture in children with Pompe disease with increased survival with ERT. We present four cases of fracture in patients with classic infantile Pompe disease treated with ERT at our institution, and review a study database for additional reports of fracture in this population. We review 19 fractures in 14 children with Pompe disease on ERT. Radiologists should be familiar with and vigilant for the association of fractures and increased survival on ERT in children with Pompe disease. We discuss potential mechanisms, implications for radiographic surveillance, potential intervention, and needs for further research. (orig.)

  1. Microbial dextran-hydrolyzing enzymes: fundamentals and applications.

    Science.gov (United States)

    Khalikova, Elvira; Susi, Petri; Korpela, Timo

    2005-06-01

    Dextran is a chemically and physically complex polymer, breakdown of which is carried out by a variety of endo- and exodextranases. Enzymes in many groups can be classified as dextranases according to function: such enzymes include dextranhydrolases, glucodextranases, exoisomaltohydrolases, exoisomaltotriohydrases, and branched-dextran exo-1,2-alpha-glucosidases. Cycloisomalto-oligosaccharide glucanotransferase does not formally belong to the dextranases even though its side reaction produces hydrolyzed dextrans. A new classification system for glycosylhydrolases and glycosyltransferases, which is based on amino acid sequence similarities, divides the dextranases into five families. However, this classification is still incomplete since sequence information is missing for many of the enzymes that have been biochemically characterized as dextranases. Dextran-degrading enzymes have been isolated from a wide range of microorganisms. The major characteristics of these enzymes, the methods for analyzing their activities and biological roles, analysis of primary sequence data, and three-dimensional structures of dextranases have been dealt with in this review. Dextranases are promising for future use in various scientific and biotechnological applications.

  2. Effervescent Granules Prepared Using Eucommia ulmoides Oliv. and Moso Bamboo Leaves: Hypoglycemic Activity in HepG2 Cells

    Directory of Open Access Journals (Sweden)

    Xiang-Zhou Li

    2016-01-01

    Full Text Available Eucommia ulmoides Oliv. (E. ulmoides Oliv. and moso bamboo (Phyllostachys pubescens leaves are used as folk medicines in central-western China to treat diabetes. To investigate the hypoglycemic activity of the effervescent granules prepared using E. ulmoides Oliv. and moso bamboo leaves (EBEG in HepG2 cells, EBEG were prepared with 5% of each of polysaccharides and chlorogenic acids from moso bamboo and E. ulmoides Oliv. leaves, respectively. HepG2 cells cultured in a high-glucose medium were classified into different groups. The results displayed EBEG-treated cells showed better glucose utilization than the negative controls; thus, the hypoglycemic effect of EBEG was much greater than that of granules prepared using either component alone, thereby indicating that this effect was due to a synergistic action of the components. Further, glucose consumption levels in the cells treated with EBEG (156.35% at 200 μg/mL and the positive controls (metformin, 162.29%; insulin, 161.52% were similar. Thus, EBEG exhibited good potential for use as a natural antidiabetic agent. The hypoglycemic effect of EBEG could be due to the synergistic action of polysaccharides from the moso bamboo leaves and chlorogenic acids from E. ulmoides Oliv. leaves via the inhibition of alpha-glucosidase and glucose-6-phosphate displacement enzyme.

  3. Immunomodulatory gene therapy prevents antibody formation and lethal hypersensitivity reactions in murine pompe disease.

    Science.gov (United States)

    Sun, Baodong; Kulis, Michael D; Young, Sarah P; Hobeika, Amy C; Li, Songtao; Bird, Andrew; Zhang, Haoyue; Li, Yifan; Clay, Timothy M; Burks, Wesley; Kishnani, Priya S; Koeberl, Dwight D

    2010-02-01

    Infantile Pompe disease progresses to a lethal cardiomyopathy in absence of effective treatment. Enzyme-replacement therapy (ERT) with recombinant human acid alpha-glucosidase (rhGAA) has been effective in most patients with Pompe disease, but efficacy was reduced by high-titer antibody responses. Immunomodulatory gene therapy with a low dose adeno-associated virus (AAV) vector (2 x 10(10) particles) containing a liver-specific regulatory cassette significantly lowered immunoglobin G (IgG), IgG1, and IgE antibodies to GAA in Pompe disease mice, when compared with mock-treated mice (P mast cell protease-1 (MMCP-1) followed the pattern associated with hypersensitivity reactions (P cells (Treg) were demonstrated to play a role in the tolerance induced by gene therapy as depletion of Treg led to an increase in GAA-specific IgG (P Treg depleted mice were challenged with GAA and had significantly stronger allergic reactions than mice given gene therapy without subsequent Treg depletion (temperature: P < 0.01; symptoms: P < 0.05). Ubiquitous GAA expression failed to prevent antibody formation. Thus, immunomodulatory gene therapy could provide adjunctive therapy in lysosomal storage disorders treated by enzyme replacement. PMID:19690517

  4. Anti-hyperglycemic and anti-hyperlipidemic effects of guava leaf extract

    Science.gov (United States)

    2010-01-01

    Psidium guajava Linn. (guava) is used not only as food but also as folk medicine in subtropical areas around the world because of its pharmacologic activities. In particular, the leaf extract of guava has traditionally been used for the treatment of diabetes in East Asia and other countries. Moreover, the anti-hyperglycemic activity of the extract has been reported in some animal models. However, little is known regarding the therapeutic activity of the extract in human clinical trials as well as its underlying therapeutic mechanisms and safety. In Japan, Guava Leaf Tea (Bansoureicha®, Yakult Honsha, Tokyo, Japan) containing the aqueous leaf extract from guava has been approved as one of the Foods for Specified Health Uses and is now commercially available. This review describes the active component of the aqueous guava leaf extract and its inhibition of alpha-glucosidase enzymes in vitro, safety of the extract and Guava Leaf Tea, reduction of postprandial blood glucose elevation, and improvement of hyperglycemia, hyperinsulinemia, hypoadiponectinemia, hypertriglycemia and hypercholesterolemia in murine models and several clinical trials. It is suggested that the chronic suppression of postprandial blood glucose elevation is important in preventing type 2 diabetes mellitus, and that Guava Leaf Tea is considered useful as an alimentotherapy for chronic treatment. PMID:20181067

  5. Diabetes therapies in hemodialysis patients: Dipeptidase-4inhibitors

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Although several previous studies have been publishedon the effects of dipeptidase-4 (DPP-4) inhibitors indiabetic hemodialysis (HD) patients, the findings haveyet to be reviewed comprehensively. Eyesight failurecaused by diabetic retinopathy and aging-relateddementia make multiple daily insulin injections difficultfor HD patients. Therefore, we reviewed the effectsof DPP-4 inhibitors with a focus on oral antidiabeticdrugs as a new treatment strategy in HD patients withdiabetes. The following 7 DPP-4 inhibitors are availableworldwide sitagliptin, vildagliptin, alogliptin, linagliptin,teneligliptin, anagliptin, and saxagliptin. All of theseare administered once daily with dose adjustmentsin HD patients. Four types of oral antidiabetic drugscan be administered for combination oral therapy withDPP-4 inhibitors, including sulfonylureas, meglitinide,thiazolidinediones, and alpha-glucosidase inhibitor. Ninestudies examined the antidiabetic effects in HD patients.Treatments decreased hemoglobin A1c and glycatedalbumin levels by 0.3% to 1.3% and 1.7% to 4.9%,respectively. The efficacy of DPP-4 inhibitor treatmentis high among HD patients, and no patients exhibitedsignificant severe adverse effects such as hypoglycemiaand liver dysfunction. DPP-4 inhibitors are key drugs innew treatment strategies for HD patients with diabetesand with limited choices for diabetes treatment.

  6. Lysosomal storage of oligosaccharide and glycosphingolipid in imino sugar treated cells.

    Science.gov (United States)

    Boomkamp, Stephanie D; Rountree, J S Shane; Neville, David C A; Dwek, Raymond A; Fleet, George W J; Butters, Terry D

    2010-04-01

    Sandhoff and Tay-Sachs disease are autosomal recessive GM2 gangliosidoses where a deficiency of lysosomal beta-hexosaminidase results in storage of glycoconjugates. Imino sugar (2-acetamido-1,4-imino-1,2,4-trideoxy-L-arabinitol) inhibition of beta-hexosaminidase in murine RAW264.7 macrophage-like cells led to lysosomal storage of glycoconjugates that were characterised structurally using fluorescence labelling of the free or glycolipid-derived oligosaccharides followed by HPLC and mass spectrometry. Stored glycoconjugates were confirmed as containing non-reducing GlcNAc or GalNAc residues resulting from the incomplete degradation of N-linked glycoprotein oligosaccharide and glycolipids, respectively. When substrate reduction therapeutics N-butyl-deoxynojirimycin (NB-DNJ) or N-butyldeoxygalactonojirimycin (NB-DGJ) were applied to the storage phenotype cells, an increase in glucosylated and galactosylated oligosaccharide species was observed due to endoplasmic reticulum alpha-glucosidases and lysosomal beta-galactosidase inhibition, respectively. Hexosaminidase inhibition triggered a tightly regulated cytokine-mediated inflammatory response that was normalised using imino sugars NB-DNJ and NB-DGJ, which restored the GM2 ganglioside storage burden but failed to reduce the levels of GA2 glycolipid or glycoprotein-derived N-linked oligosaccharides. Using a chemically induced gangliosidosis phenotype that can be modulated with substrate lowering drugs, the critical role of GM2 ganglioside in the progression of inflammatory disease is also demonstrated. PMID:20186478

  7. Late-onset Pompe disease with complicated intracranial aneurysm: a Chinese case report

    Directory of Open Access Journals (Sweden)

    Zhang B

    2016-03-01

    Full Text Available Bin Zhang,1,2,* Yuying Zhao,1,3,* Junling Liu,1,4 Ling Li,1 Jingli Shan,1 Dandan Zhao,1 Chuanzhu Yan1,3 1Laboratory of Neuromuscular Disorders and Department of Neurology, Qilu Hospital of Shandong University, Jinan, Shandong, 2Department of Neurology, Liaocheng People’s Hospital, Liaocheng, Shandong, 3Department of Neurology, Qilu Hospital of Shandong University, Key Laboratory for Experimental Teratology of the Ministry of Education, Brain Science Research Institute, Shandong University, Jinan, Shandong, 4Department of Neurology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, People’s Republic of China *These authors contributed equally to this work Abstract: Pompe disease is a rare autosomal recessive hereditary disease caused by genetic defects of acid maltase. This disease could be divided into two forms: infantile and late-onset, which mainly affect cardiac, respiratory, and skeletal muscle systems. Late-onset patients mainly show symptoms of skeletal muscle involvement, but recent reports have found that the central nervous system was also affected in some patients. Herein, we report a case of a female, adolescent-onset Pompe patient, who was diagnosed with complicated intracranial aneurysm in adulthood. Keywords: Pompe disease, glycogen storage disease II, acid maltase, acid alpha-glucosidase, cerebrovascular disorders

  8. Synthesis of alpha- and beta-D-glucopyranosyl triazoles by CuAAC 'click chemistry': reactant tolerance, reaction rate, product structure and glucosidase inhibitory properties.

    Science.gov (United States)

    Dedola, Simone; Hughes, David L; Nepogodiev, Sergey A; Rejzek, Martin; Field, Robert A

    2010-06-16

    Cu(I)-catalysed azide alkyne 1,3-dipolar cycloaddition (CuAAC) 'click chemistry' was used to assemble a library of 21 alpha-D- and beta-D-glucopyranosyl triazoles, which were assessed as potential glycosidase inhibitors. In the course of this work, different reactivities of isomeric alpha- and beta-glucopyranosyl azides under CuAAC conditions were noted. This difference was further investigated using competition reactions and rationalised on the basis of X-ray crystallographic data, which revealed significant differences in bond lengths within the azido groups of the alpha- and beta-anomers. Structural studies also revealed a preference for perpendicular orientation of the sugar and triazole rings in both the alpha- and beta-glucosyl triazoles in the solid state. The triazole library was assayed for inhibition of sweet almond beta-glucosidase (GH1) and yeast alpha-glucosidase (GH13), which led to the identification of a set of glucosidase inhibitors effective in the 100 microM range. The preference for inhibition of one enzyme over the other proved to be dependent on the anomeric configuration of the inhibitor, as expected.

  9. In-vitro Enzyme Inhibition Studies for Antidiabetic Activity of Mature and Tender Leaves of Mangifera indica var. Totapuri.

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    Bhuvaneshwari J

    2014-06-01

    Full Text Available Diabetes mellitus is a chronic disorder characterized by high blood glucose levels, whose critical management alleviates multiple complications. Ill-managed diabetes often precedes incidence of dyslipidaemia and cardiac diseases. Mangifera indica L (Anacardiaceae is a popular Indian horticultural tree also used medicinally. Hypoglycaemic and/or antidiabetic activity of leaf has been investigated in various models; however a comparative account of hypoglycaemic potential of mature and tender leaf is not reported; effect of leaves on carbohydrate digesting enzymes also is not reported. The present study is a preliminary report on comparative hypoglycaemic properties of aqueous methanolic extracts of mature and tender leaves of M indica L var. Totapuri in glucose loaded Wistar Albino rats and In-vitro glucosidase and  amylase inhibition bioassays. Significant hypoglycaemic activity was observed with both extracts in oral glucose tolerance test at 500mg/Kg b.wt. given orally one hour prior glucose loading. The extracts also showed inhibition of rat intestinal alpha glucosidase ,as well as porcine pancreatic alpha amylase with IC50: 21.03 and 35.73 for mature leaf and 27.16 and 22.01 for tender leaf extracts respectively. Thus the hypoglycaemic potential of mango leaves may be due to inhibition of carbohydrate digesting enzymes. Polyphenols, flavonoids and saponins identified in the extracts may be responsible for their hypoglycaemic activity.

  10. Natural products as promising drug candidates for the treatment of hepatitis B and C.

    Science.gov (United States)

    Wohlfarth, Carolin; Efferth, Thomas

    2009-01-01

    Hepatitis B virus (HBV) or hepatitis C virus (HCV) infections are a major threat worldwide. Combination therapy of interferon-alpha and ribavirin is currently the treatment of choice for HCV-infected patients. However, this regimen is only effective in approximately 50% of patients and provokes severe side-effects. Numerous natural alternatives for treating HCV have been suggested. Deoxynojirimycin and its derivatives are iminosugars which exert anti-HCV activity by inhibiting alpha-glucosidases. A non-immunosuppressive derivate of cyclosporine A, NIM811, exerts anti-HCV activity by binding to cyclophilin. Other natural products with promising anti-HCV activity are 2-arylbenzofuran derivatives, Mellein, and pseudoguaianolides. For HBV treatment, several drugs are available, specifically targeting the virus polymerase (lamivudine, entecavir, telbivudine, and adefovir dipivoxil). The efficacy of these drugs is hampered by the development of resistance due to point mutations in the HBV polymerase. Due to drug resistance and adverse side-effects, the search for novel drugs is mandatory. Wogonin, ellagic acid, artemisinin and artesunate, chrysophanol 8-O-beta-D-glucoside, saikosaponin C, and protostane triterpenes are active against HBV. Natural products need to be investigated in more detail to explore their potential as novel adjuncts to established HBV or HCV therapy.

  11. Discovery of insect and human dengue virus host factors.

    Science.gov (United States)

    Sessions, October M; Barrows, Nicholas J; Souza-Neto, Jayme A; Robinson, Timothy J; Hershey, Christine L; Rodgers, Mary A; Ramirez, Jose L; Dimopoulos, George; Yang, Priscilla L; Pearson, James L; Garcia-Blanco, Mariano A

    2009-04-23

    Dengue fever is the most frequent arthropod-borne viral disease of humans, with almost half of the world's population at risk of infection. The high prevalence, lack of an effective vaccine, and absence of specific treatment conspire to make dengue fever a global public health threat. Given their compact genomes, dengue viruses (DENV-1-4) and other flaviviruses probably require an extensive number of host factors; however, only a limited number of human, and an even smaller number of insect host factors, have been identified. Here we identify insect host factors required for DENV-2 propagation, by carrying out a genome-wide RNA interference screen in Drosophila melanogaster cells using a well-established 22,632 double-stranded RNA library. This screen identified 116 candidate dengue virus host factors (DVHFs). Although some were previously associated with flaviviruses (for example, V-ATPases and alpha-glucosidases), most of the DVHFs were newly implicated in dengue virus propagation. The dipteran DVHFs had 82 readily recognizable human homologues and, using a targeted short-interfering-RNA screen, we showed that 42 of these are human DVHFs. This indicates notable conservation of required factors between dipteran and human hosts. This work suggests new approaches to control infection in the insect vector and the mammalian host.

  12. Intestinal lactase (beta-galactosidase) and other glycosidase activities in suckling and adult tammar wallabies (Macropus eugenii).

    Science.gov (United States)

    Walcott, P J; Messer, M

    1980-10-01

    The activities of various glycosidases in homogenates of the small intestinal mucosa of two adult and 18 suckling tammar wallabies (M. eugenii) aged from 6 to 50 weeks were investigated. Lactase (beta-D-galactosidase), beta-N-acetylglucosaminidase, alpha-L-fucosidase and neuraminidase activities were high during the first 34 weeks post partum and then declined to very low levels. Maltase, isomaltase, sucrase and trehalase activities were very low or absent during the first 34 weeks, and then increased. The lactase activity was unusual in being greater in the distal than the middle or proximal thirds of the intestine, and in its low pH optimum (pH 4.6), inhibition by p-chloromercuribenzene sulfonate but not by Tris, and lack of cellobiase activity. These properties are those of a lysosomal acid beta-galactosidase rather than of a brush border neutral lactase. The maltase activity had the characteristics of a lysosomal acid alpha-glucosidase early in lactation and of a brush border neutral maltase in adult animals. The significance of these findings is discussed in relation to changes in dietary carbohydrates during weaning and to the mode of digestion of milk carbohydrates by the pouch young. PMID:6783021

  13. Bean amylase inhibitor and other carbohydrate absorption blockers: effects on diabesity and general health.

    Science.gov (United States)

    Preuss, Harry G

    2009-06-01

    Many believe that excessive intake of refined carbohydrates (CHO) plays a major role in the development of obesity/overweight, type 2 diabetes mellitus and insulin resistance, a collection of events commonly referred to as "diabesity," and have sought natural means to overcome these linked perturbations. As a first approach, planned diets with low portions of refined CHO have become popular. However, these diets do not satisfy everyone; and many are concerned over replacing CHO with more fats. As a second option, addition of soluble fiber to the diet can slow absorption of refined CHO, i.e., lower the glycemic index of foods and overcome or at least ameliorate many of the adverse reactions resulting from increased refined CHO ingestion. Unfortunately, the general public does not favor diets high in fiber content, and various fibers can lead to gastrointestinal problems such as gas and diarrhea. A third choice to favorably influence CHO absorption is to use natural dietary supplements that block or slow CHO absorption in the gastrointestinal tract via inhibiting enzymes necessary for CHO absorption -amylase and alpha-glucosidases. Although a number of natural supplements with anti-amylase activity have been recognized, the most studied and favored one is white kidney bean extract. Animal and human studies clearly show that this agent works in vivo and has clinical utility. This paper reviews many aspects of diabesity and the use of "carb blockers" to prevent and ameliorate the situation. In many respects, carb blockers mimic the beneficial effects of fibers. PMID:20150600

  14. Recent Trends in Therapeutic Approaches for Diabetes Management: A Comprehensive Update

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    Pragya Tiwari

    2015-01-01

    Full Text Available Diabetes highlights a growing epidemic imposing serious social economic crisis to the countries around the globe. Despite scientific breakthroughs, better healthcare facilities, and improved literacy rate, the disease continues to burden several sections, especially middle and low income countries. The present trends indicate the rise in premature death, posing a major threat to global development. Scientific and technological advances have witnessed the development of newer generation of drugs like sulphonylureas, biguanides, alpha glucosidase inhibitors, and thiazolidinediones with significant efficacy in reducing hyperglycemia. Recent approaches in drug discovery have contributed to the development of new class of therapeutics like Incretin mimetics, Amylin analogues, GIP analogs, Peroxisome proliferator activated receptors, and dipeptidyl peptidase-4 inhibitor as targets for potential drugs in diabetes treatment. Subsequently, the identification and clinical investigation of bioactive substances from plants have revolutionized the research on drug discovery and lead identification for diabetes management. With a focus on the emerging trends, the review article explores the current statistical prevalence of the disease, discussing the benefits and limitations of the commercially available drugs. Additionally, the critical areas in clinical diabetology are discussed, with respect to prospects of statins, nanotechnology, and stem cell technology as next generation therapeutics and why the herbal formulations are consistently popular choice for diabetes medication and management.

  15. Impact of infection on the secretory capacity of the male accessory glands

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    M. Marconi

    2009-06-01

    Full Text Available INTRODUCTION: Studies that compare the impact of different infectious entities of the male reproductive tract (MRT on the male accessory gland function are controversial. MATERIAL AND METHODS: Semen analyses of 71 patients with proven infections of the MRT were compared with the results of 40 healthy non-infected volunteers. Patients were divided into 3 groups according to their diagnosis: chronic prostatitis NIH type II (n = 38, chronic epididymitis (n = 12, and chronic urethritis (n = 21. RESULTS: The bacteriological analysis revealed 9 different types of microorganisms, considered to be the etiological agents, isolated in different secretions, including: urine, expressed prostatic secretions, semen and urethral smears: E. Coli (n = 20, Klebsiella (n = 2, Proteus spp. (n = 1, Enterococcus (n = 20, Staphylococcus spp. (n = 1, M. tuberculosis (n = 2, N. gonorrhea (n = 8, Chlamydia tr. (n = 16 and, Ureaplasma urealyticum (n = 1. The infection group had significantly (p < 0.05 lower: semen volume, alpha-glucosidase, fructose, and zinc in seminal plasma and, higher pH than the control group. None of these parameters was sufficiently accurate in the ROC analysis to discriminate between infected and non-infected men. CONCLUSION: Proven bacterial infections of the MRT impact negatively on all the accessory gland function parameters evaluated in semen, suggesting impairment of the secretory capacity of the epididymis, seminal vesicles and prostate. These findings were associated with an infectious related significant increase of semen pH. None of the semen parameters evaluated can be suggested as a diagnostic tool for infection.

  16. Effects of PAH biodegradation in the presence of non-ionic surfactants on a bacterial community and its exoenzymatic activity.

    Science.gov (United States)

    Chang, Yi-Tang; Thirumavalavan, Munusamy; Lee, Jiunn-Fwu

    2010-01-01

    The influence of two non-ionic surfactants (TX-100 and Brij 35) on a bacterial community and its exoenzymatic activity during polycyclic aromatic hydrocarbon (naphthalene, phenanthrene and pyrene) biodegradation was evaluated in this study. The result indicated the addition of the non-ionic surfactants altered the profiles of the microbial populations and produced exoenzymes. Fluorescence in situ hybridization found that, as PAH biodegradation progressed in the presence of non-ionic surfactant, the proportion of Bacteria presents increased significantly from the range 54.79%-57.00% to 64.17%-73.4% and there was parallel decrease in Archaea. The trends in five phyla/subclass of Bacteria, namely alpha -, beta -, or gamma -Proteobacteria, HGC bacteria and LGC bacteria, were influenced significantly by the addition of Brij 35 as either monomers or micelles. A change was ascribed to different cohesive energy density (CED) value between the PAH and surfactant. The percentage of genera Pseudomonas 4.76%-12.67%, which included two signals, namely most true Pseudomonas spp. and Pseudomonas aeruginosa, were dominant during biodegradation. For exoenzymaztic activities, trends were identified by principle component analysis of the API ZYM enzymatic activity dataset. The additions of non-ionic surfactant were identified strong activities of three esterase (esterase, esterase lipase and lipase), alpha -glucosidase, beta -glucosidase, leucine arylamidase and acid phosphatase during PAH biodegradation. These enzymes are selected as possible organic pollutant indicators when the in situ bioremediation was monitored in the presence of non-ionic surfactant additives. PMID:20390887

  17. Retrospective, Single Center Study of Clinical, Paraclinical and Natural Course of Infantile-Onset Pompe Disease

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    Noormohammad Noori

    2015-01-01

    Full Text Available Background: Infantile-onset Pompe disease is a rare genetic and lethal disorder which is caused by the lack of acid alpha-glucosidase activity (GAA. The aim of our study was to identify the demographic and clinical characteristics, and natural history of these patients. Materials and Methods: In this retrospective study, clinical file of 15 patients diagnosed with infantile-onset Pompe disease whose symptoms started before the age of 12 months were studied. Diagnosis was based on clinical history, physical examination and diagnostic parameters in chest X-ray, echocardiogram, electrocardiogram and biochemical tests after rule out the other metabolic and neuromuscular disorders. Results: Sixty percent of the patients were male and 40% were female. The mean age at the onset of symptoms was 78 days (range: 3-150 days. Most frequent clinical and paraclinical symptoms were cardiomegaly, hypotonia, hyporeflexia, macroglossia, failure to thrive, hepatomegaly, and feeding problems, respectively. The mean age at the time of death was 5.96 months (range: 4-8 months, and all patients died before one year of age. Muscle enzymes including AST, ALT, LDH, and CPK were elevated in all patients. Due to the lack of availability, enzyme replacement therapy was not possible for any patient. Conclusion: The study showed that despite the supportive measures and no specific treatment, the clinical course is not significantly different with similar studies and the overall prognosis of this form of disease is very poor and disappointing.

  18. Muscle biopsy in Pompe disease

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    Lineu Cesar Werneck

    2013-05-01

    Full Text Available Pompe disease (PD can be diagnosed by measuring alpha-glucosidase levels or by identifying mutations in the gene enzyme. Muscle biopsies can aid diagnosis in doubtful cases. Methods: A review of muscle biopsy from 19 cases of PD (infantile, 6 cases; childhood, 4 cases; and juvenile/adult, 9 cases. Results: Vacuoles with or without glycogen storage were found in 18 cases. All cases had increased acid phosphatase activity. The vacuole frequency varied (almost all fibers in the infantile form to only a few in the juvenile/adult form. Atrophy of type 1 and 2 fibers was frequent in all forms. Atrophic angular fibers in the NADH-tetrazolium reductase and nonspecific esterase activity were observed in 4/9 of the juvenile/adult cases. Conclusion: Increased acid phosphatase activity and vacuoles were the primary findings. Most vacuoles were filled with glycogen, and the adult form of the disease had fewer fibers with vacuoles than the infantile or childhood forms.

  19. Alglucosidase alfa: Long term use in the treatment of patients with Pompe disease

    Directory of Open Access Journals (Sweden)

    Michael Beck

    2009-09-01

    Full Text Available Michael BeckChildren’s Hospital, University of Mainz, Mainz, GermanyAbstract: Pompe disease is a lysosomal storage disorder characterized by muscle weakness and cardiomyopathy. It shows a broad variability regarding the clinical severity as well as the age of onset. In the past, two different recombinant enzyme preparations have been developed for the treatment of Pompe patients: α-glucosidase, produced in rabbit milk, and α-glucosidase, produced in Chinese hamster ovary (CHO cell lines. The CHO enzyme received marketing approval in 2006 after it was proven to be effective in ameliorating muscle strength and improving heart function. The other has not been approved. The clinical efficacy of this enzyme preparation could be confirmed by several clinical trials in patients with different age of onset and disease severity. Enzyme replacement therapy, however, has its limitations due to unsatisfactory access of recombinant α-glucosidase to the muscle cells and due to the formation of antibodies. To overcome these therapeutic restraints, the development of a more effective enzyme preparation may become necessary.Keywords: alglucosidase alfa, alpha glucosidase, Pompe disease, enzyme replacement therapy, glycogen storage disorder type II, acid maltase deficiency

  20. A quick overview on some aspects of endocrinological and therapeutic effects of Berberis vulgaris L.

    Science.gov (United States)

    Zarei, Ali; Changizi-Ashtiyani, Saeed; Taheri, Soheila; Ramezani, Majid

    2015-01-01

    Many herbaceous plants contain compounds that have biological effects in addition to their medicinal properties. They have compounds with numerous properties, including hypo lipidemic, hypoglycemic, antioxidant, and hepato protective ones, which have been analyzed at different levels. One of these plants, with the scientific name of Berberis vulgaris, is barberry. The most important compounds identified in this plant are berberine, oxycontin, palmatine, bervulcine, berbamine, columbamine, jatrorrhizine, coptisine, and berbamine. In addition to alkaloids, organic acids such as chelidonic acid, citric acid, malic acid, resin, tannin, pectinic, and mucilagic substances are among the ingredients of barberry. In this paper, it was attempted to determine the role and effect of the extract of barberry on various body organs. The results showed that berberine actually increases insulin sensitivity and is capable of inhibiting alpha glucosidase, adipogenesis, and thus acts as an anti-obesity and hypoglycemic agent. Berberine reduces the density of serum cholesterol and triglycerides and can improve the function of liver enzymes, therefore, it can be suggested as a hypo lipidemic and hepato protective plant extract. The hepato protective effects of this extract are probably due to its antioxidant properties. Studies showed that barberry have numerous health benefits, including anti-inflammatory ones. Moreover, it can be used as a medicinal herb to treat a variety of disorders, such as diabetes, liver disease, gallbladder pain, digestive, urinary tract diseases, and gallstones. However, more studies on this issue and doing more focused and intensive researches in this field are recommended. PMID:26693406

  1. A quick overview on some aspects of endocrinological and therapeutic effects of Berberis vulgaris L.

    Science.gov (United States)

    Zarei, Ali; Changizi-Ashtiyani, Saeed; Taheri, Soheila; Ramezani, Majid

    2015-01-01

    Many herbaceous plants contain compounds that have biological effects in addition to their medicinal properties. They have compounds with numerous properties, including hypo lipidemic, hypoglycemic, antioxidant, and hepato protective ones, which have been analyzed at different levels. One of these plants, with the scientific name of Berberis vulgaris, is barberry. The most important compounds identified in this plant are berberine, oxycontin, palmatine, bervulcine, berbamine, columbamine, jatrorrhizine, coptisine, and berbamine. In addition to alkaloids, organic acids such as chelidonic acid, citric acid, malic acid, resin, tannin, pectinic, and mucilagic substances are among the ingredients of barberry. In this paper, it was attempted to determine the role and effect of the extract of barberry on various body organs. The results showed that berberine actually increases insulin sensitivity and is capable of inhibiting alpha glucosidase, adipogenesis, and thus acts as an anti-obesity and hypoglycemic agent. Berberine reduces the density of serum cholesterol and triglycerides and can improve the function of liver enzymes, therefore, it can be suggested as a hypo lipidemic and hepato protective plant extract. The hepato protective effects of this extract are probably due to its antioxidant properties. Studies showed that barberry have numerous health benefits, including anti-inflammatory ones. Moreover, it can be used as a medicinal herb to treat a variety of disorders, such as diabetes, liver disease, gallbladder pain, digestive, urinary tract diseases, and gallstones. However, more studies on this issue and doing more focused and intensive researches in this field are recommended.

  2. A quick overview on some aspects of endocrinological and therapeutic effects of Berberis vulgaris L.

    Directory of Open Access Journals (Sweden)

    Ali Zarei

    2015-10-01

    Full Text Available Many herbaceous plants contain compounds that have biological effects in addition to their medicinal properties. They have compounds with numerous properties, including hypo lipidemic, hypoglycemic, antioxidant, and hepato protective ones, which have been analyzed at different levels. One of these plants, with the scientific name of Berberis vulgaris, is barberry. The most important compounds identified in this plant are berberine, oxycontin, palmatine, bervulcine, berbamine, columbamine, jatrorrhizine, coptisine, and berbamine. In addition to alkaloids, organic acids such as chelidonic acid, citric acid, malic acid, resin, tannin, pectinic, and mucilagic substances are among the ingredients of barberry. In this paper, it was attempted to determine the role and effect of the extract of barberry on various body organs. The results showed that berberine actually increases insulin sensitivity and is capable of inhibiting alpha glucosidase, adipogenesis, and thus acts as an anti-obesity and hypoglycemic agent. Berberine reduces the density of serum cholesterol and triglycerides and can improve the function of liver enzymes, therefore, it can be suggested as a hypo lipidemic and hepato protective plant extract. The hepato protective effects of this extract are probably due to its antioxidant properties. Studies showed that barberry have numerous health benefits, including anti-inflammatory ones. Moreover, it can be used as a medicinal herb to treat a variety of disorders, such as diabetes, liver disease, gallbladder pain, digestive, urinary tract diseases, and gallstones. However, more studies on this issue and doing more focused and intensive researches in this field are recommended.

  3. Insecticidal potential of an endophytic Cladosporium velox against Spodoptera litura mediated through inhibition of alpha glycosidases.

    Science.gov (United States)

    Singh, Bahaderjeet; Kaur, Tamanreet; Kaur, Sanehdeep; Manhas, Rajesh K; Kaur, Amarjeet

    2016-07-01

    Alpha glucosidase inhibitory activity was exhibited by partially purified fractions obtained from an endophytic Cladosporium velox, isolated from Tinospora cordifolia. Taking into account the increasing importance of digestive enzyme inhibitors as insecticidal agents, the entomopathogenic potential of the fractions obtained was evaluated against Spodoptera litura (Fab.), a polyphagous pest. Considerable mortality was obtained when the larvae were fed on diet supplemented with the partially purified extract. All the concentrations of the extract significantly prolonged the overall developmental period of S. litura. At higher concentrations, the extract influenced the longevity of females as well as their reproductive potential. Phytochemical analysis revealed the presence of phenolic compounds in the active fraction. The phenolic compound responsible for the bioactivities was purified and identified to be chlorogenic acid using HPLC and MS analysis. The content of chlorogenic acid in the extract was quantified to be 250μg/ml. The purified compound also demonstrated inhibition of alpha glycosidases in vivo. The present study indicates that the endophyte imparted resistance to the insects in the plants could be mediated through chlorogenic acid targeting the alpha glycosidases present in the gut of the insect. The isolate obtained can be exploited for the production of chlorogenic acid, which has the potential to be exploited as a biocontrol agent against S. litura. PMID:27265826

  4. Potent α-glucosidase and α-amylase inhibitory activities of standardized 50% ethanolic extracts and sinensetin from Orthosiphon stamineus Benth as anti-diabetic mechanism

    Directory of Open Access Journals (Sweden)

    Mohamed Elsnoussi Ali

    2012-10-01

    Full Text Available Abstract Background In the present study, we tested a 50% ethanolic extract of Orthosiphon stamineus plants and its isolated bioactive compound with respect to their α-glucosidase and α-amylase inhibitory activities. Methods Bioactive flavonoid sinensetin was isolated from 50% ethanolic extract of Orthosiphon stamineus. The structure of this pure compound was determined on the NMR data and the α-glucosidase and α-amylase inhibitory activities of isolated sinensetin and 50% ethanolic extract of Orthosiphon stamineus were evaluated. Results In vitro studies of a 50% ethanolic extract of O. stamineus and the isolated sinensetin compound showed inhibitory activity on α-glucosidase (IC50: 4.63 and 0.66 mg/ml, respectively and α-amylase (IC50: 36.70 mg/ml and 1.13 mg/ml, respectively. Inhibition of these enzymes provides a strong biochemical basis for the management of type 2 diabetes via the control of glucose absorption. Conclusion Alpha-glucosidase and α-amylase inhibition could the mechanisms through which the 50% ethanolic extract of O. stamineus and sinensetin exert their antidiabetic activity, indicating that it could have potential use in the management of non-insulin-dependent diabetes.

  5. Loss of the membrane anchor of the target receptor is a mechanism of bioinsecticide resistance.

    Science.gov (United States)

    Darboux, Isabelle; Pauchet, Yannick; Castella, Claude; Silva-Filha, Maria Helena; Nielsen-LeRoux, Christina; Charles, Jean-François; Pauron, David

    2002-04-30

    The mosquitocidal activity of Bacillus sphaericus is because of a binary toxin (Bin), which binds to Culex pipiens maltase 1 (Cpm1), an alpha-glucosidase present in the midgut of Culex pipiens larvae. In this work, we studied the molecular basis of the resistance to Bin developed by a strain (GEO) of C. pipiens. Immunohistochemical and in situ hybridization experiments showed that Cpm1 was undetectable in the midgut of GEO larvae, although the gene was correctly transcribed. The sequence of the cpm1(GEO) cDNA differs from the sequence we previously reported for a susceptible strain (cpm1(IP)) by seven mutations: six missense mutations and a mutation leading to the premature termination of translation. When produced in insect cells, Cpm1(IP) was attached to the membrane by a glycosylphosphatidylinositol (GPI). In contrast, the premature termination of translation of Cpm1(GEO) resulted in the targeting of the protein to the extracellular compartment because of truncation of the GPI-anchoring site. The interaction between Bin and Cpm1(GEO) and the enzyme activity of the receptor were not affected. Thus, Bin is not toxic to GEO larvae because it cannot interact with the midgut cell membrane, even though its receptor site is unaffected. This mechanism contrasts with other known resistance mechanisms in which point mutations decrease the affinity of binding between the receptor and the toxin. PMID:11983886

  6. Kaulath, a new fungal fermented food from horse gram.

    Science.gov (United States)

    Dwivedi, Minakshee; Vasantha, K Y; Sreerama, Y N; Haware, Devendra J; Singh, R P; Sattur, A P

    2015-12-01

    Horse gram (Macrotyloma uniflorum) is used in the traditional method for treatmentof several health complications. It is also known that fermentation of such substrates yields a number of compounds that enhance the overall activities against several disease states. Solid state fermentation of horse gram using Penicillium camemberti showed an inhibition of pancreatic lipase and alpha glucosidase activities. The fermented material, termed Kaulath, showed 60 % increase in fat content. A reduction in sodium and increased levels of potassium and calcium was observed in Kaulath. In addition, a higher free radical scavenging activity was noted in this product compared to unfermented horse gram. Anti-nutritional factors, such as phytic acid and trypsin inhibitors showed a reduction in Kaulath. Furthermore, Kaulath, upto 1 g per kg body weight, did not exhibit any mortality or toxic effects in experimental rats after 14 days of administration. The hematological and clinical parameters were within safe limits between the groups, supported by the histopathology of liver and kidney. These results indicate potential food use of Kaulath in diets and as functional ingredients in formulated foods. PMID:26604417

  7. Successful pregnancy and birth after intrauterine insemination using caput epididymal sperm by percutaneous aspiration

    Institute of Scientific and Technical Information of China (English)

    YiQIU; Dan-TongYANG; Su-MeiWANG; Hui-QingSUN; Yi-FangJIA

    2003-01-01

    Aim:To manage male infertility with obstructive azoospermia by means of percutaneous epididymal sperm aspiration(PESA)and intrauterine insemination(IUI),Methods:Ninety azoospermic patients with congenital bilateral absence of the vas deferens(BAVD,N=58)or bilateral caudal epididymal obstruction(BCEO,n=32)requesting for fine needle aspiration(FNA),PESA and IUI were recruited.The obstruction was diagnosed by vasography and determination of the fructose,carnitine and alpha-glucosidase levels in the seminal fluid.Results:The mean sperm motility,density,abnormal sperm and total sperm count of the caput epdidymis were 16%±22%,(12±31)×106/mL,55%±36% and (16±14)×106,respectively,In the 90 couples,a total of 74 PESA procedures and 66 cycles of IUI were performed.Three pregnancies resulted,including one twin pregnancy giving birth to two healthy boys, one single pregnancy with a healthy girl and another single pregnancy aborted at week 6 of conception.The pregnancy rate per IUI cycle was 4.5%.Conclusiong:The birth of normal,healthy infants by IUI using PESA indicates that the caput epididymal sperm possess fertilization capacity.The PESA-IUI programme is a practical and economical procedure for the management of patients with obstructive azoospermia.

  8. Rapid identification of α-glucosidase inhibitors from Phlomis tuberosa by Sepbox chromatography and thin-layer chromatography bioautography.

    Directory of Open Access Journals (Sweden)

    Yingbo Yang

    Full Text Available Alpha-glucosidase inhibitors currently form an important basis for developing novel drugs for diabetes treatment. In our preliminary tests, the ethyl acetate fraction of Phlomis tuberosa extracts showed significant α-glucosidase inhibitory activity (IC₅₀ = 100 μg/mL. In the present study, a combined method using Sepbox chromatography and thin-layer chromatography (TLC bioautography was developed to probe α-glucosidase inhibitors further. The ethyl acetate fraction of P. tuberosa extracts was separated into 150 individual subfractions within 20 h using Sepbox chromatography. Then, under the guidance of TLC bioautography, 20 compounds were successfully isolated from these fractions, including four new diterpenoids [14-hydroxyabieta-8,11,13-triene-11-carbaldehyde-18-oic-12-carboxy-13-(1-hydroxy-1-methylethyl-lactone (1, 14-hydroxyabieta-8,11,13-triene-17-oic-12-carboxy-13-(1-hydroxy-1-methylethyl-lactone (2, 14,16-dihydroxyabieta-8,11,13-triene-15,17-dioic acid (3, and phlomisol (15,16-eposy-8,13(16,14-labdatrien-19-ol (4], and 16 known compounds. Activity estimation indicated that 15 compounds showed more potent α-glucosidase inhibitory effects (with IC50 values in the range 0.067-1.203 mM than the positive control, acarbose (IC50 = 3.72 ± 0.113 mM. This is the first report of separation of α-glucosidase inhibitors from P. tuberosa.

  9. Use of specific glycosidases to probe cellular interactions in the sea urchin embryo.

    Science.gov (United States)

    Idoni, Brian; Ghazarian, Haike; Metzenberg, Stan; Hutchins-Carroll, Virginia; Oppenheimer, Steven B; Carroll, Edward J

    2010-08-01

    We present an unusual and novel model for initial investigations of a putative role for specifically conformed glycans in cellular interactions. We have used alpha- and ss-amylase and alpha- and ss-glucosidase in dose-response experiments evaluating their effects on archenteron organization using the NIH designated sea urchin embryo model. In quantitative dose-response experiments, we show that defined activity levels of alpha-glucosidase and ss-amylase inhibited archenteron organization in living Lytechinus pictus gastrula embryos, whereas all concentrations of ss-glucosidase and alpha-amylase were without substantial effects on development. Product inhibition studies suggested that the enzymes were acting by their specific glycosidase activities and polyacrylamide gel electrophoresis suggested that there was no detectable protease contamination in the active enzyme samples. The results provide evidence for a role of glycans in sea urchin embryo cellular interactions with special reference to the possible structural conformation of these glycans based on the differential activities of the alpha- and ss-glycosidases. PMID:20435035

  10. A cardiologic approach to non-insulin antidiabetic pharmacotherapy in patients with heart disease

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    Fisman Enrique Z

    2009-07-01

    Full Text Available Abstract Classical non-insulin antihyperglycemic drugs currently approved for the treatment of type 2 diabetes mellitus (T2DM comprise five groups: biguanides, sulfonylureas, meglitinides, glitazones and alpha-glucosidase inhibitors. Novel compounds are represented by the incretin mimetic drugs like glucagon like peptide-1 (GLP-1, the dipeptidyl peptidase 4 (DPP-4 inhibitors, dual peroxisome proliferator-activated receptors (PPAR agonists (glitazars and amylin mimetic drugs. We review the cardiovascular effects of these drugs in an attempt to improve knowledge regarding their potential risks when treating T2DM in cardiac patients. Metformin may lead to lethal lactic acidosis, especially in patients with clinical conditions that predispose to this complication, such as recent myocardial infarction, heart or renal failure. Sulfonylureas exert their effect by closing the ATP-dependent potassium channels. This prevents the opening of these channels during myocardial ischemia, impeding the necessary hyperpolarization that protects the cell. The combined sulfonylurea/metformin therapy reveals additive effects on mortality in patients with coronary artery disease (CAD. Meglitinides effects are similar to those of sulfonylureas, due to their almost analogous mechanism of action. Glitazones lower leptin levels, leading to weight gain and are unsafe in NYHA class III or IV. The long-term effects of alpha-glucosidase inhibitors on morbidity and mortality rates is yet unknown. The incretin GLP-1 is associated with reductions in body weight and appears to present positive inotropic effects. DPP-4 inhibitors influences on the cardiovascular system seem to be neutral and patients do not gain weight. The future of glitazars is presently uncertain following concerns about their safety. The amylin mimetic drug paramlintide, while a satisfactory adjuvant medication in insulin-dependent diabetes, is unlikely to play a major role in the management of T2DM

  11. Fiber type conversion by PGC-1α activates lysosomal and autophagosomal biogenesis in both unaffected and Pompe skeletal muscle.

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    Shoichi Takikita

    Full Text Available PGC-1α is a transcriptional co-activator that plays a central role in the regulation of energy metabolism. Our interest in this protein was driven by its ability to promote muscle remodeling. Conversion from fast glycolytic to slow oxidative fibers seemed a promising therapeutic approach in Pompe disease, a severe myopathy caused by deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA which is responsible for the degradation of glycogen. The recently approved enzyme replacement therapy (ERT has only a partial effect in skeletal muscle. In our Pompe mouse model (KO, the poor muscle response is seen in fast but not in slow muscle and is associated with massive accumulation of autophagic debris and ineffective autophagy. In an attempt to turn the therapy-resistant fibers into fibers amenable to therapy, we made transgenic KO mice expressing PGC-1α in muscle (tgKO. The successful switch from fast to slow fibers prevented the formation of autophagic buildup in the converted fibers, but PGC-1α failed to improve the clearance of glycogen by ERT. This outcome is likely explained by an unexpected dramatic increase in muscle glycogen load to levels much closer to those observed in patients, in particular infants, with the disease. We have also found a remarkable rise in the number of lysosomes and autophagosomes in the tgKO compared to the KO. These data point to the role of PGC-1α in muscle glucose metabolism and its possible role as a master regulator for organelle biogenesis - not only for mitochondria but also for lysosomes and autophagosomes. These findings may have implications for therapy of lysosomal diseases and other disorders with altered autophagy.

  12. The inhibitory effects on adult male reproductive functions of crude garlic (Allium sativum) feeding

    Institute of Scientific and Technical Information of China (English)

    Imen Hammami; Afef Nahdi; Claire Mauduit; Mohamed Benahmed; Mohamed Amri; Awatef Ben Amar; Semy Zekri; Ahmed El May; Michele Veronique El May

    2008-01-01

    Aim: To investigate the effects of crude garlic on adult male rat reproductive functions. Methods: Thirty male rats were divided into five groups: group 1 (untreated) and groups 2, 3, 4 and 5 were fed for 30 days with 5%, 10%, 15% and 30% crude garlic, respectively. Testes and accessory organs were weighed and some markers were assessed. Light and electron microscopy observations were also performed. Results: A significant decrease was observed in the body weight of groups 4 (14%; P < 0.01) and 5 (20%; P < 0.01); of the prostate weight in group 5 (29.1%; P < 0.05) and of seminal vesicle weight in groups 3 (14.4%; P < 0.01), 4 (18.3%; P < 0.01) and 5 (27.3%; P < 0.01). In contrast, testis and epididymis weights were unchanged. In epididymis tissue, the alpha glucosidase activity and the spermatozoa density were unchanged. The treatment resulted in a significant decrease in testosterone serum levels in groups 3 (77.3%; P < 0.01), 4 (77.3%; P < 0.01) and 5 (90.9%; P < 0.01), associated with a significant increase in LH serum levels (P < 0.01). Testicular histology showed a dose-dependent increase in the percentage of empty seminiferous tubules. Moreover, testicular function was affected; a significant decrease in phosphatase acid activity (P < 0.01) and testosterone (P < 0.05) contents were observed. Conclusion: Crude garlic consumption during 1 month reduced testosterone secretion and altered spermatogenesis at 10%, 15% and 30% doses. (Asian J Androl 2008 Jul; 10: 593-601)

  13. Composition and Biological Activity of Volatile Oil from Salviajudaica and S. multicaulis from Jordan.

    Science.gov (United States)

    Afifi, Fatma U; Kasabri, Violet; Al-Jaber, Hala I; Abu-Irmaileh, Barakat E; Al-Qudah, Mahmoud A; Abazaa, Ismail F

    2016-04-01

    The aim of this work was to determine the composition of the hydro-distilled essential oil of Salvia judaica Boiss. and S. multicaulis Vahl. (Lamiaceae) from Jordan by GC and GC-MS and to report the actual composition of their fresh leaves and flowers using SPME (Solid Phase Micro-Extraction).Their dual alpha-amylase/alpha glucosidase and pancreatic lipase inhibitory activities as well as their anti-proliferative potential were screened. The aroma profile of the leaves, flowers, and flowers at pre-flowering stages of S. judaica, obtained through SPME was composed of sesquiterpene hydrocarbons (87.7 %, 71.8 %, and 86.2 %, respectively) while the hydro-distilled oil of the dry leaves was rich in oxygenated sesquiterpenes (50.8%). Fresh leaves of S. multicaulis were rich in oxygenated monoterpenes (58.1%), while monoterpene hydrocarbons dominated the blooming flowers (57.2%) and the flowers at the pre-flowering stage (64.7%). The hydro-distilled oil of the dry leaves was rich in oxygenated monoterpenes (77.6%). With doxorubicin as a positive control, no anti-proliferative activity was observed against colorectal cancer cell lines HT29, HCT116, and SW620 using SRB assay for either Salvia spp. In vitro enzymatic starch digestion was evaluated with Acarbose (IC50: 0.2 ± 0.0 µg /mL) as the reference drug. The respective IC50 (mg/mL) values of S. judaica and S. multicaulis aqueous extracts were 4.9 ± 0.4 and 10.3 ± 0.9. Modulation of pancreatic lipase activity (PL) was determined by colorimetry and compared with Orlistat (IC50 : 0.11 ± 0.0 µg/mL). PL-IC50 values (µg/mL) obtained for S. judaica and S. multicaulis were 108.5±6.4 and 31.8 ± 0.8, respectively.

  14. A novel RNA binding protein that interacts with NMDA R1 mRNA: regulation by ethanol.

    Science.gov (United States)

    Anji, Antje; Kumari, Meena

    2006-05-01

    Excitatory NMDA receptors are an important target of ethanol. Chronic ethanol exposure, in vivo and in vitro, increases polypeptide levels of NR1 subunit, the key subunit of functional NMDA receptors. In vitro, chronic ethanol treatment increases the half-life of NR1 mRNA and this observation is dependent on new protein synthesis. The present study was undertaken to locate cis-acting region(s) within the NR1 3'-untranslated region (UTR) and identify NR1 3'-UTR binding trans-acting proteins expressed in mouse fetal cortical neurons. Utilizing RNA gel shift assays we identified a 156-nt cis-acting region that binds to polysomal trans-acting proteins. This binding was highly specific as inclusion of cyclophilin RNA or tRNA did not interfere with cis-trans interactions. Importantly, the 3'-UTR binding activity was significantly up-regulated in the presence of ethanol. UV cross-link analysis detected three NR1 3'-UTR binding proteins and their molecular mass calculated by Northwestern analysis was approximately 88, 60 and 47 kDa, respectively. Northwestern analysis showed a significant up-regulation of the 88-kDa protein after chronic ethanol treatment. The 88-kDa protein was purified and identified by tandem mass spectrometry as the beta subunit of alpha glucosidase II (GIIbeta). That GIIbeta is indeed a trans-acting protein and binds specifically to 3'-UTR of NR1 mRNA was confirmed by RNA gel mobility supershift assays and immuno RT-PCR. Western blotting data established a significant increase of GIIbeta polypeptide in chronic ethanol-exposed fetal cortical neurons. We hypothesize that the identified cis-acting region and the associated RNA-binding proteins are important regulators of NR1 subunit gene expression.

  15. Safety evaluation of an extract from Salacia oblonga.

    Science.gov (United States)

    Wolf, B W; Weisbrode, S E

    2003-06-01

    Plant extracts from the Salacia genus have been found to have intestinal alpha-glucosidase inhibitor activity, which may have application to the development of medical foods for people with diabetes. We evaluated the safety of a hot water extract of S. oblonga (salacinol extract) supplemented to or processed into a medical food. Thirty male Sprague-Dawley rats were assigned among one of three treatments: (1) EN-0178 (control, liquid diet), (2) EN-0178+salacinol (as 1 plus 500 mg of salacinol extract per 253 g diet, which was added to product immediately prior to feeding), (3) EN-0195 (as 1 plus 500 mg of salacinol extract per 253 g diet, which was added during product manufacture). After 14 days of free access to dietary treatments, rats were sacrificed, blood collected and organs weighed. Rats consuming salacinol extract had reduced (P <0.05) weight gain and feed intake. The relative (% of body weight) testicular weight was higher (P<0.05) for rats consuming salacinol extract, whereas, the relative liver and spleen weight was lower (P<0.05) for rats consuming salacinol extract. Of the serum chemistries analyzed, blood urea nitrogen and alkaline phosphatase was lower (P<0.05) for rats consuming salacinol extract. No differences in blood hematology were found. We conclude that salacinol extract, in a medical food consumed for 2 weeks in amounts estimated at 10-fold greater than proposed for human intake, did not result in clinical chemistry or histopathologic indications of toxic effects in male Sprague-Dawley rats. PMID:12738192

  16. Composition and Biological Activity of Volatile Oil from Salviajudaica and S. multicaulis from Jordan.

    Science.gov (United States)

    Afifi, Fatma U; Kasabri, Violet; Al-Jaber, Hala I; Abu-Irmaileh, Barakat E; Al-Qudah, Mahmoud A; Abazaa, Ismail F

    2016-04-01

    The aim of this work was to determine the composition of the hydro-distilled essential oil of Salvia judaica Boiss. and S. multicaulis Vahl. (Lamiaceae) from Jordan by GC and GC-MS and to report the actual composition of their fresh leaves and flowers using SPME (Solid Phase Micro-Extraction).Their dual alpha-amylase/alpha glucosidase and pancreatic lipase inhibitory activities as well as their anti-proliferative potential were screened. The aroma profile of the leaves, flowers, and flowers at pre-flowering stages of S. judaica, obtained through SPME was composed of sesquiterpene hydrocarbons (87.7 %, 71.8 %, and 86.2 %, respectively) while the hydro-distilled oil of the dry leaves was rich in oxygenated sesquiterpenes (50.8%). Fresh leaves of S. multicaulis were rich in oxygenated monoterpenes (58.1%), while monoterpene hydrocarbons dominated the blooming flowers (57.2%) and the flowers at the pre-flowering stage (64.7%). The hydro-distilled oil of the dry leaves was rich in oxygenated monoterpenes (77.6%). With doxorubicin as a positive control, no anti-proliferative activity was observed against colorectal cancer cell lines HT29, HCT116, and SW620 using SRB assay for either Salvia spp. In vitro enzymatic starch digestion was evaluated with Acarbose (IC50: 0.2 ± 0.0 µg /mL) as the reference drug. The respective IC50 (mg/mL) values of S. judaica and S. multicaulis aqueous extracts were 4.9 ± 0.4 and 10.3 ± 0.9. Modulation of pancreatic lipase activity (PL) was determined by colorimetry and compared with Orlistat (IC50 : 0.11 ± 0.0 µg/mL). PL-IC50 values (µg/mL) obtained for S. judaica and S. multicaulis were 108.5±6.4 and 31.8 ± 0.8, respectively. PMID:27396212

  17. Inhibitory activity of Iranian plant extracts on growth and biofilm formation by Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Mansouri, S.

    2013-01-01

    Full Text Available Aims: Pseudomonas aeruginosa is a drug resistance opportunistic bacterium. Biofilm formation is key factor for survivalof P. aeruginosa in various environments. Polysaccharides may be involved in biofilm formation. The purpose of thisstudy was to evaluate antimicrobial and anti-biofilm activities of seven plant extracts with known alpha-glucosidaseinhibitory activities on different strains of P. aeruginosa.Methodology and results: Plants were extracted with methanol by the maceration method. Antimicrobial activities weredetermined by agar dilution and by growth yield as measured by OD560nm of the Luria Bertani broth (LB culture with orwithout extracts. In agar dilution method, extracts of Quercus infectoria inhibited the growth of all, while Myrtuscommunis extract inhibited the growth of 3 out of 8 bacterial strains with minimum inhibitory concentration (MIC of 1000μg/mL. All extracts significantly (p≤0.003 reduced growth rate of the bacteria in comparison with the control withoutextracts in LB broth at sub-MIC concentrations (500 μg/mL. All plant extracts significantly (p≤0.003 reduced biofilmformation compared to the controls. Glycyrrhiza glabra and Q. infectoria had the highest anti-biofilm activities. Nocorrelation between the alpha-glucosidase inhibitory activity with growth or the intensity of biofilm formation was found.Conclusion, significance and impact of study: Extracts of Q. infectoria and M. communis had the most antimicrobial,while Q. infectoria and G. glabra had the highest anti-biofilm activities. All plant extracts had anti-biofilm activities withmarginal effect on growth, suggesting that the mechanisms of these activities are unrelated to static or cidal effects.Further work to understand the relation between antimicrobial and biofilm formation is needed for development of newmeans to fight the infectious caused by this bacterium in future.

  18. Expression and characterization of α-glucosidase Ⅲ in the dwarf honeybee, Apis florea (Hymenoptera: Apoidea:Apidae)

    Institute of Scientific and Technical Information of China (English)

    CHANPEN CHANCHAO; RUMPALAI PADOONGSUPALAI; POLKIT SANGVANICH

    2007-01-01

    Alpha-glucosidase is synthesized in the hypopharyngeal glands located in the head of worker bees including Apis florea. To analyze the developmental stage-specific expression of the α-glucosidase gene in A. florea, total RNA was isolated from eggs, and the heads of nurse and forager bees. By reverse transcription polymerase chain reaction (RTPCR), it was shown that the highest expression levels of the α-glucosidase Ⅲ gene, in the three examined developmental stadia, were found in forager bees, with much lower expression levels in nurse bees and no detectable expression in eggs. A complete α-glucosidase Ⅲ cDNA was obtained by RT-PCR and sequenced. The 1 701 bp cDNA nucleotide sequence and the predicted 567 amino acids it encodes were assayed by BLASTn,BLASTp and BLASTx programs and revealed a 95% and 94% similarity to the A. mellifera α-glucosidase Ⅲ gene at the DNA and amino acid sequence levels, respectively. For purification of the active encoded enzyme, forager bee heads were homogenized in sodium phosphate buffer solution and the crude extract (0.30 U/mg) sequentially precipitated with 95% saturated ammonium sulfate (0.18 U/mg), and purified by DEAE cellulose ion exchange chromatography (0.17 U/mg), and gel filtration on Superdex 200 (0.52 U/mg).After resolution through sodium dodecyl sulfate-polyacrylamide gel electrophoresis, a single enzymically active band (73 kDa) was identified from renatured substrate gels.Excision of this band, elution of the protein and tryptic peptide digestives identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) revealed six matching masses to the A. mellifera (Q17958) and predicted A. florea α-glucosidase Ⅲ protein with 12% coverage, supporting the probable purification of the same α-glucosidase Ⅲ protein as that encoded by the cloned cDNA.

  19. Type 2 Diabetes Mellitus: A Review of Current Trends

    Directory of Open Access Journals (Sweden)

    Abdulfatai B. Olokoba

    2012-07-01

    Full Text Available Type 2 diabetes mellitus (DM is a chronic metabolic disorder in which prevalence has been increasing steadily all over the world. As a result of this trend, it is fast becoming an epidemic in some countries of the world with the number of people affected expected to double in the next decade due to increase in ageing population, thereby adding to the already existing burden for healthcare providers, especially in poorly developed countries. This review is based on a search of Medline, the Cochrane Database of Systemic Reviews, and citation lists of relevant publications. Subject heading and key words used include type 2 diabetes mellitus, prevalence, current diagnosis, and current treatment. Only articles in English were included. Screening and diagnosis is still based on World Health Organization (WHO and American Diabetes Association (ADA criteria which include both clinical and laboratory parameters. No cure has yet been found for the disease; however, treatment modalities include lifestyle modifications, treatment of obesity, oral hypoglycemic agents, and insulin sensitizers like metformin, a biguanide that reduces insulin resistance, is still the recommended first line medication especially for obese patients. Other effective medications include non-sulfonylurea secretagogues, thiazolidinediones, alpha glucosidase inhibitors, and insulin. Recent research into the pathophysiology of type 2 DM has led to the introduction of new medications like glucagon-like peptide 1 analogoues: dipeptidyl peptidase-IV inhibitors, inhibitors of the sodium-glucose cotransporter 2 and 11ß-hydroxysteroid dehydrogenase 1, insulin-releasing glucokinase activators and pancreatic-G-protein-coupled fatty-acid-receptor agonists, glucagon-receptor antagonists, metabolic inhibitors of hepatic glucose output and quick-release bromocriptine. Inhaled insulin was licensed for use in 2006 but has been withdrawn from the market because of low patronage.

  20. Early administration of enzyme replacement therapy for Pompe disease: short-term follow-up results.

    Science.gov (United States)

    Hamdan, M A; Almalik, M H; Mirghani, H M

    2008-12-01

    Pompe disease (glycogen storage disease II, OMIM # 232300), is a hereditary lysosomal disorder. It is characterized by deficiency of acid alpha-glucosidase enzyme (acid maltase, GAA, OMIM *606800, EC 3.1.26.2), secondary to mutations in the GAA gene (HGNC:4065) on chromosome 17q25.2-q25.3. Absent enzyme activity in the infantile form of Pompe disease results in abnormal glycogen deposition in the skeletal, cardiac, and smooth muscles, leading to hypertrophic cardiomyopathy, feeding abnormalities, hypotonia, weakness, respiratory insufficiency, and ultimately death. Prenatal diagnosis is accomplished by enzyme assay, mutation analysis or electron microscopy of amniotic fluid cells or chorionic villus sample. However, these techniques may not always be available, and can result in perinatal morbidity and fetal loss. Early diagnosis of Pompe disease results in early institution of enzyme replacement therapy (ERT), which minimizes morbidity and prolongs survival. We report the case of a 35-week part-of-twin neonate, whose older sibling died earlier because of infantile Pompe disease. At 32 weeks of gestation, fetal echocardiography showed hypertrophic cardiomyopathy in twin 1, which persisted until birth at 35 weeks of gestation. Diagnosis was confirmed after birth by enzyme assay, and mutation analysis showing homozygosity for the sequence change 1327-2A>G (GAA intr 8). Administration of ERT at 18 h of age, resulted in normalization of cardiac abnormalities within 21 weeks of therapy, and normal neurodevelopmental assessment at 46 weeks, using Griffiths Mental Development Scales. To our knowledge, this is the youngest patient reported to receive ERT for Pompe disease, and the first report of prenatal diagnosis of Pompe disease by fetal echocardiography. PMID:19067231

  1. Acute effects of acarbose on post-prandial glucose and triglycerides in type 2 diabetics following intake of different Malaysian foods.

    Science.gov (United States)

    Nawawi, H M; Yazid, T N; Ismail, F; Khalid, B A

    2000-03-01

    Acarbose inhibits intestinal alpha-glucosidases resulting in diminished and delayed postprandial hyperglycaemia (PPH). Studies on effects of acarbose on postprandial lipaemia (PPL) have been inconclusive. Little is known about the effects of acarbose on PPH and PPL following intake of a polysaccharide diet. We studied 30 type 2 diabetic patients on dietary and/or oral hypoglycaemic agent(s). Thirty patients were recruited for food A (nasi lemak), 28 for food B (mee goreng) and 28 for food C (roti telur), which represent the typical diets of the three main races in Malaysia. Serial blood samples were taken at 15 min before and up to 240 min after each food intake, without acarbose. Subsequently, three doses of 50 mg acarbose were given orally and the same procedure was repeated the following day. There were significantly lower mean increments in plasma glucose levels after compared to before acarbose treatment 30, 45 and 60 min for food A and at 30, 45, 60, 120, 180 and 240 min for food C, but no significant difference was noted for food B. There was a significantly lower mean fasting glucose level after compared with before acarbose treatment following intake of food A and C but not food B. Short-term treatment with acarbose caused significant diminished and delayed PPH response with food A and C but not with food B. Acarbose was more effective in reducing PPH response in polysaccharide foods with a higher and earlier postprandial glucose peak than in those with a lower and lagged peak. There were no significant differences in the mean fasting or postprandial triglyceride levels before and after acarbose treatment, following intake of all three foods for up to 4 hours. Depending on the food absorption pattern, overnight low dose treatment with acarbose leads to diminished fasting and peak plasma glucose levels, and delayed PPH but insignificant reduction in postprandial lipaemia in poorly controlled type 2 diabetics following intake of racially different Malaysian

  2. Cardiovascular disease in the JCR:LA-cp rat.

    Science.gov (United States)

    Russell, J C; Graham, S E; Richardson, M

    1998-11-01

    The JCR:LA-cp rat is one of a number of strains that carry the mutant autosomal recessive cp gene. Animals, of all strains, that are homozygous, for the gene (cp/cp) become obese, insulin resistant, and hypertriglyceridemic. Heterozygotes or homozygous normal rats (+/+) are lean and metabolically normal. The JCR:LA-cp rat is unique in the development of a frank vasculopathy with atherosclerotic lesions and associated ischemic myocardial lesions. The cardiovascular disease is strongly correlated with the hyperinsulinemia, which develops as the animals mature from 4 to 8 weeks of age. The hyperinsulinemia can be decreased by marked food restriction, ethanol consumption, or reduction of the postprandial glucose and insulin responses through the use of alpha-glucosidase inhibitors. Any treatment that reduces plasma insulin levels is associated with a reduction in cardiovascular disease. In contrast, a reduction in plasma triglyceride concentrations, alone, has no effect on end-stage lesions. JCR:LA-cp rats, particularly those that are cp/cp, are, however, sensitive to cholesterol in the diet, unlike other strains that are highly resistant. Further, the rats have abnormal vascular smooth muscle cells that, especially in the cp/cp animals, are hyperplastic and activated and migrate into the intimal space. Our findings suggest that susceptibility to cardiovascular disease requires hypermsulinemic stress coupled with excessive dietary intake and the presence of one or more other necessary, but not sufficient, genetic factors. One of these may be a genetic abnormality of vascular smooth muscle cells. A similar situation may occur in humans.

  3. Salacia oblonga improves cardiac fibrosis and inhibits postprandial hyperglycemia in obese Zucker rats.

    Science.gov (United States)

    Li, Yuhao; Peng, Gang; Li, Qian; Wen, Suping; Huang, Tom Hsun-Wei; Roufogalis, Basil D; Yamahara, Johji

    2004-08-20

    Diabetes has a markedly greater incidence of cardiovascular disease than the non-diabetic population. The heart shows a slowly developing increase in fibrosis in diabetes. Extended cardiac fibrosis results in increased myocardial stiffness, causing ventricular dysfunction and, ultimately, heart failure. Reversal of fibrosis may improve organ function survival. Postprandial hyperglycemia plays an important role in the development of type 2 diabetes and cardiovascular complications, and has been proposed as an independent risk factor for cardiovascular diseases. Salacia oblonga (S.O.) is traditionally used in the prevention and treatment of diabetes. We investigated the effects of its water extract on cardiac fibrosis and hyperglycemia in a genetic model of type 2 diabetes, the obese Zucker rat (OZR). Chronic administration of the extract markedly improved interstitial and perivascular fibrosis in the hearts of the OZR. It also reduced plasma glucose levels in non-fasted OZR, whereas it had little effect in the fasted animals, suggesting inhibition of postprandial hyperglycemia in type 2 diabetic animals, which might play a role in improvement of the cardiac complications of OZR. Furthermore, S.O. markedly suppressed the overexpression of mRNAs encoding transforming growth factor betas 1 and 3 in the OZR heart, which may be an important part of the overall molecular mechanisms. S.O. dose-dependently inhibited the increase of plasma glucose in sucrose-, but not in glucose-loaded mice. S.O. demonstrated a strong inhibition of alpha-glucosidase activity in vitro, which is suggested to contribute to the improvement of postprandial hyperglycemia. PMID:15268973

  4. Influence of dietary carbohydrate on the metabolism of juvenile Litopenaeus stylirostris.

    Science.gov (United States)

    Rosas; Cuzon; Gaxiola; Arena; Lemaire; Soyez; Van Wormhoudt A

    2000-06-28

    The effect of dietary carbohydrates (CBH) on glucose and glycogen, digestive enzymes, ammonia excretion and osmotic pressure and osmotic capacity of Litopenaeus stylirostris juveniles was studied. The increase of CBH, ranging between 1 and 33%, stimulates activities of alpha-amylase and alpha-glucosidase in the hepatopancreas. High levels of glucose in hemolymph and of glycogen in the hepatopancreas were reached at the highest level of dietary CBH; however, the kinetics of accumulation is different. Shrimps fed with low level of CBH needed 3 h to reached glucose peak, whereas only 1 h is necessary for high CBH levels. A saturation curve was observed in glycogen level and alpha-amylase activity with maximum values in shrimp-fed diets containing 21% CBH. This level could be used to be included as a maximum shrimp dietary CBH level. Pre-prandial glycogen levels were observed in shrimp fed a diet containing 1% CBH, indicating an important gluconeogenesis, which affected the protein metabolism. The present results show that a diet containing 10% CBH may not be enough to cover the CBH requirement, which could be satisfied by dietary protein content. The low osmotic capacity observed in shrimp fed on a diet containing 10% CBH coincided with a relatively low post-prandial nitrogen excretion which reflects a low concentration of amino acids circulating in hemolymph, which affected the osmotic pressure and the osmotic capacity. These results reflect the high plasticity of shrimp species to use protein to obtain metabolic energy from food and its limited capacity for processing dietary CBH. PMID:10841934

  5. Ten years of dengue drug discovery: progress and prospects.

    Science.gov (United States)

    Lim, Siew Pheng; Wang, Qing-Yin; Noble, Christian G; Chen, Yen-Liang; Dong, Hongping; Zou, Bin; Yokokawa, Fumiaki; Nilar, Shahul; Smith, Paul; Beer, David; Lescar, Julien; Shi, Pei-Yong

    2013-11-01

    To combat neglected diseases, the Novartis Institute of Tropical Diseases (NITD) was founded in 2002 through private-public funding from Novartis and the Singapore Economic Development Board. One of NITD's missions is to develop antivirals for dengue virus (DENV), the most prevalent mosquito-borne viral pathogen. Neither vaccine nor antiviral is currently available for DENV. Here we review the progress in dengue drug discovery made at NITD as well as the major discoveries made by academia and other companies. Four strategies have been pursued to identify inhibitors of DENV through targeting both viral and host proteins: (i) HTS (high-throughput screening) using virus replication assays; (ii) HTS using viral enzyme assays; (iii) structure-based in silico docking and rational design; (iv) repurposing hepatitis C virus inhibitors for DENV. Along the developmental process from hit finding to clinical candidate, many inhibitors did not advance beyond the stage of hit-to-lead optimization, due to their poor selectivity, physiochemical or pharmacokinetic properties. Only a few compounds showed efficacy in the AG129 DENV mouse model. Two nucleoside analogs, NITD-008 and Balapiravir, entered preclinical animal safety study and clinic trial, but both were terminated due to toxicity and lack of potency, respectively. Celgosivir, a host alpha-glucosidase inhibitor, is currently under clinical trial; its clinical efficacy remains to be determined. The knowledge accumulated during the past decade has provided a better rationale for ongoing dengue drug discovery. Though challenging, we are optimistic that this continuous, concerted effort will lead to an effective dengue therapy.

  6. The physiology of the midgut of Lutzomyia longipalpis (Lutz and Neiva 1912): pH in different physiological conditions and mechanisms involved in its control.

    Science.gov (United States)

    Santos, Vânia C; Araujo, Ricardo N; Machado, Luciane A D; Pereira, Marcos H; Gontijo, Nelder F

    2008-09-01

    Nutrient digestion and absorption after blood feeding are important events for Lutzomyia longipalpis, which uses these nutrients to produce eggs. In this context, the pH inside the digestive tract is an important physiological feature as it can markedly influence the digestive process as well as interfere with Leishmania development in infected phlebotomines. It was described previously that unfed females have an acidic midgut (pH 6). In this study, the pH inside the midgut of blood-fed females was measured. The abdominal midgut (AM) pH varied from 8.15+/-0.31 in the first 10 h post-blood meal to 7.7+/-0.17 after 24 h. While the AM was alkaline during blood digestion, the pH in the thoracic midgut (TM) remained acidic (5.5-6.0). In agreement with these findings, the enzyme alpha-glucosidase, which has an optimum pH of 5.8, is mainly encountered in the acidic TM. The capacity of unfed females to maintain the acidic intestinal pH was also evaluated. Our results showed the presence of an efficient mechanism that maintains the pH almost constant at about 6 in the midgut, but not in the crop. This mechanism is promptly interrupted in the AM by blood ingestion. RT-PCR results indicated the presence of carbonic anhydrase in the midgut cells, which apparently is required to maintain the pH at 6 in the midgut of unfed females. Investigations on the phenomenon of alkalization observed after blood ingestion indicated that two mechanisms are involved: in addition to the alkalization promoted by CO2 volatilization there is a minor contribution from a second mechanism not yet characterized. Some inferences concerning Leishmania development and pH in the digestive tube are presented. PMID:18723537

  7. Acute effects of acarbose on post-prandial glucose and triglycerides in type 2 diabetics following intake of different Malaysian foods.

    Science.gov (United States)

    Nawawi, H M; Yazid, T N; Ismail, F; Khalid, B A

    2000-03-01

    Acarbose inhibits intestinal alpha-glucosidases resulting in diminished and delayed postprandial hyperglycaemia (PPH). Studies on effects of acarbose on postprandial lipaemia (PPL) have been inconclusive. Little is known about the effects of acarbose on PPH and PPL following intake of a polysaccharide diet. We studied 30 type 2 diabetic patients on dietary and/or oral hypoglycaemic agent(s). Thirty patients were recruited for food A (nasi lemak), 28 for food B (mee goreng) and 28 for food C (roti telur), which represent the typical diets of the three main races in Malaysia. Serial blood samples were taken at 15 min before and up to 240 min after each food intake, without acarbose. Subsequently, three doses of 50 mg acarbose were given orally and the same procedure was repeated the following day. There were significantly lower mean increments in plasma glucose levels after compared to before acarbose treatment 30, 45 and 60 min for food A and at 30, 45, 60, 120, 180 and 240 min for food C, but no significant difference was noted for food B. There was a significantly lower mean fasting glucose level after compared with before acarbose treatment following intake of food A and C but not food B. Short-term treatment with acarbose caused significant diminished and delayed PPH response with food A and C but not with food B. Acarbose was more effective in reducing PPH response in polysaccharide foods with a higher and earlier postprandial glucose peak than in those with a lower and lagged peak. There were no significant differences in the mean fasting or postprandial triglyceride levels before and after acarbose treatment, following intake of all three foods for up to 4 hours. Depending on the food absorption pattern, overnight low dose treatment with acarbose leads to diminished fasting and peak plasma glucose levels, and delayed PPH but insignificant reduction in postprandial lipaemia in poorly controlled type 2 diabetics following intake of racially different Malaysian

  8. Pompe disease: from pathophysiology to therapy and back again

    Directory of Open Access Journals (Sweden)

    Jeong-A eLim

    2014-07-01

    Full Text Available Pompe disease is a lysosomal storage disorder in which acid alpha-glucosidase is deficient or absent. Deficiency of this lysosomal enzyme results in progressive expansion of glycogen-filled lysosomes in multiple tissues, with cardiac and skeletal muscle being the most severely affected. The clinical spectrum ranges from fatal hypertrophic cardiomyopathy and skeletal muscle myopathy in infants to relatively attenuated forms, which manifest as a progressive myopathy without cardiac involvement. The currently available enzyme replacement therapy proved to be successful in reversing cardiac but not skeletal muscle abnormalities. Although the overall understanding of the disease has progressed, the pathophysiology of muscle damage remains poorly understood. Lysosomal enlargement/rupture has long been considered a mechanism of relentless muscle damage in Pompe disease. In past years, it became clear that this simple view of the pathology is inadequate; the pathological cascade involves dysfunctional autophagy, a major lysosome-dependent intracellular degradative pathway. The autophagic process in Pompe skeletal muscle is affected at the termination stage - impaired autophagosomal-lysosomal fusion. Yet another abnormality in the diseased muscle is the accelerated production of large, unrelated to ageing, lipofuscin deposits - a marker of cellular oxidative damage and a sign of mitochondrial dysfunction. The massive autophagic buildup and lipofuscin inclusions appear to cause a greater effect on muscle architecture than the enlarged lysosomes outside the autophagic regions. Furthermore, the dysfunctional autophagy affects the trafficking of the replacement enzyme and interferes with its delivery to the lysosomes. Several new therapeutic approaches have been tested in Pompe mouse models: substrate reduction therapy, lysosomal exocytosis following the overexpression of transcription factor EB and a closely related but distinct factor E3, and genetic

  9. ANTI-OXIDANT AND ENZYME-INHIBITORY POTENTIAL OF MARINE STREPTOMYCES

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    K. Suthindhiran

    2013-01-01

    Full Text Available Marine actinomycetes are potential source for the discovery of novel compounds and enzymes. Though extensive research on marine actinomycetes is underway globally, the actinomycetes research from Indian marine ecosystem is unexplored and understudied. Hence, the present research is focussed on the screening of bioactive compounds from marine actinomycetes isolated from Indian coastal region. This study is designed to determine the antioxidant and enzyme inhibitory potential of Streptomyces sp. VITMSS05 strain, isolated from Marakkanam, southern coast of India. An actinomycetes strain designated as VITMSS05 was isolated. This strain was cultivated in Starch Caesin Agar medium (SCA supplemented with sea water. The cultural, morphological and molecular characterization was determined for the isolate. The crude extract of the isolate was extracted with ethyl acetate. Antioxidant activity of the crude extract was determined by DPPH radical scavenging assay. Alpha amylase and alpha glucosidase inhibitory potential of the extract was determined. Based on the phenotypic and phylogenetic analysis the strain was identified as Streptomyces sp. Significant antioxidant activity of the extract was observed with an IC50 value of 92.49 μg mL-1. The extract shows 64.1% inhibition on α-amylase and 91.5% inhibition on α-glucosidase at 100 μg mL-1 with an IC50 value of 385.97 and 42.89 μg mL-1. From the results it is evident that the ethyl acetate extract of Streptomyces sp. VITMSS05 has potent antioxidant and enzyme inhibitory activity in vitro. The combined effect of free radical scavenging and enzyme inhibition makes it a potent anti diabetic drug.

  10. Trends in Antihyperglycemic Medication Prescriptions and Hypoglycemia in Older Adults: 2002-2013.

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    Kristin K Clemens

    Full Text Available Over the last decade, several new antihyperglycemic medications have been introduced including those associated with a lower hypoglycemia risk. We aimed to investigate how these medications are being prescribed to older adults in our region.We conducted population-based cross-sectional analyses of older adults (mean age 75 years with treated diabetes in Ontario, Canada from 2002 until 2013, to examine the percentage prescribed insulin, sulphonylureas, alpha-glucosidase inhibitors, metformin, thiazolidinediones, meglitinides, and dipeptidyl peptidase-4 inhibitors. Over the study period, we also examined their hospital encounters for hypoglycemia (emergency room or inpatient encounter.The mean age of treated patients increased slightly over the study quarters and the proportion that were women declined. With the exception of chronic kidney disease, cancer, dementia, and neuropathy, the percentage with a comorbidity appeared to decline. The percentage of treated patients prescribed metformin, gliclazide and dipeptidyl peptidase-4 inhibitors increased as did combination therapy. Glyburide and thiazolidinedione prescriptions declined, and insulin use remained stable. In those with newly treated diabetes, the majority were prescribed metformin, with smaller percentages prescribed insulin and other oral agents. Although the absolute number of treated patients with a hypoglycemia encounter increased until mid-2006 and then decreased, the overall percentage with an encounter declined over the study period (0.8% with an event in the first quarter, 0.4% with an event in the last quarter.Antihyperglycemic medications with safer profiles are being increasingly prescribed to older adults. In this setting there has been a decrease in the percentage of treated patients with a hospital encounter for hypoglycemia.

  11. Single nucleotide deletion of cqm1 gene results in the development of resistance to Bacillus sphaericus in Culex quinquefasciatus.

    Science.gov (United States)

    Guo, Qing-yun; Cai, Quan-xin; Yan, Jian-ping; Hu, Xiao-min; Zheng, Da-sheng; Yuan, Zhi-ming

    2013-09-01

    The entomopathogen Bacillus sphaericus is one of the most effective biolarvicides used to control the Culex species of mosquito. The appearance of resistance in mosquitoes to this bacterium, however, remains a threat to its continuous use in integrated mosquito control programs. Previous work showed that the resistance to B. sphaericus in Culex colonies was associated with the absence of the 60-kDa binary toxin receptor (Cpm1/Cqm1), an alpha-glucosidase present in the larval midgut microvilli. In this work, we studied the molecular basis of the resistance developed by Culex quinquefasciatus to B. sphaericus C3-41. The cqm1 genes were cloned from susceptible (CqSL) and resistant (CqRL/C3-41) colonies, respectively. The sequence of the cDNA and genomic DNA derived from CqRL/C3-41 colony differed from that of CqSL one by a one-nucleotide deletion which resulted in a premature stop codon, leading to production of a truncated protein. Recombinant Cqm1S from the CqSL colony expressed in Escherichia coli specifically bound to the Bin toxin and had α-glucosidase activity, whereas the Cqm1R from the CqRL/C3-41 colony, with a deletion of three quarters of the receptor's C-terminal lost its α-glucosidase activity and could not bind to the binary toxin. Immunoblotting experiments showed that Cqm1 was undetectable in CqRL/C3-41 larvae, although the gene was correctly transcribed. Thus, the cqm1R represents a new allele in C. quinquefasciatus that confers resistance to B. sphaericus. PMID:23871751

  12. Aglycone specificity of Escherichia coli alpha-xylosidase investigated by transxylosylation.

    Science.gov (United States)

    Kang, Min-Sun; Okuyama, Masayuki; Yaoi, Katsuro; Mitsuishi, Yasushi; Kim, Young-Min; Mori, Haruhide; Kim, Doman; Kimura, Atsuo

    2007-12-01

    The specificity of the aglycone-binding site of Escherichia coli alpha-xylosidase (YicI), which belongs to glycoside hydrolase family 31, was characterized by examining the enzyme's transxylosylation-catalyzing property. Acceptor specificity and regioselectivity were investigated using various sugars as acceptor substrates and alpha-xylosyl fluoride as the donor substrate. Comparison of the rate of formation of the glycosyl-enzyme intermediate and the transfer product yield using various acceptor substrates showed that glucose is the best complementary acceptor at the aglycone-binding site. YicI preferred aldopyranosyl sugars with an equatorial 4-OH as the acceptor substrate, such as glucose, mannose, and allose, resulting in transfer products. This observation suggests that 4-OH in the acceptor sugar ring made an essential contribution to transxylosylation catalysis. Fructose was also acceptable in the aglycone-binding site, producing two regioisomer transfer products. The percentage yields of transxylosylation products from glucose, mannose, fructose, and allose were 57, 44, 27, and 21%, respectively. The disaccharide transfer products formed by YicI, alpha-D-Xylp-(1-->6)-D-Manp, alpha-D-Xylp-(1-->6)-D-Fruf, and alpha-d-Xylp-(1-->3)-D-Frup, are novel oligosaccharides that have not been reported previously. In the transxylosylation to cello-oligosaccharides, YicI transferred a xylosyl moiety exclusively to a nonreducing terminal glucose residue by alpha-1,6-xylosidic linkages. Of the transxylosylation products, alpha-d-Xylp-(1-->6)-D-Manp and alpha-d-Xylp-(1-->6)-D-Fruf inhibited intestinal alpha-glucosidases. PMID:17970751

  13. Acarbose improves glycemic control and reduces body weight: Subanalysis data of South Asia region

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    S Kalra

    2013-01-01

    Full Text Available Alpha-glucosidase inhibitors (AGIs are widely used especially in Asian countries as a treatment option for type 2 diabetes patients with high postprandial glycaemia. However, data from South Asia region is very limited. In order to examine the effect of AGI in real-life setting, 10 PMS/NIS from all over the world from the launch of acarbose to date were pooled in one database and exploratory analysis was performed for glycemic parameters and weight. In total 62,905 patients were pooled from 21 countries and regions. Mean follow up (± SD was 12.2 ± 4.8 weeks (range 0.1-108.9. From South Asia region (India and Pakistan, 8,738 Asian patients were enrolled. Mean PPG decreased from 240.0 and 261.1 mg/dl at baseline by 70.26 ± 65.10 and 82.96 ± 56.59 mg/dl at the last visit in total and South Asian populations, respectively (n = 53,883; n = 7,991, P < 0.0001 for both. Mean FPG decreased from 171.6 and 176.5 mg/dl at baseline by 38.48 ± 47.83 and 49.59 ± 41.41 mg/dl at the last visit in total and South Asian populations, respectively (n = 56,672; n = 7,837, P < 0.0001 for both. Mean HbA1c decreased from 8.4 and 8.4% at baseline by 1.11 ± 1.31% and 0.91 ± 0.93% at the last visit in total and South Asian populations, respectively (n = 38,843; n = 2,343, P < 0.0001 for both. Mean relative reduction of body weight (BW was 1.40 ± 3.28% and 1.10 ± 3.39% at the last visit for mean baseline BW 73.6 and 74.2 kg in total and South Asian populations, respectively (n = 54,760; n = 7,718, P < 0.0001 for both. Consistent with RCT meta-analyses, post-hoc analysis of real-life data showed acarbose treatment improved glycaemic control and reduced the BW. Acarbose treatment in real life setting showed significant reductions in all glycemic parameters and BW in Asian patients from South Asia region.

  14. Antidiabetic treatment with gliptins: focus on cardiovascular effects and outcomes.

    Science.gov (United States)

    Fisman, Enrique Z; Tenenbaum, Alexander

    2015-01-01

    The traditional oral pharmacological therapy for type 2 diabetes mellitus (T2DM) has been based on the prescription of metformin, a biguanide, as first line antihyperglycemic agent world over. It has been demonstrated that after 3 years of treatment, approximately 50% of diabetic patients could achieve acceptable glucose levels with monotherapy; but by 9 years this had declined to only 25%. Therefore, the implementation of a combined pharmacological therapy acting via different pathways becomes necessary, and its combination with a compound of the sulfonylurea group was along decades the most frequently employed prescription in routine clinical practice. Meglitinides, glitazones and alpha-glucosidase inhibitors were subsequently developed, but the five mentioned groups of oral antihyperglycemic agents are associated with variable degrees of undesirable or even severe cardiovascular events. The gliptins-also called dipeptidyl peptidase 4 (DPP4) inhibitors--are an additional group of antidiabetic compounds with increasing clinical use. We review the status of the gliptins with emphasis on their capabilities to positively or negatively affect the cardiovascular system, and their potential involvement in major adverse cardiovascular events (MACE). Alogliptin, anagliptin, linagliptin, saxagliptin, sitagliptin, teneligliptin and vildagliptin are the compounds currently in clinical use. Regardless differences in chemical structure and metabolic pathways, gliptins as a group exert favorable changes in experimental models. These changes, as an almost general rule, include improved endothelial function, reduction of inflammatory markers, oxidative stress ischemia/reperfusion injury and atherogenesis. In addition, increased adiponectin levels and modest decreases in lipidemia and blood pressure were reported. In clinical settings, several trials--notably the longer one, employing sitagliptin, with a mean follow-up period of 3 years--did not show an increased risk for ischemic

  15. Muscle biopsy in Pompe disease Biópsia muscular na doença de Pompe

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    Lineu Cesar Werneck

    2013-05-01

    Full Text Available Pompe disease (PD can be diagnosed by measuring alpha-glucosidase levels or by identifying mutations in the gene enzyme. Muscle biopsies can aid diagnosis in doubtful cases. Methods: A review of muscle biopsy from 19 cases of PD (infantile, 6 cases; childhood, 4 cases; and juvenile/adult, 9 cases. Results: Vacuoles with or without glycogen storage were found in 18 cases. All cases had increased acid phosphatase activity. The vacuole frequency varied (almost all fibers in the infantile form to only a few in the juvenile/adult form. Atrophy of type 1 and 2 fibers was frequent in all forms. Atrophic angular fibers in the NADH-tetrazolium reductase and nonspecific esterase activity were observed in 4/9 of the juvenile/adult cases. Conclusion: Increased acid phosphatase activity and vacuoles were the primary findings. Most vacuoles were filled with glycogen, and the adult form of the disease had fewer fibers with vacuoles than the infantile or childhood forms.O diagnóstico da doença de Pompe (PD pode ser feito pela dosagem da enzima alfa-glicosidase ou pela mutação do seu gene codificador. A biópsia muscular pode ajudar em casos duvidosos. Métodos: Revisão das biópsias musculares de 19 casos de PD (forma infantil, 6 casos; infantil tardia, 4; e juvenil/adulto, 9. Resultados: Encontrados vacúolos em 18 casos, com ou sem depósito de glicogênio. Todos mostraram aumento da fosfatase ácida. Os vacúolos estavam presentes na maioria das fibras nas formas infantis, menos frequentes nas formas juvenil e mais raros nas formas do adulto. A atrofia de fibras dos tipos 1 e 2 ocorreram em todas as formas. Fibras atróficas na NADH-tetrazolium redutase e esterase não específica foram observadas em 4/9 das formas infantil tardia/adulta. Conclusões: Os dados mais frequentes foram vacúolos, preenchidos por glicogênio com atividade aumentada da fosfatase ácida. A forma adulta apresenta menor número de vacúolos que as formas infantil e infantil

  16. 糖原累积病Ⅱ型(Pompe病)17例临床特点和转归%Clinical sequelae of 17 cases with glycogen storage disease type Ⅱ/Pompe disease

    Institute of Scientific and Technical Information of China (English)

    张寒冰; 张为民; 仇佳晶; 孟岩; 邱正庆

    2012-01-01

    目的 总结分析国内糖原累积病Ⅱ型(Pompe病)患者的临床表现及疾病转归的特点.方法 回顾性分析17例经酶学确诊的糖原累积病Ⅱ型患者临床资料,通过设计临床调查表进行电话随访,总结归纳临床和转归特点.结果 17例糖原累积病Ⅱ型患者中,4例为婴儿型,生后2~6个月发病,均有肌酶升高和心脏受累,伴或不伴呼吸肌受累.4例均未进行治疗.其余13例为晚发型,发病年龄2~22岁,均有肌酶升高.其中11例以肌肉无力起病,2例表现为呼吸肌受累,2例表现为脊柱侧弯,1例表现为肌酶高伴肝功能异常.除3例曾接受呼吸机辅助治疗外,其余10例未接受相关治疗.全部患者α-1,4-葡萄糖苷酶活性数值均低于正常人10%以下;14例行病理肌活检检测,9例提示糖原累积病Ⅱ型;10例行基因检测,6例检测到2个致病突变.成功电话随访12例,随访率70%.婴儿型4例中,3例在3岁之内死于呼吸衰竭,存活的1例目前1岁7个月.成功随访的晚发型8例中,4例于发病3~5年死亡,均死于呼吸衰竭,存活的4例中3例自觉肌肉无力症状加重,1例自住院时使用呼吸机治疗,至今病情无明显改变.12例随访者中7例死亡,总死亡率58%.结论 糖原累积病Ⅱ型在临床表现上存在差异.婴儿型表现为全身性肌肉无力,心脏受累明显,病情凶险,死亡率高.晚发型以慢性进行性肌肉无力,呼吸功能不全为主.经α-1,4-葡萄糖苷酶活性测定、肌肉活检以及基因检测诊断.患者的预后与发病年龄、有无呼吸肌受累相关.%Objective To analyze and summarize the characteristics of glycogen storage disease type Ⅱ ( Pompe disease) patients according to the clinical description and prognosis.Method Seventeen Chinese patients diagnosed by acid alpha-glucosidase ( GAA ) enzyme activity test were reviewed.Clinical data tables were designed.Interviews were made via phone calls.Information was collected to

  17. Analysis of Application of Oral Hypoglycemic Drugs in Outpatient Department of the Central Hospital of Nanchong during 2012-2014%2012—2014年南充市中心医院门诊口服降糖药应用分析

    Institute of Scientific and Technical Information of China (English)

    徐秀华; 冯婧; 王龙飞

    2015-01-01

    目的:分析南充市中心医院(以下简称"我院")2012—2014年门诊口服降糖药的应用情况和发展趋势,为糖尿病药物治疗提供参考.方法:回顾性统计分析我院2012—2014年门诊降糖药的销售数量、销售总金额、用药频度( defined daily dose system,DDDs)、限定日费用( daily drug cost,DDC),并根据各药的DDDs排序和销售金额排序,算出排序比.结果:我院门诊口服降糖药销售金额整体呈上升趋势,磺酰脲类、双胍类、α-葡萄糖苷酶抑制剂的销售金额增幅大;二甲双胍使用频率高,连续3年居第1位;二甲双胍日平均费用较低,排序比连续3年大于1.结论:我院2012—2014年门诊口服降糖药临床使用基本合理,二甲双胍使用频率高,符合安全、有效、经济的用药原则.%OBJECTIVE:To analyze the status quo and development tendency of oral hypoglycemic drugs for outpatients in the Central Hospital of Nanchong( hereinafter referred to as "our hospital") during 2012-2014,and to provide reference for the medication of diabetes.METHODS: Retrospective analysis was conducted in terms of the consumption amount,consumption sum,defined daily dose system ( DDDs ),and daily drug cost ( DDC ); and the ranking ratio was calculated based on the ranking of DDDs and medication cost of oral hypoglycemic drugs.RESULTS:The consumption sum of oral hypoglycemic drugs for outpatients in our hospital showed an increase tendency in general,especially for sulfonylurea,biguanides and alpha glucosidase inhibitors.The use frequency of metformin continuously dominated the first place during the three years,which had a low cost per day,and the ranking ratio was over 1 during the three years.CONCLUSIONS: The application of oral hypoglycemic drugs for inpatients in our hospital is basically rational during 2012-2014,and metformin has a high frequency of usage,which is conform to the principle of safe,effective and economic medication.

  18. Glicogenose hereditária em bovinos Brahman no Brasil Inherited glycogenosis in Brahman cattle in Brazil

    Directory of Open Access Journals (Sweden)

    P Zlotowski

    2005-12-01

    one month of age, showed progressive difficulty to follow their mother, retarded growth, muscular weakness and tremors, lethargy and poor body condition. All affected calves were sired by the same bull. Necropsy was performed on three affected calves. The only gross lesion detected was paleness of the skeletal muscles of the trunk and limbs. Cytoplasmic vacuoles, the main histological lesion, were particularly evident in skeletal muscles, myocardium and Purkinje fibers, in neurons of the brain and spinal cord. Large amounts of periodic acid Schiff (PAS positive granules were also observed in these most severely affected tissues. Pretreatment with diastase completely abolished the PAS reactivity. The 1057?TA, a lethal mutation in the gene of the acid alpha-glucosidase, which causes generalized glycogenosis in Brahman cattle, was detected by PCR in paraffin embedded tissues of affected animals on which post-mortem examination was performed. Clinical, histological and molecular findings were similar to previous descriptions of generalized glycogenosis in Brahman cattle in Australia. No previous indexed reports about generalized glycogenosis of Brahman cattle in Brazil could be found.

  19. 婴儿型糖原累积症Ⅱ型六例临床分析%Analysis of clinical features of 6 patients with infantile type glycogen storage disease type Ⅱ

    Institute of Scientific and Technical Information of China (English)

    丁娟; 黄昱; 杨海坡; 张清友; 侯新琳; 刘雪芹; 杨艳玲; 能晖

    2015-01-01

    Objective To summarize clinical features and diagnosis of Chinese infantile patients with glycogen storage disease type Ⅱ (GSD Ⅱ).Method Six infant patients with GSD Ⅱ diagnosed from January 2012 to June 2014 in the Department of Pediatrics,Peking University First Hospital were enrolled into this study.Clinical information of the 6 patients,including clinical manifestation,blood biochemistry,chest X-ray,echocardiogram,electrocardiogram,acid alpha-glucosidase (GAA) activity and GAA gene mutation analysis by direct sequencing of polymerase chain reaction (PCR) product were reviewed.Result Of the 6 patients,five were female and one was male,five of whom were classic infantile type while the other one was atypical.The age of onset ranged from birth to 3-month-old.All patients had varying degrees of generalized muscle weakness,hypotonia and development retardation or retrogression.Other common findings were feeding difficulties in two patients,tongue weakness in two patients,respiratory distress in four patients,macroglossia in one patient,and hepatomegaly in two patients.Left ventricular hypertrophy and cardiomegaly were obvious in all the six patients.All six patients were found to have a enlarged heart in physical examination,and three patients who underwent a chest X-ray examination had an enlarged heart shadow.Four patients who had an echocardiography were found to have myocardial hypertrophy.The electrocardiogram in three patients showed short PR intervals and high voltage.The creatine kinase (CK) levels were three to seven times elevated.The mildest elevated CK was 441 IU/L,and the highest CK level was 1 238 U/L.Assay of GAA enzyme activity in whole blood showed significantly reduced activity (1.3 nmol/(spot · d) to 2 nmol/(spot · d)) in the patients tested.Gene sequencing in 4 patients showed 8 pathogenic mutations,including 6 missense mutations,one nonsense mutation and one frameshift mutation.The missense mutations were c.998C > A(p.Thr333Lys),c.1280